Relevant Randomized Clinical Trials Research Articles

Ticagrelor monotherapy for acute coronary syndrome: an individual patient data meta-analysis of TICO and T-PASS trials.

In patients with acute coronary syndrome (ACS), dual antiplatelet therapy (DAPT) with aspirin and a potent P2Y12 inhibitor is recommended for 12 months after drug-eluting stent (DES) implantation. Monotherapy with a potent P2Y12 inhibitor after short-term DAPT is an attractive option to better balance the risks of ischaemia and bleeding. Therefore, this study evaluated the efficacy and safety of ticagrelor monotherapy after short-term DAPT, especially in patients with ACS. Electronic databases were searched from inception to 11 November 2023, and for the primary analysis, individual patient data were pooled from the relevant randomized clinical trials comparing ticagrelor monotherapy after short-term (≤3 months) DAPT with ticagrelor-based 12-month DAPT, exclusively in ACS patients undergoing DES implantation. The co-primary endpoints were ischaemic endpoint (composite of all-cause death, myocardial infarction, or stroke) and bleeding endpoint [Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding] at 1 year. Individual patient data from two randomized clinical trials including 5906 ACS patients were analysed. At 1 year, the primary ischaemic endpoint did not differ between the ticagrelor monotherapy and ticagrelor-based DAPT groups [1.9% vs. 2.5%; adjusted hazard ratio (HR) 0.79; 95% confidence interval (CI) 0.56-1.13; P = .194]. The incidence of the primary bleeding endpoint was lower in the ticagrelor monotherapy group (2.4% vs. 4.5%; adjusted HR 0.54; 95% CI 0.40-0.72; P < .001). The results were consistent in a secondary aggregate data meta-analysis including the ACS subgroup of additional randomized clinical trials which enrolled patients with ACS as well as chronic coronary syndrome. In ACS patients undergoing DES implantation, ticagrelor monotherapy after short-term DAPT was associated with less major bleeding without a concomitant increase in ischaemic events compared with ticagrelor-based 12-month DAPT. PROSPERO (ID: CRD42023476470).

Digital Health Interventions and Patient Safety in Abdominal Surgery

Over the past 2 decades, several digital technology applications have been used to improve clinical outcomes after abdominal surgery. The extent to which these telemedicine interventions are associated with improved patient safety outcomes has not been assessed in systematic and meta-analytic reviews. To estimate the implications of telemedicine interventions for complication and readmission rates in a population of patients with abdominal surgery. PubMed, Cochrane Library, and Web of Science databases were queried to identify relevant randomized clinical trials (RCTs) and nonrandomized studies published from inception through February 2023 that compared perioperative telemedicine interventions with conventional care and reported at least 1 patient safety outcome. Two reviewers independently screened the titles and abstracts to exclude irrelevant studies as well as assessed the full-text articles for eligibility. After exclusions, 11 RCTs and 8 cohort studies were included in the systematic review and meta-analysis and 7 were included in the narrative review. Data were extracted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline and assessed for risk of bias by 2 reviewers. Meta-analytic estimates were obtained in random-effects models. Number of complications, emergency department (ED) visits, and readmissions. A total of 19 studies (11 RCTs and 8 cohort studies) with 10 536 patients were included. The pooled risk ratio (RR) estimates associated with ED visits (RR, 0.78; 95% CI, 0.65-0.94) and readmissions (RR, 0.67; 95% CI, 0.58-0.78) favored the telemedicine group. There was no significant difference in the risk of complications between patients in the telemedicine and conventional care groups (RR, 1.05; 95% CI, 0.77-1.43). Findings of this systematic review and meta-analysis suggest that perioperative telehealth interventions are associated with reduced risk of readmissions and ED visits after abdominal surgery. However, the mechanisms of action for specific types of abdominal surgery are still largely unknown and warrant further research.

The effects of citrus flavonoids supplementation on endothelial function: A systematic review and dose-response meta-analysis of randomized clinical trials.

The present systematic review and dose-response meta-analysis was conducted to synthesize existing data from randomized clinical trials (RCTs) concerning the impact of citrus flavonoids supplementation (CFS) on endothelial function. Relevant RCTs were identified through comprehensive searches of the PubMed, ISI Web of Science, and Scopus databases up to May 30, 2023. Weighted mean differences and their corresponding 95% confidence intervals (CI) were pooled utilizing a random-effects model. A total of eight eligible RCTs, comprising 596 participants, were included in the analysis. The pooled data demonstrated a statistically significant augmentation in flow-mediated vasodilation (FMD) (2.75%; 95% CI: 1.29, 4.20; I2 = 87.3%; p < 0.001) associated with CFS compared to the placebo group. Furthermore, the linear dose-response analysis indicated that each increment of 200 mg/d in CFS led to an increase of 1.09% in FMD (95% CI: 0.70, 1.48; I2 = 94.5%; p < 0.001). The findings from the nonlinear dose-response analysis also revealed a linear relationship between CFS and FMD (Pnon-linearity = 0.903, Pdose-response <0.001). Our findings suggest that CFS enhances endothelial function. However, more extensive RTCs encompassing longer intervention durations and different populations are warranted to establish more precise conclusions.

Reporting Quality and Risk of Bias Analysis of Published RCTs Assessing Anti-CGRP Monoclonal Antibodies in Migraine Prophylaxis: A Systematic Review.

Objective: Phase II/III randomized clinical trials (RCTs) are vulnerable to many types of bias beyond randomization. Insights into the reporting quality of RCTs involving migraine patients treated with monoclonal antibodies targeting the calcitonin gene-related peptide system (anti-CGRP MAbs) are currently lacking. Our aim was to analyze the reporting quality of phase II/III RCTs involving migraine patients treated with anti-CGRP MAbs. Methods: A systematic search was performed on the PubMed and EMBASE databases, according to PRISMA guidelines, for relevant RCTs in either episodic or chronic migraine prevention. Additionally, an adapted version of the 2010 CONSORT statement checklist was utilized. The ROBvis online tool was used to document the risk of bias. Results: From the initially identified 179 articles, we finally found 31 RCTs that were eligible for evaluation. The average CONSORT compliance was 88.7% (69.7-100%), while 93.5% (N = 29) of the articles had a compliance greater than 75%. Twenty-eight CONSORT items were reported in more than 75% of the articles. The average compliance of the analyzed RCTs was 93.9% for Galcanezumab, 91.3% for Fremanezumab, followed by 85.4% for Erenumab and Eptinezumab studies. Implementation of the ROB2 tool showed some concerning "missing information" arising from the inadequate reporting. Specifically, 50% of the studies (N = 16) were categorized as having inadequate information regarding the randomization process. Conclusions: Adequate reporting quality was disclosed in the evaluated RCTs with anti-CGRP MAbs in migraine prevention. However, some methodological issues need to be highlighted to be addressed in future studies assessing the efficacy of new molecules targeting CGRP or other candidate pathways implicated in migraine pathophysiology.

Zavegepant for Acute Treatment of Migraine: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

Evaluate the safety and efficacy of zavegepant (BHV-3500), a recently approved nasal spray containing a third-generation calcitonin gene-related peptide receptor antagonist, for treating acute migraine attacks. A comprehensive search was conducted across various databases up to 06/26/2023 to identify relevant randomized clinical trials (RCTs) on zavegepant's efficacy and safety in treatment of acute migraine attacks. Primary outcome: freedom from pain at 2 hours postdose. Safety outcomes were evaluated based on adverse events (AEs), with zavegepant 10 mg and placebo groups compared for incidence of AEs. Two RCTs, involving 2061 participants (1014 receiving zavegepant and 1047 receiving placebo), were quantitatively analyzed. An additional trial was included for qualitative synthesis. Zavegepant 10 mg exhibited a significantly higher likelihood of achieving freedom from pain at 2 hours postdose compared with the placebo group (risk ratio [RR] 1.54, 95% confidence interval [CI] 1.28 to 1.84). It also showed superior relief from the most bothersome symptoms at 2 hours postdose compared with placebo (RR 1.26, 95% CI 1.13 to 1.42). However, the zavegepant 10 mg group experienced a higher incidence of AEs compared with placebo (RR 1.78, 95% CI 1.5 to 2.12), with dysgeusia being the most reported AE (RR 4.18, 95% CI 3.05 to 5.72). Zavegepant 10 mg is more effective than placebo in treating acute migraine attacks, providing compelling evidence of its efficacy in relieving migraine pain and most bothersome associated symptoms. Further trials are necessary to confirm its efficacy, tolerability, and safety in diverse clinic-based settings with varied patient populations.

Effectiveness of Shugan Jieyu capsules for psychiatric symptoms of epilepsy: a systematic review and meta-analysis

BackgroundThe relationship between epilepsy and depression is bidirectional. One condition exacerbates the other. However, there are no current guidelines for treating depression in epilepsy patients. In some cases, seizures worsen when antidepressants (AD) are prescribed or when they are discontinued due to adverse events. The Shugan Jieyu capsule, composed of Acanthopanax senticosus and Hypericum perforatum, is a widely used herbal medicine for treating depression. This study aimed to explore the effectiveness and safety of Shugan Jieyu capsules (SJC) in relieving depression in patients with epilepsy.MethodsWe searched English, Korean, Japanese, and Chinese databases in October 2023 to collect all relevant randomized clinical trials (RCTs). The primary outcomes were the depression scale scores and seizure frequency. The secondary outcomes were quality of life (QoL) and adverse events.ResultsNine RCTs were included in this meta-analysis. Compared with AD, SJC showed significant differences in the improvement of depression (SMD: 3.82, 95% CI: 3.25, 4.39) and reduction in seizure frequency (MD: 0.39 times/month, 95% CI: 0.28, 0.50). SJC showed more beneficial results than antiepileptic drugs (AED) in terms of antidepressant effects (SMD: 1.10, 95% CI: 0.69, 1.51) and QoL (MD: 11.75, 95% CI: 10.55, 12.95). When patients were prescribed AED, the additional administration of SJC improved depression symptoms (SMD: 0.96, 95% CI: 0.28, 1.63). The SJC treatment group had a lower incidence of side effects than the control group. However, the difference was not statistically significant.ConclusionsOur results suggest that SJC may be effective in treating depression in patients with epilepsy. Additionally, SJC has the potential to help reduce seizure frequency in epilepsy patients with depression.

Nile tilapia skin in the treatment of second-degree burns: a systematic review with meta-analysis

Objective: Systematically review the effects of using Nile tilapia skin (NTFS) for management/treatment in patients with second-degree skin burns, when compared with two treatments containing silver, hydrofiber dressing or sulfadiazine cream (AgSD). Methodology: Systematic review with meta-analysis performed in january 2023, using PubMed, Web of Science, CINAHL, Scopus, Cochrane and Gale databases, to identify relevant randomized clinical trials. Results: In total, five randomized trials were identified comparing the use of NTFS with two types of silver-based treatment of second-degree skin burns. Occlusive dressings with NTFS significantly reduced pain levels, measured using the Visual Analogue Scale - VAS (p=0.0008), time (measured in days) for complete wound healing, corresponding to re-epithelialization of 95% or more of the initial burn (p=0.002), and the number of dressings needed until complete healing of the burn (p=0.0004). Conclusion: The results confirm the positive effects of using the NTFS dressing on patients with second-degree burns and can benefit public health systems, especially in developing and resource-poor countries.

Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis.

To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF). Relevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook. Of the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], p < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], p < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], p = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], p = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], p = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], p < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], p = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], p = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], p < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], p = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], p < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol (p < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG (p < 0.05). For infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future. https://www.crd.york.ac.uk PROSPERO (CRD42023421739).

Abstract 17 — Overall Infection Risks of Tofacitinib in Patient with Rheumatoid Arthritis: A Meta-Analysis of Randomized Clinical Trials

Background There is an ongoing controversy surrounding whether tofacitinib increases the risk of infections in patients with rheumatoid arthritis (RA). To address this issue, we conducted a meta-analysis using data from randomized clinical trials (RCTs) to assess the overall risk of infection in these patients. Methods We conducted a comprehensive systematic search in EMBASE, MEDLINE, and CENTRAL from their inception until December 2022 to identify relevant RCTs reporting the occurrence of infections in patients with RA who were treated with the standard clinical therapeutic dosage of tofacitinib (5mg twice daily orally). The primary outcomes of the included studies in this review focused on the incidence of total infections, serious infections, non-serious infections, and opportunistic infections (including herpes zoster and tuberculosis). Additionally, we examined secondary outcomes related to the incidence of various sites of infections, including the upper respiratory tract, lower respiratory tract, gastrointestinal tract, hepatobiliary system, urinary tract, skin and soft tissue, blood, dental and oral soft tissue, genital, reproductive tract, bone and joint, and central nervous system infections. Due to the expected anticipation of clinical and methodological heterogeneity across studies, the effect estimate was pooled with a random-effects model, to obtain the RRs and 95% CIs, using Mantel-Haenszel statistical method. Results Twelve eligible RCTs, involving a total of 6,056 patients, were included in the analysis. In comparison to the control group (placebo and other active treatments), tofacitinib exhibited a significant increase in the risk of total infections (RR, 1.21; 95% CI, 1.07-1.37; I2, 28%), serious infections (RR, 1.23; 95% CI, 1.02-1.48; I2, 0%), non-serious infections (RR, 1.20; 95% CI, 1.05-1.36; I2, 29%), and opportunistic infections (RR, 1.66; 95% CI, 1.40-1.97; I2, 0%). Secondary outcomes analyses revealed a significant increase in the risk of lower respiratory infections with tofacitinib (RR, 1.27; 95% CI, 1.10–1.47; I2, 0%). Conclusion Compared with placebo and other active treatments, tofacitinib significantly increased the overall risk of infections (total infections, serious infections, non-serious infections, and opportunistic infections). These findings can help clinicians assess the risk of infections in RA patients treated with tofacitinib.

Effectiveness of Creatine in Metabolic Performance: A Systematic Review and Meta-Analysis.

Using the guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this meta-analysis (MA) tried to figure out how well creatine (Cr) improves metabolic performance. We searched Google Scholar, PubMed, and the Cochrane Library to identify relevant randomized clinical trials (RCTs) exploring the various effects of Cr across different age groups compared to a placebo (PLA). We also investigated the synergistic effects of combining other supplements with Cr. In order to emphasize the different ways and sports where Cr has been used in the past years, we found from the selected articles that Cr demonstrated a more pronounced effect during aerobic or anaerobic exercise compared to PLA groups in the studies. Furthermore, in sports that demand significant cumulative energy, such as long-distance races, biking, or triathlons, athletes have observed performance enhancements with Cr supplementation. We also stipulate that Cr enhances resistance training in people over 50 years old and that adding other training supplements, such as β-hydroxy β-methylbutyrate (HMB), synergistically improves training outcomes when combined with Cr. The current MA was based on a thorough analysis of 10 separate studies. When these results were added together, we found that taking Cr supplements demonstrated statistically significant benefits over PLA. In conclusion, the present MA has found evidence that Cr has positive effects on metabolic outcomes for people who consume it.

Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update.

To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy. An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022. A total of 26 publications met eligibility criteria and form the evidentiary basis for the update. The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate.The Panel recommends the Practical Geriatric Assessment as one option for this purpose (https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf; https://youtu.be/jnaQIjOz2Dw; https://youtu.be/nZXtwaGh0Z0).Additional information is available at www.asco.org/supportive-care-guidelines.

Partial Breast Irradiation Compared with Whole Breast Irradiation: A Systematic Review and Meta-Analysis.

Early stage-breast cancer is among the most common cancer diagnoses. Adjuvant radiotherapy is an essential component of breast conserving therapy, and several options exist for tailoring its extent and duration. This study assesses the comparative effectiveness of partial breast irradiation (PBI) compared with whole breast irradiation (WBI). A systematic review was completed to identify relevant randomized clinical trials (RCTs) and comparative observational studies. Independent reviewers working in pairs selected studies and extracted data. Randomized trial results were pooled using a random effects model. Prespecified main outcomes were ipsilateral breast recurrence (IBR), cosmesis, and adverse events (AEs). 14 RCTs and 6 comparative observational studies with 17,234 patients evaluated the comparative effectiveness of PBI. PBI was not significantly different from WBI for IBR at 5 years (RR 1.34 [95% CI, 0.83-2.18]; high strength of evidence [SOE]) and 10 years (RR 1.29 [95% CI, 0.87-1.91]; high SOE). Evidence for cosmetic outcomes was insufficient. Significantly fewer acute AEs were reported with PBI compared to WBI, with no significant difference in late AEs. Data from subgroups according to patient, tumor, and treatment characteristics were insufficient. Intraoperative radiotherapy was associated with higher IBR at 5, 10, and >10 years (high SOE) compared to WBI. Ipsilateral breast recurrence was not significantly different between PBI and WBI. Acute AEs were less frequent with PBI. This evidence supports the effectivness of PBI among selected patients with early-stage, favorable risk breast cancer who are similar to those represented in the included studies.

Comparative effectiveness of glycyrrhizic acid preparations aimed at improving liver function of patients with chronic hepatitis B: A network meta-analysis of 53 randomized controlled trials

Background and objectivesEntecavir (ETV) has disadvantages, such as poor improvement in liver function, during the treatment of Chronic hepatitis B (CHB). Thus ETV is often used in clinical therapy with glycyrrhizic acid (GA) preparations. However, due to the lack of reliable and direct clinical studies, it remains controversial whether glycyrrhizic acid preparations have the best efficacy in CHB. Therefore, we aimed to compare and rank the different GA preparations in the treatment of CHB using network meta-analysis (NMA). MethodsWe systematically searched MEDLINE, EMBASE, Cochrane Library, Web of Science, China national knowledge internet (CNKI), Wanfang, VIP, and SinoMed databases as of August 4, 2022. Literature was screened according to predefined inclusion and exclusion criteria to extract meaningful information. A Bayesian approach was used for random effects model network meta-analysis, and Stata 17 software was used for data analysis. ResultsFrom 1074 papers, we included 53 relevant randomized clinical trials (RCTs). For the primary outcome, we used the overall effective rate in assessing the effectiveness of treatment for CHB (31 RCTs including 3007 patients): CGI, CGT, DGC and MgIGI significantly reduced the incidence of overall response compared to controls (RRs range from 1.16 to 1.24); SUCRA results showed that MgIGI was the best (SUCRA 0.923). In terms of secondary outcomes, we assessed the effect of treatment for CHB according to the level of reduction in ALT and AST: for ALT (37 RCTs including 3752 patients), CGI, CGT, DGC, DGI and MgIGI significantly improved liver function index compared to controls (MD range from 14.65 to 20.41); SUCRA results showed that CGI was the best (SUCRA 0.87); for AST, GI, CGT, DGC, DGI and MgIGI significantly improved liver function index compared to the control group (MD range from 17.46 to 24.42); SUCRA results showed that MgIGI was the best (SUCRA 0.871). ConclusionIn this study, we verified that the combination of GA and Entecavir is more effective than entecavir monotherapy in the treatment of hepatitis B. MgIGI and CGI showed clinically significant effects on liver function recovery compared with other GA preparations. MgIGI appeared to be the best choice among all GA preparations for the treatment of CHB. Our study provides some references for the treatment of CHB.

The effects of chicory supplementation on liver enzymes and lipid profiles in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis of clinical evidence

The beneficial effects of Cichorium intybus L., chicory, in patients with non-alcoholic fatty liver disease (NAFLD) are controversial. This review aimed to systematically summarize the evidence on the effects of chicory on liver function and lipid profile in patients with NAFLD. Online databases of Scopus, Web of Science, PubMed, EMBASE, Cochrane Library, and grey literature were searched for relevant randomized clinical trials. Weighted mean differences (WMD) with 95% confidence intervals (CIs) were used as effect sizes and a random-effects model was used to pool the data. Besides, sensitivity analyses and publication bias analysis were performed. In total, five articles containing 197 patients with NAFLD were included. The study showed that chicory significantly decreased the levels of both aspartate transaminase (WMD:-7.07 U/L, 95%CI:-13.82 to-0.32) and alanine transaminase (WMD:-17.53 U/L, 95%CI:-32.64 to-2.42). However, no significant effects on alkaline phosphatase and gamma-glutamyl transferase levels and the components of the lipid profile were observed with the use of chicory. This meta-analysis showed that chicory supplementation may exert potential hepatoprotective effects in patients with NAFLD. However, for widespread recommendations, more studies with a higher number of patients and longer periods of intervention are mandatory.

Avancées thérapeutiques dans la prise en charge des tumeurs rares malignes ovariennes

Even if each rare ovarian tumor (ROT) has a low incidence, the sum of all these entities represents almost the half of all ovarian neoplasms. Thus, development of dedicated clinical trial emerged as a prerequisite to improve their managements. Owing to the spreading of dedicated institutional networks and (supra)national collaborations, the number of clinical trials has increased the past few years, with different types of trials; while some focused on specific molecular features, others assessed innovative molecules. Furthermore, relevant randomized clinical trials were designed as a mean to position new treatment options. Currently, innovative molecular-driven trials, based on master protocol trials are emerging and may shed light towards the improvement of personalized medicine regarding ROT.

Abstract P3-03-28: Clinicopathological Risk Factors of Brain Metastasis in Breast Cancer Patients: A Systematic Review and Meta-analysis

Abstract BACKGROUND: Breast cancer brain metastasis (BCBM) has an incidence rate of 5.1% among Breast Cancer (BC) patients. In BCBM, cancerous cells come from a primary tumor that implant and grow in the brain leading to potentially lethal neurologic symptoms and signs. With more clinical options and therapeutics strategies becoming available, a multi-disciplinary approach for treatment is needed in order to best meet BCBM patients’ needs, however, systematic guidelines for the screening of high-risk asymptomatic patients are still lacking and the BCBM diagnoses are performed only after symptoms manifestation. Therefore, understanding the clinical and pathologic drivers of BCBM aids in improving medical interventions by guiding future research directions. This study aims to determine the clinicopathological risk factors of brain metastasis (BM) among BC patients. METHODS: Retrospective cohort studies on the clinicopathological characteristics of BM versus non-BM (NBM) patients were retrieved through reputable search databases. Review Manager version 5.4.1 was used for statistical analyses. In the presence of heterogeneities, a pragmatic approach was undertaken to employ both random-effects (RE) and fixed-effect (FE) meta-analyses. The statistical significance of the pooled effect estimates was examined by the Z-test. Interstudy variations and heterogeneities were estimated using Cochran’s Q-statistic with P &amp;lt; 0.05 indicating a statistically significant heterogeneity. The risk of bias and the quality of studies were assessed at a study level using ROBINS-I tool. RESULTS: A total of four (4) retrospective cohort studies were included in the analyses. Random-effects meta-analyses with i2 &amp;lt; 50% (P &amp;gt; 0.05) had shown significant association (P &amp;lt; 0.05) on the increased incidences of BCBM development for HER2+ expression [OR: 2.43, 95% CI: 1.88 – 3.12, P &amp;lt; 0.00001] and for pre-menopausal status [OR: 1.77, 95% CI: 1.13 – 2.76, P = 0.01]. Fixed-effect meta-analyses had shown significant association (P &amp;lt; 0.05) on the decreased incidence of BCBM development for TNBC disease [OR: 0.66; 95% CI: 0.47 – 0.92; P = 0.02]. The risk of bias was low to moderate in the majority of studies. CONCLUSION: HER2 positivity and pre-menopausal status are risk factors for increased BCBM development while the absence of regional lymph node metastases and ILC findings are less likely to progress to BCBM. Higher T and N categories, higher histological grade, ER negativity, and PR negativity may be associated with higher risks of BCBM while lower T categories, HER2 negativity, and TNBC may likely be associated to less BCBM development. More powerful relevant and upcoming randomized clinical trials with larger sample sizes among BCBM patients versus non-BM patients must be made exploring certainty on the clinicopathological factors contributing to BM among BC patients. Keyword/s: risk factors, breast cancer, brain metastasis Citation Format: Korina Blanca C. Garcia, April Ann A. Lubay. Clinicopathological Risk Factors of Brain Metastasis in Breast Cancer Patients: A Systematic Review and Meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-28.

Impact of perioperative α1-antagonists on postoperative urinary retention in orthopaedic surgery: meta-analysis.

Postoperative urinary retention (POUR) is a common complication following orthopaedic surgery. Previous studies attempted to establish the preventative role of α1-antagonist in POUR in the general surgical population; however, there is still no consensus regarding its use in orthopaedic surgery due to limited evidence. Electronic databases of Cochrane Library, Embase, MEDLINE, and ClinicalTrials.gov were searched by two independent investigators from inception to 1 March 2022 to identify relevant randomized clinical trials. Two reviewers independently completed a critical appraisal of included trials by using the Cochrane Risk of Bias tool version 2.0 and extracted data from included articles. Risk of POUR was summarized as risk ratio (RR) with 95 per cent confidence intervals (c.i.). Mean difference (MD) was used for meta-analysis of continuous outcomes. Five randomized clinical trials involving 878 patients (α1-antagonist, 434; placebo, 444) undergoing hip/knee arthroplasty and spine surgeries were included. One study was assessed as high risk of bias from the randomization process and was excluded from the final meta-analysis. There was no difference in the risk of POUR between patients taking α1-antagonist and the placebo in arthroplasty (RR, 0.64; 95 per cent c.i., 0.36 to 1.14) and in spine surgeries (RR, 1.03; 95 per cent c.i., 0.69 to 1.55). There was no difference in length of stay (MD, -0.14 days; 95 per cent c.i., -0.33 to 0.05). Use of α1-antagonist was associated with a higher risk of adverse events (RR, 1.97; 95 per cent c.i., 1.27 to 3.06), with a composite of dizziness, light-headedness, fatigue, altered mental status, and syncope being the most commonly reported symptoms. In patients undergoing spinal surgery and joint arthroplasty, routine administration of perioperative α1-antagonist does not decrease risk of POUR but does increase perioperative dizziness, light-headedness, and syncope.

Screening tests for the evaluation of cognitive impairment in multiple sclerosis patients

Multiple sclerosis (MS), the most common autoimmune neurological disease of young people, is a significant burden for the patient, significantly decreasing the quality of life. Besides motor deficits, sensory problems, and vision loss, in recent years, neurologists have focused also on the cognitive impairment related to this condition. The early detection of cognitive disturbances is currently an essential part of MS patients’ follow-ups, as any worsening suggests the inefficiency of the applied treatment and the need for a therapeutic switch. In this regard, this review aims to highlight the importance of cognitive screening tests in the periodical evaluation of MS patients. While in the first part, the most frequently used cognitive screening tests in Romania are presented in a detailed manner, in the second part of the article, the clinical impact of these tests is highlighted, based on the results of the most relevant randomized clinical trials published during the last 10 years. Finally, the authors suggest future research directions to improve cognitive screening testing in MS patients after exposing the limitations of currently used screening batteries.

Transcranial direct current stimulation with virtual reality versus virtual reality alone for upper extremity rehabilitation in stroke: A meta-analysis

BackgroundStroke is one of the most prevalent diseases. Motor impairment in patients with stroke frequently affects the upper extremities. Several randomized clinical trials (RCTs) have tried to prove whether or not the combination of transcranial direct current stimulation (tDCS) with virtual reality (VR) is superior to VR alone for upper extremity rehabilitation. MethodsWe searched Embase, MEDLINE, the Cochrane Library database, and Clinicaltrials.gov for relevant RCTs published before June 10, 2022. The results were analyzed by using standard mean differences (SMD) and 95% confidence intervals (95% CI). ResultsWe pooled 120 patients from 4 RCTs. There were no significant improvements in the Fugl-Meyer Upper Extremity scale (SMD = 0.51; 95% CI, −0.04 to 1.06), the Box and Block Test (SMD = 0.42; 95% CI, −0.02 to 0.86), and the Modified Ashworth Scale after the combined treatment of tDCS and VR. But tDCS combined with VR could enhance the Barthel Index scores in patients with stroke compared to VR alone (SMD = 0.49; 95% CI, 0.04 to 0.94). ConclusionsThe combination of tDCS and VR can improve the quality of daily living in patients with stroke. No more satisfactory efficacy has been demonstrated in terms of upper extremity function. However, we observe a distinct trend toward significance in some outcomes.

The Effects of Dietary Supplements, Nutraceutical Agents, and Physical Exercise on Myostatin Levels: Hope or Hype?

Myostatin, a secreted growth factor belonging to the transforming growth factor β (TGF-β) family, performs a role in hindering muscle growth by inhibiting protein kinase B (Akt) phosphorylation and the associated activation of hypertrophy pathways (e.g., IGF-1/PI3K/Akt/mTOR pathway). In addition to pharmacological agents, some supplements and nutraceutical agents have demonstrated modulatory effects on myostatin levels; however, the clinical magnitude must be appraised with skepticism before translating the mechanistic effects into muscle hypertrophy outcomes. Here, we review the effects of dietary supplements, nutraceutical agents, and physical exercise on myostatin levels, addressing the promise and pitfalls of relevant randomized clinical trials (RCTs) to draw clinical conclusions. RCTs involving both clinical and sports populations were considered, along with wasting muscle disorders (e.g., sarcopenia) and resistance training-induced muscle hypertrophy, irrespective of disease status. Animal models were considered only to expand the mechanisms of action, and observational data were consulted to elucidate potential cutoff values. Collectively, the effects of dietary supplements, nutraceutical agents, and physical exercise on myostatin mRNA expression in skeletal muscle and serum myostatin levels are not uniform, and there may be reductions, increases, or neutral effects. Large amounts of research using resistance protocols shows that supplements or functional foods do not clearly outperform placebo for modulating myostatin levels. Thus, despite some biological hope in using supplements or certain functional foods to decrease myostatin levels, caution must be exercised not to propagate the hope of the food supplement market, select health professionals, and laypeople.