A bibliometric analysis of immune-related adverse events in cancer patients and a meta-analysis of immune-related adverse events in patients with hepatocellular carcinoma.

Background and Objectives: Immunotherapy has become the standard treatment for hepatocellular carcinoma (HCC), but it carries a risk of immune-related adverse events (irAEs) that can be life-threatening. This study employs bibliometric analysis to understand global scientific research on irAEs in cancer, focusing on characteristics and areas of interest. Additionally, a meta-analysis provides a comprehensive overview of irAEs in HCC patients receiving immune checkpoint inhibitor (ICI)-based therapies. Methods: We conducted a thorough search of Web of Science Core Collection (WoSCC) publications from 1999 to 2022. R and VOSviewer software were used for analysis. A meta-analysis was performed using data from PubMed, Embase, and the Cochrane Library databases up to March 22, 2022. Trials with HCC patients reporting irAE incidence were included. Quality assessment followed Cochrane risk of bias, Newcastle-Ottawa Scale (NOS), and Methodological Index for Non-Randomized Studies (MINORS). We used random-effects or fixed-effects models based on I2 values. Primary outcomes included any-grade irAEs and grade ≥ 3 irAEs. This review and meta-analysis are registered in PROSPERO as CRD42022318885. Results: In bibliometric analysis, we included 2946 papers, showing a consistent rise in annual publications on irAEs in cancer research. Frequent keywords were "nivolumab", "immune checkpoint inhibitor", and "immune-related adverse event". "Hepatocellular carcinoma" emerged as a prominent research focus linked to irAEs. We conducted a comprehensive meta-analysis on irAE incidence in HCC patients, including 29 studies. The overall incidence of any-grade irAEs was 61.0% (95% CI 38.5%-81.3%), and grade ≥ 3 irAEs was 13.2% (95% CI 7.9%-19.6%). Treatment-related mortality occurred in 3.1% (95% CI 0.8%-6.3%), with treatment discontinuation at 10.7% (95% CI 6.3%-16.0%). Reactive cutaneous capillary endothelial proliferation (RCCEP) was the most common any-grade irAE, while elevated aspartate aminotransferase (AST) was the most common grade ≥ 3 irAE. Treatment strategies were independently associated with specific irAEs, as indicated by multivariable analysis. Conclusion: This study provides valuable insights into the current research landscape of irAEs in cancer and ofers a comprehensive overview of irAEs in HCC patients undergoing ICI-based therapy. The relatively high incidence of irAEs and their association with treatment strategies emphasize the need for careful management by clinicians when treating HCC patients. These findings offer significant guidance for optimizing care and treatment for HCC patients.

Efficacy and safety of antibody-drug conjugates in the treatment of urothelial cell carcinoma: a systematic review and meta-analysis of prospective clinical trials.

Introduction: Urothelial carcinoma (UC) is a refractory disease for which achieving satisfactory outcomes remains challenging with current surgical interventions. Antibody-drug conjugates (ADCs) are a novel class of targeted therapeutics that have demonstrated encouraging results for UC. Although there is a limited number of high-quality randomized control trials (RCTs) examining the use of ADCs in patients with UC, some prospective non-randomized studies of interventions (NRSIs) provide valuable insights and pertinent information. We aim to assess the efficacy and safety of ADCs in patients with UC, particularly those with locally advanced and metastatic diseases. Methods: A systematic search was conducted across PubMed, Embase, the Cochrane Library, and Web of Science databases to identify pertinent studies. Outcomes, such as the overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events (AEs), and treatment-related adverse events (TRAEs), were extracted for further analyses. Results: Twelve studies involving 1,311 patients were included in this meta-analysis. In terms of tumor responses, the pooled ORR and DCR were 40% and 74%, respectively. Regarding survival analysis, the pooled median PFS and OS were 5.66 months and 12.63 months, respectively. The pooled 6-month PFS and OS were 47% and 80%, while the pooled 1-year PFS and OS were 22% and 55%, respectively. The most common TRAEs of the ADCs were alopecia (all grades: 45%, grades ≥ III: 0%), decreased appetite (all grades: 34%, grades ≥ III: 3%), dysgeusia (all grades: 40%, grades ≥ III: 0%), fatigue (all grades: 39%, grades ≥ III: 5%), nausea (all grades: 45%, grades ≥ III: 2%), peripheral sensory neuropathy (all grades: 37%, grades ≥ III: 2%), and pruritus (all grades: 32%, grades ≥ III: 1%). Conclusion: The meta-analysis in this study demonstrates that ADCs have promising efficacies and safety for patients with advanced or metastatic UC. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier: CRD42023460232.

Treatment benefit of electrochemotherapy for superficial squamous cell carcinoma: a systematic review and single-arm meta-analysis.

OBJECTIVE: Treating aggressive superficial squamous cell carcinoma (SCC) poses challenges due to invasiveness. Palliative care is recommended for inoperable cases with extensive tumors near vital organs, risking disfigurement or functional impairment. Electrochemotherapy (ECT) is an emerging cutaneous tumor treatment, but its efficacy against superficial SCC remains uncertain. This study conducts a systematic review and single-arm meta-analysis to evaluate ECT's effectiveness against superficial SCC and provide current evidence for clinical practice. METHODS: Embase, PubMed and Cochrane Library were searched for studies up to May 2023. The random effects model analyzed complete response (CR) and partial response (PR), with subgroup assessment based on drug dosage, treatment response evaluation, tumor size, primary/recurrent status, and tumor location. RESULTS: Ten studies involving 162 patients and 208 tumors were included. Pooled CR and PR rates for ECT-treated superficial SCC were 66.5% (95% CI 48.4%-82.5%; I2 = 84%) and 20.3% (95% CI 10.5%-32.3%; I2 = 70%), respectively. Subgroup analysis indicated ECT's superiority in treating primary tumors (PR: 70%, CR: 30%) and tumors ≤ 3 cm (PR: 81.3%, CR: 10.1%) compared to recurrent tumors (PR: 56.7%, CR: 36.5%) and tumors > 3 cm (PR: 45.2%, CR: 34.4%). CONCLUSION: This single-arm meta-analysis confirms ECT's efficacy against superficial SCC, especially in primary tumors and those ≤ 3 cm in diameter. The study highlights the impact of tumor location and response evaluation on ECT's benefits, warranting further investigation through additional research.

The efficacy and safety of novel antiepileptic drugs in treatment of epilepsy of patients with brain tumors.

Objective: This meta-analysis aimed to assess the effectiveness and safety of novel antiepileptic drugs (AEDs) in treating epilepsy in patients with brain tumors (BTRE). Methods: A search was conducted on PubMed, EMBASE, Web of Science, and the Cochrane Library from inception to February 2023, with English language restriction. Results: In this meta-analysis, 18 clinical trials involving 755 BTRE patients were included to assess the efficacy and safety of novel AEDs in BTRE treatment. At the last follow-up, a ≥50% reduction in seizure frequency was experienced by 72% of patients (random-effects model, 95% CI = 0.64-0.78) using novel AEDs. At the last follow-up, seizure freedom was experienced by 34% of patients (random-effects model, 95% CI = 0.28-0.41) using novel AEDs. The pooled incidence of AEs was found to be 19% (95% CI: 13%-26%), with a withdrawal rate due to adverse effects of only 3%. Comparable efficacy and incidence of adverse effects were observed between lacosamide and perampanel. Conclusion: This meta-analysis suggests that novel antiepileptic drugs are deemed effective for seizure control in brain tumor patients, particularly when used as adjunctive therapy. Although lacosamide and perampanel received more focus in studies, no significant difference was observed in the efficacy and adverse reactions of these two drugs in seizure control. Further randomized controlled trials are deemed necessary to validate our findings.

Safety of Readministration of EGFR-TKI After Onset of Interstitial Lung Disease in Advanced EGFR-Mutated NSCLC: A Systematic Review and Meta-Analysis.

BACKGROUND: In patients with epidermal growth factor receptor (EGFR) mutated non-small-cell lung cancer (NSCLC), EGFR-tyrosine kinase inhibitor (TKI) interruption due to EGFR-TKI-induced interstitial lung disease (ILD) is a factor for shorter overall survival (OS). Several retrospective cohort studies have reported an OS-prolonging effect of the readministration of EGFR-TKIs. This study aimed to determine the safety of readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. METHODS: The PubMed, CINAHL, and Web of Science databases were systematically searched until May 30, 2023. The primary outcome was successful readministration of EGFR-TKIs after the onset of EGFR-TKI-induced ILD. RESULTS: A total of 690 patients were included in this meta-analysis. The initial EGFR-TKI-induced ILD rate was 13.6% (95% confidence interval [CI]:6.4-20.9). Readministration rate of EGFR-TKI after onset of EGFR-TKI-induced ILD was 40.2% (95% CI: 26.7-53.7). The successful readministration rate of EGFR-TKIs after onset of EGFR-TKI-induced ILD was 81.9% (95% CI: 73.8-90.0). Successful rate of EGFR-TKI readministration in patients with Grade 2 or higher adverse events post initial EGFR-TKI therapy was 76.1% (95% CI: 55.6-96.6). CONCLUSIONS: Although initial EGFR-TKI-induced ILD has a relatively high incidence, EGFR-TKI readministration after the onset of EGFR-TKI-induced ILD may be a viable treatment option.

Assessing the impact of transplant site on ovarian tissue transplantation: a single-arm meta-analysis.

BACKGROUND: Survival rates of young women undergoing cancer treatment have substantially improved, with a focus on post-treatment quality of life. Ovarian tissue transplantation (OTT) is a viable option to preserve fertility; however, there is no consensus on the optimal transplantation site. Most studies on OTT are nonrandomized controlled trials with limited sample sizes and uncontrolled statistical analyses, leaving the question of which transplant site yields the highest chance of achieving a live birth unanswered. OBJECTIVE: This meta-analysis aimed to assess the effect of different ovarian transplant sites on postoperative reproductive outcomes. METHODS: We adhered to the PRISMA Reporting Items for Systematic Reviews and Meta-Analyses recommendations. Systematic searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Library from inception to September 17, 2023. The inclusion criteria were as follows: (1) women who underwent OTT with a desire for future childbirth, and (2) reports of specific transplant sites and corresponding pregnancy outcomes. The exclusion criteria included the inability to isolate or extract relevant outcome data, case reports, non-original or duplicate data, and articles not written in English. RESULTS: Twelve studies (201 women) were included in the meta-analysis of cumulative live birth rates (CLBR) after OTT. The CLBR, which encompasses both spontaneous pregnancies and those achieved through assisted reproductive technology (ART) following OTT to the ovarian site, was 21% (95% CI: 6-40, I2: 52.81%, random effect). For transplantation to the pelvic site, the live birth rate was 30% (95% CI: 20-40, I2: 0.00%, fixed effect). Combining transplantation to both the pelvic and ovarian sites resulted in a live birth rate of 23% (95% CI: 11-36, I2: 0.00%, fixed effect). Notably, heterotopic OTT yielded a live birth rate of 3% (95% CI: 0-17, I2: 0.00%, fixed effect). CONCLUSION: Pregnancy outcomes were not significantly different after orthotopic ovarian transplantation, and pregnancy and live birth rates after orthotopic OTT were significantly higher than those after ectopic transplantation. REGISTRATION NUMBER: INPLASY202390008.

Transcatheter closure of post-myocardial infarction ventricular septal defect: A systematic review and single-arm meta-analysis.

Background: Ventricular septal defects (VSDs) are one of the mechanical complications of acute myocardial infarction (AMI). Because of the high risks of mortality and postoperative complications, a new alternative method is needed. With the development of interventional medicine, transcatheter closure has been increasingly performed for postmyocardial infarction ventricular septal defects (PMIVSDs). The aim of this study is to explore the feasibility and safety of transcatheter closure of PMIVSDs by meta-analysis. Methods: The included studies were mainly single-arm studies of transcatheter closure of PMIVSDs. We compared VSD size, device size, preoperative risk factors and interventions among PMIVSD patients. We analysed the transcatheter closure success rate, the 30-day mortality rate, and the incidence of residual shunts. Results: A total of 12 single-arm articles (284 patients) were included. The combined incidences of preoperative hypertension, hyperlipidaemia, and diabetes were 66% [95% CI 0.56-0.75], 54% [95% CI 0.40-0.68], and 33% [95% CI] 0.21-0.46], respectively. Multiple studies reported the combined incidences of preoperative PCI, IABP, and CABG, which were 46% [95% CI 0.15-0.80], 60% [95% CI 0.44-0.75], and 8% [95% CI 0.02-0.18]. Eleven studies reported the number of successful closures and the 30-day mortality rate; the success rate was 90% [95% CI 0.86-0.94], and the 30-day mortality rate reached 27% [95% CI 0.86-0.94]. Conclusion: For patients with PMIVSD, transcatheter closure in the acute phase can be used as a rescue measure, while in the chronic phase, it is more effective and has a lower mortality rate, but the effect of selection bias should be considered. Residual shunts are a long-term complication that have a high incidence and long-lasting effects on patients. More large, multicentre, randomized controlled trials are needed in the future to confirm the safety and reliability of transcatheter closure of PMIVSDs.

Complication, fusion, and revision rate in the lumbar cortical bone trajectory and pedicle screw fixation techniques: a systematic review and meta-analysis.

BACKGROUND: To obtain the complication rate, fusion rate, and revision rate of the lumbar cortical bone trajectory technique and pedicle screw fixation technique in lumbar interbody fusion surgery by single-arm meta-analysis and lay a basis for orthopedic surgeons to select the fixation techniques and perioperative management. METHODS: PubMed, Ovid Medline, Web of Science, CNKI, and Wanfang databases were searched comprehensively. Data extraction, content analysis, and quality assessment of the literature were performed by two independent reviewers according to the Cochrane Collaboration guidelines using R and STATA software for single-arm meta-analysis. RESULTS: The total complication rate of the lumbar cortical bone trajectory technique was 6%, including a hardware complication rate of 2%, ASD (adjacent segment degeneration) rate of 1%, wound infection rate of 1%, dural damage rate of 1%, hematoma rate tending to 0%, fusion rate of 94%, and revision rate of 1%. Lumbar pedicle screw fixation techniques had a total complication rate of 9%, with a hardware complication rate of 2%, ASD rate of 3%, wound infection rate of 2%, dural damage rate of 1%, hematoma rate tending to 0%, fusion rate of 94%, and revision rate of 5%. This study was registered with PROSPERO, CRD42022354550. CONCLUSION: Lumbar cortical bone trajectory was associated with a lower total complication rate, ASD rate, wound infection rate, and revision rate than pedicle screw fixation. The cortical bone trajectory technique reduces the incidence of intraoperative and postoperative complications and can be an alternative in lumbar interbody fusion surgery.

Effects of different surgical modalities for nerve-sparing robot-assisted radical prostatectomy on postoperative erectile function: a systematic review and one-arm meta-analysis.

Maintaining erectile function is an important quality of life issue for patients with localized prostate cancer treated with robotic-assisted radical prostatectomy (RARP). However, most existing studies are retrospective and inherently weak and cannot conclude which NS approach is most effective in restoring function in patients. We therefore performed a consistent and objective assessment of sexual function outcomes in RARP using different nerve-sparing methods to optimize postoperative outcomes. A systematic review and meta-analysis was performed based on PRISMA and STROBE statement criteria. Statistical analysis was performed using StataMP software version 14. The Newcastle-Ottawa scale was used to assess the risk of bias. This single-arm meta-analysis included 3 randomized controlled trials and 14 cohort studies with a total of 3756 patients. Our meta-analysis found that patients had the highest efficiency rate of 0.86 (0.78, 0.93) after the NS technique using the retrograde method. Overall, there are significant differences between RARP NS techniques and outcomes, and the ideal technical strategy to optimize outcomes remains controversial. However, there is consensus on the importance of careful separation, dissection of the NVB, reduction of traction and thermal injury, and preservation of the fascia around the prostate. We still need more well-designed randomized controlled trials with videos describing the details of the different surgical techniques before they can be replicated.

Evaluation of the safety and efficacy of a Polyzene-F nanocoated coronary stent system: A systematic review and single-arm meta-analysis.

Background: A stent for patients with coronary heart disease (CHD) provides a requirement for a long-term antiplatelet therapy because of the high possibility of the development of stent thrombosis. It was against this background that both Cobra and Catania Polyzene-F (PzF) stents were designed to reduce the occurrence of stent thrombosis (ST). In this study, we review the safety and effectiveness of a PzF-nanocoated stent. Methods: This systematic review with the title was registered in PROSPERO (No.398781). The inclusion criteria were including studies among patients with PzF-nanocoated coronary stents and reported target vessel failure (TVF) and ST as the outcomes, and the exclusion criteria were excluding reported patients who could not receive the adjunctive medical therapies or without the necessary endpoints. Reports about PzF-nanocoated stents were searched in PubMed, Embase, and Web of Science and other sources. Because of the existence of few reports and a lack of comparison groups, a single-arm meta-analysis was conducted in R software (v3.6.2), using a random-effects model with the generic inverse variance method. After a heterogeneity test, assessment of evidence quality was conducted by using GRADE software. A funnel plot Egger's test was performed to evaluate publication bias, and a sensitivity analysis was done to determine the robustness of the overall effects. Results: Six studies of 1,768 subjects were included. The primary endpoint that pooled the TVF rate was 8.9% (95% CI 7.5%-10.2%), which comprised the pooled cardiac death (CD) rate (1.5%, 95% CI 0%-3%), myocardial infarction (MI) rate (2.7%, 95% CI 0.4%-5.1%), target vessel revascularization (TVR) (4.8%, 95% CI 2.4%-7.2%), or target lesion revascularization (TLR) (5.2%, 95% CI 4.2%-6.4%), while the secondary endpoint ST was 0.4% (95% CI 0.1%-0.9%). The funnel plots of TVF, CD, TVR, and TLR did not show any serious publication bias, and TVF, TVR, and TLR showed evidence of moderate quality in GRADE assessment. The sensitivity analysis showed that TVF, TLR, and ST exhibited good stability (I 2 = 26.9%, 16.4%, and 35.5%, respectively), while the other endpoints showed moderate instability. Conclusion: These data indicated that the PzF-nanocoated coronary stents of the Cobra and Catania systems demonstrated good safety and efficacy in clinical application. However, the sample size of patients included in the reports was relatively small, and this meta-analysis will be updated if more studies are published in the future. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023398781.

Human amniotic membrane graft for refractory macular hole: A single-arm meta-analysis and systematic review.

PURPOSE: The treatment of refractory macular holes is controversial, with human amniotic membrane grafts emerging recently as an attractive option. We performed a meta-analysis and systematic review in this paper to assess the results of human amniotic membrane (hAM) in the treatment of refractory macular hole (MH). METHODS: We searched the Cochrane Database of Systematic Reviews, Web of Science, PubMed, Embase, China National Knowledge Infrastructure databases, VIP database, Wanfang Data Knowledge Service Platform, Sinomed, Chinese Clinical Trial Registry, and Clinical Trials.gov. Studies reporting hAM for the treatment of refractory MH were included. The outcomes are MH closure rate, visual acuity (VA) improvement rate, and graft dislocation/contracture rate. RESULTS: A total of 8 studies on 103 eyes were included, all of which had undergone failed vitrectomy and internal limiting membrane (ILM) peeling. In all studies, the VA improvement rate was 66% (95%CI: 45 to 84%), the MH closure rate was 94% (95%CI: 84 to 100%) and the hAM graft dislocation/contracture rate was 6% (95%CI: 0 to 15%). In the studies using cryopreserved hAM grafts, the MH closure rate was 99% (95%CI: 94 to 100%) and the hAM graft dislocation/contracture rate was 3% (0%, 10%). The VA improvement rates were 94% (95%CI: 79 to 100%) in the retinal detachment subgroup, 37% (95%CI: 20 to 56%) in the pathologic myopia subgroup, and 62% (95%CI: 14 to 100%) in the idiopathic MH subgroup. CONCLUSION: Human amniotic membrane in the treatment of refractory MH results in visual improvement. It has a high macular hole closure rate and low dislocation/contracture rate. Cryopreserved hAM grafts might have better outcomes than dehydrated grafts.

Efficacy and Safety of Absorb Everolimus-Eluting Bioresorbable Vascular Scaffold in Peripheral Artery Disease: A Single-Arm Meta-Analysis.

PURPOSE: This study aimed to evaluate the benefits and risks of patients with peripheral artery disease (PAD) treated with Absorb everolimus-eluting bioresorbable vascular scaffold (BVS) by analyzing all the published studies on the clinical characteristics of patients with PAD. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched for relevant studies. Efficacy, safety, and basic characteristics were analyzed. RESULTS: Four studies were included in meta-analysis, including a total number of 155 patients with PAD. The pooled overall primary patency, freedom from target lesion revascularization (TLR), symptom resolution, and wound healing were 90%, 96%, 94%, and 86%, respectively. The pooled perioperative complication and all-cause mortality were 4% and 9%, respectively. Preoperative total occlusion was detected in 43 of 192 lesions (22%). The mean lesion length was 27.26 mm. In terms of comorbidities, the pooled percentage of hypertension, hyperlipidemia, diabetes mellitus, coronary artery disease, chronic kidney disease history, and smoking were 65%, 74%, 49%, 43%, 20%, and 57%, respectively. CONCLUSION: Among these studies, hypertension, hyperlipidemia, and diabetes mellitus were the most common comorbidities in patients with PAD. The Absorb everolimus-eluting BVS was safe and showed the favorable clinical outcomes in both patency and TLR, especially in infrapopliteal disease with heavy calcification. The conclusions of this meta-analysis still needed to be verified by more relevant studies with more careful design, more rigorous execution, and larger sample size.

Complications of Unilateral Biportal Endoscopic Spinal Surgery for Lumbar Spinal Stenosis: A Systematic Review of the Literature and Meta-analysis of Single-arm Studies.

PURPOSE: This article aims to summarize the incidence of these complications through a meta-analysis, analyze the causes of complications and provide clinical promotion and recommendations. METHODS: Databases and retrieval platform including PubMed, Web of science, Springer link, Cochrane clinical trials, ProQuest, ScienceDirect, Europe PMC, Wiley online, OVID, Clinical trials, CNKI and WanFang, and supplement the literature through Google Scholar, collect all the unilateral biportal endoscopy (UBE) controlled trials and non-controlled trials of UBE in the treatment of lumbar spinal stenosis (LSS). The search time limit is from January 1, 2000 to December 25, 2021. After two reviewers independently screened the literature, extracted data and evaluated the risk of bias in the included studies, meta-analysis was performed using Stata 15.1 software. RESULTS: Finally, 24 studies were included, including 999 patients. The results of a single-arm rate meta-analysis showed that the overall complication rate of UBE treatment of LSS was 6.27% [95% CI (0.0412, 0.0876)], and the incidence of dural tear was 2.49% [95% CI (0.0133, 0.0390)], the incidence of transient paresthesia was 0.14% [95% CI (0.0000, 0.0072)], the incidence of postoperative spinal epidural hematoma was 0.27% [95% CI (0.0000, 0.0096)], the incidence of postop headache, inadequate decompression, root injury and infection was 0.00%. CONCLUSION: Current evidence shows that the complication rate of UBE in the treatment of LSS is low, mainly due to dural tears. Limited by the number and quality of included studies, the above conclusions still need to be confirmed by more studies.

Efficacy and safety of oncolytic virus combined with chemotherapy or immune checkpoint inhibitors in solid tumor patients: A meta-analysis.

Background: In recent years, several clinical trials have focused on oncolytic virus (OVs) combined with chemotherapy or immune checkpoint inhibitors (ICIs) in solid tumor patients, which showed encouraging effects. However, few studies have concentrated on the summary on the safety and efficacy of the combined treatments. Therefore, we conducted this meta-analysis to explore the safety and curative effect of the combined therapy. Methods: We searched the PubMed, Cochrane Library, Embase, and Clinicaltrials.gov databases to comprehensively select articles on OVs combined with chemotherapy or ICIs for the solid tumor treatment. Overall survival (OS), progression-free survival (PFS), 1-year survival rate, 2-year survival rate, objective response rate (ORR), and adverse events (AEs) were the outcomes. Results: Fifteen studies with 903 patients were included in this meta-analysis. The pooled ORR was 32% [95% confidence interval (CI): 27-36%, I2 = 24.9%, p = 0.239]. Median OS and median PFS were 6.79 months (CI: 4.29-9.30, I2 = 62.9%, p = 0.044) and 3.40 months (CI: 2.59-4.22, I2 = 0.0%, p = 0.715), respectively. The 1-year survival rate was 38% (CI: 0.29-0.47, I2 = 62.9%, p = 0.044), and the 2-year survival rate was 24% (CI: 12-37%, I2 = 0.0%, p = 0.805). The most common AEs were fever (63%, CI: 57-69%, I2 = 2.3%, p = 0.402), fatigue (58%, CI: 51-65%, I2 = 49.2%, p = 0.096), chill (52%, CI: 43-60%, I2 = 0.0%, p = 0.958), and neutropenia (53%, CI: 47-60%, I2 = 0.0%, p = 0.944). Conclusion: OVs combined with ICIs showed a better efficacy than OVs combined with chemotherapy, which lends support to further clinical trials of OVs combined with ICIs. In addition, OVs combined with pembrolizumab can exert increased safety and efficacy. The toxicity of grades ≥3 should be carefully monitored and observed. However, high-quality, large-scale clinical trials should be completed to further confirm the efficacy and safety of OVs combined with ICIs. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/login.php], identifier [RD42022348568].

Adverse Events in Isotretinoin Therapy: A Single-Arm Meta-Analysis.

Isotretinoin (ISO) is an oral prescription-only retinoid, well known for its acne-treating effect. However, it affects a substantial number of human cell types, causing a broad spectrum of adverse effects. The purpose of this study is to establish the isotretinoin therapy adverse events among human clinical trials and their prevalence. Two authors (J.K., J.L.) systematically performed the literature review and assessment from December 2021-February 2022. Three databases (PubMed, ClinicalTrials, and Cochrane Library) were searched using the following terms: "isotretinoin acne vulgaris" for published studies in English from 1980-2021. Finally, 25 randomized controlled clinical trials (RCTs) and five open-label clinical trials provided 3274 acne vulgaris suffering patients. Isotretinoin therapy affects almost all of the systems in the human body, causing numerous adverse events. However, they mainly concern mild mucocutaneous conditions (severe cases are rare) and represent individual responses to a drug. In addition, all adverse events are reversible and can be avoided by specific preparations.

Transjugular Intrahepatic Portosystemic Shunt for Portal Vein Cavernous Transformation: A Systematic Review and Single-Arm Meta-Analysis.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is technically challenging in the treatment of portal vein cavernous transformation (PVCT), and there is no high-quality evidence regarding whether it is an option for patients with PVCT. We carried out a systematic review and meta-analysis to assess the feasibility and safety of TIPS for PVCT. METHODS: Systematic search of PubMed, Chinese National Knowledge Infrastructure (CNKI) database, Cochrane Library, Embase, and Wanfang database through December 2021 for appropriate studies reporting efficacy and safety in patients with PVCT undergoing TIPS. The main outcome included the technical success rate, postoperative rebleeding rate, postoperative hepatic encephalopathy rate, stent patency rate, preoperative, and postoperative portal pressure. RESULTS: Ten studies, including 292 patients were included. Our results showed that TIPS was technically successful in 82.97% (95% confidence interval [CI]: 77.14%-88.41%, p = 0.297) with low heterogeneity (I2 = 18.39%, p = 0.279). Postoperative rebleeding occurred in 9.56% (95% CI: 4.55%-16.77%, p = 0.073) with moderate heterogeneity (I2 = 46.45%, p = 0.06). Postoperative hepatic encephalopathy occurred in 18.55% (95% CI: 9.23%-27.05%, p = 0.343) with moderate heterogeneity (I2 = 48.62%, p = 0.049). Stent patency during follow-up was in 78.43% (95% CI: 70.74%-85.20%, p = 0.805) with low heterogeneity (I2 = 0%, p = 0.654). Postoperative portal pressure significantly reduced (WMD = 12.79 mm Hg, 95% CI: 12.09-13.48 mm Hg, p < 0.00001) with high heterogeneity (I2 = 61.4%, p = 0.02). Both Begg test and funnel plot showed that there was no significant publication bias. CONCLUSIONS: TIPS is feasible and safe in patients with PVCT and PVCT should not be considered an absolute contraindication to TIPS.

DSAEK or DMEK for failed penetrating keratoplasty: a systematic review and single-arm meta-analysis.

PURPOSE: To review the published literature on indications and outcomes of DSAEK/DSEK and DMEK for the treatment of failed penetrating keratoplasty. DESIGN: This is a systematic review and single-arm meta-analysis. METHODS: Literature searches were conducted in PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews. Prospective and retrospective studies reporting DSAEK/DSEK or DMEK after failed penetrating keratoplasty were included. Primary outcome measures are graft survival and detachment rates, as well as postoperative visual outcomes. RESULTS: A total of 25 studies with 970 patients/989 eyes were included, comprising 735 patients with 746 eyes which underwent DSAEK/DSEK surgery and 235 patients with 243 eyes which underwent DMEK surgery, all of them following a previously failed PK. There were no randomized controlled studies. In all of the DSAEK-PK studies, the graft failure rate was 18% (10%, 26%), the detachment rate was 15% (9%, 22%) and the rejection rate was 7% (3%, 12%) by the time of the last follow-up. And in all of the DMEK-PK studies, the graft failure rate was 14% (4%, 27%), the detachment rate was 42% (28%, 56%) and the rejection rate was 7% (2%, 16%). The mean visual acuity of the DSAEK-PK and DMEK-PK groups is 0.65 ± 0.18 and 0.43 ± 0.23 logMAR, respectively, at 6 months postoperatively. CONCLUSIONS: Endothelial keratoplasty for treatment of failed penetrating keratoplasty led to improved vision and graft clarity in most recipients. Though graft survival rates and rejection rates were comparable between the two groups, the DMEK-PK group showed better visual outcomes with higher detachment rate.

Does Epidural Bupivacaine with or Without Steroids Provide Long-Term Relief? A Systematic Review and Meta-analysis.

PURPOSE OF REVIEW: Low back and lower extremity pain have been treated since 1901 with local anesthetics alone and since 1952 in combination with steroids. Over the years, multiple randomized controlled trials, systematic reviews with or without meta-analysis have been reaching discordant conclusions regarding the effectiveness of sodium chloride solution, local anesthetics, and steroids in managing spinal pain. Further, related to lack of understanding, multiple reviewers have considered local anesthetics including lidocaine and bupivacaine as equivalent to placebo based on theory that steroid is the only drug effective in the epidural space. In this review, we assessed effectiveness of epidurally administered bupivacaine with or without steroids to rule out misconceptions of placebo and to show the comparative effectiveness of epidural bupivacaine alone compared to epidural bupivacaine with steroids. RECENT FINDINGS: Multiple systematic reviews performed in assessing the effectiveness of epidural injections have converted epidurally administered lidocaine and bupivacaine to placebo. This led to inappropriate conclusions of lack of effectiveness of epidural local anesthetics with or without steroids as showing equal effectiveness when analyzed with conventional dual-arm meta-analysis. Thus, true placebo control trials with injection of an inactive substance into unrelated structures have been almost non-existent. Epidurally administered bupivacaine alone or with steroids are effective in managing low back and lower extremity pain. The findings of this review provide appropriate information of epidurally administered bupivacaine as an active agent (not a placebo) with level 1 evidence and almost equally effective as bupivacaine with steroids with level II evidence.

Factors Affecting Clinical and Endoscopic Outcomes of Placebo Arm in Trials of Biologics and Small Molecule Drugs in Ulcerative Colitis: A Meta-Analysis.

BACKGROUND: Previous systematic cumulative analyses of the placebo arm in ulcerative colitis (UC) were limited by the wide heterogeneity in the scores and definitions of response. We aimed at estimating the placebo rates of remission, response, and mucosal healing (MH) in phase 2 and 3 randomized placebo-controlled trials of biologics and small molecule drugs that used homogeneous criteria for the assessment of outcomes. METHODS: PubMed Central, Embase, and reference lists of articles were systematically searched through July 2017. Only studies that employed the Mayo score were included. RESULTS: Thirty-one randomized placebo-controlled trials consisting of 2702 patients met the inclusion criteria. At induction, the pooled estimates of the placebo rates of remission, response, and MH were 9% (95% confidence interval [CI], 7%-12%; range: 0%-29%; I2 = 75.0%), 34% (95% CI, 31%-38%; range: 12%-75%; I2 = 61.3%), and 26% (95% CI, 22%-30%; range: 2%-65%; I2 = 77.7%), respectively. At maintenance, the pooled estimates of the placebo rates of remission, response, and MH were 14% (95% CI, 10%-18%; range: 6%-30%; I2 = 73.0%), 23% (95% CI, 20%-27%; range: 18%-36%; I2 = 53.0%), and 19% (95% CI, 15%-23%; range: 12%-30%; I2 = 65.0%), respectively. Among the variables assessed by logistic regression analysis, multiple factors influenced the outcomes of placebo arms, including concomitant systemic steroids at baseline, endoscopic central reading, being naïve or non-naïve to anti-TNFs, and disease duration. CONCLUSIONS: Despite the wide use of homogeneous criteria for the assessment of clinical and endoscopic outcomes, a high heterogeneity among placebo arms of modern trials in UC still exists.

The benefit and risk of nivolumab in non-small-cell lung cancer: a single-arm meta-analysis of noncomparative clinical studies and randomized controlled trials.

Nivolumab is a programmed cell death 1 (PD-1) receptor inhibitor antibody that enhances immune system antitumor activity. Although it is used for treating advanced non-small-cell lung cancer (NSCLC), its actual efficacy has not been determined. We searched PubMed, the Cochrane Library, Embase, MEDLINE, and Web of Science for related noncomparative clinical studies and randomized controlled trials (RCTs) to assess nivolumab benefit and risk in NSCLC. The main outcomes were objective response rate (ORR), 1-year overall survival rate (1-yOS rate), and progression-free survival rate at 24 weeks (PFS at 24 weeks rate), any-grade adverse effects rate (any-grade AEs%), and grade 3-4 AE rate (grade 3-4 AEs%). Relative risk (RR) was used to compare ORR in patients with positive and negative programmed cell death ligand 1 (PD-L1) expression. Random-effects models were used to determine pooled effect size and two-sided 95% confidence intervals (95% CI). We included 20 studies (17 noncomparative open-label cohort studies, three RCTs) involving 3404 patients in our meta-analysis. The modified nivolumab ORR was 18% (95% CI: 15-20%), the 1-yOS rate was 45% (95% CI: 40-50%), PFS at 24 weeks rate was 42% (95% CI: 37-48%), any-grade AEs% was 61% (95% CI: 50-73%), and grade 3-4 AEs% was 12% (95% CI: 9-16%). PD-L1 expression was related with the nivolumab ORR. Nivolumab potentially causes ongoing response, long-term PFS, and reduced treatment-related AEs. PD-L1 expression predicts the outcome of nivolumab immunotherapy. More high-quality and well-designed RCTs with large sample sizes are warranted to prove our findings.