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World Journal of Surgical Oncology Aug 2016Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed... (Review)
Review
Gliadel wafer implantation combined with standard radiotherapy and concurrent followed by adjuvant temozolomide for treatment of newly diagnosed high-grade glioma: a systematic literature review.
Since 2003, only two chemotherapeutic agents, evaluated in phase III trials, have been approved by the US Food and Drug Administration for treatment of newly diagnosed high-grade glioma (HGG): Gliadel wafers (intracranially implanted local chemotherapy) and temozolomide (TMZ) (systemic chemotherapy). Neither agent is curative, but each has been shown to improve median overall survival (OS) compared to radiotherapy (RT) alone. To date, no phase III trial has tested these agents when used in sequential combination; however, a number of smaller trials have reported favorable results. We performed a systematic literature review to evaluate the combination of Gliadel wafers with standard RT (60 Gy) plus concurrent and adjuvant TMZ (RT/TMZ) for newly diagnosed HGG. A literature search was conducted for the period of January 1995 to September 2015. Data were extracted and categorized, and means and ranges were determined. A total of 11 publications met criteria, three prospective trials and eight retrospective studies, representing 411 patients who received Gliadel plus standard RT/TMZ. Patients were similar in age, gender, and performance status. The weighted mean of median OS was 18.2 months (ten trials, n = 379, range 12.7 to 21.3 months), and the weighted mean of median progression-free survival was 9.7 months (seven trials, n = 287, range 7 to 12.9 months). The most commonly reported grade 3 and 4 adverse events were myelosuppression (10.22 %), neurologic deficit (7.8 %), and healing abnormalities (4.3 %). Adverse events reflected the distinct independent safety profiles of Gliadel wafers and RT/TMZ, with little evidence of enhanced toxicity from their use in sequential combination. In the 11 identified trials, an increased benefit from sequentially combining Gliadel wafers with RT/TMZ was strongly suggested. Median OS tended to be improved by 3 to 4 months beyond that observed for Gliadel wafers or TMZ when used alone in the respective phase III trials. Larger prospective trials of Gliadel plus RT/TMZ are warranted.
Topics: Antineoplastic Agents, Alkylating; Brain Neoplasms; Carmustine; Chemoradiotherapy; Chemotherapy, Adjuvant; Clinical Trials, Phase III as Topic; Combined Modality Therapy; Dacarbazine; Decanoic Acids; Disease-Free Survival; Drug Implants; Glioblastoma; Humans; Middle Aged; Neoplasm Grading; Polyesters; Temozolomide; United States; United States Food and Drug Administration
PubMed: 27557526
DOI: 10.1186/s12957-016-0975-5 -
Frontiers in Pharmacology 2022To compare the efficacy and safety of advanced intravitreal therapeutic regimens, including a dexamethasone implant at 350 and 700 μg; a fluocinolone acetonide (FA)...
To compare the efficacy and safety of advanced intravitreal therapeutic regimens, including a dexamethasone implant at 350 and 700 μg; a fluocinolone acetonide (FA) implant, 0.2 µg/day, 0.59 and 2.1 mg; intravitreal bevacizumab, 1.25 mg; intravitreal ranibizumab, 0.5 mg; intravitreal triamcinolone acetonide (IVTA), 2 and 4 mg; and standard of care (SOC, systemic therapy) for noninfectious uveitis. We searched the Cochrane Library database, EMBASE, Medline, clinicaltrials.gov until April 2021 with 13 RCTs (1806 participants) identified and conducted a pairwise and Bayesian network meta-analysis with random effects. No specific regimen showed a statistically significant advantage or disadvantage to another treatment regimen with regard to efficacy. However, the FA implant, 0.59 mg was associated with a higher risk of cataract (RR 4.41, 95% CI 1.51-13.13) and raise in intraocular pressure (IOP) (RR 2.53 95% CI 1.14-6.25) compared with SOC at 24 months. IVTA, 4 mg at 6 months was associated with lower risk of IOP rising compared with FA implant, 0.2 µg/day at 36 months (RR 3.43 95% CI 1.12-11.35). No intravitreal therapeutic regimens showed a significant advantage or disadvantage with regard to efficacy. However, SOC was associated with lower risk of side effects compared with FA implants. IVTA, 4 mg, might be the best choice with lowest risk of IOP rising. clinicaltrials.gov, identifier CRD42020172953.
PubMed: 35450045
DOI: 10.3389/fphar.2022.749312 -
Nutrients Jan 2020Several factors affect dental implant osseointegration, including surgical issues, bone quality and quantity, and host-related factors, such as patients' nutritional...
Several factors affect dental implant osseointegration, including surgical issues, bone quality and quantity, and host-related factors, such as patients' nutritional status. Many micronutrients might play a key role in dental implant osseointegration by influencing some alveolar bone parameters, such as healing of the alveolus after tooth extraction. This scoping review aims to summarize the role of dietary supplements in optimizing osseointegration after implant insertion surgery. A technical expert panel (TEP) of 11 medical specialists with expertise in oral surgery, bone metabolism, nutrition, and orthopedic surgery performed the review following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) model. The TEP identified micronutrients from the "European Union (EU) Register of nutrition and health claims made on foods" that have a relationship with bone and tooth health, and planned a PubMed search, selecting micronutrients previously identified as MeSH (Medical Subject Headings) terms and adding to each of them the words "dental implants" and "osseointegration". The TEP identified 19 studies concerning vitamin D, magnesium, resveratrol, vitamin C, a mixture of calcium, magnesium, zinc, and vitamin D, and synthetic bone mineral. However, several micronutrients are non-authorized by the "EU Register on nutrition and health claims" for improving bone and/or tooth health. Our scoping review suggests a limited role of nutraceuticals in promoting osseointegration of dental implants, although, in some cases, such as for vitamin D deficiency, there is a clear link among their deficit, reduced osseointegration, and early implant failure, thus requiring an adequate supplementation.
Topics: Animals; Bone-Anchored Prosthesis; Dental Implantation, Endosseous; Dental Implants; Dietary Supplements; Humans; Nutritional Status; Osseointegration; Prosthesis Design; Treatment Outcome
PubMed: 31968626
DOI: 10.3390/nu12010268 -
Journal of Orthopaedic Translation Mar 2024Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in... (Review)
Review
OBJECTIVE
Fracture-related infection (FRI) remains a major concern in orthopaedic trauma. Functionalizing implants with antibacterial coatings are a promising strategy in mitigating FRI. Numerous implant coatings have been reported but the preventive and therapeutic effects vary. This systematic review aimed to provide a comprehensive overview of current implant coating strategies to prevent and treat FRI in animal fracture and bone defect models.
METHODS
A literature search was performed in three databases: PubMed, Web of Science and Embase, with predetermined keywords and criteria up to 28 February 2023. Preclinical studies on implant coatings in animal fracture or defect models that assessed antibacterial and bone healing effects were included.
RESULTS
A total of 14 studies were included in this systematic review, seven of which used fracture models and seven used defect models. Passive coatings with bacteria adhesion resistance were investigated in two studies. Active coatings with bactericidal effects were investigated in 12 studies, four of which used metal ions including Ag and Cu; five studies used antibiotics including chlorhexidine, tigecycline, vancomycin, and gentamicin sulfate; and the other three studies used natural antibacterial materials including chitosan, antimicrobial peptides, and lysostaphin. Overall, these implant coatings exhibited promising efficacy in antibacterial effects and bone formation.
CONCLUSION
Antibacterial coating strategies reduced bacterial infections in animal models and favored bone healing . Future studies of implant coatings should focus on optimal biocompatibility, antibacterial effects against multi-drug resistant bacteria and polymicrobial infections, and osseointegration and osteogenesis promotion especially in osteoporotic bone by constructing multi-functional coatings for FRI therapy.
THE TRANSLATIONAL POTENTIAL OF THIS PAPER
The clinical treatment of FRI is complex and challenging. This review summarizes novel orthopaedic implant coating strategies applied to FRI in preclinical studies, and offers a perspective on the future development of orthopaedic implant coatings, which can potentially contribute to alternative strategies in clinical practice.
PubMed: 38495742
DOI: 10.1016/j.jot.2023.12.006 -
The Japanese Dental Science Review Nov 2020This review aimed to evaluate the effects of the local delivery of antibiotics incorporated in implant surfaces on some quantitative parameters of bone formation. (Review)
Review
PURPOSE
This review aimed to evaluate the effects of the local delivery of antibiotics incorporated in implant surfaces on some quantitative parameters of bone formation.
MATERIALS AND METHODS
An electronic search was undertaken in three databases (PubMed, Scopus, Embase) in addition to hand searching. The search was limited to animal experiments using endosseous implants combined with localized antibiotics release. Meta-analyses were performed for the percentages of bone volume (BV) and bone-to-implant contact (BIC).
RESULTS
Nine studies met the inclusion criteria. Several methods were identified for local delivery of antibiotics at the bone-implant interface, but the most commonly used method was by coating (incorporating the implant surface with the antibiotic agents). Different antibiotic agents were used, namely bacitracin, doxycycline, enoxacin, gentamicin, minocycline, tobramycin, and vancomycin. There was no statistically significant difference in the percentage of BIC between implants with or without localized antibiotic release ( = 0.59). The meta-analysis revealed higher BV around implants coated with antibiotics compared to control groups (without antibiotics) ( < 0.01).
CONCLUSION
It is suggested that the local administration of antibiotics around implants did not adversely affect the percentage of direct bone contact around implants, with a tendency for a slightly better bone formation around implants when combined with local administration of antibiotics. It is a matter of debate whether these in vivo results will have the same effect in the clinical setting. However, the risk of bias of these studies may, to some extent, question the validity of these results.
PubMed: 33294060
DOI: 10.1016/j.jdsr.2020.09.003 -
BioMed Research International 2021The objective of this systematic review was to evaluate current studies available reporting the antibiotic spacer combined with Ilizarov methods in the treatment of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The objective of this systematic review was to evaluate current studies available reporting the antibiotic spacer combined with Ilizarov methods in the treatment of infected nonunion of tibia and to perform meta-analysis of bone results and infection recurrence to assess the efficacy of an antibiotic spacer combined with Ilizarov methods.
METHODS
The MEDLINE, Embase, Cochrane Library, CNKI, and CBM (Chinese Biological Medicine) databases were searched for articles published between January 2000 and July 2020. Assessment of study quality was performed using a modified version of the Newcastle-Ottawa scale. Effect size and 95% confidence intervals were calculated for the main outcome. Heterogeneity was assessed. Fixed-effect modeling and Stata version 15.1 were used to analyze the data. Sensitivity analyses were conducted with the evidence of heterogeneity.
RESULTS
11 studies involving 210 patients with infected nonunion of tibia were finally included in our meta-analysis. Bone results and infection recurrence were analyzed based on the single-arm meta-analysis. The average of external fixation index (EFI) was 46.88 days/cm in all studies included. The excellent rate in bone results and the rate of infection recurrence was 65% (95% CI: [0.22, 0.97], = 0.0%, = 0.932) and 6.99% (95% CI: [0.052, 0.325], = 0.0%, = 1.000) in patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods.
CONCLUSIONS
Our meta-analysis revealed that the patients with infected nonunion of tibia treated with an antibiotic spacer combined with Ilizarov methods had a high rate of excellent bone results and a low rate of infection recurrence. Therefore, combining the antibiotic spacer with Ilizarov methods may be an applicable choice for repairing and reconstructing infected nonunion of tibia.
Topics: Adult; Anti-Bacterial Agents; Bone Diseases, Infectious; Drug Implants; Female; Fracture Healing; Fractures, Ununited; Humans; Ilizarov Technique; Male; Middle Aged; Recurrence; Tibia; Tibial Fractures; Young Adult
PubMed: 33532493
DOI: 10.1155/2021/6668617 -
Medicine Nov 2017Even if drug-eluting stents (DES) showed beneficial effects in patients with coronary artery diseases (CADs), limitations have been observed with the first-generation... (Comparative Study)
Comparative Study Meta-Analysis Review
Biodegradable polymer drug-eluting stents versus first-generation durable polymer drug-eluting stents: A systematic review and meta-analysis of 12 randomized controlled trials.
BACKGROUND
Even if drug-eluting stents (DES) showed beneficial effects in patients with coronary artery diseases (CADs), limitations have been observed with the first-generation durable polymer DES (DP-DES). Recently, biodegradable polymer DES (BP-DES) have been approved to be used as an alternative to DP-DES, with potential benefits. We aimed to systematically compare BP-DES with the first-generation DP-DES using a large number of randomized patients.
METHODS
Electronic databases were searched for randomized controlled trials (RCTs) comparing BP-DES with first-generation DP-DES. The main endpoints were the long-term (≥2 years) adverse clinical outcomes that were reported with these 2 types of DES. We calculated odds ratios (ORs) with 95% confidence intervals (CIs) and the analysis was carried out by RevMan 5.3 software.
RESULTS
Twelve trials with a total number of 13,480 patients (7730 and 5750 patients were treated by BP-DES and first-generation DP-DES, respectively) were included. During a long-term follow-up period of ≥2 years, mortality, myocardial infarction (MI), target lesion revascularization (TLR), and major adverse cardiac events (MACEs) were not significantly different between these 2 groups with OR: 0.84, 95% CI: 0.66-1.07; P = .16, I = 0%, OR: 1.01, 95% CI: 0.45-2.27; P = .98, I = 0%, OR: 0.91, 95% CI: 0.75-1.11; P = .37, I = 0% and OR: 0.86, 95% CI: 0.44-1.67; P = .65, I = 0%, respectively. Long-term total stent thrombosis (ST), definite ST, and probable ST were also not significantly different between BP-DES and the first-generation DP-DES with OR: 0.77, 95% CI: 0.50-1.18; P = .22, I = 0%, OR: 0.71, 95% CI: 0.43-1.18; P = .19, I = 0% and OR: 1.31, 95% CI: 0.56-3.08; P = .53, I = 6%, respectively.
CONCLUSION
Long-term mortality, MI, TLR, MACEs, and ST were not significantly different between BP-DES and the first-generation DP-DES. However, the follow-up period was restricted to only 3 years in this analysis.
Topics: Absorbable Implants; Coronary Artery Disease; Drug-Eluting Stents; Humans; Polymers; Postoperative Complications; Prosthesis Design; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 29382011
DOI: 10.1097/MD.0000000000008878 -
Clinical Cardiology Dec 2023Because of the advancement of bioabsorbable polymers and thinner struts, bioabsorbable-polymer sirolimus-eluting stents (BP-SES) with ultrathin struts may be related to... (Meta-Analysis)
Meta-Analysis Review
Long-term safety of ultrathin bioabsorbable-polymer sirolimus-eluting stents versus thin durable-polymer drug-eluting stents in acute coronary syndrome: A systematic review and meta-analysis.
BACKGROUND
Because of the advancement of bioabsorbable polymers and thinner struts, bioabsorbable-polymer sirolimus-eluting stents (BP-SES) with ultrathin struts may be related to superior performance when compared to durable-polymer drug-eluting stents (DP-DES) with thin struts. Nonetheless, the long-term safety of ultrathin BP-SES in acute coronary syndrome (ACS) remains unknown.
METHODS
We sought to assess the long-term safety of ultrathin BP-SES in ACS patients, conducting a thorough meta-analysis of all relevant trials drawing a comparison between ultrathin BP-SES and contemporary thin DP-DES. Target lesion failure (TLF), which includes cardiac death (CD), target-vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (CD-TLR) was considered the primary endpoint. Multiple databases comprising Embase, MEDLINE, Cochrane Library, and Pubmed were all thoroughly searched.
RESULTS
There were seven randomized controlled trials included in our study with 7522 randomized patients with ACS (BP-SES = 3888, DP-DES = 3634). TLF occurred in 371 (9.5% in BP-SES) and 393 (10.8% in DP-DES) patients, respectively, across a 40.7-month weighted mean follow-up, with no statistically significant group differences (risk ratio [RR]: 0.87; 95% confidence interval [CI]: 0.73-1.04; p = .12). Furthermore, no significant differences in cardiac death (RR: 0.96; 95% CI: 0.68-1.35; p = .81), TV-MI (RR: 0.63; 95% CI: 0.36-1.10; p = .10) and CD-TLR (RR: 0.77; 95% CI: 0.46-1.29; p = .32) were detected between two groups.
CONCLUSION
During a follow-up of 40.7 months, ultrathin BP-SES and thin DP-DES had a comparable risk of TLF and its individual components (CD, TV-MI, and CD-TLR), indicating that ultrathin BP-SES held at least the same safety and efficiency as thin DP-DES presented in patients with ACS.
Topics: Humans; Sirolimus; Drug-Eluting Stents; Everolimus; Acute Coronary Syndrome; Polymers; Coronary Artery Disease; Absorbable Implants; Treatment Outcome; Myocardial Infarction; Stents; Death; Percutaneous Coronary Intervention; Prosthesis Design; Randomized Controlled Trials as Topic
PubMed: 37661458
DOI: 10.1002/clc.24139 -
International Journal of Oncology Aug 2020Over the past two decades, quantitative proteomics has emerged as an important tool for deciphering the complex molecular events involved in cancers. The number of...
Over the past two decades, quantitative proteomics has emerged as an important tool for deciphering the complex molecular events involved in cancers. The number of references involving studies on the cancer metastatic process has doubled since 2010, while the last 5 years have seen the development of novel technologies combining deep proteome coverage capabilities with quantitative consistency and accuracy. To highlight key findings within this huge amount of information, the present review identified a list of tumor invasive biomarkers based on both the literature and data collected on a biocollection of experimental cell lines, tumor models of increasing invasiveness and tumor samples from patients with colorectal or breast cancer. Crossing these different data sources led to 76 proteins of interest out of 1,245 mentioned in the literature. Information on these proteins can potentially be translated into clinical prospects, since they represent potential targets for the development and evaluation of innovative therapies, alone or in combination. Herein, a systematical review of the biology of each of these proteins, including their specific subcellular/extracellular or multiple localizations is presented. Finally, as an important advantage of quantitative proteomics is the ability to provide data on all these molecules simultaneously in cell pellets, body fluids or paraffin‑embedded sections of tumors/invaded tissues, the significance of some of their interconnections is discussed.
Topics: Animals; Biomarkers, Tumor; Cell Line, Tumor; Disease Models, Animal; Humans; Neoplasm Invasiveness; Neoplasms; Proteomics
PubMed: 32468071
DOI: 10.3892/ijo.2020.5075 -
Open Heart Oct 2020Determine whether an ultrathin biodegradable polymer sirolimus-eluting stent ('Orsiro'-BP-SES) has clinical benefits over second-generation durable polymer drug-eluting... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Determine whether an ultrathin biodegradable polymer sirolimus-eluting stent ('Orsiro'-BP-SES) has clinical benefits over second-generation durable polymer drug-eluting stents (DP-DES).
METHODS
We conducted a prospective systematic review and meta-analysis of randomised clinical trials comparing Orsiro BP-SES against DP-DES (PROSPERO Registration: CRD42019147136). The primary outcome was target lesion failure (TLF): composite of cardiac death, target vessel myocardial infarction (TVMI) and clinically indicated target lesion revascularisation (TLR)) evaluated at the longest available follow-up.
RESULTS
Nine trials randomised 11 302 patients to either Orsiro BP-SES or DP-DES. At mean weighted follow-up of 2.8 years, the primary outcome (TLF) occurred in 501 of 6089 (8.2%) participants with BP-SES compared with 495 of 5213 (9.5%) participants with DP-DES. This equates to an absolute risk reduction of 1.3% in TLF in favour of Orsiro BP-SES (OR 0.82; 95% CI 0.69 to 0.98; p=0.03). This was driven by a reduction in TVMI (OR 0.80; 95% CI 0.65 to 0.98; p=0.03). There were no significant differences in other clinical endpoints: cardiac death, TLR and stent thrombosis.
CONCLUSION
The Orsiro BP-SES shows promising clinical outcomes in patients undergoing percutaneous coronary intervention compared with contemporary second-generation DES at a short to medium term follow-up. More research is warranted to evaluate performance over a longer follow-up period and in different clinical and lesion subsets.
Topics: Absorbable Implants; Aged; Coronary Artery Disease; Drug-Eluting Stents; Female; Humans; Male; Middle Aged; Percutaneous Coronary Intervention; Polymers; Prosthesis Design; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 33046595
DOI: 10.1136/openhrt-2020-001394