Brillouin-Raman micro-spectroscopy and machine learning techniques to classify osteoarthritic lesions in the human articular cartilage.

In this study, Brillouin and Raman micro-Spectroscopy (BRamS) and Machine Learning were used to set-up a new diagnostic tool for Osteoarthritis (OA), potentially extendible to other musculoskeletal diseases. OA is a degenerative pathology, causing the onset of chronic pain due to cartilage disruption. Despite this, it is often diagnosed late and the radiological assessment during the routine examination may fail to recognize the threshold beyond which pharmacological treatment is no longer sufficient and prosthetic replacement is required. Here, femoral head resections of OA-affected patients were analyzed by BRamS, looking for distinctive mechanical and chemical markers of the progressive degeneration degree, and the result was compared to standard assignment via histological staining. The procedure was optimized for diagnostic prediction by using a machine learning algorithm and reducing the time required for measurements, paving the way for possible future in vivo characterization of the articular surface through endoscopic probes during arthroscopy.

An Observational Prospective Clinical Study for the Evaluation of a Collagen-Hydroxyapatite Composite Scaffold in Hip Revision Surgery.

One of the greatest challenges of hip revision surgery is the need to restore extensive bone loss by creating a stable reconstruction with long-term durability. The present observational, investigator-initiated prospective study was carried out to evaluate the clinical and radiological results of the use of a commercial biomimetic collagen-hydroxyapatite composite biomaterial (RegenOss) applied in hip revision surgery. Thirty-three patients who underwent hip revision were included in this study, and 29 received up to 2 years of follow-up. The acetabulum was reconstructed using an uncemented hemispherical shell both with or without an iliac fixation stem. Functional recovery was assessed according to the Harris Hip Score (HHS) at the pre-hospitalisation check-up, and at 6-, 12-, and 24-month follow-ups. Radiological evaluation consisting of X-ray analyses (6, 12, and 24 month follow-ups) and CT scan exams (within 10 weeks post-surgery and at 12-month follow-up) were performed to evaluate the reduction in bone defect and new bone regeneration. All the patients reported a complete recovery and a considerable improvement in functional outcome assessed by the HHS, which was significantly higher at all the follow-ups than at pre-hospitalisation. Moreover, radiological assessments revealed good scaffold integration. Overall, collected data suggest that RegenOss is a valid and safe alternative to restoring acetabular bone loss in revision hip arthroplasty.

Umbilical Cord PRP vs. Autologous PRP for the Treatment of Hip Osteoarthritis.

Umbilical cord platelet-rich plasma (C-PRP) has more growth factors and anti-inflammatory molecules compared with autologous PRP (A-PRP) derived from peripheral blood. The aim of this study was to compare intra-articular C-PRP or A-PRP injections in terms of safety and clinical efficacy for the treatment of patients with hip osteoarthritis (OA). This study investigated the results of 100 patients with hip OA treated with three weekly ultrasound-guided injections of either C-PRP or A-PRP. Clinical evaluations were performed before the treatment and after two, six, and twelve months with the HHS, WOMAC, and VAS scores. No major adverse events were recorded. Overall, the improvement was limited with both treatments. Significant improvements in VAS (p = 0.031) and HHS (p = 0.011) were documented at two months for C-PRP. Patients with a low OA grade (Tonnis 1-2) showed a significantly higher HHS improvement with C-PRP than A-PRP at twelve months (p = 0.049). C-PRP injections are safe but offered only a short-term clinical improvement. The comparative analysis did not demonstrate benefits compared with A-PRP in the overall population, but the results are influenced by OA severity, with C-PRP showing more benefits when advanced OA cases were excluded. Further studies are needed to confirm the most suitable indications and potential of this biological injective approach.

Randomised, double-blind comparison of a fixed co-formulation of intra-articular polynucleotides and hyaluronic acid versus hyaluronic acid alone in the treatment of knee osteoarthritis: two-year follow-up.

BACKGROUND: A first-year interim analysis of this two-year study suggested that intra-articular injections of highly purified, natural-origin polynucleotides and hyaluronic acid (HA) as a fixed combination (PNHA) might improve knee function and joint pain more effectively than HA alone in patients with knee osteoarthritis (OA). The purpose of the second-year analysis herein described was to verify whether the first-year interim outcomes persist over the whole two-year period. METHODS: Randomised, double-blind, HA-controlled clinical trial in 100 knee OA patients (98 randomised, 79 completing the study) in a high-specialisation tertiary care setting. The hypothesised difference of efficacy between PNHA and HA for the original sample size estimate is 20%. Treatment cycle: three intra-articular knee injections of either PNHA or HA, at baseline and weekly for two weeks. EVALUATIONS: Western Ontario and McMaster Universities (WOMAC) score and Knee Society Score (KSS) as, respectively, primary and secondary endpoints, evaluated at baseline and after 2, 6, 12, and 24 months; synovial fluid levels of mediators (at baseline and the end of the treatment cycle). Adverse effects investigated at each control visit. STATISTICAL ANALYSIS: Kruskal-Wallis test for independent samples (nonparametric one-way analysis of variance) after correction of means for age, Body Mass Index and Kellgren-Lawrence grade. If significant, pairwise post-hoc Sidak multiple comparisons. RESULTS: KSS total score and KSS pain item: significant improvement in both groups, with significantly more pain improvement in patients treated with PNHA (2-point reduction) than HA (1-point reduction). Both groups experienced significant long-term reductions in WOMAC total scores: significantly stronger in PNHA-treated patients after 24 months with a steady difference of 16% favouring PNHA in WOMAC pain subscore. No clinically significant adverse events in either group. CONCLUSIONS: The outcomes of the 2-year study confirmed that a short cycle of intra-articular treatment (3 weekly double-blind injections) with polynucleotides (long-acting viscosupplementation properties, chondrocyte activation, pain-relieving properties) in fixed combination with high molecular weight hyaluronic acid is more effective in improving knee function and pain in knee OA patients than HA alone. PNHA may be elective for viscosupplementation in knee OA patients with fastidious and resistant pain and worsening disease. TRIAL REGISTRATION: NCT02417610 . Registration, 15/04/2015. ClinicalTrials.gov database link.

Commercial Bone Grafts Claimed as an Alternative to Autografts: Current Trends for Clinical Applications in Orthopaedics.

In the last twenty years, due to an increasing medical and market demand for orthopaedic implants, several grafting options have been developed. However, when alternative bone augmentation materials mimicking autografts are searched on the market, commercially available products may be grouped into three main categories: cellular bone matrices, growth factor enhanced bone grafts, and peptide enhanced xeno-hybrid bone grafts. Firstly, to obtain data for this review, the search engines Google and Bing were employed to acquire information from reports or website portfolios of important competitors in the global bone graft market. Secondly, bibliographic databases such as Medline/PubMed, Web of Science, and Scopus were also employed to analyse data from preclinical/clinical studies performed to evaluate the safety and efficacy of each product released on the market. Here, we discuss several products in terms of osteogenic/osteoinductive/osteoconductive properties, safety, efficacy, and side effects, as well as regulatory issues and costs. Although both positive and negative results were reported in clinical applications for each class of products, to date, peptide enhanced xeno-hybrid bone grafts may represent the best choice in terms of risk/benefit ratio. Nevertheless, more prospective and controlled studies are needed before approval for routine clinical use.

Bone marrow aspirate concentrate/platelet-rich fibrin augmentation accelerates healing of aseptic upper limb nonunions.

INTRODUCTION: Nonunions remain a significant burden in orthopedics, often afflicting young males of working age. Positive findings have been published using bone marrow aspirate concentrate (BMAC) and platelet-rich fibrin (PRF) for the treatment augmentation of lower limb nonunions. The aim of this study was to investigate if the treatment augmentation with BMAC and PRF can also accelerate the healing of nonunions of the upper limb. MATERIALS AND METHODS: Sixty-eight patients (45 men, 23 women) affected by 75 nonunions of long bones of the upper limb were treated and divided into two groups. The first series was treated with standard surgery alone (group A); afterwards, the second series benefited from standard surgery with the addition of BMAC and PRF applied on lyophilized bone chips. Nonunions were classified radiographically according to the Weber-Cech method and prognostically using the Calori and Moghaddam scores. All patients were radiographically assessed at 1.5, 3, 6, 12, and 24 months of follow-up. RESULTS: Baseline demographic characteristics did not present differences between groups. No differences were documented in terms of complications (two in group A and three in group B). Significant differences were instead documented in terms of healing time. The first healing signs were observed 1.5 months after surgery in 90.7% of patients in group B and 34.4% of group A (p < 0.0005). At 1.5, 3, 6, and 12 months, a higher radiographic score was found for group B (all p < 0.0005), while no difference was found at final follow-up of 24 months (90.6% of group A and 97.7% of group B achieved radiological healing). Faster healing with BMAC/PRF augmentation was confirmed for all bones, as well as for the subgroup of patients affected by atrophic nonunions (p = 0.001). CONCLUSION: This study showed the benefits of restoring both mechanical and biological aspects when addressing nonunions of the long bones of the upper limb. In particular, the association of BMAC and PRF to lyophilized bone chips was safe and able to accelerate healing time. These good results were confirmed for humerus, radius, and ulna sites, as well as for challenging atrophic nonunions of the upper limb.

Comparison of a fast track protocol and standard care after hip arthroplasty in the reduction of the length of stay and the early weight-bearing resumption: study protocol for a randomized controlled trial.

BACKGROUND: To date, hip arthroplasty is one of the most commonly performed surgical procedures, with growing worldwide demand. In recent decades, major progress made in terms of surgical technique, biomechanics, and tribology knowledge has contributed to improve the medical and functional management of the patient. This study aims to assess if the application of a fast track protocol, consisting of a preoperative educational intervention, adequate postoperative pain control, and intensive rehabilitation intervention, reduces the length of stay (LOS) and allows the early functional recovery compared to standard clinical practice for patients undergoing hip arthroplasty. METHODS: The study population consists of 90 patients with primary arthrosis of the hip with an anterior indication of hip arthroplasty. The exclusion criteria are older than 70 years, a contraindication to performing spinal anesthesia, and bone mass index (BMI) greater than 32. Participants, 45 for each group, are randomly allocated to one of two arms: fast track clinical pathway or standard care protocol. During allocation, baseline parameters such as Harris Hip Score (HHS) and Western Ontario and McMaster Universities (WOMAC) index are collected. On the third postoperative day, the functional autonomy for each patient is assessed by the Iowa Level of Assistance (ILOA) scale, and it is expected the discharge for patients in the fast track group (primary outcome). On the other hand, standard care patient discharge is expected after 5-7 days after surgery. During follow-up fixed at 6 weeks and 3, 6, and 12 months, HHS and WOMAC scores are collected for each patient (secondary outcomes). DISCUSSION: Although total hip replacement has become a widespread standardized procedure, to the authors' knowledge, only few randomized controlled trials were performed to evaluate the effectiveness of fast track pathway vs. standard care procedure in the reduction of the LOS after hip arthroplasty. It is expected that our results collected by the application of minimally invasive surgical interventions with concomitant management of perioperative pain and bleeding and early functional rehabilitation will contribute to enriching the understanding of clinical and organizational aspects linked to fast track arthroplasty. TRIAL REGISTRATION: ClinicalTrials.gov NCT03875976 . Registered on 15 March 2019-"retrospectively registered".

Core decompression with bone chips allograft in combination with fibrin platelet-rich plasma and concentrated autologous mesenchymal stromal cells, isolated from bone marrow: results for the treatment of avascular necrosis of the femoral head after 2 years minimum follow-up.

INTRODUCTION: Avascular necrosis of femoral head (AVN) is 1 of the main factors causing disability in young adults. Hip prosthesis can be considered an effective treatment of the painful symptoms but it is a major surgical intervention for this type of population. Thus, a large space should be left to therapeutic alternatives such as regenerative medicine.This retrospective study evaluates 52 AVN treated by core decompression, bone chips allograft, fibrin platelet-rich plasma (PRF) and concentrated autologous mesenchymal stromal cells (MSCs). METHODS: The AVN was diagnosed using magnetic resonance imaging (MRI) and graded according to ARCO classification: a patient was classified stage 1 (21 patients), stage 3 (26 patients), and 4 patients were classified as stage 4. We evaluated patients with functional scores (Harris Hip Score) and radiological analysis at 3, 6, 12 and 24 months after the procedure. Patients requiring prosthetic replacement of the joint were included; in these cases, follow-up was interrupted at the time of the joint replacement procedure. RESULTS: Our statistical analysis showed differences between survived and failed treatments, in terms of patient profile and ARCO radiological classification.The best result occurred in patients with ARCO grades 1 and 2, while the more advanced grades showed a high failure rate. It is interesting to note that ARCO quantification, conceived as the joint surface involved in the necrosis, has a negative influence on the outcome of the procedure. Indeed, patients affected by ARCO 3a, where necrosis involved a small portion of the femoral epiphysis and the collapse of the articular surface was limited to 2 mm, showed results similar to those obtained in patients with ARCO 1 and 2. CONCLUSIONS: In conclusion, compared with the alternative technique of decompression, our data suggest that post-collapse cases with a small area of necrosis and the use of bone grafts may show better results compared to those of the literature.

Return to sports activity with short stems or standard stems in total hip arthroplasty in patients less than 50 years old.

BACKGROUND: The aim of this study was to compare return to sport activity between a short femoral cementless stem and a conventional femoral cementless stem in total hip arthroplasty in patients 50 years old and younger. METHODS: We retrospectively reviewed 55 patients (61 hips) treated with a short femoral cementless stem and 28 patients (32 hips) treated with a conventional femoral cementless stem 50 years old and younger from December 2009 and December 2014.Their mean age was 39.86 (22-49) years and 38.68 (18-49) years, respectively. The mean follow-up was 54.1 (15-68) months and 52.7 (15-72) months, respectively. They were pre- and postoperatively evaluated by the clinical and radiological examination. RESULTS: No patients with the short stem had intraoperative fracture, but 1 patient with the conventional stem had intraoperative fracture. At final follow-up, there was no statistically significant difference in Harris Hip Score, and radiographic review level between 2 stems. No hip with the short stem had thigh pain, but 6 hips with the conventional stem had thigh pain at the final follow-up. No component was revised for aseptic loosening in either group. There were no differences observed in the return to sports activity between the 2 groups. CONCLUSIONS: Our study demonstrated that both short cementless stem and conventional cementless stem provided stable fixation and achieved a satisfactory result in patients 50 years old and younger. There is no difference in return to sports activity level after the procedure.

Infiltrative therapy as conservative treatment in hip osteoarthritis: a literature review.

Osteoarthritis (OA) is a very common disease, its prevalence increases with age and is a frequent cause of disability.Osteoarthritis is characterised by joint pain, stiffness and loss of range of motion. Overall, as many as 40% of those aged over 65 years in the community may have symptomatic OA of the knee or hip (1). OA results from a complex interaction of biomechanical and biochemical factors and is characterised by cartilage disruption and hypertrophy of bone. Intraarticular proinflammatory cytokines and proteinases in OA interfere with the synthesis of hyaluronic acid (HA), a complex glycosaminoglycan composed of repeated disaccharide units to form a linear polymer, resulting in an HA with a significantly reduced molecular weight and a reduction in synovial fluid viscoelasticity (2-3). Loss of normal characteristics of HA leads to the degradation of the articular cartilage and the disruption of the mechanical and homeostasis of the joint.Several pharmaceutical approaches, such as analgesics, non steroidal antiinflammatory drugs, COX-2 inhibitors and steroids, have been proposed (4), with the aim of reducing pain and maintaining and/or improving joint function. However, none of these options has shown to delay the progression of osteoarthritis or reverse joint damage.Infiltrative hip therapy involves injecting into the joint the drugs or medicinal substances that are used primarily to control the symptoms of the disease, such as pain and functional limitation.The aim of this review is to analyse existing infiltrative alternatives for hip osteoarthritis, and describe our experience.

Ultrasound-Guided Injection of Platelet-Rich Plasma and Hyaluronic Acid, Separately and in Combination, for Hip Osteoarthritis: A Randomized Controlled Study.

BACKGROUND: The effectiveness of intra-articular platelet-rich plasma (PRP) injections has been evaluated in knee chondroplasty and osteoarthritis (OA); however, little evidence of its efficacy in hip OA exists. PURPOSE: To compare the therapeutic efficacy of autologous PRP, hyaluronic acid (HA), or a combination of both (PRP+HA) in hip OA. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: Patients aged between 18 and 65 years who were treated with outpatient surgery and who had hip OA and pain intensity at baseline of >20 on a 100-mm visual analog scale (VAS) were recruited for this study. Exclusion criteria were extensive surgery; presence of excessive deformities; or rheumatic, infective, cardiovascular, or immune system disorders. The primary outcome measure was a change in pain intensity as assessed by the VAS at 2, 6, and 12 months after treatment. Secondary outcome measures were the Harris Hip Score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and concentration of growth factors in PRP and their correlation with clinical outcomes. Clinical outcomes were evaluated by assessors and collectors blinded to the type of treatment administered. RESULTS: A total of 111 patients were randomly assigned to 3 groups and received 3 weekly injections of either PRP (44 patients), PRP+HA (31 patients), or HA (36 patients). At all follow-ups, the PRP group had the lowest VAS scores. In particular, at 6-month follow-up, the mean VAS score was 21 (95% CI, 15-28) in the PRP group, 35 (95% CI, 26-45) in the PRP+HA group, and 44 (95% CI, 36-52) in the HA group (P < .0005 [PRP vs HA] and P = .007 [PRP vs PRP+HA]; F = 0.663). The WOMAC score of the PRP group was significantly better at 2-month follow-up (mean, 73; 95% CI, 68-78) and 6-month follow-up (mean, 72; 95% CI, 67-76) but not at 12-month follow-up. A significant, "moderate" correlation was found between interleukin-10 and variations of the VAS score (r = 0.392; P = .040). Significant improvements were achieved in reducing pain and ameliorating quality of life and functional recovery. CONCLUSION: Results indicated that intra-articular PRP injections offer a significant clinical improvement in patients with hip OA without relevant side effects. The benefit was significantly more stable up to 12 months as compared with the other tested treatments. The addition of PRP+HA did not lead to a significant improvement in pain symptoms.

Total hip arthroplasty with shortening osteotomy in congenital major hip dislocation sequelae.

We retrospectively evaluated the postoperative results of total hip arthroplasty (THA) in patients presenting with Crowe group IV dislocated hips. Overall, results were compared with regard to the type of osteotomy performed (Z or oblique) to define the correct indications for surgical technique and choice of prosthetic implant. Thirty-three subtrochanteric shortening and derotational osteotomies in primary THA were performed in 26 patients secondary to congenital hip dislocation. A Z osteotomy was performed in 14 cases and an oblique osteotomy in 19. The surgical approach was direct lateral, and surgery was aimed at restoring the anatomic hip center. Femoral and acetabular fixation was uncemented. The most used stem was the S-ROM (DePuy, Leeds, United Kingdom), and the couplings used were ceramic-ceramic (7 cases), ceramic-polyethylene (3 cases), metal-polyethylene (15 cases), and metal-metal (3 cases). Mean follow-up was 88±45 months. According to the Merle D'Aubigné score, the overall clinical results were good in 23 cases, satisfactory in 6, and fair in 4. Union of the osteotomy occurred in 97% of cases, and the mean time required for osteotomy union was 6±2 months without significant differences between Z and oblique osteotomies. At last follow-up, there was loosening of 1 cup and 1 stem, and revision was necessary. Twelve percent of patients experienced postoperative dislocation and 9% developed neuropraxia of the femoral nerve. The clinical and radiological results were similar in both groups, with a high rate of pain relief, an improvement in limb-length discrepancy, and reduced limping, leading to a smaller or no insole. Currently, the more complex Z osteotomy has been abandoned, because a modular stem prosthesis with metaphyseal sleeve allows the oblique osteotomy to be used with an easier and shorter surgical procedure.

Two stage hip revision in periprosthetic infection: results of 41 cases.

BACKGROUND: two-stage revision is considered the best treatment approach for the eradication of chronic joint infection. We report the outcome of 41 consecutive patients with infected hip prostheses, treated between 2000 and 2005, with two-stage revision using an antibiotic-loaded cement spacer. METHODS: Patients underwent a treatment protocol which included clinical and radiographic evaluation, laboratory investigations, hip aspiration, 99mTc-MDP and 99mTc-leukocyte-labeled scintigraphy and intraoperative assessment. All patients were diagnosed with a late chronic infection and classified as B-host according to the Cierny-Mader classification system. 9 patients out of 41 (22%) required a second interim treatment period, with exchange of the spacer. The proportion of methicillin-resistant Staphylococcus was similar between the one-spacer group and two-spacer group (28% vs 33%), whereas the proportion of patients with three or more risk factors was significantly higher in the two-spacer group than in the one-spacer group (28% vs 55%, respectively). RESULTS: Forty patients had final reimplantation, one patient had a resection arthroplasty. At an average follow-up of 5.3 years no recurrence of infection occurred. The average post-operative Harris hip score improved from 41 to 80. CONCLUSIONS: In the treatment of two-stage revision arthroplasty the adherence to the protocol proved to be effective for infection eradication and final reimplantation.

Effects of pulsed electromagnetic stimulation on patients undergoing hip revision prostheses: a randomized prospective double-blind study.

In this prospective, randomized, double-blind study, the effect of Pulsed Electromagnetic Fields (PEMFs) was investigated in 30 subjects undergoing hip revision using the Wagner SL stem. The subjects were treated for 6 h/day up to 90 days after revision. Study end points were assessed clinically by the functional scale of Merle D'Aubigné and instrumentally by Dual-Energy X-ray Absorptiometry (DXA) at the Gruen zones. Subject improvement according to Merle D'Aubigné scale was higher (P < 0.05) in subjects undergoing active stimulation compared to placebo. In analyzing the DXA findings, we subtracted for each area the postoperative bone mineral density (BMD) values from those measured at 90 days and we considered all results above 3.5% as responders. There were no significant differences in the average BMD values at each Gruen zone between the two groups both postoperatively and at 90 days investigation. In Gruen zones 5 and 6, corresponding to the medial cortex, we observed six responders (40%) in both areas in the control group, while in the stimulated group we observed 14 (93%) and 10 (66%) responders, respectively (both P < 0.05). This study showed that PEMF treatment aids clinical recovery and bone stock restoration.

In vitro evaluation of freeze-dried bone allografts combined with platelet rich plasma and human bone marrow stromal cells for tissue engineering.

Freeze-dried bone allograft (FDBA) might be more effective in combination with platelet rich plasma (PRP) and bone marrow stromal cells (BMSC) in accelerating bone healing. The isolation of BMSC through density gradient (pBMSC) is not extensively applicable in clinical practice, because it increases the risk of infection. Alternatively, BMSC can be concentrated by simple centrifugation (wBMSC) directly in the operating room. However, we do not know if wBMSC act in the same way as pBMSC. BMSC from 10 donors were tested whether, in the presence of a combination of FDBA and autologous PRP, the osteogenic differentiation of the cells concentrated by simple centrifugation (wBMSC + FDBA + PRP) was similar to that of pBMSC. Cell-associated alkaline phosphatase, osterix and fibroblast growth factor-2 were higher in wBMSC + FDBA + PRP. In conclusion, the combination of FDBA and PRP had a favouring effect on the differentiation towards osteoblasts and allowed BMSC concentrated by simple centrifugation to differentiate as fast as BMSC purified by density gradient.

Relationship between mortality and proximal femur fractures in the elderly.

Four hundred ninety-three patients aged > 65 years with proximal femur fractures were examined to assess the mortality rate within 1 year postoperatively. The risk factors that are most often associated with death were identified. Within the inhomogeneous group of patients, mortality was significantly higher in patients with poor mental status, with > or = 2 pre-existing diseases, a 3 or 4 American Society of Anesthetists class rating, and a lateral fracture. Regarding treatment and rehabilitation, special attention needs to be paid to these patients postoperatively.