Central Register Of Clinical Trials Research Articles

The effects of grape seed extract supplementation on cardiovascular risk factors, liver enzymes and hepatic steatosis in patients with non-alcoholic fatty liver disease: a randomised, double-blind, placebo-controlled study.

Despite the high antioxidant potential of grape seed extract (GSE), very limited studies have investigated its effect on non-alcoholic fatty liver disease (NAFLD). Therefore, this study was conducted with the aim of investigating the effect of GSE on metabolic factors, blood pressure and steatosis severity in patients with NAFLD. In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention. The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all < 0.05). Also, before and after adjustment based on baseline, the average changes indicated that the levels of insulin, HOMA-IR, TC, TG, LDL-c, SBP, DBP, MAP in the GSE group decreased more than in the control group (p for all < 0.05). Furthermore, the changes in HDL-c were significantly higher in the GSE group (p < 0.05). The between-groups analysis showed a significant decrease in the HOMA-β and AST before and after adjustment based on baseline levels (p < 0.05). Moreover, the changes in QUICKi after adjustment based on baseline levels were higher in the GSE group than in the control group. Also, between-groups analysis showed that the severity of hepatic steatosis was reduced in the intervention group compared to the placebo group (P = 0.002). It seems that GSE can be considered one of the appropriate strategies for controlling insulin resistance, hyperlipidemia, hypertension and hepatic steatosis in NAFLD patients. The clinical trial was registered in the Iranian Clinical Trial Registration Center (IRCT20190731044392N1). https://irct.behdasht.gov.ir/trial/61413 . (The registration date: 30/03/2022).

Preventing CXCL12 elevation helps to reduce acute exacerbation of COPD in individuals co-existing type-2 diabetes: A bioinformatics and clinical pharmacology study

AimsTo investigate the immunology shared mechanisms underlying chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) and examine the impact of anti-diabetic drugs on acute exacerbation of COPD (AECOPD). MethodsWe analyzed GSE76925, GSE76894, GSE37768, and GSE25724 to identify differentially expressed genes. Hub-genes were identified through protein–protein interaction network analysis and evaluated by the receiver operating characteristic curve. CXCL12 emerged as a robust biomarker, and its correlation with lung function and CD8+ T cells were further quantified and validated. The activated signaling pathways were inferred through Gene set enrichment analysis (GSEA). The retrospective clinical analysis was executed to identify the influence of dipeptidyl peptidase-4 inhibitors (DPP-4i) on CXCL12 and evaluate the drug’s efficacy in AECOPD. ResultsThe significant up-regulation of CXCL12 expression in patients with two diseases were revealed. CXCL12 exhibited a negative correlation with pulmonary function (r = -0.551, p < 0.05). Consistent with analysis in GSE76925 and GSE76894, the positive correlation between the proportion of CD8+ T cells was demonstrated(r=0.469, p<0.05). GSEA identified “cytokines interaction” as an activated signaling pathway, and the clinical study revealed the correlation between CXCL12 and IL-6 (r=0.668, p<0.05). In patients with COPD and T2DM, DDP-4i treatment exhibited significantly higher serum CXCL12, compared to GLP-1RA. Analysis of 187 COPD patients with T2DM indicated that the DPP-4i group had a higher frequency of AECOPD compared to the GLP-1RA group (OR 1.287, 95%CI [1.018–2.136]). ConclusionsCXCL12 may represent a therapeutic target for COPD and T2DM. GLP-1RA treatment may be associated with lower CXCL12 levels and a lower risk of AECOPD compared to DPP-4i treatment.Clinical Trial Registration: China Clinical Trial Registration Center（ChiCTR2200055611）.

Characteristics of the oral and gastric microbiome in patients with early-stage intramucosal esophageal squamous cell carcinoma

BackgroundOral microbiome dysbacteriosis has been reported to be associated with the pathogenesis of advanced esophageal cancer. However, few studies investigated the potential role of oral and gastric microbiota in early-stage intramucosal esophageal squamous carcinoma (EIESC).MethodA total of 104 samples were collected from 31 patients with EIESC and 21 healthy controls. The compositions of oral and gastric microbiota were analyzed using 16 S rRNA V3-V4 amplicon sequencing. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between groups. The correlation between oral microbiota and clinicopathological factors was evaluated using Spearman correlation analysis. Additionally, co-occurrence networks were established and random forest models were utilized to identify significant microbial biomarkers for distinguishing between the EIESC and control groups.ResultsA total of 292 oral genera and 223 species were identified in both EIESC and healthy controls. Six oral genera were remarkably enriched in EIESC groups, including the genera Porphyromonas, Shigella, Subdoligranulum, Leptotrichia, Paludibacter, and Odoribacter. LEfSe analysis identified genera Porphyromonas and Leptotrichia with LDA scores > 3. In the random forest model, Porphyromonas endodontalis ranked the top microbial biomarker to differentiate EIESC from controls. The elimination rate of Porphyromonas endodontalis from the oral cavity to the stomach was also dramatically decreased in the EIESC group than controls. In the microbial co-occurrence network, Porphyromonas endodontalis was positively correlated with Prevotella tannerae and Prevotella intermedia and was negatively correlated with Veillonella dispar.ConclusionOur study potentially indicates that the dysbacteriosis of both the oral and gastric microbiome was associated with EIESC. Larger scale studies and experimental animal models are urgently needed to confirm the possible role of microbial dysbacteriosis in the pathogenesis of EIESC. (Chinese Clinical Trial Registry Center, ChiCTR2200063464, Registered 07 September 2022, https://www.chictr.org.cn/showproj.html?proj=178563)

Status of outcome measures in randomized controlled trials of kidney-tonifying and blood-activating method in treatment of knee osteoarthritis

This study assesses the status of outcome measures in the randomized controlled trial(RCT) involving the kidney-tonif-ying and blood-activating method for treating knee osteoarthritis(KOA), aiming to establish a theoretical foundation for the development of a core set of outcome measures in traditional Chinese medicine(TCM) treatment of KOA. The relevant articles were retrieved from CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, Cochrane Library, and Web of Science, in addition to ClinicalTrials.gov and the China Clinical Trial Registration Center, with the time interval from inception to August 2023. The RCT of treating KOA with the kidney-tonifying and blood-activating method was included. Two assessors independently conducted literature screening, data collection, and qualitative analysis to compile the outcome measure results. A total of 350 RCTs were included, involving 165 outcome measures with the total frequency of 1 462. These outcome measures were categorized into six domains: symptom and sign measures(23) with the frequency of 718(49.1%), TCM symptom and syndrome measures(3) with the frequency of 53(3.6%), physical examination measures(130) with the frequency of 506(34.6%), quality of life measures(4) with the frequency of 20(1.3%), long-term efficacy measures(2) with the frequency of 6(0.4%), and safety measures(3) with the frequency of 159(10.9%). Additionally, 53 studies used TCM syndrome and symptom scores as indicators of efficacy, employing eight distinct measurement tools. The RCTs involving the kidney-tonifying and blood-activating method for treating KOA had a variety of problems, such as unclear prio-ritization of outcome measures, diversity in measurement tools, absence of standardized assessment criteria for specific measures, and non-standardized usage. These problems affected the research quality and reliability. Hence, it is advisable to draw upon international expertise, improve research design, and merge TCM efficacy characteristics with clinical research to establish a core set of KOA outcome measures aligned with TCM principles.

Current progress towards prevention of Nipah and Hendra disease in humans: A scoping review of vaccine and monoclonal antibody candidates being evaluated in clinical trials.

Nipah and Hendra are deadly zoonotic diseases with pandemic potential. To date, no human vaccine or monoclonal antibody (mAb) has been licensed to prevent disease caused by these pathogens. The aim of this scoping review was to identify and describe all Phase I, II, and III clinical trials of vaccine candidates or mAbs candidates designed to prevent Nipah and Hendra in humans and to compare the characteristics of the vaccine candidates to characteristics outlined in the Target Product Profiledrafted by the World Health Organisation as part of the WHO Research & Development Blueprint for Action to Prevent Epidemics. We searched 23 clinical trial registries, the Cochrane Central Register of Clinical Trials, and grey literature up to June 2023 to identify vaccine and mAb candidates being evaluated in registered clinical trials. Vaccine candidate and trial characteristics were double-extracted for evaluation and the vaccine candidate characteristics were compared with the preferred and critical criteria of the World Health Organisation's Target Product Profile for Nipah virus vaccine. Three vaccine candidates (Hendra Virus Soluble Glycoprotein Vaccine [HeV-sG-V], PHV02, and mRNA-1215) and one mAb (m102.4) had a registered human clinical trial by June 2023. All trials were phase 1, dose-ranging trials taking place in the United States of America or Australia and enrolling healthy adults. Although all vaccine candidates meet the dose regimen and route of administration criteria of the Target Product Profile, other criteria such as measures of efficacy and reactogenicity will need to be evaluated in the future as evidence becomes available. Multiple vaccine candidates and one mAb candidate have reached the stage of human clinical trials and are reviewed here. Monitoring progress during evaluation of these candidates and candidates entering clinical trials in the future can help highlight many of the challenges that remain.

Effective dose of propofol combined with intravenous esketamine for smooth flexible laryngeal mask airway insertion in two distinct age groups of preschool children

BackgroundThere is limited research on the combined use of propofol and esketamine for anesthesia induction during flexible laryngeal mask airway (FLMA) in pediatric patients, and the effective dosage of propofol for FLMA smooth insertion remains unclear. We explored the effective dose of propofol combined with intravenous esketamine for the smooth insertion of FLMA in two distinct age groups of preschool children.MethodsThis is a prospective, observer-blind, interventional clinical study. Based on age, preschool children scheduled for elective surgery were divided into group A (aged 1–3 years) and group B (aged 3–6 years). Anesthesia induction was started with intravenous administration of esketamine (1.0 mg.kg− 1) followed by propofol administration. The FLMA was inserted 2 min after propofol administration at the target dose. The initial dose of propofol in group A and group B was 3.0 mg.kg− 1 and 2.5 mg.kg− 1, respectively. The target dose of propofol was determined with Dixon’s up-and-down method, and the dosing interval of propofol was 0.5 mg.kg− 1. If there was smooth insertion of FLMA in the previous patient, the target dose of propofol for the next patient was reduced by 0.5 mg.kg− 1; otherwise, it was increased by 0.5 mg.kg− 1. The median 50% effective dose (ED50) for propofol was estimated using Dixon’s up-and-down method and Probit analysis, while the 95% effective dose (ED95) was estimated through Probit analysis. Vital signs and adverse events during induction were recorded.ResultsEach group included 24 pediatric patients. Using Dixon’s up-and-down method, the ED50 of propofol combined with esketamine for smooth insertion of FLMA in group A was 2.67 mg.kg− 1 (95%CI: 1.63–3.72), which was higher than that in group B (2.10 mg. kg− 1, 95%CI: 1.36–2.84) (p = 0.04). Using Probit analysis, the ED50 of propofol was calculated as 2.44 (95% CI: 1.02–3.15) mg.kg− 1 in group A and 1.93 (95% CI: 1.39–2.32) mg.kg− 1 in group B. The ED95 of propofol was 3.72 (95%CI: 3.07–15.18) mg.kg− 1 in group A and 2.74 (95%CI: 2.34–5.54) mg.kg− 1 in group B. In Group B, one pediatric patient experienced laryngospasm.ConclusionThe effective dose of propofol when combined with intravenous esketamine for smooth insertion of FLMA in children aged 1–3 years is 2.67 mg.kg− 1, which is higher than that in children aged 3–6 years (2.10 mg. kg− 1).Trial registrationChinese Clinical Trial Registry Center (Registration Number: ChiCTR2100044317; Registration Date: 2021/03/16)

Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study

BackgroundIn Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule’s efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice.MethodsThis randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators.ResultsCompared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group.ConclusionsZhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA.Trial registration: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.

Comparing the glycaemic outcomes between real-time continuous glucose monitoring (rt-CGM) and intermittently scanned continuous glucose monitoring (isCGM) among adults and children with type 1 diabetes: A systematic review and meta-analysis of randomized controlled trials.

To conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the effectiveness of real-time continuous glucose monitoring (rtCGM) versus intermittently scanned continuous glucose monitoring (isCGM) on key glycaemic metrics (co-primary outcomes HbA1c and time-in-range [TIR] 70-180 mg/dL, 3.9-10.0 mmol/L) among people with type 1 diabetes (T1D). Medline, PubMed, Scopus, Web of Science and Cochrane Central Register of clinical trials were searched. Inclusion criteria were RCTs; T1D populations of any age and insulin regimen; comparing any type of rtCGM with isCGM (only the first generation had been compared to date); and reporting the glycaemic outcomes. Glycaemic outcomes were extracted post-intervention and expressed as mean differences and 95% CIs between the two comparators. Results were pooled using a random-effect meta-analysis. The risk of bias was assessed using the Cochrane RoB2 tool. The quality of evidence was assessed by the GRADE approach. Five RCTs met the inclusion criteria (4 parallel and 1 crossover design; 4 with CGM use <8 weeks), involving 446 participants (354 adults; 92 children and adolescents). Overall, meta-analysis showed rtCGM compared to isCGM improved absolute TIR by +7.0% (95% CI: 5.8%-8.3%, I2 = 0%, p < 0.01) accompanied by a favorable effect on time-below-range <70 mg/dL (3.9 mmol/L) - 1.7% (95%CI: -3.0% to -0.4%; p = 0.03). No differences were seen regarding HbA1c. This meta-analysis highlights that for people with T1D, rtCGM confers benefits over isCGM primarily related to increased TIR, with improvements in hypo- and hyperglycaemia.

Eficacia de la serratiopeptidasa en cirugía del tercer molar. Una revisión sistemática y un metanálisis

Objective: To determine the efficacy of serratiopeptidase in third molar surgery. Materials and Methods: A bibliographic search was carried out until April 2022, in the biomedical databases: Pubmed/Medline, Cochrane Central Registry of Clinical Trials, Scopus, Scielo and Google Scholar. Studies reporting the ef-ficacy of serratiopeptidase in third molar surgery, which were randomized clinical trials, in English and without time limits, were included. The RoB 2.0 tool was used to assess the risk of the included studies and the GRADEPro GDT tool to assess Results: The preliminary search yielded a total of 116 articles, discarding those that did not meet the selection criteria, leaving only 10 articles. Six articles entered a meta-analysis and found that serratiopeptidase reduces trismus but not reduce inflammation and pain after third molar surgery. Conclusions: The literature reviewed suggests that ser-ratiopeptidase is effective in reducing trismus after third molar surgery. Keywords: Serratiopeptidase; Molar, Third; Inflammation; Pain; Trismus; Meta-Analysis.

Efficacy and safety of rifampicin-based triple therapy for non-puerperal mastitis: A single-arm, open-label, prospective clinical trial

ObjectivesTo assess the efficacy and safety of rifampicin-based triple therapy (rifampicin, isoniazid, and ethambutol) for treating NPM. MethodsThis single-center, single-arm, prospective clinical trial was conducted at the Second Hospital of Shandong University (Jinan, China). Patients with pathologically diagnosed granulomatous lobular mastitis and periductal mastitis received triple drugs, i.e., rifampicin (450 mg/day), isoniazid (300 mg/day), and ethambutol (15 mg/kg/day), until complete response or the investigator decided to discontinue treatment. The primary endpoint was the complete response rate (CRR) assessed by the investigator. The secondary endpoints included the overall remission rate (ORR), recurrence rate (RR), and safety. ResultsA total of 218 patients were enrolled in the study between January 1, 2013 and October 31, 2020. With a median follow-up time of 48 months, the CRR and the ORR were 78.44% and 94.04%, respectively. While 13 patients (5.96%) demonstrated no response and 19 relapsed (8.72%). Adverse events (AEs) were not common. The most common AEs during treatment were liver dysfunction (1.83%), gastrointestinal reactions (1.83%), fatigue (1.83%), erythema (1.38%), and menstrual disorders (0.92%). ConclusionRifampicin, isoniazid, and ethambutol demonstrated promising response rates with acceptable safety profiles in patients with NPM. Further confirmatory trial is warranted in the future. Trial registrationThe study was approved by the Ethics Committee of the Second Hospital of Shandong University and retrospectively registered at the China Clinical Trial Registration Center (registration number: ChiCTR2100049591).

Evaluation of the efficacy, safety and influencing factors of concomitant and sequential administration of viral respiratory infectious disease vaccines: a systematic review and meta-analysis.

There is no clear conclusion on the immunogenicity and adverse events of concomitant administration the viral respiratory infectious disease vaccines. We aimed to evaluate the impact of concomitant administering viral respiratory infectious disease vaccines on efficiencies, safety and influencing factors. This meta-analysis included studies from PubMed, Embase, Cochrane Central Register of Clinical Trials, Web of Science, WHO COVID-19 Research, and ClinicalTrials.gov databases. Randomized controlled trials of the adult participants concomitant administered with viral respiratory infectious disease vaccine and other vaccines were included. The main outcomes were the seroconversion rate and seroprotection rate of each vaccine. Used the Mantel-Haenszel fixed effects method as the main analysis to estimate the pooled RRs and the corresponding 95% confidence intervals. The risk of bias for each trial was assessed using the Cochrane Handbook for Systematic Reviews of Interventions, while evidence certainty was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. A total of 21 studies comprising 14060 participants with two types of vaccines were retained for the meta-analysis. Concomitant immunization reduced the geometric mean titer (RR: 0.858, 95% CI: (0.785 to 0.939)) and the geometric mean fold rise (0.754 (0.629 to 0.902)) in the SARS-COV-2 vaccine group but increased the seroconversion rate (1.033 (1.0002 to 1.067)) in the seasonal influenza vaccine group. Concomitant administration were influenced by the type of vaccine, adjuvant content, booster immunization, and age and gender of the recipient. This meta-analysis suggested that the short-term protection and safety of concomitant administered were effective. Appropriate adjuvants, health promotion and counselling and booster vaccines could improve the efficiency and safety of Concomitant vaccination. https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022343709.

Neurobiomechanical mechanism of Tai Chi to improve upper limb coordination function in post-stroke patients: a study protocol for a randomized controlled trial

BackgroundUpper limb dysfunction seriously affects the ability of stroke patients to perform activities of daily living. As a popular exercise therapy, Tai Chi may become an alternative intervention. However, the neurophysiological mechanism by which Tai Chi improves upper limb dysfunction in stroke patients is still unclear, which limits its further promotion and application. Therefore, conducting a strict randomized clinical trial is necessary to observe how Tai Chi affects upper limb dysfunction in stroke patients and to explore its neurophysiological mechanism.Methods/designThis report describes a randomized, parallel-controlled trial with distributive concealment and evaluator blinding. A total of 84 eligible participants will be randomly assigned to the Tai Chi group or the control group in a 1:1 ratio. The participants in the Tai Chi group will receive 4 weeks of Tai Chi training: five 60-min sessions a week for a total of 20 sessions. The participants in the control group will not receive Tai Chi training. Both groups will receive medical treatment and routine rehabilitation training. The primary outcome measure is the mean change in the Fugl-Meyer Assessment Upper Extremity (FMA-UE) scale score between baseline and 4 weeks; the secondary outcomes are the mean changes in kinematic characteristics and the Wolf Motor Function Test (WMFT) and Stroke Impact Scale (SIS) scores. In addition, the corticomuscular coupling level and near-infrared brain functional imaging will be monitored to explore the mechanism by which Tai Chi improves upper limb function of stroke patients.DiscussionThis randomized controlled trial will examine the effectiveness of Tai Chi in stroke patients with upper limb dysfunction and explore the neurophysiological mechanism. Positive results will verify that Tai Chi can improve upper limb function of stroke patients.Trial registrationChinese Clinical Trial Registration Center, ChiCTR2200061376 (retrospectively registered). Registered June 22, 2022. http://www.chictr.org.cn/listbycreater.aspx. Manuscript Version: 3.0 Manuscript Date: October 10, 2023.

BCMA CAR-T-Cell Therapy in Combination with Long-Term Pomalidomide Is a Safe and Effective Treatment for Relapsed/Refractory Multiple Myeloma

Background: B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR-T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed in some cases within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality and has direct antimyeloma effects, might enhance the efficacy of BCMA CAR-T-cell therapy. Here, we present the efficacy of this combination regimen for R/R MM. Methods: We performed a single-center prospective clinical study that was registered with the Chinese Clinical Trial Registration Center (ChiCTR2000036350). Patients with relpased or refractory multiple myeloma receiving BCMA CAR-T cell infusion were randomized to receive long-term pomalidomide treatment (4 mg/day) one month after infusion. The primary endpoint is overall survival (OS) in R/R MM with long-term pomalidomide administration compared to those without pomalidomide therapy after CAR T-cell infusion. The secondary endpoints include time to progression (TTP) and therapeutic response. Also, the copy numbers of CAR were assessed after infusion. Results: A total of 14 R/R MM patients who received BCMA CAT T-cell therapy, were included in this study. The median age of the enrolled R/R MM patients was 59.5 years (44-71). Five patients had high-risk cytogenetic abnormalities (IGH rearrangement, 1q21 amplification, and P53 deletion) at the time of initial diagnosis. In addition, high-risk genetic alterations were newly detected in patient 2 during first-line therapy. All patients had previously received 3 to 6 lines of treatment with proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), or anti-CD38 monoclonal antibodies. As shown in Figure 1, all patients had demonstrated progressive disease prior to CAR T-cell infusion. The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR-T-cell infusion, of the 6 patients receiving pomalidomide, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response）, while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 19.7 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 4.5 (1-14) months, while the TTP was not reached in patients who received long-term pomalidomide treatment. Moreover, the dynamic abundance of circulating BCMA CAR-T cells was monitored as shown in Figure 2. In patients who received pomalidomide treatment after CAR-T-cell therapy, the CAR copy numbers of circulating CAR-T cells peaked 8 to 10 days after CAR-T-cell infusion, with a peak copy number of up to 10 6. In addition, BCMA CAR-T cells persisted (&amp;gt;1*10 3 copies/µg DNA) for 3 months in vivo. Without pomalidomide administration, BCMA CAR-T cells persisted for up to 2.5 months in the peripheral circulation (results not shown). Conclusion: Our results confirm the efficacy of the long-term oral pomalidomide administration (4 mg/day) after BCMA CAR T-cell infusion in patients with R/R MM. Notably, this combination regieme reduced the recurrence rate and prolonged progression-free survival for R/R MM patients, providing a promising option for treating R/R MM. In addition, oral administration of pomalidomide did not significantly prolong the persistence of BCMA CAR T-cells in vivo. However, data from studies with larger sample sizes are required to draw valid conclusions.

EFFECTIVENESS OF PHONOPHORESIS VERSUS THERAPEUTIC ULTRASOUND FOR KNEE OSTEOARTHRITIS: A SYSTEMATIC REVIEW OF RANDOMIZED CONTROLLED TRIALS

AbstractObjectivesTo compare the effectiveness of phonophoresis (PH) and conventional therapeutic ultrasound (US) on the functional and pain outcomes of patients with knee osteoarthritis.MethodsWe conducted an electronic search through PubMed, Cochrane Central Register of Clinical Trials (CENTRAL), Web of Science (WOS), and Scopus databases. We screened the retrieved articles to include only English full-text randomized controlled trials that examined the effect of phonophoresis versus conventional therapeutic ultrasound on patients with knee osteoarthritis. Two reviewers screened, extracted the data, and independently assessed the quality of the included articles.ResultsA total of five randomized controlled trials met our inclusion criteria out of 267 studies screened. Our results showed no statistically significant differences between the PH and US groups (1), (2), (3),(4), and (5). The PH group demonstrated more significant effects than the UT group in reducing VAS pain scores (P=0.009) and improving WOMAC scores, although this did not reach the level of significance (P=0.143) (5). In the long term, PH therapy was found to be superior to US in improving painless walking duration and distance VAS scores (p=0.034, 0.017) respectively, as well as walking and resting walking VAS scores (p=0.03, 0.007) respectively, which were found to be permanent (3).ConclusionsBoth therapies improve pain and function. However, we suggest conducting more high-quality trials with larger sample sizes and do not recommend the use of these therapies in clinical practice due to limitations in gender selection and high risk of bias.Declaration of Interest(b) declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported:I declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Prehospital characteristics that identify major trauma patients: A hybrid systematic review protocol

Background International evidence has demonstrated significant improvements both in the trauma care process and outcomes for patients through re-configuring care services from that which is fragmented to integrated trauma networks. A backbone of any trauma network is a trauma triage tool. This is necessary to support paramedic staff in identifying major trauma patients based on prehospital characteristics. However, there is no consensus on an optimal triage tool and with that, no consensus on the minimum criteria for prehospital identification of major trauma. Objective Examine the prehospital characteristics applied in the international literature to identify major trauma patients. Methods To ensure the systematic review is both as comprehensive and complete as possible, we will apply a hybrid overview of reviews approach in accordance with best practice guidelines. Searches will be conducted in Pubmed (Ovid MEDLINE), Embase, Cochrane Library of Systematic Reviews and Cochrane Central Register of Clinical Trials. We will search for papers that analyse prehospital characteristics applied in trauma triage tools that identify major trauma patients. These papers will be all systematic reviews in the area, not limited by year of publication, supplemented with an updated search of original papers from November 2019. Duplication screening of all articles will be conducted by two reviewers and a third reviewer to arbitrate disputes. Data will be extracted using a pre-defined data extraction form, and quality appraised by the Newcastle Ottawa Quality Assessment form. Conclusions An exhaustive search for both systematic reviews and original papers will identify the range of tools developed in the international literature and, importantly, the prehospital characteristics that have been applied to identify major trauma patients. The findings of this review will inform the development of a national clinical prediction rule for triage of major trauma patients.

Chronic total occlusion rotational atherectomy (CTO RA) versus non-CTO RA in coronary artery disease: A meta-analysis of clinical outcomes and complications

BackgroundChronic total occlusion rotational atherectomy (CTO RA) is an emerging intervention in coronary artery disease (CAD), although data comparing its outcomes and complications with non-CTO RA are scarce. We sought to evaluate the outcomes of RA in CTO lesions compared to those in non-CTO lesions by performing a meta-analysis. MethodsWe conducted a systematic review and meta-analysis of studies comparing the clinical outcomes and complications between CTO RA and non-CTO RA in patients with CAD. We searched PUBMED, CINAHL, EMBASE and Cochrane Central Register of Clinical Trials for any studies that compared the outcomes of RA in CTO and non-CTO lesions. The outcomes analyzed included in-hospital major adverse cardiovascular events (MACE), target vessel revascularization (TVR), angiographic success, procedural success, periprocedural complications, coronary perforation, and all-cause mortality. ResultsFour studies with a total of 1868 patients were included, spanning from 2018 to 2022, from Germany, Taiwan, and Korea. The median age of included patients was 71. The rate of the pooled results indicated a moderate, non-significant increase in in-hospital MACE and TVR for CTO RA compared to non-CTO RA. There was a small, non-significant decrease in angiographic and procedural success in CTO RA compared to non-CTO RA. CTO RA was associated with a non-significant increase in periprocedural complications and a significant increase in coronary perforation compared to non-CTO RA. All-cause mortality showed a non-significant increase in the CTO RA group. ConclusionThis meta-analysis provides evidence that while CTO RA may be associated with a higher risk of coronary perforation, the risk of other outcomes including MACE, TVR, and all-cause mortality is not significantly different compared to non-CTO RA. More research is needed to further understand these relationships and to optimize treatment strategies in patients with CAD undergoing CTO RA.

Individualized PEEP without Recruitment Maneuvers Improves Intraoperative Oxygenation: A Randomized Controlled Study.

Individualized positive end-expiratory pressure (PEEP) combined with recruitment maneuvers improves intraoperative oxygenation in individuals undergoing robot-assisted prostatectomy. However, whether electrical impedance tomography (EIT)-guided individualized PEEP without recruitment maneuvers can also improve intraoperative oxygenation is unknown. To test this, fifty-six male patients undergoing elective robot-assisted laparoscopic prostatectomy were randomly assigned to either individualized PEEP (Group PEEPIND, n = 28) or a control with a fixed PEEP of 5 cm H2O (Group PEEP5, n = 28). Individualized PEEP was guided by EIT after placing the patients in the Trendelenburg position and performing intraperitoneal insufflation. Patients in Group PEEPIND maintained individualized PEEP without intermittent recruitment maneuvers, and those in Group PEEP5 maintained a PEEP of 5 cm H2O intraoperatively. Both groups were extubated in a semi-sitting position once the extubation criteria were met. The primary outcome was arterial oxygen partial pressure (PaO2)/inspiratory oxygen fraction (FiO2) prior to extubation. Other outcomes included intraoperative driving pressure, plateau pressure and dynamic, respiratory system compliance, and the incidence of postoperative hypoxemia in the post-operative care unit (PACU). Our results showed that the intraoperative median for PEEPIND was 16 cm H2O (ranging from 12 to 18 cm H2O). EIT-guided PEEPIND was associated with higher PaO2/FiO2 before extubation compared to PEEP5 (71.6 ± 10.7 vs. 56.8 ± 14.1 kPa, p = 0.003). Improved oxygenation extended into the PACU with a lower incidence of postoperative hypoxemia (3.8% vs. 26.9%, p = 0.021). Additionally, PEEPIND was associated with lower driving pressures (12.0 ± 3.0 vs. 15.0 ± 4.4 cm H2O, p = 0.044) and better compliance (44.5 ± 12.8 vs. 33.6 ± 9.1 mL/cm H2O, p = 0.017). Our data indicated that individualized PEEP guided by EIT without intraoperative recruitment maneuvers also improved perioperative oxygenation in patients undergoing robot-assisted laparoscopic radical prostatectomy, which could benefit patients with the risk of intraoperative hemodynamic instability caused by recruitment maneuvers. Trial registration: China Clinical Trial Registration Center Identifier: ChiCTR2100053839. This study was registered on 1 December 2021. The first patient was recruited on 15 December 2021.

Traditional Chinese medicine for age-related macular degeneration: A clinical evidence map between 2000 and 2022

Abstract Background We systematically searched and summarized clinical studies on traditional Chinese medicine (TCM) for age-related macular degeneration (AMD) with the method of evidence map. We aimed to provide evidence and research direction for the prevention or treatment of AMD with TCM in the future. Materials and methods We searched PubMed, Web of Science, EMBASE, and Chinese databases including CNKI (Chinese National Knowledge Infrastructure), WanFang and VIP, ClinicalTrials.gov, and Chinese Clinical Trial Registry Center studies on the prevention or treatment of TCM for AMD from January 2000 to November 2022. We showed distribution features of these studies in the form of text description, graphs, and tables. Results The final 258 articles included 245 clinical studies, 9 systematic reviews or meta-analyses, and 4 guidelines, expert consensus, or clinical pathway. After analyzing the articles with a focus on the stage of AMD, study type, sample size, intervention measures, outcome indicators, and the quality of evidence, we found that the studies were increasing, most of which were wet AMD, the main study type was randomized controlled trials, and the sample size was mostly fewer than 100 cases. Different interventions of TCM, such as Chinese medicine, Chinese patent medicine, or acupuncture, showed the potential benefits of improving vision, reducing fundus lesions, and alleviating some uncomfortable symptoms. However, the sample size of these studies was small. The outcome indicators were not unified, and the stage of AMD was unclear. The quality of articles was lower, and there were few studies on early AMD. The advantages of TCM for the prevention or treatment of AMD remained unclear. Conclusions Early intervention will be the focus and direction of AMD in the prevention or treatment of TCM, and more standardized clinical studies of TCM for early AMD need to be designed and carried out in the future.

Outcomes Associated With Intracranial Aneurysm Treatments Reported as Safe, Effective, or Durable

Testing new medical devices or procedures in terms of safety, effectiveness, and durability should follow the strictest methodological rigor before implementation. To review and analyze studies investigating devices and procedures used in intracranial aneurysm (IA) treatment for methods and completeness of reporting and to compare the results of studies with positive, uncertain, and negative conclusions. Embase, MEDLINE, Web of Science, and The Cochrane Central Register of Clinical Trials were searched for studies on IA treatment published between January 1, 1995, and the October 1, 2022. Grey literature was retrieved from Google Scholar. All studies making any kind of claims of safety, effectiveness, or durability in the field of IA treatment were included. Using a predefined data dictionary and analysis plan, variables ranging from patient and aneurysm characteristics to the results of treatment were extracted, as were details pertaining to study methods and completeness of reporting. Extraction was performed by 10 independent reviewers. A blinded academic neuro-linguist without involvement in IA research evaluated the conclusion of each study as either positive, uncertain, or negative. The study followed Preferring Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The incidence of domain-specific outcomes between studies with positive, uncertain, or negative conclusions regarding safety, effectiveness, or durability were compared. The number of studies that provided a definition of safety, effectiveness, or durability and the incidence of incomplete reporting of domain-specific outcomes were evaluated. Overall, 12 954 studies were screened, and 1356 studies were included, comprising a total of 410 993 treated patients. There was no difference in the proportion of patients with poor outcome or in-hospital mortality between studies claiming a technique was safe, uncertain, or not safe. Similarly, there was no difference in the proportion of IAs completely occluded at last follow-up between studies claiming a technique was effective, uncertain, or noneffective. Less than 2% of studies provided any definition of safety, effectiveness, or durability, and only 1 of the 1356 studies provided a threshold under which the technique would be considered unsafe. Incomplete reporting was found in 546 reports (40%). In this systematic review and meta-analysis of IA treatment literature, studies claiming safety, effectiveness, or durability of IA treatment had methodological flaws and incomplete reporting of relevant outcomes supporting these claims.

Immediate analgesic effect of acupuncture intervention within 10 min during acute migraine attacks: protocol of a randomised controlled trial

IntroductionMigraine is a widespread neurological disorder characterised by recurrent moderate-to-severe headaches. These headaches can seriously affect patients’ daily life and work, especially during acute attacks when patients often need immediate...