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Orthopaedics & Traumatology, Surgery &... Apr 2024Recent studies have shown a growing concern regarding the cost-effectiveness and the lack of supporting data for the biologic agents that are being increasingly used in... (Review)
Review
INTRODUCTION
Recent studies have shown a growing concern regarding the cost-effectiveness and the lack of supporting data for the biologic agents that are being increasingly used in the orthopedic field. Our aim was to conduct a systematic scoping review of recent publications (last five years) on the use of orthobiologics to treat fracture non-union and summarize the latest available data.
PATIENTS AND METHODS
The inclusion criteria for this review were articles published in English, from 2016 to 2022, and focusing on the use of orthobiologics for the surgical treatment of non-union. Searches were conducted in March 2023 using Pubmed/MEDLINE and Embase. Studies on spinal fusion or gene therapy were excluded. Reviews, case reports with five cases or less, conference proceedings, preliminary reports, pediatric or non-human studies were excluded as well.
RESULTS
The search found 1807 articles, 15 were eligible after PRISMA checklist and exclusions. The evidence was heterogenous and there was only one level II RCT. Recent data suggests that bone morphogenic protein (BMP-2) products could be effective for septic and aseptic tibial non-unions. However, the evidence was not conclusive regarding BMP-7, plasma rich platelets (PRP), stem cells or demineralized bone matrix (DBM).
DISCUSSION
Every non-union case is different in terms of bone defect, biology, mechanical stability, surgical technique and host factors, which contributes to the conflicting reports on the efficacy of orthobiologics in the literature. We might never see a level 1, high powered and robust study defining the efficacy, safety profile and cost-effectiveness of such products.
LEVEL OF EVIDENCE
IV.
PubMed: 38663743
DOI: 10.1016/j.otsr.2024.103896 -
Journal of Cellular and Molecular... Apr 2024Interleukin-6 (IL-6), a pivotal pro-inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL-6 levels are largely... (Meta-Analysis)
Meta-Analysis
Interleukin-6 (IL-6), a pivotal pro-inflammatory cytokine, is closely linked to vascular wall thickening and atherosclerotic lesion. Since serum IL-6 levels are largely determined by the genetic variant in IL-6, this study was conducted to investigate whether the IL-6 variant impacts cardiometabolic profile and the risk of premature coronary artery disease (PCAD). PubMed, Cochrane Library, Central, Cumulative Index to Nursing and Allied Health Literature (CINAHL), and ClinicalTrials.gov were searched from May 13, 2022 to June 28, 2023. In total, 40 studies (26,543 individuals) were included for the analysis. The rs1800795 (a function variant in the IL-6 gene) C allele was linked to higher levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), fasting plasma glucose (FPG), body mass index (BMI), and waist circumference (WC), and a lower levels of high-density lipoprotein cholesterol (HDL-C). However, no significant association was observed of rs1800795 with triglycerides (TG), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Interestingly, a significant association was detected between rs1800795 and PCAD. Subgroup analyses indicted that the impacts of rs1800795 on cardiometabolic risk factors were significant in Caucasians but stronger in obese patients. In contrast, the impact of rs1800795 on PCAD was significant in brown race population. In summary, rs1800795 had a slight but significant impact on cardiometabolic risk factors and PCAD. IL-6 inhibition with ziltivekimab or canakinumab may benefit high-risk populations (e.g. brown race population, Caucasians, obese patients, etc.) with rs1800795 to prevent PCAD.
Topics: Humans; Cardiovascular Diseases; Cholesterol, HDL; Coronary Artery Disease; Cytokines; Interleukin-6; Obesity; Risk Factors; Triglycerides
PubMed: 38634217
DOI: 10.1111/jcmm.18311 -
CytoJournal 2024Multiple myeloma (MM) is a bone marrow cancer that profoundly affects plasma cells involved in the immune response. Myeloma cells alter the average production of cells...
OBJECTIVE
Multiple myeloma (MM) is a bone marrow cancer that profoundly affects plasma cells involved in the immune response. Myeloma cells alter the average production of cells in the bone marrow. Anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy allows genetic modifications of an individual's T-cells to increase the expression of CARs used to identify and attach BCMA proteins to the malignant cells. Our main objective is to perform a systematic review and meta-analysis to explore the efficacy and safety of anti-BCMA CAR T-cell therapy for MM.
MATERIAL AND METHODS
We searched five databases, PubMed, CNKI, EMBASE, Cochrane, Web of Science, and CNKI, for studies published on anti-BCMA,CAR-T-cell treatment for MM. Inclusion criteria involved prospective single-arm studies either single or multi-center, in various MM phases and studies that reported anti-BCMA,CAR-T-cell treatment for MM. We excluded non-English publications and conference papers. All statistical analyses were performed in R software and Review Manager 5.4.1.
RESULTS
Thirteen articles were included in the analysis. We found that the overall response survival complete response increase was statistically significant. Similarly, the reduction in cytokine release syndrome grades 3 and 4 and neurotoxicity after follow-up was statistically significant. However, the reduction in minimal residual disease negativity (MRDN) was not statistically significant.
CONCLUSION
Using anti-BCMA CAR T-cell therapy in MM was highly efficacious and safe in lowering the adverse outcomes and improving the survival outcomes, complete response, and overall response.
PubMed: 38628287
DOI: 10.25259/Cytojournal_64_2023 -
Reproductive Biology and Endocrinology... Apr 2024Intra-uterine infusion treatments were reported to be beneficial to embryo implantation and pregnancy outcomes, and considered as potential therapies for infertile... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Intra-uterine infusion treatments were reported to be beneficial to embryo implantation and pregnancy outcomes, and considered as potential therapies for infertile patients with recurrent implantation failure (RIF). Nevertheless, their efficiencies were controversial and there lack of consensus on which intrauterine treatment is the most effective.
METHODS
All prospective trials (in Chinese or English) were searched in Databases PubMed, Cochrane, Web of Science, and CNKI from July 2013 to July 2023. We included studies that investigated various uterine infusions, including chorionic gonadotropin, granulocyte colony-stimulating factor, monocytes, platelet-rich plasma, etc. during IVF treatment and reported subsequent pregnancy outcomes.
RESULTS
We finally included 56 researches, including 40 randomized controlled trials, 14 non-randomized controlled trials, and 3 prospective cohort studies. This study included a total of 11 uterine perfusion methods: Placebo, Human Chorionic Gonadotropin (HCG), Granulocyte Colony-Stimulating Factor (G-CSF), platelet-rich plasma (PRP), Peripheral Blood Mononuclear Cell (PBMC), Growth hormone (GH), dexamethasone (DEX), Embryo culture supernatant (ESC), PRP combined with G-CSF (PRP + G-CSF), RPR combined with subcutaneous injection of G-CSF (RPR + G-CSFsc), G-CSF combined with subcutaneous injection of AXaIU (G-CSF + AXaIUsc). Intrauterine infusion of HCG, PBMC, G-CSF, and PRP significantly improves pregnancy outcomes in patients with repeated implantation failure compared with blank controls or placebo, and PRP improved the clinical pregnancy and live birth most. GH and ESC infusion might improve the pregnancy outcomes, but uterine infusion of DEX was shown with high miscarriage. The combination therapy did not show a significant advantage over the mono-therapy.
CONCLUSIONS
Intrauterine infusion of HCG, PBMC, G-CSF, and PRP are promising strategies for improving pregnancy outcomes for infertile patients with recurrent implantation failure. Among these treatments, PRP may be the best. More researches are required to explore the effect of drug combinations and less commonly used drugs as well.
TRIAL REGISTRATION
Our study was registered in PROSPERO and the ID was CRD42023467188.
Topics: Pregnancy; Female; Humans; Prospective Studies; Leukocytes, Mononuclear; Network Meta-Analysis; Embryo Implantation; Chorionic Gonadotropin; Infertility, Female; Granulocyte Colony-Stimulating Factor; Pregnancy Rate
PubMed: 38627790
DOI: 10.1186/s12958-024-01221-x -
Bone Reports Jun 2024Fracture healing poses a significant challenge in orthopedics. Successful regeneration of bone is provided by mechanical stability and a favorable biological... (Review)
Review
BACKGROUND
Fracture healing poses a significant challenge in orthopedics. Successful regeneration of bone is provided by mechanical stability and a favorable biological microenvironment. This systematic review aims to explore the clinical application of orthobiologics in treating aseptic delayed union and non-union of long bones in adults.
METHODS
A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Three databases were explored, with no date restrictions, using keywords related to orthobiologics and delayed union and non-union. Eligible studies included human clinical studies in English, with available full texts, examining orthobiologics such as platelet-rich plasma (PRP), mesenchymal stem cells (MSCs), and bone morphogenetic protein (BMPs) for treating aseptic delayed unions and non-unions in adults. Animal studies, in vitro research, and studies on non-unions due to congenital defects, tumors or infections were excluded.
RESULTS
The initial search identified 9417 studies, with 20 ultimately included in the review. These studies involved 493 patients affected by non-union and 256 patients affected by delayed union, with an average age respectively of 40.62 years and 41.7 years. The mean follow-up period was 15.55 months for non-unions and 8.07 months for delayed unions. PRP was the most used orthobiologic, and outcomes were evaluated through time to union, functional scores, and clinical examinations. The results indicated that orthobiologics, especially PRP, tended to yield better outcomes compared to surgical procedures without biological factors.
CONCLUSION
This systematic review suggests that orthobiologics, such as PRP, BMPs, and MSCs, can be effective and safe in the management of delayed union and non-union fractures. These biological treatments have the potential to improve union rates, reduce healing times, and enhance functional outcomes in patients with non-union fractures. Further research is essential to refine treatment protocols and determine the most suitable orthobiologic for specific patient populations and fracture types.
PubMed: 38618008
DOI: 10.1016/j.bonr.2024.101760 -
Hypertension Research : Official... Jun 2024Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos....
Extracellular vesicles (EVs) are released from all cell types studied to date and act as intercellular communicators containing proteins, nucleic acids and lipid cargos. They have been shown to be involved in maintaining homoeostasis as well as playing a role in the development of pathology including hypertension and cardiovascular disease. It is estimated that there is 10-10 circulating EVs/mL in the plasma of healthy individuals derived from various sources. While the effect of EVs on vascular haemodynamic parameters will be dependent on the details of the model studied, we systematically searched and summarized current literature to find patterns in how exogenously injected EVs affected vascular haemodynamics. Under homoeostatic conditions, evidence from wire and pressure myography data demonstrate that injecting isolated EVs derived from cell types found in blood and blood vessels resulted in the impairment of vasodilation in blood vessels ex vivo. Impaired vasodilation was also observed in rodents receiving intravenous injections of human plasma EVs from cardiovascular diseases including valvular heart disease, acute coronary syndrome, myocardial infarction and end stage renal disease. When EVs were derived from models of metabolic syndromes, such as diabetes, these EVs enhanced vasoconstriction responses in blood vessels ex vivo. There were fewer publications that assessed the effect of EVs in anaesthetised or conscious animals to confirm whether effects on the vasculature observed in ex vivo studies translated into alterations in vascular haemodynamics in vivo. In the available conscious animal studies, the in vivo data did not always align with the ex vivo data. This highlights the importance of in vivo work to determine the effects of EVs on the integrative vascular haemodynamics.
Topics: Animals; Humans; Cardiovascular Diseases; Extracellular Vesicles; Hemodynamics
PubMed: 38600279
DOI: 10.1038/s41440-024-01659-x -
Arthroscopy : the Journal of... Apr 2024We conducted our network meta-analysis to compare the efficacy of the steroid injections to other injectable therapies in partial-thickness rotator cuff tears (PTRCTs).
Hyaluronate acid plus platelet-rich plasma is superior to steroids for pain relief less than 6 months using injection therapy of partial rotator cuff tears: A systematic review and network meta-analysis.
PURPOSE
We conducted our network meta-analysis to compare the efficacy of the steroid injections to other injectable therapies in partial-thickness rotator cuff tears (PTRCTs).
METHODS
A systematic literature search was performed until October 25, 2021 in three databases (CENTRAL, Embase, MEDLINE). Eligible studies compared the efficacy of steroid, hyaluronic acid (HA), platelet-rich plasma (PRP), the combination of HA and PRP (HA+PRP), and adipose-derived regenerative cells (ADRC) in RC tears. The primary outcomes were the Visual Analogue Scale (VAS), Constant Murley Score (CMS), and American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form. Using paired and network meta-analysis, we calculated pooled mean differences (MDs) with 95% confidence intervals (CIs).
RESULTS
We included a total of seven articles in the quantitative synthesis. In shorter periods, the HA+PRP combination was superior to the other substances we investigated (HA+PRP: VAS (0-4 weeks): MD: -0.99 [CI = -1.62, -0.36]; CMS (0-3 months): 20.56 [CI = 16.18, 24.94]. This combination was followed by the use of HA or PRP alone, depending on the duration of follow-up and the outcome being studied. In our study, short-term results suggest that saline is superior to steroids for partial tears, but this trend is reversed at six-month follow-up.
CONCLUSION
Our results suggest the combination of HA and PRP to be a more effective therapeutic option for partial RC ruptures for short terms, but there is no significant difference after 6 months.
LEVEL OF EVIDENCE
II, Included of Level of Evidence studies I-II.
PubMed: 38599539
DOI: 10.1016/j.arthro.2024.03.035 -
Annals of Medicine Dec 2024Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Circulating plasma cells (CPCs) are defined by the presence of peripheral blood clonal plasma cells, which would contribute to the progression and dissemination of multiple myeloma (MM). An increasing number of studies have demonstrated the predictive potential of CPCs in the past few years. Therefore, there is a growing need for an updated meta-analysis to identify the specific relationship between CPCs and the prognosis of MM based on the current research status.
METHODS
The PubMed, Embase, and Cochrane Library databases were screened to determine eligible studies from inception to November 5, 2023. Publications that reported the prognostic value of CPCs in MM patients were included. Hazard ratios (HRs) with 95% confidence intervals (CIs) of overall survival (OS) and progression-free survival (PFS) were extracted to pool the results. Subgroup analyses were performed based on region, sample size, cut-off value, detection time, initial treatment, and data type. The association between CPCs level and clinicopathological characteristics, including the International Staging System (ISS), Revised-ISS (R-ISS), and cytogenetic abnormalities were also evaluated. Statistical analyses were conducted using STATA 17.0 software.
RESULTS
Twenty-two studies with a total of 5637 myeloma patients were enrolled in the current meta-analysis. The results indicated that myeloma patients with elevated CPCs were expected to have a poor OS (HR = 2.19, 95% CI: 1.81-2.66, < 0.001) and PFS (HR = 2.45, 95% CI: 1.93-3.12, < 0.001). Subgroup analyses did not alter the prognostic role of CPCs, regardless of region, sample size, cut-off value, detection time, initial treatment, or data type. Moreover, the increased CPCs were significantly related to advanced tumour stage (ISS III vs. ISS I-II: pooled OR = 2.89, 95% CI: 2.41-3.46, < 0.001; R-ISS III vs. R-ISS I-II: pooled OR = 3.65, 95% CI: 2.43-5.50, < 0.001) and high-risk cytogenetics (high-risk vs. standard-risk: OR = 2.22, 95% CI: 1.60-3.08, < 0.001).
CONCLUSION
Our meta-analysis confirmed that the increased number of CPCs had a negative impact on the PFS and OS of MM patients. Therefore, CPCs could be a promising prognostic biomarker that helps with risk stratification and disease monitoring.
Topics: Humans; Multiple Myeloma; Plasma Cells; Prognosis; Biomarkers; Proportional Hazards Models
PubMed: 38599340
DOI: 10.1080/07853890.2024.2338604 -
Sexual Medicine Reviews Apr 2024Platelet-rich plasma (PRP) is rich in factors that play a role in stem cell recruitment, inflammation modulation, and angiogenesis. With numerous preclinical and...
INTRODUCTION
Platelet-rich plasma (PRP) is rich in factors that play a role in stem cell recruitment, inflammation modulation, and angiogenesis. With numerous preclinical and clinical studies exploring PRP as a potential treatment for erectile dysfunction (ED), this study focused on assessing the effectiveness of intracorporeal PRP injection for ED patients based on randomized controlled trials (RCTs).
OBJECTIVES
The study sought to evaluate the efficacy and safety of intracorporeal injection of PRP in treating ED through a systematic review and meta-analysis of RCTs.
METHODS
This study adhered to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search was conducted on online databases (PubMed, Scopus, and ScienceDirect) to identify RCTs comparing PRP with a placebo for ED treatment. The primary outcomes assessed were the proportion of patients achieving the minimal clinically important difference in the International Index of Erectile Function (IIEF) domain and the change in the IIEF domain from baseline. The results were combined as a standardized mean difference between the PRP and placebo groups.
RESULTS
Three RCTs comprising 230 patients were included. The overall effect favored PRP over placebo: total patients attaining minimal clinically important difference in the IIEF domain (odds ratio [OR], 5.64; 95% confidence interval [CI], 2.05 to 15.55; P = .0008), IIEF change from baseline (mean difference [MD], 2.99; 95% CI, 1.74 to 4.24; P = .00001), PSV (MD, 9.34; 95% CI, 0.84 to 17.84; P = .03), end-diastolic volume (standardized MD, 0.50; 95% CI, 0.17 to 0.83; P = .003), Sexual Encounter Profile question 3 (standardized MD, 0.78; 95% CI, 0.45 to 1.12; P = .00001), and visual analog scale score (MD, -0.30; 95% CI, -0.53 to -0.08; P = .008).
CONCLUSION
PRP appears to be a safe and effective treatment for mild-to-moderate ED. However, further support from high-quality RCTs is needed to strengthen these findings.
PubMed: 38590115
DOI: 10.1093/sxmrev/qeae018 -
European Journal of Neurology Jul 2024This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
Beyond T cell toxicity - Intrathecal chemokine CXCL13 indicating B cell involvement in immune-related adverse events following checkpoint inhibition: A two-case series and literature review.
BACKGROUND AND PURPOSE
This study was undertaken to raise awareness of a role of B cells in immune checkpoint inhibitor (ICI)-associated neurological immune-related adverse events (nirAE).
METHODS
A systematic literature review was made, with case observations of a melanoma and a non-small cell lung cancer (NSCLC) patient who developed ICI-associated nirAE with cerebrospinal fluid (CSF) findings indicating B cell involvement.
RESULTS
Two patients receiving ipilimumab/nivolumab for melanoma and chemotherapy/pembrolizumab for NSCLC developed nirAE in the form of myocarditis/myositis/myasthenia gravis overlap syndrome (triple M) and cerebellitis plus longitudinal transverse myelitis (c-LETM), respectively. Intrathecal inflammation with chemokine C-X-C motif ligand (CXCL13) elevation was present in both patients; the triple M case had acetylcholine receptor antibodies, antititin reactivity, altered CD4/CD8 T cell ratio in blood, and depressed programmed death-1 (PD-1) expression on CSF T cells; the c-LETM case showed intrathecal antibody production and plasma cells. Both patients insufficiently responded to first-line treatment. The NSCLC case improved upon administration of B cell-depleting therapy with rituximab, whereas the melanoma patient died before escalation therapy was initiated. Literature research revealed one additional ICI-associated LETM case with intrathecal CXCL13 elevation, three cases with ICI-associated aquaporin-4 antibody neuromyelitis spectrum disorder, and evidence of B cell-mediated toxicity based on antibody-mediated immune pathologies in ICI-associated immune-related adverse events.
CONCLUSIONS
The case observations highlight the plethora of uncertainties in diagnosis and treatment of ICI-associated nirAE, exemplify the heterogeneity of immune mechanisms involved, and suggest a role of B cells, which may be underdiagnosed. Intrathecal CXCL13 may serve as a biomarker of B cell involvement in nirAE, supported by intrathecal immunoglobulin synthesis, presence of plasma cells, and/or recruitment of cognate immune cells.
Topics: Aged; Female; Humans; Antibodies, Monoclonal, Humanized; B-Lymphocytes; Chemokine CXCL13; Immune Checkpoint Inhibitors; Ipilimumab; Lung Neoplasms; Melanoma; Myelitis, Transverse; Nivolumab; T-Lymphocytes
PubMed: 38556899
DOI: 10.1111/ene.16279