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Annals of Global Health Jun 2021Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can't excrete excess iron from the bloodstream.
OBJECTIVE
To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major (TM) patients.
METHODS
We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major (TM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses.
FINDINGS
Seventy-four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3-62.6) and in male was higher than female (61.9%, 95% CI 53.4-69.7 vs. 50.9%, CI 41.8-59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8-84 vs. 33.1%, CI 9.4-70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16-40.8).
CONCLUSION
Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients' complications.
Topics: Adolescent; Blood Transfusion; Body Height; Dwarfism; Endocrine System Diseases; Female; Humans; Iron Overload; Male; beta-Thalassemia
PubMed: 34164261
DOI: 10.5334/aogh.3184 -
Neuroendocrinology 2023Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement...
INTRODUCTION
Survival of childhood-onset craniopharyngioma (cCP) is excellent; however, many survivors suffer from hypothalamic-pituitary dysfunction. Growth hormone replacement therapy (GHRT) is of high importance for linear growth and metabolic outcome. Optimal timing for initiation of GHRT in cCP is on debate because of concerns regarding tumor progression or recurrence.
METHODS
A systematic review and cohort studys were performed for the effect and timing of GHRT on overall mortality, tumor progression/recurrence, and secondary tumors in cCP. Within the cohort, cCP receiving GHRT ≤1 year after diagnosis were compared to those receiving GHRT >1 year after diagnosis.
RESULTS
Evidence of 18 included studies, reporting on 6,603 cCP with GHRT, suggests that GHRT does not increase the risk for overall mortality, progression, or recurrent disease. One study evaluated timing of GHRT and progression/recurrence-free survival and found no increased risk with earlier initiation. One study reported a higher than expected prevalence of secondary intracranial tumors compared to a healthy population, possibly confounded by radiotherapy. In our cohort, 75 of 87 cCP (86.2%) received GHRT for median of 4.9 years [0.0-17.1]. No effect of timing of GHRT was found on mortality, progression/recurrence-free survival, or secondary tumors.
CONCLUSION
Although the quality of the evidence is low, the available evidence suggests no effect of GHRT or its timing on mortality, tumor progression/recurrence, or secondary neoplasms in cCP. These results support early initiation of GHRT in cCP aiming to optimize linear growth and metabolic outcome. Prospective studies are needed to increase the level of evidence upon the optimal timing to start GHRT in cCP patients.
Topics: Humans; Cohort Studies; Craniopharyngioma; Human Growth Hormone; Neoplasm Recurrence, Local; Hormone Replacement Therapy; Pituitary Neoplasms; Growth Hormone
PubMed: 37231961
DOI: 10.1159/000531226 -
International Journal of Endocrinology 2022Arginine (ARG) can modulate growth hormone (GH) release by suppressing its endogenous inhibitory regulator, somatostatin. ARG also induces the release of the... (Review)
Review
BACKGROUND
Arginine (ARG) can modulate growth hormone (GH) release by suppressing its endogenous inhibitory regulator, somatostatin. ARG also induces the release of the GH-releasing hormone (GHRH). This study aims to review the effects of L-arginine supplementation alone and combined with GHRH in different doses on GH secretion.
METHODS
In this systematic review and meta-analysis, an electronic literature search was conducted on Medline database (PubMed), Scopus, and Web of Science databases. All eligible studies were randomized clinical trials that reported the effects of ARG supplementation alone or with GHRH on GH levels. Mean difference (MD) and 95% confidence intervals (CI) were computed as the effect size.
RESULTS
Meta-analyses showed significant effects of ARG alone on GH release (MD = 10.07, 95% CI: 7.87, 12.28). Moreover, the response of GH was greater with ARG in combination with GHRH (MD = 24.96, 95% CI: 17.51, 32.42). There was no significant difference between the patients and healthy individuals and between oral and injection use of ARG. The systematic review revealed the important role of ARG in combination with other amino acids on GH secretion in patients with GH deficiency.
CONCLUSION
This study revealed that in GH-deficient individuals, high doses of ARG supplementation in combination with GHRH and/or other amino acids might have potential therapeutic effects on increasing GH concentrations. These findings propose that ARG supplementation can be considered as a potential stimulator in management of GH deficiency.
PubMed: 36467462
DOI: 10.1155/2022/8739289 -
ESMO Open Jun 2023Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a distinct subtype with different prognosis and response... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer is a distinct subtype with different prognosis and response to treatment. HER2-targeted therapy is currently recommended for patients with HR+/HER2+ advanced breast cancer. However, there is debate over which drugs to add on the basis of HER2 blockade yield the optimal efficacy. This systematic review and network meta-analysis was conducted to solve the problem.
METHODS
Eligible randomized controlled trials (RCTs) comparing different interventions in HR+/HER2+ metastatic breast cancer were included. The outcomes of interest included progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Pooled hazard ratios or odds ratios with credible intervals (CrIs) were calculated to estimate the predefined outcomes. The optimal therapeutics were identified by comparing the surface under the cumulative ranking curves (SUCRA).
RESULTS
Totally, 23 literatures of 20 RCTs were included. Regarding PFS, significant differences were detected between single or dual HER2 blockade plus endocrine therapy (ET) versus ET alone and dual HER2 blockade plus ET versus physician's choice. Trastuzumab, pertuzumab plus chemotherapy significantly improved PFS than trastuzumab plus chemotherapy (hazard ratio 0.69, 95% CrI 0.50-0.92). The SUCRA values suggested the relatively better efficacy of dual HER2-targeted therapy plus ET (86%-91%) than chemotherapy (62%-81%) in prolonging PFS and OS. The HER2 blockade-containing regimens showed similar safety profiles in eight documented TRAEs.
CONCLUSIONS
Prominent status of dual-targeted therapy for patients with HR+/HER2+ metastatic breast cancer was revealed. Compared with chemotherapy-containing regimens, the ET-containing ones showed better efficacy and similar safety profiles, which could be recommended in clinical practice.
Topics: Humans; Female; Network Meta-Analysis; Receptor, ErbB-2; Breast Neoplasms; Trastuzumab; Progression-Free Survival
PubMed: 37084609
DOI: 10.1016/j.esmoop.2023.101216 -
International Journal of Molecular... Apr 2023Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between... (Review)
Review
Uterine fibroids are the most common benign tumors in women, with abnormal uterine bleeding (AUB) as the main reported symptom. Additionally, an association between fibroids and infertility has been established, especially if the fibroid protrudes in the uterine cavity. Hormonal therapy is associated with side-effects and as well as hysterectomy, which is incompatible with a desire to conceive. To improve treatment, it is essential to unravel the etiology of fibroid-related symptoms. We aim to evaluate endometrial angiogenesis in women with fibroids, with and without AUB, and the influence of pharmaceutical therapies in these patients. Furthermore, we explore the possible role of altered angiogenesis in patients with fibroids and infertility. We performed a systematic review according to PRISMA-guidelines (PROSPERO: CRD42020169061), and included 15 eligible studies. Endometrial expression of vascular endothelial growth factor (VEGF) and adrenomedullin was increased in patients with fibroids. This suggests aberrant angiogenesis, potentially involving disturbed vessel maturation, resulting in immature and fragile vessels. Treatment with gonadotropin-releasing hormone agonist, ulipristal acetate, and continuous oral contraception pills reduced several angiogenic parameters, including VEGF. If infertile and fertile patients with fibroids were compared, a significant decreased expression of the bone morphogenetic protein/Smad-protein pathway was found, possibly caused by the increased expression of transforming growth factor-beta. For future therapeutic development, these different angiogenic pathways could be of interest as possible targets to treat fibroid-related symptoms.
Topics: Humans; Female; Vascular Endothelial Growth Factor A; Uterine Neoplasms; Leiomyoma; Infertility; Uterine Hemorrhage
PubMed: 37108180
DOI: 10.3390/ijms24087011 -
Biology of Sex Differences Jul 2017In adults, hypothalamus-pituitary-adrenal (HPA) axis activity shows sexual dimorphism, and this is thought to be a mechanism underlying sex-specific disease incidence.... (Review)
Review
BACKGROUND
In adults, hypothalamus-pituitary-adrenal (HPA) axis activity shows sexual dimorphism, and this is thought to be a mechanism underlying sex-specific disease incidence. Evidence is scarce on whether these sex differences are also present in childhood. In a meta-analysis, we recently found that basal (non-stimulated) cortisol in saliva and free cortisol in 24-h urine follow sex-specific patterns. We explored whether these findings could be extended with sex differences in HPA axis reactivity.
METHODS
From inception to January 2016, PubMed and EMBASE.com were searched for studies that assessed HPA axis reactivity in healthy girls and boys aged ≤18 years. Articles were systematically assessed and reported in the categories: (1) diurnal rhythm, (2) cortisol awakening response (CAR), (3) protocolled social stress tests similar or equal to the Trier Social Stress Test for children (TSST-C), (4) pharmacological (ACTH and CRH) stress tests, and (5) miscellaneous stress tests.
RESULTS
Two independent assessors selected 109 out of 6158 records for full-text screening, of which 81 studies (with a total of 14,591 subjects) were included. Studies showed that girls had a tendency towards a more variable diurnal rhythm (12 out of 29 studies), a higher CAR (8 out of 18 studies), and a stronger cortisol response to social stress tests (9 out of 21 studies). We found no evidence for sex differences in cortisol response after a pharmacological challenge or to miscellaneous stress tests.
DISCUSSION
Sex differences in HPA axis reactivity appear to be present in childhood, although evidence is not unequivocal. For a better evaluation of sex differences in HPA axis reactivity, standardization of protocols and reports of stress tests is warranted.
Topics: Adolescent; Child; Child, Preschool; Humans; Hypothalamo-Hypophyseal System; Infant; Infant, Newborn; Pituitary-Adrenal System; Sex Characteristics
PubMed: 28693541
DOI: 10.1186/s13293-017-0144-8 -
Life Sciences Apr 2022Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for... (Review)
Review
AIMS
Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for mammals is still fragmented. We used a systematic review framework to investigate the reproductive impact of microplastics and nanoplastics (MNP) on mammals.
MATERIALS AND METHODS
Research records were screened from Embase, Medline, Scopus and Web of Science. Twelve original papers were identified and reviewed. Immunological, oxidative and morphofunctional outcomes, and the risk of bias in all studies reviewed were analyzed.
KEY FINDINGS
These studies indicated that PP can accumulate in the gonads, triggering seminiferous degeneration, Sertoli cells death, blood-testis barrier disruption, sperm degeneration, malformation, reduced number and mobility, ovarian cysts, reduced follicular growth and granulosa cells death. Gonadal damage was associated with upregulation of prooxidant mediators (oxygen reactive species, lipid and DNA oxidation), cell death, proinflammatory molecular pathways and cytokines, as well as inhibition of enzymatic and non-enzymatic antioxidant defense mechanisms. Spermatogenesis, folliculogenesis, testosterone, progesterone and estrogen levels were also impaired in PP-treated animals, which were potentially associated with down-regulation of molecules involved in germ cells microstructural organization (occludin, N-cadherin, β-catenin and connexin 43) and steroidogenesis, such as hydroxysteroid dehydrogenases, steroidogenic acute regulatory proteins, follicle stimulating and luteinizing hormones. Selection, performance and detection bias were the main limitations identified.
SIGNIFICANCE
Current evidence indicates that PP can induce dose-dependent microstructural and functional gonadal damage, which is orchestrated by pro-oxidant and pro-inflammatory mechanisms that disrupt genes, molecular effectors, and hormones that control spermatogenesis and folliculogenesis.
Topics: Animals; Estrogens; Female; Genitalia; Germ Cells; Granulosa Cells; Inflammation; Intestinal Mucosa; Luteinizing Hormone; Male; Mammals; Microplastics; Ovarian Follicle; Ovary; Oxidative Stress; Plastics; Progesterone; Reproduction; Sertoli Cells; Spermatogenesis; Testis; Testosterone
PubMed: 35176278
DOI: 10.1016/j.lfs.2022.120404 -
International Journal of Molecular... Dec 2022Human placental lactogen (hPL) is a placental hormone which appears to have key metabolic functions in pregnancy. Preclinical studies have putatively linked hPL to... (Meta-Analysis)
Meta-Analysis Review
Human placental lactogen (hPL) is a placental hormone which appears to have key metabolic functions in pregnancy. Preclinical studies have putatively linked hPL to maternal and fetal outcomes, yet-despite human observational data spanning several decades-evidence on the role and importance of this hormone remains disparate and conflicting. We aimed to explore (via systematic review and meta-analysis) the relationship between hPL levels, maternal pre-existing and gestational metabolic conditions, and fetal growth. MEDLINE via OVID, CINAHL plus, and Embase were searched from inception through 9 May 2022. Eligible studies included women who were pregnant or up to 12 months post-partum, and reported at least one endogenous maternal serum hPL level during pregnancy in relation to pre-specified metabolic outcomes. Two independent reviewers extracted data. Meta-analysis was conducted where possible; for other outcomes narrative synthesis was performed. 35 studies met eligibility criteria. No relationship was noted between hPL and gestational diabetes status. In type 1 diabetes mellitus, hPL levels appeared lower in early pregnancy (possibly reflecting delayed placental development) and higher in late pregnancy (possibly reflecting increased placental mass). Limited data were found in other pre-existing metabolic conditions. Levels of hPL appear to be positively related to placental mass and infant birthweight in pregnancies affected by maternal diabetes. The relationship between hPL, a purported pregnancy metabolic hormone, and maternal metabolism in human pregnancy is complex and remains unclear. This antenatal biomarker may offer value, but future studies in well-defined contemporary populations are required.
Topics: Pregnancy; Female; Humans; Placental Lactogen; Placenta; Placental Hormones; Fetal Development; Biomarkers
PubMed: 36555258
DOI: 10.3390/ijms232415621 -
Reproductive Biology and Endocrinology... Oct 2016Women with PCOS have elevated levels of the harmful Advanced Glycation End Products (AGEs), which are highly reactive molecules formed after glycation of lipids and... (Review)
Review
BACKGROUND
Women with PCOS have elevated levels of the harmful Advanced Glycation End Products (AGEs), which are highly reactive molecules formed after glycation of lipids and proteins. Additionally, AGEs accumulate in the ovaries of women with PCOS potentially contributing to the well-documented abnormal steroidogenesis and folliculogenesis.
MAIN BODY
A systematic review of articles and abstracts available in PubMed was conducted and presented in a systemic manner. This article reports changes in steroidogenic enzyme activity in granulosa and theca cells in PCOS and PCOS-models. It also described the changes in AGEs and their receptors in the ovaries of women with PCOS and presents the underlying mechanism(s) whereby AGEs could be responsible for the PCOS-related changes in granulosa and theca cell function thus adversely impacting steroidogenesis and follicular development. AGEs are associated with hyperandrogenism in PCOS possibly by altering the activity of various enzymes such as cholesterol side-chain cleavage enzyme cytochrome P450, steroidogenic acute regulatory protein, 17α-hydroxylase, and 3β-hydroxysteroid dehydrogenase. AGEs also affect luteinizing hormone receptor and anti-Mullerian hormone receptor expression as well as their signaling pathways in granulosa cells.
CONCLUSIONS
A better understanding of how AGEs alter granulosa and theca cell function is likely to contribute meaningfully to a conceptual framework whereby new interventions to prevent and/or treat ovarian dysfunction in PCOS can ultimately be developed.
Topics: 3-Hydroxysteroid Dehydrogenases; Animals; Cholesterol Side-Chain Cleavage Enzyme; Female; Glycation End Products, Advanced; Gonadal Steroid Hormones; Granulosa Cells; Humans; Ovary; Phosphoproteins; Polycystic Ovary Syndrome; Receptors, LH; Receptors, Peptide; Receptors, Transforming Growth Factor beta; Steroid 17-alpha-Hydroxylase; Theca Cells
PubMed: 27769286
DOI: 10.1186/s12958-016-0205-6 -
The Cochrane Database of Systematic... Jan 2009Congenital hypothyroidism (CHT) affects approximately one in 3000 to 4000 infants. CHT is one of the most common preventable causes of learning difficulties. Optimal... (Review)
Review
BACKGROUND
Congenital hypothyroidism (CHT) affects approximately one in 3000 to 4000 infants. CHT is one of the most common preventable causes of learning difficulties. Optimal management of CHT requires early diagnosis and prompt treatment to avoid abnormal neurodevelopmental outcome. One of the main issues in the management of CHT relates to the initial dose of levothyroxine to be used in order to achieve optimal results in terms of intellectual development. Currently, it remains unclear whether high dose thyroid hormone replacement is more effective than low dose in the treatment of CHT. Further research is required to determine an appropriate dose that improves mental and psychomotor developmental outcomes.
OBJECTIVES
To determine the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism.
SEARCH STRATEGY
Randomised controlled trials were identified by searching The Cochrane Library, MEDLINE and EMBASE and reference lists of published papers.
SELECTION CRITERIA
Randomised controlled clinical trials investigating the effects of high versus low dose of initial thyroid hormone replacement for congenital hypothyroidism were included.
DATA COLLECTION AND ANALYSIS
Both authors independently selected trials, assessed risk of bias and extracted data.
MAIN RESULTS
The initial search identified 1014 records which identified 13 publications for further examination. After screening the full text of the 13 selected papers, only one study evaluating 47 babies finally met the inclusion criteria. Using the same cohort at two different time periods, the study investigated the effects of high versus low dose thyroid hormone replacement in relation to (1) time taken to achieve euthyroid status and (2) neurodevelopmental outcome. The study reported that a high dose is more effective in rising serum thyroxine and free thyroxine concentrations to the target range and earlier normalisation of thyroid stimulating hormone compared to a lower dose. Similarly, full scale intelligence quotient was noted to be significantly higher in children who received the high dose compared to the lower dose. However, the verbal intelligence quotient and performance intelligence quotient were similar in both groups. Growth and adverse effects were not reported in the included trial.
AUTHORS' CONCLUSIONS
There is currently only one randomised controlled trial evaluating the effects of high versus low dose of initial thyroid hormone replacement for CHT. There is inadequate evidence to suggest that a high dose is more beneficial compared to a low dose initial thyroid hormone replacement in the treatment of CHT.
Topics: Congenital Hypothyroidism; Hormone Replacement Therapy; Humans; Infant; Infant, Newborn; Thyroxine
PubMed: 19160309
DOI: 10.1002/14651858.CD006972.pub2