Current Therapeutic Research-clinical and Experimental最新文献_第3页

Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics 造血干细胞移植方案对他克莫司药代动力学的影响。

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2024.100775

Haruno Oku BS , Saki Yoshida BS , Takumi Hotta BS , Hirohito Muroi BS , Keizo Fukushima PhD , Kei Irie PhD , Tatsuya Hirano BS , Yoshimitsu Shimomura MD , Takayuki Ishikawa MD, PhD , Hiroaki Ikesue PhD , Nobuyuki Muroi PhD , Tohru Hashida PhD , Nobuyuki Sugioka PhD

Objectives

Treatment with tacrolimus requires strict control of the whole-blood concentration in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). In patients undergoing cord blood transplantation (CBT), there is a negative correlation between volume of distribution of tacrolimus and hemoglobin levels, which reflect the red blood cell (RBC) count. In this study, we evaluated the influence of the conditioning regimen (myeloablative and reduced-intensity conditioning) or donor source (cord blood, bone marrow, and peripheral blood stem cells) on the pharmacokinetics of tacrolimus in patients undergoing HSCT, including those undergoing CBT. We also examined applicability of dosing strategy of tacrolimus considering the RBC count.

Methods

We retrospectively analyzed clinical data—including whole-blood tacrolimus concentrations—from patients with HSCT. The observation period spanned from first continuous intravenous infusions until switch to oral medication, transfer to another hospital, relapse, or death. Population pharmacokinetic analysis was performed on whole-blood tacrolimus concentrations obtained from therapeutic drug monitoring during the observation period. Patient characteristics and laboratory data were evaluated as covariates.

Results

We enrolled 91 patients undergoing HSCT (CBT: n = 56; bone marrow transplantation: n = 22; and peripheral blood stem cell transplantation: n = 13); 58 and 33 patients received myeloablative conditioning and reduced-intensity conditioning, respectively. Whole-blood tacrolimus concentrations were accurately captured (n = 1,658 measurements) using a one-compartment and additive error model. The conditioning regimen and donor source did not have an impact on the pharmacokinetics of tacrolimus. Therefore, these factors were not considered when forming the dosing strategy. Nevertheless, a negative correlation between volume of distribution and hemoglobin level was confirmed, indicating that monitoring the RBC count is useful in assessing the dosing strategy.

Conclusions

A tacrolimus dosing strategy that considers the variability in hemoglobin levels applies to all patients undergoing HSCT.

目的：他克莫司治疗需要严格控制异基因造血干细胞移植（HSCT）患者的全血浓度。在接受脐带血移植（CBT）的患者中，他克莫司的分布容积与反映红细胞（RBC）计数的血红蛋白水平呈负相关。在这项研究中，我们评估了调节方案（清髓和低强度调节）或供体来源（脐带血、骨髓和外周血干细胞）对他克莫司在接受HSCT患者（包括接受CBT的患者）中的药代动力学的影响。我们还研究了考虑红细胞计数的他克莫司给药策略的适用性。方法：我们回顾性分析了HSCT患者的临床资料，包括他克莫司全血浓度。观察期从第一次连续静脉输注到改用口服药物、转院、复发或死亡。对观察期间治疗药物监测所得的他克莫司全血浓度进行群体药动学分析。患者特征和实验室数据作为协变量进行评估。结果：我们招募了91例接受HSCT的患者(CBT: n = 56；骨髓移植：n = 22；外周血干细胞移植：n = 13)；58例和33例患者分别接受清骨髓调节和降低强度调节。使用单室加性误差模型准确捕获全血他克莫司浓度（n = 1,658个测量值）。调理方案和供体来源对他克莫司的药代动力学没有影响。因此，在制定给药策略时没有考虑这些因素。然而，体积分布和血红蛋白水平之间的负相关被证实，这表明监测红细胞计数对评估给药策略是有用的。结论：考虑血红蛋白水平变化的他克莫司给药策略适用于所有接受造血干细胞移植的患者。

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引用次数: 0

Effect of a Pleuran-Based Supplement on Salivary IgA Secretion in Children With Recurrent Respiratory Infections 胸脯糖对反复呼吸道感染患儿唾液IgA分泌的影响

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2025.100780

Peter Kunc MD, PhD , Jaroslav Fabry MD, PhD , Michaela Matiscakova MD , Katarina Istvankova DVM , Zuzana Diamant MD, PhD , Juraj Majtan PhD, DSc , Milos Jesenak MD, PhD

Background

ß-glucans isolated from natural sources have demonstrated pluripotent immunomodulatory potential, making them a promising supportive treatment for the management of recurrent respiratory infections (RRIs) in children. This study aimed to evaluate the effects of a pleuran-based supplement (ß-glucan isolated from Pleurotus ostreatus in combination with vitamin D and zinc) on mucosal immunity –through modulating salivary secretory immunoglobulin A (sIgA) levels –in children with RRIs.

Methods

This monocentric, prospective, open-label pilot study investigated the effect of an orally administered pleuran/vitamin D/zinc supplement (1–2 chewable tablets daily depending on body weight) on the dynamics of sIgA secretion measured in saliva samples collected at three timepoints: at baseline and after 4–6 and 8–10 days.

Results

This study included 49 children aged 6-11 years (mean age: 8.2 ± 1.6 years) with a history of one or more of the following conditions in the inclusion criteria: RRIs, allergy, and asthma. After 8–10 days with daily administration of the chewable pleuran/vitamin D/zinc supplement, children exhibited a statistically significant increase in salivary sIgA concentrations compared with baseline (227 ± 211 µg/mL; P = 0.045). No adverse events were observed during the course of the study in relation to the administration of pleuran-based supplement.

Conclusions

We demonstrated the beneficial effects of the short-term administration of a pleuran-based chewable supplement on mucosal immunity through increasing salivatory sIgA levels. This study confirms the favourable safety profile of this pleuran/vitamin D/zinc combination, which could be beneficial for children with acute or recurrent respiratory infections, including children with allergies and/or asthma. Moreover, the significant increases in salivary sIgA concentrations that were observed after a few days of supplementation support the use of pleuran in not only the prevention but also the treatment of acute respiratory infections.

从天然来源分离的ß-葡聚糖已显示出多能性免疫调节潜力，使其成为治疗儿童复发性呼吸道感染（RRIs）的有希望的支持性治疗。本研究旨在通过调节RRIs患儿唾液分泌免疫球蛋白a （sIgA）水平，评估以胸脯蛋白为基础的补充剂（从平菇中分离的ß-葡聚糖与维生素D和锌联合使用）对粘膜免疫的影响。方法：这项单中心、前瞻性、开放标签的试点研究调查了口服胸膜酸/维生素D/锌补充剂（根据体重每天1-2片咀嚼片）对三个时间点唾液样本中sIgA分泌动态的影响：基线时、4-6天和8-10天后。结果本研究纳入49名年龄在6-11岁的儿童（平均年龄：8.2 ± 1.6岁），纳入标准中有以下一种或多种病史：RRIs、过敏和哮喘。每天服用可咀嚼胸膜聚糖/维生素D/锌补充剂8-10天后，与基线相比，儿童唾液sIgA浓度有统计学意义的增加(227 ± 211µg/mL； = 0.045页)。在研究过程中未观察到与胸膜基补剂有关的不良事件。结论：我们证实了短期服用胸膜基咀嚼补剂通过增加唾液sIgA水平对粘膜免疫的有益作用。这项研究证实了这种胸膜酸/维生素D/锌组合的良好安全性，它可能对患有急性或复发性呼吸道感染的儿童有益，包括过敏和/或哮喘儿童。此外，在补充几天后观察到唾液sIgA浓度的显著增加，支持胸膜炎不仅在预防而且在治疗急性呼吸道感染方面的使用。

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引用次数: 0

Randomized, Double-Blind, Crossover Study Comparing the Bioavailability of 4 Ashwagandha (Withania somnifera (L.) Dunal) Extracts in Healthy Adults Under Fasting Condition 随机、双盲、交叉研究比较4种印度稻（Withania somnifera）的生物利用度健康成人禁食条件下的杜纳尔提取物

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2025.100805

Priyank Rathi MD , Se-Kwon Kim PhD

Background

Withania somnifera (L.) Dunal, commonly known as ashwagandha, is a well-known plant in ayurvedic medicine, widely valued for its therapeutic potential. Although numerous clinical studies have explored its diverse health benefits, limited data are available on the pharmacokinetic (PK) properties and comparative bioavailability of its key bioactive constituents in humans.

Objective

This study aimed to evaluate and compare the oral bioavailability of 4 commercially standardized ashwagandha extracts under fasting conditions in healthy adults.

Methods

This randomized, double-blind, 4-treatment, 4-period, 4-sequence, single dose, 4-way crossover study was conducted in 16 healthy human volunteers. Participants received a single oral dose of 1 of 4 ashwagandha extracts, with varying compositions of 35% (Withania somnifera [WS]-35) or 10% (WS-10) withanolide glycosides, or 5% (WS-5) or 2.5% (WS-2.5) withanolides, each standardized to deliver 185 mg of total withanolides. Seventeen blood samples were collected over a 24-hour period after dose administration. Plasma concentrations of withanolide A, withanoside IV, withaferin A, and total withanolides were quantified, and PK parameters were calculated.

Results

Withania somnifera-35 had significantly superior bioavailability compared with the other extracts. The AUC_0–t for total withanolides per gram of WS-35 was 118.28, 226.11, and 267.83 times better than WS-10, WS-5, and WS-2.5 respectively. Withania somnifera-35 exhibited a significantly higher C_max, longer half-life, extended mean residence time, and lower systemic clearance, attributable to its higher withanolide glycoside content.

Conclusions

These findings emphasize the critical role of withanolide glycosides in determining the PK performance of ashwagandha supplements. The enhanced bioavailability of WS-35 supports its preferential use in therapeutic applications and provides a strong rationale for further investigation into dose-response relationships and the long-term efficacy of standardized, high-bioavailability formulations. Clinical Trial Registry of India identifier: CTRI/2020/10/028397.

背景：withania somnifera （L.）杜鹃花，通常被称为阿育吠陀，是印度草药中著名的植物，因其治疗潜力而受到广泛重视。尽管许多临床研究已经探索了其多种健康益处，但关于其关键生物活性成分在人体中的药代动力学（PK）特性和比较生物利用度的数据有限。目的评价和比较4种市售标准ashwagandha提取物在健康成人空腹条件下的口服生物利用度。方法采用随机、双盲、4治疗、4周期、4序列、单剂量、4向交叉的方法对16名健康志愿者进行研究。参与者接受单次口服剂量的4种ashwagandha提取物中的1种，其不同成分为35% （Withania somnifera [WS]-35）或10% （WS-10）的withanolides苷，或5% （WS-5）或2.5% （WS-2.5）的withanolides，每种提取物的标准含量为185 mg总withanolides。在给药后24小时内采集17份血样。测定血药浓度，并计算药代动力学参数。结果与其他提取物相比，苦参-35具有显著的生物利用度。WS-35每克总戊内酯的AUC0-t分别比WS-10、WS-5和WS-2.5高118.28倍、226.11倍和267.83倍。Withania somnifera-35表现出较高的Cmax、较长的半衰期、较长的平均停留时间和较低的全身清除率，这主要归因于其较高的Withania somnifera-35的内酯苷含量。结论这些研究结果强调了缬草内酯苷在决定缬草补剂PK性能中的关键作用。WS-35提高的生物利用度支持其优先用于治疗应用，并为进一步研究标准化、高生物利用度制剂的剂量-反应关系和长期疗效提供了强有力的理论依据。印度临床试验注册编号：CTRI/2020/10/028397。

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引用次数: 0

A Clinical Nomogram for Predicting Substandard Serum Valproic Acid Concentrations in Chinese Patients With Epilepsy 预测中国癫痫患者血清丙戊酸浓度不达标的临床Nomogram。

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2024.100771

Zi-Hao Duan MS , Chun-Yuan He MS , Jie Chen BS , Jun-Jie Jiang BS , Zhi-Xiang Zhu PhD , Jing Li MS , Fa-Cai Wang MD

Background

It is well-known that substandard serum valproic acid (VPA) concentrations may lead to treatment failure of epilepsy. However, there is still a lack of a quick method to predict whether a patient's serum VPA concentration will reach the standard.

Objective

The aims of this study were to investigate the factors leading to substandard serum VPA concentrations in Chinese patients with epilepsy and develop a related nomogram for risk prediction.

Methods

From January 2019 to March 2022, a total of 1143 serum VPA concentrations were collected from 630 hospitalized Chinese patients with epilepsy who were monitored by the Department of Pharmacy of Lu'an People's Hospital, and complete clinical data were collected from the corresponding patients for retrospective analysis. All monitored serum VPA concentrations were further divided into a training cohort and a validation cohort. For the training cohort, serum VPA concentrations below 50 µg/mL and between 50 and 100 µg/mL were classified into the subtherapeutic group and therapeutic group, respectively. The variables were selected from the clinical data, and differences between the variables of the subtherapeutic and therapeutic groups were analyzed. The influencing factors leading to substandard serum VPA concentrations were screened via logistic regression analysis, and the screened influencing factors were used to establish the nomogram prediction model.

Results

Multivariate logistic regression analysis revealed that the daily dose per unit of body weight (mg/kg/d), route of administration, presence of hepatic lesions, hypoalbuminemia, and combination with carbapenems or barbiturates were independent factors influencing the occurrence of substandard serum VPA concentrations. On the basis of the results of the multivariate logistic regression analysis, a nomogram risk prediction model for substandard serum VPA concentration was established. The values of the C-index and internal verification results indicated that the nomogram model had good accuracy and discrimination. The decision curve revealed that the nomogram that predicted the risk of substandard serum VPA concentration had a greater net benefit value (ranging from 12% to 94%), indicating that the model had a wide prediction interval.

Conclusions

Our study established a nomogram risk prediction model for substandard serum VPA concentrations in Chinese patients with epilepsy, which can help doctors or patients control the serum VPA concentration within the target concentration range as soon as possible.

背景：众所周知，血清丙戊酸（VPA）浓度不达标可能导致癫痫治疗失败。然而，目前仍缺乏一种快速预测患者血清VPA浓度是否达标的方法。目的：探讨导致中国癫痫患者血清VPA浓度不达标的因素，并建立相关的图图进行风险预测。方法：采集2019年1月至2022年3月六安市人民医院药剂科监测的630例中国住院癫痫患者血清VPA浓度1143份，收集完整的临床资料进行回顾性分析。所有监测的血清VPA浓度进一步分为训练组和验证组。对于训练组，血清VPA浓度低于50 µg/mL和在50 ~ 100 µg/mL之间分别被分为亚治疗组和治疗组。从临床资料中选取变量，分析亚治疗组和治疗组变量之间的差异。通过logistic回归分析筛选出导致血清VPA浓度不达标的影响因素，并利用筛选出的影响因素建立nomogram预测模型。结果：多因素logistic回归分析显示，单位体重日剂量（mg/kg/d）、给药途径、是否存在肝脏病变、低白蛋白血症、是否联用碳青霉烯类药物或巴比妥类药物是影响血清VPA浓度不达标的独立因素。在多元logistic回归分析结果的基础上，建立血清VPA浓度不达标的nomogram风险预测模型。c指数值和内部验证结果表明，模态图模型具有较好的准确性和鉴别性。决策曲线显示，预测血清VPA浓度不达标风险的nomogram具有较大的净效益值（范围为12% ~ 94%），说明该模型具有较宽的预测区间。结论：本研究建立了中国癫痫患者血清VPA浓度不达标的nomogram风险预测模型，可以帮助医生或患者尽快将血清VPA浓度控制在目标浓度范围内。

{"title":"A Clinical Nomogram for Predicting Substandard Serum Valproic Acid Concentrations in Chinese Patients With Epilepsy","authors":"Zi-Hao Duan MS , Chun-Yuan He MS , Jie Chen BS , Jun-Jie Jiang BS , Zhi-Xiang Zhu PhD , Jing Li MS , Fa-Cai Wang MD","doi":"10.1016/j.curtheres.2024.100771","DOIUrl":"10.1016/j.curtheres.2024.100771","url":null,"abstract":"<div><h3>Background</h3><div>It is well-known that substandard serum valproic acid (VPA) concentrations may lead to treatment failure of epilepsy. However, there is still a lack of a quick method to predict whether a patient's serum VPA concentration will reach the standard.</div></div><div><h3>Objective</h3><div>The aims of this study were to investigate the factors leading to substandard serum VPA concentrations in Chinese patients with epilepsy and develop a related nomogram for risk prediction.</div></div><div><h3>Methods</h3><div>From January 2019 to March 2022, a total of 1143 serum VPA concentrations were collected from 630 hospitalized Chinese patients with epilepsy who were monitored by the Department of Pharmacy of Lu'an People's Hospital, and complete clinical data were collected from the corresponding patients for retrospective analysis. All monitored serum VPA concentrations were further divided into a training cohort and a validation cohort. For the training cohort, serum VPA concentrations below 50 µg/mL and between 50 and 100 µg/mL were classified into the subtherapeutic group and therapeutic group, respectively. The variables were selected from the clinical data, and differences between the variables of the subtherapeutic and therapeutic groups were analyzed. The influencing factors leading to substandard serum VPA concentrations were screened via logistic regression analysis, and the screened influencing factors were used to establish the nomogram prediction model.</div></div><div><h3>Results</h3><div>Multivariate logistic regression analysis revealed that the daily dose per unit of body weight (mg/kg/d), route of administration, presence of hepatic lesions, hypoalbuminemia, and combination with carbapenems or barbiturates were independent factors influencing the occurrence of substandard serum VPA concentrations. On the basis of the results of the multivariate logistic regression analysis, a nomogram risk prediction model for substandard serum VPA concentration was established. The values of the C-index and internal verification results indicated that the nomogram model had good accuracy and discrimination. The decision curve revealed that the nomogram that predicted the risk of substandard serum VPA concentration had a greater net benefit value (ranging from 12% to 94%), indicating that the model had a wide prediction interval.</div></div><div><h3>Conclusions</h3><div>Our study established a nomogram risk prediction model for substandard serum VPA concentrations in Chinese patients with epilepsy, which can help doctors or patients control the serum VPA concentration within the target concentration range as soon as possible.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100771"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11783061/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Effect of Berberis (Vulgaris and Integerrima) on Cardiovascular Risk Factors in Patients With Type 2 Diabetes Mellitus: A Systematic Review, Meta-Analysis, and GRADE Assessment 小檗（Vulgaris和Integerrima）对2型糖尿病患者心血管危险因素的影响：系统回顾、meta分析和GRADE评估

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2025.100788

Vali Musazadeh , Niloofar Hamidi , Morvarid Noormohammadi , Farzad Shidfar

Introduction and Aim

Type 2 diabetes mellitus (T2DM) raises cardiovascular disease risk, but evidence on Berberis's impact is limited and inconsistent. This systematic review and meta-analysis aimed to assess effect of Berberis supplement on cardiovascular risk factors in patients with T2DM.

Materials and Methods

We extensively searched Embase, Web of Science, Scopus, PubMed, and the Cochrane Library for randomized controlled trials (RCTs) up to October 25, 2024. This study primarily assesses Berberis's impact on improving glycemic indices, with secondary measures including obesity, blood pressure and lipid profile parameters.

Findings

After reviewing 784 articles, we included data from eight RCTs involving 451 participants with T2DM. The results of meta-analysis indicated that Berberis administration significantly reduced weight (WMD: -2.25; 95% CI: -3.11 to -1.39), body mass index (BMI, WMD: -0.57; 95% CI: -0.98 to -0.17), TG (WMD: -19.32; 95% CI: -30.95 to -1.69), TC (WMD: -28.57; 95% CI: -30.22 to -21.51), LDL-C (WMD: -17.47; 95% CI: -24.18 to -10.75), FBS (WMD: -14.54; 95% CI: -23.83, -5.25), HbA1c (WMD: -0.65; 95% CI: -1.30, -0.00), HOMA-IR (WMD: -1.82; 95% CI: -3.60, -0.05), and insulin (WMD: -4.40; 95% CI: -7.15, -1.65). However, no statistically significant effect on blood pressure and HDL-C level was observed with Berberis intervention.

Conclusion

This meta-analysis hints at Berberis's potential benefits for T2DM. However, more extensive trials are needed to confirm its advantages definitively.

2型糖尿病（T2DM）增加心血管疾病风险，但小檗影响的证据有限且不一致。本系统综述和荟萃分析旨在评估小檗补充剂对T2DM患者心血管危险因素的影响。材料与方法我们广泛检索Embase、Web of Science、Scopus、PubMed、Cochrane Library，检索截止到2024年10月25日的随机对照试验（RCTs）。本研究主要评估了小檗对改善血糖指数的影响，次要指标包括肥胖、血压和血脂参数。研究结果：在回顾了784篇文章后，我们纳入了8项随机对照试验的数据，涉及451名T2DM患者。meta分析结果显示，小檗治疗组体重显著降低(WMD: -2.25；95% CI: -3.11 ~ -1.39)，体重指数(BMI, WMD: -0.57；95% CI: -0.98 ~ -0.17), TG (WMD: -19.32；95% CI: -30.95 ~ -1.69), TC (WMD: -28.57；95% CI: -30.22 ~ -21.51), LDL-C (WMD: -17.47；95% CI: -24.18 ~ -10.75), FBS (WMD: -14.54；95% CI: -23.83, -5.25), HbA1c (WMD: -0.65；95% ci: -1.30, -0.00), homa-ir (wmd: -1.82；95% CI: -3.60, -0.05)和胰岛素(WMD: -4.40；95% ci: -7.15, -1.65)。然而，小檗干预对血压和HDL-C水平没有统计学意义上的显著影响。结论：本荟萃分析提示小檗对2型糖尿病的潜在益处。然而，需要更广泛的试验来确定其优势。

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引用次数: 0

Safety and Efficacy of a Mesenchymal Stem Cell Secretome Therapy (KPI-012) for Persistent Corneal Epithelial Defects: A Phase 1b Trial 间充质干细胞分泌组疗法（KPI-012）治疗持续性角膜上皮缺陷的安全性和有效性：1b期试验

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2025.100799

Valeria Sánchez Huerta MD , Hugo Quiroz-Mercado MD , Enrique O. Graue-Hernández MD, MSc , Alejandro Navas MD, MSc , Spencer Alford PhD , Darius Kharabi JD, MBA , Stephen Pflugfelder MD

Background

Persistent corneal epithelial defect (PCED) is a condition often refractory to conventional treatments. KPI-012 is a topical mesenchymal stem cell secretome therapy under investigation for PCED management.

Objective

To assess the safety, tolerability, and corneal wound healing efficacy of KPI-012 in a phase 1b, proof-of-concept, open-label, single-arm clinical trial.

Methods

The safety profile and tolerability of topical self-administered KPI-012 therapy (twice daily, 1-week duration) were first evaluated in an initial safety cohort of participants with pre-existing permanent vision loss and no active corneal disease (n = 3). The safety profile and efficacy of KPI-012 were then assessed in participants with PCED of several etiologies (n = 9), who self-administered KPI-012 twice daily for up to 4 weeks with one participant self-administering for 8 weeks (efficacy cohort).

Results

KPI-012 was well tolerated in both the safety profile and efficacy cohorts. In the efficacy cohort (n = 9), 6 of 8 participants (75%) demonstrated complete healing of the lesion during the treatment period, with 4 of 8 (50%) achieving complete healing within 1 week of commencing KPI-012 therapy (a nontreatment-related adverse event meant 1 participant was withdrawn by the investigator). KPI-012 was well tolerated, with only 1 participant experiencing treatment-related adverse events. In patients who reported PCED-related ocular pain at baseline (n = 7), pain levels decreased in all participants after 1 week, and after 3 weeks, no participant reported ocular pain.

Conclusions

The results from this small phase 1b open-label trial suggest that in participants with PCED of multiple etiologic origin, twice daily KPI-012 therapy exhibits a favorable safety profile-efficacy profile and may promote rapid wound healing. The small sample size limits the generalizability of the findings, and thus a later-phase clinical investigation with a larger sample size is warranted to establish the statistically driven therapeutic effect.

背景：持续性角膜上皮缺损（PCED）是一种常规治疗难以治愈的疾病。KPI-012是一种局部间充质干细胞分泌组疗法，正在研究用于PCED治疗。目的在一项1b期、概念验证、开放标签、单臂临床试验中评估KPI-012的安全性、耐受性和角膜创面愈合效果。方法：首先在一个预先存在永久性视力丧失且无活动性角膜疾病（ = 3）的参与者的初始安全性队列中评估局部自我给药KPI-012治疗（每天两次，持续1周）的安全性和耐受性。然后在几种病因的PCED患者（n = 9）中评估KPI-012的安全性和有效性，这些患者每天两次自我服用KPI-012，持续4周，其中一名参与者自我服用8周（疗效队列）。结果skpi -012在安全性和有效性队列中均具有良好的耐受性。在疗效队列中（n = 9），8名参与者中有6名（75%）在治疗期间表现出病变完全愈合，8名参与者中有4名（50%）在开始KPI-012治疗后1周内实现完全愈合（非治疗相关不良事件意味着1名参与者被研究者撤回）。KPI-012耐受性良好，只有1名参与者出现与治疗相关的不良事件。在基线时报告pced相关眼部疼痛的患者中（n = 7），所有参与者的疼痛水平在1周后下降，3周后，没有参与者报告眼部疼痛。这项小型1b期开放标签试验的结果表明，对于多种病因的PCED患者，每天两次的KPI-012治疗显示出良好的安全性和有效性，并可能促进伤口快速愈合。小样本量限制了研究结果的普遍性，因此需要更大样本量的后期临床研究来确定统计学驱动的治疗效果。

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引用次数: 0

Meta-Analysis of the Efficacy and Safety of Sintilimab in Combination With Chemotherapy for Advanced Non–Small-Cell Lung Cancer 辛替单抗联合化疗治疗晚期非小细胞肺癌疗效和安全性的meta分析

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2025.100796

Liling Pan MPharm , Qiongqing Chen MPharm , Ningsheng Liang PhD , Jinying Liang MBBS , Youjia Guo MMed

Objective

Sintilimab is an innovative immune checkpoint inhibitor (ICI), domestically produced in China, that exhibits significant efficacy in the treatment of lung cancer. However, due to the delayed initiation of ICI development in China, its use is currently restricted to domestic markets, resulting in a limited volume of clinical data, which poses a challenge in postmarketing evaluation. This study aimed to assess the safety and efficacy of sintilimab through a meta-analysis.

Methods

We conducted independent searches for relevant articles in both Chinese and international databases, followed by independent screening, after which the data were extracted from the selected studies. Statistical analysis was performed using RevMan software, version 5.4, and the results were estimated using the risk ratio with 95% confidence interval.

Results

Efficacy analysis revealed that sintilimab, when combined with chemotherapy, significantly enhanced the objective response rate and disease control rate in patients with non-small-cell lung cancer (NSCLC) while reducing the risk of disease progression. Evaluation of the safety of sintilimab revealed that the risks of hypothyroidism, pneumonia, and rash in patients with advanced NSCLC following treatment were higher than those of the control group by 3.70-fold, 2.22-fold, and 1.58-fold, respectively. There were no significant differences between the combination therapy and chemotherapy groups in terms of the incidence of blood system toxicity, impairment of liver function, and fever; however, nausea, vomiting, and diarrhea appeared to be less severe in the combination therapy group.

Conclusions

Sintilimab, combined with chemotherapy, demonstrates promising efficacy in the treatment of advanced NSCLC; however, it is imperative to closely monitor for adverse events, particularly immune-related adverse events.

Clinical trial registration

Not available.

目的：intilimab是一种创新的免疫检查点抑制剂（ICI），在中国国内生产，在治疗肺癌方面表现出显著的疗效。然而，由于ICI在中国的开发起步较晚，其使用目前仅限于国内市场，导致临床数据量有限，这给上市后评价带来了挑战。本研究旨在通过荟萃分析评估辛替单抗的安全性和有效性。方法分别在国内外数据库中独立检索相关文献，进行独立筛选，并从所选研究中提取数据。采用RevMan 5.4版软件进行统计分析，采用95%置信区间的风险比对结果进行估计。结果疗效分析显示，辛替单抗联合化疗可显著提高非小细胞肺癌（NSCLC）患者的客观有效率和疾病控制率，同时降低疾病进展风险。对辛替单抗的安全性评价显示，晚期NSCLC患者治疗后发生甲状腺功能减退、肺炎和皮疹的风险分别比对照组高3.70倍、2.22倍和1.58倍。联合治疗组与化疗组在血液系统毒性、肝功能损害和发热发生率方面无显著差异；然而，在联合治疗组中，恶心、呕吐和腹泻似乎不那么严重。结论辛替单抗联合化疗治疗晚期非小细胞肺癌疗效良好；然而，必须密切监测不良事件，特别是与免疫有关的不良事件。临床试验注册不可用。

{"title":"Meta-Analysis of the Efficacy and Safety of Sintilimab in Combination With Chemotherapy for Advanced Non–Small-Cell Lung Cancer","authors":"Liling Pan MPharm , Qiongqing Chen MPharm , Ningsheng Liang PhD , Jinying Liang MBBS , Youjia Guo MMed","doi":"10.1016/j.curtheres.2025.100796","DOIUrl":"10.1016/j.curtheres.2025.100796","url":null,"abstract":"<div><h3>Objective</h3><div>Sintilimab is an innovative immune checkpoint inhibitor (ICI), domestically produced in China, that exhibits significant efficacy in the treatment of lung cancer. However, due to the delayed initiation of ICI development in China, its use is currently restricted to domestic markets, resulting in a limited volume of clinical data, which poses a challenge in postmarketing evaluation. This study aimed to assess the safety and efficacy of sintilimab through a meta-analysis.</div></div><div><h3>Methods</h3><div>We conducted independent searches for relevant articles in both Chinese and international databases, followed by independent screening, after which the data were extracted from the selected studies. Statistical analysis was performed using RevMan software, version 5.4, and the results were estimated using the risk ratio with 95% confidence interval.</div></div><div><h3>Results</h3><div>Efficacy analysis revealed that sintilimab, when combined with chemotherapy, significantly enhanced the objective response rate and disease control rate in patients with non-small-cell lung cancer (NSCLC) while reducing the risk of disease progression. Evaluation of the safety of sintilimab revealed that the risks of hypothyroidism, pneumonia, and rash in patients with advanced NSCLC following treatment were higher than those of the control group by 3.70-fold, 2.22-fold, and 1.58-fold, respectively. There were no significant differences between the combination therapy and chemotherapy groups in terms of the incidence of blood system toxicity, impairment of liver function, and fever; however, nausea, vomiting, and diarrhea appeared to be less severe in the combination therapy group.</div></div><div><h3>Conclusions</h3><div>Sintilimab, combined with chemotherapy, demonstrates promising efficacy in the treatment of advanced NSCLC; however, it is imperative to closely monitor for adverse events, particularly immune-related adverse events.</div></div><div><h3>Clinical trial registration</h3><div>Not available.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100796"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144270652","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

Cardiovascular Events and Heart Failure in Patients With Type 2 Diabetes Treated With Dipeptidyl Peptidase-4 Inhibitors: A Meta-Analysis 二肽基肽酶-4抑制剂治疗2型糖尿病患者的心血管事件和心力衰竭：一项荟萃分析

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2025.100804

Adili Tuersun PhD , Shufen Cui BS , Li Han BS , Alimu Aikebaier BS , Yanyan Shi BS , Gang Cheng PhD , Lei Cheng BS , Guo Ma PhD

Background

The global prevalence of type 2 diabetes mellitus (T2DM) continues to rise, with patients facing significantly elevated risks of cardiovascular complications, particularly heart failure (HF).

Objective

This examination sought to methodically examine cardiovascular sequelae, notably heart failure, among users of dipeptidyl peptidase 4 (DPP-4) inhibitors when compared with nonusers.

Methods

Cochrane, Embase, and PubMed databases, which compared the use of DPP-4 inhibitors and reported cardiovascular outcomes and heart failure events in patients with type 2 diabetes mellitus (T2DM), were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: they were randomized trials comparing DPP-4 inhibitor use in patients with T2DM; study duration was longer than 24 weeks; and they reported cardiovascular outcomes as their main or secondary end points. Stata 15 MP (StataCorp LLC, College Station, Texas, USA) was used to analyze the data, and odds ratios (ORs) with 95% CIs were used to represent the results.

Results

A total of 79,010 participants with T2DM were included. A total of 37,895 patients were assigned to the DPP-4 inhibitor group, whereas 41,115 patients were assigned to the control group. Results of the analysis showed that during a mean follow-up period ranging from 24 to 302 weeks, heart failure incidence did not differ significantly between T2DM patients treated with DPP-4 inhibitors and those who were not (OR = 1.06; 95% CI, 0.96–1.18; P = 0.452). Major adverse cardiovascular events (including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death; OR = 1.01; 95% CI, 0.95–1.08; P = 0.354), stroke (OR = 1.01; 95% CI, 0.78–1.30; P = 0.968), myocardial infarction (OR = 0.89; 95% CI, 0.73–1.07; P = 0.49), and all-cause mortality (OR = 1.03; 95% CI, 0.96–1.11; P = 0.309) were also similarly manifested in both groups.

Conclusions

The present analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes and heart failure in these patients with T2DM, indicating that these drugs may be safe to use in terms of cardiovascular events.

背景2型糖尿病（T2DM）的全球患病率持续上升，患者面临心血管并发症，特别是心力衰竭（HF）的风险显著升高。目的：本研究旨在系统地检查二肽基肽酶4 （DPP-4）抑制剂使用者与非使用者的心血管后遗症，特别是心力衰竭。方法使用特定术语对scochrane、Embase和PubMed数据库进行检索，这些数据库比较了2型糖尿病（T2DM）患者使用DPP-4抑制剂和报告的心血管结局和心力衰竭事件。满足以下纳入标准的研究被纳入：比较T2DM患者使用DPP-4抑制剂的随机试验；研究持续时间大于24周；他们报告了心血管结局作为主要或次要终点。使用Stata 15mp （StataCorp LLC, College Station, Texas， USA）分析数据，使用95% ci的优势比（or）来表示结果。结果共纳入T2DM患者79,010例。共有37,895名患者被分配到DPP-4抑制剂组，而41,115名患者被分配到对照组。分析结果显示，在24至302周的平均随访期间，接受DPP-4抑制剂治疗的T2DM患者与未接受DPP-4抑制剂治疗的T2DM患者的心力衰竭发生率无显著差异(OR = 1.06；95% ci, 0.96-1.18；P = 0.452)。主要不良心血管事件（包括非致死性心肌梗死、非致死性卒中和心血管性死亡）；Or = 1.01；95% ci, 0.95-1.08；P = 0.354)，中风(OR = 1.01；95% ci, 0.78-1.30；P = 0.968)，心肌梗死(OR = 0.89；95% ci, 0.73-1.07；P = 0.49)，全因死亡率(OR = 1.03；95% ci, 0.96-1.11；P = 0.309)。结论：本分析显示，DPP-4抑制剂治疗并没有显著增加这些T2DM患者的心血管结局和心力衰竭，表明这些药物在心血管事件方面可能是安全的。

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引用次数: 0

The Effects of Cocoons of Larinus Hedenborgi (Coleoptera: Curculionidae) Extracts on Inflammation and Clinical Outcomes in Patients With Coronavirus Disease 2019: A Double-Blinded Randomized Controlled Clinical Trial Hedenborgi Larinus茧提取物对2019冠状病毒病患者炎症和临床结局的影响：双盲随机对照临床试验

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2025.100811

Mahdi Keshani , Sayid Mahdi Mirghazanfari , Naseh Pahlavani , Faezeh Baniyaghoobi , Vahid Hadi , Mohammad Bagherniya , Zahra Heidari , Amirhossein Sahebkar , Mohsen Mohajeri , Saeid Hadi

Background

Severe acute respiratory syndrome coronavirus 2, the causative agent of coronavirus disease 2019 (COVID-19), is an inflammatory disease that manifests with symptoms including dry cough, fever, myalgia, and even pneumonia. Despite antiviral treatments, no definitive therapy has been proven effective. Trehala manna (TM), the edible cocoon of Larinus hedenborgi (Coleoptera: Curculionidae) weevil, as a natural product, is traditionally used to alleviate respiratory symptoms because of its antibacterial, anti-inflammatory, and antifungal properties.

Objective

The current study aimed to determine the effects of TM add-on treatment on inflammatory biomarkers and some clinical outcomes in patients with COVID-19.

Methods

The present study was a randomized controlled trial conducted on 60 patients who were randomly allocated to TM (5 g, twice a day) or a placebo for 1 week. The main outcomes of the current study include C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), blood urea nitrogen level, creatinine level, fasting blood sugar level, systolic blood pressure, and visual analog scale (VAS) score for cough, which were evaluated at both the beginning and end of the study.

Results

Our finding revealed that CRP level, ESR, blood urea nitrogen level, creatinine level, fasting blood sugar level, systolic blood pressure, and VAS score for cough were significantly reduced in the TM group after intervention (P < 0.05), and CRP level, ESR, VAS score for cough, and fever were significantly reduced in the TM group compared with the control after 7 days (P < 0.05).

Conclusions

Trehala mann is a natural remedy with potential as an adjunctive therapy for reducing inflammatory biomarkers and improving certain clinical symptoms in patients with COVID-19. No adverse effects were observed during the trial. Iranian Registry of Clinical Trials identifier: IRCT20211029052904N1.

严重急性呼吸综合征冠状病毒2是2019冠状病毒病（COVID-19）的病原体，是一种炎症性疾病，其症状包括干咳、发烧、肌痛甚至肺炎。尽管有抗病毒治疗，但尚无确切的治疗方法被证明有效。甘露海藻（Trehala manna， TM）是一种天然产物，是黑登博吉（Larinus hedenborgi）象鼻虫的可食用蚕茧，由于其抗菌、抗炎和抗真菌的特性，传统上被用于缓解呼吸道症状。目的本研究旨在确定TM加药治疗对COVID-19患者炎症生物标志物和一些临床结局的影响。方法本研究是一项随机对照试验，60例患者随机分配给TM （5 g，每天2次）或安慰剂，为期1周。本研究的主要结局包括c反应蛋白（CRP）水平、红细胞沉降率（ESR）、血尿素氮水平、肌酐水平、空腹血糖水平、收缩压、咳嗽视觉模拟量表（VAS）评分，并在研究开始和结束时进行评估。结果干预后TM组CRP水平、ESR、血尿素氮水平、肌酐水平、空腹血糖水平、收缩压、咳嗽VAS评分均显著降低（P < 0.05），干预后7 d TM组CRP水平、ESR、咳嗽VAS评分、发烧评分均显著低于对照组（P < 0.05）。结论strehala mann是一种天然药物，具有降低COVID-19患者炎症生物标志物和改善某些临床症状的辅助治疗潜力。试验期间未观察到不良反应。伊朗临床试验注册中心标识：IRCT20211029052904N1。

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引用次数: 0

The Effect of Anthocyanin Supplementation on Pro-Inflammatory Biomarkers in Patients With Metabolic Disorders: A Grade-Assessed Systematic Review and Meta-Analysis 补充花青素对代谢紊乱患者促炎生物标志物的影响：一项分级评估的系统评价和荟萃分析

IF 1.6 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Current Therapeutic Research-clinical and Experimental

Pub Date : 2025-01-01 DOI: 10.1016/j.curtheres.2024.100772

Fatemeh Babaee Kiadehi MSc , Pegah Samani MSc , Sanaz Barazandeh MSc , Pedram Pam MSc , Ali Hajipour MSc , Narges Goli MSc , Ali Asadi PhD

Introduction and Aim

Patients with metabolic disorders benefit from using anthocyanins. Nevertheless, the findings drawn from extant trials remain contentious. Thus, this meta-analysis evaluated anthocyanin's effect on inflammatory biomarkers in patients with metabolic disorders.

Materials and Methods

We comprehensively searched electronic databases, including PubMed, Scopus, Web of Science, and CENTRAL, from their inception to June 14, 2024.

Findings

A total of 11 randomized controlled clinical trials with 14 arms were analyzed. There was no significant effect of anthocyanin supplementation on interleukin (IL)-1β levels (standardized mean difference [SMD] = –0.01, 95% CI: –0.33, 0.31; P = 0.941, I² = 62.4%, P = 0.031), tumor necrosis factor-α (TNF-α) (SMD = –0.49, 95% CI: –1.07, 0.09; P = 0.098, I² = 94.0%, P < 0.001) and IL-6 (SMD = –0.69, 95% CI: –1.45, 0.06; P = 0.073, I² = 95.2%, P < 0.001), respectively. A significant between-study heterogeneity was identified, which was reduced when subgrouping by sample size, dosage, and study population. However, subgroup analysis showed that it might decrease TNF-α and IL-6 in patients with hypertension, and if the intervention lasted less than 12 weeks.

Conclusions

There was no significant impact of anthocyanin supplementation on IL-1β, TNF-α, and IL-6; however, it should be noted that the intervention has a decreasing impact on individuals with hypertension. Our observed effect sizes on IL-1β, TNF-α, and IL-6 are not clinically important.

介绍和目的代谢紊乱患者受益于使用花青素。然而，从现有试验中得出的结论仍然存在争议。因此，本荟萃分析评估了花青素对代谢紊乱患者炎症生物标志物的影响。材料与方法我们全面检索了PubMed、Scopus、Web of Science、CENTRAL等电子数据库，检索时间从建站到2024年6月14日。结果：共分析了11项随机对照临床试验，共14组。添加花青素对白介素(IL)-1β水平无显著影响(标准化平均差[SMD] = -0.01,95% CI: -0.33, 0.31；0.941 P = ,I2 = 62.4%,P = 0.031),肿瘤坏死因子-α(TNF -α)(SMD = -0.49,95%置信区间CI: -1.07, 0.09;0.098 P = ,I2 = 94.0%,P & lt; 0.001)和il - 6 (SMD = -0.69,95%置信区间CI: -1.45, 0.06;P = 0.073, I2 = 95.2%,P & lt;分别 0.001)。研究发现了显著的研究间异质性，当按样本量、剂量和研究人群进行亚分组时，这种异质性降低了。然而，亚组分析显示，如果干预持续时间少于12周，它可能会降低高血压患者的TNF-α和IL-6。结论补充花青素对IL-1β、TNF-α、IL-6无显著影响；然而，应该注意的是，干预对高血压患者的影响逐渐减弱。我们观察到的IL-1β、TNF-α和IL-6的效应大小在临床上并不重要。

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引用次数: 0