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International Journal of Radiation... Jun 2024Children who receive cranial radiation therapy (RT) as a component of treatment for malignancy are often at risk of long-term central endocrine toxicity secondary to...
PURPOSE
Children who receive cranial radiation therapy (RT) as a component of treatment for malignancy are often at risk of long-term central endocrine toxicity secondary to radiation to the hypothalamic-pituitary axis (HPA). A comprehensive analysis was performed of central endocrine late effects in survivors of childhood cancer treated with RT as part of the Pediatric Normal Tissue Effects in the Clinic (PENTEC) consortium.
METHODS AND MATERIALS
A systematic review of the risk of RT-related central endocrine effects was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 4629 publications were identified, of which 16 met criteria for inclusion in dose modeling analysis, with a total of 570 patients in 19 cohorts. Eighteen cohorts reported outcomes for growth hormone deficiency (GHD), 7 reported outcomes for central hypothyroidism (HT), and 6 reported outcomes for adrenocorticotropic hormone (ACTH) deficiency.
RESULTS
Normal tissue complication probability modeling for GHD (18 cohorts, 545 patients) yielded D = 24.9 Gy (95% CI, 20.9-28.0) and γ = 0.5 (95% CI, 0.27-0.78). The normal tissue complication probability model fit for whole brain irradiation in children with a median age of >5 years indicated a 20% risk of GHD for patients who receive a mean dose of 21 Gy in 2-Gy fractions to the HPA. For HT, among 7 cohorts (250 patients), D = 39 Gy (95% CI, 34.1-53.2) and γ = 0.81 (95% CI, 0.46-1.35), with a 20% risk of HT in children who receive a mean dose of 22 Gy in 2-Gy fractions to the HPA. For ACTH deficiency (6 cohorts, 230 patients), D = 61 Gy (95% CI, 44.7-119.4) and γ = 0.76 (95% CI, 0.5-1.19); there is a 20% risk of ACTH deficiency in children who receive a mean dose of 34 Gy in 2-Gy fractions to the HPA.
CONCLUSIONS
RT dose to the HPA increases the risk of central endocrine toxicity, including GHD, HT, and ACTH deficiency. In some clinical situations, these toxicities may be difficult to avoid, and counseling of patients and families with respect to anticipated outcomes is important.
Topics: Humans; Child; Cancer Survivors; Hypothyroidism; Cranial Irradiation; Adrenocorticotropic Hormone; Adolescent; Child, Preschool; Hypothalamo-Hypophyseal System; Radiation Injuries; Endocrine System Diseases
PubMed: 37269265
DOI: 10.1016/j.ijrobp.2023.04.024 -
Cureus Feb 2024This systematic review aims to determine the role of the growth hormone receptor (GHR) gene in skeletal malocclusion and its significant influence on the growth of the... (Review)
Review
Role of the Growth Hormone Receptor (GHR) Gene in Skeletal Class II Malocclusion and Its Significant Influence on the Skeletal Facial Profile in Both the Sagittal and Vertical Dimensions: A Systematic Review.
This systematic review aims to determine the role of the growth hormone receptor (GHR) gene in skeletal malocclusion and its significant influence on the growth of the maxilla and the mandible in both sagittal and vertical dimensions. A search of the electronic databases of PubMed, Google Scholar, and Cochrane up to and including the year 2023 was made. In addition to this, a hand search of orthodontic and dentofacial orthopaedic journals was carried out. This search included randomized control trials. The Mesh terms used were "skeletal class II malocclusion", "mandibular retrognathism", "sagittal malocclusion", "genetic expression", "genetic factors", "genetic study", "genetic polymorphism", and "single nucleotide polymorphism". The inclusion criteria included studies such as clinical trials and orthopaedic appliances in the presurgical phase. The exclusion criteria for the study were studies not in the English language, case reports, case series, and studies with irrelevant data. It has been cited in various literature that polymorphic variations of the GHR gene could cause variations in mandibular morphogenesis affecting both the mandibular body length and ramal height. However, its effects are quite variable and are based on different population groups. Polymorphism of the GHR gene can be considered a reliable indicator predicting variations in affecting the growth of the mandible with greater significance in affecting the vertical ramal height compared to the body length of the mandible. Its effects on the maxillary skeletal base are rather limited comparatively.
PubMed: 38449954
DOI: 10.7759/cureus.53596 -
Growth Hormone & IGF Research :... Apr 2024Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate... (Review)
Review
OBJECTIVE
Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects.
DESIGN
A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library.
INCLUSION CRITERIA
participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis.
RESULTS
The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life.
CONCLUSION
Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.
Topics: Aged; Humans; Comorbidity; Growth Hormone; Human Growth Hormone; Insulin-Like Growth Factor I; Quality of Life; Randomized Controlled Trials as Topic; Aging
PubMed: 38489867
DOI: 10.1016/j.ghir.2024.101584 -
Children (Basel, Switzerland) Feb 2024Growth hormone treatment has effectively restored normal growth in children with growth hormone deficiency (GHD); however, it poses challenges in compliance with a daily... (Review)
Review
Once-Weekly Somapacitan as an Alternative Management of Growth Hormone Deficiency in Prepubertal Children: A Systematic Review and Meta-Analysis of Randomized Controlled Trial.
Growth hormone treatment has effectively restored normal growth in children with growth hormone deficiency (GHD); however, it poses challenges in compliance with a daily growth hormone injection regimen, leading to low adherence and persistence rates. Once-weekly Somapacitan is a potential alternative for treating children with GHD. This study aimed to evaluate the efficacy, safety, and adherence of once-weekly subcutaneous Somapacitan compared to daily growth hormone injection in prepubertal children with GHD. A search for the published records was carried out on 17 October 2023 utilizing the searching feature available on PubMed, Embase, and Scopus. Primary study outcomes included (1) efficacy, measured by height velocity (HV), standard deviation score (SDs), height SDs, insulin-like growth factor-SDs (IGF-I SDs), and bone age vs. chronological age ratio (BA vs. CA); (2) safety, assessed through adverse events and injection site reactions; and (3) adherence, determined by the percentage of the sample completing treatments. Secondary outcomes evaluated disease burden scores, divided into three subgroup domains: emotional well-being, physical functional, and social well-being scores. We retrieved 6 studies that were eligible for the systematic review (417 versus 186 for intervention and control, respectively). Only 2 of the total included studies were eligible for pooled analysis (175 versus 82 for intervention and control, respectively). The efficacy profile of Somapacitan was similar to daily growth hormones, indicated by HV (mean difference (MD = 0.04; = 0.96), HV SDs (MD = -0.71; = 0.09), height SDs (MD = 0.11; = 0.69), IGF-I SDs (MD = 0.06; = 0.70), and CA vs. BA (MD = 0.67; = 0.70)), demonstrated similar and non-inferior outcomes. Treatment adherence is 3 times higher in the Somapacitan group as compared to control (OR = 3.02; = 0.03) with adherence rates reaching 95% and 88% for Somapacitan and Norditropin, respectively. The disease burden measurement is similar in Somapacitan and daily growth hormones (MD = -0.62; = 0.83), as indicated by the Growth Hormone Deficiency-Child Impact Measure. In almost all outcomes, the level of confidence is strong. The confidence level in the data is generally strong, but for CA vs. BA and the subgroup of severe adverse events with heterogeneity >50%, the confidence level is moderate. Although the efficacy and safety profiles of Somapacitan were found to be similar to those of daily growth hormones, a reduced frequency of once-weekly Somapacitan injections led to increased adherence. PROSPERO registration: CRD42023473209.
PubMed: 38397339
DOI: 10.3390/children11020227 -
Nutrients May 2024Vitamin D deficiency is very common worldwide, particularly in old age, when people are at the highest risk of the negative adverse consequences of hypovitaminosis D.... (Meta-Analysis)
Meta-Analysis Review
Vitamin D deficiency is very common worldwide, particularly in old age, when people are at the highest risk of the negative adverse consequences of hypovitaminosis D. Additionally to the recognized functions in the regulation of calcium absorption, bone remodeling, and bone growth, vitamin D plays a key role as a hormone, which is supported by various enzymatic, physiological, metabolic, and pathophysiological processes related to various human organs and systems. Accruing evidence supports that vitamin D plays a key role in pancreatic islet dysfunction and insulin resistance in type 2 diabetes. From an epidemiological viewpoint, numerous studies suggest that the growing incidence of type 2 diabetes in humans may be linked to the global trend of prevalent vitamin D insufficiency. In the past, this association has raised discussions due to the equivocal results, which lately have been more convincing of the true role of vitamin D supplementation in the prevention of incident type 2 diabetes. Most meta-analyses evaluating this role have been conducted in adults or young older persons (50-60 years old), with only one focusing on older populations, even if this is the population at greater risk of both hypovitaminosis D and type 2 diabetes. Therefore, we conducted an update of the previous systematic review and meta-analysis examining whether hypovitaminosis D (low serum 25OHD levels) can predict incident diabetes in prospective longitudinal studies among older adults. We found that low 25OHD was associated with incident diabetes in older adults even after adjusting for several relevant potential confounders, confirming and updating the results of the only previous meta-analysis conducted in 2017.
Topics: Humans; Diabetes Mellitus, Type 2; Vitamin D; Vitamin D Deficiency; Aged; Incidence; Risk Factors; Middle Aged; Male; Female
PubMed: 38892495
DOI: 10.3390/nu16111561 -
Breast Cancer : Basic and Clinical... 2024Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2... (Review)
Review
Association Between Ki-67 Proliferative Index and Oncotype-Dx Recurrence Score in Hormone Receptor-Positive, HER2-Negative Early Breast Cancers. A Systematic Review of the Literature.
BACKGROUND
Oncotype-Dx (ODx) is a 21-gene assay used as a prognostic and predictive tool for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative, node-negative, or 1 to 3 lymph node-positive early breast cancers (EBCs). The cost of the test, which is not available in low-middle income countries (LMICs), is not within the means of most individuals. The Ki-67 index is a marker of tumor proliferation that is cost-effective and easily performed and has been substituted in many cases to obtain prognostic information.
OBJECTIVE
We aimed to identify the correlation between the ODx recurrence score (RS) and the Ki-67 index in HR-positive EBCs and to determine whether Ki-67, like the ODx, can help facilitate clinical decision-making.
DESIGN
Systematic review correlating Ki-67 index and ODx in HR-positive and HER2-negative EBCs as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
DATA SOURCES AND METHODS
We searched different databases between January 2010 and May 2023 and included retrospective/prospective cohorts, clinical trials, case-control, and cross-sectional studies involving HR-positive and HER2-negative EBCs correlating the Ki-67 index and ODx RS categories.
RESULTS
Of the 18 studies included, 16 indicated a positive or weakly positive correlation between ODx and the Ki-67 index. The combined value of the included studies is <0.05 ( = .000), which shows a statistical significance between the 2. Our review also discusses the potential of machine learning and artificial intelligence (AI) in Ki-67 assessment, offering a cost-effective and reproducible alternative.
CONCLUSION
Even although there are limitations, studies indicate a favorable association between ODx and the Ki-67 index in specific situations. This implies that Ki-67 can offer important predictive details, especially regarding the likelihood of relapse in HR-positive EBC. This is particularly significant in LMICs where financial constraints often hinder the availability of costly diagnostic tests.
PubMed: 38779417
DOI: 10.1177/11782234241255211 -
International Journal of Environmental... Aug 2023Children with short stature can experience a range of burdens due to their chronic condition. However, little is known about parents' experiences dealing with their... (Review)
Review
Children with short stature can experience a range of burdens due to their chronic condition. However, little is known about parents' experiences dealing with their child's short stature and the potential caregiving burdens and concerns they may face. We aim to review the literature on health-related quality of life (HRQOL), caregiving burden, and special needs among parents caring for a child with isolated growth hormone deficiency (IGHD) or idiopathic short stature (ISS). Using pre-defined inclusion and exclusion criteria, we systematically searched for literature using PubMed and Web of Science from its inception to December 2022. We identified 15 articles assessing HRQOL, special needs, or caregiving burdens in parents of IGHD/ISS children. The main problems included concerns about the future, organizational issues, side effects from growth hormone treatment, and social stigmatization. Furthermore, two studies assessed parents' special needs to cope with caregiving stress, mainly the dialogue between them and their families or parent support groups. This review outlines parental burdens, needs, and resources when caring for an IGHD/ISS child. Furthermore, it provides information about previously used measures appraising parents' special needs and underlines the need for disease-specific measurements.
Topics: Humans; Quality of Life; Caregiver Burden; Drug-Related Side Effects and Adverse Reactions; PubMed; Self-Help Groups
PubMed: 37623144
DOI: 10.3390/ijerph20166558 -
Reproductive Biology and Endocrinology... Apr 2024Intra-uterine infusion treatments were reported to be beneficial to embryo implantation and pregnancy outcomes, and considered as potential therapies for infertile... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intra-uterine infusion treatments were reported to be beneficial to embryo implantation and pregnancy outcomes, and considered as potential therapies for infertile patients with recurrent implantation failure (RIF). Nevertheless, their efficiencies were controversial and there lack of consensus on which intrauterine treatment is the most effective.
METHODS
All prospective trials (in Chinese or English) were searched in Databases PubMed, Cochrane, Web of Science, and CNKI from July 2013 to July 2023. We included studies that investigated various uterine infusions, including chorionic gonadotropin, granulocyte colony-stimulating factor, monocytes, platelet-rich plasma, etc. during IVF treatment and reported subsequent pregnancy outcomes.
RESULTS
We finally included 56 researches, including 40 randomized controlled trials, 14 non-randomized controlled trials, and 3 prospective cohort studies. This study included a total of 11 uterine perfusion methods: Placebo, Human Chorionic Gonadotropin (HCG), Granulocyte Colony-Stimulating Factor (G-CSF), platelet-rich plasma (PRP), Peripheral Blood Mononuclear Cell (PBMC), Growth hormone (GH), dexamethasone (DEX), Embryo culture supernatant (ESC), PRP combined with G-CSF (PRP + G-CSF), RPR combined with subcutaneous injection of G-CSF (RPR + G-CSFsc), G-CSF combined with subcutaneous injection of AXaIU (G-CSF + AXaIUsc). Intrauterine infusion of HCG, PBMC, G-CSF, and PRP significantly improves pregnancy outcomes in patients with repeated implantation failure compared with blank controls or placebo, and PRP improved the clinical pregnancy and live birth most. GH and ESC infusion might improve the pregnancy outcomes, but uterine infusion of DEX was shown with high miscarriage. The combination therapy did not show a significant advantage over the mono-therapy.
CONCLUSIONS
Intrauterine infusion of HCG, PBMC, G-CSF, and PRP are promising strategies for improving pregnancy outcomes for infertile patients with recurrent implantation failure. Among these treatments, PRP may be the best. More researches are required to explore the effect of drug combinations and less commonly used drugs as well.
TRIAL REGISTRATION
Our study was registered in PROSPERO and the ID was CRD42023467188.
Topics: Pregnancy; Female; Humans; Prospective Studies; Leukocytes, Mononuclear; Network Meta-Analysis; Embryo Implantation; Chorionic Gonadotropin; Infertility, Female; Granulocyte Colony-Stimulating Factor; Pregnancy Rate
PubMed: 38627790
DOI: 10.1186/s12958-024-01221-x -
International Urology and Nephrology May 2024Mineral and bone disease in children with chronic kidney disease can cause abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D and when left... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Mineral and bone disease in children with chronic kidney disease can cause abnormalities in calcium, phosphorus, parathyroid hormone, and vitamin D and when left untreated can result in impaired growth, bone deformities, fractures, and vascular calcification. Cinacalcet is a calcimimetic widely used as a therapy to reduce parathyroid hormone levels in the adult population, with hypocalcemia among its side effects. The analysis of safety in the pediatric population is questioned due to the scarcity of randomized clinical trials in this group.
OBJECTIVE
To assess the onset of symptomatic hypocalcemia or other adverse events (serious or non-serious) with the use of cinacalcet in children and adolescents with mineral and bone disorder in chronic kidney disease.
DATA SOURCES AND STUDY ELIGIBILITY CRITERIA
The bibliographic search identified 2699 references from 1927 to August/2023 (57 LILACS, 44 Web of Science, 686 PubMed, 131 Cochrane, 1246 Scopus, 535 Embase). Four references were added from the bibliography of articles found and 12 references from the gray literature (Clinical Trials). Of the 77 studies analyzed in full, 68 were excluded because they did not meet the following criteria: population, types of studies, medication, publication types and 1 article that did not present results (gray literature).
PARTICIPANTS AND INTERVENTIONS
There were 149 patients aged 0-18 years old with Chronic Kidney Disease and mineral bone disorder who received cinacalcet.
STUDY APPRAISAL AND SYNTHESIS METHODS
Nine eligible studies were examined for study type, size, intervention, and reported outcomes.
RESULTS
There was an incidence of 0.2% of fatal adverse events and 16% of serious adverse events (p < 0.01 and I = 69%), in addition to 10.7% of hypocalcemia, totaling 45.7% of total adverse events.
LIMITATIONS
There was a bias in demographic information and clinical characteristics of patients in about 50% of the studies and the majority of the studies were case series.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
If used in the pediatric population, the calcimimetic cinacalcet should be carefully monitored for serum calcium levels and attention to possible adverse events, especially in children under 50 months.
SYSTEMATIC REVIEW REGISTRATION NUMBER (PROSPERO REGISTER)
CRD42019132809.
Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Bone Diseases; Calcimimetic Agents; Calcium; Chronic Kidney Disease-Mineral and Bone Disorder; Cinacalcet; Hyperparathyroidism, Secondary; Hypocalcemia; Minerals; Parathyroid Hormone; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 37964112
DOI: 10.1007/s11255-023-03844-2 -
Asia-Pacific Journal of Clinical... Oct 2023Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been approved for breast cancer (BC) treatment. Several trials suggested... (Meta-Analysis)
Meta-Analysis Review
Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) have been approved for breast cancer (BC) treatment. Several trials suggested that arthralgia was reduced in patients treated with ET plus CDK4/6i compared with that in those with ET-alone. We aimed to compare arthralgia rates in BC patients treated with/without CDK4/6i. We reviewed randomized controlled phase II/III trials investigating CDK4/6i with ET in hormone receptor-positive and epidermal growth factor 2-negative BC. Publications were retrieved from PubMed from January 2014 to April 2021. We compared arthralgia rates between patients who were administered ET plus CDK4/6i (CDK4/6i group) and those treated with ET-alone (control group). We reviewed 12 trials that reported data on adverse effects for arthralgia. These trials included 17,440 patients (9255 in the CDK4/6i group and 8185 in the control group). The arthralgia rate in the CDK4/6i group was significantly lower than that in the control group (27.6% vs. 34.8%, p < .001), especially in early BC (28.8% vs. 37.3%, p < .001). These suggested that the arthralgia rate in patients treated with ET plus CDK4/6i was lower than that in patients treated with ET-alone and that CDK4/6i may decrease the arthralgia rate in BC patients treated with ET, especially in early BC.
Topics: Humans; Female; Breast Neoplasms; Cyclin-Dependent Kinase 4; Protein Kinase Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Clinical Trials, Phase II as Topic; Randomized Controlled Trials as Topic
PubMed: 36085411
DOI: 10.1111/ajco.13840