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World Journal of Surgical Oncology Mar 2023Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However,... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Transarterial chemoembolization (TACE) with tyrosine kinase inhibitors (TKIs) has been increasingly used to treat unresectable hepatocellular carcinoma (uHCC). However, the superiority of combination therapy to TACE monotherapy remains controversial. Therefore, here we performed a meta-analysis to evaluate the efficacy and safety of TACE plus TKIs in patients with uHCC.
METHODS
We searched four databases for eligible studies. The primary outcome was time to progression (TTP), while the secondary outcomes were overall survival (OS), tumor response rates, and adverse events (AEs). Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were collected for TTP and OS, and the data were analyzed using random-effects meta-analysis models in STATA software. OR and 95% CIs were used to estimate dichotomous variables (complete remission[CR], partial remission[PR], stable disease[SD], progressive disease[PD], objective response rate[ORR], disease control rate[DCR], and AEs) using RStudio's random-effects model. Quality assessments were performed using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane risk of bias tool for randomized controlled trials (RCTs).
RESULTS
The meta-analysis included 30 studies (9 RCTs, 21 observational studies) with 8246 patients. We judged the risk of bias as low in 44.4% (4/9) of the RCTs and high in 55.6% (5/9) of the RCTs. All observational studies were considered of high quality, with a NOS score of at least 6. Compared with TACE alone or TACE plus placebo, TACE combined with TKIs was superior in prolonging TTP (combined HR 0.72, 95% CI 0.65-0.80), OS (combined HR 0.57, 95% CI 0.49-0.67), and objective response rate (OR 2.13, 95% CI 1.23-3.67) in patients with uHCC. However, TACE plus TKIs caused a higher incidence of AEs, especially hand-foot skin reactions (OR 87.17%, 95%CI 42.88-177.23), diarrhea (OR 18.13%, 95%CI 9.32-35.27), and hypertension (OR 12.24%, 95%CI 5.89-25.42).
CONCLUSIONS
Our meta-analysis found that TACE plus TKIs may be beneficial for patients with uHCC in terms of TTP, OS, and tumor response rates. However, combination therapy is also associated with a significantly increased risk of adverse reactions. Therefore, we must evaluate the clinical benefits and risks of combination therapy. Further well-designed RCTs are needed to confirm our findings.
TRIAL REGISTRATION
PROSPERO registration number: CRD42022298003.
Topics: Humans; Carcinoma, Hepatocellular; Liver Neoplasms; Tyrosine Kinase Inhibitors; Chemoembolization, Therapeutic; Combined Modality Therapy; Treatment Outcome
PubMed: 37004052
DOI: 10.1186/s12957-023-02961-7 -
The American Journal of Gastroenterology Sep 2023Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Rapidity of symptom resolution informs treatment choice in patients with moderate-severe ulcerative colitis (UC). We conducted a systematic review and network meta-analysis comparing early symptomatic remission with approved therapies.
METHODS
Through a systematic literature review to December 31, 2022, we identified randomized trials in adult outpatients with moderate-severe UC treated with approved therapies (tumor necrosis factor α antagonists, vedolizumab, ustekinumab, janus kinase inhibitors, or ozanimod), compared with each other or placebo, reporting rates of symptomatic remission (based on partial Mayo score, with resolution of rectal bleeding and near-normalization of stool frequency) at weeks 2, 4, and/or 6. We performed random-effects network meta-analysis using a frequentist approach and estimated relative risk (RR) and 95% confidence interval values.
RESULTS
On network meta-analysis, upadacitinib was more effective than all agents in achieving symptomatic remission at weeks 2 (range of RR, 2.85-6.27), 4 (range of RR, 1.78-2.37), and 6 (range of RR, 1.84-2.79). Tumor necrosis factor α antagonists and filgotinib, but not ustekinumab and vedolizumab, were more effective than ozanimod in achieving symptomatic remission at week 2, but not at weeks 4 and 6. With approximately 10% placebo-treated patients achieving symptomatic remission at 2 weeks, we estimated 68%, 22%, 23.7%, 23.9%, 22.2%, 18.4%, 15.7%, and 10.9% of upadacitinib-, filgotinib-, infliximab-, adalimumab-, golimumab-, ustekinumab-, vedolizumab-, and ozanimod-treated patients would achieve early symptomatic remission, ustekinumab and vedolizumab achieving rapid remission only in biologic-naïve patients.
DISCUSSION
In a systematic review and network meta-analysis, upadacitinib was most effective in achieving early symptomatic remission, whereas ozanimod was relatively slower acting.
Topics: Adult; Humans; Colitis, Ulcerative; Tumor Necrosis Factor-alpha; Network Meta-Analysis; Adalimumab; Ustekinumab; Treatment Outcome
PubMed: 36976548
DOI: 10.14309/ajg.0000000000002263 -
The Neuroradiology Journal Apr 2024Thromboembolism complication is considered the most common complication associated with the treatment of endovascular. This systematic review and meta-analysis aimed to... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND AIMS
Thromboembolism complication is considered the most common complication associated with the treatment of endovascular. This systematic review and meta-analysis aimed to assess the studies investigating the effect of glycoprotein IIb/IIIa inhibitor agents on thromboembolic complications during endovascular aneurysm coiling.
MATERIALS AND METHODS
This systematic review investigated the outcome of the use of three glycoprotein IIb/IIIa inhibitor agents (ie abciximab, tirofiban, and eptifibatide) on the thromboembolic complications during endovascular aneurysm coiling. The electronic databases of PubMed, Web of Science, Scopus, and Medline were searched up to 25 June 2021, using the keywords "Abciximab," "Tirofiban," and "Eptifibatide" incombination with "Thromboembolism Complication," "Aneurysms," and "Endovascular Aneurysm Coiling."
RESULTS
A total of 21 articles were found to be eligible and included in this review. The rates of complete and partial recanalization were estimated to be 56% and 92% in patients who underwent abciximab and tirofiban therapy, respectively. Rupture aneurysms were found in the majority of patients. In general, the mortality rate of the patients treated for thromboembolic complications during endovascular treatment of cerebral aneurysms with glycoprotein IIb/IIIa inhibitors was found to be 4.8% (CI 95%:0.027-0.067; < .005). The average remission rate in studies investigating thromboembolism was 91% (CI 95%:0.88-0.95, I : 65.65/ < .001).
CONCLUSION
Based on the obtained results, a higher mean rate of complete recanalization by eptifibatide was found in studies in which abciximab or tirofiban were used, compared to other mentioned agents. Moreover, the amount of hemorrhage was reported to be less after using tirofiban rather than abciximab.
Topics: Humans; Abciximab; Tirofiban; Platelet Aggregation Inhibitors; Eptifibatide; Intracranial Aneurysm; Aortic Aneurysm, Abdominal; Antibodies, Monoclonal; Tyrosine; Immunoglobulin Fab Fragments; Peptides; Endovascular Procedures; Blood Vessel Prosthesis Implantation; Thromboembolism; Platelet Glycoprotein GPIIb-IIIa Complex
PubMed: 36961079
DOI: 10.1177/19714009231166090 -
Acta Psychiatrica Scandinavica Aug 2023A growing body of evidence suggests that pediatric bipolar disorder (PBD) frequently co-occurs with comorbid psychiatric disorders that may impact functioning. (Review)
Review
BACKGROUND
A growing body of evidence suggests that pediatric bipolar disorder (PBD) frequently co-occurs with comorbid psychiatric disorders that may impact functioning.
OBJECTIVE
To review existing literature on the prevalence of psychiatric comorbidity and general functioning in patients with a primary diagnosis of PBD.
METHODS
We performed a systematic literature search on the PubMed, Embase and PsycInfo databases on November 16th, 2022. We included original papers on patients ≤18 years with primary PBD and any comorbid psychiatric disorder, diagnosed according to a validated diagnostic tool. Risk of bias of the individual studies was assessed using the STROBE checklist. We calculated weighted means to assess the comorbidity prevalence. The review complied with PRISMA statement guidelines.
RESULTS
Twenty studies with a total study population of 2722 patients with PBD were included (mean age = 12.2 years). We found an overall high prevalence of comorbidity in patients with PBD. The most common comorbidities were attention-deficit-hyperactivity disorder (ADHD) (60%) and oppositional defiant disorder (ODD) (47%). Anxiety disorders, obsessive-compulsive disorder, conduct disorder, tic disorders and substance-related disorders affected between 13.2% and 29% of patients, while one in 10 had comorbid mental retardation or autism spectrum disorder (ASD). The prevalence of comorbid disorders was lower in studies that assessed the current prevalence in patients in full or partial remission. General functioning was overall not specifically decreased in patients with comorbidity.
CONCLUSIONS
Comorbidity across a broad range of disorders was high in children diagnosed with PBD, especially regarding ADHD, ASD, behavioral and anxiety disorders including OCD. Future original studies should assess current prevalence of comorbidities in patients with PBD who are in remission to obtain more reliable estimates of psychiatric comorbidity in this patient group. The review highlights the clinical and scientific importance of comorbidity in PBD.
Topics: Humans; Child; Bipolar Disorder; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity; Obsessive-Compulsive Disorder; Comorbidity
PubMed: 36941106
DOI: 10.1111/acps.13548 -
EClinicalMedicine Mar 2023Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but...
BACKGROUND
Onset of effect of advanced therapies is an important parameter due to symptom load and risk of disease complications in moderate-to-severe ulcerative colitis (UC), but comparative data are lacking. Therefore, we aimed to assess the comparative onset of efficacy of biological therapies and small molecules for this patient population.
METHODS
In this systematic review and network meta-analysis, we searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to 24 August 2022, for randomised controlled trials or open-label studies assessing the efficacy of biologics or small molecule drugs within the first six weeks of treatment in adults with UC. The co-primary outcomes were the induction of clinical response and clinical remission at week 2. Network meta-analyses was conducted under the Bayesian framework. This study is registered with PROSPERO: CRD42021250236.
FINDINGS
The systematic literature search identified 20,406 citations, of which 25 studies comprising 11,074 patients fulfilled the eligibility criteria. Upadacitinib ranked highest for induction of clinical response and clinical remission at week 2 and was significantly superior to all agents but tofacitinib, which ranked second highest. Although the rankings remained consistent, no differences between upadacitinib and biological therapies were demonstrated in the sensitivity analyses of partial Mayo clinic score response or resolution of rectal bleeding at week 2. Tumor necrosis factor-α (TNF) inhibitors were significantly superior to vedolizumab and ustekinumab for patient-reported outcome-2 (PRO-2) remission at week 2 in bio-naïve patients. Filgotinib 100 mg, ustekinumab, and ozanimod ranked lowest across all endpoints.
INTERPRETATION
In this network meta-analysis, we found upadacitinib to be significantly superior to all agents but tofacitinib for the induction of clinical response and clinical remission two weeks after treatment initiation. In contrast, ustekinumab and ozanimod ranked lowest. Our findings help to establish the evidence regarding the onset of efficacy of advanced therapies.
FUNDING
None.
PubMed: 36864986
DOI: 10.1016/j.eclinm.2023.101866 -
Medicine Mar 2023Idiopathic membranous nephropathy (IMN) is a noninflammatory autoimmune glomerulonephropathy. Based on the risk stratification for disease progression, conservative... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Idiopathic membranous nephropathy (IMN) is a noninflammatory autoimmune glomerulonephropathy. Based on the risk stratification for disease progression, conservative nonimmunosuppressive and immunosuppressive therapy strategies have been recommended. However, there remains challenges. Therefore, novel approaches to treat IMN are needed. We evaluated the efficacy of Astragalus membranaceus (A membranaceus) combined with supportive care or immunosuppressive therapy in the treatment of moderate-high risk IMN.
METHODS
We comprehensively searched PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Database for Chinese Technical Periodicals, Wanfang Knowledge Service Platform, and SinoMed. We then performed a systematic review and cumulative meta-analysis of all randomized controlled trials assessing the two therapy methods.
RESULTS
The meta-analysis included 50 studies involving 3423 participants. The effect of A membranaceus combined with supportive care or immunosuppressive therapy is better than that of supportive care or immunosuppressive therapy along in regulating for improving 24 hours urinary total protein (MD = -1.05, 95% CI [-1.21, -0.89], P = .000), serum albumin (MD = 3.75, 95% CI [3.01, 4.49], P = .000), serum creatinine (MD = -6.24, 95% CI [-9.85, -2.63], P = .0007), complete remission rate (RR = 1.63, 95% CI [1.46, 1.81], P = .000), partial remission rate (RR = 1.13, 95% CI [1.05, 1.20], P = .0004).
CONCLUSIONS
Adjunctive use of A membranaceus preparations combined with supportive care or immunosuppressive therapy have a promising treatment for improving complete response rate, partial response rate, serum albumin, and reducing proteinuria, serum creatinine levels compared to immunosuppressive therapy in people with MN being at moderate-high risk for disease progression. Given the inherent limitations of the included studies, future well-designed randomized controlled trials are required to confirm and update the findings of this analysis.
Topics: Humans; Astragalus propinquus; Creatinine; Glomerulonephritis, Membranous; Disease Progression; Serum Albumin
PubMed: 36862887
DOI: 10.1097/MD.0000000000032918 -
International Journal of Molecular... Feb 2023Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor...
Patients with IgA nephropathy (IgAN), including Henoch-Schönlein purpura nephritis (HSP), who present with rapidly progressive glomerulonephritis (RPGN) have a poor prognosis despite aggressive immunosuppressive therapy. The utility of plasmapheresis/plasma exchange (PLEX) for IgAN/HSP is not well established. This systematic review aims to assess the efficacy of PLEX for IgAN and HSP patients with RPGN. A literature search was conducted using MEDLINE, EMBASE, and through Cochrane Database from inception through September 2022. Studies that reported outcomes of PLEX in IgAN or HSP patients with RPGN were enrolled. The protocol for this systematic review is registered with PROSPERO (no. CRD42022356411). The researchers systematically reviewed 38 articles (29 case reports and 9 case series articles) with a total of 102 RPGN patients (64 (62.8%) had IgAN and 38 (37.2%) had HSP). The mean age was 25 years and 69% were males. There was no specific PLEX regimen utilized in these studies, but most patients received at least 3 PLEX sessions that were titrated based on the patient's response/kidney recovery. The number of PLEX sessions ranged from 3 to 18, and patients additionally received steroids and immunosuppressive treatment (61.6% of patients received cyclophosphamide). Follow-up time ranged from 1 to 120 months, with the majority being followed for at least 2 months after PLEX. Among IgAN patients treated with PLEX, 42.1% ( = 27/64) achieved remission; 20.3% ( = 13/64) achieved complete remission (CR) and 18.7% ( = 12/64) partial remission (PR). 60.9% ( = 39/64) progressed to end-stage kidney disease (ESKD). Among HSP patients treated with PLEX, 76.3% (n = 29/38) achieved remission; of these, 68.4% ( = 26/38) achieved CR and 7.8% achieved ( = 3/38) PR. 23.6% ( = 9/38) progressed to ESKD. Among kidney transplant patients, 20% (n = 1/5) achieved remission and 80% ( = 4/5) progressed to ESKD. Adjunctive plasmapheresis/plasma exchange with immunosuppressive therapy showed benefits in some HSP patients with RPGN and possible benefits in IgAN patients with RPGN. Future prospective, multi-center, randomized clinical studies are needed to corroborate this systematic review's findings.
Topics: Adult; Female; Humans; Male; Glomerulonephritis, IGA; IgA Vasculitis; Kidney Failure, Chronic; Plasma Exchange
PubMed: 36835388
DOI: 10.3390/ijms24043977 -
The British Journal of Nutrition Oct 2023Corticosteroids (CS) and exclusive and partial enteral nutrition (EEN and PEN) are effective therapies in paediatric Crohn's disease (CD). This systematic review of... (Meta-Analysis)
Meta-Analysis Review
Microbiota signatures and mucosal healing in the use of enteral nutrition therapy . corticosteroids for the treatment of children with Crohn's disease: a systematic review and meta-analysis.
Corticosteroids (CS) and exclusive and partial enteral nutrition (EEN and PEN) are effective therapies in paediatric Crohn's disease (CD). This systematic review of randomised controlled trials (RCT) and cohort studies analyses the impact of EEN/PEN . CS on intestinal microbiota, mucosal healing as well as other clinically important outcomes, including clinical remission, relapse, adherence, adverse events and health-related quality of life (HRQL) in paediatric CD. Three RCT ( 76) and sixteen cohort studies ( 1104) compared EEN . CS. With limited available data (one RCT), the effect on intestinal microbiome indicated a trend towards EEN regarding Shannon diversity. Based on two RCT, EEN achieved higher mucosal healing than CS (risk ratio (RR) 2·36, 95 % CI (1·22, 4·57), low certainty). Compared with CS, patients on EEN were less likely to experience adverse events based on two RCT (RR 0·32, 95 % CI (0·13, 0·80), low certainty). For HRQL, there was a trend in favour of CS based on data from two published abstracts of cohort studies. Based on thirteen cohort studies, EEN achieved higher clinical remission than CS (RR 1·18, 95 % CI (1·02, 1·38), very low certainty). Studies also reported no important differences in relapse and adherence. Compared with CS, EEN may improve mucosal healing with fewer adverse events based on RCT data. While limited data indicate the need for further trials, this is the first systematic review to comprehensively summarise the data on intestinal microbiome, mucosal healing and HRQOL when comparing enteral nutrition and CS in paediatric CD.
Topics: Humans; Child; Crohn Disease; Enteral Nutrition; Remission Induction; Adrenal Cortex Hormones; Gastrointestinal Microbiome; Recurrence
PubMed: 36788671
DOI: 10.1017/S0007114523000405 -
Renal Failure Dec 2023This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis...
PURPOSE
This study aimed to assess efficacy of extracorporeal plasma therapy (EPT), including plasmapheresis (PE), immunoadsorption (IA), low-density lipoprotein apheresis (LDL-A), and lymphocytapheresis (LCAP) for adult native kidney patients with primary focal segmental glomerulosclerosis (FSGS).
METHODS
A literature search was conducted using MEDLINE, EMBASE and Cochrane Databases through August 2022. Studies that reported outcomes of EPT in adult native kidneys with primary FSGS were enrolled.
RESULTS
18 studies with 104 therapy-resistant or refractory primary native FSGS patients were identified. Overall EPT response rate was 56%, with long-term benefit of 46%. Of the 101 non-hemodialysis (HD) patients, 54% achieved remission, with 30% complete remission (CR) and 23% partial remission (PR). Of 31 patients with PE, response rate was 65%; CR and PR rates were 27% and 37% in 30 non-HD patients. Of 61 patients with LDL-A, the response rate was 54%; CR and PR rates were 41% and 3% in 29 non-HD patients. Of 10 patients with IA, response rate was 40%. Of 2 patients with LCAP, 1 achieved CR, and one developed renal failure. All 3 HD patients showed increase in urine output and gradual decrease in urine protein excretion following PE ( = 1) or LDL-A ( = 2). 2 of 3 HD patients ultimately discontinued dialysis.
CONCLUSION
EPT with immunosuppressive therapy showed benefit in some patients with refractory primary FSGS, and PE appeared to have a higher response rate.
Topics: Humans; Adult; Glomerulosclerosis, Focal Segmental; Proteinuria; Treatment Outcome; Kidney Transplantation; Kidney; Recurrence
PubMed: 36762994
DOI: 10.1080/0886022X.2023.2176694 -
Frontiers in Immunology 2023Conventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better...
BACKGROUND
Conventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better outcomes of the disease is dupilumab.
OBJECTIVE
The objective of this study was to systematically review dupilumab-related treatment outcomes in prurigo nodularis.
METHODS
Several databases like Embase, PubMed, Web of Science, and Cochrane library were searched for data acquisition on October 8, 2022. Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, 24 publications were included in this study.
RESULTS
After 4,12,16 and more than 16 weeks of dupilumab treatment, 8.3% (n=5/60), 34.4% (n=11/32), 3.6% (n=2/56), and 45.3% (n=29/64) of patients had complete remission, respectively. In addition, 85.0% (n=51/60), 59.4% (n=19/32), 83.9% (n=47/56), and 43.8% (n=28/64) had partial remission, respectively. Moreover, 6.7% (n=4/60), 6.3% (n=2/32), 12.5% (n=7/56), and 10.9% (n=7/64) showed no remission, respectively, and significant reduction of numeric rating scale itch intensity (from 9.0 to 4.9, 2.1, 2.8, 0.9) was attained. There were no serious adverse events observed during treatment, but the most common event observed was conjunctivitis (12.6%, n=15/119).
CONCLUSIONS
Dupilumab has definite effectiveness and safety in prurigo nodularis treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier (CRD42022365802).
Topics: Humans; Prurigo; Pruritus; Antibodies, Monoclonal, Humanized; Treatment Outcome
PubMed: 36742321
DOI: 10.3389/fimmu.2023.1092685