Stem cells and discogenic back pain.

BACKGROUND: Chronic low back pain, common from the sixth decade, negatively impacts the quality of life of patients and health care systems. Recently, mesenchymal stem cells (MSCs) have been introduced in the management of degenerative discogenic pain. The present study summarizes the current knowledge on the effectiveness of MSCs in patients with discogenic back pain. SOURCES OF DATA: We performed a systematic review of the literature following the PRISMA guidelines. We searched PubMed and Google Scholar database, and identified 14 articles about management of chronic low back pain with MSCs injection therapy. We recorded information on type of stem cells employed, culture medium, clinical scores and MRI outcomes. AREAS OF AGREEMENT: We identified a total of 303 patients. Ten studies used bone marrow stem cells. In the other four studies, different stem cells were used (of adipose, umbilical, or chondrocytic origin and a pre-packaged product). The most commonly used scores were Visual Analogue Scale and Oswestry Disability Index. AREAS OF CONTROVERSY: There are few studies with many missing data. GROWING POINTS: The studies analysed demonstrate that intradiscal injections of MSCs are effective on discogenic low-back pain. This effect may result from inhibition of nociceptors, reduction of catabolism and repair of injured or degenerated tissues. AREAS TIMELY FOR DEVELOPING RESEARCH: Further research should define the most effective procedure, trying to standardize a single method.

Knee osteoarthritis, joint laxity and PROMs following conservative management versus surgical reconstruction for ACL rupture: a meta-analysis.

INTRODUCTION: Patients whose rupture of the anterior cruciate ligament (ACL) can be managed conservatively or undergo reconstruction surgery. SOURCE OF DATA: Current scientific literature published in Web of Science, PubMed and Scopus. AREAS OF AGREEMENT: Several studies published by July 2022 compare surgical and conservative management following ACL rupture. The latest evidence suggests that surgical management may expose patients to an increased risk of early-onset knee osteoarthritis (OA). AREAS OF CONTROVERSY: The state of art does not recommend a systematic ACL reconstruction to all patients who tore their ACL. After the initial trauma, surgical reconstruction may produce even greater damage to the intra-articular structures compared to conservative management. GROWING POINTS: The state of art does not recommend systematic surgical reconstruction to all patients who tore their ACL. The present study compared surgical reconstruction versus conservative management for primary ACL ruptures in terms of joint laxity, patient reported outcome measures (PROMs) and rate of osteoarthritis. AREAS TIMELY FOR DEVELOPING RESEARCH: ACL reconstruction provides significant improvement in joint laxity compared to conservative management, but is associated with a significantly greater rate of knee osteoarthritis, despite similar results at PROM assessment.

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.

No evidence in support of arthroscopic partial meniscectomy in adults with degenerative and nonobstructive meniscal symptoms: a level I evidence-based systematic review.

PURPOSE: It is unclear whether the results of arthroscopic partial meniscectomy (APM) are comparable to a structured physical therapy (PT). This systematic review investigated efficacy of APM in the management of symptomatic meniscal damages in middle aged patients. Current available randomised controlled trials (RCTs) which compared APM performed in isolation or combined with physical therapy versus sham arthroscopy or isolated physical therapy were considered in the present systematic review. METHODS: This systematic review was conducted according to the 2020 PRISMA statement. All the level I RCTs which investigated the efficacy of AMP were accessed. Studies which included elderlies with severe OA were not eligible, nor were those in which APM was combined with other surgical intervention or in patients with unstable knee or with ligaments insufficiency. The risk of bias was assessed using the software Review Manager 5.3 (The Nordic Cochrane Collaboration, Copenhagen). To rate the quality of evidence of collected outcomes, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) was used. RESULTS: Data from 17 studies (2037 patients) were collected. 48.5% (988 of 2037 patients) were women. The mean age of the patients was 52.7 ± 3.9 years, the mean BMI 27.0 ± 1.3 kg/m2. The current evidence suggests no difference in functional PROMs (quality of the evidence: high), clinical PROMs (quality of the evidence: high), pain (quality of the evidence: high), quality of life (quality of the evidence: high), physical performance measures (quality of the evidence: moderate), and OA progression (quality of the evidence: moderate). CONCLUSIONS: The benefits of APM in adults with degenerative and nonobstructive meniscal symptoms are limited. The current evidence reports similarity in the outcome between APM and PT. Further long-term RCTs are required to investigate whether APM and PT produce comparable results using validated and reliable PROMs. Moreover, future RCTs should investigate whether patients who might benefit from APM exist, clarifying proper indications and outcomes. High quality investigations are strongly required to establish the optimal PT regimes. LEVEL OF EVIDENCE: Level I.

Allografts as alternative to autografts in primary posterior cruciate ligament reconstruction: a systematic review and meta-analysis.

PURPOSE: Following posterior cruciate ligament (PCL) rupture, autografts and allografts are routinely used for its reconstruction. This study investigated the efficacy and safety of allografts for primary PCL reconstruction, comparing them to autografts in terms of patient-reported outcome measures (PROMs), functional tests, and complications. METHODS: This study followed the PRISMA guidelines. PubMed, Web of Science, Google Scholar, Embase, and Scopus were accessed in October 2022. All the clinical studies investigating the outcomes of primary PCL reconstruction using allografts, or comparing the outcomes of allografts versus autografts, were accessed. The outcomes of interests were: instrumental laxity, range of motion (ROM), Telos stress radiography, drawer test, International Knee Documentation Committee (IKDC), Tegner Activity Scale, and the Lysholm Knee Scoring Scale. Data on complications were also recorded. RESULTS: A total of 445 patients were included. The mean follow-up was 45.2 ± 23.8 months. The mean age of the patients was 30.6 ± 2.2 years. The time span between the injury and surgical intervention was 12.9 ± 10 months. Overall, 28% (125 of 445 patients) were women. Good baseline comparability was found between the two cohorts. No difference was found in terms of Lysholm Score, ROM, Tegner Scale, IKDC, arthrometer laxity, drawer test, and Telos stress radiography. No difference was found in the rates of anterior knee pain and revision. CONCLUSION: Allografts can be considered a suitable alternative to autografts for PCL reconstruction. LEVEL OF EVIDENCE: III.

Primary augmentation of percutaneous repair with flexor hallucis longus tendon for Achilles tendon ruptures reduces tendon elongation and may improve functional outcome.

PURPOSE: Achilles tendon ruptures (ATR) result in loss of strength and function of the gastrosoleus-Achilles tendon complex, probably because of gradual tendon elongation and calf muscle atrophy, even after surgical repair. Flexor hallucis longus (FHL) augmentation not only reinforces the repair and provides new blood supply to the tendon, but also protects the repair, internally splinting the repaired Achilles tendon, maintaining optimal tension. We prospectively compared the clinical outcomes of patients with acute ATR, managed with either percutaneous repair only or percutaneous repair and FHL augmentation. METHODS: Patients with acute ATR undergoing operative management were divided into two groups. Thirty patients underwent percutaneous repair under local anesthesia, and 32 patients underwent percutaneous repair augmented by FHL tendon, harvested through a 3 cm longitudinal posteromedial incision, and transferred to the calcaneus, under epidural anesthesia. All patients were treated by a single surgeon between 2015 and 2019 and were followed prospectively for 24 months. RESULTS: The percutaneous only group was younger than the augmented one (35.4 ± 8.0 vs 40.4 ± 6.6 years, p = 0.01). In the augmented group, 25 patients stayed overnight and only 5 were day cases, whereas in the percutaneous only group 4 patients stayed overnight and 28 of them were day cases (p < 0.001). The duration of the procedure was significantly longer in the augmented group (38.9 ± 5.2 vs 13.2 ± 2.2 min, p < 0.001). At 24 months after repair, the Achilles tendon resting angle (ATRA) was better in the augmented group (-0.5 ± 1.7 vs -4.0 ± 2.7, p < 0.001), as was Achilles tendon rupture score (ATRS) (91.7 ± 2.2 vs 89.9 ± 2.4, p = 0.004). Calf circumference of the injured and the non-injured leg did not differ between the groups, as did the time interval to single toe raise and the time interval to walking in tiptoes. Although plantarflexion strength of the operated leg was significantly weaker than the non-operated leg in both groups, the difference in isometric strength of the operated leg between the groups was not significant at 24 months (435 ± 37.9 vs 436 ± 39.7 N, n.s.). CONCLUSION: Percutaneous repair and FHL tendon augmentation may have a place in the management of acute Achilles tendon ruptures, reducing tendon elongation and improving functional outcome. LEVEL OF EVIDENCE: Level II.

Free tendon grafts for surgical management of chronic tears of the main body of the Achilles tendon: a systematic review.

PURPOSE: After four weeks from injury, tears of the Achilles tendon are considered chronic. Their management is challenging, and the use of a graft is suggested when the gap between proximal and distal stumps is greater than 6 cm. The present study systematically reviews the outcome of free tendon grafts in chronic ruptures of the Achilles tendon, evaluating clinical outcomes, complications and return to sport. METHODS: The present study was conducted according to the PRISMA 2020 guidelines. PubMed, Google Scholar, Embase, and Web of Science databases were accessed in February 2023. All the published clinical studies reporting clinical outcome, return to sport and complications of free tendon grafts used the treatment of chronic rupture of the midportion of the Achilles Tendon were accessed. The mean CMS (Coleman Methodology Score) of 65.7 suggested an overall good quality of the available published articles, attesting to the low risk of bias. RESULTS: Data from 22 articles (368 patients with a mean age of 47 years) were retrieved. The average time from rupture to surgery was 25.1 week. At last follow-up, the AOFAS (American Orthopaedic Foot and Ankle Surgery) and ATRS (Achilles Tendon Total Rupture Score) scores improved of 33.8 (P = 0.0004), and 45.1 points (P = 0.0001) respectively. Return to activity was reported in 105 patients, and 82 (78.1%) had no activity limitations, while 19 (18.1%) had limited recreational but not daily activity limitations, and 4 (3.8%) reported limitations in daily activities. Return to sport data was reported in six studies, and 45 of 93 (48.4%) patients returned to sport at an average of 22.6 weeks. CONCLUSION: In chronic tears of the Achilles tendon, with a gap of at least 6 cm, free tendon grafts allow predictable return to sport and acceptable recovery function. LEVEL OF EVIDENCE: Level IV.

One double-loaded suture anchor is sufficient for all-inside arthroscopic anterior talofibular ligament repair.

PURPOSE: All-inside anterior talofibular ligament (ATFL) repair using anchors is frequently used to manage chronic lateral ankle instability (CLAI) with satisfactory functional outcomes. It remains unclear whether there are differences in the functional results between the use of one or two double-loaded anchors. METHODS: This retrospective cohort study included 59 CLAI patients who underwent an all-inside arthroscopic ATFL repair procedure from 2017 to 2019. Patients were divided into two groups according to the number of anchors used. In the one-anchor group (n = 32), the ATFL was repaired with one double-loaded suture anchor. In the two-anchors group (n = 27), the ATFL was repaired with two double-loaded suture anchors. At the last follow-up time point, the Visual Analogue Scale (VAS) scores, American Orthopedic Foot and Ankle Society (AOFAS) scores, Karlsson Ankle Function Score (KAFS), Anterior Talar Translation (ATT), Active Joint Position Sense (AJPS), and the rate of return to sports in both groups were compared. RESULTS: All the patients were followed up for at least 24 months. Improvement in the functional results (VAS, AOFAS, KAFS, ATT, and AJPS) were recorded at the final follow-up time point. No significant differences were observed regarding VAS, AOFAS, KAFS, ATT, and AJPS between the two groups. CONCLUSION: In patients with CLAI undergoing all-inside arthroscopic ATFL repair, the use of either one or two double-loaded suture anchors produces comparable and predictably good functional outcomes. LEVEL OF EVIDENCE: Level III.

Muscle herniae: Conservative and surgical management. Systematic review.

BACKGROUND: Muscle herniae are often unrecognized. The primary objective of this systematic review is to evaluate the outcomes of conservative and surgical management for muscle herniae. The secondary objective is to define the most appropriate management for muscle herniae depending on aetiology and size of the fascial defect. METHODS: The PRISMA guidelines were used to organize this systematic review to assess the different management modalities and identify possible criteria useful to guide the management of muscle herniae. An electronic search of PubMed and Scopus databases was performed. RESULTS: A total of 132 patients were identified. Conservative management was carried out in 22 (16.7%) patients, and 110 (83.3%) patients underwent surgical procedures. Pain was reported in 3/22 (13.6%) patients managed conservatively. Post-surgical pain was reported in 0/5 (0%) patients treated with autologous graft repair, 1/15 (6.7%) patient with mesh repair, 2/13 (15.4%) patients with direct repair and 11/77 (14.3%) patients with fasciotomy. Return to normal activity was possible in 16/22 (72.7%) patients treated conservatively, 5/5 (100%) patients undergoing autologous graft repair, 13/15 (86.7%) with mesh repair, 62/77 (80.52%) with fasciotomy and 4/12 (33.3%) with direct repair. CONCLUSION: In congenital muscle herniae, fasciotomy should be considered the surgical choice to prevent complications. In post-traumatic muscle hernia, a small fascial defect can be treated with the direct suture repair, while mesh repair and autologous graft repair should be considered the most appropriate procedures to avoid severe complications such as compartment syndrome.

Minimally invasive fasciotomy for symptomatic tibialis anterior muscle hernia.

BACKGROUND: Symptomatic muscle herniae are an uncommon cause of chronic exercise induced leg pain. The most common site for muscle hernia is the tibialis anterior muscle. This study evaluates the outcome of a minimal incision fasciotomy in patients with a symptomatic muscle hernia of the tibialis anterior muscle, and their return to normal daily activities including sport. METHODS: The study reports mid-term results in a series of 22 consecutive patients (17 males and 5 females, median age: 22 years) with a unilateral tibialis anterior MH who had undergone minimally invasive fasciotomy between 2008 and 2019. Clinical outcomes were assessed with SF-36 and European Quality of Life-5 Dimensions scale (EQ-5D). 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: At a median follow up after surgery of 23 months, both questionnaires showed a statistically significant improvement (P < 0.005). At the latest follow up, 16 of patients (73%) had returned to pre-injury or higher levels of sport/activity. The median time to return to training and to return to sport was 7 and 11 weeks respectively. No severe complications and no recurrence of symptoms were recorded. CONCLUSION: Minimally invasive fasciotomy is effective and safe for patients suffering from muscle hernia of the tibialis anterior muscle with good results in the mid-term. LEVEL OF EVIDENCE: IV.

Greater rate of return to play and re-injury following all-inside meniscal repair compared to the inside-out technique: a systematic review.

INTRODUCTION: Inside-out and all-inside arthroscopic meniscal repairs are widely performed. However, it remains unclear which method promotes greater clinical outcomes. This study compared inside-out versus all-inside arthroscopic meniscal repair in terms of patient-reported outcome measures (PROMs), failures, return to play, and symptoms. METHODS: This systematic review was conducted in accordance with the PRISMA guidelines. Two authors independently performed the literature search by accessing the following databases: PubMed, Google Scholar, and Scopus in February 2023. All clinical studies which investigated the outcomes of all-inside and/or inside-out meniscal repair were considered. RESULTS: Data from 39 studies (1848 patients) were retrieved. The mean follow-up was 36.8 (9 to 120) months. The mean age of the patients was 25.8 ± 7.9 years. 28% (521 of 1848 patients) were women. No difference was found in PROMs: Tegner Activity Scale (P = 0.4), Lysholm score (P = 0.2), and International Knee Document Committee score (P = 0.4) among patients undergoing meniscal repair with all inside or inside-out techniques. All-inside repairs showed a greater rate of re-injury (P = 0.009) but also a greater rate of return to play at the pre-injury level (P = 0.0001). No difference was found in failures (P = 0.7), chronic pain (P = 0.05), reoperation (P = 0.1) between the two techniques. No difference was found in the rate of return to play (P = 0.5) and to daily activities (P = 0.1) between the two techniques. CONCLUSION: Arthroscopic all-inside meniscal repair may be of special interest in patients with a particular interest in a fast return to sport, while, for less demanding patients, the inside-out suture technique may be recommended. High-quality comparative trials are required to validate these results in a clinical setting. LEVEL OF EVIDENCE: Level III, systematic review.

Patient outcomes and return to play after arthroscopic rotator cuff repair in overhead athletes: a systematic review.

BACKGROUND: Rotator cuff tear injuries in overhead athletes are common and may lead to chronic pain and joint disability, impairing sport participation and leading to premature retirement. The improvement of the patient reported outcome measures (PROMs) was evaluated, as were the time and level of return to sport and the rate of complication in overhead athletes who had undergone arthroscopic rotator cuff repair. METHODS: This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the 2020 PRISMA statement. In September 2022, the following databases were accessed: Pubmed, Web of Science, Google Scholar and Embase. No time constraints were used for the search. All the clinical trials investigating arthroscopic rotator cuff repair in overhead athletes were accessed. RESULTS: Data from 20 studies were collected. The mean length of the follow-up was 40 months. All PROMs improved at last follow-up: Kerlan-Jobe Orthopaedic Clinic score (P = 0.02), visual analogue scale (P = 0.003), Constant score (P < 0.0001), University of California Los Angeles Shoulder score (P = 0.006) and American Shoulder and Elbow Surgeons' score (P < 0.0001). Elevation also improved (P = 0.004). No difference was found in external and internal rotation (P = 0.2 and P = 0.3, respectively). In total, 75.4% (522 of 692 of patients) were able to return to play within a mean of 6.4 ± 6.0 months. Of 692 patients, 433 (62.5%) were able to return to sport at pre-injury level. Fourteen out of 138 patients (10.1%) underwent a further reoperation. The overall rate of complications was 7.1% (20 of 280). CONCLUSION: Arthroscopic reconstruction of the rotator cuff is effective in improving function of the shoulder in overhead athletes, with a rate of return to sport in 75.4% of patients within an average of 6.4 months. LEVEL OF EVIDENCE: III, systematic review. TRIAL REGISTRATION: Not applicable.

Small interfering RNAs in the management of human rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) has unclear pathogenesis, but the molecules that feed its inflammatory state are known. Small interfering RNAs (siRNAs) are useful to identify molecular targets and evaluate the efficacy of specific drugs, and can themselves be used for therapeutic purposes. SOURCES OF DATA: A systematic search of different databases to March 2022 was performed to define the role of siRNAs in RA therapy. Twenty suitable studies were identified. AREAS OF AGREEMENT: Small interfering RNAs can be useful in the study of inflammatory processes in RA, and identify possible therapeutic targets and drug therapies. AREAS OF CONTROVERSY: Many genes and cytokines participate in the inflammatory process of RA and can be regulated with siRNA. However, it is difficult to determine whether the responses to siRNAs and other drugs studied in human cells in vitro are similar to the responses in vivo. GROWING POINTS: Inflammatory processes can be affected by the gene dysregulation of siRNAs on inflammatory cytokines. AREAS TIMELY FOR DEVELOPING RESEARCH: To date, it is not possible to determine whether the pharmacological response of siRNAs on cells in vitro would be similar to what takes place in vivo for the diseases studied so far.

Antiresorptive treatments for corticosteroid-induced osteoporosis: a Bayesian network meta-analysis.

INTRODUCTION: Corticosteroid-induced osteoporosis (CIO) is the most common type of secondary osteoporosis, leading to fractures, and increased morbidity and mortality. SOURCE OF DATA: Pubmed, EMBASE, Scopus and Google Scholar databases. AREAS OF AGREEMENT: Prolonged glucocorticoids administration leads to secondary osteoporosis. AREAS OF CONTROVERSY: The optimal management for CIO is controversial. GROWING POINTS: The present study compared bone mineral density, fractures and adverse events in patients undergoing treatment with risedronate, alendronate, zoledronate, denosumab or etidronate for CIO. AREAS TIMELY FOR DEVELOPING RESEARCH: For selected patients with CIO, alendronate performed better overall. These results must be interpreted within the limitations of the present study. LEVEL OF EVIDENCE: I, Bayesian network meta-analysis of randomized clinical trials.

Ligament Advanced Reinforcement System (LARS) synthetic graft for PCL reconstruction: systematic review and meta-analysis.

INTRODUCTION: Several strategies are available for posterior cruciate ligament (PCL) reconstruction. SOURCE OF DATA: Recently published literature in PubMed, Google Scholar and Embase databases. AREAS OF AGREEMENT: The Ligament Advanced Reinforcement System (LARS) is a scaffold type artificial ligament, which has been widely used for ligament reconstruction of the knee. AREAS OF CONTROVERSY: Current evidence on the reliability and feasibility of LARS for primary isolated PCL reconstruction is limited. GROWING POINTS: The primary outcome of interest of the present work was to investigate the outcomes of PCL reconstruction using the LARS. The secondary outcome of interest was to compare the LARS versus four-strand hamstring tendon (4SHT) autograft for PCL reconstruction. AREAS TIMELY FOR DEVELOPING RESEARCH: LARS for primary isolated PCL reconstruction seems to be effective and safe, with results comparable to the 4SHT autograft.

Hamstring, bone-patellar tendon-bone, quadriceps and peroneus longus tendon autografts for primary isolated posterior cruciate ligament reconstruction: a systematic review.

INTRODUCTION: Several autografts are available to reconstruct the posterior cruciate ligament (PCL). SOURCE OF DATA: Current scientific literature published in PubMed, Google scholar, Embase and Scopus. AREAS OF AGREEMENT: Hamstring, bone-patellar tendon-bone (BPTB), quadriceps and peroneus longus (PLT) are the most common tendon autografts used for primary isolated PCL reconstruction. AREAS OF CONTROVERSY: The optimal tendon source for PCL reconstruction remains nevertheless debated. Identifying the most suitable tendon autograft could assist the surgeon during primary PCL reconstruction. GROWING POINTS: The present study compared the outcome of PCL reconstruction using hamstring, BPTB, quadriceps and PLT autografts. The focus was on patient-reported outcome measures (PROMs), joint laxity, range of motion and complications. AREAS TIMELY FOR DEVELOPING RESEARCH: All autografts are viable options for PCL reconstruction, with BTB and hamstring autografts demonstrating superior PROMs. However, further clinical investigations are required to determine the ideal autograft construct.

The use of long head biceps tendon autograft for massive rotator cuff tears: a PRISMA compliant systematic review.

INTRODUCTION: Rotator cuff tears (RCT) are a common cause of shoulder pain and disability, with massive RCT accounting for 10-40% of all rotator cuff tears. SOURCES OF DATA: A systematic search of PubMed and Scopus electronic databases was performed up to August 2022, and a total of 17 scientific articles were included in the present PRISMA compliant systematic review. AREAS OF AGREEMENT: Understanding the geometric patterns in RCT is essential to achieve appropriate repositioning of the injured tendons in their anatomic location. The long head of the biceps tendon (LHBT) is usually exposed when defects of the anterolateral corner are present and can be easily used to augment rotator cuff repairs. AREAS OF CONTROVERSY: There are no definite guideline regarding the management of massive rotator cuff tears. GROWING POINTS: The use of LHBT graft is safe and effective, but technically demanding. All studies were level IV articles of medium to high quality. AREAS TIMELY FOR DEVELOPING RESEARCH: Prospective long term follow-up studies and randomized controlled trials are needed, adding imaging evaluation and appropriate clinical outcome measures at follow-up.

Insertional Calcific Tendinopathy of the Achilles Tendon and Dysmetabolic Diseases: An Epidemiological Survey.

OBJECTIVE: This study reports the incidence of insertional calcific tendinopathy (ICT) of the Achilles tendon in the general population and the percentage of symptomatic patients. The secondary aim is to ascertain whether ICT is associated with diabetes mellitus, thyroid disorders, obesity, and hypercholesterolemia. We hypothesized that metabolic diseases increase the risk of ICT of the Achilles tendon. DESIGN: Prospective observational study (level III study). SETTING: Orthopedic Outpatients Clinic and Emergency Department of Tor Vergata University Hospital, Rome, Italy. PARTICIPANTS: Four hundred thirty-three subjects who met the inclusion criteria. INTERVENTION METHODS: We collected the plain radiographs of the foot and ankle of patients who attended the hospital. Personal data were recorded [age, sex, and body mass index (BMI)], and comorbidities investigated (diabetes mellitus, hypothyroidism, hyperthyroidism, obesity, and hypercholesterolemia). Multivariate regression analyses were performed to study the predictors of the occurrence of Achilles ICT. RESULTS: A total of 101 patients (23.3%) showed radiographic evidence of ICT, and 3% (13 patients) were symptomatic. Age [odds ratio (OR) 1.05], diabetes (OR 2.95), hypercholesterolemia (OR 2.27), and hypothyroidism (OR 3.32) were significantly associated with the presence of ICT of the Achilles tendon. Independent predictors of ICT were age, diabetes, hypercholesterolemia, and hypothyroidism. A BMI >30 was associated with a higher incidence of calcifications, and patients with 2 or more comorbidities had more than 10 times higher risk to develop ICT. CONCLUSION: Insertional calcific tendinopathy of the Achilles tendon is common, but few patients are symptomatic. The incidence of ICT increases with age and is significantly higher in patients with diabetes mellitus and hypothyroidism.

Melatonin and adolescent idiopathic scoliosis: The present evidence.

INTRODUCTION: Adolescent idiopathic scoliosis (AIS) is a multifactorial condition with genetic predisposing factors, and several causes have been put forward for its aetiopathogenesis, including possible hormonal dysfunction. Melatonin seems to play significant role in AIS. METHODS: A systematic search in different database, to July 2021, was performed to define the role of melatonin in the pathophysiology of adolescent idiopathic scoliosis. Eight suitable studies were identified. RESULTS: The concentration and rhythm of melatonin secretion can play an important role by influencing the pathogenesis of adolescent idiopathic scoliosis. CONCLUSIONS: Although there are many alterations of melatonin in subjects with adolescent idiopathic scoliosis, the many variables present do not allow to establish a direct cause-effect relationship. LEVEL OF EVIDENCE: Level IV.

CD200 as a Potential New Player in Inflammation during Rotator Cuff Tendon Injury/Repair: An In Vitro Model.

Rotator cuff tendon (RCT) disease results from multifactorial mechanisms, in which inflammation plays a key role. Pro-inflammatory cytokines and tendon stem cell/progenitor cells (TSPCs) have been shown to participate in the inflammatory response. However, the underlying molecular mechanism is still not clear. In this study, flow cytometry analyses of different subpopulations of RCT-derived TSPCs demonstrate that after three days of administration, TNFα alone or in combination with IFNγ significantly decreases the percentage of CD146+CD49d+ and CD146+CD49f+ but not CD146+CD109+ TSPCs populations. In parallel, the same pro-inflammatory cytokines upregulate the expression of CD200 in the CD146+ TSPCs population. Additionally, the TNFα/IFNγ combination modulates the protein expression of STAT1, STAT3, and MMP9, but not fibromodulin. At the gene level, IRF1, CAAT (CAAT/EBPbeta), and DOK2 but not NF-κb, TGRF2 (TGFBR2), and RAS-GAP are modulated. In conclusion, although our study has several important limitations, the results highlight a new potential role of CD200 in regulating inflammation during tendon injuries. In addition, the genes analyzed here might be new potential players in the inflammatory response of TSPCs.