Sagittal Balance Parameters and Proximal Junctional Kyphosis in Adolescent Idiopathic Scoliosis.

Background: To review and evaluate multiple preoperative and postoperative sagittal parameters and their association with the risk of developing proximal junctional kyphosis (PJK) in patients with adolescent idiopathic scoliosis (AIS) who undergo correction surgery. Methods: A systematic search was performed in December 2022 in PubMed, Embase and the Cochrane Library to retrieve all the studies relevant to our research. After the study selection and data extraction following PRISMA guidelines, RevMan 5.3 was used for statistical analysis. All the analyzed factors were evaluated by using odds ratios and weighted mean differences with 95% confidence intervals. Moreover, the meta-analysis of proportions via MedCalc was used for analyzing quantitative data from the studies. Results: A total of 22 studies were included in our meta-analysis. All the available values of sagittal parameters were evaluated. Among all the potential risk factors, higher preoperative thoracic kyphosis (Test for overall effect Z = 11.79, p < 0.00001), higher preoperative sagittal vertical axis (SVA) (test for overall effect Z = 11.19, p < 0.00001), greater thoracic kyphosis change post-op. compared to pre-op. (test for overall effect Z = 6.02, p < 0.00001), increased postoperative lumbar lordosis (test for overall effect Z = 3.65, p = 0.0003), higher post-op. SVA (test for overall effect Z = 24.93, p < 0.00001) and a larger pelvic incidence/lumbar lordosis (PI/LL) mismatch (test for overall effect Z = 20.50, p < 0.00001) were found to be the risk factors for PJK after AIS surgery. Moreover, a decreased rod contour angle (RCA) (test for overall effect Z = 3.79, p < 0.0002) and higher proximal junctional angle-rod contour angle (PJA-RCA) (test for overall effect Z = 39.18, p < 0.00001) play a significant role in the risk of developing PJK after AIS correction. Conclusions: Sagittal balance is of great importance when considering the surgical correction of AIS. Many factors in our meta-analysis were found to increase the incidence for PJK such as higher preoperative thoracic kyphosis and pre-op. SVA. Furthermore, increased thoracic kyphosis change, increased post-operative lumbar lordosis, SVA and PI/LL mismatch are also factors that influence the possibility of post-op. PJK. Lastly, RCA and PJA-RCA are two important factors that need attention during AIS, as over-contouring of the rod could lead to PJK in AIS patients.

Assessing the Effects and Challenges of Total Hip Arthroplasty before Pregnancy and Childbirth: A Systematic Review.

Total hip arthroplasty is indubitably one of the most performed operations worldwide. On the other hand, especially in the western world, the average age that women get pregnant has raised confoundedly. Consequently, a steadily increasing number of women become pregnant after they had hip arthroplasty surgery, with copious potential implications. The amount of knowledge on this particular field is considered inadequate in the existing literature. This paper aims to augment clinicians understanding surrounding this topic. A systematic literature review was conducted in accordance with the PRISMA guidelines. Papers from various computerized databases were scrutinized. Article selection was carried out by three authors independently employing specific pre-determined inclusion and exclusion criteria, while disagreements were elucidated with the contribution of other authors. A patently limited number of research articles were detected from our rigorous literature review, with only 12 papers meeting the inclusion criteria. The vast majority of studies were small-scale and examined confined population groups. Most studies had been performed in Finland, utilizing data from nationwide registries. Women with previous history of total hip arthroplasty feature increased rates of c-section delivery, although vaginal labor can be attempted with certain precautions. Hip implants' survival does not appear to be affected from gestation, which is predominately well-tolerated from these women. Metal ion circulation in mothers' blood has not been proven to trigger substantial complications concerning either mothers or offspring. It can be considered safe for women with such medical history to get pregnant; however, further multinational studies and pertinent research on this field are vital to attain more solid inferences.

Current Progress and Future Perspectives in Contact and Releasing-Type Antimicrobial Coatings of Orthopaedic Implants: A Systematic Review Analysis Emanated from In Vitro and In Vivo Models.

Background: Despite the expanding use of orthopedic devices and the application of strict pre- and postoperative protocols, the elimination of postoperative implant-related infections remains a challenge. Objectives: To identify and assess the in vitro and in vivo properties of antimicrobial-, silver- and iodine-based implants, as well as to present novel approaches to surface modifications of orthopedic implants. Methods: A systematic computer-based review on the development of these implants, on PubMed and Web of Science databases, was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results: Overall, 31 in vitro and 40 in vivo entries were evaluated. Regarding the in vitro studies, antimicrobial-based coatings were assessed in 12 entries, silver-based coatings in 10, iodine-based in 1, and novel-applied coating technologies in 8 entries. Regarding the in vivo studies, antimicrobial coatings were evaluated in 23 entries, silver-coated implants in 12, and iodine-coated in 1 entry, respectively. The application of novel coatings was studied in the rest of the cases (4). Antimicrobial efficacy was examined using different bacterial strains, and osseointegration ability and biocompatibility were examined in eukaryotic cells and different animal models, including rats, rabbits, and sheep. Conclusions: Assessment of both in vivo and in vitro studies revealed a wide antimicrobial spectrum of the coated implants, related to reduced bacterial growth, inhibition of biofilm formation, and unaffected or enhanced osseointegration, emphasizing the importance of the application of surface modification techniques as an alternative for the treatment of orthopedic implant infections in the clinical settings.

Are the Spinal Changes in the Course of Scoliogeny Primary but Secondary?

In this opinion article, there is an analysis and discussion regarding the effects of growth on the spinal and rib cage deformities, the role of the rib cage in scoliogeny, the lateral spinal profile in adolescent idiopathic scoliosis (AIS), the genetics and epigenetics of AIS, and the interesting and novel field investigating the sleep impact at nighttime on AIS in relation to the sequence of the scoliogenetic changes in scoliotics. The expressed opinions are mainly based on the published peer-reviewed research of the author and his team of co-authors. Based on the analysis noted above, it can be postulated that the vertebral growth changes in the spine during initial idiopathic scoliosis (IS) development are not primary-intrinsic but secondary changes. The primary cause starting the deformity is not located within the vertebral bodies. Instead, the deformations seen in the vertebral bodies are the secondary effects of asymmetrical loads exerted upon them, due to muscular loads, growth, and gravity.

A Comprehensive Review of COVID-19-Infection- and Steroid-Treatment-Associated Bone Avascular Necrosis: A Multi-Study Analysis.

BACKGROUND: The COVID-19 pandemic has presented numerous challenges to the global healthcare system and emerging evidence suggests a potential link between COVID-19 treatment, specifically steroid therapy, and the development of avascular necrosis (AVN) of the hip. This review aims to provide a comprehensive overview of recent studies and case reports investigating the relationship between COVID-19, corticosteroid therapy, and the development of AVN. Understanding the nuances of AVN in the context of COVID-19 is crucial for healthcare professionals to navigate treatment decisions and mitigate potential complications. MATERIALS AND METHODS: The Preferred Reporting Items for Systematic Reviews and a Meta-Analysis (PRISMA) were used in the systematic review until 1 September 2023. The full texts of the remaining twenty-three (n = 23) articles were independently reviewed by the authors of this review. CONCLUSIONS: The association between steroid therapy for COVID-19 and the development of hip AVN is a noteworthy concern even though no relationship is evident between the duration of treatment, cumulative dosage of medication, maximum daily dosage received, and presence of AVN. Further research with larger cohorts and long-term follow up is needed to better understand the causative relationship and optimal management strategies for hip AVN in the context of COVID-19 and steroid therapy.

The Role of Interleukin-10 in the Pathogenesis and Treatment of a Spinal Cord Injury.

Spinal cord injury (SCI) is a devastating condition that often leads to severe and permanent neurological deficits. The complex pathophysiology of an SCI involves a cascade of events, including inflammation, oxidative stress, and secondary injury processes. Among the myriad of molecular players involved, interleukin-10 (IL-10) emerges as a key regulator with the potential to modulate both the inflammatory response and promote neuroprotection. This comprehensive review delves into the intricate interplay of IL-10 in the pathogenesis of an SCI and explores its therapeutic implications in the quest for effective treatments. IL-10 has been found to regulate inflammation, oxidative stress, neuronal apoptosis, and glial scars after an SCI. Its neuroprotective properties have been evaluated in a plethora of animal studies. IL-10 administration, either isolated or in combination with other molecules or biomaterials, has shown neuroprotective effects through a reduction in inflammation, the promotion of tissue repair and regeneration, the modulation of glial scar formation, and improved functional outcomes. In conclusion, IL-10 emerges as a pivotal player in the pathogenesis and treatment of SCIs. Its multifaceted role in modulating inflammation, oxidative stress, neuronal apoptosis, glial scars, and neuroprotection positions IL-10 as a promising therapeutic target. The ongoing research exploring various strategies for harnessing the potential of IL-10 offers hope for the development of effective treatments that could significantly improve outcomes for individuals suffering from spinal cord injuries. As our understanding of IL-10's intricacies deepens, it opens new avenues for innovative and targeted therapeutic interventions, bringing us closer to the goal of alleviating the profound impact of SCIs on patients' lives.

The 'Holy Grail' of shoulder dislocations: a systematic review on traumatic bilateral luxatio erecta; is it in reality a once-in-a-lifetime experience for an orthopaedic surgeon?

INTRODUCTION: Even though shoulder dislocation is thought to be the most common dislocation treated in the Emergency Department, inferior ones, known as Luxatio Erecta, comprise only 0.5% of them. Taking into consideration the rareness of unilateral Luxatio Erecta, bilateral cases should be even fewer. The purpose of this paper is to identify the reported number of cases of Traumatic Bilateral Luxatio Erecta in the literature over the last 100 years and to summarize the mechanism of injury, the initial management, and the complications of these patients. MATERIALS AND METHODS: We performed a systematic review of the literature regarding Traumatic Bilateral Luxatio Erecta. All articles published until 31st of December 2022 in PubMed and Google Scholar databases were searched using the terms "luxatio erecta", 'inferior dislocation", and "bilateral". RESULTS: Eighty-two articles were retrieved from PubMed and Google Scholar search. Forty-four of them were initially included in our review. Six additional articles meeting the inclusion criteria were found from cross-references. CONCLUSION: The presence of this injury is extremely rare with only 51 cases in the literature. The incidence of concomitant injuries and complications seems to be extremely high and neurological deficits were detected on 42.8% of patients with Bilateral Luxatio Erecta. To our knowledge, this is the first systematic review of the literature regarding Traumatic Bilateral Luxatio Erecta that includes articles not only in English, a fact that provides more reliability on the estimation of the real number of cases of this rare injury compared to any other review on this subject to date.

Bone mineral density, vitamin D and osseous metabolism indices in neurofibromatosis type 1: A systematic review and meta-analysis.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a genetic autosomal neurocutaneous syndrome correlated with skeletal dysplasia and defects in the osseous microarchitecture. The physiological mechanism for the development of NF1-related bone abnormal turnover is still unclear. OBJECTIVES: A meta-analysis was performed to investigate the effects of NF1 on bone mineral density (BMD) and osseous metabolic indices in order to provide clinical evidence for the pathogenesis of the associated skeletal deformities. METHODS: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed/Medline and Web of Science databases from the date of inception of each database through to 10 September 2023. Specific inclusion and exclusion criteria were applied for the identification of studies examining the effects of NF1 on bone strength and metabolism. The Newcastle-Ottawa and Jadad scales were applied to assess the quality of the included studies. RevMan 5.3 software was used for the analysis of the data, and MedCalc was applied to examine publication bias. RESULTS: Overall, 13 studies met the inclusion criteria comprised of 5 cross-sectional, 6 case-control and 2 retrospective studies. 703 patients and 973 healthy subjects formed the NF1 and control group, respectively. The results of the meta-analysis displayed that lumbar (SMD = -3.85, 95%CI = -7.53 to -0.18, Z = 2.05, p = 0.04) and femoral (SMD = -4.78, 95%CI = -8.86 to -0.69, Z = 2.29, p = 0.02) BMD was reduced in the NF1 group. Both in children and adults the serum levels of 25 hydroxyvitamin D3 were also decreased in NF1 group, but without any statistical significance (SMD = -0.62, 95%CI = -1.34 to -0.11, Z = 1.66, p = 0.10). Serum Parathyroid hormone (PTH) (SMD = 0.73, 95%CI = 0.31 to 1.15, Z = 3.43, p = 0.0006) and C-telopeptide of type 1 collagen (CTX) (SMD = 0.82, 95%CI = 0.33 to 1.30, Z = 3.29, p = 0.001) were elevated in NF1 patients, while serum calcium (SMD = -0.10, 95%CI = -0.74 to 0.53, Z = 0.32, p = 0.75) phosphorous (SMD = 0.33, 95%CI = -0.38 to 1.05, Z = 0.92, p = 0.36), alkaline phosphatase (ALP) (SMD = -0.36, 95%CI = -0.77 to 0.05, Z = 1.71, p = 0.09), osteocalcin (SMD = 1.81, 95%CI = -0.37 to -3.98, Z = 1.63, p = 0.10) and bone formation markers (SMD = 0.28, 95%CI = -0.37 to -0.94, Z = 0.85, p = 0.39) were not. CONCLUSION: NF1 is associated with decreased BMD at the lumbar spine and femur. Taking into account that the serum levels of PTH, CTX were increased whereas the concentrations of vitamin D, calcium, phosphorous, ALP, osteocalcin and bone formation markers were not altered significantly in the NF1 patients compared with the healthy subjects, a vitamin D independent dysregulated bone cellular activity could be considered. STUDY REGISTRATION: Registered on PROSPERO (CRD42023424751).

Treatment and Rehabilitation Approaches for Stress Fractures in Long-Distance Runners: A Literature Review.

Stress fractures (SFs) result from repetitive mechanical stress on bones, leading to an imbalance in osseous tissue adaptation and resulting in cortical fractures. The majority of SFs occur in the lower limb due to excessive mechanical loads. Long-distance runners are highly susceptible to SFs, especially when there is a significant increase in the load or intensity of their activity. Various intrinsic and extrinsic factors contribute to the development of SFs. Common SF locations in long-distance runners include the tibial shaft, femur, metatarsal, and pelvic region. Diagnosis may be delayed due to mild symptoms and unremarkable imaging tests. However, the chronicity and recurrence of misdiagnosed SFs may lead to debilitating complete fractures that are even more challenging to treat. In this review, we present data revealed from published case reports and case series studies obtained through PubMed and Embase databases focusing on the management of SFs in long-distance runners and correlate treatment outcomes with rehabilitation and return to high-level athletic performance.

Impact of COVID-19 Pandemic on Fragility Fractures of the Hip: An Interrupted Time-Series Analysis of the Lockdown Periods in Western Greece and Review of the Literature.

Since December 2019, the COVID-19 pandemic has had a significant impact on healthcare systems worldwide, prompting policymakers to implement measures of isolation and eventually adopt strict national lockdowns, which affected mobility, healthcare-seeking behavior, and services, in an unprecedented manner. This study aimed to analyze the effects of these lockdowns on hip-fracture epidemiology and care services, compared to nonpandemic periods in previous years. We retrospectively collected data from electronic patient records of two major hospitals in Western Greece and included patients who suffered a fragility hip fracture and were admitted during the two 5-week lockdown periods in 2020, compared to time-matched patients from 2017-2019. The results showed a drop in hip-fracture incidence, which varied among hospitals and lockdown periods, and conflicting impacts on time to surgery, time to discharge after surgery, and total hospitalization time. The study also found that differences between the two differently organized units were exaggerated during the COVID-19 lockdown periods, highlighting the impact of compliance with social-distancing measures and the reallocation of resources on the quality of healthcare services. Further research is needed to fully understand the specific variations and patterns of geriatric hip-fracture care during emergency health crises characterized by limited resources and behavioral changes.

Knee Arthrodesis with a Modular Silver-Coated Endoprosthesis for Infected Total Knee Arthroplasty with Extensive Bone Loss: A Retrospective Case-Series Study.

INTRODUCTION: Knee arthrodesis is a limb salvage intervention for persistent periprosthetic joint infection (PJI) when revision total knee arthroplasty fails. Conventional arthrodesis techniques are associated with the increased rate of complications, especially in patients with extensive bone loss and extensor tendon deficiency. METHODS: Eight patients with a modular silver-coated arthrodesis implant after failed exchange arthroplasty for infection, were retrospectively reviewed. All patients had significant bone loss, while 5 displayed extensor tendon deficiency. Survivorship, complications, leg length discrepancy, median Visual Analogue Scale (VAS) and Oxford Knee score (OKS) were evaluated. RESULTS: The median follow up was 32 months (range 24-59 months). The survivorship rate of the prosthesis was 86% during the minimum time of follow up of 24 months. In one patient recurrence of the infection was observed and above-knee amputation was performed. The median postoperative leg length discrepancy was 2.07 ± 0.67 cm. Patients were able to ambulate with mild or no pain. The median VAS and OKS was 2.14 ± 0.9 and 34.7 ± 9.3, respectively. CONCLUSIONS: The results of our study demonstrated that knee arthrodesis with a silver coated arthrodesis implant, performed for persistent PJI in patients with significant bone loss and extensor tendon deficit, provided a stable construct, allowed eradication of infection and was associated with good functional outcome.

Impact of Preoperative Quality of Life and Related Factors on the Development of Surgical Site Infections Following Primary Total Joint Arthroplasty: A Prospective Case-Control Study with a Five-Year Follow-Up.

Introduction: As surgical site infections (SSIs) after joint arthroplasty contribute to increased morbidity and mortality, they require further surgical intervention, prolonged hospitalisation, and antimicrobial treatment. The aim of our study is to examine the association between preoperative quality of life (QoL) and other predictive factors on the development of SSIs after primary arthroplasty. Methods: This is a prospective study that enrolled 56 patients with hip and knee primary osteoarthritis who underwent joint replacement. Data were collected from January to March 2017, including patient demographic characteristics, comorbidities, laboratory results, and perioperative clinical data. The patients' QoL was evaluated preoperatively by applying the knee injury and osteoarthritis outcome score (KOOS) and the hip disability and osteoarthritis outcome score (HOOS) for total knee replacement (TKR) and total hip replacement (THR), respectively. A 5-year follow-up was conducted to assess the clinical status of the patients. Results: 66.1% of patients underwent TKR, with 4.9 ± 1.2 days of hospitalisation, 16% of them required autologous blood transfusion, while 33.9% of patients were treated with THR, with 5.7 ± 1 days hospitalisation and 36.8 of them required this type of transfusion. 16 patients were diagnosed with SSIs, with the older of them (>65 years old) presenting lower probability (odds ratio: 0.13, 95% CI: 0.03-0.62) requiring treatment with additional antibiotics, while revision surgery was performed in 3 of these cases, following periprosthetic joint infection (PJI). Overall preoperative QoL was not statistically associated with SSIs, but low QoL scores were associated with higher rates of SSIs and increased levels of postoperative pain (p = 0.009 < 0.05). Conclusions: The duration of each operation (>90 min), the length of hospitalisation (>4 days), and the presence of comorbidities including hypothyroidism and recurrent urinary tract infections were associated with a high risk for SSIs following arthroplasties. On the contrary, this study revealed no association between other comorbidities, including heart coronary disease, hypertension, and diabetes mellitus, with close monitoring of plasma glucose and SSIs. Moreover, the younger the patients, the more likely they were to require treatment with antibiotics. Overall, high QoL index scores were mainly accompanied by low rates of postoperative SSIs and pain.

Subchondral Bone Cyst Development in Osteoarthritis: From Pathophysiology to Bone Microarchitecture Changes and Clinical Implementations.

Osteoarthritis is a degenerative joint disease affecting middle-aged and elderly patients. It mainly involves weight-bearing joints such as the hip, knee and spine as well as the basilar joint of the thumb, causing dysfunction and painful symptoms. Often, joint arthritis is accompanied by cartilage defects, joint space narrowing, osteophytes, bone sclerosis and subchondral bone cysts (SBC). The aim of the present study was to explore the pathophysiology responsible for the development of SBCs as well as the association between SBCs and disease progress, the level of clinical symptoms and their impact on postoperative outcomes and risk of possible complications following joint replacements if left untreated. A literature review on PubMed articles was conducted to retrieve and evaluate all available evidence related to the main objective mentioned above. A few theories have been put forth to explain the formation process of SBCs. These involve MMPs secretion, angiogenesis, and enhanced bone turnover as a biological response to abnormal mechanical loads causing repeated injuries on cartilage and subchondral tissue during the development of arthritis. However, the application of novel therapeutics, celecoxib-coated microspheres, local administration of IGF-1 and activated chondrocytes following surgical debridement of SBCs hinders the expansion of SBCs and prevents the progression of osteoarthritis.

Hypophosphatemic osteomalacia in neurofibromatosis 1 associated with intracranial gliomas and congenital renal agenesis: A rare case report and review of the literature.

Introduction: Neurofibromatosis Type 1 (Nf1), also termed von Recklinghausen disease, is a rare autosomal dominant genetic disorder accompanied by several osseous and skeletal manifestations. In NF, hypophosphatemia linked to secondary hyperparathyroidism due to Vitamin D deficiency and low calcium intake has been reported as a risk factor for low bone mass density (BMD), but reports of NF1 associated oncogenic hypophosphatemic osteomalacia (HO) are extremely rare. Case Report: We report a patient with NF1 associated with intracranial low-grade gliomas and congenital renal agenesis suffering from HO. Bone defects and deformities such as generalized bone pains located in feet, ankles and lower limbs, thoracic scoliosis, mild bowing of long bones of lower limbs, stress fractures, and old fractures as well as with altered bone metabolic serum markers were present. After 8 weeks of follow-up, it was observed that the combination of oral administration of phosphate and Vitamin D improved her medical symptoms without significant changes in phosphate levels or BMD. Conclusion: Although renal agenesis is not correlated with hypophosphatemia, the coexistence of NF1, renal congenital deformities, and low-grade gliomas may contribute to disease severity. Conventional treatment with high doses of oral calcitriol associated with phosphate is efficient to improve the clinical and laboratory symptoms of the disease.

Prosthetic Reconstruction of the Shoulder After Resection of Proximal Humerus Bone Tumor.

Prosthetic reconstruction after wide resection of tumors of the proximal humerus presents a unique challenge. The shoulder is a complex articulation, and patients have high expectations for postoperative function. The goal of this study is to compare functional outcomes, oncologic outcomes, and complication rates for 2 reconstructive methods. Forty patients with proximal humeral tumors were reviewed retrospectively. Proximal humeral endoprosthesis (PHE) was used for 21 patients, and reverse shoulder arthroplasty (RSA) was used for 19 patients. Clinical results, oncologic outcomes, and complication rates were assessed. The functional outcomes of the patients were assessed with the Musculoskeletal Tumor Society scoring system (MSTS), the shortened version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, and shoulder range of motion. The mean follow-up was 62±15 months. Shoulder dislocations occurred among 8 patients with PHE and 1 patient with RSA (P=.021). The other complication rates were similar for the 2 groups (P<.05). At the latest follow-up, the mean MSTS score was 68±10.3 for those with PHE and 76±7.7 for the patients with RSA (P=.72). However, the QuickDASH score was significantly better (P=.031) for those with RSA (mean, 19±6.3) compared with patients with PHE (mean, 30±4.8). Additionally, shoulder active abduction and forward flexion were significantly greater for the RSA group (P=.04 and P=.03, respectively). Five patients had local recurrence. Prosthetic reconstruction after oncologic re-section of the proximal humerus is associated with significant limitation of shoulder range of motion and a high rate of revision surgery. However, in this study, RSA was associated with fewer dislocations, improved Quick-DASH score, and greater abduction and forward flexion compared with PHE. [Orthopedics. 2022;45(6):e335-e341.].

Doxycycline inhibits the progression of metastases in early-stage osteosarcoma by downregulating the expression of MMPs, VEGF and ezrin at primary sites.

INTRODUCTION: Osteosarcoma (OS) is the most common primary osseous malignant tumour, with high propensity to metastasise in lungs. Pulmonary micro-metastases are present in up to 80% of patients at initial diagnosis and they are associated with significantly worse prognosis. Doxycycline (Dox) is a synthetic tetracycline that has been shown to have anti-cancer properties in vitro and in vivo, and inhibit angiogenesis - effects that may prove beneficial for several types of cancer. The aim of the present work was to study how Dox affects OS cell growth in vitro and in vivo and OS-driven pulmonary metastasis in vivo. METHODS: In vitro, the effect of Dox was measured in MG-63 and 143B human OS cell viability, apoptosis, invasion and migration. In vivo, highly metastatic 143B cells were orthotopically implanted into the tibia of SCID mice. The tumour growth and pulmonary metastases between Dox treated and untreated, non-amputated and early amputated xenografts were examined. RESULTS: In vitro, Dox decreased viability, inhibited invasion, migration, and induced the apoptosis of OS cells. In vivo, Dox significantly enhanced tumour necrosis at primary OS sites, similarly to its in vitro effect, and downregulated the expression of Ki67, MMP2, MMP9, VEGFA and ezrin. It also decreased circulating VEGFA and MMP9 protein levels, in line with the decreased metastatic burden in Dox-treated mice (non-amputated and early-amputated). CONCLUSIONS: Reprofiling of Dox can prevent the evolvement of pulmonary micro-metastases to clinically detectable macro-metastases and suppress the lethal progress of OS by inhibiting the expression of MMPs, VEGFA and ezrin at primary sites.

Sonication of revised hip and knee prostheses detects occult infections, improves clinical outcomes and prevents re - revisions. A case series study.

Introduction: Periprosthetic joint infection (PJI) is a devastating complication occurring in 1-2% of primary and up to 10% of revised total hip and knee arthroplasties (THA and TKA) impairing patient's quality of life. Occult infections are underdiagnosed, sub-treated and sub-clinically experienced by patients. This study aimed to correlate patients' clinical outcomes with early antibiotic treatment based on use or non-use of a sonication technique on explanted prostheses. Methods: 33 patients with revised THA or TKA were retrospectively evaluated. Clinical outcomes were assessed via Oxford hip or knee scores, and correlated with administration or not of antibiotic treatment based on sonication results. Results: According to laboratory findings the patients were divided in the following three groups: 1. Septic loosening (conventional cultures and/or sonication positive), 2. Aseptic loosening (conventional cultures and sonication negative) and 3. Occult loosening (conventional cultures negative, sonication not performed). The average Oxford score was poor (27.9/60) for the septic, excellent (43.8/60) for the aseptic and intermediate (37.7/60) for the occult group. Additionally, conventional cultures were negative, but sonication-positive, in 6 individuals with patient-related risk factors (male gender, BMI > 30 kg/m2, diabetes, hypertension, steroids and rheumatoid arthritis). Conclusions: Sonication represents a valuable diagnostic technique to guide administration of effective antibiotic treatment for patients, especially for detection of persistent post-revision occult infections. We recommend the systematic investigation of revised prostheses with a sonication technique, but especially in cases with risk factors for infection who it is suspected may have occult loosening.

Therapeutic Efficacy and Safety of Osteoinductive Factors and Cellular Therapies for Long Bone Fractures and Non-Unions: A Meta-Analysis and Systematic Review.

BACKGROUND: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. METHODS: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. RESULTS: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I2 = 60%, 95% CI = 1.59 [0.99-2.54], Z =1.93, p = 0.05). CONCLUSION: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores.

Three-dimensional Printed Endoprosthesis for Reconstruction of the Distal Tibia and Ankle Joint After Tumor Resection.

Below-knee amputation is the treatment of choice for distal tibia malignancies, considering the specific anatomic features of the distal leg and ankle. However, advances in imaging modalities and adjuvant therapies and improved surgical techniques have made limb salvage surgery increasingly possible. The distal tibia is an uncommon location for malignant bone tumors, and there is limited information about limb salvage and reconstruction. Currently, 3-dimensional printed implants may successfully address reconstruction challenges after tumor resection. We present a patient with high-grade osteosarcoma of the distal tibia who underwent limb salvage and distal tibia and ankle joint replacement with a 3-dimensional printed endoprosthesis. [Orthopedics. 2022;45(6):e348-e352.].

Oncological and Functional Outcomes after Hemicortical Resection and Biological Reconstruction Using Allograft for Parosteal Osteosarcoma of the Distal Femur.

Background: Parosteal osteosarcoma (PAOS) is a surface osteosarcoma. Treatment options include wide excision and endoprosthetic or allograft. However, due to the low local recurrence and metastasis rate, when it appears in the posterior surface of the distal femur, the lesion can be managed with hemicortical wide resection and biological reconstruction with hemicortical allograft. The purpose of this study is to evaluate the oncological and functional outcomes of patients with parosteal osteosarcoma (PAOS) of the posterior cortex of the distal femur who underwent biological reconstruction after hemicortical resection. Methods: Eleven patients who underwent wide tumor resection and defect reconstruction of the posterior surface of the distal femur using hemicortical allograft were retrospectively studied. Local recurrence, metastasis, complications, and the functional outcome using the Musculoskeletal Tumor Society (MSTS) scoring system were evaluated. Results: The average postoperative follow-up period was 53.64 months (range, 30 to 84 months). At the latest follow-up, all patients had no evidence of disease without metastases. One patient with local recurrence underwent revision surgery with fibula autograft reconstruction. The mean MSTS score was 93.45 ± 3.56. Conclusions: Treatment of patients with PAOS of the posterior aspect of the distal femur with hemicortical resection and allograft reconstruction has satisfactory oncological and functional outcome and low complication rates.