Hyaluronic Acid Alleviates Oxidative Stress and Apoptosis in Human Tenocytes via Caspase 3 and 7.

Rotator cuff tendinopathy (RCT) is the primary reason for shoulder surgery and its clinical management is still challenging. Hyaluronic acid (HA) has been shown to have anti-inflammatory effects in vitro and in vivo under RCT conditions, characterized by an exaggerated oxidative stress (OS). However, molecular mechanisms underlying HA-related effects are still partially disclosed. With these aims, a cell model of RCT was established by exposing primary human tenocytes to H2O2 for up to 72 h. Four different HAs by molecular weight were administered to measure nitric oxide (NO) and OS, apoptosis, and collagen 1 expression. In parallel, the well-known antioxidant ascorbic acid was administered for comparison. The present study highlights that HAs characterized by a low molecular weight are able to counteract the H2O2-induced OS by decreasing the percentage of apoptotic cells and reversing the activation of caspase 3 and 7. Likewise, NO intracellular levels are comparable to the ones of controls. In parallel, collagen 1 expression was ameliorated by HAs characterized by higher molecular weights compared to AA. These findings confirm that HA plays an antioxidant role comparable to AA depending on the molecular weight, and highlight the molecular mechanisms underlying the HA anti-apoptotic effects.

Pulsed electromagnetic fields after intramedullary nailing of tibial fractures: a case control study.

PURPOSE: To compare clinical and functional outcomes of two groups of patients undergoing reduction and nailing fixation for diaphyseal fractures of the tibia with (PEMF group) and without (control group) post-operative pulsed electromagnetic field (PEMF) application. METHODS: This is a retrospective study on 50 patients (mean age 43.3 years, 28 males and 22 females) with diaphyseal tibial fractures managed between 2017 and 2019. Twenty-five patients underwent reduction, nailing fixation, and PEMF application post-operatively (PEMF group) and 25 patients underwent nailing fixation. Radiographic imaging assessment was performed every month until fracture healing had been evident. Use of analgesics, fracture healing time, post-operative lower limb alignment, and post-operative complications were recorded. Patients were asked about return to preinjury activity. All patients were assessed at 3 months and at an average follow-up of 13 months. The VAS scale and Johner-Wruhs criteria were used for pain assessment and functional recovery, respectively. RESULTS: Comparing groups, VAS values were significantly lower in the PEMF group at three months and comparable at one year. The patients in the PEMF group took an average of 4.1 months to resume their preinjury activities, and control patients took an average of 5.3 months (P < 0.0001). According to the Johner-Wruhs score, the effective rate was 100% (25/25) in the PEMF group and 92% (23/25) in the control group (P = 0.14). CONCLUSIONS: PEMF application after intramedullary nailing is safe and reduces post-operative pain, use of analgesics, and the time of healing fracture. At one year, there is no difference in outcome measures, regardless of PEMF application.

Subacromial spacer implantation: an alternative to arthroscopic superior capsular reconstruction. A systematic review.

INTRODUCTION: This systematic review evaluated and compared the use of a subacromial spacer implantation (SSI) with arthroscopic superior capsular repair (ASCR) in the management of massive irreparable rotator cuff tears (MIRCTs) with an assessment of clinical and imaging outcomes. SOURCES OF DATA: This systematic review was carried out following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched in PubMed, Medline and Embase database literature using the keywords 'subacromial spacer', 'subacromial balloon', 'subacromial device', 'arthroscopy', 'superior capsular reconstruction', 'irreparable rotator cuff tears', 'satisfaction' and 'quality of life'. AREAS OF AGREEMENT: We included a total of 29 articles (14 about SSI and 15 about ASCR) dealing with outcomes, satisfaction and patients' quality of life. AREAS OF CONTROVERSY: The use of a subacromial spacer showed similar results in terms of patients' satisfaction and quality of life when compared with ASCR. GROWING POINTS: SSI can be implanted quickly and has a low complication rate. It can therefore be considered a good alternative for the management of MIRCTs. AREAS TIMELY FOR DEVELOPING RESEARCH: The subacromial spacer is a biodegradable implant easily implanted at arthroscopy. It can lead good clinical and imaging outcomes in MIRCTs. Similarly, ASCR can be performed with either an autograft or synthetic allograft transplantation, with satisfactory results. Long-term prospective studies are needed to compare SSI and ASCR to verify their effectiveness.

Arthroscopic superior capsular reconstruction versus latissimus dorsi transfer for irreparable rotator cuff lesions: a systematic review.

INTRODUCTION: The present systematic review compared arthroscopic superior capsular reconstruction (ASCR) and latissimus dorsi transfer (ALDT) for the management of massive irreparable rotator cuff lesions. SOURCES OF DATA: We performed a systematic review searching the literature on Medline, Cochrane and Scopus databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. AREAS OF AGREEMENT: We included a total of 20 articles, 10 on ASCR and 10 on ALDT (12 retrospective and 8 prospective studies), all published between 2013 and 2019. AREAS OF CONTROVERSY: ASCR and ALDT are technical demanding procedures. When compared to each other, they do not produce significantly different improvements in clinical outcome. GROWING POINTS: Both ASCR and ALDT are valid options for surgical management of MIRCLs. Although ALDT has shown a greater complication rate and a less improvement in acromion-humeral distance, its clinical outcomes overlap those obtained with ASCR. AREAS TIMELY FOR DEVELOPING RESEARCH: Further comparative prospective and retrospective studies with longer follow-up could confirm which surgical procedure can lead to better outcomes with a lower complication rate.

Adjuvant Therapy Reduces Fat Mass Loss during Exercise Prescription in Breast Cancer Survivors.

Improvements in cancer care over the years have increased the numbers of cancer survivors. Therefore, quality of life, fat mass management and physical activity are growing areas of interest in these people. After the surgical removal of a breast cancer, adjuvant therapy remains anyway a common strategy. The aim of this study was to assess how adjuvant therapy can affect the effectiveness of an unsupervised exercise program. Forty-two women were enrolled (52.0 ± 10.1 years). Assessments performed at baseline and after six months of exercise prescription were body composition, health-related quality of life, aerobic capacity by Six-Minute Walk Test, limbs strength by hand grip and chair test and flexibility by sit and reach. Statistical analyses were conducted by ANOVA tests and multiple regression. Improvements in body composition, physical fitness and quality of life (physical functioning, general health, social functioning and mental health items) were found. The percentage change in fat mass has been associated with adjuvant cancer therapy (intercept = -0.016; b = 8.629; p < 0.05). An unsupervised exercise prescription program improves body composition, physical fitness and health-related quality of life in breast cancer survivors. Adjuvant therapy in cancer slows down the effectiveness of an exercise program in the loss of fat mass.

Nrf2-mediated cytoprotective effect of four different hyaluronic acids by molecular weight in human tenocytes.

Non-traumatic rotator cuff tears (RCTs) are a frequent and potentially disabling injury. There is growing evidence that hyaluronic acid (HA) is effective for pain relief and to counteract inflammation in RCTs, however, its effective role in tendinopathies remains poorly studied. This study aims to disclose a possible molecular mechanism underlying the cytoprotective effects of four different HA preparations (Artrosulfur HA®, Synolis VA®, Hyalgan® and Hyalubrix®) under H2O2-induced oxidative stress. Expression-levels of Lactate dehydrogenase (LDH) released were quantified in cell supernatants, CD44 expression levels were analysed by fluorescence microscopy, the mitochondrial membrane depolarisation (TMRE assay) was measured by flow cytometry and the role of the transcription factor Nrf2 was investigated as a potential therapeutic target for RCT treatment. The modulation of extracellular matrix- (ECM) related protein expression (Integrin ß1, pro-collagen 1A2 and collagen 1A1) and autophagy occurrence (Erk 1/2 and phosphoErk 1/2 and LC3B), were all investigated by Western Blot. Results demonstrate that Artrosulfur HA, Hyalubrix and Hyalgan improve cell escape from H2O2-induced oxidative stress, decreasing cytotoxicity, reducing Nrf2 expression and enhancing catalase recovery. This study lays the grounds for further investigations insight novel pharmaceutical strategies targeting key effectors involved in the molecular cascade triggered by HA.

Transtendon repair in partial articular supraspinatus tendon tear.

Introduction: Partial thickness rotator cuff tears (PTRCTs) are common, with an incidence between 17% and 37%, and a high prevalence in throwing athletes. Different surgical procedures are suggested when partial tears involve the articular portion of the rotator cuff, including arthroscopic debridement of the tear, debridement with acromioplasty, tear completion and repair, and lately transtendon repair. This systematic review describes the transtendon repair and examines indications, contraindications, complications and clinical outcome. Source of data: We identified clinical studies listed in the Pubmed Google Scholar, CINAHL, Cochrane Central and Embase Biomedical databases in English and Italian concerning the clinical outcomes following treatment of partial articular supraspinatus tendon tear using transtendon surgical repair. Areas of agreement: Eighteen studies fulfilled our inclusion criteria. All were published between 2005 and 2016, three were retrospective, and 15 prospective. The total number of patients was 507 with a mean age of 50.8 years. Areas of controversy: Tear completion and repair and transtendon repair alone produce similar results. Growing points: Transtendon surgical repair allows to obtain good-excellent results in the treatment of partial articular supraspinatus tendon tears. Areas timely for developing research: Further studies are needed to produce clear guidelines in the treatment of partial articular supraspinatus tendon tears. Level of evidence: IV.

I.S.Mu.L.T. first-time patellar dislocation guidelines.

Primary traumatic patellar dislocation is common, particularly in young active individuals. A consensus on its management is still lacking. The present work provides easily accessible guidelines to be considered as recommendations for a good clinical practice developed through a process of systematic review of the literature and expert opinion, to improve the quality of care and rationalize the use of resources. LEVEL OF EVIDENCE: Ia.

Apoptosis and rotator cuff tears: scientific evidence from basic science to clinical findings.

Introduction: Excessive apoptosis has been hypothesized as possible cause of tendinopathy and tear in the tendons of the rotator cuff (RC). Different mechanisms and molecules play a key role in cell regulation. Biological interventions can affect the process of apoptosis to control the tendinopathy process, and may be useful to design new treatments. Source of data: We identified basic science, in vitro and in vivo preclinical and clinical studies listed in the Pubmed Google Scholar, CINAHL, Cochrane Central and Embase Biomedical databases in English, Spanish, Italian and French concerning the effects of apoptosis on RC tendons. Areas of agreement: The homeostasis between the apoptotic and inflammatory processes is dynamic and controlled by pro- and anti-apoptotic mechanisms and signals, with variable balance in different areas of the RC tendons in human specimens. Areas of controversy: Apoptosis can be identified along the whole tendon, not only in the area of the lesion. Therefore, it is not necessary to undertake wide debridement of the torn edges of the tendon when undertaking a repair. Growing points: The identification of the various factors that control apoptosis and its mechanisms can help to design new treatments and exert positive effects in the recovery from tendon tears. Areas timely for developing research: Further studies are needed to produce clear guidelines to determine how to balance the apoptosis process to reduce the failed healing response found in non-traumatic RC tears.

Preoperative Planning for ACL Revision Surgery.

The number of patients undergoing revision surgery following failure of anterior cruciate ligament (ACL) reconstruction has increased over the recent past, following the overall increased number of primary ACL reconstruction performed. Failure of primary ACL reconstruction can be attributed to technical errors, biological failures, or new traumatic injuries. Technical errors include femoral and/or tibial tunnels malposition, untreated associated ligaments insufficiencies, uncorrected lower limb malalignment, and graft fixation failures. Candidates for revision surgery should be carefully selected, and the success of ACL revision requires precise preoperative planning to obtain successful results. Preoperative planning begins with the analysis of the mechanisms of ACL reconstruction failure, and information regarding previous surgery, such as the type of graft implanted, and the position of existing hardware. Appropriate imaging is necessary to evaluate the position of the femoral and tibial tunnels, and abnormal tunnel widening. On the basis of clinical examination and imaging, surgeon can perform an ACL revision procedure in 1 or 2 stages.

Arthroscopic treatment of tibial eminence fracture: a systematic review of different fixation methods.

INTRODUCTION: Arthroscopy procedures are the gold standard for the management of tibial spine avulsion. This review evaluates and compares different arthroscopic treatment options for tibial spine fractures. SOURCE OF DATA: PubMed, Medline, Ovid, Google Scholar and Embase databases were systematically searched with no limit regarding the year of publication. AREAS OF AGREEMENT: An arthroscopic approach compared with arthrotomy reduces complications such as soft-tissue lesions, post-operative pain and length of hospitalization. AREAS OF CONTROVERSY: The use of suture techniques, compared to cannulated screw technique, avoids a second surgery for removal of the screws, but requires longer immobilization and partial weight bearing. GROWING POINTS: Clinical outcomes and radiographic results do not seem to differ in relation to the chosen method of fixation. AREAS TIMELY FOR DEVELOPING RESEARCH: Further studies are needed to produce clear guidelines to define the best choice in terms of clinical outcomes, function and complications.

Arthroscopic debridement of the ankle for mild to moderate osteoarthritis: a midterm follow-up study in former professional soccer players.

BACKGROUND: The aim of this study is to report the clinical and functional outcomes following arthroscopic management of anterior impingement, grade III-IV cartilage lesions, and mild to moderate osteoarthritis of the ankle in former soccer players. METHODS: The study included 15 former male professional soccer players with mild to moderate degenerative changes of the ankle who had undergone arthroscopic debridement and management of secondary injuries of the ankle. Preoperatively and at the last follow-up, at an average of 7.4 years, the American Orthopaedic Foot and Ankle Society (AOFAS) and the Kaikkonen scales and visual analogue scale (VAS) assessment were administered to all patients. Ankle osteoarthritis was assessed from weightbearing anteroposterior and lateral radiographs of both ankles. RESULTS AND DISCUSSION: At the last follow-up, the average AOFAS score had increased significantly from 48 (range, 29-69) to 86 (range, 63-94) (P < 0.0001), with good to excellent scores in 11 patients (74 %). The average Kaikkonen preoperative score of 43 (range, 28-70) had significantly improved to 85 (range, 61-95) (P < 0.0001), with good excellent scores in 11 patients (74 %). VAS values were also improved at the last follow-up. At the last appointment, only one (7 %) patient had abandoned altogether any sport, as he did not feel safe with his ankle and he felt too old to continue. CONCLUSIONS: Anterior ankle arthroscopy for management of mild to moderate ankle arthritis is safe, effective, and low cost and allows former athletes to safely return to ordinary daily activities and recreational sport activities.

Hyaluronic acid increases tendon derived cell viability and collagen type I expression in vitro: Comparative study of four different Hyaluronic acid preparations by molecular weight.

BACKGROUND: Hyaluronic Acid (HA) has been already approved by Food and Drug Administration (FDA) for osteoarthritis (OA), while its use in the treatment of tendinopathy is still debated. The aim of this study was to evaluate in human rotator cuff tendon derived cells the effects of four different HA on cell viability, proliferation, apoptosis and the expression of collagen type I and collagen type III. METHODS: An in vitro model was developed on human tendon derived cells from rotator cuff tears to study the effects of four different HA preparations (Ps) (sodium hyaluronate MW: 500-730 KDa - Hyalgan®, 1000 kDa Artrosulfur HA®, 1600 KDa Hyalubrix® and 2200 KDa Synolis-VA®) at various concentrations. Tendon derived cells morphology were evaluated after 0, 7 and 14 d of culture. Viability, proliferation, apoptosis were evaluated after 0, 24 and 48 h of culture. The expression and deposition of collagen type I and collagen type III were evaluated after 1, 7 and 14 d of culture. RESULTS: All HAPs tested increased viability and proliferation, in dose dependent manner. HAPs already reduce apoptosis at 24 h compared to control cells (without HAPs). Furthermore, HAPs stimulated the synthesis of collagen type I in a dose dependent fashion over 14 d, without increase in collagen type III; moreover, in the presence of Synolis-VA® the expression and deposition of collagen type I was significantly higher as compare with the other HAPs. CONCLUSIONS: HAPs enhanced viability, proliferation and expression of collagen type I in tendon derived cells.

Application of pulsed electromagnetic fields after microfractures to the knee: a mid-term study.

PURPOSE: Pulsed electromagnetic fields (PEMFs) may improve clinical outcomes following microfractures and prevent their decline over time. METHODS: Sixty-eight patients who underwent partial medial meniscectomy and microfractures to the medial femoral condyle for management of grade III-IV cartilage lesions were randomly divided into two groups using a block randomization procedure. After surgery, 34 patients underwent PEMFs application in the I-ONE group; 34 patients underwent placebo treatment in the placebo group. All patients had the same postoperative rehabilitation protocol. Sixty patients (28 in the I-ONE group, 32 in the placebo group) were assessed at an intermediate follow-up of two years and a minimum follow-up of five years after surgery. RESULTS: The two groups were homogeneous. There was a significant improvement from baseline to the last minimum follow up of two years. At two years, IKDC and Lysholm and Constant scores were significantly improved compared to baseline in both groups with no significant inter-group differences. At the last follow up (minimum five years), clinical and functional outcomes were decreased in both the groups, with significant better outcomes in the I-ONE group. At five years, the percentage of patients still active at the same level they were pre-operatively was greater in the I-ONE group (82% vs 68%, P = 0.28). At radiographic assessment, at the latest evaluation, six patients (21.4%) in the I-ONE group and nine (28.1%) in the placebo group demonstrated grade I-II degenerative changes according to Fairbank grading system (Χ = 0.36, P = 0.55). CONCLUSIONS: PEMFs application can improve the effectiveness of microfracture in the long term.

Pulsed electromagnetic fields after rotator cuff repair: a randomized, controlled study.

The current study tested the hypothesis that the use of pulsed electromagnetic fields after rotator cuff repair is effective in the short term as an adjuvant treatment to reduce local inflammation, postoperative joint swelling, and recovery time, as well as to induce pain relief. Sixty-six patients who underwent shoulder arthroscopy for repair of small to medium rotator cuff tears were randomly divided into 2 groups with a block randomization procedure. Thirty-two patients underwent arthroscopic rotator cuff repair and application of pulsed electromagnetic fields postoperatively; 34 patients underwent rotator cuff repair and placebo treatment (placebo group). All patients had the same postoperative rehabilitation protocol. At 3 months from the index procedure, visual analog scale, range of motion, and University of California at Los Angeles and Constant scores were significantly better in the pulsed electromagnetic fields group than in the placebo group (P<.05). Three patients in the pulsed electromagnetic fields group and 7 patients in the placebo group had mild to moderate capsulitis (P=.2). Severe capsulitis occurred in 1 patient in the pulsed electromagnetic fields group and 2 patients in the placebo group (P=.6). At the last follow-up (minimum, 2 years), clinical and functional outcomes were further improved in both groups, with no significant intergroup differences. Application of pulsed electromagnetic fields after rotator cuff repair is safe and reduces postoperative pain, analgesic use, and stiffness in the short term. At 2 years, no difference was seen in outcomes in patients who did or did not undergo treatment with pulsed electromagnetic fields.

I.S.Mu.L.T - Rotator Cuff Tears Guidelines.

Despite the high level achieved in the field of shoulder surgery, a global consensus on rotator cuff tears management is lacking. This work is divided into two main sessions: in the first, we set questions about hot topics involved in the rotator cuff tears, from the etiopathogenesis to the surgical treatment. In the second, we answered these questions by mentioning Evidence Based Medicine. The aim of the present work is to provide easily accessible guidelines: they could be considered as recommendations for a good clinical practice developed through a process of systematic review of the literature and expert opinion, in order to improve the quality of care and rationalize the use of resources.

Clinical evidence in the treatment of rotator cuff tears with hyaluronic acid.

PURPOSE: the aim of this quantitative review is to document potential benefit and adverse effects of hyaluronic acid (HA) injection into the shoulder with rotator cuff tears. METHODS: a systematic literature search was performed in english PubMed, Medline, Ovid, Google Scholar and Embase databases using the combined key words "hyaluronic acid", "rotator cuff tear", "hyaluronate", "shoulder", "viscosupplementation", with no limit regarding the year of publication. Articles were included if they reported data on clinical and functional outcomes, complications in series of patients who had undergone HA injection for management of rotator cuff tears. Two Authors screened the selected articles for title, abstract and full text in accordance with predefined inclusion and exclusion criteria. The papers were accurately analyzed focusing on objective rating scores reported. RESULTS: a total of 11 studies, prospective, 7 were randomized were included by full text. A total of 1102 patients were evaluated clinically after different HA injection compare with corticosteroid injection, physically therapies, saline solution injection and control groups. The use of HA in patients with rotator cuff tears improve VAS and functional score in all trials that we have analyzed. CONCLUSION: intra-articular injection with HA is effective in reducing pain and improving function in shoulder with rotator cuff tears and without severe adverse reaction. LEVEL OF EVIDENCE: Level I.

Epidemiology of the rotator cuff tears: a new incidence related to thyroid disease.

BACKGROUND: in the last years the incidence of rotator cuff tears increased and one main cause still waiting to be clarified. Receptors for thyroid hormones in rotator cuff tendons suggest possible effects on tendons metabolism and status. We undertook a retrospective, observational cohort study of 441 patients who underwent arthroscopic and mini-open repair for non traumatic degenerative rotator cuff tears. METHODS: all the patients, predominantly females (63%), were interview to assess the relationship (frequency for class age "20 yrs" and factor analysis) between lesions of the rotator cuff with the following variables: gender, thyroid disease, smoker, taking medications for diabetes, hypertension or high cholesterol; presence of associated conditions (diabetes, hypertension, hypercholesterolemia). RESULTS: thyroid disease is highly frequently (until 63% for 60<80 yrs) in females group independent to the age. Conversely, males showed a high frequency for smoker 37<62% until 80 yrs and 50% hypercholesterolemia over 80 yrs for the clinical variable studied. CONCLUSIONS: this is the first clinical report that shown a relationship between thyroid pathologies and non-traumatic rotator cuff tear as increased risk factors.