The Clinical Use of Platelet-Rich Plasma in Knee Disorders and Surgery-A Systematic Review and Meta-Analysis.

In recent years, the interest in biological treatment of knee lesions has increased, especially the application of platelet-rich plasma is of particular note. The number of articles evaluating platelet-rich plasma (PRP) efficacy in the recovery of knee disorders and during knee surgery has exponentially increased over the last decade. A systematic review with meta-analyses was performed by assessing selected studies of local PRP injections to the knee joint. The study was completed in accordance with 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A multistep search of PubMed, Embase, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov was performed to identify studies on knee surgery and knee lesion treatment with PRP. Of the 4004 articles initially identified, 357 articles focusing on knee lesions were selected and, consequently, only 83 clinical trials were analyzed using the revised Cochrane risk-of-bias tool to evaluate risk. In total, seven areas of meta-analysis reported a positive effect of PRP. Among them, 10 sub-analyses demonstrated significant differences in favor of PRP when compared to the control groups (p < 0.05). This study showed the positive effects of PRP, both on the recovery of knee disorders and during knee surgery; however further prospective and randomized studies with a higher number of subjects and with lower biases are needed.

Fluctuations in circulating endothelial progenitor cell levels and acute cardiac graft rejection.

INTRODUCTION: Endothelial progenitor cells (EPCs) in nontransplant settings have reparative properties. However, their role in heart transplantation (HT) is not well defined. OBJECTIVES: The aim of this study was to prospectively evaluate changes in EPC levels in relation to post­HT rejection. PATIENTS AND METHODS: EPC levels were measured in 27 HT recipients for 6 months after HT. Acute cellular rejection (ACR) or antibody­mediated rejection (AMR) were assessed by right ventricular endomyocardial biopsy. RESULTS: ACR and AMR were observed in 7 (25.9%) and 6 (22.2%) patients, respectively. The ACR status at 1 month post­HT did not differ with respect to EPC immediately post­HT. At 1 month post­HT in patients without ACR or AMR, EPC levels were significantly reduced compared with the measurements immediately post­HT (P <0.001). On further follow­up, EPC levels were similar regardless of the rejection events. Nonetheless, greater changes (coefficient of variation) in EPClog (logarithmic transformation) were associated with the risk of AMR or ACR compared with those without any rejection event (median [lower-upper quartile], 15 [13-18] vs 8 [5-13]; P = 0.02 and 22 [14-26] vs 8 [5-13]; P = 0.01, respectively). The receiver operating characteristic curve showed that the coefficient of variation of EPClog of 12 was the optimal cutoff value for the prediction of rejection (area under the curve = 0.85). Higher levels were associated with greater risk of ACR or AMR (P <0.005). CONCLUSIONS: Early reduction of EPC levels was related to a lower risk of ACR or AMR. Greater changes of EPC­levels during follow­up were associated with a significantly higher risk of rejection.

microRNA expression profile in Smooth Muscle Cells isolated from thoracic aortic aneurysm samples.

PURPOSE: Thoracic aortic aneurysm (TAA) is a cardiovascular disease characterized by increased aortic diameter, treated with surgery and endovascular therapy in order to avoid aortic dissection or rupture. The mechanism of TAA formation has not been thoroughly studied and many factors have been proposed to drive its progression; however strong focus is attributed to modification of smooth muscle cells (SMCs). Latest research indicates, that microRNAs (miRNAs) may play a significant role in TAA development - these are multifunctional molecules consisting of 19-24 nucleotides involved in regulation of the gene expression level related to many biological processes, i.e. cardiovascular disease pathophysiology, immunity or inflammation. MATERIALS AND METHODS: Primary SMCs were isolated from aortic scraps of TAA patients and age- and sex-matched healthy controls. Purity of isolated SMCs was determined by flow cytometry using specific markers: α-SMA, CALP, MHC and VIM. Real-time polymerase chain reaction (RT-PCR) was conducted for miRNA analysis. RESULTS: We established an isolation protocol and investigated the miRNA expression level in SMCs isolated from aneurysmal and non-aneurysmal aortic samples. We identified that let-7 g (0.71-fold, p = 0.01), miR-130a (0.40-fold, p = 0.04), and miR-221 (0.49-fold, p = 0.05) significantly differed between TAA patients and healthy controls. CONCLUSIONS: Further studies are required to improve our understanding of the pathophysiology underlying TAA, which may aid the development of novel, targeted therapies. The pivotal role of miRNAs in the cardiovascular system provides a new perspective on the pathophysiology of thoracic aortic aneurysms.

Repair Augmentation of Unstable, Complete Vertical Meniscal Tears With Bone Marrow Venting Procedure: A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study.

PURPOSE: To compare the effectiveness and safety of meniscal repair in 2 groups of patients: meniscal repair with biological augmentation using a bone marrow venting procedure (BMVP) of the intercondylar notch versus meniscal repair only. METHODS: This single-center, prospective, randomized, double-blind, placebo-controlled, parallel-arm study included 40 patients (21 menisci in control, 23 in BMVP group) with complete vertical meniscus tears. Patients underwent all-inside and outside-in meniscal repair and a concomitant BMVP of the intercondylar notch or meniscal repair alone during an index arthroscopy. The primary endpoint was the rate of meniscus healing in the 2 groups assessed during a second-look arthroscopy (at week 35). The secondary endpoints were changes in the International Knee Documentation Committee score, Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, and visual analog scale in the 2 groups at 30 months. RESULTS: After 36 weeks, the meniscus healing rate was significantly higher in the BMVP-treated group than in the control group (100% vs. 76%, P = .0035). Functional outcomes were significantly better 30 months after treatment than at baseline in both groups. The International Knee Documentation Committee, Knee Injury and Osteoarthritis Outcome Score, Western Ontario and McMaster Universities Osteoarthritis Index, and visual analog scale scores were significantly better in the BMVP-treated group than in the control group. No adverse events were reported during the study period. CONCLUSIONS: Our blinded, prospective, randomized, controlled trial on the role of BMVP augmentation in meniscus repair, indicates that BMVP augmentation results in a significant improvement in the rate of meniscus healing (100% vs. 76%, P = .0035). The risk of adverse events related to augmentation with BMVP of the arthroscopic meniscal repair is very low. LEVEL OF EVIDENCE: Level I, randomized controlled trial.

Short-Term Outcomes of Percutaneous Trephination with a Platelet Rich Plasma Intrameniscal Injection for the Repair of Degenerative Meniscal Lesions. A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study.

Meniscal tears are the most common orthopaedic injuries, with chronic lesions comprising up to 56% of cases. In these situations, no benefit with surgical treatment is observed. Thus, the purpose of this study was to investigate the effectiveness and safety of percutaneous intrameniscal platelet rich plasma (PRP) application to complement repair of a chronic meniscal lesion. This single centre, prospective, randomized, double-blind, placebo-controlled study included 72 patients. All subjects underwent meniscal trephination with or without concomitant PRP injection. Meniscal non-union observed in magnetic resonance arthrography or arthroscopy were considered as failures. Patient related outcome measures (PROMs) were assessed. The failure rate was significantly higher in the control group than in the PRP augmented group (70% vs. 48%, P = 0.04). Kaplan-Meyer analysis for arthroscopy-free survival showed significant reduction in the number of performed arthroscopies in the PRP augmented group. A notably higher percentage of patients treated with PRP achieved minimal clinically significant difference in visual analogue scale (VAS) and Knee injury and Osteoarthritis Outcome Score (KOOS) symptom scores. Our trial indicates that percutaneous meniscal trephination augmented with PRP results in a significant improvement in the rate of chronic meniscal tear healing and this procedure decreases the necessity for arthroscopy in the future (8% vs. 28%, P = 0.032).

A Prospective, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Evaluating Meniscal Healing, Clinical Outcomes, and Safety in Patients Undergoing Meniscal Repair of Unstable, Complete Vertical Meniscal Tears (Bucket Handle) Augmented with Platelet-Rich Plasma.

OBJECTIVE: The present study aimed to investigate the effectiveness and safety of platelet-rich plasma (PRP) application in arthroscopic repair of complete vertical tear of meniscus located in the red-white zone. METHODS: This single center, prospective, randomized, double-blind, placebo-controlled, parallel-arm study included 37 patients with complete vertical meniscus tears. Patients received an intrarepair site injection of either PRP or sterile 0.9% saline during an index arthroscopy. The primary endpoint was the rate of meniscus healing in the two groups. The secondary endpoints were changes in the International Knee Documentation Committee (IKDC) score, Knee Injury and Osteoarthritis Outcome Score (KOOS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and analog scale (VAS) in the two groups at 42 months. RESULTS: After 18 weeks, the meniscus healing rate was significantly higher in the PRP-treated group than in the control group (85% versus 47%, P = 0.048). Functional outcomes were significantly better 42 months after treatment than at baseline in both groups. The IKDC score, WOMAC, and KOOS were significantly better in the PRP-treated group than in the control group. No adverse events were reported during the study period. CONCLUSIONS: The findings of this study indicate that PRP augmentation in meniscus repair results in improvements in both meniscus healing and functional outcome.

MicroRNA in cardiovascular biology and disease.

MicroRNAs (miRNAs) are members of a non-coding RNA family. They act as negative regulators of protein translation by affecting messenger RNA (mRNA) stability; they modulate numerous signaling pathways and cellular processes, and are involved in cell-to-cell communication. Thus, studies on miRNAs offer an opportunity to improve our understanding of complex biological mechanisms. In the cardiovascular system, miRNAs control functions of various cells, such as cardiomyocytes, endothelial cells, smooth muscle cells and fibroblasts. The pivotal role of miRNAs in the cardiovascular system provides a new perspective on the pathophysiology of disorders like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation and atherosclerosis. MiRNAs are differentially expressed in diseased tissue and can be released into circulation. Manipulation of miRNA activity may influence the course of a disease. Therefore, miRNAs have become an active field of research for developing new diagnostic and therapeutic tools. This review discusses emerging functions of miRNAs in cardiogenesis, heart regeneration and the pathophysiology of cardiovascular diseases.

Homozygous truncating mutation in NRAP gene identified by whole exome sequencing in a patient with dilated cardiomyopathy.

The genetic background of dilated cardiomyopathy is highly heterogeneous, with close to 100 known genes and a number of candidates described to date. Nebulin-related-anchoring protein (NRAP) is an actin-binding cytoskeletal protein expressed predominantly in striated and cardiac muscles, and is involved in myofibrillar assembly in the foetal heart and in force transmission in the adult heart. The homozygous NRAP truncating variant (rs201084642), which is predicted to introduce premature stop codon into all NRAP isoforms, was revealed in the dilated cardiomyopathy patient using whole exome sequencing. The same genotype was detected in the asymptomatic proband's brother. The expression of the NRAP protein was undetectable in the patient's heart muscle by the Western blot. Genotyping for rs201084642 in the ethnically matched cohort of 231 dilated cardiomyopathy patients did not reveal any additional subjects with this variant. Our findings suggest that the biallelic loss-of-function mutation in NRAP could constitute a relatively rare, low-penetrance genetic risk factor for dilated cardiomyopathy.

Severe chronic heart failure in patients considered for heart transplantation in Poland.

BACKGROUND: Based on the results of clinical trials, the prognosis for patients with severe heart failure (HF) has improved over the last 20 years. However, clinical trials do not reflect 'real life' due to patient selection. Thus, the aim of the POLKARD-HF registry was the analysis of survival of patients with refractory HF referred for orthotopic heart transplantation (OHT). METHODS: Between 1 November 2003 and 31 October 2007, 983 patients with severe HF, referred for OHT in Poland, were included into the registry. All patients underwent routine clinical and hemodynamic evaluation, with NT-proBNP and hsCRP assessment. Death or an emergency OHT were assumed as the endpoints. The average observation period was 601 days. Kaplan-Meier curves with log-rank and univariate together with multifactor Cox regression model the stepwise variable selection method were used to determine the predictive value of analyzed variables. RESULTS: Among the 983 patients, the probability of surviving for one year was approximately 80%, for two years 70%, and for three years 67%. Etiology of the HF did not significantly influence the prognosis. The patients in NYHA class IV had a three-fold higher risk of death or emergency OHT. The univariate/multifactor Cox regression analysis revealed that NYHA IV class (HR 2.578, p < 0.0001), HFSS score (HR 2.572, p < 0.0001) and NT-proBNP plasma level (HR 1.600, p = 0.0200), proved to influence survival without death or emergency OHT. CONCLUSIONS: Despite optimal treatment, the prognosis for patients with refractory HF is still not good. NYHA class IV, NT-proBNP and HFSS score can help define the highest risk group. The results are consistent with the prognosis of patients enrolled into the randomized trials.