The regulatory role of microRNA (miRNA) in several conditions has been studied, but their function in tendon healing remains elusive. This review summarizes how miRNAs are related to the pathogenesis ...of tendon injuries and highlights their clinical potential, focusing on the issues related to their delivery for clinical purposes.
We searched multiple databases to perform a systematic review on miRNA in relation to tendon injuries. We included in the present work a total of 15 articles.
The mechanism of repair of tendon injuries is probably mediated by resident tenocytes. These maintain a fine equilibrium between anabolic and catabolic events of the extracellular matrix. Specific miRNAs regulate cytokine expression and orchestrate proliferation and differentiation of stromal cell lines involved in the composition of the extracellular matrix.
The lack of effective delivery systems poses serious obstacles to the clinical translation of these basic science findings.
In vivo studies should be planned to better explore the relationship between miRNA and tendon injuries and evaluate the most suitable delivery system for these molecules.
Investigations ex vivo suggest therapeutic opportunities of miRNA for the management of tendon injuries. Given the poor pharmacokinetic properties of miRNAs, these must be delivered by an adequate adjuvant transport system.
Osteoarthritis (OA) is the most orthopedic condition. The pattern of gene expression and the transcription factors that exert control of chondrogenesis have been extensively studied.
A systematic ...search (up to July 2018) of articles assessing the role of microRNA (miRNA) in physiopathology, diagnosis and therapy of OA was performed, with the purpose of giving a critical perspective of the possibilities for diagnostic and therapeutic use of miRNA in the management of OA.
miRNAs are small noncoding RNAs that can regulate gene expression in human cells. miRNAs can be expressed in a different fashion in osteoarthritic compared to nonosteoarthritic cartilage.
The mechanisms that produce alteration of gene expression in OA are still not completely understood. miRNAs may be involved in the diagnosis of OA as well as in its treatment.
There are complex interactions between miRNAs and their multiple target genes. These interactions may be important in gene regulation and the control of homeostatic pathways in OA.
miRNA could be useful for diagnostic or management purposes, but the issue of delivery of miRNA targeting agents needs to be overcome before miRNA can be applied in clinical practice.
Purpose
The aim of this study is to prospectively evaluate the medium-term effectiveness and regenerative capability of autologous adult mesenchymal stem cells, harvested as bone marrow aspirate ...concentrate (BMAC), along with a hyaluronan-based scaffold (Hyalofast) in the treatment of ICRS grade 4 chondral lesions of the knee joint, in patients older than 45 years.
Methods
A study group of 20 patients with an age >45 years (mean 50.0 ± 4.1 years) was compared to a control group of 20 patients with an age <45 years (mean 36.6 ± 5.0). Patients were prospectively evaluated for 4 years. All patients were evaluated with MRI, KOOS, IKDC, VAS and Tegner scores preoperatively and at two-year and final follow-up.
Results
At final follow-up, all scores significantly improved (
P
< 0.001) as follows: all KOOS score categories; Tegner 2 (range 0–4) to 6 (range 4–8) and 3 (range 0–6) to 6 (range 3–10); IKDC subjective (39.2 ± 16.5 to 82.2 ± 8.9) and (40.8 ± 13.9 to 79.4 ± 14.6), in the study and control group respectively. In addition, we show that results are affected by lesion size and number but not from concomitant surgical procedures. MRI showed complete filling in 80 % of patients in the study group and 71 % of patients in the control group. Histological analysis conducted in three patients from the study and two patients from the control group revealed good tissue repair with a variable amount of hyaline-like tissue.
Conclusion
Treatment of cartilage lesions with BMAC and Hyalofast is a viable and effective option that is mainly affected by lesion size and number and not by age. In particular, it allows to address the >45 years population with functional outcomes that are comparable to younger patients at final follow-up.
Level of evidence
Prospective cohort study, Level II.
Osteoarthritis (OA) is a chronic disease and the most common orthopedic disorder. A vast majority of the social OA burden is related to hips and knees. The prevalence of knee OA varied across studies ...and such differences are reflected by the heterogeneity of data reported by studies conducted worldwide. A complete understanding of the pathogenetic mechanisms underlying this pathology is essential. The OA inflammatory process starts in the synovial membrane with the activation of the immune system, involving both humoral and cellular mediators. A crucial role in this process is played by the so-called "damage-associated molecular patterns" (DAMPs). Mesenchymal stem cells (MSCs) may be a promising option among all possible therapeutic options. However, many issues are still debated, such as the best cell source, their nature, and the right amount. Further studies are needed to clarify the remaining doubts. This review provides an overview of the most recent and relevant data on the molecular mechanism of cartilage damage in knee OA, including current therapeutic approaches in regenerative medicine.
The recent randomised controlled trials comparing non-surgical and surgical treatment of patients with acute tears of the Achilles tendon found no evidence of difference in functional outcome or ...re-rupture rate;5 hence, in some countries, including the UK, non-surgical management is quickly becoming the default. Of note, the risk of a re-tear is low nowadays, regardless of whether surgical or non-surgical treatment is used.5 The rate of postoperative complications is also low, and the clinically relevant difference between surgical and non-surgical management is remarkably small, especially if, instead of an open technique, percutaneous or minimally invasive repair of the Achilles tendon is done.6,7 Because the majority of patients with acute ruptures of the Achilles tendon are not professional athletes, from a societal perspective and to appropriately allocate limited state-funded resources, non-surgical management is a logical option. Have we found the best strategy for treating acute Achilles tendon ruptures? A major issue is that most trials, although accurately planned and executed, do not take into account that patients undergoing non-surgical treatment take longer to return to sport, are less strong, and are less confident in their Achilles tendon than patients who underwent surgery.6 As such, future studies should probably be powered for functional recovery of the gastroc-soleus complex and a return to high-level physical activities; the incidence of re-rupture should not be considered as the main outcome.8 Paul Rapson/Science Photo Library In clinical practice, an increasing number of patients managed non-surgically have no re-rupture, but the healed Achilles tendon has elongated, thus altering its relationship with the gastroc-soleus muscle complex.9 These patients present with a more acute Achilles tendon resting angle,9 are not able to push off properly, and behave similarly to patients with chronic Achilles tendon rupture.
Early osteoarthritis of the knee Madry, Henning; Kon, Elizaveta; Condello, Vincenzo ...
Knee Surgery, Sports Traumatology, Arthroscopy,
06/2016, Letnik:
24, Številka:
6
Journal Article, Book Review
Recenzirano
There is an increasing awareness on the importance in identifying early phases of the degenerative processes in knee osteoarthritis (OA), the crucial period of the disease when there might still be ...the possibility to initiate treatments preventing its progression. Early OA may show a diffuse and ill-defined involvement, but also originate in the cartilage surrounding a focal lesion, thus necessitating a separate assessment of these two entities. Early OA can be considered to include a maximal involvement of 50 % of the cartilage thickness based on the macroscopic ICRS classification, reflecting an OARSI grade 4. The purpose of this paper was to provide an updated review of the current status of the diagnosis and definition of early knee OA, including the clinical, radiographical, histological, MRI, and arthroscopic definitions and biomarkers. Based on current evidence, practical classification criteria are presented. As new insights and technologies become available, they will further evolve to better define and treat early knee OA.
Level of evidence
IV.
Non-surgical treatments are usually the first choice for the management of knee degeneration, especially in the early osteoarthritis (OA) phase when no clear lesions or combined abnormalities need to ...be addressed surgically. Early OA may be addressed by a wide range of non-surgical approaches, from non-pharmacological modalities to dietary supplements and pharmacological therapies, as well as physical therapies and novel biological minimally invasive procedures involving injections of various substances to obtain a clinical improvement and possibly a disease-modifying effect. Numerous pharmaceutical agents are able to provide clinical benefit, but no one has shown all the characteristic of an ideal treatment, and side effects have been reported at both systemic and local level. Patients and physicians should have realistic outcome goals in pharmacological treatment, which should be considered together with other conservative measures. Among these, exercise is an effective conservative approach, while physical therapies lack literature support. Even though a combination of these therapeutic options might be the most suitable strategy, there is a paucity of studies focusing on combining treatments, which is the most common clinical scenario. Further studies are needed to increase the limited evidence on non-surgical treatments and their combination, to optimize indications, application modalities, and results with particular focus on early OA. In fact, most of the available evidence regards established OA. Increased knowledge about degeneration mechanisms will help to better target the available treatments and develop new biological options, where preliminary results are promising, especially concerning early disease phases. Specific treatments aimed at improving joint homoeostasis, or even counteracting tissue damage by inducing regenerative processes, might be successful in early OA, where tissue loss and anatomical changes are still at very initial stages.
Level of evidence
IV.
Background:
Rotator cuff repair typically results in a satisfactory, although variable, clinical outcome. However, anatomic failure of the repaired tendon often occurs.
Hypothesis:
Patch augmentation ...can improve the results of open rotator cuff repair by supporting the healing process, protecting the suture, and reducing friction in the subacromial space.
Study Design:
Cohort study; Level of evidence, 3.
Methods:
A total of 152 patients with a posterosuperior massive rotator cuff tear were treated by open repair only (control group; n = 51; mean age, 67.06 ± 4.42 years), open repair together with collagen patch augmentation (collagen group; n = 49; mean age, 66.53 ± 5.17 years), or open repair together with polypropylene patch augmentation (polypropylene group; n = 52; mean age, 66.17 ± 5.44 years) and were retrospectively studied. Patients were evaluated preoperatively and after 36 months with a visual analog scale (VAS) and the University of California, Los Angeles (UCLA) shoulder rating scale and by measuring elevation of the scapular plane and strength with a dynamometer. The VAS and UCLA scores were also obtained 2 months postoperatively. Tendon integrity was assessed after 1 year by ultrasound. Patients were homogeneous as per the preoperative assessment.
Results:
After 2 months, results (mean ± standard deviation) for the control, collagen, and polypropylene groups, respectively, were as follows: VAS scores were 6.96 ± 1.11, 6.46 ± 1.02, and 4.92 ± 0.90, while UCLA scores were 11.29 ± 1.46, 11.40 ± 1.51, and 19.15 ± 1.99. After 36 months, the mean scores for the respective groups were 3.66 ± 1.05, 4.06 ± 1.02, and 3.28 ± 1.10 for the VAS and 14.88 ± 1.98, 14.69 ± 1.99, and 24.61 ± 3.22 for the UCLA scale. In addition, after 36 months, elevation on the scapular plane was 140.68° ± 9.84°, 140.61° ± 12.48°, and 174.71° ± 8.18°, and abduction strength was 8.73 ± 0.54 kg, 9.03 ± 0.60 kg, and 13.79 ± 0.64 kg for the control, collagen, and polypropylene groups, respectively. The retear rate after 12 months was 41% (21/51) for the control group, 51% (25/49) for the collagen group, and 17% (9/52) for the polypropylene group. In particular, the reduced 12-month retear rate and the increased UCLA scores, abduction strength, and elevation at 3-year follow-up were statistically significant for patients treated with a polypropylene patch compared with those treated with repair only or with a collagen patch.
Conclusion:
Polypropylene patch augmentation of rotator cuff repair was demonstrated to significantly improve the 36-month outcome in terms of function, strength, and retear rate.
Biochemical markers of bone turnover (BTMs), such as bone alkaline phosphatase (bALP), procollagen type I N propeptide (PINP), serum cross-linked C-telopeptides of type I collagen (bCTx), and urinary ...cross-linked N-telopeptides of type I collagen (NTx), are commonly used for therapy monitoring purposes for osteoporotic patients. The present study evaluated the potential role of BTMs as therapy monitoring.
All randomized clinical trials (RCTs) comparing two or more pharmacological treatments for postmenopausal osteoporosis were accessed. Only studies that reported the value of bALP, PINP, bCTx, and NTx at last follow-up were included. A multivariate analysis was performed to assess associations between these biomarkers and clinical outcomes and rate of adverse events in patients with postmenopausal osteoporosis. A multiple linear model regression analysis through the Pearson product-moment correlation coefficient was used.
A total of 16 RCTs (14,446 patients) were included. The median age was 67 years, and the median BMI 25.4 kg/m
. The median vertebral BMD was 0.82, hip BMD 0.79, and femur BMD 0.64 g/cm
. The ANOVA test found optimal within-group variance concerning mean age, body mass index, and BMD. Greater bALP was associated with lower femoral BMD (P = 0.01). Greater NTx was associated with a greater number of non-vertebral fractures (P = 0.02). Greater NTx was associated with greater rate of therapy discontinuation (P = 0.04). No other statistically significant associations were detected.
Our analysis supports the adoption of BTMs in therapy monitoring of osteoporotic patients.
Level I, systematic review of RCTs.
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