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Frontiers in Endocrinology 2023Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in... (Meta-Analysis)
Meta-Analysis
Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models.
BACKGROUND
Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility.
MATERIAL AND METHODS
We systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen's d) and 95% confidence interval.
RESULTS
24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high-fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen's testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress.
CONCLUSIONS
Melatonin can reduce damage to male rodents' gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.
Topics: Animals; Male; Mice; Rats; Body Weight; Diabetes Mellitus; Hyperthyroidism; Infertility, Male; Melatonin; Metabolic Diseases; Obesity; Oxidative Stress; Rodentia; Semen; Testis
PubMed: 37476491
DOI: 10.3389/fendo.2023.1202560 -
Brazilian Journal of Otorhinolaryngology 2024To assess the safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy in thyroid tumor. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To assess the safety and effectiveness of bilateral axillo-breast approach robotic thyroidectomy in thyroid tumor.
METHODS
Bilateral axillo-breast approach robotic thyroidectomy and other approaches (open thyroidectomy, transoral robotic thyroidectomy, and bilateral axillo-breast approach endoscopic thyroidectomy) were compared in studies from 6 databases.
RESULTS
Twenty-two studies (8830 individuals) were included. Bilateral axillo-breast approach robotic thyroidectomy had longer operation time, greater cosmetic satisfaction, and reduced transient hypoparathyroidism than conventional open thyroidectomy. Compared to bilateral axillo-breast approach endoscopic thyroidectomy, bilateral axillo-breast approach robotic thyroidectomy had greater amount of drainage, lower chances of transient vocal cord palsy and permanent hypothyroidism, and better surgical completeness (postopertive thyroblobulin level and lymph node removal). Bilateral axillo-breast approach robotic thyroidectomy induced greater postoperative drainage and greater patient dissatisfaction than transoral robotic thyroidectomy.
CONCLUSION
Bilateral axillo-breast approach robotic thyroidectomy is inferior to transoral robotic thyroidectomy in drainage and cosmetic satisfaction but superior to bilateral axillo-breast approach endoscopic thyroidectomy in surgical performance. Its operation time is longer, but its cosmetic satisfaction is higher than open thyroidectomy.
Topics: Humans; Thyroidectomy; Robotic Surgical Procedures; Neck Dissection; Breast; Thyroid Neoplasms; Retrospective Studies; Treatment Outcome; Postoperative Complications
PubMed: 38228051
DOI: 10.1016/j.bjorl.2023.101376 -
Systematic Reviews May 2024Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Thyroid dysfunction is common in older people, with females at higher risk. Evidence suggests that thyroid-stimulating hormone (TSH) levels naturally increase with age. However, as uniform serum TSH reference ranges are applied across the adult lifespan, subclinical hypothyroidism (SCH) diagnosis is more likely in older people, with some individuals also being commenced treatment with levothyroxine (LT4). It is unclear whether LT4 treatment in older people with SCH is associated with adverse cardiovascular or bone health outcomes.
METHODS
A systematic review and meta-analysis were performed to synthesise previous studies evaluating cardiovascular and bone health outcomes in older people with SCH, comparing LT4 treatment with no treatment. PubMed, Embase, Cochrane Library, MEDLINE, and Web of Science databases were searched from inception until March 13, 2023, and studies that evaluated cardiovascular and bone health events in people with SCH over 50 years old were selected.
RESULTS
Six articles that recruited 3853 participants were found, ranging from 185 to 1642 participants, with the proportion of females ranging from 45 to 80%. The paucity of data resulted in analysis for those aged over 65 years only. Additionally, a study with 12,212 participants aged 18 years and older was identified; however, only data relevant to patients aged 65 years and older were considered for inclusion in the systematic review. Of these 7 studies, 4 assessed cardiovascular outcomes, 1 assessed bone health outcomes, and 2 assessed both. A meta-analysis of cardiovascular outcomes revealed a pooled hazard ratio of 0.89 (95% CI 0.71-1.12), indicating no significant difference in cardiovascular risk between older individuals with SCH treated with LT4 compared to those without treatment. Due to overlapping sub-studies, meta-analysis for bone health outcomes was not possible.
CONCLUSIONS
This systematic review and meta-analysis found no significant association between LT4 use and cardiovascular and bone health outcomes in SCH participants over 65 years.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42022308006.
Topics: Humans; Hypothyroidism; Thyroxine; Aged; Cardiovascular Diseases; Female; Bone Density; Male; Middle Aged
PubMed: 38720372
DOI: 10.1186/s13643-024-02548-7 -
Frontiers in Immunology 2024The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND PURPOSE
The objective of this study is to evaluate the risk of secondary autoimmune diseases in multiple sclerosis (MS) patients treated with alemtuzumab (ALZ) through a meta-analysis.
METHODS
PubMed, Web of Science, OVID, EMBASE, and Cochrane central register of controlled trials were searched. Information and data were screened and extracted by 2 researchers. The obtained data were analyzed using the R software meta package. Quality assessment was conducted using the Newcastle-Ottawa Scale (NOS). The causes of heterogeneity were analyzed using subgroup analysis and sensitivity analysis. Publication bias was evaluated using funnel plots and Egger's test.
RESULTS
The search retrieved a total of 3530 papers from the databases. After screening, a total of 37 studies were included in the meta-analysis. The analysis results indicate that the pooled incidence rate of overall secondary autoimmune events (SAEs) in the included studies was 0.2824 [0.2348, 0.3300] (I²=94%, p<0.01). The overall incidence of autoimmune thyroid events (ATE) was 0.2257 [0.1810, 0.2703] (I²=94%, p<0.01). Among them, the rate of serious autoimmune thyroid events (SATE) was 0.0541 [0.0396, 0.0687] (I²=0%, p=0.44). The incidence rates of different thyroid events were as follows: Graves' disease (GD), 0.2266 [0.1632, 0.2900] (I²=83%, p<0.01); Hashimoto thyroiditis (HT), 0.0844 [0.0000, 0.2262] (I²=81%, p=0.02); Hashimoto thyroiditis with hypothyroidism (HTwH), 0.0499 [0.0058, 0.0940] (I²=37%, p=0.21); fluctuating thyroid dysfunction (FTD), 0.0219 [0.0015, 0.0424] (I²=0%, p=0.40); transient thyroiditis (TT), 0.0178 [0.0062, 0.0295] (I²=0%, p=0.94). The overall incidence of hematological events was 0.0431 [0.0274, 0.0621] (I²=70%, p<0.01). The incidence rates from high to low were as follows: lymphopenia, 0.0367 [0.0000, 0.0776] (I²=81%, p=0.02); Idiopathic thrombocytopenic purpura (ITP), 0.0258 [0.0199, 0.0323] (I²=25%, p=0.15); Hemolytic anemia (HA), 0.0177 [0.0081, 0.0391] (I²=29%, p=0.23); pancytopenia, 0.0136 [0.0000, 0.0314] (I²=0%, p=0.67); Neutropenia, 0.0081 [0.0000, 0.0183] (I²=0%, p=0.42). After excluding thyroid and hematological diseases, the combined incidence of other related SAEs was 0.0061 [0.0014, 0.0109] (I²=50%, p=0.02). The incidence of each disease ranked from highest to lowest as: skin psoriasis (SP), 0.0430 [0.0000, 0.0929] (I²=0%, p=0.57); alopecia areata (AA), 0.0159 [0.0024, 0.0372] (I²=19%, p=0.29); vitiligo, 0.0134 [0.0044, 0.0223] (I²=0%, p=0.81); inflammatory atrichia (IA), 0.0103 [0.0000, 0.0232] (I²=0%, p=0.43); chronic urticaria (CU), 0.0107 [0.0000, 0.0233] (I²=0%, p=0.60); and nephropathy, 0.0051 [0.0000, 0.0263] (I²=62%, p=0.02).
CONCLUSION
The occurrence of secondary autoimmune diseases in patients with MS treated with ALZ is noteworthy, particularly in the form of thyroid events and hematological events. Clinicians should monitor the overall condition of patients promptly for early management and avoid delayed diagnosis and treatment.
SYSTEMATIC REVIEW REGISTRATION
inplasy.com/inplasy-2024-4-0048/, identifier INPLASY202440048.
Topics: Humans; Alemtuzumab; Multiple Sclerosis; Autoimmune Diseases; Incidence; Hashimoto Disease
PubMed: 38690271
DOI: 10.3389/fimmu.2024.1343971 -
BMC Pulmonary Medicine Dec 2023Tislelizumab is an anti-programmed death-1 (PD-1) monoclonal antibody with a construction that enables it to have a higher affinity to its target. We aimed to evaluate...
The safety and efficacy of tislelizumab, alone or in combination with chemotherapy, for the treatment of non-small cell lung cancer: a systematic review of clinical trials.
BACKGROUND
Tislelizumab is an anti-programmed death-1 (PD-1) monoclonal antibody with a construction that enables it to have a higher affinity to its target. We aimed to evaluate tislelizumab's safety and efficacy for treating non-small cell lung cancer (NSCLC).
METHODS
Embase, Scopus, PubMed, Web of Science, and Google Scholar were searched up to December 20, 2022. The review only included randomized controlled trials (RCTs) that evaluated the safety or efficacy of tislelizumab for treating patients with lung cancer. The revised Cochrane risk-of-bias tool (RoB2) was utilized to evaluate study quality.
RESULTS
There were four RCTs identified, which included 1565 patients with confirmed locally advanced or metastatic squamous and/or non-squamous types of NSCLC. Treatment with tislelizumab was associated with better progression-free survival (PFS) and objective response rate (ORR), particularly when used in combination with chemotherapy. Almost all patients in both arms reported at least one treatment-emergent adverse event (TEAE). Decreased hematologic indexes accounted for more than 20% of the grade ≥ 3 TEAEs in the tislelizumab plus chemotherapy group. The proportion of TEAE that led to death in the tislelizumab plus chemotherapy arms ranged from 3.2 to 4.2%. Hypothyroidism, pneumonitis, and hyperglycemia were the most frequently noted immune-mediated adverse events in the tislelizumab group.
CONCLUSIONS
Tislelizumab, whether used alone or in combination with chemotherapy, seems to demonstrate both a safety and efficacy as a treatment for NSCLC.
Topics: Humans; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Randomized Controlled Trials as Topic
PubMed: 38066549
DOI: 10.1186/s12890-023-02755-3 -
Medicine Jun 2024Chronic systolic heart failure (CSHF) is a significant health burden with high morbidity and mortality. The role of subclinical hypothyroidism (SCH) in the prognosis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic systolic heart failure (CSHF) is a significant health burden with high morbidity and mortality. The role of subclinical hypothyroidism (SCH) in the prognosis of CSHF patients remains a critical area of inquiry. This systematic review and meta-analysis aim to elucidate the impact of SCH on the prognosis of patients with CSHF.
METHODS
Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, this meta-analysis employed a comprehensive search strategy across major databases including PubMed, Embase, Web of Science, and the Cochrane Library. The Patient, Intervention, Comparison, Outcome framework guided the inclusion of studies focusing on patients with CSHF, comparing those with and without SCH. Quality assessment was performed using the Newcastle-Ottawa scale. Statistical analyses assessed heterogeneity and publication bias, employing fixed-effect or random-effects models based on heterogeneity levels.
RESULTS
From an initial pool of 1439 articles, 8 studies met the stringent inclusion criteria. These studies, conducted across diverse geographical regions, highlighted the relationship between SCH and all-cause mortality, cardiac events, and subgroup differences in CSHF patients. The meta-analysis revealed SCH as a significant risk factor for all-cause mortality (HR = 1.42) and cardiac events (HR = 1.46). Subgroup analysis indicated variability in risk based on region, sample size, age, and follow-up duration. Sensitivity analysis confirmed the stability of these findings, and publication bias assessment indicated symmetric funnel plot and nonsignificant Egger test results.
CONCLUSIONS
SCH emerges as a predictive factor for all-cause mortality, cardiovascular events, and rehospitalization in CSHF patients. This finding underscores the importance of screening for SCH in CSHF patients, highlighting its potential role in improving patient prognosis.
Topics: Humans; Hypothyroidism; Heart Failure, Systolic; Prognosis; Chronic Disease; Risk Factors
PubMed: 38847701
DOI: 10.1097/MD.0000000000038410 -
BMC Endocrine Disorders Jun 2024Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Persistent symptoms in hypothyroid patients despite normalized TSH levels suggest the need for alternative treatments. This study aims to evaluate the effectiveness of combined T4 and T3 therapy or desiccated thyroid (DTE) compared to T4 monotherapy, with a focus on thyroid profile, lipid profile, and quality of life metrics.
METHODS
We conducted a systematic review in Embase, Medline/PubMed, and Web of Science up to 11/23/2023. We used the following keywords: "Armour Thyroid," OR "Thyroid extract," OR "Natural desiccated thyroid," OR "Nature-Throid," "desiccated thyroid," OR "np thyroid," OR "Synthroid," OR "levothyroxine," OR "Liothyronine," "Cytomel," OR "Thyroid USP," OR "Unithroid." AND "hypothyroidism. " We only included RCTs and excluded non-RCT, case-control studies, and non-English articles.
RESULTS
From 6,394 identified records, 16 studies qualified after screening and eligibility checks. We included two studies on desiccated thyroid and 15 studies on combined therapy. In this meta-analysis, combination therapy with T4 + T3 revealed significantly lower Free T4 levels (mean difference (MD): -0.34; 95% CI: -0.47, -0.20), Total T4 levels (mean difference: -2.20; 95% CI: -3.03, -1.37), and GHQ-28 scores (MD: -2.89; 95% CI: -3.16, -2.63), compared to T4 monotherapy. Total T3 levels were significantly higher in combined therapy (MD: 29.82; 95% CI: 22.40, 37.25). The analyses demonstrated moderate to high heterogeneity. There was no significant difference in Heart Rate, SHBG, TSH, Lipid profile, TSQ-36, and BDI Score. Subjects on DTE had significantly higher serum Total T3 levels (MD: 50.90; 95% CI: 42.39, 59.42) and significantly lower serum Total T4 (MD: -3.11; 95% CI: -3.64, -2.58) and Free T4 levels (MD: -0.50; 95% CI: -0.57, -0.43) compared to T4 monotherapy. Moreover, DTE treatment showed modestly higher TSH levels (MD: 0.49; 95% CI: 0.17, 0.80). The analyses indicated low heterogeneity. There was no significant difference in Heart Rate, SHBG, Lipid profile, TSQ-36, GHQ-28, and BDI Score.
CONCLUSIONS
Our study revealed that combined therapy and DTE lead to higher T3 and lower T4 levels, compared to T4 monotherapy in hypothyroidism. However, no significant effects on heart rate, lipid profile, or quality of life were noted. Given the heterogeneity of results, personalized treatment approaches are recommended.
Topics: Humans; Hypothyroidism; Thyroxine; Triiodothyronine; Drug Therapy, Combination; Quality of Life; Treatment Outcome; Hormone Replacement Therapy; Thyroid Gland
PubMed: 38877429
DOI: 10.1186/s12902-024-01612-6 -
Frontiers in Endocrinology 2024Subacute thyroiditis (SAT) is a self-limiting and inflammatory thyroid disease. Although SAT usually improves on its own within weeks, it needs treatment when patients... (Meta-Analysis)
Meta-Analysis Comparative Study
IMPORTANCE
Subacute thyroiditis (SAT) is a self-limiting and inflammatory thyroid disease. Although SAT usually improves on its own within weeks, it needs treatment when patients have pain, fever, and symptoms of thyrotoxicosis. Therapeutic drugs mainly include non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids. Currently, there is no systematic review or meta-analysis of the comparison of outcomes between NSAIDs and glucocorticoids for the treatment of SAT.
OBJECTIVES
To conduct a systematic review and meta-analysis on the outcomes in subacute thyroiditis patients treated with glucocorticoids or NSAIDs.
DATA SOURCES
Using the four electronic databases, including PubMed, Embase, Cochrane Library, Wanfang database and Web of Science. All publications until 21 June 2023 were searched. The reference lists of all selected articles were independently screened to identify additional studies left out in the initial search.
STUDY SELECTION
The literature comparing outcomes between glucocorticoids and non-steroidal anti-inflammatory drugs for patients with subacute thyroiditis will be included.
DATA EXTRACTION AND SYNTHESIS
Two independent investigators (Anqi Yuan and Jialu Wu) extracted the data following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines (PRISMA) and then evaluated the quality of the eligible studies with the Newcastle-Ottawa Scale. Fixed-effects models for the meta-analyses were applied. Heterogeneity was assessed with the chi-squared (x²) test (Cochran's Q) and inconsistency index (I²). The robustness of the results was tested with the sensitivity analyses. The bias of publication was assessed with the Harbord test.
MAIN OUTCOMES AND MEASURES
The incidence of permanent hypothyroidism in SAT patients treated with corticosteroids or NSAIDs.
RESULTS
Our study included a total of ten comparative cohort studies with 1337 participants. We found that the incidence of developing permanent hypothyroidism in the SAT patients who received glucocorticoids treatment was significantly lower than those who received NSAIDs treatment. (OR, 0.56; 95% CI, 0.36-0.88; P = 0.01). The risk of permanent hypothyroidism in patients who received prednisone at an average initial dose < 40 mg/d was significantly lower than that in patients who received NSAIDs (OR, 0.37; 95% CI, 0.14-0.94; P = 0.04). There was no significant difference in the occurrence of permanent hypothyroidism between SAT patients who received an average initial dose ≥ 40 mg/d of prednisone and those who received only NSAIDs (OR, 0.7; 95% CI, 0.14-3.53; P = 0.67). In addition, the recurrence rate was observably higher in those receiving glucocorticoids than in those receiving NSAIDs (OR, 1.98; 95% CI, 1.12-3.5; p = 0.02). The recurrence rate was significantly higher in patients with an average initial prednisone dose of < 40 mg/d than in the NSAIDs group. There was no significant difference in the recurrence rate between patients in the mean initial prednisone dose ≥ 40 mg/d group and those in the NSAIDs group.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, we compared the treatment outcomes of SAT patients between glucocorticoids and NSAIDs. Our results indicated that glucocorticoid treatment was associated with a lower incidence of permanent hypothyroidism than NSAID treatment. Patients treated with NSAIDs might have a lower recurrence rate. This finding might help to understand the outcome of the disease when choosing different drugs and help physicians to make appropriate decisions.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/, identifier CRD42023427332.
Topics: Humans; Anti-Inflammatory Agents, Non-Steroidal; Thyroiditis, Subacute; Glucocorticoids; Treatment Outcome
PubMed: 38715797
DOI: 10.3389/fendo.2024.1384365 -
BMC Pregnancy and Childbirth Apr 2024In this umbrella review, we systematically evaluated the evidence from meta-analyses and systematic reviews of maternal factors associated with low birth weight.
BACKGROUND
In this umbrella review, we systematically evaluated the evidence from meta-analyses and systematic reviews of maternal factors associated with low birth weight.
METHODS
PubMed, Scopus, and Web of Science were searched to identify all relevant published studies up to August 2023. We included all meta-analysis studies (based on cohort, case-control, cross-sectional studies) that examined the association between maternal factors (15 risk factors) and risk of LBW, regardless of publication date. A random-effects meta-analysis was conducted to estimate the summary effect size along with the 95% confidence interval (CI), 95% prediction interval, and heterogeneity (I) in all meta-analyses. Hedges' g was used as the effect size metric. The effects of small studies and excess significance biases were assessed using funnel plots and the Egger's test, respectively. The methodological quality of the included studies was assessed using the AMSTAR 2 tool.
RESULTS
We included 13 systematic Review with 15 meta-analysis studies in our study based on the inclusion criteria. The following 13 maternal factors were identified as risk factors for low birth weight: crack/cocaine (odds ratio [OR] 2.82, 95% confidence interval [CI] 2.26-3.52), infertility (OR 1.34, 95% CI 1.2-1.48), smoking (OR 2.00, 95% CI 1.76-2.28), periodontal disease (OR 2.41, 95% CI 1.67-3.47), depression (OR 1.84, 95% CI 1.34-2.53), anemia (OR 1.32, 95% CI 1.13-1.55), caffeine/coffee (OR 1.34, 95% CI 1.14-1.57), heavy physical workload (OR 1.87, 95% CI 1.00-3.47), lifting ≥ 11 kg (OR 1.59, 95% CI 1.02-2.48), underweight (OR 1.79, 95% CI 1.20-2.67), alcohol (OR 1.23, 95% CI 1.04-1.46), hypertension (OR 3.90, 95% CI 2.73-5.58), and hypothyroidism (OR 1.40, 95% CI 1.01-1.94). A significant negative association was also reported between antenatal care and low birth weight.
CONCLUSIONS
This umbrella review identified drug use (such as crack/cocaine), infertility, smoking, periodontal disease, depression, caffeine and anemia as risk factors for low birth weight in pregnant women. These findings suggest that pregnant women can reduce the risk of low birth weight by maintaining good oral health, eating a healthy diet, managing stress and mental health, and avoiding smoking and drug use.
Topics: Humans; Infant, Low Birth Weight; Female; Risk Factors; Pregnancy; Infant, Newborn; Pregnancy Complications; Meta-Analysis as Topic; Systematic Reviews as Topic
PubMed: 38664680
DOI: 10.1186/s12884-024-06487-y -
Frontiers in Oncology 2024Endocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive...
OBJECTIVE
Endocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive systematic review and meta-analysis to evaluate the risk of immune-related endocrinopathies in patients treated with PD-1 inhibitors.
METHODS
We performed a systematic search in the PubMed, Embase, and Cochrane Library databases to retrieve all randomized controlled trials (RCTs) involving PD-1 inhibitors, spanning from their inception to November 24, 2023. The comparative analysis encompassed patients undergoing chemotherapy, targeted therapy, or receiving placebo as control treatments. This study protocol has been registered with PROSPERO (CRD42023488303).
RESULTS
A total of 48 clinical trials comprising 24,514 patients were included. Compared with control groups, patients treated with PD-1 inhibitors showed an increased risk of immune-related adverse events, including hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, diabetes mellitus, and adrenal insufficiency. Pembrolizumab was associated with an increased risk of all aforementioned endocrinopathies (hypothyroidism: RR=4.76, 95%CI: 3.55-6.39; hyperthyroidism: RR=9.69, 95%CI: 6.95-13.52; hypophysitis: RR=5.47, 95%CI: 2.73-10.97; thyroiditis: RR=5.95, 95%CI: 3.02-11.72; diabetes mellitus: RR=3.60, 95%CI: 1.65-7.88; adrenal insufficiency: RR=4.80, 95%CI: 2.60-8.88). Nivolumab was associated with an increased risk of hypothyroidism (RR=7.67, 95%CI: 5.00-11.75) and hyperthyroidism (RR=9.22, 95%CI: 4.71-18.04). Tislelizumab and sintilimab were associated with an increased risk of hypothyroidism (RR=19.07, 95%CI: 5.46-66.69 for tislelizumab and RR=18.36, 95%CI: 3.58-94.21 for sintilimab). For different tumor types, both hypothyroidism and hyperthyroidism were at high risks. Besides, patients with non-small cell lung cancer were at a higher risk of thyroiditis and adrenal insufficiency. Patients with melanoma were at a higher risk of hypophysitis and diabetes mellitus. Both low- and high-dose group increased risks of hypothyroidism and hyperthyroidism.
CONCLUSION
Risk of endocrine irAEs may vary in different PD-1 inhibitors and different tumor types. Increased awareness and understanding of the risk features of endocrine irAEs associated with PD-1 inhibitors is critical for clinicians.
SYSTEMATIC REVIEW REGISTRATION
crd.york.ac.uk/prospero, identifier PROSPERO (CRD42023488303).
PubMed: 38756658
DOI: 10.3389/fonc.2024.1381250