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Optimizing blood glucose predictions in type 1 diabetes patients using a stacking ensemble approach 使用堆叠集成方法优化1型糖尿病患者的血糖预测
Q3 Medicine Pub Date : 2025-05-26 DOI: 10.1016/j.endmts.2025.100253
Vincent B. Liu , Laura Y. Sue , Oscar Madrid Padilla , Yingnian Wu

Introduction

The diabetes pandemic, including 828 million adults worldwide in 2022, would benefit from continued development of novel, effective and accurate blood glucose prediction systems. Using the DiaTrend dataset, this study used stacking machine learning optimized by Grey Wolf Optimizer to construct and assess prediction models for blood glucose levels in type 1 diabetes patients.

Methods

The DiaTrend dataset includes 27,561 days of continuous glucose monitoring and 8220 days of insulin pump data for 54 patients with type 1 diabetes. Grey Wolf optimization was used to tune and evaluate three machine learning algorithms – Random Forest, LSTM, GRU – for blood glucose predictions, whose predictions were then combined into an XGBoost stacking ensemble meta-learner.

Results

This study looked at three baseline algorithms for predicting blood glucose levels. Machine learning models Random Forest, LSTM, and GRU served as baselines, with MAE, RMSE, and MARD values. GRU had the best predictive accuracy of the initial models. Grey Wolf optimization contributed to achieving optimal baseline model results. Stacking ensemble learning via XGBoost meta-learner (MAE = 10.65, RMSE = 14.59, MARD = 6.98) achieved higher performance than the baseline models.

Conclusion

The GRU method with Grey Wolf optimization outperformed the other models with the lowest MAE, RMSE, and MARD, but the Stacked XGBoost model fared best. These findings emphasize the need to improve parameter selection with approaches such as Grey Wolf or stacking ensemble methods to achieve accurate blood glucose predictions. These prediction models can aid in the continued development of monitoring devices, and algorithms for these devices, which contain alert systems for impending abnormal blood glucose levels, allowing for timely diabetes self-management.
到2022年,全球将有8.28亿成年人患有糖尿病,新型、有效和准确的血糖预测系统的持续发展将使糖尿病大流行受益。本研究使用ditrend数据集,使用灰狼优化器优化的堆叠机器学习构建和评估1型糖尿病患者血糖水平的预测模型。方法ditrend数据集包括54例1型糖尿病患者27561天连续血糖监测和8220天胰岛素泵数据。灰狼优化用于调整和评估三种机器学习算法——随机森林、LSTM、GRU——用于血糖预测,然后将其预测合并到XGBoost堆叠集成元学习器中。结果:本研究着眼于预测血糖水平的三种基线算法。机器学习模型Random Forest, LSTM和GRU作为基线,具有MAE, RMSE和MARD值。在初始模型中,GRU具有最好的预测精度。灰狼优化有助于获得最佳的基线模型结果。通过XGBoost元学习器的叠加集成学习(MAE = 10.65, RMSE = 14.59, MARD = 6.98)取得了比基线模型更高的性能。结论采用灰狼优化的GRU方法在MAE、RMSE和MARD方面均优于其他模型,但以Stacked XGBoost模型表现最好。这些发现强调需要改进参数选择的方法,如灰狼或堆叠集成方法,以实现准确的血糖预测。这些预测模型有助于监测设备和这些设备的算法的持续发展,这些设备包含即将出现的异常血糖水平的警报系统,允许及时的糖尿病自我管理。
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引用次数: 0
Impending thyroid storm in a case of Down syndrome with burr hole surgery: A case report 唐氏综合征伴钻孔手术的甲状腺风暴:1例报告
Q3 Medicine Pub Date : 2025-05-21 DOI: 10.1016/j.endmts.2025.100250
Ayyesha Yuanita , Hermina Novida

Introduction

An accidental injury requiring surgery in a patient with Down syndrome (DS) and hyperthyroidism is an uncommon case, in which thyroid hormone control plays a crucial role in successful surgery.

Case presentation

An Indonesian woman, 33 years old, suffered an accidental brain injury and gradually lost consciousness. She was born with DS and had no prior medical consultation. At the emergency room, she was diagnosed with hyperthyroidism and an acute subdural hematoma. According to the Burch-Wartofsky (BW) score, the examination revealed an impending thyroid storm (40 points). Management of hyperthyroidism aims to avoid the thyroid storm before, during, and after double burr hole drainage, which is treated with glucocorticoid and antithyroid drugs. She was followed up for 6 months after surgery and had considerable improvement.

Conclusion

Management of hyperthyroidism have a crucial role in DS patient with burr hole drainage to improve surgical outcomes, control of cardiac output, and minimize thyroid storm.
唐氏综合征(DS)合并甲状腺功能亢进患者发生意外伤害需要手术治疗是一种罕见的病例,其中甲状腺激素的控制对手术成功起着至关重要的作用。病例介绍:一名33岁的印度尼西亚妇女意外脑损伤并逐渐失去意识。她出生时患有退行性椎体滑移,事先没有接受过医疗咨询。在急诊室,她被诊断为甲状腺功能亢进和急性硬膜下血肿。根据Burch-Wartofsky (BW)评分,检查显示甲状腺风暴即将来临(40分)。治疗甲状腺功能亢进的目的是避免双钻孔引流前、引流中、引流后甲状腺风暴的发生,并给予糖皮质激素和抗甲状腺药物治疗。术后随访6个月,病情明显好转。结论处理甲状腺功能亢进对DS钻孔引流术患者改善手术效果、控制心排血量、减少甲状腺风暴有重要作用。
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引用次数: 0
l-carnitine protects against bile acid-induced mitochondrial dysfunction and IGF-1 impairment in hepatocyte cultures 左旋肉碱对肝细胞培养中胆汁酸诱导的线粒体功能障碍和IGF-1损伤具有保护作用
Q3 Medicine Pub Date : 2025-05-20 DOI: 10.1016/j.endmts.2025.100249
Wafa'a Alqabandi, Maira Alsaeid, Gursev Dhaunsi

Background and aims

Excessive amounts of bile acids (ΒΑ) exert hepatotoxic effects. We investigated the effects of glycochenodeoxycholic acid (GCDC) on mitochondrial function and insulin-like growth factor-1 (IGF-1) activity in hepatocytes and also examined if l-carnitine (CRNT) has any protective role.

Methods

Primary hepatocyte cultures were treated with 0–100 μM GCDC with or without 5 mM l-carnitine (CRNT). DNA synthesis was measured by bromodeoxyuridine incorporation assay. Enzymic activities of carnitine palmitoyltransferase-1 (CPT-1), cytochrome c oxidase (CcO) and medium chain-acylCoA dehydrogenase (MCAD), were measured in hepatocyte homogenates. Expression of peroxisome proliferator activated receptor gamma coactivator 1-α (PGC-1α) and IGF-1 receptor (IGF-1R) was detected by RT- PCR and Western blot analysis, respectively.

Results

Treatment with GCDC significantly decreased the enzymatic activity of MCAD, CPT-1 and CcO (P < 0.01), and mitochondrial ATP content. Additionally, GCDC significantly increased malondialdehyde (MDA) levels in mitochondria and downregulated PGC-1α (p < 0.01). Furthermore, the IGF-1-induced DNA synthesis and IGF-1R gene expression were also notably reduced in GCDC-treated hepatocytes. However, co-treatment with 5 mM CRNT markedly abrogated the GCDC-induced impairment of CcO activity and PGC-1α downregulation, while it had no effect on MCAD activity. In addition, CRNT treatment also restored the enzymatic activity of CPT-1 and the gene expression levels of IGF-1 in GCDC-treated hepatocytes (p < 0.05).

Conclusions

GCDC-induced hepatotoxic effects could be triggered by mitochondrial dysfunction and impairment of IGF-1 activity. CRNT has potential beneficial effects against ΒΑ-induced cytotoxicity via enhancing the CPT-1 and CcO enzyme activities, and ATP production in addition to upregulation of PGC-1α and IGF-1R.
背景和目的过量的胆汁酸(ΒΑ)会产生肝毒性作用。我们研究了糖鹅脱氧胆酸(GCDC)对肝细胞线粒体功能和胰岛素样生长因子-1 (IGF-1)活性的影响,并研究了左旋肉碱(CRNT)是否具有任何保护作用。方法用0 ~ 100 μM GCDC加或不加5 mM左旋肉碱(CRNT)处理原代肝细胞。采用溴脱氧尿苷掺入法测定DNA合成。测定肝细胞匀浆中肉碱棕榈酰基转移酶-1 (CPT-1)、细胞色素c氧化酶(CcO)和中链酰基辅酶a脱氢酶(MCAD)的酶活性。RT- PCR和Western blot分别检测过氧化物酶体增殖物激活受体γ辅助激活因子1-α (PGC-1α)和IGF-1受体(IGF-1R)的表达。结果GCDC治疗可显著降低MCAD、CPT-1和CcO的酶活性(P <;0.01),线粒体ATP含量。此外,GCDC显著增加线粒体中丙二醛(MDA)水平,下调PGC-1α (p <;0.01)。此外,在gcdc处理的肝细胞中,igf -1诱导的DNA合成和IGF-1R基因表达也显著降低。然而,与5 mM CRNT共处理可明显消除gcd诱导的CcO活性损伤和PGC-1α下调,而对MCAD活性没有影响。此外,CRNT处理还恢复了gcdc处理的肝细胞中CPT-1的酶活性和IGF-1的基因表达水平(p <;0.05)。结论线粒体功能障碍和IGF-1活性损伤可触发sgcdc诱导的肝毒性作用。除了上调PGC-1α和IGF-1R外,CRNT还通过增强CPT-1和CcO酶活性,以及ATP的产生,对ΒΑ-induced细胞毒性具有潜在的有益作用。
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引用次数: 0
The correlation between COVID-19 severity and elevated level of serum glucose COVID-19严重程度与血糖升高的相关性
Q3 Medicine Pub Date : 2025-05-19 DOI: 10.1016/j.endmts.2025.100248
Zahraa Q. Ali , Nawar S. Mohammed , Hussam H. Muhammed
The collision of COVID-19 and type 2 diabetes (T2D) highlights T2D as the second most prevalent comorbidity in COVID-19. This infection exacerbates complications in diabetics. It elevates blood glucose through excessive glucocorticoid and catecholamine release. This hyperglycemia triggers pro-inflammatory monocytes, heightens platelet reactivity, and amplifies cardiovascular deaths in diabetics. This cross-sectional study, conducted at Private Nursing Home Hospital in Baghdad, focused on 143 COVID-19 patients diagnosed via RNA detection in nasopharyngeal secretions using PCR from May to August 2021. The patients, aged 18 to 76, had no prior history of diabetes upon admission. An 86-member control group, free from COVID-19 and diabetes history, aged 20 to 73, was also included. BMI, platelet count, WBC, ESR, RBG, and serum levels of the alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels were measured. The results revealed statistically highly differences in RBG between the two groups (p-value = 0.001), and significant variations in the Mean ± SD values of ALT and AST enzyme levels, as well as in WBC and ESR, when comparing COVID patients to non-COVID patients. In summary, our findings show a positive correlation between admission hyperglycemia and the risk of severe COVID-19, emphasizing the significance of monitoring and managing blood glucose levels. Effective glycemic control could aid in mitigating COVID-19 progression and is integral to comprehensive treatment. These glucose-related changes and COVID-19 impact on the pancreas may contribute to the development of T2D.
COVID-19和2型糖尿病(T2D)的冲突表明,T2D是COVID-19中第二大常见合并症。这种感染加剧了糖尿病患者的并发症。它通过释放过量的糖皮质激素和儿茶酚胺来升高血糖。这种高血糖会触发促炎单核细胞,提高血小板反应性,并增加糖尿病患者的心血管死亡。这项横断面研究是在巴格达私立养老院医院进行的,重点研究了2021年5月至8月期间通过PCR在鼻咽分泌物中检测RNA诊断的143名COVID-19患者。患者年龄18至76岁,入院时无糖尿病病史。对照组86人,无新冠肺炎和糖尿病病史,年龄在20至73岁之间。测定BMI、血小板计数、WBC、ESR、RBG、血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、碱性磷酸酶(ALP)水平。结果显示,两组患者的RBG差异具有统计学意义(p值= 0.001),ALT和AST酶水平的Mean±SD值以及WBC和ESR的差异具有统计学意义,与未患COVID的患者相比。综上所述,我们的研究结果表明入院时高血糖与重症COVID-19的风险呈正相关,强调了监测和管理血糖水平的重要性。有效的血糖控制有助于缓解COVID-19的进展,是综合治疗的组成部分。这些血糖相关的变化和COVID-19对胰腺的影响可能导致T2D的发展。
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引用次数: 0
CRF1 receptor antagonists in congenital adrenal hyperplasia: A systematic review and meta-analysis of phase 2 open-label and phase 3 clinical trials CRF1受体拮抗剂治疗先天性肾上腺增生:2期开放标签和3期临床试验的系统回顾和荟萃分析
Q3 Medicine Pub Date : 2025-05-19 DOI: 10.1016/j.endmts.2025.100247
Mir wajid Majeed , Emma Finnegan , Mariano Gallo Ruelas , Marco Quirós , Marina Barbosa da Silva , Issa Salha , Catalina Herrán-Fonseca , Helen Michaela de Oliveira , Melissa Chacón Quirós , Raheel Ahmed , Zainab Humayun , Tajamul Hussain Shah , Mohammad Ashraf Ganie

Introduction

Classical Congenital Adrenal Hyperplasia (CAH) due to 21 hydroxylase deficiency is a rare autosomal recessive disorder. Recent clinical trials indicate that type 1 Corticotropin-releasing hormone receptor OR CRFR1 receptor OR CRF1 antagonists could provide a new treatment option for CAH. Hence, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these drugs in patients with CAH.

Methods

Medline, Embase, and Cochrane Library were searched for eligible studies. Analysis of Phase 2b and Phase 3 clinical trials was carried out. Mean percent changes and event numbers were pooled to perform a single-arm meta-analysis. Binary data was pooled from Phase 3 clinical trials. Statistical analysis was performed using RStudio version 4.1.2 (R Foundation for Statistical Computing), under a random-effects model. Heterogeneity was assessed using I2 statistics.

Results

From Phase 2 clinical trials, pooled efficacy data from studies with CRF1 antagonists resulted in a mean decrease from baseline levels in adrenocorticotropic hormone (ACTH) -57.86 %; 95 % CI -71.15 to −44.58 %; I2 = 0 %), 17-OHP (17-hydroxyprogesterone) (Mean − 40.01 %;95 % CI -66.31 to −13.71 %; I2 = 66 %) and androstenedione (−39.24 %; 95 % CI -62.77 to −15.70 %; I2 = 78 %). Overall, 71 % (95 % CI 53.91 % to 85.39 %) of the included patients experienced adverse events of any grade, with no significant difference between drug-type subgroups (P = 0.83). In Phase 3 trials, compared to placebo, CRF1 receptor antagonists resulted in a significant reduction of 17-OHP (MD: −6049.40 ng/dL; 95 % CI: −6665.23 to −5433.58 ng/dL; p < 0.01; I2 = 0 %), androstenedione levels (MD: −313.58 ng/dL; 95 % CI: −400.14 to −227.02 ng/dL; p < 0.01; I2 = 0 %) and need for glucocorticoid dose reduction (MD: −20.37 %; 95 % CI: −26.73 % to −14.00 %; p < 0.01; I2 = 47 %) No statistically significant difference was found between the two groups with respect to treatment emergent adverse effects 1.02 (95 % CI: 0.91 to 1.15; p = 0.72; I2 = 0 %) or treatment discontinuation 3.28 (95 % CI: 0.41 to 26.51; p = 0.27; I2 = 0 %).

Conclusion

CRF1 antagonists, especially Crinecerfont, are promising in the treatment of CAH. Phase 2b and Phase 3 clinical trials of CRF1 antagonists involving Crinecerfont demonstrated consistent results supporting its efficacy and safety. These studies showed significant reductions in ACTH, 17-OHP and androstenedione levels, as well as a decreased need for glucocorticoid doses, with no notable difference in adverse effects compared to placebo.
摘要经典先天性肾上腺增生症(CAH)是一种罕见的常染色体隐性遗传病。最近的临床试验表明,1型促肾上腺皮质激素释放激素受体或CRFR1受体或CRF1拮抗剂可能为CAH提供新的治疗选择。因此,我们进行了系统回顾和荟萃分析,以评估这些药物对CAH患者的疗效和安全性。方法检索medline、Embase和Cochrane图书馆中符合条件的研究。对2b期和3期临床试验进行分析。平均百分比变化和事件数合并进行单臂荟萃分析。二进制数据来自3期临床试验。采用随机效应模型,采用RStudio 4.1.2版本(R Foundation for Statistical Computing)进行统计分析。采用I2统计量评估异质性。结果:从2期临床试验中,来自CRF1拮抗剂研究的综合疗效数据显示,促肾上腺皮质激素(ACTH)从基线水平平均下降57.86%;95% CI -71.15 ~ - 44.58%;I2 = 0%), 17-OHP (17-hydroxyprogesterone)(意味着−40.01%;95%可信区间-66.31−13.71%;I2 = 66%)和雄烯二酮(- 39.24%;95% CI -62.77 ~ - 15.70%;i2 = 78%)。总体而言,71% (95% CI 53.91% ~ 85.39%)的纳入患者经历了任何级别的不良事件,药物类型亚组之间无显著差异(P = 0.83)。在3期试验中,与安慰剂相比,CRF1受体拮抗剂导致17-OHP显著降低(MD: - 6049.40 ng/dL;95% CI:−6665.23 ~−5433.58 ng/dL;p & lt;0.01;I2 = 0%),雄烯二酮水平(MD:−313.58 ng/dL;95% CI:−400.14 ~−227.02 ng/dL;p & lt;0.01;I2 = 0%)和糖皮质激素减量需求(MD:−20.37%;95% CI:−26.73% ~−14.00%;p & lt;0.01;I2 = 47%)两组在治疗紧急不良反应1.02方面差异无统计学意义(95% CI: 0.91 ~ 1.15;p = 0.72;I2 = 0%)或停止治疗3.28 (95% CI: 0.41 ~ 26.51;p = 0.27;i2 = 0%)。结论crf1拮抗剂在治疗CAH方面具有较好的应用前景,尤其是criecerfont。涉及criecerfont的CRF1拮抗剂的2b期和3期临床试验显示一致的结果支持其有效性和安全性。这些研究表明,ACTH、17-OHP和雄烯二酮水平显著降低,糖皮质激素剂量需求减少,与安慰剂相比,不良反应无显著差异。
{"title":"CRF1 receptor antagonists in congenital adrenal hyperplasia: A systematic review and meta-analysis of phase 2 open-label and phase 3 clinical trials","authors":"Mir wajid Majeed ,&nbsp;Emma Finnegan ,&nbsp;Mariano Gallo Ruelas ,&nbsp;Marco Quirós ,&nbsp;Marina Barbosa da Silva ,&nbsp;Issa Salha ,&nbsp;Catalina Herrán-Fonseca ,&nbsp;Helen Michaela de Oliveira ,&nbsp;Melissa Chacón Quirós ,&nbsp;Raheel Ahmed ,&nbsp;Zainab Humayun ,&nbsp;Tajamul Hussain Shah ,&nbsp;Mohammad Ashraf Ganie","doi":"10.1016/j.endmts.2025.100247","DOIUrl":"10.1016/j.endmts.2025.100247","url":null,"abstract":"<div><h3>Introduction</h3><div>Classical Congenital Adrenal Hyperplasia (CAH) due to 21 hydroxylase deficiency is a rare autosomal recessive disorder. Recent clinical trials indicate that type 1 Corticotropin-releasing hormone receptor OR CRFR1 receptor OR CRF1 antagonists could provide a new treatment option for CAH. Hence, we conducted a systematic review and meta-analysis to evaluate the efficacy and safety of these drugs in patients with CAH.</div></div><div><h3>Methods</h3><div>Medline, Embase, and Cochrane Library were searched for eligible studies. Analysis of Phase 2b and Phase 3 clinical trials was carried out. Mean percent changes and event numbers were pooled to perform a single-arm meta-analysis. Binary data was pooled from Phase 3 clinical trials. Statistical analysis was performed using RStudio version 4.1.2 (R Foundation for Statistical Computing), under a random-effects model. Heterogeneity was assessed using I<sup>2</sup> statistics.</div></div><div><h3>Results</h3><div>From Phase 2 clinical trials, pooled efficacy data from studies with CRF1 antagonists resulted in a mean decrease from baseline levels in adrenocorticotropic hormone (ACTH) -57.86 %; 95 % CI -71.15 to −44.58 %; I<sup>2</sup> = 0 %), 17-OHP (17-hydroxyprogesterone) (Mean − 40.01 %;95 % CI -66.31 to −13.71 %; I<sup>2</sup> = 66 %) and androstenedione (−39.24 %; 95 % CI -62.77 to −15.70 %; I<sup>2</sup> = 78 %). Overall, 71 % (95 % CI 53.91 % to 85.39 %) of the included patients experienced adverse events of any grade, with no significant difference between drug-type subgroups (<em>P</em> = 0.83). In Phase 3 trials, compared to placebo, CRF1 receptor antagonists resulted in a significant reduction of 17-OHP (MD: −6049.40 ng/dL; 95 % CI: −6665.23 to −5433.58 ng/dL; <em>p</em> &lt; 0.01; I<sup>2</sup> = 0 %), androstenedione levels (MD: −313.58 ng/dL; 95 % CI: −400.14 to −227.02 ng/dL; p &lt; 0.01; I<sup>2</sup> = 0 %) and need for glucocorticoid dose reduction (MD: −20.37 %; 95 % CI: −26.73 % to −14.00 %; p &lt; 0.01; I<sup>2</sup> = 47 %) No statistically significant difference was found between the two groups with respect to treatment emergent adverse effects 1.02 (95 % CI: 0.91 to 1.15; <em>p</em> = 0.72; I<sup>2</sup> = 0 %) or treatment discontinuation 3.28 (95 % CI: 0.41 to 26.51; <em>p</em> = 0.27; I<sup>2</sup> = 0 %).</div></div><div><h3>Conclusion</h3><div>CRF1 antagonists, especially Crinecerfont, are promising in the treatment of CAH. Phase 2b and Phase 3 clinical trials of CRF1 antagonists involving Crinecerfont demonstrated consistent results supporting its efficacy and safety. These studies showed significant reductions in ACTH, 17-OHP and androstenedione levels, as well as a decreased need for glucocorticoid doses, with no notable difference in adverse effects compared to placebo.</div></div>","PeriodicalId":34427,"journal":{"name":"Endocrine and Metabolic Science","volume":"18 ","pages":"Article 100247"},"PeriodicalIF":0.0,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144169616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The safety and effectiveness of oxandrolone on different clinical conditions: A systematic review 奥胺龙在不同临床条件下的安全性和有效性:一项系统综述
Q3 Medicine Pub Date : 2025-05-14 DOI: 10.1016/j.endmts.2025.100246
Izabelle de Mello Gindri , Gabriel Almeida , Caio Saraiva , Gustavo Ferrari , Darlan Dallacosta , Carlos Rodrigo de Mello Roesler

Background

Oxandrolone is a synthetic chemical compound derived from testosterone with a 17-alpha-alkylated structure, showing high potential to enhance the hypermetabolic response and improve clinical outcomes.

Objectives

We aimed to synthesize evidence regarding the safety and effectiveness of Oxandrolone for recognized health problems.

Data sources

A systematic review was performed across six databases using Medical Subject Headings (MeSH) terms and keywords.

Study eligibility criteria, participants, and interventions

We included randomized controlled trials involving children, adolescents, adults, and older adults treated with oral Oxandrolone at doses ranging from 5 to 80 mg.

Study appraisal and synthesis methods

Two reviewers independently conducted the selection, extraction, and quality assessment processes. A protocol was registered in PROSPERO (CRD42024539483).

Results

A total of 24 studies with 1905 participants were included. In children with burns, Oxandrolone increased bone mineral content, preserved lean body mass, and reduced intensive care length of stay. In children with Klinefelter Syndrome, it improved lean body mass and measures of cardiometabolic health. Positive effects on weight and well-being were noted in adults with HIV, and improvements in lean mass and muscle strength were observed in older women. Most reported adverse events were elevated liver enzymes and musculoskeletal complaints.

Limitations

Studies showed heterogeneity in populations, interventions, and outcomes assessed.

Conclusions and implications of key findings

Oxandrolone administration appears to be associated with improvements in body mass, composition indices, and reduced hospitalization time, with a low incidence of side effects. Further investigations are necessary to confirm clinical benefits for specific diseases.

Systematic review registration

PROSPERO CRD42024539483.
doxandrolone是一种由睾酮衍生的合成化合物,具有17-烷基化结构,具有增强高代谢反应和改善临床结果的潜力。目的:综合有关奥山龙治疗公认健康问题的安全性和有效性的证据。数据来源使用医学主题词(MeSH)术语和关键词对六个数据库进行系统评价。研究资格标准、参与者和干预措施我们纳入了随机对照试验,涉及儿童、青少年、成人和老年人,口服奥雄龙的剂量范围为5 - 80mg。研究评价和综合方法两名审稿人独立进行选择、提取和质量评估过程。协议在PROSPERO中注册(CRD42024539483)。结果共纳入24项研究,受试者1905人。在烧伤儿童中,奥雄龙增加骨矿物质含量,保持瘦体重,缩短重症监护时间。在患有克氏综合征的儿童中,它改善了瘦体重和心脏代谢健康指标。艾滋病毒对成年艾滋病毒感染者的体重和幸福感产生了积极影响,老年妇女的瘦质量和肌肉力量也有所改善。大多数报告的不良事件是肝酶升高和肌肉骨骼不适。局限性:研究显示人群、干预措施和评估结果存在异质性。结论和关键发现的意义:给药索雄龙似乎与改善体重、成分指数和缩短住院时间有关,而且副作用发生率低。需要进一步的研究来证实对特定疾病的临床益处。系统评价注册号prospero CRD42024539483。
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引用次数: 0
Alpha-lipoic acid regulates pro-inflammatory cytokines and hormones in letrozole-induced polycystic ovary syndrome in rats 硫辛酸调节来曲唑诱导的多囊卵巢综合征大鼠的促炎细胞因子和激素
Q3 Medicine Pub Date : 2025-05-03 DOI: 10.1016/j.endmts.2025.100245
Fehintoluwa Joy Femi-Olabisi , Olawunmi Rashidat Oyerinde , Opeyemi Olubunmi Faokunla , Sikemi Adejoke Omar , Precious Evy Igene , Olamide Esther Asaluwala , Bisi Olajumoke Adeoye , Odunayo Olowolehin Oladoye
Polycystic ovary syndrome (PCOS) a common endocrine disorder affecting 5–10 % of women in their reproductive age with reproductive and metabolic disorders such as anovulation/oligo-ovulation, hyperinsulinemia, glucose intolerance, obesity and dyslipidemia. Among other heterogeneous symptoms, studies have linked PCOS to low-grade chronic inflammation. Alpha-lipoic acid (ALA), an essential mitochondrial co-factor and safe natural molecule acts as an antioxidant. In this study, letrozole-induced PCOS rat model was used to investigate the effect of ALA on inflammatory cytokines such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and hormones such as testosterone (T), luteinizing hormone (LH) and insulin. Twenty-eight rats were randomly divided into four groups of seven rats each- Group 1,2,3 and 4 (Control, PCOS, PCOS+metformin (MET) + clomiphene citrate (CC), and PCOS+ALA respectively). PCOS was induced by orally administering 1 mg/kg/day of letrozole for 21 days. ALA (1 mg/day) was administered orally to PCOS rats, and the reference drugs (7.14 mg/kg/day of MET co-administered with 2 mg/kg/day CC) were given orally for 14 days. Results revealed acyclicity in the oestrous cycle of PCOS rats characterized by persistent estrus and diestrus phases was completely reversed by ALA compared to the reference drug-treated PCOS group. ALA decreased serum fasting blood sugar, IL-6, TNF-α, total cholesterol (TC), Triglycerides (trigs), low-density lipoprotein-cholesterol (LDL-C), insulin, and LH. Serum high-density lipoprotein-cholesterol (HDLC) was significantly increased (p < 0.05) in the ALA-treated group compared to the control rats. Therefore, the efficacy of ALA as a regulator of pro-inflammatory cytokines and reproductive factors can be exploited in developing treatments for PCOS.
多囊卵巢综合征(PCOS)是一种常见的内分泌紊乱,影响5 - 10%的育龄妇女,伴有生殖和代谢紊乱,如无排卵/少排卵、高胰岛素血症、葡萄糖耐受不良、肥胖和血脂异常。在其他异质性症状中,研究已将多囊卵巢综合征与低度慢性炎症联系起来。α -硫辛酸(ALA)是线粒体必需的辅助因子,也是一种安全的天然分子,具有抗氧化剂的作用。本研究采用来曲唑诱导的PCOS大鼠模型,研究ALA对炎性细胞因子如白细胞介素-6 (IL-6)、肿瘤坏死因子-α (TNF-α)以及激素如睾酮(T)、黄体生成素(LH)和胰岛素的影响。将28只大鼠随机分为1、2、3、4组(对照组、PCOS、PCOS+二甲双胍(MET) +柠檬酸克罗米芬(CC)、PCOS+ALA),每组7只。口服来曲唑1 mg/kg/d诱导PCOS 21 d。PCOS大鼠口服ALA (1 mg/d),对照药(7.14 mg/kg/d MET与2 mg/kg/d CC共给药),连续14 d。结果显示,与对照药物治疗PCOS组相比,ALA完全逆转了PCOS大鼠持续发情和发情期的不周期性。ALA降低血清空腹血糖、IL-6、TNF-α、总胆固醇(TC)、甘油三酯(trigs)、低密度脂蛋白-胆固醇(LDL-C)、胰岛素和LH。血清高密度脂蛋白-胆固醇(HDLC)显著升高(p <;0.05),与对照组比较差异有统计学意义(p < 0.05)。因此,ALA作为促炎细胞因子和生殖因子的调节因子的功效可用于开发多囊卵巢综合征的治疗方法。
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引用次数: 0
The association between serum leptin, adiponectin and resistin levels with chronic kidney disease with and without hemodialysis patients 血清瘦素、脂联素和抵抗素水平与慢性肾病伴和不伴血液透析患者的关系
Q3 Medicine Pub Date : 2025-04-24 DOI: 10.1016/j.endmts.2025.100244
Maha Elttayef Jasim , Firas Faris Rija , Sura Zahim Hussein
Chronic kidney disease (CKD) is major and urgent public health problem caused by a progressive reduce in renal function during some months or years which cause functional or structural abnormalities of the kidney. In renal failure, many adipokines are important in endothelial dysfunction, like inflammation and oxidative stress. This study aims to evaluate the changes of some adipokines in chronic kidney disease (CKD) with and without hemodialysis (HD) Patients. Blood samples were collected from dialysis Unit in Tikrit Teaching Hospital in Tikrit city which started from January- July 2024 who aged (18 - 68) years old. The study subjects were 90 individuals who consist of 30 healthy individuals, 30 CKD patients with hemodialysis treatment and 30 CKD patients without hemodialysis treatment. The present study showed that leptin, adiponectin and resistin were increased in CKD patients with HD and (adiponectin and resistin) were decreased in CKD patients without HD while leptin was increased in CKD patients without HD when compared with control group. Adipokines changes in hemodialysis patients rather than pre dialysis CKD patients.
慢性肾脏疾病(CKD)是一种严重而紧迫的公共卫生问题,它是由几个月或几年的肾功能进行性下降引起的,导致肾脏的功能或结构异常。在肾衰竭中,许多脂肪因子在内皮功能障碍中起重要作用,如炎症和氧化应激。本研究旨在评估慢性肾脏疾病(CKD)伴和不伴血液透析(HD)患者中一些脂肪因子的变化。从2024年1月至7月在提克里特市提克里特教学医院透析室采集了年龄在(18 - 68)岁的血液样本。研究对象为90人,包括30名健康个体,30名接受血液透析治疗的CKD患者和30名未接受血液透析治疗的CKD患者。本研究显示,与对照组相比,合并HD的CKD患者瘦素、脂联素和抵抗素升高,不合并HD的CKD患者瘦素(脂联素和抵抗素)降低,而不合并HD的CKD患者瘦素升高。血液透析患者而非透析前CKD患者的脂肪因子变化。
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引用次数: 0
Optimizing pre-genetic diagnosis of monogenic diabetes: clinical thresholds for targeted testing 优化单基因糖尿病的遗传前诊断:靶向检测的临床阈值
Q3 Medicine Pub Date : 2025-04-23 DOI: 10.1016/j.endmts.2025.100243
Pichakacheri Sureshkumar , Sidharth S. Kumar

Background

Monogenic Diabetes Mellitus (MDM) represents a minority of Diabetes Mellitus (DM) cases but poses diagnostic complexities owing to its clinical overlap with other forms of DM. Preliminary clinical screening is crucial for diagnosis due to the paucity of genetic testing facilities.

Aim

We aimed to identify clinical thresholds that could enhance the likelihood of obtaining positive genetic test results while excluding young-onset T2DM in suspected cases of MDM.

Methodology

We analyzed the demographic, anthropometric, and biochemical details of genetically confirmed MDM participants (n = 10) from our center and compared them with those of clinically suspected patients who tested negative for MDM (n = 67), excluding two neonatal DM (NDM) cases. Using Receiver Operating Characteristic curves, we determined the thresholds for various parameters, prioritizing a sensitivity of ≥75 %.

Results

The upper cut-off values obtained for identifying individuals with a potential for genetic positivity were age of onset of DM 25.5 years, BMI 23.5 kg/m2, visceral fat 7 %, waist circumference (irrespective of gender) 86 cm, random C-peptide 1.41 ng/mL, AST 31 units/dL, ALT 41 units/dL, triglyceride 150 mg/dL, and for HDL, the lower cut-off point was 48.5 mg/dL.

Conclusion

These defined thresholds offer a potential to enhance the efficient use of genetic testing by ensuring more targeted utilization, thus optimizing resource allocation and improving diagnostic accuracy in the assessment of MDM.
背景单基因糖尿病(MDM)占糖尿病(DM)病例的少数,但由于其与其他形式的DM的临床重叠,使诊断变得复杂。由于缺乏基因检测设施,初步的临床筛查对诊断至关重要。我们旨在确定临床阈值,以提高获得阳性基因检测结果的可能性,同时排除疑似MDM病例中年轻发病的T2DM。方法:我们分析了我们中心遗传证实的MDM参与者(n = 10)的人口学、人体测量学和生化细节,并将其与临床疑似MDM阴性患者(n = 67)进行比较,不包括2例新生儿DM (NDM)病例。使用受试者工作特征曲线,我们确定了各种参数的阈值,优先考虑灵敏度≥75%。结果识别潜在遗传阳性个体的上限临界值为DM发病年龄25.5岁,BMI 23.5 kg/m2,内脏脂肪7%,腰围(不分性别)86 cm,随机c肽1.41 ng/mL, AST 31单位/dL, ALT 41单位/dL,甘油三酯150 mg/dL, HDL的下限临界值为48.5 mg/dL。结论这些定义的阈值有可能通过确保更有针对性的利用来提高基因检测的效率,从而优化资源分配,提高MDM评估的诊断准确性。
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引用次数: 0
Screening of MKRN3, DLK1, KISS1, KISS1R, and PROKR2 genes sequences in related girls with central precocious puberty for a personalized management 筛选中枢性性早熟相关女孩的MKRN3、DLK1、KISS1、KISS1R和PROKR2基因序列以进行个性化管理
Q3 Medicine Pub Date : 2025-04-22 DOI: 10.1016/j.endmts.2025.100242
Ayah Alhusseni , Mariam Moalla , Mona Mahfood , Faten Hadj Kacem , Wafa Belabed , Wajdi Safi , Mohamed Abid , Mouna Mnif-Feki , Hassen Hadj Kacem

Purpose

Central precocious puberty (CPP) occurs when the hypothalamus prematurely releases gonadotropin-releasing hormone (GnRH), triggering early sexual maturation and the onset of puberty. Mutations in five genes, including KISS1, KISS1R, DLK1, MKRN3, and PROKR2, have been reported in both sporadic and familial CPP cases. Routine screening of these genes is essential for distinguishing between CPP and early physiological puberty. This study aims to evaluate the role of genetic diagnosis in offering personalized management for familial cases of CPP.

Methods

Clinical, biochemical, and imaging assessments were conducted on two related girls. The coding regions and flanking intronic sequences of the five genes were sequenced using Sanger sequencing and screened for potential mutations.

Results

We identified a heterozygous MKRN3 c.482insC (rs763195944) loss-of-function mutation in a girl diagnosed with CPP at 6.1 years (Tanner stage: P2A2B3). She was treated with a GnRH analogue for five years, and her pubertal development has been well managed (Tanner stage: P3A3B3, at 11 years). No pathogenic variants were found in the KISS1, KISS1R, DLK1, or PROKR2 genes. Consequently, we recommended clinical follow-up only for her unmutated maternal cousin, who was diagnosed with premature thelarche (Tanner stage: P3A3B3, at 8.8 years).

Conclusions

Routine genetic screening of CPP-related genes can assist clinicians in making accurate treatment decisions for patients exhibiting a growth spurt, rapid onset of puberty, and a family history of CPP. This approach enables more targeted and personalized management of the condition.
目的中枢性性早熟(CPP)是下丘脑过早释放促性腺激素释放激素(GnRH),引发性成熟提前和青春期的发生。在散发性和家族性CPP病例中报道了5种基因的突变,包括KISS1、KISS1R、DLK1、MKRN3和PROKR2。常规筛查这些基因对于区分CPP和早期生理性青春期至关重要。本研究旨在评估基因诊断在提供家族性CPP个体化治疗中的作用。方法对2例相关患者进行临床、生化及影像学检查。采用Sanger测序法对5个基因的编码区和侧翼内含子序列进行测序,并进行潜在突变筛选。结果我们在一名6.1岁确诊为CPP的女孩(Tanner期:P2A2B3)中发现了一个杂合mkrn3c .482 insc (rs763195944)功能缺失突变。她用GnRH类似物治疗了5年,她的青春期发育得到了很好的控制(Tanner期:P3A3B3, 11岁)。未发现KISS1、KISS1R、DLK1或PROKR2基因的致病变异。因此,我们建议仅对她未突变的表兄妹进行临床随访,她被诊断为早产儿(Tanner期:P3A3B3, 8.8岁)。结论常规的CPP相关基因筛查有助于临床医生对具有生长突增、青春期早发、有CPP家族史的患者做出准确的治疗决策。这种方法可以对病情进行更有针对性和个性化的管理。
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引用次数: 0
期刊
Endocrine and Metabolic Science
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