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Sökning: L773:0021 972X > Forskningsöversikt

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  • Beamish, Andrew J., et al. (författare)
  • Long-term Outcomes Following Adolescent Metabolic and Bariatric Surgery
  • 2023
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 108:9, s. 2184-2192
  • Forskningsöversikt (refereegranskat)abstract
    • Severe obesity in adolescence negatively impacts upon health and wellbeing. Lifestyle modifications do not usually achieve a sufficient degree or durability of weight loss to mitigate the risk of medical complications. In recent years, metabolic and bariatric surgery (MBS), already a well-established treatment for adults with severe obesity, has emerged as an option in adolescents. Controlled studies in this age group have demonstrated substantial and sustained weight loss, improvements in associated health parameters, and a safety profile surpassing that observed in adult patients. This review aims to present published data on the results of MBS in adolescents with a focus on long-term outcomes. Indications for bariatric surgery and aspects of timing in the young persons life are also presented, along with safety considerations and factors influencing patient selection for surgery. We conclude, predominantly from short- to medium-term outcomes data, that MBS is a safe and valuable therapeutic option for adolescents with severe obesity. Considering the poor health and social wellbeing prognosis in this group, MBS appears to be underutilized. The need for continued research, multiprofessional specialist provision, coherent contemporary clinical guidelines, and routine long-term follow-up in adolescents undergoing MBS is highlighted.
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  • Burman, Pia, et al. (författare)
  • Aggressive Pituitary Tumors and Pituitary Carcinomas : From Pathology to Treatment
  • 2023
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Endocrine Society. - 0021-972X .- 1945-7197. ; 108:7, s. 1585-1601
  • Forskningsöversikt (refereegranskat)abstract
    • Aggressive pituitary tumors (APTs) and pituitary carcinomas (PCs) are heterogeneous with regard to clinical presentation, proliferative markers, clinical course, and response to therapy. Half of them show an aggressive course only many years after the first apparently benign presentation. APTs and PCs share several properties, but a Ki67 index greater than or equal to 10% and extensive p53 expression are more prevalent in PCs. Mutations in TP53 and ATRX are the most common genetic alterations; their detection might be of value for early identification of aggressiveness. Treatment requires a multimodal approach including surgery, radiotherapy, and drugs. Temozolomide is the recommended first-line chemotherapy, with response rates of about 40%. Immune checkpoint inhibitors have emerged as second-line treatment in PCs, with currently no evidence for a superior effect of dual therapy compared to monotherapy with PD-1 blockers. Bevacizumab has resulted in partial response (PR) in few patients; tyrosine kinase inhibitors and everolimus have generally not been useful. The effect of peptide receptor radionuclide therapy is limited as well. Management of APT/PC is challenging and should be discussed within an expert team with consideration of clinical and pathological findings, age, and general condition of the patient. Considering that APT/PCs are rare, new therapies should preferably be evaluated in shared standardized protocols. Prognostic and predictive markers to guide treatment decisions are needed and are the scope of ongoing research.
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  • Dean, B, et al. (författare)
  • P450 Oxidoreductase Deficiency: A Systematic Review and Meta-analysis of Genotypes, Phenotypes, and Their Relationships
  • 2020
  • Ingår i: JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 105:3, s. E43-E54
  • Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
    • ContextP450 oxidoreductase deficiency (PORD) is a rare genetic disorder that is associated with significant morbidity. However there has been limited analysis of reported PORD cases.ObjectiveTo determine, based on the cohort of reported PORD cases, genotype-phenotype relationships for skeletal malformations, maternal virilisation in pregnancy, adrenal insufficiency, and disorders of sexual development (DSD).Data SourcesPubMed and Web of Science from January 2004 to February 2018.Study SelectionPublished case reports/series of patients with PORD. Eligible patients were unique, had biallelic mutations, and their clinical features were reported.Data ExtractionPatient data were manually extracted from the text of case reports/series. A malformation score, representing the severity of skeletal malformations, was calculated for each patient.Data SynthesisOf the 211 patients published in the literature, 90 were eligible for inclusion. More than 60 unique mutations were identified in this cohort. Four groups of mutations were identified, through regression modeling, as having significantly different skeletal malformation scores. Maternal virilization in pregnancy, reported for 21% of patients, was most common for R457H mutations. Adrenal insufficiency occurred for the majority of patients (78%) and was typically mild, with homozygous R457H mutations being the least deficient. DSD affected most patients (72%), but were less common for males (46XY) with homozygous R457H mutations.ConclusionsPORD is a complex disorder with many possible mutations affecting a large number of enzymes. By analyzing the cohort of reported PORD cases, this study identified clear relationships between genotype and several important phenotypic features.
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  • Wang, Katharina, et al. (författare)
  • Targeted Therapies in Pheochromocytoma and Paraganglioma
  • 2022
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:11, s. 2963-2972
  • Forskningsöversikt (refereegranskat)abstract
    • Molecular targeted therapy plays an increasingly important role in the treatment of metastatic pheochromocytomas and paragangliomas (PPGLs), which are rare tumors but remain difficult to treat. This mini-review provides an overview of established molecular targeted therapies in present use, and perspectives on those currently under development and evaluation in clinical trials. Recently published research articles, guidelines, and expert views on molecular targeted therapies in PPGLs are systematically reviewed and summarized. Some tyrosine kinase inhibitors (sunitinib, cabozantinib) are already in clinical use with some promising results, but without formal approval for the treatment of PPGLs. Sunitinib is the only therapeutic option which has been investigated in a randomized placebo-controlled clinical trial. It is clinically used as a first-, second-, or third-line therapeutic option for the treatment of progressive metastatic PPGLs. Some other promising molecular targeted therapies (hypoxia-inducible factor 2 alpha [HIF2 alpha] inhibitors, tumor vaccination together with checkpoint inhibitors, antiangiogenic therapies, kinase signaling inhibitors) are under evaluation in clinical trials. The HIF2 alpha inhibitor belzutifan may prove to be particularly interesting for cluster 1B-/VHL/EPAS1-related PPGLs, whereas antiangiogenic therapies seem to be primarily effective in cluster 1A-/SDHx-related PPGLs. Some combination therapies currently being evaluated in clinical trials, such as temozolomide/olaparib, temozolomide/talazoparib, or cabozantinib/atezolizumab, will provide data for novel therapy for metastatic PPGLs. It is likely that advances in such molecular targeted therapies will play an essential role in the future treatment of these tumors, with more personalized therapy options paving the way towards improved therapeutic outcomes.
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