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Frontiers in Endocrinology 2023To analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To analyze and determine the safety and efficacy of growth hormone (GH) treatment in Down syndrome (DS) pediatric patients and to weigh ethical aspects involved.
DESIGN
Systematic review and mini meta-analysis of the literature.
METHODS
A search was performed in PubMed, Embase, Scopus, and PsycINFO through August 2022. Eligible studies included those who answered at least one of the following two questions: 1) What is the effect of growth hormone treatment in children with Down syndrome? 2) What are the ethical arguments in favor and against growth hormone treatment for children with Down syndrome? Multiple reviewers independently screened each article for eligibility.
RESULTS
In total sixteen reports detailed medical effects of GH treatment in pediatric DS patients and eight studies dealt with ethical aspects of GH treatment. Treatment with GH resulted in significantly higher growth velocity in patients with DS. The ethical complexity is great but does not present insurmountable difficulties to the therapeutic option.
CONCLUSIONS
As GH treatment is safe and effective for short-term height growth, GH therapy should be considered in long-term treatment of DS children.
Topics: Humans; Child; Human Growth Hormone; Down Syndrome; Body Height; Insulin-Like Growth Factor I
PubMed: 37152958
DOI: 10.3389/fendo.2023.1135768 -
Frontiers in Endocrinology 2023To investigate the efficacy of monotherapy with AIs or GnRHa in improving the height of boys with idiopathic short stature (ISS). (Meta-Analysis)
Meta-Analysis
Comparative efficacy of aromatase inhibitors and gonadotropin-releasing hormone analogue in increasing final height of idiopathic short stature boys: a network meta-analysis.
OBJECTIVE
To investigate the efficacy of monotherapy with AIs or GnRHa in improving the height of boys with idiopathic short stature (ISS).
METHOD
We performed a systematic search in Pubmed, The Cochrane Library, Chinese National Knowledge Infrastructure databases, and Wanfang Database for eligible studies. The network meta-analysis was conducted using STATA software.
RESULTS
We identified a total of four studies that included 136 individuals. We used FAH/PAH as the main outcome of final height. The results revealed a statistically higher final height after treatment with AI or GnRHa in idiopathic short stature children(MD= 4.63, 95% CI[3.29,5.96]). In network meta-analysis, the direct and indirect comparison between AI and GnRHa was presented in the forest plot. Compared with control group, both AI and GnRHa were effective in increasing the final height, with the mean effect of 4.91(95%CI:1.10,8.17) and 5.55(95%CI:1.12,9.98) respectively. However, there was no statistical difference between the GnRHa and AI treatment, of which the mean effect was 0.65(95%CI: -4.30,5.60).
CONCLUSION
Both AIs and GnRHa monotherapy were effective in augmenting the final height of boys with idiopathic short stature when compared to placebo groups. However, there was no statistical difference between the GnRHa and AI treatments.
Topics: Male; Child; Humans; Aromatase Inhibitors; Gonadotropin-Releasing Hormone; Network Meta-Analysis; Body Height; Human Growth Hormone; Dwarfism
PubMed: 37124748
DOI: 10.3389/fendo.2023.1167351 -
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 -
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 -
BMC Neurology Apr 2023Pituitary dysfunction (PD) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). The prevalence of PD varies widely at a global level and no recent... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pituitary dysfunction (PD) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). The prevalence of PD varies widely at a global level and no recent meta-analysis is available. Therefore, the aim of our systematic review and meta-analysis was to summarize the updated estimates of worldwide prevalence of PD after aSAH.
METHODS
Scopus, Embase, Web of Science, and PubMed databases were used to comprehensively search the appropriate literature and a random-effects meta-analysis on the results of the available studies was performed. The heterogeneity in the prevalence estimates was evaluated by subgroup analysis in terms of types of PD, and acute and chronic phases of aSAH. The onset of PD within 6 months after aSAH was considered as acute, while that after 6 months was considered as chronic.
RESULTS
Twenty-seven studies with 1848 patients were included in this analysis. The pooled prevalence of PD in the acute phase was 49.6% (95% CI, 32.4-66.8%), and 30.4% (95% CI, 21.4-39.4%) in the chronic phase. Among the hormonal deficiencies, growth hormone dysfunction was the most prevalent in the acute phase, being 36.0% (95% CI, 21.0-51.0%), while hypoadrenalism was the most prevalent in the chronic phase, being 21.0% (95% CI, 12.0-29.0%). Among the six World Health Organization regions, the South-East Asia Region has the highest prevalence of PD in the acute phase (81.0%, 95%CI, 77.0-86.0%, P < 0.001), while the European Region had the highest prevalence of PD in the chronic phase (33.0%, 95%CI, 24.0-43.0%, P < 0.001). Moreover, single pituitary hormonal dysfunction occurred more frequently than the multiple one, regardless of acute or chronic phase.
CONCLUSIONS
Almost half (49.6%) of the included patients with aSAH developed PD complication in the acute phase, while 30.4% of the patients developed them in the chronic phase. Although prevalence varies globally, the high healthcare burden, morbidity and mortality require greater awareness among clinicians.
Topics: Humans; Subarachnoid Hemorrhage; Prevalence
PubMed: 37081429
DOI: 10.1186/s12883-023-03201-x -
Hormone Research in Paediatrics 2024Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Recombinant human growth hormone (rhGH) therapy effectively increases height in various disorders of childhood growth. However, whether rhGH affects pubertal timing is unclear. We aimed to review systematically published evidence on the effect of rhGH on pubertal timing.
METHODS
Embase, MEDLINE, and Cochrane Library databases were searched until December 2021 on randomized and non-randomized controlled studies of rhGH in children.
RESULTS
Twenty-five articles (n = 1,433 children) were identified, describing 12 randomized and 13 non-randomized controlled studies in children with idiopathic short stature (ISS; 15 studies), small for gestational age (n = 6 studies), chronic renal failure (n = 3), Noonan syndrome (n = 1), and growth hormone deficiency (n = 1). Significant differences in the effects of rhGH on pubertal timing were found by clinical indication. Only among children with ISS, rhGH promoted earlier age at pubertal timing (mean difference = -0.46 years; 95% CI, -0.90 to -0.03; 9 studies; n total = 397) or higher relative risk for pubertal onset during study follow-up (1.26; 95% CI, 1.03 to 1.54; 6 studies; n total = 284).
CONCLUSIONS
Treatment with rhGH appears to promote earlier pubertal timing among children with ISS. Evidence was lacking in children with growth hormone deficiency due to the absence of studies with untreated controls.
Topics: Child; Humans; Human Growth Hormone; Growth Hormone; Body Height; Growth Disorders; Dwarfism, Pituitary; Recombinant Proteins
PubMed: 37075730
DOI: 10.1159/000530578 -
ESMO Open Jun 2023In hormone receptor-positive (HoR+) breast cancer (BC), gene expression analysis identifies luminal A (LumA), luminal B (LumB), human epidermal growth factor receptor 2... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In hormone receptor-positive (HoR+) breast cancer (BC), gene expression analysis identifies luminal A (LumA), luminal B (LumB), human epidermal growth factor receptor 2 (HER2)-enriched (HER2-E), basal-like (BL) intrinsic subtypes and a normal-like group. This classification has an established prognostic value in early-stage HoR+ BC. Here, we carried out a trial-level meta-analysis to determine the prognostic ability of subtypes in metastatic BC (MBC).
MATERIALS AND METHODS
We systematically reviewed all the available prospective phase II/III trials in HoR+ MBC where subtype was assessed. The primary endpoint was progression-free survival (PFS)/time to progression (TTP) of the LumA subtype compared to non-LumA. Secondary endpoints were PFS/TTP of each individual subtype, according to treatment, menopausal and HER2 status and overall survival (OS). The random-effect model was applied, and heterogeneity assessed through Cochran's Q and I. Threshold for significance was set at P < 0.05. The study was registered in PROSPERO (ID: CRD42021255769).
RESULTS
Seven studies were included (2536 patients). Non-LumA represented 55.2% and was associated with worse PFS/TTP than LumA [hazard ratio (HR) 1.77, P < 0.001, I = 61%], independently of clinical HER2 status [P (P) = 0.16], systemic treatment (P = 0.96) and menopausal status (P = 0.12). Non-LumA tumors also showed worse OS (HR 2.00, P < 0.001, I = 65%), with significantly different outcomes for LumB (PFS/TTP HR 1.46; OS HR 1.41), HER2-E (PFS/TTP HR 2.39; OS HR 2.08) and BL (PFS/TTP HR 2.67; OS HR 3.26), separately (PFS/TTP P = 0.01; OS P = 0.005). Sensitivity analyses supported the main result. No publication bias was observed.
CONCLUSIONS
In HoR+ MBC, non-LumA disease is associated with poorer PFS/TTP and OS than LumA, independently of HER2, treatment and menopausal status. Future trials in HoR+ MBC should consider this clinically relevant biological classification.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Prospective Studies; Antineoplastic Agents; Proportional Hazards Models
PubMed: 37075698
DOI: 10.1016/j.esmoop.2023.101214 -
Frontiers in Oncology 2023The axillary lymph node positive (ypN+) rate in patients with clinically node-negative (cN0) breast cancer who have achieved breast pathologic complete response (bpCR)...
The nodal positivity rate in breast pCR patients with initially, clinically node-negative breast cancer after neoadjuvant systemic therapy: A systematic review and meta-analysis.
BACKGROUND
The axillary lymph node positive (ypN+) rate in patients with clinically node-negative (cN0) breast cancer who have achieved breast pathologic complete response (bpCR) after neoadjuvant systemic therapy (NST) is extremely low, and this population has the potential to be exempt from sentinel lymph node biopsy (SLNB). However, an overview of the ypN+ rate in this population for different breast cancer subtypes is lacking.
OBJECTIVE
To provide the pooled ypN+ rate in cN0 patients who achieved bpCR after NST in different breast cancer subtypes defined by hormone receptor (HR) status and human epidermal growth factor receptor 2 (HER2) status.
METHODS
A systematic literature search was conducted in Embase and PubMed on July 20, 2022. Two authors independently selected studies that met the inclusion criteria and extracted all data. The pooled ypN+ rates for each subtype were calculated by a random-effects model using the Stata 16.0 command.
RESULTS
The pooled analysis of 9609 cN0 patients who achieved bpCR showed that the ypN+ rate was lowest for the HR+/HER2+ (0%) subtype, followed by HR+/HER2- (5.1%), HR-/HER2+ (0.6%), and HR-/HER2- (0.3%). Additionally, 6571 cT-TN0 patients who achieved bpCR had a pooled ypN+ rate of 0.6%, and the ypN+ rates for different subtypes were as follows: HR+/HER2+ (1.7%), HR+/HER2- (2.7%), HR-/HER2+ (0.1%), and HR-/HER2- (0.8%).
CONCLUSION
Our results suggested that cN0 patients who achieve bpCR may be exempt from axillary surgery in the HR+/HER2-, HR+/HER2+, and HR-/HER2- subtypes because of the extremely low probability of residual axillary lymph node disease. However, the safety of omitting axillary surgery needs to be further confirmed by prospective studies.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier CRD42022351739.
PubMed: 37064127
DOI: 10.3389/fonc.2023.1167912 -
Annals of Translational Medicine Mar 2023Neoadjuvant therapy has become the standard treatment for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer, with most regimens using a...
BACKGROUND
Neoadjuvant therapy has become the standard treatment for early human epidermal growth factor receptor 2 (HER2)-positive breast cancer, with most regimens using a combination of anti-HER2-targeted drugs and chemotherapy. However, the combination of anthracyclines and trastuzumab has high cardiac toxicity, and the efficacy evaluation of targeted therapy with or without anthracyclines is not unified. The purpose of this meta-analysis was to evaluate the relative efficacy and safety of anti-HER2-targeted therapy combined with . without anthracyclines neoadjuvant treatment.
METHODS
The following databases: PubMed, Medline, Embase, and Cochrane Library were systematically searched. Study inclusion was determined according to PICOS principles. PICOS: Patients, HER2-positive breast cancer; Intervention, anti-HER2-targeted therapy combined with anthracyclines; Control, without anthracyclines; Outcomes, the percentage of pathologic complete response (pCR), breast-conserving surgery (BCS), and grade 3 or worse adverse events according to CTCAE version 4.03; Studies, randomized controlled trials (RCTs) and retrospective studies. The meta-analysis was performed using RevMan5.3 software, and the odds ratio (OR) with 95% confidence intervals (CIs) was performed.
RESULTS
In total, 11 articles involving 1,998 patients were included with 1,155 patients in the anthracycline-containing group and 843 patients in the anthracycline-free group. For efficacy, there was no statistically significant difference in the percentage of pCR (OR 0.95; 95% CI: 0.61-1.48; P=0.83) and BCS (OR 1.18; 95% CI: 0.93-1.49; P=0.17) on anthracycline-free regimens compared with anthracycline-containing regimens. For safety, the combined effect values showed a significantly lower incidence of left ventricular ejection fraction decreases with the anthracycline-free regimen than with the anthracycline-containing regimen (OR 0.50; 95% CI: 0.35-0.71; P=0.0001). Other adverse effects and survival events were generally not statistically different in incidence between the two groups. The subgroup analysis suggested that hormone receptor status might be the source of heterogeneity in this study.
CONCLUSIONS
Our study demonstrated that the targeted therapy combined with anthracyclines was associated with an increased risk of cardiac adverse events compared with the anthracycline-free group, with no significant difference in the percentage of pCR and BCS. Due to the high heterogeneity of this meta-analysis, more studies with longer follow-up are needed to validate the current findings and to further explore the removal and retention of anthracyclines.
PubMed: 37007556
DOI: 10.21037/atm-22-4030 -
Frontiers in Psychiatry 2023Alcohol use disorder (AUD) is often described as repeated phases of binge drinking, compulsive alcohol-taking, craving for alcohol during withdrawal, and drinking with...
Alcohol use disorder (AUD) is often described as repeated phases of binge drinking, compulsive alcohol-taking, craving for alcohol during withdrawal, and drinking with an aim to a reduce the negative consequences. Although multifaceted, alcohol-induced reward is one aspect influencing the former three of these. The neurobiological mechanisms regulating AUD processes are complex and one of these systems is the gut-brain peptide ghrelin. The vast physiological properties of ghrelin are mediated growth hormone secretagogue receptor (GHSR, ghrelin receptor). Ghrelin is well known for its ability to control feeding, hunger, and metabolism. Moreover, ghrelin signaling appears central for alcohol-mediated responses; findings reviewed herein. In male rodents GHSR antagonism reduces alcohol consumption, prevents relapse drinking, and attenuates the motivation to consume alcohol. On the other hand, ghrelin increases the consumption of alcohol. This ghrelin-alcohol interaction is also verified to some extent in humans with high alcohol consumption. In addition, either pharmacological or genetic suppression of GHSR decreases several alcohol-related effects (behavioral or neurochemical). Indeed, this suppression blocks the alcohol-induced hyperlocomotion and dopamine release in nucleus accumbens as well as ablates the alcohol reward in the conditioned place preference model. Although not fully elucidated, this interaction appears to involve areas central for reward, such as the ventral tegmental area (VTA) and brain nodes targeted by VTA projections. As reviewed briefly, the ghrelin pathway does not only modulate alcohol-mediated effects, it regulates reward-related behaviors induced by addictive drugs. Although personality traits like impulsivity and risk-taking behaviors are common in patients with AUD, the role of the ghrelin pathway thereof is unknown and remains to be studied. In summary, the ghrelin pathway regulates addiction processes like AUD and therefore the possibility that GHSR antagonism reduces alcohol or drug-taking should be explored in randomized clinical trials.
PubMed: 36970276
DOI: 10.3389/fpsyt.2023.1050973