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International Ophthalmology Oct 2020Trabeculectomy is the most commonly performed surgery for the definitive treatment of glaucoma. Despite its high resolvability, the postoperative period requires high... (Review)
Review
INTRODUCTION
Trabeculectomy is the most commonly performed surgery for the definitive treatment of glaucoma. Despite its high resolvability, the postoperative period requires high caution so that excessive filtration or scarring does not occur. This paper aimed to research alternative options to those most used as healing modulators, mitomycin C (MMC) and 5-fluorouracil, commonly associated with complications.
METHODS
This systematic review used the PubMed and SciELO databases, covering publications from 1972 to 2019.
RESULTS
A total of 31 substances and methods were analyzed.
CONCLUSION
Some, such as anti-VEGF, glucocorticoids and betatherapy, did not show results statistically superior to those of MMC. Others, such as the enzyme α5β1-integrin and Ologen, demonstrated efficacy and safety at least similar to that of this drug. In conclusion, further research is still needed for drugs that lead to the same results as mitomycin, but with fewer side effects. More recent studies have focused on technologies that increase communication between target tissues and antifibrotic molecules at the cellular level, being a promising bet for the future.
Topics: Cicatrix; Glaucoma; Humans; Intraocular Pressure; Mitomycin; Trabeculectomy; Wound Healing
PubMed: 32504309
DOI: 10.1007/s10792-020-01454-w -
The Australasian Journal of Dermatology Nov 2021Sirolimus is a mammalian target of rapamycin inhibitor (mTORI) with anti-proliferative, antiangiogenic and immunosuppressive properties. While approved in Australia as...
Sirolimus is a mammalian target of rapamycin inhibitor (mTORI) with anti-proliferative, antiangiogenic and immunosuppressive properties. While approved in Australia as an anti-rejection medication for renal transplant patients, there is mounting evidence regarding the utility of oral and topical sirolimus in treating a plethora of dermatological conditions or conditions with cutaneous manifestations. Our aim was to present an overview of the evidence for current usage and breadth of the application of sirolimus in dermatology. We carried out a systematic review of all the literature published up to 31 August 2019 on oral and topical sirolimus with respect to dermatological conditions or conditions otherwise relevant to dermatology. While 3368 papers were initially produced in our search, 238 papers met our inclusion criteria and were examined in our review. The conditions examined were categorised into genodermatoses (9 conditions), infection (1 condition), inflammatory/autoimmune (10 conditions), neoplasm (3 conditions) and vascular (17 conditions). We extracted data on first author, publication year, journal, characteristics of the study and study patients, condition, drug modalities, drug efficacy, side effects, blood level of mTORI, co-interventions and follow-up. While there is level 1 evidence for the efficacy of sirolimus in conditions such as tuberous sclerosis complex (TSC) and GVHD prophylaxis, for many other conditions, the evidence is limited to level 4 evidence. Regarding oral systemic therapy, dosing regimens varied with the most common for children 0.8mg/m twice daily and for adults 1 mg twice daily. Doses were often adjusted to reach a typical trough level of between 5 and 15 ng/mL, though targets often varied. In the overall majority of cases, side effects were minimal or tolerable, including mucositis, cytopenias, lipid abnormalities and nausea/vomiting, and only a few cases had to stop due to adverse effects. Regarding topical therapy, concentration of formulations varied from 0.1% to 1% and were compounded into creams, ointments or gels and administered typically once or twice per day. The most common side effect was skin irritation. There were a number of limitations to our study. In particular, many of the published studies were case reports or case series with no comparator arm, leading to susceptibility of bias in conclusions drawn, in particular a high likelihood of publication bias. Given the heterogeneity amongst studies, comparisons or aggregation of results was difficult. There continues to be growing use of oral and topical sirolimus in dermatological conditions. It provides new therapeutic options to patients where previous therapies have either failed or are limited due to toxicity. However, further studies are warranted.
Topics: Humans; Immunosuppressive Agents; Sirolimus; Skin Diseases
PubMed: 34328215
DOI: 10.1111/ajd.13671 -
European Archives of... Aug 2023This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on... (Review)
Review
PURPOSE
This PRISMA-compliant systematic review aimed to assess risks and benefits of sirolimus treatment for paediatric lymphatic malformations by focusing not only on treatment efficacy but also on possible treatment-related adverse events, and treatment combinations with other techniques.
METHODS
Search criteria were applied to MEDLINE, Embase, Web of Science, Scopus, Cochrane Library, and ClinicalTrials.gov databases and included all studies published up to March 2022 reporting paediatric lymphatic malformations treated with sirolimus. We selected all original studies that included treatment outcomes. After the removal of duplicates, selection of abstracts and full-text articles, and quality assessment, we reviewed eligible articles for patient demographics, lymphatic malformation type, size or stage, site, clinical response rates, sirolimus administration route and dose, related adverse events, follow-up time, and concurrent treatments.
RESULTS
Among 153 unique citations, 19 studies were considered eligible, with reported treatment data for 97 paediatric patients. Most studies (n = 9) were case reports. Clinical response was described for 89 patients, in whom 94 mild-to-moderate adverse events were reported. The most frequently administered treatment regimen was oral sirolimus 0.8 mg/m twice a day, with the aim of achieving a blood concentration of 10-15 ng/mL.
CONCLUSION
Despite promising results for sirolimus treatment in lymphatic malformation, the efficacy and safety profile of remains unclear due to the lack of high-quality studies. Systematic reporting of known side effects, especially in younger children, should assist clinicians in minimising treatment-associated risks. At the same time, we advocate for prospective multicentre studies with minimum reporting standards to facilitate improved candidate selection.
Topics: Humans; Child; Sirolimus; Prospective Studies; Treatment Outcome; Neck; Head; Lymphatic Abnormalities; Vascular Malformations
PubMed: 37115326
DOI: 10.1007/s00405-023-07991-1 -
Journal of Vascular Surgery. Venous and... Jan 2023Sclerotherapy for venous malformation has been widely used; however, no guidelines are available to assess the effectiveness of different sclerotherapy agents. We... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Sclerotherapy for venous malformation has been widely used; however, no guidelines are available to assess the effectiveness of different sclerotherapy agents. We conducted a systematic review and network meta-analysis to investigate the effectiveness of sclerotherapy agents for venous malformations.
METHODS
Three electronic databases were searched from their inception (1950) to April 29, 2021. Studies comparing the effectiveness of different sclerotherapy agents were included. The risk of bias within and across studies was assessed. Pairwise meta-analyses were conducted, followed by a network meta-analysis. We also assessed inconsistency and publishing bias using various approaches.
RESULTS
Seven studies with 547 patients in six arms were included in the present study. We defined the response and complete response as two separate outcomes. Significant differences were observed in four comparisons with respect to the response (ethanol vs bleomycin, ethanol vs polidocanol, ethanol vs sodium tetradecyl sulfate, polidocanol vs sodium tetradecyl sulfate). No statistically significant differences were found in the other comparisons. The evidence network revealed that for the response outcome, ethanol ranked first, followed by pingyangmycin, polidocanol, sodium morrhuate, bleomycin, and, finally, sodium tetradecyl sulfate. For the complete response outcome, pingyangmycin had the best results, followed by sodium morrhuate, polidocanol, ethanol, bleomycin, and, finally, sodium tetradecyl sulfate. Major complications, such as facial nerve palsy, serious local swelling, and necrosis, had occurred mostly in the ethanol group and rarely in the other groups. Because of the limited data, no further analysis of major complications was conducted. Our confidence in the comparisons and rankings was low. We found no verified inconsistency or publishing bias in the present study using the existing approaches.
CONCLUSIONS
Ethanol showed a significantly better response statistically compared with the other agents. However, ethanol had also resulted in the highest incidence of complications. Pingyangmycin showed the second-best response, best complete response, and a low rate of complications, respectively. Overall, pingyangmycin achieved excellent performance and balance in terms of the different outcomes. However, they could not be adequately recommended from the available data. More superior trials, especially randomized controlled trials, are needed in the future.
Topics: Humans; Sclerotherapy; Polidocanol; Sclerosing Solutions; Sodium Tetradecyl Sulfate; Sodium Morrhuate; Network Meta-Analysis; Treatment Outcome; Vascular Malformations; Bleomycin; Ethanol
PubMed: 36179784
DOI: 10.1016/j.jvsv.2022.08.004 -
The Canadian Journal of Neurological... May 2021Venolymphatic malformations are rare benign vascular lesions of the head and neck. Sclerotherapy has become the first-line therapy of these lesions with bleomycin being...
BACKGROUND
Venolymphatic malformations are rare benign vascular lesions of the head and neck. Sclerotherapy has become the first-line therapy of these lesions with bleomycin being a sclerosing agent commonly used.
PURPOSE
To perform a systematic review of the published literature to synthesize evidence on the safety and efficacy of bleomycin for the treatment of head and neck venolymphatic malformations.
DATA SOURCES
A systematic review of the literature (January 1995-May 2019) was performed in PubMed, Embase, and Cochrane Library databases to identify studies on sclerotherapy of venolymphatic malformations of the head and neck.
STUDY SELECTION
A total of 32 studies with participants met the inclusion criteria among which 1121 patients were included in the systematic review.
DATA ANALYSIS
Two reviewers independently screened and extracted data and assessed the risk of bias. The primary outcome was the subjective or objective reduction of lesion size as well as minor and major complications.
DATA SYNTHESIS
The bleomycin/pingyangmycin sclerotherapy achieved subjective or objective lesion size reduction in 96.3% (95% CI 94.1%-98.5%) of patients. Minor complications were observed in 16.2% and major complications in 1.1%.
CONCLUSION
Bleomycin is a highly effective treatment of venolymphatic malformations of the head and neck with a low rate of major adverse events. This study represents an update on the "available" evidence, but only low-to-moderate quality studies were available.
LIMITATIONS
This study reviewed 32 studies performed in different parts of the world, but there was heterogeneity of the study designs and interventions.
Topics: Bleomycin; Head; Humans; Neck; Sclerosing Solutions; Sclerotherapy; Treatment Outcome
PubMed: 32799947
DOI: 10.1017/cjn.2020.178 -
Renal Failure 2023This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF)... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study was to assess the safety and effectiveness of immunosuppressive agents, specifically Voclosporin, when used in conjunction with mycophenolate mofetil (MMF) induction therapy for the management of lupus nephritis (LN).
METHODS
A systematic review and network meta-analysis (NMA) was conducted on randomized controlled trials investigating the efficacy of immunosuppressant-induced therapy for LN. The random effects model was used in the analysis. I was used to evaluate the heterogeneity of the model. Odds ratios (OR) and 95% credible intervals (CrI) were computed to assess and compare the relative effectiveness and safety of various treatment protocols.
RESULTS
The study included a total of 16 randomized controlled trials (RCTs) involving 2444 patients with LN. The analysis results indicated that there was no significant difference in terms of partial remission (PR) between the drugs. However, when considering complete remission (CR), the combination of Voclosporin with MMF showed the highest remission rate, followed by Tacrolimus (TAC). Unfortunately, Voclosporin in combination with MMF had the highest risk of infection and serious infection, indicating a lower safety profile.
CONCLUSIONS
Voclosporin in combination with MMF demonstrated the highest efficacy as an induction therapy for LN. However, it should be noted that the risk of infection and serious infection was found to be high with this regimen. On the other hand, TAC not only showed efficacy but also had a lower risk of infection and serious infection, making it a favorable option in terms of safety. This study did' not include results on other adverse events.
Topics: Humans; Lupus Nephritis; Cyclophosphamide; Induction Chemotherapy; Network Meta-Analysis; Treatment Outcome; Immunosuppressive Agents; Tacrolimus; Mycophenolic Acid; Remission Induction; Randomized Controlled Trials as Topic
PubMed: 38087473
DOI: 10.1080/0886022X.2023.2290365 -
Neoadjuvant therapy in triple-negative breast cancer: A systematic review and network meta-analysis.Breast (Edinburgh, Scotland) Dec 2022Evidence for the preferred neoadjuvant therapy regimen in triple-negative breast cancer (TNBC) is not yet established. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence for the preferred neoadjuvant therapy regimen in triple-negative breast cancer (TNBC) is not yet established.
METHODS
Literature search was conducted from inception to February 12, 2022. Phase 2 and 3 randomized controlled trials (RCTs) investigating neoadjuvant therapy for TNBC were eligible. The primary outcome was pathologic complete response (pCR); the secondary outcomes were all-cause treatment discontinuation, disease-free survival or event-free survival (DFS/EFS), and overall survival. Odd ratios (OR) with 95% credible intervals (CrI) were used to estimate binary outcomes; hazard ratios (HR) with 95% CrI were used to estimate time-to-event outcomes. Bayesian network meta-analysis was implemented for each endpoint. Sensitivity analysis and network meta-regression were done.
RESULTS
41 RCTs (N = 7109 TNBC patients) were eligible. Compared with anthracycline- and taxane-based chemotherapy (ChT), PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with a significant increased pCR rate (OR 3.95; 95% CrI 1.81-9.44) and a higher risk of premature treatment discontinuation (3.25; 1.26-8.29). Compared with dose-dense anthracycline- and taxane-based ChT, the combined treatment was not associated with significantly improved pCR (OR 2.57; 95% CrI 0.69-9.92). In terms of time-to-event outcomes, PD-1 inhibitor plus platinum plus anthracycline- and taxane-based ChT was associated with significantly improved DFS/EFS (HR 0.42; 95% CrI 0.19-0.81).
CONCLUSIONS
PD-1 inhibitor plus platinum and anthracycline- and taxane-based ChT was currently the most efficacious regimen for pCR and DFS/EFS improvement in TNBC. The choice of chemotherapy backbone, optimization of patient selection with close follow-up and proactive symptomatic managements are essential to the antitumor activity of PD-1 inhibitor.
Topics: Female; Humans; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Immune Checkpoint Inhibitors; Neoadjuvant Therapy; Network Meta-Analysis; Platinum; Taxoids; Triple Negative Breast Neoplasms
PubMed: 36265208
DOI: 10.1016/j.breast.2022.08.006 -
Arquivos Brasileiros de Cardiologia 2023The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial.
OBJECTIVE
We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity.
METHODS
The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted.
RESULTS
The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study.
CONCLUSION
The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615).
Topics: Adult; Humans; Renin-Angiotensin System; Stroke Volume; Cardiotoxicity; Ventricular Function, Left; Anthracyclines; Prospective Studies; Adrenergic beta-Antagonists; Antibiotics, Antineoplastic; Heart Failure
PubMed: 37255127
DOI: 10.36660/abc.20220298 -
Pharmacotherapy Jun 2023Cytomegalovirus (CMV) and BK polyomavirus (BKPyV) infections after kidney transplant have become increasingly prevalent. Based on previous studies, the mammalian target... (Meta-Analysis)
Meta-Analysis Review
Cytomegalovirus (CMV) and BK polyomavirus (BKPyV) infections after kidney transplant have become increasingly prevalent. Based on previous studies, the mammalian target of rapamycin (mTOR) inhibitors seem like attractive alternatives with antiviral activity. The objective of this systematic review and meta-analysis was to investigate the incidence of CMV and BKPyV infections in kidney transplantation recipients receiving mTOR inhibitors. This meta-analysis included three comparisons of immunosuppressant regimens commonly used after kidney transplantation: Comparison 1: mTOR inhibitors versus calcineurin inhibitors (CNI); Comparison 2: mTOR inhibitors versus antimetabolites (AM); and Comparison 3: mTOR inhibitors plus a reduced-dose of CNI versus AM plus a standard-dose of CNI. The group containing mTOR inhibitors was the study group and the remaining one was the control group. The incidence of CMV or BKPyV infection defined by positive culture, serology, or polymerase chain reaction testing was the primary outcome. A total of 61 studies involving 13,609 patients were included. As compared with the control group, a significantly decreased risk of CMV and BKPyV infections favoring the mTOR inhibitors-based group was shown in comparisons 1, 2, and 3 (p < 0.05). Compared with the control group in all three comparisons, mTOR inhibitors made no difference in regard to death and graft loss (p > 0.05). Compared with CNI, the incidence of biopsy-proven acute rejection (BPAR) and anemia was higher with mTOR inhibitors (p < 0.05). In comparisons 2 and 3, the risk of new-onset diabetes mellitus (NODM) was higher with mTOR inhibitors (p < 0.05). Early introduction of mTOR inhibitors reduced more CMV infections in comparisons 1 and 2 (p < 0.05). The mTOR inhibitor-based regimen is an attractive alternative with lower risk of CMV and BKPyV infections in kidney transplant recipients. The combination regimen is more appropriate and acceptable than the mTOR-inhibitor monotherapy-based regimen. Early introduction of mTOR inhibitors is recommended, although it is worth noting that attention should be paid to wound healing when mTOR inhibitors are introduced early.
Topics: Humans; Calcineurin Inhibitors; Cytomegalovirus; Cytomegalovirus Infections; Incidence; Kidney Transplantation; MTOR Inhibitors; Polyomavirus Infections; Sirolimus; TOR Serine-Threonine Kinases
PubMed: 37002621
DOI: 10.1002/phar.2799 -
Clinical Rheumatology Feb 2024Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Immune thrombocytopenic purpura (ITP) is a challenging disease in its presentation and management as it may cause life-threatening hemorrhaging in vital organs and may resist several lines of treatment. This systematic review and meta-analysis aimed to evaluate the safety and efficacy of mycophenolate mofetil (MMF) in treating patients with ITP.
METHODS
We systematically searched four electronic databases (PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials) from inception until 10 October 2022. We included all clinical trials, either controlled or single arm, and prospective and retrospective observational studies that evaluate the efficacy and safety of MMF in patients with ITP. We assessed the risk of bias using three tools (ROBINS-I, Cochrane ROB-2, and NIH), each for eligible study design.
RESULTS
Nine studies were included in this meta-analysis, with a total of 411 patients with ITP. We found that MMF demonstrated an overall response rate of (62.09%; 95% CI = [43.29 to 77.84]) and the complete response rate was (46.75%; 95% CI = [24.84 to 69.99]). The overall proportion of adverse events was (12%; 95% CI = [6 to 24]). After the sensitivity analysis, the overall response rate became 50%; 95% CI = [38 to 63]) and the complete response rate became (32%; 95% CI = [24 to 42]). However, MMF did not appear to affect white blood cell counts or hemoglobin levels significantly.
CONCLUSION
This systematic review and meta-analysis demonstrate that MMF appears to be an effective and relatively safe treatment option for patients with ITP when combined with steroids and even in those who have not responded to standard therapies (steroid-resistant cases). Further research with well-designed studies is warranted to better understand the factors influencing treatment response and to refine the use of MMF in the management of ITP. An interactive version of our analysis can be accessed from here: https://databoard.shinyapps.io/mycophenolate_meta/.
Topics: Humans; Mycophenolic Acid; Purpura, Thrombocytopenic, Idiopathic; Retrospective Studies; Prospective Studies; Steroids; Immunosuppressive Agents
PubMed: 37981614
DOI: 10.1007/s10067-023-06820-4