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.

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.

Cephalomedullary nailing for reverse oblique intertrochanteric fractures 31A3 (AO/OTA).

Introduction: Reverse oblique intertrochanteric fractures are classified by the Orthopaedic Trauma Association [OTA]/[AO] as 31A3, and account for up to one-third of all hip fractures, and 2-23% of all trochanteric fractures. The treatment of choice of those fractures is intramedullary nailing as it decreases soft tissue damage and permits early weight bearing. Material and methods: A retrospective comparative study was conducted on patients surgically treated for 31A3 fractures from October 2018 to January 2022 in a high-volume regional referral centre. All the patients had been treated with intramedullary nailing. Results: The selected group included 11 males (16%) and 59 females (84%), with a mean age of 83.6 years (range 61 to 96 years). A Trigen Intertan Nail was the most frequent choice of intramedullary nailing in 33 patients (47%), an Elos Long nail was chosen in 19 cases (27%), while a ZNN nail was used in 18 patients (26%). The mean time between admission and surgery was 2.5 days, with a mean Hb value of 10.5 g/dl reported preoperatively. Conclusion: Patients treated with an Intertan nail reported the lowest TAD, CALTAD, and TALCALTAD mean radiographic values, and the lowest rate of Hb loss and blood transfusions.

Achilles Tendon Rupture and Dysmetabolic Diseases: A Multicentric, Epidemiologic Study.

Introduction: Achilles tendon ruptures are common. Metabolic disorders, such as diabetes mellitus, hypercholesterolemia, thyroid disorders, and obesity, impair tendons health, leading to Achilles tendinopathy and likely predisposing patients to Achilles tendon ruptures. Materials and methods: Patients who visited the Orthopedic Outpatient Clinics and the Accident and Emergency Departments of five different hospitals in Italy were recruited. Through telephone interviews, we administered a questionnaire to all the patients who had undergone surgical ATR repair, evaluating their past medical history, sport- and work-related activities, drug use, and post-operative rehabilitation outcomes. Results: "Return to work activities/sport" was negatively predicted by the presence of a metabolic disorder (ß = -0.451; OR = 0.637) and 'open' surgery technique (ß = -0.389; OR = 0.678). "Medical complications" were significantly predicted by metabolic disorders (ß = 0.600 (0.198); OR = 1.822) and was negatively related to 'mini-invasive' surgery (i.e., not 'open' nor 'percutaneous') (ß = -0.621; OR = 0.537). "Immediate weightbearing" and "immediate walking without assistance" were negatively predicted by 'open' technique (ß = -0.691; OR = 0.501 and ß = -0.359 (0.174; OR = 0.698)). Conclusions: Metabolic conditions can strongly affect post-operative outcomes following surgical repair of acute Achilles tendon tears.

A comprehensive update on the pharmacological management of heterotopic ossification following hip arthroplasty: a level I evidenced based expert opinion.

INTRODUCTION: Heterotopic ossification (HO) of the hip joint may happen accompanying skeletal muscle trauma or surgical procedures. The pharmacological prophylaxis of heterotopic ossification (HO) following total hip arthroplasty (THA) is debated. AREAS COVERED: This expert opinion aims to systematically investigate the efficacy of current pharmacological options as prophylaxis for HO following THA. EXPERT OPINION: The current evidence identified celecoxib, naproxen, and diclofenac as best option for the prevention of HO in patients who undergo primary THA. The most appropriate pharmacotherapy for the prevention of HO is still debated and should be customized according to patients' comorbidities and medical history. For patients with cardiovascular comorbidities, naproxen, or diclofenac should be considered along with proton pump inhibitors to prevent gastrointestinal complications. For patients with history of gastrointestinal disease, celecoxib can be recommended. These conclusions must be considered within the limitations of the present investigation. Between studies, heterogeneities in the administration protocols were evident. In some RCTs, the length of the follow-up was shorter than 12 months. The current clinical practice would benefit of high-quality recommendations and the development of the shared official guidelines.

The Impact of Hyaluronic Acid on Tendon Physiology and Its Clinical Application in Tendinopathies.

The physical-chemical, structural, hydrodynamic, and biological properties of hyaluronic acid within tendons are still poorly investigated. Medical history and clinical applications of hyaluronic acid for tendinopathies are still debated. In general, the properties of hyaluronic acid depend on several factors including molecular weight. Several preclinical and clinical experiences show a good efficacy and safety profile of hyaluronic acid, despite the absence of consensus in the literature regarding the classification according to molecular weight. In in vitro and preclinical studies, hyaluronic acid has shown physical-chemical properties, such as biocompatibility, mucoadhesivity, hygroscopicity, and viscoelasticity, useful to contribute to tendon healing. Additionally, in clinical studies, hyaluronic acid has been used with promising results in different tendinopathies. In this narrative review, findings encourage the clinical application of HA in tendinopathies such as rotator cuff, epicondylitis, Achilles, and patellar tendinopathy.

Anhedonia and functional dyspepsia in obese patients: Relationship with binge eating behaviour.

BACKGROUND: Obese patients (Ob) with a binge eating disorders (BED) behavior pattern have a higher prevalence of postprandial distress syndrome (PDS) compared to Ob without a BED behavior pattern, while an increase of PDS has been described in Ob after sleeve gastrectomy (SG). Hedonic response to a meal is dissociable from satiation in healthy subjects. Anhedonia is the lowered ability to experience pleasure. There are no studies investigating the presence of anhedonia in Ob with and without SG and its relationship to PDS symptoms. AIM: To assess the relationship among anhedonia, BED and upper gastrointestinal symptoms in two group of morbidly Ob with and without SG. METHODS: Eighty-one Ob without SG, 45 Ob with SG and 55 healthy controls (HC) were studied. All subjects fulfilled the binge eating scale (BES) to investigate BED, the validated 14 items Snaith-Hamilton pleasure scale (SHAPS) to assess Anhedonia as well as the Beck Depression Inventory-II (BDI II) and State Trait Anxiety Inventory (STAI) questionnaires to screen for depression and anxiety. All patients underwent a standardized questionnaire investigating the intensity-frequency scores (0-6) of upper gastrointestinal symptoms and were diagnosed for the presence of functional dyspepsia (FD) and its subtypes according to ROME IV criteria. RESULTS: Ob without SG who were positive for BED had a 4.7 higher risk of FD compared to Ob without SG who were negative for BED (OR: 4.7; 95.0%CI 1.23-18.24; P = 0.02). STAI-Y2 scores were significantly higher in Ob without SG positive for BED (42.2 ± 1.5 vs Ob negative for BED: 39.6 ± 1 .0, P = 0.04), while SHAPS scores and BDI II did not differ in the two groups (1.16 ± 1.30 vs 0.89 ± 1.02, P = 0.49). A lower prevalence of BED (BES > 17: 11.4% vs 40.7%, P = 0.001) and BDI-II (6.8 ± 1.2 vs 13.8 ± 1.9, P = 0.005) was reported in Ob with SG than Ob without SG, on the contrary total mean scores of STAI-Y1 and STAI-Y2 were significantly higher in Ob with SG than Ob without SG. Thirty-five percent of Ob with SG fulfilled the diagnosis of FD. SHAPS mean scores and the prevalence of anhedonia did not differ among the two groups (18.2 vs 8.1%, P = 0.2). Fifty-four percent of Ob with SG achieved surgical success excess weight loss > 50%. Excess weight loss was negatively related to SHAPS total mean scores [adjusted B: -7. 099 (95%CI: -13.91 to -0.29), P = 0.04]. CONCLUSION: Ob without SG showed a higher prevalence of PDS, mood disorders and anxiety when positive for BE behavior compared to those negative for BE behavior, whereas no differences were found in SHAPS score. Ob with SG showed a higher prevalence of PDS compared to Ob without SG. Concerning psychological aspect, BED and depression are less frequent in the Ob with SG, while both state and trait anxiety are significantly higher. Moreover, the more an Ob with SG is anhedonic, less surgical success was achieved.