Current Therapeutic Research-clinical and Experimental最新文献

{"title":"Pharmacodynamics, Safety, and Tolerability of Pyridostigmine Bromide in Heart Failure","authors":"Randal Goldberg MD ,&nbsp;Lucy Norcliffe-Kaufmann PhD ,&nbsp;Horacio Kaufmann MD ,&nbsp;Ikoa Jeschke-Lopez MD ,&nbsp;Yu Guo MS ,&nbsp;Judy Zhong PhD ,&nbsp;Kenneth I. Berger MD ,&nbsp;Roberta M. Goldring MD ,&nbsp;David S. Goldstein MD, PhD ,&nbsp;Carey Pope PhD ,&nbsp;Lara Maxwell DVM, PhD ,&nbsp;Manushree Bharadwaj PhD ,&nbsp;Alex Reyentovich MD ,&nbsp;Stuart D. Katz MD, MS","doi":"10.1016/j.curtheres.2025.100814","DOIUrl":"10.1016/j.curtheres.2025.100814","url":null,"abstract":"<div><h3>Background</h3><div>Pyridostigmine bromide is a short-acting carbamate acetylcholinesterase inhibitor that has been shown to acutely augment parasympathetic signaling in cardiovascular disease populations.</div></div><div><h3>Objective</h3><div>This study was undertaken to characterize pharmacodynamics, safety, and tolerability of pyridostigmine during repeated dosing in patients with heart failure.</div></div><div><h3>Methods</h3><div>A prospective ascending-dose, forced titration, double-blind Phase II randomized clinical trial was conducted to compare the effects of pyridostigmine bromide (15, 30, and 60 mg TID over 8 weeks) versus matching placebo on red blood cell (RBC) acetylcholinesterase activity, cholinergic side effects, and physiologic measures of parasympathetic heart rate modulation and sympathovagal balance in ambulatory patients with chronic systolic heart failure.</div></div><div><h3>Results</h3><div>Fifty subjects were screened, and 33 eligible subjects were randomly assigned (mean age, 55 years; mean left ventricular ejection fraction, 23%). Pyridostigmine bromide significantly decreased RBC acetylcholinesterase activity (<em>P</em> &lt; 0.02 vs placebo) and increased the frequency of participant-reported cholinergic excess symptoms (<em>P</em> &lt; 0.001 vs placebo). Physiologic measures of parasympathetic heart rate modulation and sympathovagal balance did not differ between treatment groups. In the pyridostigmine bromide group, RBC acetylcholinesterase activity was not significantly associated with postexercise parasympathetic heart modulation.</div></div><div><h3>Conclusions</h3><div>Pyridostigmine bromide administered over 8 weeks was associated with a significant reduction of RBC acetylcholinesterase activity and relatively mild symptoms of cholinergic excess, but changes in parasympathetic signaling in the sinoatrial node previously reported after acute administration were not observed. Further investigations are needed to delineate pharmacodynamic and pathobiological factors contributing to these findings. ClinicalTrials.gov identifier: NCT01415921.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100814"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568203","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}

{"title":"The Effect of Stem Cell Secretome on the Improvement of Diabetic Wound Recovery: A Systematic Review and Meta-Analysis of In Vivo Studies","authors":"Cecep Suhandi MSc ,&nbsp;Gofarana Wilar PhD ,&nbsp;Khaled M. Elamin PhD ,&nbsp;Audry Rahma Dewayani BSc ,&nbsp;Salsabil Ghaliya BSc ,&nbsp;Astriani Abdullah BSc ,&nbsp;Nasrul Wathoni PhD","doi":"10.1016/j.curtheres.2025.100778","DOIUrl":"10.1016/j.curtheres.2025.100778","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic wounds, characterized by their chronic nature, represent a critical challenge for patients with diabetes, often leading to amputation and mortality. Although stem cells show great promise, their use is limited by challenges related to stability and tumorigenicity. The secretome of stem cells, comprising molecules released by these cells, offers a potential alternative to the challenges associated with stem cell therapy and provides a promising solution for diabetic wound healing.</div></div><div><h3>Objective</h3><div>We conducted a systematic review and meta-analysis of relevant preclinical studies to evaluate the effectiveness of stem cell secretomes in treating diabetic wounds.</div></div><div><h3>Methods</h3><div>The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023473726). Databases were searched from their inception until November 20, 2023. The quality assessment of the included studies was performed utilizing the CAMARADES 10-item Quality Checklist. Statistical analyses were conducted using a random-effects model to calculate standardized mean differences (SMD) and 95% confidence intervals (CI), with heterogeneity assessed via the <em>I²</em> statistic. The primary outcome evaluated was the wound closure rate, while secondary outcomes included parameters such as the number of fibroblasts, neutrophils, and macrophages.</div></div><div><h3>Results</h3><div>Twenty studies were included, comprising 382 animal subjects, and five of which were eligible for quantitative evaluation in a meta-analysis. The stem cell secretome significantly improved the wound closure rate (SMD = 9.63; 95% CI = 2.01 −17.25; <em>P</em> = 0.01, I² = 76%) and reduced the number of neutrophils (SMD =  −8.47; 95% CI =  −13.05 to −3.90; <em>P</em> = 0.0003) and macrophages (SMD = −5.32; 95% CI = −9.09 to −1.55; <em>P</em> = 0.006).</div></div><div><h3>Conclusion</h3><div>This review suggests that stem cell secretomes have potential as a novel therapeutic strategy for diabetic wound healing, enhancing wound closure rates and reducing inflammation. These findings support the use of stem cell secretomes as a safer and more stable alternative to direct stem cell therapy, but further clinical studies are needed to confirm these results in human patients.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100778"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143526717","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}

{"title":"Effect of Hematopoietic Stem Cell Transplantation Regimen on Tacrolimus Pharmacokinetics","authors":"Haruno Oku BS ,&nbsp;Saki Yoshida BS ,&nbsp;Takumi Hotta BS ,&nbsp;Hirohito Muroi BS ,&nbsp;Keizo Fukushima PhD ,&nbsp;Kei Irie PhD ,&nbsp;Tatsuya Hirano BS ,&nbsp;Yoshimitsu Shimomura MD ,&nbsp;Takayuki Ishikawa MD, PhD ,&nbsp;Hiroaki Ikesue PhD ,&nbsp;Nobuyuki Muroi PhD ,&nbsp;Tohru Hashida PhD ,&nbsp;Nobuyuki Sugioka PhD","doi":"10.1016/j.curtheres.2024.100775","DOIUrl":"10.1016/j.curtheres.2024.100775","url":null,"abstract":"<div><h3>Objectives</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>We enrolled 91 patients undergoing HSCT (CBT: <em>n</em> = 56; bone marrow transplantation: <em>n</em> = 22; and peripheral blood stem cell transplantation: <em>n</em> = 13); 58 and 33 patients received myeloablative conditioning and reduced-intensity conditioning, respectively. Whole-blood tacrolimus concentrations were accurately captured (<em>n</em> = 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.</div></div><div><h3>Conclusions</h3><div>A tacrolimus dosing strategy that considers the variability in hemoglobin levels applies to all patients undergoing HSCT.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100775"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122229","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}

{"title":"Effect of a Pleuran-Based Supplement on Salivary IgA Secretion in Children With Recurrent Respiratory Infections","authors":"Peter Kunc MD, PhD ,&nbsp;Jaroslav Fabry MD, PhD ,&nbsp;Michaela Matiscakova MD ,&nbsp;Katarina Istvankova DVM ,&nbsp;Zuzana Diamant MD, PhD ,&nbsp;Juraj Majtan PhD, DSc ,&nbsp;Milos Jesenak MD, PhD","doi":"10.1016/j.curtheres.2025.100780","DOIUrl":"10.1016/j.curtheres.2025.100780","url":null,"abstract":"<div><h3>Background</h3><div>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 <em>Pleurotus ostreatus</em> in combination with vitamin D and zinc) on mucosal immunity –through modulating salivary secretory immunoglobulin A (sIgA) levels –in children with RRIs.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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; <em>P</em> = 0.045). No adverse events were observed during the course of the study in relation to the administration of pleuran-based supplement.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100780"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576715","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}

{"title":"Randomized, Double-Blind, Crossover Study Comparing the Bioavailability of 4 Ashwagandha (Withania somnifera (L.) Dunal) Extracts in Healthy Adults Under Fasting Condition","authors":"Priyank Rathi MD ,&nbsp;Se-Kwon Kim PhD","doi":"10.1016/j.curtheres.2025.100805","DOIUrl":"10.1016/j.curtheres.2025.100805","url":null,"abstract":"<div><h3>Background</h3><div><em>Withania somnifera</em> (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.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate and compare the oral bioavailability of 4 commercially standardized ashwagandha extracts under fasting conditions in healthy adults.</div></div><div><h3>Methods</h3><div>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% (<em>Withania somnifera</em> [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.</div></div><div><h3>Results</h3><div><em>Withania somnifera</em>-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. <em>Withania somnifera</em>-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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100805"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144738188","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}

{"title":"A Clinical Nomogram for Predicting Substandard Serum Valproic Acid Concentrations in Chinese Patients With Epilepsy","authors":"Zi-Hao Duan MS ,&nbsp;Chun-Yuan He MS ,&nbsp;Jie Chen BS ,&nbsp;Jun-Jie Jiang BS ,&nbsp;Zhi-Xiang Zhu PhD ,&nbsp;Jing Li MS ,&nbsp;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}

{"title":"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","authors":"Vali Musazadeh ,&nbsp;Niloofar Hamidi ,&nbsp;Morvarid Noormohammadi ,&nbsp;Farzad Shidfar","doi":"10.1016/j.curtheres.2025.100788","DOIUrl":"10.1016/j.curtheres.2025.100788","url":null,"abstract":"<div><h3>Introduction and Aim</h3><div>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.</div></div><div><h3>Materials and Methods</h3><div>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.</div></div><div><h3>Findings</h3><div>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.</div></div><div><h3>Conclusion</h3><div>This meta-analysis hints at Berberis's potential benefits for T2DM. However, more extensive trials are needed to confirm its advantages definitively.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"102 ","pages":"Article 100788"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134708","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}

{"title":"Safety and Efficacy of a Mesenchymal Stem Cell Secretome Therapy (KPI-012) for Persistent Corneal Epithelial Defects: A Phase 1b Trial","authors":"Valeria Sánchez Huerta MD ,&nbsp;Hugo Quiroz-Mercado MD ,&nbsp;Enrique O. Graue-Hernández MD, MSc ,&nbsp;Alejandro Navas MD, MSc ,&nbsp;Spencer Alford PhD ,&nbsp;Darius Kharabi JD, MBA ,&nbsp;Stephen Pflugfelder MD","doi":"10.1016/j.curtheres.2025.100799","DOIUrl":"10.1016/j.curtheres.2025.100799","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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).</div></div><div><h3>Results</h3><div>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.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100799"},"PeriodicalIF":1.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144241091","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}

{"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 ,&nbsp;Qiongqing Chen MPharm ,&nbsp;Ningsheng Liang PhD ,&nbsp;Jinying Liang MBBS ,&nbsp;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}

{"title":"Cardiovascular Events and Heart Failure in Patients With Type 2 Diabetes Treated With Dipeptidyl Peptidase-4 Inhibitors: A Meta-Analysis","authors":"Adili Tuersun PhD ,&nbsp;Shufen Cui BS ,&nbsp;Li Han BS ,&nbsp;Alimu Aikebaier BS ,&nbsp;Yanyan Shi BS ,&nbsp;Gang Cheng PhD ,&nbsp;Lei Cheng BS ,&nbsp;Guo Ma PhD","doi":"10.1016/j.curtheres.2025.100804","DOIUrl":"10.1016/j.curtheres.2025.100804","url":null,"abstract":"<div><h3>Background</h3><div>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).</div></div><div><h3>Objective</h3><div>This examination sought to methodically examine cardiovascular sequelae, notably heart failure, among users of dipeptidyl peptidase 4 (DPP-4) inhibitors when compared with nonusers.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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; <em>P</em> = 0.452). Major adverse cardiovascular events (including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death; OR = 1.01; 95% CI, 0.95–1.08; <em>P</em> = 0.354), stroke (OR = 1.01; 95% CI, 0.78–1.30; <em>P</em> = 0.968), myocardial infarction (OR = 0.89; 95% CI, 0.73–1.07; <em>P</em> = 0.49), and all-cause mortality (OR = 1.03; 95% CI, 0.96–1.11; <em>P</em> = 0.309) were also similarly manifested in both groups.</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"103 ","pages":"Article 100804"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144809603","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}