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The Possible Outcomes of Poor Adherence to Conventional Treatment in Patients with X-Linked Hypophosphatemic Rickets/Osteomalacia x连锁低磷佝偻病/骨软化症患者对常规治疗依从性差的可能结果
Pub Date : 2023-02-13 DOI: 10.3390/endocrines4010010
Hiroaki Zukeran, K. Ikegawa, C. Numakura, Y. Hasegawa
X-linked hypophosphatemic rickets/osteomalacia is an inherited disease caused by the loss of function in PHEX. Elevated plasma FGF23 in patients with XLH leads to hypophosphatemia. The conventional treatment for XLH, consisting of oral phosphate and active vitamin D, is often poorly adhered to for various reasons, such as the requirement to take multiple daily doses of phosphate. Burosumab, an anti-FGF23 antibody, is a new drug that directly targets the mechanism underlying XLH. We report herein three adult patients with poor adherence to the conventional treatment. In Patient 1, adherence was poor throughout childhood and adolescence. The treatment of Patients 2 and 3 became insufficient after adolescence. All of the patients suffered from gait disturbance caused by pain, fractures, and lower extremity deformities early in life. We prescribed burosumab for the latter two patients, and their symptoms, which were unaffected by resuming conventional treatment, dramatically improved with burosumab. Maintaining adherence to the conventional treatment is crucial but challenging for patients with XLH. Starting burosumab therapy from childhood or adolescence in pediatric patients with poor adherence may help prevent the early onset of complications.
X连锁低磷血症性软骨病/骨软化症是一种由PHEX功能丧失引起的遗传性疾病。XLH患者血浆FGF23升高导致低磷血症。XLH的常规治疗方法由口服磷酸盐和活性维生素D组成,但由于各种原因,如需要每天多次服用磷酸盐,通常依从性较差。Burosumab是一种抗FGF23抗体,是一种直接靶向XLH机制的新药。我们在此报告了三名对传统治疗依从性差的成年患者。在患者1中,整个儿童期和青少年期的依从性较差。患者2和3的治疗在青春期后变得不足。所有患者早期都患有由疼痛、骨折和下肢畸形引起的步态障碍。我们为后两名患者开了burosumab,他们的症状没有受到恢复常规治疗的影响,使用burosuma后症状显著改善。对XLH患者来说,坚持传统治疗至关重要,但具有挑战性。对于依从性差的儿童患者,从儿童或青少年时期开始使用burosumab治疗可能有助于预防并发症的早期发作。
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引用次数: 0
Clinical Features of Transient Growth Hormone Deficiency 短暂性生长激素缺乏症的临床特点
Pub Date : 2023-02-13 DOI: 10.3390/endocrines4010009
Yuki Sakai, K. Ikegawa, Kazuhiro Shimura, Y. Hasegawa
Background: Most patients with idiopathic growth hormone deficiency (iGHD) in childhood have normal GH stimulation test results in adulthood. The present study aimed to investigate the characteristics and possible etiology of transient iGHD. Methods: Patients with childhood-onset iGHD who completed their GH treatment between March 2010 and March 2021 were retrospectively studied. Patients with a clear history of child abuse or constitutional delay of growth and puberty were excluded. Ten patients with a diagnosis of iGHD based on a decreased growth rate and growth hormone stimulation test findings at the time of onset were included. Retesting demonstrated that these patients had a normal GH level. Results: Five patients had insufficient weight gain (BMI SD score < −1.0 at the start of treatment or a decrease in BMI SD score > 1.0 from one year before treatment to the start of treatment). The other five patients had no remarkable clinical features. One patient had decreased height velocity at the same time as their sibling. Conclusion: Insufficient pre-treatment weight gain or a familial cluster of cases may be related to low GH peaks of GHST, leading to a diagnosis of transient GHD.
背景:大多数儿童期特发性生长激素缺乏症(iGHD)患者成年后GH刺激测试结果正常。本研究旨在探讨短暂性iGHD的特点和可能的病因。方法:对2010年3月至2021年3月期间完成GH治疗的儿童期发病iGHD患者进行回顾性研究。有明显虐待儿童史或生长发育和青春期发育迟缓的患者被排除在外。包括10名根据发病时生长速率下降和生长激素刺激测试结果诊断为iGHD的患者。重新测试表明这些患者的生长激素水平正常。结果:5名患者的体重增加不足(治疗开始时BMI SD评分<−1.0,或从治疗前一年到治疗开始,BMI SD评分下降>1.0)。其他5例患者无明显临床特征。一名患者的身高速度与他们的兄弟姐妹同时下降。结论:治疗前体重增加不足或家族性聚集性病例可能与GHST的GH峰值低有关,从而诊断为短暂性GHD。
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引用次数: 0
Evaluating the Efficacy and Safety of Long-Acting GLP-1 Receptor Agonists in T1DM Patients 评估长效GLP-1受体激动剂治疗T1DM患者的疗效和安全性
Pub Date : 2023-02-06 DOI: 10.3390/endocrines4010008
Deene Mohandas, Jamie Calma, Catherine Gao, M. Basina
(1) Background: Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are a class of therapeutic agents that mimic the endogenous incretin hormone GLP-1. While this class of agents is not approved for Type 1 Diabetes (T1DM) due to concern of increased diabetic ketoacidosis (DKA) risk, long-acting GLP-1 medications are being commonly prescribed off label for T1DM in clinical practice. Several studies addressed the efficacy and safety of short-acting GLP-1 agonists therapy in patients with T1DM, but the data on long-acting agents are lacking. In our study, we aim to fill in this gap and help healthcare providers in their clinical decision making on the use of these agents for T1DM patients. (2) Methods: We conducted a retrospective chart review of T1DM patients on a long-acting GLP-1 for at least six months. Our retrospective chart review included information starting two years prior to starting GLP-1, and six or more months after starting GLP-1. Parameters collected included HbA1c, 14-day Continuous Glucose Monitor (CGM) and blood glucose (BG) data, and metabolic data (weight, systolic and diastolic blood pressure, and cholesterol levels). Statistical analysis was conducted using paired t-tests on R and Excel with α of 0.05. (3) Results: Our cohort consisted of 54 participants with T1DM on a long-acting GLP-1 (semaglutide, dulaglutide, exenatide extended-release [ER], albiglutide). Mean GLP-1 treatment duration was 23.85 ± 15.46 months. HbA1c values decreased significantly by an average of 0.71% percentage points (%-points, p = 0.002) comparing pre-therapy vs. on GLP-1 treatment. Similarly, for pre-therapy vs. on GLP-1 treatment values, CGM results were significant for increased time in range by 12.15%-points (p = 0.0009) showing a decreased average time in hyperglycemia (BG > 180 mg/dL) by a mean difference of 11.97%-points (p = 0.006), decreased 14-day mean BG by 19 mg/dl (p = 0.01), decreased 14-day BG standard deviation by 8.45 mg/dl (p = 0.01), decreased incidence of DKA hospitalization, and a decrease in weight by 3.16 kg (p = 0.007). (4) Conclusions: As more data emerges on cardiovascular and renal benefits of long acting GLP-1 in type 2 diabetes, there have been no reported outcomes in T1DM. Our study is the first to demonstrate glycemic and metabolic benefits of this class of medication as an adjunct therapy to insulin in T1DM, and safety of its use over an average of 1.5–2 years’ time. This study represents real life experience and the data warrants confirmation by additional prospective studies.
(1) 背景:胰高血糖素样肽1受体激动剂(GLP-1 RA)是一类模拟内源性肠促生长素GLP-1的治疗剂。虽然由于担心糖尿病酮症酸中毒(DKA)风险增加,这类药物未被批准用于1型糖尿病(T1DM),但在临床实践中,长效GLP-1药物通常是针对T1DM的标示外处方。几项研究探讨了短效GLP-1激动剂治疗T1DM患者的疗效和安全性,但缺乏长效药物的数据。在我们的研究中,我们旨在填补这一空白,并帮助医疗保健提供者在T1DM患者使用这些药物的临床决策中。(2) 方法:我们对服用长效GLP-1至少六个月的T1DM患者进行了回顾性图表审查。我们的回顾性图表审查包括开始GLP-1前两年和开始GLP-1后六个月或更长时间的信息。收集的参数包括HbA1c、14天连续血糖监测(CGM)和血糖(BG)数据,以及代谢数据(体重、收缩压和舒张压以及胆固醇水平)。在R和Excel上使用配对t检验进行统计分析,α为0.05。(3) 结果:我们的队列由54名服用长效GLP-1(赛马鲁肽、杜拉鲁肽、艾塞那肽缓释[ER]、阿比鲁肽)的T1DM参与者组成。GLP-1的平均治疗时间为23.85±15.46个月。与GLP-1治疗相比,治疗前HbA1c值平均下降0.71%(%-点,p=0.002)。类似地,对于治疗前与GLP-1治疗值相比,CGM结果显著增加了12.15%的时间(p=0.0009),显示高血糖(BG>180 mg/dL)的平均时间减少了11.97%的平均差异(p=0.006),14天平均BG减少了19 mg/dL(p=0.01),DKA住院率降低,体重减轻3.16kg(p=0.007)。(4)结论:随着更多关于长效GLP-1对2型糖尿病心血管和肾脏益处的数据出现,T1DM的结果尚未报告。我们的研究首次证明了这类药物作为胰岛素辅助治疗T1DM的血糖和代谢益处,以及在平均1.5-2年内使用的安全性。这项研究代表了真实的生活经历,数据值得进一步的前瞻性研究证实。
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引用次数: 2
Histological Assessment of Endochondral Ossification and Bone Mineralization 软骨内成骨和骨矿化的组织学评价
Pub Date : 2023-02-02 DOI: 10.3390/endocrines4010006
Tomoka Hasegawa, Hiromi Hongo, Tomomaya Yamamoto, Takafumi Muneyama, Yukina Miyamoto, N. Amizuka
Finely tuned cartilage mineralization, endochondral ossification, and normal bone formation are necessary for normal bone growth. Hypertrophic chondrocytes in the epiphyseal cartilage secrete matrix vesicles, which are small extracellular vesicles initiating mineralization, into the intercolumnar septa but not the transverse partitions of the cartilage columns. Bone-specific blood vessels invade the unmineralized transverse septum, exposing the mineralized cartilage cores. Many osteoblast precursors migrate to the cartilage cores, where they synthesize abundant bone matrices, and mineralize them in a process of matrix vesicle-mediated bone mineralization. Matrix vesicle-mediated mineralization concentrates calcium (Ca) and inorganic phosphates (Pi), which are converted into hydroxyapatite crystals. These crystals grow radially and are eventually get out of the vesicles to form spherical mineralized nodules, leading to collagen mineralization. The influx of Ca and Pi into the matrix vesicle is regulated by several enzymes and transporters such as TNAP, ENPP1, PiT1, PHOSPHO1, annexins, and others. Such matrix vesicle-mediated mineralization is regulated by osteoblastic activities, synchronizing the synthesis of organic bone material. However, osteocytes reportedly regulate peripheral mineralization, e.g., osteocytic osteolysis. The interplay between cartilage mineralization and vascular invasion during endochondral ossification, as well as that of osteoblasts and osteocytes for normal mineralization, appears to be crucial for normal bone growth.
微调软骨矿化、软骨内骨化和正常骨形成是正常骨生长所必需的。骨骺软骨中的肥大软骨细胞分泌基质小泡,这是一种启动矿化的细胞外小泡,进入柱间隔膜,但不进入软骨柱的横向分区。骨特异性血管侵入未矿化的横隔,暴露矿化的软骨核心。许多成骨细胞前体迁移到软骨核心,在那里它们合成丰富的骨基质,并在基质囊泡介导的骨矿化过程中矿化。基质囊泡介导的矿化浓缩了钙(Ca)和无机磷酸盐(Pi),它们被转化为羟基磷灰石晶体。这些晶体呈放射状生长,最终从囊泡中出来,形成球形矿化结节,导致胶原蛋白矿化。Ca和Pi流入基质小泡受到几种酶和转运蛋白的调节,如TNAP、ENPP1、PiT1、Phosphor1、膜联蛋白等。这种基质囊泡介导的矿化受成骨细胞活性的调节,使有机骨材料的合成同步。然而,据报道,骨细胞调节外周矿化,例如骨细胞骨溶解。软骨内骨化过程中软骨矿化和血管侵袭之间的相互作用,以及成骨细胞和骨细胞的正常矿化作用,似乎对正常骨生长至关重要。
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引用次数: 1
Does Health Literacy Have an Impact on Adherence to Diabetes Mellitus Treatment? 健康素养对糖尿病治疗依从性有影响吗?
Pub Date : 2023-02-02 DOI: 10.3390/endocrines4010007
C. Ngoatle, L. S. Hlahla, M. Mphasha, T. Mothiba, M. Themane
(1) Background: Health literacy is the intersection of general literacy, health, and healthcare, but it can also incorporate elements of other types of literacies to varying degrees. The notion of literacy surfaced from the fear that individuals would require more than general literacy skills to manage the complexities of health and health system issues. There is a substantial overlap between general literacy and health literacy. Diabetes patients frequently misinterpret medication instructions, resulting in non-adherence and poor health outcomes. (2) Aim: This study sought to review the literature on the impacts of health literacy on adherence and compliance to diabetes mellitus treatment. (3) Methods: A Narrative Literature Review method was used to identify, analyze, assess, and interpret the available information on health literacy regarding prescribed medication instructions. The following databases and search engines were used to locate the literature: electronic databases, search engines, and hand searches. Fifty-three (53) quantitative and qualitative studies and two books were reviewed. (4) Result: The review pointed out the following: the importance of health literacy, the implications of health illiteracy versus medication non-adherence, factors influencing health literacy versus medication adherence, and the interventions to improve medication non-adherence. (5) Conclusion: Relatively few studies have been conducted on how people living with diabetes should carry out their treatment. Therefore, more research on how people living with diabetes carry out their treatment daily is required. (6) Contributions: This study has identified that health literacy plays a role in adherence to treatment and contributes to improved health outcomes.
(1) 背景:健康素养是一般素养、健康和医疗保健的交叉点,但它也可以在不同程度上融入其他类型的素养。识字的概念源于人们担心,个人需要的不仅仅是一般的识字技能,才能应对卫生和卫生系统问题的复杂性。普通识字和健康识字之间有很大的重叠。糖尿病患者经常误解药物说明书,导致不依从和健康状况不佳。(2) 目的:本研究旨在回顾有关健康知识对糖尿病治疗依从性和依从性的影响的文献。(3) 方法:采用叙述性文献综述法来识别、分析、评估和解释有关处方药说明书的健康素养的可用信息。以下数据库和搜索引擎用于查找文献:电子数据库、搜索引擎和手动搜索。审查了五十三(53)项定量和定性研究以及两本书。(4) 结果:综述指出了以下内容:健康素养的重要性,健康文盲与药物不依从性的关系,影响健康素养与药物依从性的因素,以及改善药物不依从的干预措施。(5) 结论:关于糖尿病患者应该如何进行治疗的研究相对较少。因此,需要对糖尿病患者如何进行日常治疗进行更多的研究。(6) 贡献:这项研究表明,健康知识在坚持治疗方面发挥作用,并有助于改善健康状况。
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引用次数: 0
Oral Health Professionals’ and Patients’ Opinions of Type-2 Diabetes Screenings in an Oral Healthcare Setting 口腔卫生专业人员和患者对口腔卫生机构2型糖尿病筛查的意见
Pub Date : 2023-01-20 DOI: 10.3390/endocrines4010005
R. Mariño, Andre Priede, Michelle King, G. Adams, Maria Sicari, M. Morgan
Objectives: As part of an evaluation of an oral healthcare practice-based model that identifies patients with prediabetes or type-2 diabetes (T2D), this study reports on the experiences and opinions of oral health professionals and patients on the screening program. Methodology: Urban and rural oral healthcare practices were invited to participate. Participating practices invited eligible patients to participate in the screening program. Patients were categorised as low, intermediate, or high-risk for prediabetes/T2D. Patients in the intermediate or high-risk category were referred to their general practitioner (GP) for further investigation. Post-screening surveys were used to assess acceptability, barriers and facilitators of the screening program among participating oral health professionals (OHP) and patients. Results: The post-screening survey was completed by 135 patient, and 38 OHPs (i.e., dentists, dental hygienists, oral health therapists). the majority of OHPs (94.6%) who delivered the protocol were satisfied with the approach. Most patients reported satisfaction with the approach (73.2%) and would recommend it to others. Several barriers for implementation were identified by OHPs and patients. Conclusion: OHPs feedback indicated that the screening model was generally acceptable. The feedback from patients following their participation in this study was overwhelmingly positive, indicating that the screening protocols were accepted by patients.
目的:作为口腔保健实践为基础的模型评估的一部分,识别糖尿病前期或2型糖尿病(T2D)患者,本研究报告了口腔卫生专业人员和患者对筛查计划的经验和意见。方法:邀请城市和农村口腔保健实践参与。参与实践邀请符合条件的患者参加筛查项目。患者被分为低、中、高风险糖尿病前期/T2D。中等或高危类别的患者被转介给他们的全科医生(GP)进行进一步的调查。筛查后调查用于评估参与口腔卫生专业人员(OHP)和患者对筛查计划的可接受性、障碍和促进因素。结果:135名患者和38名ohp(即牙医、口腔卫生员、口腔卫生治疗师)完成了筛查后调查。执行该方案的大多数ohp(94.6%)对该方法感到满意。大多数患者对该方法表示满意(73.2%),并将其推荐给其他人。ohp和患者确定了实施的几个障碍。结论:ohp反馈表明该筛选模型是可接受的。患者参与本研究后的反馈绝大多数是积极的,表明筛查方案被患者接受。
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引用次数: 0
Acknowledgment to the Reviewers of Endocrines in 2022 2022年《内分泌》杂志审稿人致谢
Pub Date : 2023-01-18 DOI: 10.3390/endocrines4010004
High-quality academic publishing is built on rigorous peer review [...]
高质量的学术出版建立在严格的同行评审的基础上[…]
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引用次数: 0
Obesity Is Associated with Increased F2-Isoprostanes and IL-6 in Black Women 黑人女性肥胖与f2 -异前列腺素和IL-6升高有关
Pub Date : 2023-01-18 DOI: 10.3390/endocrines4010003
Mohammad Saleem, Paul D. Kastner, Pouya Mehr, Ginger L. Milne, Jeanne A. Ishimwe, Jennifer H. Park, Cyndya A. Shibao, Annet Kirabo
Obesity affects over 40% of the adult population and is a major risk factor for morbidity and mortality due to cardiovascular disease. Black women have one of the highest prevalences of obesity, insulin resistance, hypertension, and cardiovascular events in the US. We previously found that free radical-mediated lipid peroxidation contributes to IL-6 production in dendritic cells leading to inflammation and hypertension. Thus, we hypothesized that F2-isoprostanes (F2-IsoPs), products and biomarkers of endogenous lipid peroxidation, contribute to increased inflammation and IL-6 production among obese Black women. We studied a total of 88 obese Black women of age 42.0 ± 9.8 years, weight 102 ± 16 kg, and body mass index (BMI) 37.68 ± 5.08. Systolic and diastolic blood pressure were 124 ± 14/76.2 ± 9.9 mmHg, heart rate was 68.31 ± 10.26 beats/min, and fasting insulin was 15.0 ± 8.7 uU/mL. Plasma F2-IsoPs were measured using gas chromatography/negative ion chemical ionization mass spectrometry (GC/NICI-MS). Plasma cytokines, including IL-6, IL-8, IL-10, IL-1β, TNF-a, and C-reactive proteins were measured using multiplex Luminex technology. Anthropometric measurements were performed using dual-energy X-ray absorptiometry. Using Pearson’s correlation analysis, we found that BMI was positively correlated with plasma F2-IsoPs, while inversely correlated with insulin sensitivity in obese Black women. Further, F2-IsoPs were positively correlated with inflammatory marker IL-6 levels while negatively correlated with anti-inflammatory marker IL-10. In addition, we found that plasma F2-IsoPs levels were significantly associated with reduced insulin sensitivity. These results suggest that F2-IsoPs may be associated with obesity-induced cardiovascular risk in Black women by increasing the production of inflammatory cytokine IL-6 and decreasing the production of anti-inflammatory IL-10.
肥胖影响着超过40%的成年人口,是心血管疾病发病率和死亡率的主要危险因素。黑人女性是美国肥胖、胰岛素抵抗、高血压和心血管疾病发病率最高的人群之一。我们之前发现自由基介导的脂质过氧化有助于树突状细胞中IL-6的产生,导致炎症和高血压。因此,我们假设f2 -异前列腺素(F2-IsoPs),内源性脂质过氧化的产物和生物标志物,有助于肥胖黑人女性炎症和IL-6产生的增加。研究对象为88例肥胖黑人女性,年龄42.0±9.8岁,体重102±16 kg,体重指数(BMI) 37.68±5.08。收缩压、舒张压124±14/76.2±9.9 mmHg,心率68.31±10.26次/min,空腹胰岛素15.0±8.7 uU/mL。采用气相色谱/负离子化学电离质谱(GC/NICI-MS)测定血浆F2-IsoPs。血浆细胞因子,包括IL-6、IL-8、IL-10、IL-1β、TNF-a和c反应蛋白使用多重Luminex技术测量。采用双能x射线吸收仪进行人体测量。通过Pearson相关分析,我们发现肥胖黑人女性BMI与血浆F2-IsoPs呈正相关,与胰岛素敏感性呈负相关。F2-IsoPs与炎症标志物IL-6水平呈正相关,与抗炎标志物IL-10水平负相关。此外,我们发现血浆F2-IsoPs水平与胰岛素敏感性降低显著相关。这些结果表明F2-IsoPs可能通过增加炎症细胞因子IL-6的产生和减少抗炎细胞因子IL-10的产生而与肥胖诱导的黑人女性心血管风险相关。
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引用次数: 1
Dysmetabolic Iron Overload Syndrome: Going beyond the Traditional Risk Factors Associated with Metabolic Syndrome 代谢异常铁过载综合征:超越与代谢综合征相关的传统危险因素
Pub Date : 2023-01-16 DOI: 10.3390/endocrines4010002
S. Barbalho, LUCAS FORNARI LAURINDO, R. J. Tofano, U. Flato, C. G. Mendes, R. de Alvares Goulart, Ana Maria Gonçalves Milla Briguezi, M. Bechara
Dysmetabolic iron overload syndrome (DIOS) corresponds to the increase in iron stores associated with components of metabolic syndrome (MtS) and in the absence of an identifiable cause of iron excess. The objective of this work was to review the main aspects of DIOS. PUBMED and EMBASE were consulted, and PRISMA guidelines were followed. DIOS is usually asymptomatic and can be diagnosed by investigating MtS and steatosis. About 50% of the patients present altered hepatic biochemical tests (increased levels of γ-glutamyl transpeptidase itself or associated with increased levels of alanine aminotransferase). The liver may present parenchymal and mesenchymal iron overload, but the excess of iron is commonly mild. Steatosis or steatohepatitis is observed in half of the patients. Fibrosis is observed in about 15% of patients. Hyperferritinemia may damage the myocardium, liver, and several other tissues, increasing morbidity and mortality. Furthermore, DIOS is closely related to oxidative stress, which is closely associated with several pathological conditions such as inflammatory diseases, hypertension, diabetes, heart failure, and cancer. DIOS is becoming a relevant finding in the general population and can be associated with high morbidity/mortality. For these reasons, investigation of this condition could be an additional requirement for the early prevention of cardiovascular diseases.
代谢异常铁过载综合征(DIOS)对应于与代谢综合征(MtS)成分相关的铁储存增加,并且在没有可识别的铁过量原因的情况下。这项工作的目的是审查DIOS的主要方面。咨询PUBMED和EMBASE,并遵循PRISMA指南。DIOS通常是无症状的,可以通过调查MtS和脂肪变性来诊断。约50%的患者的肝脏生化测试发生改变(γ-谷氨酰转肽酶本身水平升高或与丙氨酸氨基转移酶水平升高有关)。肝脏可能出现实质和间充质铁过载,但铁过量通常是轻微的。一半的患者出现脂肪变性或脂肪性肝炎。在大约15%的患者中观察到纤维化。高铁蛋白血症可能损害心肌、肝脏和其他一些组织,增加发病率和死亡率。此外,DIOS与氧化应激密切相关,氧化应激与炎症性疾病、高血压、糖尿病、心力衰竭和癌症等多种病理状况密切相关。DIOS正在成为普通人群中的一个相关发现,并可能与高发病率/死亡率有关。出于这些原因,对这种情况的调查可能是早期预防心血管疾病的额外要求。
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引用次数: 1
Idiopathic Short Stature: What to Expect from Genomic Investigations 特发性身材矮小:基因组调查的预期
Pub Date : 2023-01-09 DOI: 10.3390/endocrines4010001
N. Andrade, L. P. Cellin, R. Rezende, Gabriela A. Vasques, A. Jorge
Short stature is a common concern for physicians caring for children. In traditional investigations, about 70% of children are healthy, without producing clinical and laboratory findings that justify their growth disorder, being classified as having constitutional short stature or idiopathic short stature (ISS). In such scenarios, the genetic approach has emerged as a great potential method to understand ISS. Over the last 30 years, several genes have been identified as being responsible for isolated short stature, with almost all of them being inherited in an autosomal-dominant pattern. Most of these defects are in genes related to the growth plate, followed by genes related to the growth hormone (GH)–insulin-like growth factor 1 (IGF1) axis and RAS-MAPK pathway. These patients usually do not have a specific phenotype, which hinders the use of a candidate gene approach. Through multigene sequencing analyses, it has been possible to provide an answer for short stature in 10–30% of these cases, with great impacts on treatment and follow-up, allowing the application of the concept of precision medicine in patients with ISS. This review highlights the historic aspects and provides an update on the monogenic causes of idiopathic short stature and suggests what to expect from genomic investigations in this field.
身材矮小是照顾儿童的医生普遍关心的问题。在传统调查中,约70%的儿童是健康的,没有产生证明其生长障碍的临床和实验室结果,被归类为体质性身材矮小或特发性身材矮小(ISS)。在这种情况下,基因方法已经成为了解国际空间站的一种很有潜力的方法。在过去的30年里,有几个基因被确定为导致孤立性身材矮小的原因,几乎所有基因都是以常染色体显性遗传模式遗传的。这些缺陷大多存在于与生长板相关的基因中,其次是与生长激素(GH)-胰岛素样生长因子1(IGF1)轴和RAS-MAPK途径相关的基因。这些患者通常没有特定的表型,这阻碍了候选基因方法的使用。通过多基因测序分析,有可能为其中10-30%的病例提供身材矮小的答案,这对治疗和随访有很大影响,从而使精准医学的概念能够应用于ISS患者。这篇综述强调了历史方面,并提供了特发性身材矮小的单基因原因的最新情况,并提出了该领域基因组研究的期望。
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引用次数: 1
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Endocrines
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