Intra-articular drug delivery has a number of advantages over systemic administration; however, for the past 20 years, intra-articular treatment options for the management of knee osteoarthritis (OA) ...have been limited to analgesics, glucocorticoids, hyaluronic acid (HA) and a small number of unproven alternative therapies. Although HA and glucocorticoids can provide clinically meaningful benefits to an appreciable number of patients, emerging evidence indicates that the apparent effectiveness of these treatments is largely a result of other factors, including the placebo effect. Biologic drugs that target inflammatory processes are used to manage rheumatoid arthritis, but have not translated well into use in OA. A lack of high-level evidence and methodological limitations hinder our understanding of so-called 'stem' cell therapies and, although the off-label administration of intra-articular cell therapies (such as platelet-rich plasma and bone marrow aspirate concentrate) is common, high-quality clinical data are needed before these treatments can be recommended. A number of promising intra-articular treatments are currently in clinical development in the United States, including small-molecule and biologic therapies, devices and gene therapies. Although the prospect of new, non-surgical treatments for OA is exciting, the benefits of new treatments must be carefully weighed against their costs and potential risks.
Background:
Stem cell therapy is emerging as a potential treatment of osteoarthritis (OA) and chondral defects (CDs). However, there is a great deal of heterogeneity in the literature. The ...indications for stem cell use, the ideal tissue source, and the preferred outcome measures for stem cell–based treatments have yet to be determined.
Purpose:
To provide clinicians with a comprehensive overview of the entire body of the current human literature investigating the safety and efficacy of intra-articular mesenchymal stem cell (MSC) therapy in all joints.
Methods:
To provide a comprehensive overview of the current literature, all clinical studies investigating the safety and efficacy of intra-articular MSC therapy were included. PubMed, MEDLINE, and Cochrane Library databases were searched for published human clinical trials involving the use of MSCs for the treatment of OA and CDs in all joints. A total of 3867 publications were screened.
Results:
Twenty-eight studies met the criteria to be included in this review. Fourteen studies treating osteoarthritis and 14 studies treating focal chondral defects were included. MSCs originating from bone marrow (13), adipose tissue (12), synovial tissue (2), or peripheral blood (2) were administered to 584 distinct individuals. MSCs were administered into the knee (523 knees), foot/ankle (61), and hip (5). The mean follow-up time was 24.4 months after MSC therapy. All studies reported improvement from baseline in at least 1 clinical outcome measure, and no study reported major adverse events attributable to MSC therapy.
Discussion:
The studies included in this review suggest that intra-articular MSC therapy is safe. While clinical and, in some cases, radiological improvements were reported for both OA and CD trials, the overall quality of the literature was poor, and heterogeneity and lack of reproducibility limit firm conclusions regarding the efficacy of these treatments.
Conclusion:
This review provides strong evidence that autologous intra-articular MSC therapy is safe, with generally positive clinical outcomes.
Continuous Fibre composite 3D printing (CF-3DP) technology is a newly developed Additive Manufacturing (AM) process. By employing continuous fibre as a reinforcement for the composite, the mechanical ...properties of the 3D printed part can be significantly improved. However, owing to the process's early stage of development, the mechanical performance of the printed material is still unable to compete with composites produced using conventional manufacturing processes. This can manly be attributed to lower fibre volume fractions and/or higher void content. The grand objective of the research project is to establish a demonstrator of practical applications, and in this paper, preparatory developments were carried out to pave the ground for the subsequent developments, including feedstock materials development, printing process development, and materials properties evaluation. Efforts has been made to increase fibre volume fracture, to reduce voids contents, to evaluate effective properties systematically. The static mechanical test results showed relatively good longitudinal tensile properties while matrix sensitive properties were low, as to be expected in UD composites with a relatively weak matrix material. The advantage of CF-3DP is to achieve fibre steering, and the steered fibre design can be achieved by the current process to realize novel composite structures in future study.
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It is unknown whether kinematic alignment (KA) objectively improves knee balance in total knee arthroplasty (TKA), despite this being the biomechanical rationale for its use. This study aimed to ...determine whether restoring the constitutional alignment using a restrictive KA protocol resulted in better quantitative knee balance than mechanical alignment (MA).
We conducted a randomized superiority trial comparing patients undergoing TKA assigned to KA within a restrictive safe zone or MA. Optimal knee balance was defined as an intercompartmental pressure difference (ICPD) of 15 psi or less using a pressure sensor. The primary endpoint was the mean intraoperative ICPD at 10° of flexion prior to knee balancing. Secondary outcomes included balance at 45° and 90°, requirements for balancing procedures, and presence of tibiofemoral lift-off.
A total of 63 patients (70 knees) were randomized to KA and 62 patients (68 knees) to MA. Mean ICPD at 10° flexion in the KA group was 11.7 psi (SD 13.1) compared with 32.0 psi in the MA group (SD 28.9), with a mean difference in ICPD between KA and MA of 20.3 psi (p < 0.001). Mean ICPD in the KA group was significantly lower than in the MA group at 45° and 90°, respectively (25.2 psi MA vs 14.8 psi KA, p = 0.004; 19.1 psi MA vs 11.7 psi KA, p < 0.002, respectively). Overall, participants in the KA group were more likely to achieve optimal knee balance (80% vs 35%; p < 0.001). Bone recuts to achieve knee balance were more likely to be required in the MA group (49% vs 9%; p < 0.001). More participants in the MA group had tibiofemoral lift-off (43% vs 13%; p < 0.001).
This study provides persuasive evidence that restoring the constitutional alignment with KA in TKA results in a statistically significant improvement in quantitative knee balance, and further supports this technique as a viable alternative to MA. Cite this article:
2020;102-B(1):117-124.
Background:
There has been a surge in high-level studies investigating platelet-rich plasma (PRP) for tendon and ligament injuries. A number of meta-analyses have been published, but few studies have ...focused exclusively on tendon and ligament injuries.
Purpose:
To perform a meta-analysis assessing the ability of PRP to reduce pain in patients with tendon and ligament injuries.
Study Design:
Systematic review and meta-analysis.
Methods:
This study followed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A comprehensive search of the literature was carried out in April 2017 using electronic databases PubMed, MEDLINE, and the Cochrane Library. Only level 1 studies were included. Platelet and leukocyte count, injection volume, kit used, participant age/sex, comparator, and activating agent used were recorded. The short-term and long-term efficacy of PRP was assessed using the visual analog scale (VAS) to measure pain intensity. Injury subgroups (rotator cuff, tendinopathy, anterior cruciate ligament, and lateral epicondylitis) were evaluated. Funnel plots and the Egger test were used to screen for publication bias, and sensitivity analysis was performed to evaluate the effect of potential outliers by removing studies one at a time.
Results:
Thirty-seven articles were included in this review, 21 (1031 participants) of which could be included in the quantitative analysis. The majority of studies published investigated rotator cuff injuries (38.1%) or lateral epicondylitis (38.1%). Seventeen studies (844 participants) reported short-term VAS data, and 14 studies (771 participants) reported long-term VAS data. Overall, long-term follow-up results showed significantly less pain in the PRP group compared with the control group (weighted mean difference WMD, –0.84; 95% CI, –1.23 to –0.44; P < .01). Patients treated with PRP for rotator cuff injuries (WMD, –0.53; 95% CI, –0.98 to –0.09; P = .02) and lateral epicondylitis (WMD, –1.39; 95% CI, –2.49 to –0.29; P = .01) reported significantly less pain in the long term. Substantial heterogeneity was reported at baseline (I2 = 72.0%; P < .01), short-term follow-up (I2 = 72.5%; P < .01), long-term follow-up (I2 = 76.1%; P < .01), and overall (I2 = 75.8%; P < .01). The funnel plot appeared to be asymmetric, with some missingness at the lower right portion of the plot suggesting possible publication bias.
Conclusion:
This review shows that PRP may reduce pain associated with lateral epicondylitis and rotator cuff injuries.
Dual-mycorrhizal plants Teste, François P.; Jones, Melanie D.; Dickie, Ian A.
New phytologist,
03/2020, Letnik:
225, Številka:
5
Journal Article
Recenzirano
Odprti dostop
Dual-mycorrhizal plants are capable of associating with fungi that form characteristic arbuscular mycorrhizal (AM) and ectomycorrhizal (EM) structures. Here, we address the following questions: (1) ...Howmany dual-mycorrhizal plant species are there? (2) What are the advantages for a plant to host two, rather than one, mycorrhizal types? (3) Which factors can provoke shifts in mycorrhizal dominance (i.e. mycorrhizal switching)? We identify a large number (89 genera within 32 families) of confirmed dual-mycorrhizal plants based on observing arbuscules or coils for AM status and Hartig net or similar structures for EM status within the same plant species. We then review the possible nutritional benefits and discuss the possible mechanisms leading to net costs and benefits. Cost and benefits of dual-mycorrhizal status appear to be context dependent, particularly with respect to the life stage of the host plant. Mycorrhizal switching occurs under a wide range of abiotic and biotic factors, including soil moisture and nutrient status. The relevance of dual-mycorrhizal plants in the ecological restoration of adverse sites where plants are not carbon limited is discussed. We conclude that dual-mycorrhizal plants are underutilized in ecophysiological-based experiments, yet are powerful model plant–fungal systems to better understand mycorrhizal symbioses without confounding host effects.
The minimal clinically important difference (MCID) is used when interpreting the importance of outcome data. However, a consensus regarding the MCID for commonly used patient-reported outcomes in ...shoulder surgery has not been established. The purpose of this systematic review was to evaluate the available literature on shoulder MCID to improve clinical interpretation of shoulder outcome data.
A systematic review of the literature was conducted to identify studies reporting anchor-based MCID values for the patient-reported outcomes recommended by the American Shoulder and Elbow Surgeons (ASES): Veterans Rand 12 score, ASES score, Single Assessment Numeric Evaluation (SANE) score, Western Ontario Rotator Cuff (WORC) score, Western Ontario Osteoarthritis Score (WOOS), Western Ontario Shoulder Instability Index (WOSI), Pennsylvania Shoulder Score, and Oxford Shoulder Score (OSS).
A total of 14 articles reporting anchor-based MCID values were included in the final analysis. No studies reporting the Western Ontario Osteoarthritis Score (WOOS) were identified. The ASES score (6 studies), OSS (4 studies), and WORC score (2 studies) were the only instruments investigated in more than 1 study. The average reported MCID values for the ASES, OSS, and WORC scores were 15.5 (15% total difference), 275.7 (13% total difference), and 6 (13% total difference), respectively. The vast majority of studies failed to report information necessary to validate the credibility of these MCID values.
The current utility of the MCID for patient-report shoulder outcome instruments is limited by poor study methodology, inadequate reporting, and a lack of data. Further research is needed to more clearly define the MCID values for commonly used patient-reported outcomes in shoulder surgery.
Background:
Many clinical trials have investigated the use of platelet-rich plasma (PRP) to treat rotator cuff–related abnormalities. Several meta-analyses have been published, but none have focused ...exclusively on level 1 randomized controlled trials.
Purpose:
To assess the efficacy of PRP for rotator cuff–related abnormalities and evaluate how specific tendon involvement, the inclusion of leukocytes, and the use of gel/nongel formulations affect pain and functional outcomes.
Study Design:
Systematic review and meta-analysis.
Methods:
The literature was screened following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Baseline, short-term, and long-term data were extracted for the Constant score, University of California, Los Angeles (UCLA) score, visual analog scale (VAS) for pain, retear rate, Simple Shoulder Test (SST), and American Shoulder and Elbow Surgeons (ASES) score. The 100-point modified Coleman Methodology Score (CMS) was used to assess methodological quality. Funnel plots and the Egger test were used to screen for publication bias, and sensitivity analysis was performed to evaluate the effect of potential outliers.
Results:
A total of 18 level 1 studies were included in this review, 17 (1116 patients) of which could be included in quantitative analysis. The mean modified CMS was 79.4 ± 10.39. The Constant scores of patients who received PRP were significantly better short term (weighted mean difference WMD, 2.89 95% CI, 0.89-4.90; P < .01) and long term (WMD, 2.66 95% CI, 1.13-4.19; P < .01). The VAS scores were significantly improved short term (WMD, –0.45 95% CI, –0.75 to −0.15; P < .01). Sugaya grade IV and V retears in PRP-treated patients were significantly reduced long term (odds ratio OR, 0.34 95% CI, 0.20-0.57; P < .01). In PRP-treated patients with multiple tendons torn, there were reduced odds of retears (OR, 0.28 95% CI, 0.13-0.60; P < .01). Patients who received leukocyte-rich PRP had significantly better Constant scores compared with the leukocyte-poor PRP group, but there was no difference in VAS scores. Patients receiving PRP gel reported higher Constant scores compared with the controls, whereas those receiving nongel PRP treatments did not, although there was no difference in VAS scores. Long-term odds of retears were decreased, regardless of leukocyte content (leukocyte-poor PRP: OR, 0.36 95% CI, 0.16-0.82; leukocyte-rich PRP: OR, 0.32 95% CI, 0.16-0.65; all P < .05) or usage of gel (nongel: OR, 0.42 95% CI, 0.23-0.76; gel: OR, 0.17 95% CI, 0.05-0.51; all P < .01).
Conclusion:
Long-term retear rates were significantly decreased in patients with rotator cuff–related abnormalities who received PRP. Significant improvements in PRP-treated patients were noted for multiple functional outcomes, but none reached their respective minimal clinically important differences. Overall, our results suggest that PRP may positively affect clinical outcomes, but limited data, study heterogeneity, and poor methodological quality hinder firm conclusions.
Despite the growing similarities between allopathic (MD) and osteopathic (DO) medical education, few studies have examined allopathic-osteopathic collaboration. The following study focused on ...stereotypes and student readiness for interprofessional learning. Patient perceptions were also evaluated. Osteopathic and allopathic students were randomly allocated 1:1:1 to work in pairs (MD/DO, MD/MD, DO/DO) at the start of each shift. A questionnaire evaluating student communication was collected from patients at the end of each encounter. Surveys assessing stereotypes and interprofessional readiness were obtained from students at the end of each workday. Data collection was stopped early due to Coronavirus-related safety measures. In the ITT analysis, there were a total of 126 participants (57 students 69 patients). A per-protocol analysis was performed to account for repeat clinic volunteers. No significant differences were detected between student pairs; however, the sensitivity analysis of the questionnaire assessing interprofessional readiness was 8 points higher in the DO/DO group compared to the MD/MD and MD/DO groups (P = 0.0503). In the content analysis of qualitative responses, the MD/DO group was more likely to respond with themes of enjoyment and less concern about stereotypes than the DO/DO group. The MD/DO group was also less likely to report concerns about differences in expectations, methods, and thinking than the MD/MD group. Early trends from this study suggest that DO students may be better positioned to engage in interprofessional learning than their MD counterparts. Additionally, the findings from our content analysis provide evidence that the collaborative experience improved feelings associated with professional legitimacy and credibility among DO students. Taken in aggregate, this study provides justification for a follow-up investigation, as well as a framework for how such studies could best be executed in the future.
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