A meta-analysis of treatment for early-stage cervical cancer: open versus minimally invasive radical trachelectomy.

BACKGROUND: In previous systematic reviews, meta-analysis was lacking, resulting in the statistical difference between the data of different surgeries being impossible to judge. This meta-analysis aims to contrast the fertility results and cancer outcomes between open and minimally invasive surgery. METHOD: We systematically searched databases including PubMed, Embase, Cochrane, and Scopus to collect studies that included open and minimally invasive radical trachelectomy. A random-effect model calculated the weighted average difference of each primary outcome via Review Manager V.5.4. RESULT: Eight studies (1369 patients) were incorporated into our study. For fertility results, the Open group excels MIS group in pregnancies-Third trimester delivery [OR = 2.68; 95% CI (1.29, 5.59); P = 0.008]. Nevertheless, there is no statistical difference in clinical pregnancy, miscarriage, and second-trimester rate. Concerning cancer outcomes, no difference was detected in the overall survival [OR = 1.56; 95% CI (0.70, 3.45); P = 0.27] and recurrence [OR = 0.63; 95% CI (0.35, 1.12); P = 0.12]. Concerning surgery-related outcomes, the comprehensive effects revealed that the estimated blood loss of the Open group was higher than that of the MIS group[MD = 139.40; 95% CI (79.05, 199.75); P < 0.0001]. However, there was no difference between the postoperative complication rate in the two groups [OR = 1.52; 95% CI (0.89, 2.60); P = 0.12]. CONCLUSION: This meta-analysis suggested that the fertility result of the Open group may be better than the MIS group, while the MIS group has better surgery-related outcomes. Owing to the poor cases of our study, a more robust conclusion requires more relevant articles in the future. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022352999.

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

A landscape of methodology and implementation of adaptive designs in cancer clinical trials.

BACKGROUND: The use of adaptive designs in cancer trials has considerably increased worldwide in recent years, along with the release of various guidelines for their application. This systematic review aims to comprehensively summarize the key methodological and executive features of adaptive designs in cancer clinical trials. METHODS: A comprehensive search from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials was conducted to screen eligible clinical trials that employed adaptive designs and were conducted in cancer patients. The methodological and executive characteristics of adaptive designs were the main measurements extracted. Descriptive analyses, primarily consisting of frequency and percentage, were employed to analyzed and reported the data. RESULTS: A total of 180 cancer clinical trials with adaptive designs were identified. The first three most common type of adaptive design was the group sequential design (n=114, 63.3 %), adaptive dose-finding design (n=22, 12.2 %), and adaptive platform design (n=16, 8.9 %). The results showed that 4.4 % (n=8) of trials conducted post hoc modifications, and around 29.4 % (n=53) did not provide the methods for controlling type I errors. Among phase II or above trials, 79.9 % (112/140) applied the surrogate endpoint as the primary outcome in these trials. Importantly, 27.2 % (49/180) of trials did not report clear information on the independent data monitoring committee (iDMC), and 13.3 % (n=24) without clear information on interim analyses. Interim analyses suggested 34.4 % (62/180) of trials being stopped for futility, 10.6 % (n=19) for efficacy, and 2.2 % (n=4) for safety concerns in the early stage. CONCLUSIONS: This study emphasizes adaptive designs in cancer trials face significant challenges in their design or strict implementation according to protocol, which might significantly compromise the validity and integrity of trials. It is thus important for researchers, sponsors, and policymakers to actively oversee and guide their application.

Effect of omentopexy/gastropexy on gastrointestinal symptoms after laparoscopic sleeve gastrectomy: A meta-analysis of randomized controlled trials and systematic review.

INTRODUCTION: The increased prevalence of obesity worldwide and low incidence of postoperative complications make the laparoscopic sleeve gastrectomy (LSG) a clear public choice for obese-related individuals. Pre-existing studies reported contentious outcomes regarding the association with gastrointestinal symptoms after adding omentopexy (Ome) or gastropexy (Gas) to LSG. The present meta-analysis attempted to evaluate the pros and cons of operating Ome/Gas after LSG concerning gastrointestinal symptoms. METHODS: The data extraction and study quality assessment were independently performed by two individuals. The PubMed, EMBASE, Scopus, and Cochrane Library databases were systematically searched up to October 1, 2022, using the keywords LSG, omentopexy, and gastropexy to identify randomized controlled trial studies. RESULTS: Of the original 157 records, 13 studies with 3515 patients were included. LSG with Ome/Gas excels the LSG group in nausea (odds ratio [OR] = 0.57; 95% CI[0.46, 0.70]; P < .00001), reflux (OR = 0.57; 95% CI [0.46, 0.70]; P < .00001), vomiting (OR = 0.41; 95% CI [0.25, 0.67]; P = .0004) on gastrointestinal symptoms and bleeding (OR = 0.36; 95% CI [0.22, 0.59]; P < .0001), leakage (OR = 0.19; 95% CI [0.09, 0.43]; P < .0001), gastric torsion (OR = 0.23; 95% CI [0.07, 0.75]; P = .01) on post-LSG complications. Further, LSG with Ome/Gas was superior to LSG regarding the result of excess body mass index loss in 1 year after surgery (mean difference = 1.83; 95% CI [0.59, 3.07]; P = .004). However, no significant associations were shown between groups in wound infection and the resulting weight or body mass index 1 year after surgery. Of note, subgroup analysis indicated that gastroesophageal reflux disease can be alleviated by adding Ome/Gas post-LSG in those who used small bougies from 32 to 36 Fr (OR = 0.24; 95% CI [0.17, 0.34]; P < .00001) in contrast with large bougies over 36 Fr. CONCLUSION: Most results elucidated the impact of adding Ome/Gas after LSG in reducing the incidence of gastrointestinal symptoms. Additionally, more studies should be conducted to find the relations between other indicators in the present analysis due to the poor cases.

Different Effects and Mechanisms of Selenium Compounds in Improving Pathology in Alzheimer's Disease.

Owing to the strong antioxidant capacity of selenium (Se) in vivo, a variety of Se compounds have been shown to have great potential for improving the main pathologies and cognitive impairment in Alzheimer's disease (AD) models. However, the differences in the anti-AD effects and mechanisms of different Se compounds are still unclear. Theoretically, the absorption and metabolism of different forms of Se in the body vary, which directly determines the diversification of downstream regulatory pathways. In this study, low doses of Se-methylselenocysteine (SMC), selenomethionine (SeM), or sodium selenate (SeNa) were administered to triple transgenic AD (3× Tg-AD) mice for short time periods. AD pathology, activities of selenoenzymes, and metabolic profiles in the brain were studied to explore the similarities and differences in the anti-AD effects and mechanisms of the three Se compounds. We found that all of these Se compounds significantly increased Se levels and antioxidant capacity, regulated amino acid metabolism, and ameliorated synaptic deficits, thus improving the cognitive capacity of AD mice. Importantly, SMC preferentially increased the expression and activity of thioredoxin reductase and reduced tau phosphorylation by inhibiting glycogen synthase kinase-3 beta (GSK-3ß) activity. Glutathione peroxidase 1 (GPx1), the selenoenzyme most affected by SeM, decreased amyloid beta production and improved mitochondrial function. SeNa improved methionine sulfoxide reductase B1 (MsrB1) expression, reflected in AD pathology as promoting the expression of synaptic proteins and restoring synaptic deficits. Herein, we reveal the differences and mechanisms by which different Se compounds improve multiple pathologies of AD and provide novel insights into the targeted administration of Se-containing drugs in the treatment of AD.

Reversal of Lipid Metabolism Dysregulation by Selenium and Folic Acid Co-Supplementation to Mitigate Pathology in Alzheimer's Disease.

Aberrant lipid metabolism is reported to be closely related to the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD). Selenium (Se) and folate are two ideal and safe nutritional supplements, whose biological effects include regulating redox and homocysteine (Hcy) homeostasis in vivo. Here, to achieve effective multitarget therapy for AD, we combined Se and folic acid in a co-supplementation regimen (Se-FA) to study the therapeutic potential and exact mechanism in two transgenic mouse models of AD (APP/Tau/PSEN and APP/PS1). In addition to a reduction in Aß generation and tau hyperphosphorylation, a restoration of synaptic plasticity and cognitive ability was observed in AD mice upon Se-FA administration. Importantly, by using untargeted metabolomics, we found that these improvements were dependent on the modulation of brain lipid metabolism, which may be associated with an antioxidant effect and the promotion of Hcy metabolism. Thus, from mechanism to effects, this study systematically investigated Se-FA as an intervention for AD, providing important mechanistic insights to inform its potential use in clinical trials.

Advances in metformin for the treatment of non-alcoholic fatty liver disease in children.

INTRODUCTION: The increased economic and social burdens for NAFLD worldwide make treating such a disease a significant public health issue. Metformin, a kind of insulin sensitizer generally used to treat type 2 diabetes, has been recently found to have efficacy on children's NAFLD in various areas such as glucolipid metabolism, intestinal bacterial metabolism, oxidative stress, and anti-inflammatory response. This article aims to provide an overview of the possible mechanisms of NAFLD in children and the potential therapeutic application of metformin. AREAS COVERED: The Cochrane Library, PubMed, Scopus, and EMBASE database was systematically searched on 12 April 2022, using the keywords metformin; non-alcoholic fatty liver disease; and children to identify similar studies. An additional search for recently published research was performed in June 2020. EXPERT OPINION: Although metformin has been proved to have an excellent therapeutic effect on children's NAFLD; we can still explore its potential impacts and mechanisms from different angles, such as combined medication. At the same time, we should also pay attention to its side effects.