Role of VEGF, Nitric Oxide, and Sympathetic Neurotransmitters in the Pathogenesis of Tendinopathy: A Review of the Current Evidences

Chronic tendinopathy is a painful common condition affecting athletes as well as the general population undergoing to tendon overuse. Although its huge prevalence, little is known about tendinopathy pathogenesis, and even cloudier is its treatment. Traditionally, tendinopathy has been defined as a lack of tendon ability to overcome stressing stimuli with appropriate adaptive changes. Histologic studies have demonstrated the absence of inflammatory infiltrates, as a consequence conventional antinflammatory drugs have shown little or no effectiveness in treating tendinopathies. New strategies should be therefore identified to address chronic tendon disorders. Angiofibroblastic changes have been highlighted as the main feature of tendinopathy, and vascular endothelial growth factor (VEGF) has been demonstrated as one of the key molecules involved in vascular hyperplasia. More recently, attention has been focused on new peptides such as Substance P, nitric oxide, and calcitonin gene-related peptide (CGRP). Those new findings support the idea of a nerve-mediated disregulation of tendon metabolism. Each of those molecules could be a target for new treatment options. This study aimed to systematically review the current available clinical and basic science in order to summarize the latest evidences on the pathophysiology and its effect on treatment of chronic tendinopathy, and to spread suggestions for future research on its treatment

Predictors for readmission following primary total hip and total knee arthroplasty.

Background: Readmission following total joint arthroplasty has become a closely watched metric for many hospitals in the United States due to financial penalties imposed by Centers for Medicare and Medicaid Services. The purpose of this study was to identify both preoperative and postoperative reasons for readmission within 30 days following primary total hip and total knee arthroplasty (TKA). Methods: Retrospective data were collected for patients who underwent elective primary total hip arthroplasty (THA; CPT code 27130) and TKA (27447) from 2008 to 2013 at our institution. The sample was separated into readmitted and nonreadmitted cohorts. Demography, comorbidities, Charlson comorbidity index (CCI), operative parameters, readmission rates, and causes of readmission were compared between the groups using univariate and multivariate regression analysis. Results: There were 42 (3.4%) and 28 (2.2%) readmissions within 30 days for THA and TKA, respectively. The most common cause of readmission within 30 days following total joint arthroplasty was infection. Trauma was the second most common reason for readmission of a THA while wound dehiscence was the second most common cause for readmission following TKA. With univariate regression, there were multiple associated factors for readmission among THA and TKA patients, including body mass index, metabolic equivalent (MET), and CCI. Multivariate regression revealed that hospital length of stay was significantly associated with 30-day readmission after THA and TKA. Conclusion: Patient comorbidities and preoperative functional capacity significantly affect 30-day readmission rate following total joint arthroplasty. Adjustments for these parameters should be considered and we recommend the use of CCI and METs in risk adjustment models that use 30-day readmission as a marker for quality of patient care. Level of Evidence: Level III/Retrospective cohort stud

Prevalence of articular cartilage lesions and surgical clinical outcomes in football (soccer) players' knees: a systematic review

"Article in Press" ; "Published Online: April 16, 2016"Purpose: To systematize the available scientific literature on the prevalence of articular cartilage and/or osteo- chondral lesions in football (soccer) playersâ knees, and overview the surgical procedures and functional outcomes and return to sports. Methods: A comprehensive search using Pubmed, Cochrane Library, SPORTDiscus, and CINAHL databases was carried out until September 30, 2015. All English language studies that assessed the outcomes of a surgical technique for the treatment of articular cartilage lesions in football playersâ knees, with a minimum follow-up of 12 months, were included. The reference list of the most relevant papers was screened. The main outcomes of interest were the clinical, arthroscopy or imaging primary outcomes and the return to sports rate. The methodological and reporting qualities were assessed according to Coleman methodology score. Results: The search provided 485 titles and abstracts. Five studies were eligible for inclusion (mean Coleman score of 37.2 points), comprising a total of 183 football players with a mean age of 25.7 years. A total of 217 articular cartilage and/or osteochondral lesions were reported, where the medial and lateral femoral condyles were the most common sites of lesion. The surgical procedures investigated were mosaicplasty, microfracture, autologous chondrocyte implantation, and chondral debridement. Conclusions: No definitive conclusion could be made in respect to the best current surgical technique for articular cartilage and osteochondral lesions. Microfracture and mosaicplasty can provide a faster return to competition and faster clinical and functional results, whereas autologous chondrocyte implantation and/or matrix-induced autologous chondrocytes implantation procedures can enhance longstanding clinical and functional results. Level of Evidence: Level IV, systematic review of Level III and IV studies

Bone marrow ectopic expression of a non-coding RNA in childhood T-cell acute lymphoblastic leukemia with a novel t(2;11)(q11.2;p15.1) translocation

Chromosomal translocations play a crucial role in tumorigenesis, often resulting in the formation of chimeric genes or in gene deregulation through position effects. T-cell acute lymphoblastic leukemia (T-ALL) is associated with a large number of such rearrangements. We report the ectopic expression of the 3' portion of EST DA926692 in the bone marrow of a childhood T-ALL case showing a t(2;11)(q11.2;p15.1) translocation as the sole chromosome abnormality. The breakpoints, defined at the sequence level, mapped within HPS5 ( Hermansky Pudlak syndrome 5) intron 1 at 11p15.1, and DA926692 exon 2 at 2q11.2. The translocation was accompanied by a submicroscopic inversion that brought the two genes into the same transcriptional orientation. No chimeric trancript was detected. Interestingly, Real-Time Quantitative (RQ)-PCR detected, in the patient's bone marrow, expression of a 173 bp product corresponding to the 3' portion of DA926692. Samples from four T-ALL cases with a normal karyotype and normal bone marrow used as controls were negative. It might be speculated that the juxtaposition of this genomic segment to the CpG island located upstream HPS5 activated DA92669 expression. RQ-PCR analysis showed expression positivity in 6 of 23 human tissues examined. Bioinformatic analysis excluded that this small non-coding RNA is a precursor of micro-RNA, although it is conceivable that it has a different, yet unknown, functional role. To the best of our knowledge, this is the first report, in cancer, of the activation of a small non-coding RNA as a result of a chromosomal translocation

Cartilage restoration of patellofemoral lesions: a systematic review

Purpose This study aimed to systematically analyze the postoperative clinical, functional, and imaging outcomes, complications, reoperations, and failures following patellofemoral cartilage restoration surgery. Methods This review was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). PubMed, EMBASE, and Cochrane Library databases were searched up to August 31, 2018, to identify clinical studies that assessed surgical outcomes of patellofemoral cartilage restoration surgery. The Methodological Index for Non-Randomized Studies (MINORS) was used to assess study quality. Results Forty-two studies were included comprising 1,311 knees (mean age of 33.7 years and 56% males) and 1,309 patellofemoral defects (891 patella, 254 trochlear, 95 bipolar, and 69 multiple defects, including the patella or trochlea) at a mean follow-up of 59.2 months. Restoration techniques included autologous chondrocyte implantation (56%), particulated juvenile allograft cartilage (12%), autologous matrix-induced chondrogenesis (9%), osteochondral autologous transplantation (9%), and osteochondral allograft transplantation (7%). Significant improvement in at least one score was present in almost all studies and these surpassed the minimal clinically important difference threshold. There was a weighted 19%, 35%, and 6% rate of reported complications, reoperations, and failures, respectively. Concomitant patellofemoral surgery (51% of patients) mostly did not lead to statistically different postoperative outcomes. Conclusion Numerous patellofemoral restoration techniques result in significant functional improvement with a low rate of failure. No definitive conclusions could be made to determine the best surgical technique since comparative studies on this topic are rare, and treatment choice should be made according to specific patient and defect characteristics

THE ORTHOPAEDIC REHABILITATION OF BALANCE: AN EXPERIMENTAL STUDY ON THE ROLE OF MENTAL IMAGERY AND EMOTIONAL VARIABLES.

Mental Imagery (i.e., processing of objects’ properties and spatial relations, including the ability of mentally rotating and manipulating objects in the space), is relevant for movement and its development, and particularly for rehabilitation of motor skills. Few studies aimed at assessing  the efficacy of imagery training used objective scores of Mental Imagery skills, preferring self-evaluations of these abilities reported by the subjects themselves. The aim of the paper was to explore the relevance of Mental Imagery, assessed by objective tests, in predicting the improvement of balance skills, after a standard rehabilitative training in orthopaedic settings; taking into account also emotional variables as anxiety and depression. A controlled study was conducted assessing the changes in balance skills after rehabilitative training. The sample was composed of 30 orthopaedic inpatients (females 66.7%, age range 47-91 years). To measure the dependent variable for pre-post assessment, B-scale from Performance-oriented mobility assessment test (POMA) was used. Independent variables were measured using Mental Imagery Test, Mini-Mental State Examination, Hamilton Depression Rating Scale and Hamilton Anxiety Rating Scales. The best predictor of improvement in balance after rehabilitation is the Mental Imagery test, followed by age and mental efficiency. Anxiety predicts negatively the improvement, while education and depression appear to influence less the rehabilitation process. In conclusion, the study demonstrates that mental imagery is relevant in helping balance rehabilitation. A training of this function could be essential for clinical practice; the trainers should assess preliminarily the subject's attitude and ability to use mental imagery, with the aim of optimizing the rehabilitative process

Rectus femoris tendon calcification: Arthroscopic excision in 6 top amateur athletes

Background: Since it was developed, hip arthroscopy has become the favored treatment for femoroacetabular impingement. Due to recent considerable improvements, the indications for this technique have been widely extended. Injuries of the rectus femoris tendon origin, after an acute phase, could result in a chronic tendinopathy with calcium hydroxyapatite crystal deposition, leading to pain and loss of function. Traditionally, this condition is addressed by local injection of anesthetic and corticosteroids or, when conservative measures fail, by open excision of the calcific lesion by an anterior approach. Purpose: To assess whether arthroscopic excision of calcification of the proximal rectus is a safe and effective treatment. Study Design: Case series; Level of evidence, 4. Methods: Outcomes were studied from 6 top amateur athletes (age range, 30-43 years; mean, 32.6 years) affected by calcification of the proximal rectus who underwent arthroscopic excision of the calcification. Patients were preoperatively assessed radiographically, and diagnosis was confirmed by a 3-dimensional computed tomography scan. To evaluate the outcome, standardized hip rating scores were used pre- and postoperatively (at 6 and 12 months): the Hip disability and Osteoarthritis Outcome Score, Oxford Hip Score, and Modified Harris Hip Score. Moreover, visual analog scales (VAS) for pain, sport activity level (SAL), and activities of daily living (ADL) were also used. Results: One year after surgery, all patients reported satisfactory outcomes, with 3 of 6 rating their return-to-sport level as high as preinjury level, and the remaining 3 with a percentage higher than 80%. Five patients ranked their ability to carry on daily activities at 100%. Statistical analysis showed significant improvement of the Oxford Hip Score, the Modified Harris Hip Score, and all 3 VAS subscales (pain, SAL, and ADL) from pre- to latest postoperative assessment (P < .05). Conclusion: Arthroscopic excision of rectus femoris tendon calcification yields satisfying results with few risks to the patient as well as rapid recovery. Clinical Relevance: The recent improvements in hip arthroscopy give the opportunity to address an increasing number of hip conditions effectively and safely, with rapid recovery for the patient. Arthroscopic excision of rectus femoris tendon calcification can be considered a feasible option, with few risks to the patient, rapid recovery, and satisfying outcomes

Why Do Osteochondral Allografts Survive?

Background: Transplantation of osteochondral allografts (OCAs) freshly preserved for 6530 days has proven to be a reliable technique for cartilage resurfacing. However, the prolonged storage of allografts comes at the expense of chondrocyte viability, which declines precipitously after 14 days under refrigeration. Despite this, radiographic data indicate that most allograft cartilage remains stable for years after implantation. The apparent durability of partially devitalized cartilage begs the question of how the extracellular matrix is maintained. Hypothesis: Compared with patients defect cartilage, replacement OCAs freshly preserved for 36 days on average contain significantly lower levels of cartilage matrix-destructive metalloproteinases, which may contribute to the long-term stability of implanted grafts. Study Design: Descriptive laboratory study. Methods: Chondrocyte density was determined by the cell yield from digested cartilage and by double-strand DNA content quantified with PicoGreen assay. Chondrocyte viability was estimated by staining enzymatically isolated chondrocytes with calcein AM and ethidium homodimer-2. Cartilage proteoglycan (PG) content was analyzed with dimethylmethylene blue assay. The in vitro 48-hour release of PG-depleting metalloproteinases including matrix metalloproteinase (MMP)-1, -3, -13, and ADAMTS-5 from cartilage was examined with Western blotting. The data were compared between diseased cartilage from patients and samples from matched grafts. The relative amount of MMP-3 to its endogenous inhibitor, tissue inhibitor of MMP-1 (TIMP-1), was also determined with Western blotting. Results: Chondrocyte density decreased linearly with allograft storage time and declined by an average of 43%. PG content decreased while the percentage of nonviable chondrocytes increased with storage time, with the former showing less linearity. However, PG content remained in the normal range and was significantly higher than that in patients defect cartilage. Correspondingly, significantly less PG-depleting metalloproteinases and a much lower MMP-3/TIMP-1 ratio were detected in allograft cartilage than in patients diseased cartilage. Conclusion: These findings indicated that, at the time of implantation, fresh-preserved OCAs contained significantly lower levels of PG-depleting metalloproteinases compared with patients defect cartilage, which might contribute to their long-term stability in vivo. Clinical Relevance: The comparatively low expression of cartilage-dissolving metalloproteinases in human OCAs freshly preserved over 30 days offers support to the long-term durability of implanted grafts. Based on study data that showed similarity in the response to inflammatory cytokines between patients cartilage and OCA cartilage, strategies that can alleviate inflammation may provide extra benefit for the survival of implanted grafts. In terms of the practice of graft preservation, agents that can keep balance between the ATP supply and demand or stabilize the cell membrane or inhibit the activation of metalloproteinases may significantly improve cell viability in fresh-preserved OCAs with a storage time longer than 5 weeks

The Role of Physical Activity as Conservative Treatment for Hip and Knee Osteoarthritis in Older People: A Systematic Review and Meta-Analysis

The aim of this systematic review and meta-analysis is to determine the role of physical activity as a conservative treatment for older people with knee or hip osteoarthritis. The effect on pain, physical function, stiffness, quality of life, and dynamic balance of Aquatic Exercise, Land-based Exercise, and Sports were compared in a specific population composed of osteoarthritic patients aged 65 or over. A systematic search using Pubmed-Medline, Google Scholar, and the Cochrane Library was carried out to select randomized clinical trials, observational studies, or case series that evaluated outcome measures after physical activity. Twenty randomized controlled trials (RCTs) and two case series were included in this review. Four trials were at low risk of bias (A), 12 at unclear risk of bias (B), and four at high risk of bias (C). Compared to controls, Aquatic Exercise, Land-based Exercise, Tai Chi, and Yoga showed a small to high effect for improving pain, physical function, quality of life, and stiffness. Active exercise and sport are effective to improve pain and physical function in elderly people with osteoarthritis. Nevertheless, further studies are required to validate the use of land-based exercise, aquatic exercise, or sport to treat the symptoms of older adults that suffer from knee and hip osteoarthritis

A prospective, randomized, comparative study of intravenous alone and combined intravenous and intraarticular administration of tranexamic acid in primary total knee replacement

Background: Studies on the use of tranexamic acid (TXA) to improve clinical outcomes after joint arthroplasty have reported contrasting results between intravenous (IV) TXA alone and combined IV and intraarticular (IA) administration. We compared the effectiveness of the 2 methods in providing higher postoperative hemoglobin (Hb) levels in patients undergoing primary total knee arthroplasty (TKA). Methods: A total of 100 TKA patients were randomly assigned to receive either IV TXA alone (group 1) or combined IV and topical IA TXA (group 2). Hb and hematocrit levels were measured before and after surgery. The amount of drained blood and transfused blood for the 2 groups was compared. Results: The Hb level was significantly higher at postoperative day 4, together with a positive, albeit not significant, trend toward less postoperative blood loss in the group that received combined IV and IA TXA. No postoperative infections or deep venous thrombosis events occurred. Conclusions: This study reinforces evidence that, as compared to IV TXA alone, combined IV and IA administration of TXA has a synergic effect, leading to higher postoperative Hb levels without influencing drug safety in TKA patients. Keywords: Postoperative blood loss, Total knee arthroplasty, Tranexamic acid, Postoperative hemoglobin, Intravenous, Intraarticula