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The Anatomic and Functional Outcomes of Ozurdex-Aided Vitrectomy in Proliferative Diabetic Retinopathy.
Wang, M, Luan, R, Liu, B, Gong, Y, Zhao, J, Chen, X, Yang, Q, Liu, J, Liu, J, Shao, Y, et al
Diabetes, metabolic syndrome and obesity : targets and therapy. 2024;:1199-1213
Abstract
PURPOSE To investigate the 3-months outcomes of patients who underwent intraoperative intravitreal injection of Ozurdex for proliferative diabetic retinopathy (PDR). METHODS This is a prospective randomized controlled clinical trial (ChiCTR2100043399). Seventy-one patients with PDR who had indications for surgery without intravitreal injection history within 3 months preoperatively were enrolled. Patients were randomly divided into three groups based on the medicine injected intraoperatively: Ozurdex, Conbercept, and Control group. The primary outcome is the best-corrected visual acuity (BCVA) within 3 months postoperatively. The secondary outcomes include the intraocular pressure (IOP), mean sensitivity, central retinal thickness and vessels perfusion. RESULTS The BCVA and the mean sensitivity improved in the three groups (F = 130.8, P < 0.0001; F = 34.18, P < 0.0001), but there was no statistical difference among the three groups (F = 0.858, P = 0.552; F = 0.964, P = 0.452). The IOP was no significant differences among the three groups within 3 months postoperatively (F = 0.881, P = 0.533). Compared with the other two groups, central retinal thickness (CRT) and outer retinal layer (ORL) thickness decreased significantly in patients of the Ozurdex group (F = 3.037, P = 0.008; F = 2.626, P = 0.018), especially in the diabetic macular edema (DME) patients (F = 2.761, P = 0.0164; F = 2.572, P = 0.0240). In macular region, superficial vascular plexus (SVP), intermediate capillary plexus (ICP) and deep capillary plexus (DCP) perfusion were not shown statistical difference at 3 months postoperatively in the all three groups compared with 1 day postoperatively (P > 0.05). CONCLUSION Compared with the other two groups, anatomical outcomes was improved significantly in Ozurdex group for DR patients. Ozurdex may help to improve the visual acuity and visual sensitivity, and there is no significant difference in the change of IOP and microvascular improvement. CLINICAL TRIAL REGISTRATION This trial is registered with the Chinese Clinical Trial Registry (http://www.chictr.org.cn, registration number ChiCTR2100043399).
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Roxadustat and Oral Iron Absorption in Chinese Patients with Anemia of Chronic Kidney Disease: A Randomized, Open-Label, Phase 4 Study (ALTAI).
Wu, H, Cheng, H, Wang, C, Yao, L, Qin, S, Zuo, L, Hu, Z, Zhang, C, Wu, Y, Hofherr, A, et al
Advances in therapy. 2024;(3):1168-1183
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Abstract
INTRODUCTION Anemia of chronic kidney disease (CKD) has a high incidence and is associated with many disease conditions. Iron dysmetabolism is an important contributor to anemia in CKD patients. METHODS ALTAI, a randomized, active-controlled, phase 4 trial, investigated the efficacy of roxadustat versus recombinant human erythropoietin (rHuEPO) on gastrointestinal iron absorption in patients with anemia of CKD (stage 4/5). The primary endpoint was change from baseline to day 15 in gastrointestinal iron absorption (serum iron area under the concentration-time curve; AUC0-3h) following single-dose oral iron. RESULTS Twenty-five patients with a mean age of 55.1 years were randomized 1:1 to roxadustat (n = 13) or rHuEPO (n = 12). Baseline iron profiles were similar between treatment groups. Change from baseline to day 15 in serum iron AUC0-3h was not statistically significantly different between the roxadustat and rHuEPO groups. Mean (SD) change from baseline in serum iron AUC0-3h was 11.3 (28.2) g × 3 h/dl in the roxadustat group and - 0.3 (9.7) g × 3 h/dl in the rHuEPO group. Roxadustat treatment was associated with decreased hepcidin and also increased transferrin, soluble transferrin receptor, and total iron-binding capacity (TIBC), with nominal significance. The proportion of patients experiencing one or more adverse events was 38.5% when treated with roxadustat and 16.7% with rHuEPO. CONCLUSIONS The study showed no significant difference between roxadustat and rHuEPO in iron absorption but was underpowered because of recruitment challenges. TRIAL REGISTRATION ClinicalTrials.gov Identifier NCT04655027.
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Association between Body Composition and Peripheral Neurotoxicity in Cancer Patients from North China Taking Nab-Paclitaxel.
Guo, J, Zhao, J, Gu, M, Hou, J, Xu, T, Jiang, Y, Jiang, C, Li, H, Li, X, Liu, G, et al
Nutrition and cancer. 2023;(3):805-814
Abstract
Determine the association of lean body mass (LBM) on the incidence and severity of peripheral neurotoxicity in cancer patients who received nab-paclitaxel alone or combined with cisplatin or carboplatin. This prospective clinical study examined 32 cancer patients classified into a sarcopenia or non-sarcopenia group according to the Asian L3 vertebra skeletal muscle index (L3-SMI) at Ordos Central Hospital (China) from December 2020-2021, to compare the incidence and severity of neurotoxicity and analizing the relationship between nab-paclitaxel dose per kg LBM and neurotoxicity. There were 18 patients (56.25%) in the sarcopenia group and 14 (43.75%) in the non-sarcopenia group. The incidences of peripheral and severe neurotoxicity were higher in the sarcopenia group (both P < 0.05). Patients in three different body surface area (BSA) groups received the same nab-paclitaxel dose (260 mg/m2 BSA). However, when patients were divided into three groups according to LBM, they received different doses (low-LBM: 15.18 mg/kg LBM, middle-LBM: 12.82 mg/kg LBM, and high-LBM: 11.14 mg/kg LBM). The incidence of grade-C or higher neurotoxicity of these three groups was 61.54% (8/13), 20.00% (1/5), and 11.11% (1/9). Sarcopenia and a higher dose of nab-paclitaxel per kg LBM were associated with peripheral and severe neurotoxicity. Chemotherapy dosing based on body composition may reduce neurotoxicity in patients receiving nab-paclitaxel.Registration number of Clinical Trial: ChiCTR2000040918.
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Challenging obesity and sex based differences in resting energy expenditure using allometric modeling, a sub-study of the DIETFITS clinical trial.
Haddad, F, Li, X, Perelman, D, Santana, EJ, Kuznetsova, T, Cauwenberghs, N, Busque, V, Contrepois, K, Snyder, MP, Leonard, MB, et al
Clinical nutrition ESPEN. 2023;:43-52
Abstract
BACKGROUND & AIMS Resting energy expenditure (REE) is a major component of energy balance. While REE is usually indexed to total body weight (BW), this may introduce biases when assessing REE in obesity or during weight loss intervention. The main objective of the study was to quantify the bias introduced by ratiometric scaling of REE using BW both at baseline and following weight loss intervention. DESIGN Participants in the DIETFITS Study (Diet Intervention Examining The Factors Interacting with Treatment Success) who completed indirect calorimetry and dual-energy X-ray absorptiometry (DXA) were included in the study. Data were available in 438 participants at baseline, 340 at 6 months and 323 at 12 months. We used multiplicative allometric modeling based on lean body mass (LBM) and fat mass (FM) to derive body size independent scaling of REE. Longitudinal changes in indexed REE were then assessed following weight loss intervention. RESULTS A multiplicative model including LBM, FM, age, Black race and the double product (DP) of systolic blood pressure and heart rate explained 79% of variance in REE. REE indexed to [LBM0.66 × FM0.066] was body size and sex independent (p = 0.91 and p = 0.73, respectively) in contrast to BW based indexing which showed a significant inverse relationship to BW (r = -0.47 for female and r = -0.44 for male, both p < 0.001). When indexed to BW, significant baseline differences in REE were observed between male and female (p < 0.001) and between individuals who are overweight and obese (p < 0.001) while no significant differences were observed when indexed to REE/[LBM0.66 × FM0.066], p > 0.05). Percentage predicted REE adjusted for LBM, FM and DP remained stable following weight loss intervention (p = 0.614). CONCLUSION Allometric scaling of REE based on LBM and FM removes body composition-associated biases and should be considered in obesity and weight-based intervention studies.
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Sintilimab Plus Modified FOLFIRINOX in Metastatic or Recurrent Pancreatic Cancer: The Randomized Phase II CISPD3 Trial.
Fu, Q, Chen, Y, Huang, D, Guo, C, Zhang, X, Xiao, W, Xue, X, Zhang, Q, Li, X, Gao, S, et al
Annals of surgical oncology. 2023;(8):5071-5080
Abstract
BACKGROUND Folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) or modified FOLFIRINOX (mFFX) is the first-line standard of care for metastatic pancreatic adenocarcinoma; effective and safe treatment strategies are needed as survival remains poor. Sintilimab, a human immunoglobulin G4 monoclonal antibody for programmed cell death-1, has shown efficacy in various cancers. We evaluated the efficacy and safety of sintilimab with mFFX for metastatic/recurrent pancreatic ductal adenocarcinoma in China. PATIENTS AND METHODS This was a single-center, randomized, controlled, open-label phase II study. Patients were assigned 1:1 to sintilimab + mFFX or mFFX (n = 55, each). RESULTS In the intention-to-treat population, median overall survivals (primary endpoint) were similar in the sintilimab + mFFX and mFFX groups: 10.9 and 10.8 months, respectively [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.69-1.68]. The objective response rate was higher [50.0% (95% CI 34.6-65.4%) versus 23.9% (95% CI 11.1-36.7%)] in the sintilimab + mFFX group (P < 0.05). Median (HR, 95% CI) progression-free survival and disease control rates (95% CI) were also similar at 5.9 and 5.7 months (0.93, 0.62-1.40), and 84.1% (72.8-95.3%) and 71.7%, (58.2-85.3%), respectively. Incidences of grade ≥ 3 treatment-emergent adverse events were 84.9% (45/53) and 74.1% (40/54), and that of grade ≥ 3 immune-related adverse events were 5.7% (3/53) and 0 in each group, respectively. CONCLUSIONS The study did not meet its primary endpoint, no clear survival benefit was observed, and the benefit of sintilimab + mFFX for advanced pancreatic cancer was not supported; however, the findings suggest that using this regimen for pancreatic cancer is feasible, has an acceptable safety profile, and leads to an objective response rate of 50%. Trial registration ClinicalTrials.Gov; NCT03977272.
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Psoriasis complicated with metabolic disorder is associated with traditional Chinese medicine syndrome types: a hospital-based retrospective case-control study.
Sun, X, Zhao, H, Wang, R, Li, H, Wu, Y, Ze, K, Su, Y, Li, B, Li, X
Current medical research and opinion. 2023;(1):19-25
Abstract
OBJECTIVE To explore the distribution law of traditional Chinese medicine (TCM) syndrome types in patients with psoriasis vulgaris complicated by metabolic disorders based on the same pathogenic factors as blood-heat and blood-stasis in the pathogenesis of psoriasis and metabolic disorders and to further analyze the correlation between adiponectin and the distribution law. METHODS From 1 January 2018 to 31 December 2019, patients diagnosed with psoriasis in the inpatient or outpatient department of Dermatology Ward of Shanghai Yueyang Hospital and normal participants who underwent physical examination in the physical examination center over the same period were retrospectively reviewed. Demographic data, medical history, metabolic disorder indices, and TCM syndrome indices of psoriasis patients and healthy volunteers were evaluated. RESULTS We included 307 patients with psoriasis and 613 healthy controls. On analyzing past medical history, the proportion of overweight and obesity and the comorbidity of diabetes in the psoriasis group (53.42 and 14.66%) were significantly higher than in the control group (43.88 and 7.67%, respectively; p < .05). The abnormal rates of triglyceride (34.20%), high-density lipoprotein cholesterol (50.49%), and HbA1c (18.57%) levels in the psoriasis group were higher than those in the normal control group (26.75, 17.13, and 12.56%, respectively). Overall, the incidence of metabolic disorders in psoriasis patients (267/307, 86.97%) was higher than that in the normal controls (484/613, 78.96%). Among the different syndrome types, the blood-stasis group had significantly higher rates of hypertension, diabetes, and abnormal glycosylated hemoglobin (46.07, 19.10, and 24.72%, respectively) than those of the control group (27.57, 7.67, and 12.56%; p < .05). Patients with blood stasis syndrome had the highest metabolic disorder comorbidity rate (93.26%) and lowest adiponectin level (p < .05). CONCLUSIONS TCM syndrome differentiation of psoriasis, especially the diagnosis of blood-stasis syndrome, prompts the early screening of patients with metabolic comorbidities. For patients with psoriasis with metabolic disorder, TCM for promoting blood circulation and removing blood stasis can be compatibly applied without contraindications. TRIAL REGISTRATION The trial was registered at ClinicalTrials.gov (Trial ID: NCT03942185).
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Sorafenib maintenance after allogeneic haemopoietic stem-cell transplantation in patients with FLT3-ITD acute myeloid leukaemia: long-term follow-up of an open-label, multicentre, randomised, phase 3 trial.
Xuan, L, Wang, Y, Yang, K, Shao, R, Huang, F, Fan, Z, Chi, P, Xu, Y, Xu, N, Deng, L, et al
The Lancet. Haematology. 2023;(8):e600-e611
Abstract
BACKGROUND Our open-label, multicentre, randomised, phase 3 trial showed that sorafenib maintenance after haematopoietic stem-cell transplantation (HSCT) improved overall survival and reduced relapse for patients with FLT3 internal tandem duplication (FLT3-ITD) acute myeloid leukaemia undergoing allogeneic HSCT. Here, we present a post-hoc analysis on the 5-year follow-up data of this trial. METHODS This phase 3 trial, done in seven hospitals in China, included patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic HSCT, who were aged 18-60 years, had an Eastern Cooperative Oncology Group performance status of 0-2, had composite complete remission before and after transplantation, and had haematopoietic recovery within 60 days after transplantation. Patients were randomly assigned (1:1) to receive sorafenib maintenance (400 mg orally twice daily) or non-maintenance (control) at 30-60 days after transplantation. Randomisation was done with permuted blocks (block size four) via an interactive web-based system. Investigators and participants were not masked to group assignment. The primary endpoint was the 1-year cumulative incidence of relapse, which was reported previously. For this updated analysis, the 5-year endpoints were overall survival; cumulative incidence of relapse; non-relapse mortality; leukaemia-free survival; graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS); cumulative incidence of chronic GVHD; and late effects in the intention-to-treat population. The trial is registered with ClinicalTrials.gov, NCT02474290, and is complete. FINDINGS Between June 20, 2015, and July 21, 2018, 202 patients were randomly assigned to sorafenib maintenance (n=100) or non-maintenance (n=102). Median follow-up was 60·4 months (IQR 16·7-73·3). Extended follow-up showed improved overall survival (72·0% [95% CI 62·1-79·7] vs 55·9% [45·7-64·9]; hazard ratio [HR] 0·55, 95% CI 0·34-0·88; p=0·011), leukaemia-free survival (70·0% [60·0-78·0] vs 49·0% [39·0-58·3]; 0·47, 0·30-0·73; p=0·0007), and GRFS (58·0% [47·7-67·0] vs 39·2% [29·8-48·5]; 0·56, 0·38-0·83; p=0·0030), lower cumulative incidence of relapse (15·0% [8·8-22·7] vs 36·3% [27·0-45·6]; 0·33, 0·18-0·60; p=0·0003), and no increase in non-relapse mortality (15·0% [8·8-22·7] vs 14·7% [8·6-22·3]; 0·79, 0·39-1·62; p=0·98) for patients in the sorafenib group compared with those in the control group. The 5-year cumulative incidence of chronic GVHD (54·0% [43·7-63·2] vs 51·0% [40·8-60·3]; 0·82, 0·56-1·19; p=0·73) did not differ significantly between the two groups and we did not find substantial differences in late effects between the two groups. There were no treatment-related deaths. INTERPRETATION With extended follow-up, sorafenib maintenance after transplantation is associated with improved long-term survival and reduced relapse rates compared with non-maintenance, further supporting this strategy as a standard of care for patients with FLT3-ITD acute myeloid leukaemia undergoing allogeneic HSCT. FUNDING None. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.
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Phase I, Randomized, Placebo-Controlled, Dose-Escalation Study of GB223, a Fully-Humanized Monoclonal Antibody to RANKL, in Healthy Chinese Adults.
Li, C, Liu, H, Liao, Y, Zhu, Y, Tian, J, Wang, X, Hu, Z, Zhan, Y, Li, X, Liang, X, et al
BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy. 2023;(5):721-735
Abstract
BACKGROUND GB223 is a novel, fully-humanized monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL). In this phase I study, the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of GB223 were investigated. PATIENTS AND METHODS This was a randomized, double-blinded, placebo-controlled, single-dose escalation study conducted in 44 healthy Chinese adults. Participants were randomly assigned to receive a single subcutaneous injection dose of 7, 21, 63, 119, or 140 mg of GB223 (n = 34) or placebo (n = 10) and were followed up for 140-252 days. RESULTS The results of noncompartmental analysis showed that GB223 was slowly absorbed after dosing, with a time to reach maximum concentration (Tmax) ranging from 5 to 11 days. Serum GB223 concentrations decreased slowly, with a long half-life ranging from 7.91 to 19.60 days. A two-compartment Michaelis-Menten model was found to best describe the pharmacokinetics of GB223, and the absorption rate of GB223 differed between males (0.0146 h-1) and females (0.0081 h-1). Serum C-terminal telopeptide of type I collagen decreased significantly postdose, and the inhibition lasted 42-168 days. No deaths or drug-related serious adverse events occurred. The most frequent adverse events were blood parathyroid hormone increased (94.1%), blood phosphorus decreased (67.6%) and blood calcium decreased (58.8%). In the GB223 group, 44.1% (15/34) of subjects were antidrug antibody positive after dosing. CONCLUSION In this study, we demonstrated for the first time that a single subcutaneous injection of GB223, from 7 to 140 mg, is safe and well tolerated in healthy Chinese subjects. GB223 has a nonlinear pharmacokinetic profile, and sex was a potential covariate that may affect the absorption rate of GB223. CLINICAL TRIAL REGISTRATION NCT04178044 and ChiCTR1800020338.
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Safety, tolerability, pharmacokinetics and effects of diet on AD16, a novel neuroinflammatory inhibitor for Alzheimer's disease: a randomized phase 1 study.
Peng, D, Xu, S, Zou, T, Wang, Y, Ouyang, W, Zhang, Y, Dong, C, Li, D, Guo, J, Shen, Q, et al
BMC medicine. 2023;(1):459
Abstract
BACKGROUND AD16 is a Class 1.1 new drug candidate for Alzheimer's disease (AD), which has demonstrated potential benefits in AD by reducing neuroinflammation in preclinical studies. Herein, the pharmacokinetics (PK), safety, and tolerability of single and multiple-dose AD16 and the effect of food were assessed in healthy Chinese adults. METHODS Single-center, randomized, placebo-controlled, double-blind studies were conducted for single and multiple ascending doses. A total of 62 subjects were enrolled in single-dose groups; 10 each in 5, 10, 20, 30, and 40 mg groups, and 6 each in 60 and 80 mg dose groups. Twenty subjects were divided equally into 30 and 40 mg groups for the multiple-dose study. To determine the effect of a high-fat diet on AD16, 16 subjects were administered a single 20 mg dose of AD16 under the fasted and fed condition in a single-center, randomized, open-label, two-cycle, two-crossover study. Moreover, safety and PK parameters were also assessed. RESULTS Plasma exposure to a single oral dose of AD16 increased at an approximate dose-increasing rate. The pharmacodynamic dose of the AD16 can be maintained through the accumulation effect of the drug within the safety window. Compared to fasting, ingesting a high-fat meal decelerated the rate of AD16 absorption, albeit without effect on its overall absorption. No dose-related toxicities were seen in any of the studies, all treatment-emergent adverse events were grade I/II, and no serious adverse event occurred. CONCLUSIONS The present study exhibited favorable safety, tolerability, and PK profile of AD16, supporting its further research as a potential drug treatment for AD. TRIAL REGISTRATION ClinicalTrials.gov; NCT05787028, NCT05787041, NCT05806177. The SAD and FE studies were retrospectively registered on 28 March 2023. The MAD study was retrospectively registered on 10 April 2023.
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Efficacy and safety of empagliflozin in combination with insulin in Chinese patients with type 2 diabetes and insufficient glycaemic control: A phase III, randomized, double-blind, placebo-controlled, parallel study.
Ji, L, Lu, Y, Li, Q, Fu, L, Luo, Y, Lei, T, Li, L, Ye, S, Shi, B, Li, X, et al
Diabetes, obesity & metabolism. 2023;(7):1839-1848
Abstract
AIM: To evaluate the efficacy and safety of empagliflozin in combination with insulin ± oral antidiabetic drugs (OADs) over 24 weeks, in Chinese patients with type 2 diabetes (T2D) who had insufficient glycaemic control. MATERIALS AND METHODS This was a randomized, double-blind, placebo-controlled, parallel group, multicentre phase III study. Adult patients with T2D and insufficient glycaemic control who received insulin ± up to two OADs were randomized (1:1:1) to receive empagliflozin 10 or 25 mg, or placebo for 24 weeks. The primary endpoint was change from baseline in HbA1c at week 24. RESULTS Of 219 randomized patients, 73 patients were in each treatment group; baseline characteristics were comparable among the groups. There was a significantly larger decrease from baseline in HbA1c (adjusted mean treatment difference -0.99 and -0.98 for in the empagliflozin 10 and 25 mg groups, respectively; P < .0001) with both doses of empagliflozin than with placebo. There were also significantly larger decreases from baseline in fasting plasma glucose, 2-hour postprandial glucose and body weight with both empagliflozin doses than with placebo. Among patients in the empagliflozin 10 mg, 25 mg and placebo groups, 17.8%, 9.6% and 11.0% reported confirmed hypoglycaemic events, respectively (nominal P = .2422 and .7661 in the empagliflozin 10 and 25 mg groups, respectively), and no Clinical Events Committee-confirmed diabetic ketoacidosis events were reported. CONCLUSIONS In Chinese patients with T2D, empagliflozin combined with insulin ± OADs improved glycaemic control and was well tolerated, without an increased risk of hypoglycaemia.