Diagnosis and management of Achilles tendon ailments: the Scottish mist.

The diagnosis and management of Achilles tendon ailments continue to be widely discussed by the scientific community. Also, the nomenclature used to describe the tendinopathic lesion in patients changed over the last decades together with the evolution in the knowledge of the physiopathology of Achilles tendinopathy, and unfortunately, through ignorance and possibly laziness, confusion still abounds. To emerge from these foggy paths, some clarifications are still necessary. The present Editorial tries to clarify some of these issues.

Small interfering RNAs in the management of human osteoporosis.

BACKGROUND: Osteoporosis results in reduced bone mass and consequent bone fragility. Small interfering RNAs (siRNAs) can be used for therapeutic purposes, as molecular targets or as useful markers to test new therapies. SOURCES OF DATA: A systematic search of different databases to May 2023 was performed to define the role of siRNAs in osteoporosis therapy. Fourteen suitable studies were identified. AREAS OF AGREEMENT: SiRNAs may be useful in studying metabolic processes in osteoporosis and identify possible therapeutic targets for novel drug therapies. AREAS OF CONTROVERSY: The metabolic processes of osteoporosis are regulated by many genes and cytokines that can be targeted by siRNAs. However, it is not easy to predict whether the in vitro responses of the studied siRNAs and drugs are applicable in vivo. GROWING POINTS: Metabolic processes can be affected by the effect of gene dysregulation mediated by siRNAs on various growth factors. AREAS TIMELY FOR DEVELOPING RESEARCH: Despite the predictability of pharmacological response of siRNA in vitro, similar responses cannot be expected in vivo.

Synthetic graft for medial patellofemoral ligament reconstruction: a systematic review.

BACKGROUND: This systematic review investigates the role of synthetic graft for primary medial patellofemoral ligament (MPFL) reconstruction in patients with recurrent patellofemoral instability, focusing on clinical scores and the rate of complications. METHODS: This systematic review was conducted according to the PRISMA statement. The main online databases were accessed in January 2022 without time constraints. All clinical studies investigating the use of synthetic grafts for MPFL reconstruction were accessed. Revision settings were not considered. Only articles reporting data on patients with recurrent patellofemoral instability were eligible. Studies regarding congenital or acute patellofemoral dislocation were excluded. Only studies performing a follow-up longer than 24 months were considered. RESULTS: Data on 199 patients [mean age 22.3 (range 19.0-28.0) years] were collected. The mean follow-up was 60.5 (39.0-142.8) months. All the scores of interest improved at last follow-up: Kujala (+ 24.8; P = 0.0002), Lysholm (+ 42.0; P = 0.02), Tegner (+ 1.2; P = 0.03), IKDC (+ 20.9; P = 0.02). Post-operatively, a positive apprehension test was detected in 6.1% (7/115) of patients, and a sensation of instability was reported by 1.5% (3/199) of patients. The rate of re-dislocations was 2.5% (5 of 199 patients), and revision procedures were performed in less than 1% (1 of 199) of patients. CONCLUSION: Synthetic graft may be reliable and feasible for primary MPFL reconstruction in patients with recurrent patellofemoral instability.

Intensive Physical Activity Increases the Risk of Knee and Hip Arthroplasty: A Systematic Review.

PURPOSE: The present study investigated the type of sport and activity level of athletes before they underwent knee and/or hip arthroplasty for osteoarthritis (OA), and compared them with a control group of subjects who did not undergo knee and hip arthroplasty. We hypothesed athletes exposed to high physical loads during sports had the highest risk of developing OA requiring arthroplasty. MATERIALS AND METHODS: This systematic review was conducted according to the PRISMA guidelines. All the comparative clinical trials to August 2021 investigating the sport activity level between subjects who underwent arthroplasty versus those who did not undergo arthroplasty for OA were considered. RESULTS: Data from 5 studies and 3638 patients were collected. The mean age for both groups was 47.61±15.5 years, and the mean body mass index was 24.6±2.1 kg/m2 17.6% were women. The Newcastle-Ottawa scale attested good quality of the methodology of the investigations included in the present study. CONCLUSION: Intense physical exercise, implying a high cumulative number of hours of exercise which can lead to excessive joint overload, in both sexes is associated with greater likelihood of early knee and hip OA which may lead to prosthetic surgery. Moderate and recreational exposure to sport has minor degenerative effects, and is not associated with early onset OA requiring arthroplasty.

Single versus double bundle in posterior cruciate ligament (PCL) reconstruction: a meta-analysis.

Posterior cruciate ligament (PCL) reconstruction can be performed using single bundle (SB) and double bundle (DB) techniques. The present study investigated whether DB PCL reconstruction is superior to SB reconstruction in terms of patient reported outcome measures (PROMs) and joint stability. In December 2021 Embase, Google Scholar, Pubmed, Scopus databases were accessed. All clinical trials comparing SB versus DB reconstruction to address PCL insufficiency in skeletally mature patients were considered. Data from 483 procedures were retrieved. The mean follow-up was 31.0 (28.0 to 107.6) months, and the mean timespan between injury and surgery was 11.3 (6 to 37) months. The mean age of the patients was 29.3 ± 3.8 years. 85 of 483 patients (18%) were women. At a mean of 31.0 months post reconstruction, ROM (P = 0.03) was slightly greater in the SB group, while the Tegner score (P = 0.03) and the Telos stress (P = 0.04) were more favorable in the DB cohort. Similarity was found in instrumental laxity (P = 0.4) and Lysholm score (P = 0.3). The current evidence does not support the use of DB techniques for PCL reconstruction. Both methods could restore knee stability and motion with satisfactory short term patient reported outcome measures. Further high quality clinical trials are required to validate these results on a larger scale.

Autologous Bone Grafting in Trauma and Orthopaedic Surgery: An Evidence-Based Narrative Review.

Autologous bone grafting is common in trauma and orthopaedic surgery. Both the Reamer Irrigator Aspirator (RIA) and Iliac Crest Bone Graft (ICBG) aim to obtain autologous bone graft. Although the process of harvesting a bone graft is considered simple, complications may occur. This study examined morbidity and pain at the donor site, blood loss, and iatrogenic fractures, comparing RIA and ICBG. The source of the autologous bone graft, the alternative graft sites, and the storage modalities of the harvested bone marrow were also evaluated. In May 2021, PubMed, Embase, Scopus, and Google Scholar were accessed, with no time constraints. RIA may produce greater blood loss, but with less morbidity and complications, making it a potential alternative source of bone grafting.

Strategies for large bone defect reconstruction after trauma, infections or tumour excision: a comprehensive review of the literature.

Large bone defects resulting from musculoskeletal tumours, infections, or trauma are often unable to heal spontaneously. The challenge for surgeons is to avoid amputation, and provide the best functional outcomes. Allograft, vascularized fibular or iliac graft, hybrid graft, extracorporeal devitalized autograft, distraction osteogenesis, induced-membrane technique, and segmental prostheses are the most common surgical strategies to manage large bone defects. Given its optimal osteogenesis, osteoinduction, osteoconduction, and histocompatibility properties, along with the lower the risk of immunological rejection, autologous graft represents the most common used strategy for reconstruction of bone defects. However, the choice of the best surgical technique is still debated, and no consensus has been reached. The present study investigated the current reconstructive strategies for large bone defect after trauma, infections, or tumour excision, discussed advantages and disadvantages of each technique, debated available techniques and materials, and evaluated complications and new perspectives.

Fragility Fractures: Risk Factors and Management in the Elderly.

Given the progressive ageing of Western populations, the fragility fractures market has a growing socioeconomic impact. Fragility fractures are common in the elderly, negatively impacting their quality of life, limiting autonomy, increasing disability, and decreasing life expectancy. Different causes contribute to the development of a fractures in frail individuals. Among all, targeting fragile patients before the development of a fracture may represent the greatest challenge, and current diagnostic tools suffer from limitations. This study summarizes the current evidence on the management of fragility fractures, discussing risk factors, prevention, diagnosis, and actual limitations of the clinical therapeutic options, putting forward new ideas for further scientific investigation.

Association between HLA genotypes and COVID-19 susceptibility, severity and progression: a comprehensive review of the literature.

The COVID-19 pandemic has markedly impacted on cultural, political, and economic structures all over the world. Several aspects of its pathogenesis and related clinical consequences have not yet been elucidated. Infection rates, as well morbidity and mortality differed within countries. It is intriguing for scientists to understand how patient genetics may influence the outcome of the condition, to clarify which aspects could be related the clinical variability of SARS-CoV-2 disease. We reviewed the studies exploring the role of human leukocyte antigens (HLA) genotypes on individual responses to SARS-CoV-2 infection and/or progression, discussing also the contribution of the immunological patterns MHC-related. In March 2021, the main online databases were accessed. All the articles that investigated the possible association between the HLA genotypes and related polymorphisms with susceptibility, severity and progression of COVID-19 were considered. Although both genetic and environmental factors are certainly expected to influence the susceptibility to or protection of individuals, the HLA and related polymorphisms can influence susceptibility, progression and severity of SARS-CoV-2 infection. The crucial role played by HLA molecules in the immune response, especially through pathogen-derived peptide presentation, and the huge molecular variability of HLA alleles in the human populations could be responsible for the different rates of infection and the different patients following COVID-19 infection.

Arthroscopy versus mini-arthrotomy approach for matrix-induced autologous chondrocyte implantation in the knee: a systematic review.

BACKGROUND: Matrix-induced autologous chondrocyte implantation (mACI) can be performed in a full arthroscopic or mini-open fashion. A systematic review was conducted to investigate whether arthroscopy provides better surgical outcomes compared with the mini-open approach for mACI in the knee at midterm follow-up. METHODS: This systematic review was conducted following the PRISMA guidelines. The literature search was performed in May 2021. All the prospective studies reporting outcomes after mACI chondral defects of the knee were accessed. Only studies that clearly stated the surgical approach (arthroscopic or mini-open) were included. Only studies reporting a follow-up longer than 12 months were eligible. Studies reporting data from combined surgeries were not eligible, nor were those combining mACI with less committed cells (e.g., mesenchymal stem cells). RESULTS: Sixteen studies were included, and 770 patients were retrieved: 421 in the arthroscopy group, 349 in the mini-open. The mean follow-up was 44.3 (12-60) months. No difference between the two groups was found in terms of mean duration of symptoms, age, body mass index (BMI), gender, defect size (P > 0.1). No difference was found in terms of Tegner Score (P = 0.3), Lysholm Score (P = 0.2), and International Knee Documentation Committee (IKDC) Score (P = 0.1). No difference was found in the rate of failures (P = 0.2) and revisions (P = 0.06). CONCLUSION: Arthroscopy and mini-arthrotomy approaches for mACI in knee achieve similar outcomes at midterm follow-up. LEVEL OF EVIDENCE: II, systematic review of prospective studies.

Potential of biomarkers during pharmacological therapy setting for postmenopausal osteoporosis: a systematic review.

BACKGROUND: Biochemical markers of bone turnover (BTMs), such as the 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 used to manage therapy monitoring in osteoporotic patients. This systematic review analyzed the potential of these BMTs in predicting the clinical outcomes in terms of BMD, t-score, rate of fractures, and adverse events during the therapy setting in postmenopausal osteoporosis. METHODS: All randomized clinical trials (RCTs) reporting data on biomarkers for postmenopausal osteoporosis were accessed. Only articles reporting quantitative data on the level of biomarkers at baseline and on the outcomes of interest at the last follow-up were eligible. RESULTS: A total of 36,706 patients were retrieved. Greater values of bALP were associated with a greater rate of vertebral (P = 0.001) and non-vertebral fractures (P = 0.0001). Greater values of NTx at baseline were associated with a greater rate of adverse events at the last follow-up (P = 0.02). Greater values of CTx at baseline were associated with a greater rate of adverse events leading to discontinuation (P = 0.04), gastrointestinal adverse events (P = 0.0001), musculoskeletal adverse events (P = 0.04), and mortality (P = 0.04). Greater values of PINP at baseline were associated with greater rates of gastrointestinal adverse events (P = 0.02) at the last follow-up. CONCLUSION: The present analysis supports the adoption of BMTs during pharmacological therapy setting of patients suffering from osteoporosis. LEVEL OF EVIDENCE: I, systematic review of RCTs.

Biomarkers as therapy monitoring for postmenopausal osteoporosis: a systematic review.

BACKGROUND: 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. METHODS: 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. RESULTS: A total of 16 RCTs (14,446 patients) were included. The median age was 67 years, and the median BMI 25.4 kg/m2. The median vertebral BMD was 0.82, hip BMD 0.79, and femur BMD 0.64 g/cm2. 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. CONCLUSION: Our analysis supports the adoption of BTMs in therapy monitoring of osteoporotic patients. LEVEL OF EVIDENCE: Level I, systematic review of RCTs.

Isolated Arthroscopic Lateral Retinacular Release for Lateral Patellar Compression Syndrome.

INTRODUCTION: Evidence concerning the role of isolated lateral retinacular release (LRR) for lateral patellar compression syndrome (LPCS) dates back at least three decades. Appropriate indications, execution and outcomes still remain unclear and controversial. The present investigation analyzed the midterm result of isolated and arthroscopic LRR for LPCS in a cohort of patients who underwent such procedure at our institution. MATERIAL AND METHODS: Patients undergoing isolated arthroscopic LRR for LPCS were identified retrospectively from our electronic database. All procedures were performed by two experienced surgeons. Patients with bony and/or soft tissues abnormalities, patellofemoral instability, moderate to severe chondral damage were not included. Patients with previous surgeries were not included, as were those who underwent combined interventions. Clinical scores and complications were recorded. RESULTS: 31 patients were recruited in the present investigation. The mean follow-up was 86.0 ± 22.8 months. The mean age of the patients at the index operation was 34.2 ± 13.1 years. A total 55% (17 of 31) were women, and 58% (18 of 31) had involved the right knee. The mean hospitalization length was 3.5 ± 1.4 days. At a mean follow-up of 86.0 ± 22.8 months, the numeric rating scale (NRS) was 1.2 ± 0.8, the Kujala score was 91.3 ± 11.3, the Lysholm score was 93.1 ± 15.0, and the Tegner score was 5.0 ± 1.8. At the latest follow-up, 9 of 31 (29.0%) of patients experienced compilations. One patient (3.2%) had a post-operative hemarthrosis which was managed conservatively. Six patients (19.4%) reported a persistent sensation of instability, without signs of patellar dislocation or subluxation. One patient underwent an arthroscopic meniscectomy, and another patient an anterior cruciate ligament (ACL) reconstruction. CONCLUSION: isolated arthroscopic lateral retinacular release for lateral patellar compression syndrome is feasible and effective, achieving satisfying results at more than seven years following the procedure.

Arthroscopic anterior talofibular ligament reconstructin in chronic ankle instability: Two years results.

PURPOSE: In chronic lateral ankle instability, primary ligament repair is not always possible because of poor quality of the local tissues. A free autologous or allograft tendon graft or synthetic grafts are suitable alternative. We describe middle term results of arthroscopic reconstruction of the anterior talofibular ligament (ATFL) using a free autologous ipsilateral gracilis graft in patients with chronic ankle instability. METHODS: Eleven patients with chronic lateral ankle instability with imaging evidence of isolated ATFL tear underwent arthroscopic reconstruction of the ATFL using a free ipsilateral gracilis graft. Functional and subjective assessment were performed after an average of 24 months following the index procedure. RESULTS: At 24 months, all patients showed objective improvements. One patient reported transient dysaesthesiae on the dorsolateral aspect of the foot and heel. CONCLUSIONS: Arthroscopic isolated reconstruction of the ATFL with a free ipsilateral gracilis grafts is safe, allowing restoration of joint stability and low surgical morbidity. STUDY DESIGN: Case series.

Achilles tendinopathy.

BACKGROUND: Achilles Tendinopathy (AT) is essentially a failed healing response with haphazard proliferation of tenocytes, abnormalities in tenocytes with disruption of collagen fibers, and subsequent increase in non-collagenous matrix. METHODS: The diagnosis of Achilles tendinopathy is clinical, and MRI and utrasound imaging can be useful in differential diagnosis. Conservative manegement, open surgery or minimally invasive techniques are available. Injections and physical therapy are also vauable options. RESULTS: Eccentric exercises are useful tools to manage the pathology. If the condition does not ameliorate, shock wave therapy, or nitric oxide patches might be considered. Peritendinous injections or injections at the interface between the Achilles tendon and Kager's triangle could be considered if physical therapy should fail. Surgery is indicated after 6 months of non-operative management. CONCLUSIONS: The clinical diagnosis and management of AT are not straightforward. Hence, patients should understand that symptoms may recur with either conservative or surgical approaches.

Isokinetic functional outcomes of open versus percutaneous repair following Achilles tendon tears.

BACKGROUND: Rupture of the Achilles tendon (AT) is frequent in young recreational athletes. Conservative management, open surgery and percutaneous/minimally invasive approaches are all advocated, and conflicting data are available. This study compared functional and anthropometric outcomes of patients who underwent open or percutaneous repair. METHODS: A retrospective comparative study, in which 38 patients underwent open and percutaneous techniques to manage AT ruptures. For functional assessment, the calf circumference of both injured and uninjured legs was evaluated. Isokinetic testing included total plantar flexion work, peak plantar flexion torque, total dorsiflexion work peak and dorsiflexion torque. The Achilles Tendon Rupture Score (ATRS) and the American Orthopedic Foot and Ankle Score (AOFAS) were evaluated at a final minimum follow-up of 12months. RESULTS: No major complications were observed. The average time to return to sport was 9months. AOFAS and ATRS values did not differ statistically between groups. Isokinetic variables and circumference were similar in the operated and non-operated limb in both groups, and did not differ either when comparing open and percutaneous repair. CONCLUSIONS: Open and percutaneous repair of a torn Achilles tendon produced similar functional outcomes.

The Royal London Hospital Test for the clinical diagnosis of patellar tendinopathy.

PURPOSE: To ascertain whether the Royal London Hospital test is reproducible, sensitive, and specific for diagnosis of patellar tendinopathy. METHODS: Fifteen consecutive athletes with patellar tendinopathy were prospectively enrolled and compared with a control group of 15 non consecutive athletes with Achilles tendinopathy. Two testers examined separately each patient, using manual palpation and the Royal London Hospital test for diagnosis of patellar tendinopathy. High resolution real time ultrasonography was used as standard for diagnosis of tendinopathy and assessment of tendon thickness. RESULTS: The palpation test presented significantly higher sensitivity compared to the Royal London Hospital test (98 vs 88%; P=0.01); specificity was 94% for the palpation test and 98% for the Royal London Hospital test (P>0.05). Positive and negative predictive values were 94 and 98% for palpation test, 98 and 89% for the Royal London Hospital test, respectively. The two tests showed good to very good intra-tester and inter-tester agreement. At ultrasonography, pathological patellar tendons were significantly thicker compared to controlateral healthy tendon (P<0.001). CONCLUSIONS: In symptomatic patients with patellar tendinopathy, the Royal London Hospital test showed lower sensitivity and higher specificity than manual palpation. Both tests should be performed for a correct clinical diagnosis of patellar tendinopathy. Imaging assessment should be performed as a confirmatory test. LEVEL OF EVIDENCE: III.

Cabozantinib targets bone microenvironment modulating human osteoclast and osteoblast functions.

Cabozantinib, a c-MET and vascular endothelial growth factor receptor 2 inhibitor, demonstrated to prolong progression free survival and improve skeletal disease-related endpoints in castration-resistant prostate cancer and in metastatic renal carcinoma. Our purpose is to investigate the direct effect of cabozantinib on bone microenvironment using a total human model of primary osteoclasts and osteoblasts.Osteoclasts were differentiated from monocytes isolated from healthy donors; osteoblasts were derived from human mesenchymal stem cells obtained from bone fragments of orthopedic surgery patients. Osteoclast activity was evaluated by tartrate resistant acid phosphatase (TRAP) staining and bone resorption assays and osteoblast differentiation was detected by alkaline phosphatase and alizarin red staining.Our results show that non-cytotoxic doses of cabozantinib significantly inhibit osteoclast differentiation (p=0.0145) and bone resorption activity (p=0.0252). Moreover, cabozantinib down-modulates the expression of osteoclast marker genes, TRAP (p=0.006), CATHEPSIN K (p=0.004) and Receptor Activator of Nuclear Factor k B (RANK) (p=0.001). Cabozantinib treatment has no effect on osteoblast viability or differentiation, but increases osteoprotegerin mRNA (p=0.015) and protein levels (p=0.004) and down-modulates Receptor Activator of Nuclear Factor k B Ligand (RANKL) at both mRNA (p<0.001) and protein levels (p=0.043). Direct cell-to-cell contact between cabozantinib pre-treated osteoblasts and untreated osteoclasts confirmed the indirect anti-resorptive effect of cabozantinib.We demonstrate that cabozantinib inhibits osteoclast functions "directly" and "indirectly" reducing the RANKL/osteoprotegerin ratio in osteoblasts.

The Management of Extensor Mechanism Disruption After Total Knee Arthroplasty: A Systematic Review.

We performed a literature search on PubMed, Web of Science, Science Direct/Scopus, Google Scholar, and Google to evaluate results of several techniques to manage disruption of the extensor mechanism after total knee arthroplasty. Different methods to manage extensor mechanism disruption are available at present, with no level I studies informing surgeons in an evidence-based fashion. Primary repair is not indicated. Allograft reconstruction could be effective, providing that appropriate surgical technique and allograft tensioning are implemented.

Single minimal incision fasciotomy for chronic exertional compartment syndrome of the lower leg.

BACKGROUND: Chronic exertional compartment syndrome (CECS) involves a painful increase in compartment pressure caused by exercise and relieved by rest, common in athletes. The most common site for CECS in the lower limbs is the anterior leg compartment. The aim of this study is to evaluate the outcomes of a single minimal incision fasciotomy in athletes and their capability to return to high level sport activity. METHODS: The study reports mid-term results in a series of 18 consecutive athletes with chronic exertional compartment syndrome of the leg who had undergone minimally invasive fasciotomy. Between 2000 and 2007, we prospectively enrolled 18 consecutive athletes (12 males and six females, median age 27 years) with unilateral or bilateral chronic exertional compartment syndrome undergoing unilateral or bilateral minimally invasive fasciotomy. Clinical outcomes were assessed with Short-Form Health Survey-36 (SF-36) and European Quality of Life-5 Dimension (EQ-5D) scale. The ability to participate in sport before and after surgery and the time to return to training (RTT) and to sport (RTS) were recorded. RESULTS: The median follow-up after surgery was 36 months. Both questionnaires showed a statistically significant improvement (P < 0.0001) after surgery. At the time of the latest follow-up, 17 of 18 patients (94 %) had returned to pre-injury or higher levels of sport. Only one patient (6 %) returned to sport at lower levels than those of pre-injury status. The median time to return to training and to return to sport was 8 and 13 weeks, respectively. No severe complications or recurrence of the symptoms were recorded. CONCLUSIONS: Minimally invasive fasciotomy is effective and safe for athletes suffering from unilateral or bilateral chronic exertional compartment syndrome of the anterior and lateral compartments of the leg with good results in the mid-term.