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Cancers Aug 2023(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to... (Review)
Review
(1) Background: Radiotherapy (RT) is a central component for the treatment of many head and neck cancers. In this systematic review of the literature, we aimed to characterize and quantify the published evidence on RT-related hypothyroidism, including estimated incidence, clinical risk factors, and dosimetric parameters that may be used to guide clinical decision making. Furthermore, we aimed to identify potential areas of improvement in the prevention and clinical management of RT-induced hypothyroidism, including the role of modern advanced therapeutic techniques. (2) Methods: We conducted a systemic review of the literature in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. PubMed and Google Scholar were searched to identify original research articles describing the incidence, mechanism, dosimetry, treatment, or prevention of radiation-related hypothyroidism for adults receiving RT for the treatment of head and neck cancers. The snowball method was used to identify additional articles. For identified articles, we tabulated several datapoints, including publication date, patient sample size, estimated hypothyroidism incidence, cancer site/type, follow-up period, radiation modality and technique, use of multimodality therapy, method of thyroid function evaluation, and proposed dosimetric predictors of hypothyroidism. (3) Results: One hundred and eleven articles met inclusion criteria, reflecting a range of head and neck cancer subtypes. There was a large variation in the estimated incidence of RT-related hypothyroidism, with a median estimate of 36% (range 3% to 79%). Reported incidence increased in later publication dates, which was likely related to improved screening and longer follow up. There were a wide variety of predictive metrics used to identify patients at high risk of hypothyroidism, the most common of which were volumetric and mean dosimetrics related to the thyroid gland (Vxx%, Dmean). More recently, there has been increasing evidence to suggest that the thyroid gland volume itself and the volume of the thyroid gland spared from high-dose radiation (VSxx) may better predict thyroid function after RT. There were no identified studies investigating the role of advanced radiotherapeutic techniques such as MRI-guided RT or particle therapy to decrease RT-related hypothyroidism. Conclusions: Hypothyroidism is a common toxicity resulting from therapeutic radiation for head and neck cancer with recent estimates suggesting 40-50% of patients may experience hypothyroidism after treatment. Dosimetric predictive models are increasingly able to accurately identify patients at risk of hypothyroidism, especially those utilizing thyroid VS metrics. Further investigation regarding the potential for advanced radiotherapeutic therapies to decrease RT-induced thyroid dysfunction is needed.
PubMed: 37686597
DOI: 10.3390/cancers15174321 -
Ear, Nose, & Throat Journal Aug 2023Thyroid nodules are common entities, with 5% malignancy. Differentiated thyroid cancer represents 90% of thyroid malignancies, with papillary carcinoma being the most... (Review)
Review
Effectiveness and Safety of Percutaneous Treatment in Lesions Suggestive of Thyroid Cancer (Bethesda V and VI-T1aN0M0) Compared to Surgical Treatment: Systematic Review and Meta-Analysis.
INTRODUCTION
Thyroid nodules are common entities, with 5% malignancy. Differentiated thyroid cancer represents 90% of thyroid malignancies, with papillary carcinoma being the most common. Management is generally surgical; among its complications are injury to the recurrent laryngeal and superior laryngeal nerve, causing hoarseness, postsurgical hypoparathyroidism, hypothyroidism, and pain. Other noninvasive percutaneous interventions of thermal ablation such as microwave, radiofrequency, or laser incur lower costs and could be an option for treatment.
OBJECTIVE
To determine the effectiveness and safety of thermal ablation in lesions suspected of thyroid cancer (Bethesda V and VI/T1aN0M0) compared to surgical treatment.
METHODS
Systematic review/meta-analysis of observational studies and clinical trials. Database search includes MEDLINE/PUBMED, Embase, Scopus, Scielo, and BVS/LILACS. Studies on patients over 18 years of age with lesions suspicious of thyroid cancer were included.
RESULTS
A total of 10 studies were obtained, with 2939 patients: 1468 subjected to thermal ablation and 1471 to surgery. Regarding effectiveness, no differences were found in local recurrence [relative risk (RR) 1.17 (95% CI 0.69-1.99)] and cervical lymph node metastasis [RR 0.76 (95% CI 0.43-1.36)]. Regarding safety, infection [RR 0.29 (95% CI 0.05-1.74)], hematoma [RR 0.57 (95% CI 0.17-1.94)], and transient hoarseness [RR 0.77 (95% CI 0.39-1.51)] were evaluated, without difference. However, permanent hoarseness had significant differences in favor of thermal ablation [RR 0.29 (95% CI 0.11-0.75)].
CONCLUSIONS
Thermal ablation for the treatment of T1aN0M0 papillary thyroid carcinoma is equally effective when compared to surgical techniques and offers a better safety profile, particularly in permanent hoarseness.
PubMed: 37605444
DOI: 10.1177/01455613231189067 -
Acta Endocrinologica (Bucharest,... 2023Graves' disease is the most prevalent cause of hyperthyroidism worldwide. Adiponectin, the most abundant adipokine, plays a significant role in a cluster of prevalent... (Review)
Review
CONTEXT
Graves' disease is the most prevalent cause of hyperthyroidism worldwide. Adiponectin, the most abundant adipokine, plays a significant role in a cluster of prevalent diseases connected to metabolic disorders.
OBJECTIVE
Although the association between adiponectin and Graves' disease has been studied, the existing data is inconsistent. Therefore, we conducted this systematic review and meta-analysis to evaluate the relationship between adiponectin levels and Graves' disease.
METHODS
We performed a systematic electronic search on PubMed, EMBASE, Scopus and Cochrane Library using predefined keywords. We used the NHLBI quality assessment tools to assess the included studies.
RESULTS
There were 11 studies involving 781 subjects included in our qualitative synthesis, while 6 studies were included in our quantitative synthesis. We observed significantly increased adiponectin levels in Graves' disease patients compared to controls (MD 2.983 [95% CI 0.138-5.828]) and hypothyroidism patients (MD 3.389 [95% CI 1.332-5.446]). Nevertheless, no significant MD was observed when comparing Graves' disease patients with and without Graves' ophthalmopathy (MD -27.124 [95% CI -88.893 - 34.645]).
CONCLUSIONS
Adiponectin levels were significantly higher in patients with Graves' disease compared to controls and hypothyroidism patients. However, patients with and without Graves' ophthalmopathy did not present a significant mean difference in adiponectin levels.
PubMed: 37601709
DOI: 10.4183/aeb.2023.87 -
Frontiers in Immunology 2023The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
The combination of nanoparticle albumin-bound paclitaxel (nab-PTX)/paclitaxel (PTX) with immune checkpoint inhibitors (ICIs) has demonstrated significant efficacy in cancer patients. However, the safety of these combination regimens remains conflicting in former researches. Therefore, in order to address this issue, we performed a systematic review and network meta-analysis (NMA) to evaluate and compare the safety profile.
METHODS
We performed a systematic review by searching randomized controlled trials (RCTs) from PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, and Web of Science up to August 15, 2022. The primary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) immune-related adverse events (irAEs). Secondary outcomes were all-grade (grade 1-5) and high-grade (grade 3-5) irAEs of subgroups of ICIs.
RESULTS
There were 22 RCTs included in the NMA, involving a total of 15 963 patients diagnosed with any type of cancer. ICIs+nab-PTX was associated with a noticeably decreased risk of grade 3-5 pneumonitis (odds ratio [OR]=0.28, 95% credible interval [CrI]: 0.09,0.90) compared to ICI monotherapy; ICIs+PTX showed a lower risk of grade 1-5 hyperthyroidism (OR=0.46, 95% CrI: 0.22-0.96) and grade 1-5 hypothyroidism (OR=0.49, 95% CrI: 0.26-0.93) than ICIs. Compared with PD-1, PD-1+PTX was associated with a statistically significantly lower risk of grade 1-5 pneumonitis (OR=0.32, 95% CrI: 0.11-0.92). PD-L1 resulted in a noticeably lower risk of grade 1-5 hypothyroidism (OR=0.34, 95% CrI: 0.12-1.00) than PD-L1+PTX. Nearly all treatment regimens containing ICIs demonstrated significantly higher risks of irAEs compared to the standard chemotherapy groups.
CONCLUSION
Nab-PTX/PTX+ICIs demonstrated an approach leading to decreased risk of irAEs compared with ICI monotherapy. This finding supports that ICIs+nab-PTX/PTX may be a safer treatment strategy. Moreover, we also found that the combination regimens containing ICIs had a higher risk of irAEs than standard chemotherapy. Additionally, ICIs+nab-PTX demonstrated a decreased risk of irAEs compared to ICIs+PTX. PD-1 inhibitors were associated with a higher risk of irAEs than PD-L1 inhibitors.
Topics: Humans; Immune Checkpoint Inhibitors; B7-H1 Antigen; Antineoplastic Agents, Immunological; Programmed Cell Death 1 Receptor; Network Meta-Analysis; Neoplasms; Paclitaxel; Hypothyroidism; Pneumonia
PubMed: 37520574
DOI: 10.3389/fimmu.2023.1175809 -
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 -
The Journal of Maternal-fetal &... Dec 2023This study aimed to explore the effects of levothyroxine on pregnancy outcomes and thyroid function in recurrent pregnancy loss (RPL) women with subclinical... (Meta-Analysis)
Meta-Analysis Review
Effect of levothyroxine on the pregnancy outcomes in recurrent pregnancy loss women with subclinical hypothyroidism and thyroperoxidase antibody positivity: a systematic review and meta-analysis.
OBJECTIVE
This study aimed to explore the effects of levothyroxine on pregnancy outcomes and thyroid function in recurrent pregnancy loss (RPL) women with subclinical hypothyroidism (SCH) or thyroperoxidase antibody positivity (TPOAb).
METHODS
Literature search was performed from inception to 24 June 2022. The heterogeneity for each outcome was evaluated using Cochran's test and quantified with I-squared (). Pooled effect sizes were expressed as relative risk (RR) and weighted mean differences (WMD) with 95% confidence intervals (95% CIs). Stability of the results were assessed using the sensitivity analysis.
RESULTS
Fifteen eligible studies with 1911 participants were included in this meta-analysis. The pooled data showed that levothyroxine decreased premature delivery rate (RR = 0.48, 95%CI: 0.32, 0.72), miscarriage rate (RR = 0.59, 95%CI: 0.44, 0.79), premature rupture of membranes (PROM) rate (RR = 0.44, 95%CI: 0.29, 0.66), and fetal growth restriction rate (RR = 0.33, 95%CI: 0.12, 0.89) in RPL women with TPOAb. In RPL women with SCH, live birth rate was elevated (RR = 1.20, 95%CI: 1.01, 1.42) and miscarriage rate was reduced (RR = 0.65, 95%CI: 0.44, 0.97) by levothyroxine. In addition, levothyroxine substantially decreased TSH level (WMD = -0.23, 95% CI: -0.31, -0.16) and TPO level (WMD = -23.48, 95%CI: -27.50, -19.47).
CONCLUSIONS
Levothyroxine improved pregnancy outcomes and thyroid function in RPL women with TPOAb or SCH, indicating that levothyroxine may be beneficial for RPL women if TPOAb or SCH occurs. Future studies are needed to verify our findings.
Topics: Pregnancy; Female; Humans; Thyroxine; Pregnancy Outcome; Hypothyroidism; Premature Birth; Abortion, Habitual
PubMed: 37433649
DOI: 10.1080/14767058.2023.2233039 -
Annals of Agricultural and... Jun 2023A number of studies indicate the presence of a thyroid-gut axis and the important influence of the gut microbiota on thyroid function. As prebiotics, probiotics and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION AND OBJECTIVE
A number of studies indicate the presence of a thyroid-gut axis and the important influence of the gut microbiota on thyroid function. As prebiotics, probiotics and synbiotics show therapeutic potential in the treatment of intestinal dysbiosis, the aim of this review is to evaluate the efficacy of their supplementation in primary thyroid diseases.
REVIEW METHODS
Electronic databases (Ovid MEDLINE, Embase, CENTRAL), registers of clinical trials, and grey literature up to 6 October 2022 were searched for randomised controlled trials (RCTs) meeting pre-specified inclusion criteria. The protocol was registered in PROSPERO (CRD42021235054).
BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE
After screening 1,721 references, two RCTs were identified, which included 136 hypothyroid participants in total. Meta-analysis of the results after eight weeks of supplementation with predominantly Lactobacillus and Bifidobacterium strains indicated a clinically and statistically nonsignificant decrease in TSH (MD -0.19 mIU/L; 95% CI -0.43 to 0.06; I= 0%), and no effect on fT levels (MD 0.01 pg/mL; 95% CI-0.16 to 0.18; I= 0%). Data from single studies indicated no significant change in the levels of fT4, thyroid auto-antibodies, BMI, levothyroxine doses, and severity of symptoms measured with validated scales. Only constipation scores showed significant improvement (MD -8.71 points in the Faecal Incontinence Questionnaire; 95% CI -15.85 to -1.57; I= 0%).
SUMMARY
Low-certainty evidence from two randomised trials, suggests that routine administration of probiotics, prebiotics or synbiotics may result in little to no benefit in patients with primary hypothyroidism.
Topics: Humans; Prebiotics; Synbiotics; Probiotics; Thyroid Diseases
PubMed: 37387369
DOI: 10.26444/aaem/162732 -
The Lancet Regional Health. Southeast... Oct 2022Congenital hypothyroidism (CH) is the leading cause of preventable mental retardation, which is currently not universally screened in India. Knowledge of the...
BACKGROUND
Congenital hypothyroidism (CH) is the leading cause of preventable mental retardation, which is currently not universally screened in India. Knowledge of the country-specific prevalence of the disease can guide in establishing a universal screening program.
METHODS
We performed a systematic review and meta-analysis to assess the prevalence, screen positivity rates, compliance to recall and etiology of CH in India. The databases of PubMed, Embase, Google scholar and IMSEAR were searched on 1 October 2021. All observational studies reporting at least one of the outcomes of interest were included. Two reviewers independently extracted the data and appraised the quality of studies using the Joanna Briggs tool for prevalence studies. Estimates were pooled using a random-effects model with double arcsine transformation (MetaXL software). PROSPERO database registration number was CRD42021277523.
FINDINGS
Of the 2 073 unique articles retrieved, 70 studies were eligible for inclusion. The prevalence of CH (per 1 000 neonates screened) was 0·97 (95% confidence intervals/CI: 0·9, 1·04) in non-endemic areas (54 studies and 819 559 neonates), 79 (95% CI: 72, 86) in endemic areas (3 studies, 5 060 neonates), 50 (95% CI: 31, 72) in neonates born to mothers with thyroid disorders, and 14 (95% CI: 8, 22) in preterm neonates. At thyroid stimulation hormone cut-off of 20 mIU/L, the screen positivity rates were 5·6% (95% CI: 5·4%, 5·9%) for cord blood samples and 0·19% (95% CI: 0·18%, 0·2%) for postnatal sample. About 70% (95% CI: 70, 71) of screen positive neonates were retested with diagnostic tests. Among neonates with permanent hypothyroidism, thyroid dysgenesis 56·6% (95% CI: 50·9%, 62·2%) was more common than dyshormonogenesis 38·7% (95% CI: 33·2%, 44·3%).
INTERPRETATION
The prevalence of congenital hypothyroidism in India is higher than global estimates. Screen positivity rate was higher for cord blood screening when compared to postnatal screening. Compliance with confirmatory testing was higher for cord blood screening.
FUNDING
The study was not funded by any source.
PubMed: 37383660
DOI: 10.1016/j.lansea.2022.100040 -
Journal of Maxillofacial and Oral... Mar 2023Mucormycosis emerged as a wildfire in post-covid-19 infected patients. Most frequently involved sites of mucormycosis are rhino-orbital, rhino-sinusal and... (Review)
Review
INTRODUCTION
Mucormycosis emerged as a wildfire in post-covid-19 infected patients. Most frequently involved sites of mucormycosis are rhino-orbital, rhino-sinusal and rhino-orbito-cerebral. The hallmark sign of mucormycosis is tissue necrosis, which is often a late sign. The fatality rate of mucormycosis is 46% globally. Despite early aggressive combined surgical and medical therapy, the prognosis of mucormycosis is poor.
METHODS
We searched the electronic database of PubMed, web of science, Embase, Scopus and Google Scholar from Jan 2020 until December 2021 using keywords. We retrieved all the granular details of original research articles, case reports/series of patients with rhino-orbito-cerebral mucormycosis (ROCM), and COVID-19 reported worldwide. Subsequently, we analyzed the patient characteristics, associated comorbidities, location of mucormycosis, treatment given and its outcome in people with COVID-19. (Prospero registration-CRD42021256830, June 4, 2021).
RESULTS
Overall, 544 rhino-orbito-cerebral mucormycosis patients were included in our review with a history of Covid-19 infection. Out of which 410 patients had diabetes mellitus which has proven to be major contributing immunocompromised disease. Other diseases like hypertension, chronic kidney diseases, hypothyroidism, etc., were also attributed as an immunocompromised disease causing increased number of covid associated mucormycosis cases. We found out that total number of patients alive after taking only antifungal drug treatment were 25 in number, whereas total number of patients alive when antifungal drugs were combined with surgical intervention were 428 which was significantly higher.
CONCLUSION
Our systematic review concluded that surgical debridement should be performed whenever feasible in parallel to antifungal treatment in order to reduce the mortality rate of COVID-19 associated rhino-orbito-cerebral mucormycosis patients.
PubMed: 37362874
DOI: 10.1007/s12663-023-01878-8 -
Frontiers in Endocrinology 2023The optimal first-line immune checkpoint inhibitor (ICI) treatment strategy for metastatic or early triple-negative breast cancer (TNBC) has not yet been determined as a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal first-line immune checkpoint inhibitor (ICI) treatment strategy for metastatic or early triple-negative breast cancer (TNBC) has not yet been determined as a result of various randomized controlled trials (RCTs). The purpose of this study was to compare the efficacy and safety of ICIs in patients with metastatic or early TNBC.
METHODS
RCTs comparing the efficacy and safety of ICIs in patients with TNBC were included in the studies. Based on PRISMA guidelines, we estimated pooled hazard ratios (HRs) and odds ratios (ORs) using random-effects models of Bayesian network meta-analysis. Primary outcomes were progression-free survival (PFS) and overall survival (OS). Secondary outcomes included pathologic complete response rate (pCR), grade ≥ 3 treatment-related adverse events (trAEs), immune-related adverse events (irAEs), and grade ≥ 3 irAEs.
RESULTS
The criteria for eligibility were met by a total of eight RCTs involving 4,589 patients with TNBC. When ICIs were used in patients without programmed death-ligand 1 (PD-L1) selection, there was a trend toward improved PFS, OS, and pCR, without significant differences. Pembrolizumab plus chemotherapy is superior to other treatment regimens in terms of survival for TNBC patients based on Bayesian ranking profiles. Subgroup analysis by PD-L1 positive population indicated similar results, and atezolizumab plus chemotherapy provided better survival outcomes. Among grade ≥ 3 trAEs and any grade irAEs, there was no statistically significant difference among different ICI agents. The combination of ICIs with chemotherapy was associated with a higher incidence of grade ≥ 3 irAEs. Based on rank probability, the ICI plus chemotherapy group was more likely to be associated with grade ≥ 3 trAEs, any grade irAEs, and grade ≥ 3 irAEs. Hypothyroidism and hyperthyroidism were the most frequent irAEs in patients receiving ICI.
CONCLUSIONS
ICI regimens had relatively greater efficacy and safety profile. Pembrolizumab plus chemotherapy and atezolizumab plus chemotherapy seem to be superior first-line treatments for intention-to-treat and PD-L1-positive TNBC patients, respectively. It may be useful for making clinical decisions to evaluate the efficacy and safety of different ICIs based on our study.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354643.
Topics: Humans; Immune Checkpoint Inhibitors; Triple Negative Breast Neoplasms; B7-H1 Antigen; Network Meta-Analysis; Decision Making
PubMed: 37229447
DOI: 10.3389/fendo.2023.1137464