Micro-CT, Mechanical, and Histological Examination of the Effect of Local Adjuvants on Porcine Cortical Bone Following Intralesional Curettage of Bone Tumors.

BACKGROUND AND OBJECTIVES: Curettage is the removal of a tumor from the bone while preserving the surrounding healthy cortical bone, and is associated with higher rates of local recurrence. To lower these rates, curettage should be combined with local adjuvants, although their use is associated with damage to nearby healthy bone. OBJECTIVE: The purpose of this analysis is to determine the effect of local adjuvants on cortical porcine bone by using micro-computed tomography (micro-CT) along with histological and mechanical examination. METHODS: Local adjuvants were applied to porcine specimens under defined conditions. To assess changes in bone mineral density (BMD), a micro-CT scan was used. The pixel gray values of the volume of interest (VOI) were evaluated per specimen and converted to BMD values. The Vickers hardness test was employed to assess bone hardness (HV). The depth of necrosis was measured histologically using hematoxylin and eosin-stained tissue sections. RESULTS: A noticeable change in BMD was observed on the argon beam coagulation (ABC) sample. Comparable hardness values were measured on samples following electrocautery and ABC, and lowering of bone hardness was obtained in the case of liquid nitrogen. Extensive induced depth of necrosis was registered in the specimen treated with liquid nitrogen. CONCLUSION: This study determined the effect of local adjuvants on cortical bone by using micro-CT along with histological and mechanical examination. Phenolization and liquid nitrogen application caused a decrease in bone hardness. The bone density was affected in the range of single-digit percentage values. Liquid nitrogen induced extensive depth of necrosis with a wide variance of values.

Clinical outcomes and survival comparison between NexGen all-poly and its metal-backed equivalent in total knee arthroplasty.

PURPOSE: This study aims to compare total knee replacement (TKA) with NexGen All-Poly (APT) and NexGen Metal-Backed (MBT) in terms of implant survivorship, reasons leading to implant failure and functional results of defined age categories. METHODS: A single-centre, retrospective evaluation of 812 patients who underwent knee replacement with NexGen CR between 2005 and 2021, comparing a modern congruent APT component to a modular MBT equivalent component using a similar surgical technique at a notable mean follow-up duration. Implant survival, functional outcomes using the Knee Society Score and range of motion were evaluated and compared in different age categories. RESULTS: Of the 812 NexGen CR TKAs performed at our institution, 410 (50.4%) used APT components and 402 (49.6%) MBT components. The survival rate of NexGen APT was 97.1% and that of NexGen MBT was 93.2% (p = 0.36). Removal of the implant occurred overall in 15 cases, for MBT in ten cases, and for APT in four cases. The FS was proved to be significantly higher when APT components were implanted in younger patients than for MBT (p = 0.005). A similar range of motion between the components was recorded (p = 0.1926). CONCLUSION: Under defined conditions, we measured the clinical results of implants from a single manufacturer implanted in a single department using a similar surgical technique. Considering the limitations, we suggest that all-polyethylene tibial components are equal or even superior to metal-backed ones across the examined age categories.

[Complications of peripheral parenteral nutrition. Clinical observations of 2 cases]. / Complicaciones de la nutrición parenteral periférica. Observación clínica de 2 casos.

INTRODUCTION: Peripheral parenteral nutrition (PPN) is artificial nutrition used when digestive absorption is insufficient. It supplies the nutritional needs of the patient and permits administration through a peripheral catheter. WE PRESENT 2 CLINICAL CASES: The first one entails an epidermolisis through extravasation masked by temporo-spatial disorientation of the patient with appearance of flictenes (blisters). Prolonged treatment and consultation with plastic surgery were required. The second case entails a chemical phlebitis with early detection by nursing professionals. It was resolved with short term treatment and did not require consultation with the plastic surgeon. PLANNING CARE: We elaborated a care plan aimed at identifying real or potential problems related with possible complications of intravenous PPN administration, such as phlebitis and extravasation. The aim of this research was prevention, early detection and treatment. DISCUSSION: Phlebitis is related with catheter characteristics, in-dwelling time and high osmolarity of PPN. Early action decreases injury of the affected tissue. In case 1, the patient requires 19 days of curing. This was only 72 h in case 2. CONCLUSION: The nursing staff plays an essential role in catheter election, localization, administration and preventing complications. Staff training and a procedure protocol greatly reduce the incidence of phlebitis, avoid discomfort for the patient and reduce health care cost.

Clear surgical margins as a prognostic indicator for disease recurrence, with no impact on survival rates in patients with myxofibrosarcoma.

Myxofibrosarcoma presents an infiltrating growth pattern that results in a high tendency for local recurrence. Clear margin resection is challenging because of microscopic infiltration. The purpose of the present study was to analyze the overall and disease-free survival rates of patients with myxofibrosarcoma and the prognostic factors that determine both survival and disease recurrence. Among the 111 patients included in our study, the 5-year overall survival rate was 65.5%. An age of more than 65 years (hazard ratio [HR] 1.9 [95% confidence interval (CI) 1.4-5.6]; p < 0.001), a tumor size of more than 5 cm (HR 2.8 [95% CI 0.9-8.1]; p = 0.049) and the G3 tumor grade (HR 14.1 [95% CI 2.1-105.0]; p < 0.001) negatively affected overall survival. The 5-year recurrence-free survival rate was 49.4%. R1/R2-type resection (HR 2.4 [95% CI 1.0-5.6]; p = 0.048) had a detrimental effect on tumor recurrence. Clear margins had a positive impact on recurrence-free survival, but did not significantly affect overall patient survival, suggesting that other factors may play a more significant role in determining patient outcomes. A surgical margin of 2 mm was not sufficient to significantly influence the incidence of recurrence. Consequently, a wider surgical margin may be necessary to reduce the risk of myxofibrosarcoma recurrence.

Biomechanical comparison of all-polyethylene total knee replacement and its metal-backed equivalent on periprosthetic tibia using the finite element method.

BACKGROUND: Total knee arthroplasty (TKA) with all-polyethylene tibial (APT) components has shown comparable survivorship and clinical outcomes to that with metal-backed tibial (MBT). Although MBT is more frequently implanted, APT equivalents are considered a low-cost variant for elderly patients. A biomechanical analysis was assumed to be suitable to compare the response of the periprosthetic tibia after implantation of TKA NexGen APT and MBT equivalent. METHODS: A standardised load model was used representing the highest load achieved during level walking. The geometry and material models were created using computed tomography data. In the analysis, a material model was created that represents a patient with osteopenia. RESULTS: The equivalent strain distribution in the models of cancellous bone with an APT component showed values above 1000 µÎµ in the area below the medial tibial section, with MBT component were primarily localised in the stem tip area. For APT variants, the microstrain values in more than 80% of the volume were in the range from 300 to 1500 µÎµ, MBT only in less than 64% of the volume. CONCLUSION: The effect of APT implantation on the periprosthetic tibia was shown as equal or even superior to that of MBT despite maximum strain values occurring in different locations. On the basis of the strain distribution, the state of the bone tissue was analysed to determine whether bone tissue remodelling or remodelling would occur. Following clinical validation, outcomes could eventually modify the implant selection criteria and lead to more frequent implantation of APT components.

Plastic response of macrophages to metal ions and nanoparticles in time mimicking metal implant body environment.

The paradigm of using metal biomaterials could be viewed from two sides - treatment of wide spectrum of degenerative diseases, and debris release from materials. After implant insertion, metal nanoparticles (NPs) and ions are released not only upon the first contact with cells/tissues, but in continual manner, which is immediately recognized by immune cells. In this work, the effects of metal nanoparticles (TiO2, Ni) and ions (Ni2+, Co2+, Cr3+, Mo6+) on primary human M0 macrophages from the blood samples of osteoarthritic patients undergoing total arthroplasty were studied in order to monitor immunomodulatory effects on the cells in a real-time format. The highest NiNPs concentration of 10 µg/ml had no effect on any of macrophage parameters, while the Ni2+ ions cytotoxicity limit for the cells is 0.5 mM. The cytotoxic effects of higher Ni2+ concentration revealed mitochondrial network fragmentation leading to mitochondrial dysfunction, accompanied by increased lysosomal activity and changes in pro-apoptotic markers. The suppression of M2 cell formation ability was connected to presence of Ni2+ ions (0.5 mM) and TiO2NPs (10 µg/ml). The immunomodulatory effect of Mo6+ ions, controversially, inhibit the formation of the cells with M1 phenotype and potentiate the thread-like shape M2s with increased chaotic cell movement. To summarize, metal toxicity depends on the debris form. Both, metal ions and nanoparticles affect macrophage size, morphological and functional parameters, but the effect of ions is more complex and likely more harmful, which has potential impact on healing and determines post-implantation reactions.

Mechanical complications and infection control comparison of custom-made and prefabricated articular hip spacers in the treatment of periprosthetic infection.

OBJECTIVES: The purpose of our study was to compare the complication rate and the outcomes of custom-made spacers (C-spacers) and prefabricated articular spacers (P-spacers) in the treatment of periprosthetic infection. PATIENTS AND METHODS: In this retrospective study, 78 patients (44 females, 34 males; mean age: 68.5±9.48 years; range, 47 to 82 years) with articular spacers implanted in our institution were analyzed between January 2009 and December 2019. We recorded implant results as per mechanical complications, infection control, the interval from surgery to definitive hip replacement, and the rate of achieving recovery of joint function after stage two arthroplasty. RESULTS: There were 29 revised spacers; 18 of them were C-spacers and 11 were P-spacers (p=0.0383). A total of 16 dislocations were recorded, of which six were dislocations of C-spacers, and 10 were dislocations of P-spacers (p=0.0082). Additionally, we registered four spacer breakages, all of which occurred in C-spacers (p=0.295). C-spacers failed early, at an mean interval of 2.2 weeks after implantation, and P-spacers failed later, with an mean of 9.3 weeks after implantation (p=0.0187). A total of nine reinfection complications of spacers were registered; only one infection of P-spacers, and eight infections related to C-spacers (p=0.2583). Definitive revision total hip arthroplasty (rTHA) after spacer explantation and successful treatment of the infection occurred in 63 cases out of 78 patients. Definitive rTHA occurred after the use of C-spacers in 41 (78%) patients and after the use of C-spacers in 22 (84%) patients (p=0.7816). C-spacers had a mean interval from spacer implantation to definitive rTHA of 6.56±6.03 months, and P-spacers had a mean interval of 4±1.93 months (p=0.0164). CONCLUSION: Custom-made spacers were shown to have lower mechanical complication rates than prefabricated ones but more infection complications. Prefabricated spacers had more dislocations and fewer breakages. Custom-made spacer mechanical failures occurred earlier compared to prefabricated ones.

Implant Preference and Clinical Outcomes of Patients with Staged Bilateral Total Knee Arthroplasty: All-Polyethylene and Contralateral Metal-Backed Tibial Components.

Numerous studies have compared metal-backed components (MBTs) and all-polyethylene tibial components (APTs), but none of them specifically analysed the clinical results and the overall patient preference in patients who had undergone a staged bilateral knee replacement. The purpose of this study is to compare clinical results, perceived range of motion, and overall implant preference among patients who had undergone staged bilateral knee replacement with an APT and contralateral knee replacement with MBTs. A dataset of 62 patients from a single centre who underwent staged bilateral TKA between 2009 and 2022 was selected and retrospectively analysed. Tibial component removal was performed in three knees overall, all of which had MBTs. The mean measured Knee Score (KS) of knees with APTs was 78.37 and that of contralateral knees with MBTs was 77.4. The mean measured Function (FS) of knees with APTs was 78.22, and that of contralateral knees with MBs was 76.29. The mean flexion angle of knees with APTs was 103.8 and that for knees with MBTs was 101.04 degrees. A total of 54.8% of the patients preferred the knee that received APTs over contralateral MBTs. In our cohort, TKA with an APT in one knee and an MBT in the contralateral knee recorded similar clinical results and perceived ranges of motion. Patients in general preferred the knee that received an APT over contralateral knee with an MBT.

Proximal Tibia Tumour Location and Curettage Are Major Risk Factors of Local Recurrence in Giant Cell Tumour of Bone.

Giant cell tumour of bone (GCTB) is one of the most common local aggressive tumourous lesions with a wide variety of biological behaviour. However, there are no clear indicative criteria when choosing the type of procedure and the complication rates remain high, especially in terms of local recurrence. The purpose of the study was to (1) identify the main risk factors for local recurrence, (2) evaluate the recurrence-free survival in dependence on neoadjuvant denosumab use and the type of procedure, and (3) compare the functional outcomes after curettage and en bloc resection. The group included 102 patients with GCTB treated between 2006 and 2020. The mean age of patients was 34.4 years (15-79). The follow-up period was 8.32 years (2-16) on average. Local recurrence occurred in 14 patients (29.8%) who underwent curettage and in 5 patients (10.6%) after en bloc resection. Curettage was shown to be a factor in increasing recurrence rates (OR = 3.64 [95% CI: 1.19-11.15]; p = 0.023). Tibial location was an independent risk factor for local recurrence regardless of the type of surgery (OR = 3.22 [95% CI: 1.09-9.48]; p = 0.026). The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments at five years postoperatively (p = 0.0307). Functional ability and pain as reported by patients at the latest follow-up were superior after curettage compared to resection for upper and lower extremity (mean difference: -4.00 [95% CI: -6.81 to -1.18]; p < 0.001 and mean difference: -5.36 [95% CI: -3.74 to -6.97]; p < 0.001, respectively). Proximal tibia tumour location and curettage were shown to be major risk factors for local recurrence in GCTB regardless of neoadjuvant denosumab treatment. The recurrence-free survival rate of patients treated with resection and denosumab was higher compared to other treatments. The functional outcome of patients after curettage was better compared to en bloc resection.

Biomechanical analysis of all-polyethylene total knee arthroplasty on periprosthetic tibia using the finite element method.

BACKGROUND AND OBJECTIVE: Total knee arthroplasty (TKA) with modern all-polyethylene tibial (APT) components has shown high long-term survival rates and comparable results to those with metal-backed tibial components. Nevertheless, APT components are primarily recommended for older and low-demand patients. There are no evidence-based biomechanical guidelines for orthopaedic surgeons to determine the appropriate lower age limit for implantation of APT components. A biomechanical analysis was assumed to be suitable to evaluate the clinical results in patients under 70 years. The scope of this study was to determine biomechanically the appropriate lower age limit for implantation of APT components. METHODS: To generate data of the highest possible quality, the geometry of the computational models was created based on computed tomography (CT) images of a representative patient. The cortical bone tissue model distinguishes the change in mechanical properties described in three parts from the tibial cut. The cancellous bone material model has a heterogeneous distribution of mechanical properties. The values used to determine the material properties of the tissues were obtained from measurements of a CT dataset comprising 45 patients. RESULTS: Computational modeling showed that in the majority of the periprosthetic volume, the von Mises strain equivalent ranges from 200 to 2700 µÎµ; these strain values induce bone modeling and remodeling. The highest measured deformation value was 2910 µÎµ. There was no significant difference in the induced mechanical response between bone models of the 60-year and 70-year age groups, and there was <3% difference from the 65-year age group. CONCLUSIONS: Considering in silico limitations, we suggest that APT components could be conveniently used on a bone with mechanical properties of the examined age categories. Under defined loading conditions, implantation of TKA with APT components is expected to induce modeling and remodeling of the periprosthetic tibia. Following clinical validation, the results of our study could modify the indication criteria of the procedure, and lead to more frequent implantation of all-polyethylene TKA in younger patients.

Outcomes of Intercalary Endoprostheses as a Treatment for Metastases in the Femoral and Humeral Diaphysis.

BACKGROUND: The purpose of this study was to evaluate the implant survival, functional score and complications of intercalary endoprostheses implanted for metastatic involvement of the femoral and humeral diaphysis. METHODS: The selected group covered patients with bone metastasis who were surgically treated with an intercalary endoprosthesis between 2012 and 2021. The functional outcome was evaluated with the Musculoskeletal Tumor Society (MSTS) scoring system, and complications were evaluated by using the failure classification for prosthetics designed by Henderson. RESULTS: The mean follow-up was 29.8 months. In our group of 25 patients with 27 intercalary endoprostheses (18 femurs, 9 humeri), there were 7 implant-related complications (25.9%), which were more common on the humerus (4 cases, 44.4%) than on the femur (3 cases, 16.7%). Only type II failure-aseptic loosening (5 cases, 18.5%)-and type III failure-structural failure (2 cases, 7.4%)-occurred. There was a significantly higher risk of aseptic loosening of the endoprosthesis in the humerus compared with that in the femur (odds ratio 13.79, 95% confidence interval 1.22-151.05, p = 0.0297). The overall cumulative implant survival was 92% 1 year after surgery and 72% 5 years after surgery. The average MSTS score was 82%. The MSTS score was significantly lower (p = 0.008) in the humerus (75.9%) than in the femur (84.8%). CONCLUSIONS: The resection of bone metastases and replacement with intercalary endoprosthesis has excellent immediate functional results with an acceptable level of complications in prognostically favourable patients.

New Target for Precision Medicine Treatment of Giant-Cell Tumor of Bone: Sunitinib Is Effective in the Treatment of Neoplastic Stromal Cells with Activated PDGFRß Signaling.

Giant-cell tumor of bone (GCTB) is an intermediate type of primary bone tumor characterized by locally aggressive growth with metastatic potential. The aim of this study was to identify new druggable targets among the cell signaling molecules involved in GCTB tumorigenesis. Profiles of activated signaling proteins in fresh-frozen tumor samples and tumor-derived cell lines were determined using phosphoprotein arrays. Analysis of the obtained data revealed epidermal growth factor receptor (EGFR) and platelet-derived growth factor receptor beta (PDGFRß) as potential targets, but only the PDGFR inhibitor sunitinib caused a considerable decrease in stromal cell viability in vitro. Furthermore, in the case of a 17-year-old patient suffering from GCTB, we showed that the addition of sunitinib to the standard treatment of GCTB with the monoclonal antibody denosumab resulted in the complete depletion of multinucleated giant cells and mononuclear stromal cells in the tumor tissue. To summarize, the obtained data showed that a specific receptor tyrosine kinase (RTK) signaling pattern is activated in GCTB cells and plays an important role in the regulation of cell proliferation. Thus, activated RTKs and their downstream signaling pathways represent useful targets for precision treatment with low-molecular-weight inhibitors or with other types of modern biological therapy.

Improved osteosarcoma survival with addition of mifamurtide to conventional chemotherapy - Observational prospective single institution analysis.

PURPOSE: Conventional osteosarcoma is an orphan disease. Current treatment approaches include combining a three drug chemotherapy schedule and surgery. The 3- and 5-year event-free survival (EFS) in localized disease is roughly 65 and 60%, respectively. The registration study of mifamurtide reported survival benefit, but some methodological controversies have been insufficient for FDA market authorization in contrast to EMA. METHODS: prospective single centre survival analysis of a mifamurtide addition to conventional therapy in 23 patients over a 5.5 year enrolment period is reported and compared to a historical control of 26 patient with localized disease. Bias arising from observational methodology was addressed using Landmark analysis and time-dependent Cox models. Blood count dynamics were analysed during the treatment. RESULTS: The adverse event profile was as expected with no dose limiting toxicities. There were no local relapses observed, one patient died in the first complete remission due to doxorubicin cardiotoxicity, one patient had pulmonary metastatic relapse. The observed 3- and 5-year EFS was 87.4% (CI 72.4-100%) and 87.4% (CI 72.4-100%), progression free survival (PFS) was 92.9% (CI 80.3-100%) and 92.9% (CI 80.3-100%), overall survival was 94.1% (CI 83.6-100) and 80.7% (CI 58.3-100), respectively. Comparison to the historical control showed statistically significant better PFS for mifamurtide patients (Landmark analysis; p = 0.044). Risk of progression was 5-times lower for the mifamurtide group (Cox model; HR 0.21, p = 0.136). Only subtle differences in lymphocyte counts were observed across treatment. CONCLUSION: the PFS benefit of mifamurtide is reported herein. The addition of mifamurtide could be considered as a best treatment option for localized osteosarcoma.

Advantages in Prognosis of Adult Patients with Ewing Sarcoma: 11-years Experiences and Current Treatment Management.

Ewing sarcoma (ES) is an exceptionally rare tumor in adults. Data regarding outcomes of adult patients with ES and experiences with age-adapted therapeutic strategies are very limited. The aim of this study was to evaluate prognostic factors and clinical outcome in a cohort of adult patients treated according to pediatric protocols in the Czech Republic. The records of 58 adult ES patients diagnosed between 2002 and 2013 were reviewed and factors relevant to prognosis and survival were analyzed. The median age of study cohort was 29 years (range, 18-59). The most frequent location was axial (36.2%), followed by involvement of extraskeletal tissues (34.5%) and bones of the extremities (29.3%). Twenty-eight (48.3%) patients had metastatic disease. In cases with localized ES, the 5-year overall survival (OS) was 76.5%. Using the log-rank test, the presence of metastasis at diagnosis, local treatment without surgery and a failure to achieve complete remission were associated with significantly shorter survival. In a multivariate Cox proportional hazard analysis, the achievement of complete remission was an independent predictor of patients's survival time. Outcomes of adults with localized ES treated according to multimodal pediatric protocols are similar to children. The achievement of complete remission is an independent predictor of survival time in ES patients. Severe hematological toxicity is foreseeable and manageable. Prognosis of patients with metastases or progression remains dismal.

The PHQ-PD as a Screening Tool for Panic Disorder in the Primary Care Setting in Spain.

INTRODUCTION: Panic disorder is a common anxiety disorder and is highly prevalent in Spanish primary care centres. The use of validated tools can improve the detection of panic disorder in primary care populations, thus enabling referral for specialized treatment. The aim of this study is to determine the accuracy of the Patient Health Questionnaire-Panic Disorder (PHQ-PD) as a screening and diagnostic tool for panic disorder in Spanish primary care centres. METHOD: We compared the psychometric properties of the PHQ-PD to the reference standard, the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) interview. General practitioners referred 178 patients who completed the entire PHQ test, including the PHQ-PD, to undergo the SCID-I. The sensitivity, specificity, positive and negative predictive values and positive and negative likelihood ratios of the PHQ-PD were assessed. RESULTS: The operating characteristics of the PHQ-PD are moderate. The best cut-off score was 5 (sensitivity .77, specificity .72). Modifications to the questionnaire's algorithms improved test characteristics (sensitivity .77, specificity .72) compared to the original algorithm. The screening question alone yielded the highest sensitivity score (.83). CONCLUSION: Although the modified algorithm of the PHQ-PD only yielded moderate results as a diagnostic test for panic disorder, it was better than the original. Using only the first question of the PHQ-PD showed the best psychometric properties (sensitivity). Based on these findings, we suggest the use of the screening questions for screening purposes and the modified algorithm for diagnostic purposes.

Use of the harmonic system in total hip arthroplasty: a prospective, comparative, observational study.

We compared technical issues, postoperative outcomes and surgical complications of total hip arthroplasty when using the harmonic scalpel (HS) when compared with conventional techniques (CT) in a prospective, comparative observational study. Thirty patients undergoing total hip arthroplasty were assessed. Operative time, blood loss in drains, postoperative pain, soft tissue injury and complications were recorded. We found no significant differences between the HS and CT groups at baseline. Mean operative time was longer in the HS group compared with the CT of total hip arthroplasty (61 minutes vs. 54 minutes; P<0.05). We found no difference in postoperative pain using a visual analogue scale score, or use of paracetamol. The use of tramadol was reduced in the HS group compared to CT group at the 7th day (83.3 mg vs. 113.3 mg; P<0.05). Drainage volume was significantly lower in the HS group at 24 hours (332 ml vs. 429 ml; P<0.05) and at 48 hours (429 vs. 537 ml; P<0.05). C-reactive protein blood levels were significantly lower in the HS group 75 mg/l vs. 96 mg/l at the third day (P<0.05) and 26 mg /l vs. 54 mg /l at the seventh day (P<0.01). Creatine kinase blood levels were significantly lower in the HS group at 3 and 7 days (2.4 ukat/l compared to 5.3 ukat/l at the 3rd day (P<0.01), respectively 1.1 ukat/l compared to 1.8 ukat/l at the 7th day (P<0.01). We found no significant differences in blood myoglobin levels between the two groups. The use of the HS may reduce postoperative pain, drainage volume, and soft tissue injury in patients undergoing total hip arthroplasty, which may justify the cost of the technique. The use of HS may have further applications in revision hip arthroplasty and tumour surgery.