Capacitive biophysical stimulation improves the healing of vertebral fragility fractures: a prospective multicentre randomized controlled trial.

BACKGROUND: Capacitively coupling electric fields (CCEF) is a method of non-invasive biophysical stimulation that enhances fracture repair and spinal fusion. This multicentre randomized controlled trial aimed to further examine the roles of CCEF in (1) the resolution of vertebral bone marrow oedema (VBME) using a follow-up MRI study and (2) pain relief, analgesic drug consumption and quality of life improvement in stimulated patients who were referred with acute vertebral fragility fractures (VFFs) compared to non-stimulated patients. METHODS: Between September 2016 and December 2019, patients who were referred to the spine centres that participated in this multicentre randomized clinical study with acute VFFs of type OF1 or OF2 were included in the present study. All the VFFs were conservatively managed according to Good Clinical Practice. Moreover, the patients were randomized into two groups: the CCEF group received, as an adjunct to the clinical study protocol, biophysical stimulation with a CCEF device (Osteospine, IGEA) for 8 h per day for 60 days, whereas the control group was treated according to the clinical study protocol. At baseline (T0), the 30-day follow-up (T1), the 60-day follow-up (T2), and the 6-month follow-up (T3), each patient underwent clinical evaluation using the Visual Analogue Scale (VAS) for Pain and the Oswestry Disability Index (ODI). Analgesic therapy with paracetamol 1000 mg tablets for 7 days-or longer, depending on the pain intensity-was performed; patients were required to report their paracetamol consumption on a specific sheet between study day 8 to 180 days of follow-up. MRI studies of the thoracolumbar spine were performed at 0 (T0), 30 (T1) and 60 days of follow-up (T2) using a 1.5-T MRI system in all of the centres that took part in the study. For each VBME area examined via MRI, the vertebral body geometry (i.e. anterior wall height/posterior wall height and vertebral kyphosis) were assessed. RESULTS: A total of 66 patients (male: 9, 13.63%; mean age: 73.15 years old) with 69 VFFs were included in the present study and randomized as follows: 33 patients were included in the control group and the remaining 33 patients were randomized into the CCEF group. In the CCEF group, good compliance with CCEF therapy was observed (adherence = 94%), and no adverse effects were recorded. In the stimulated patients, faster VBME resolution and significantly less vertebral body collapse during follow-up were observed compared to the control patients. Moreover, in the active group, faster pain reduction and improvement in the ODI mean score were observed. Stimulated patients also reported a significantly lower paracetamol consumption rate from the third follow-up after treatment until the 6-month follow-up. In terms of sex-related differences, in the CCEF group, VBME showed a faster resolution in male patients compared with females. CONCLUSION: Biophysical stimulation with CCEF, as an adjunct to traditional conservative treatment, is a useful tool to hasten the VBME resolution process and prevent vertebral body deformation. These MRI findings also correlate with faster back pain resolution and quality of life improvement. From the third follow-up after treatment until the 6-month follow-up, stimulated patients reported a significantly lower paracetamol consumption than control patients, even though back pain and quality of life showed no significant differences between the two groups. LEVEL OF EVIDENCE: II. Trial Registration Register: ClinicalTrials.gov, number: NCT05803681.

Factors associated with increased length of stay and risk of complications in 336 patients submitted to spine surgery. The role of a validated capture system (SAVES v2) as a first-line tool to properly face the problem.

PURPOSE: In this study, we analyzed the use of a validated capture system (Spinal Adverse Events Severity system, SAVES V2) as a first non-technical skill to properly face the relevant problem of surgical complications (SCs) and adverse events (AEs) in spinal surgery. METHODS: We retrospectively collected AEs occurring in a tertiary referral center for spine surgery from January 2017 to January 2018 and classified them according to SAVES V2 system. We compared this collection of AEs with a prospective collection performed without any classification system. Univariate and multivariate logistic regression models were used to determined odds ratio (ORs) for selected potential risk factors of AEs and prolonged length of stay. RESULTS: Overall a higher number of AEs was retrospectively recorded using SAVES system compared to the prospective recording without the use of any capture system (97/336 vs 210/336, p < 0.001). The length of stay (LOS) increased in the group of complicated patients for all the procedures examined. In the non-oncological group, LOS was significantly higher for complicated patients compared to uncomplicated patients (F = 44.11, p = 0.0000). Similar results have been obtained in the oncological group of patients. In the multivariate regression model surgical time and postoperative AEs emerged as risk factors for prolonged LOS, while only the presence of previous surgeries was confirmed as risk factor for AEs. CONCLUSION: Considering that the rate of AEs and SCs in spinal surgery is still high despite the improvement of technical skills, we suggest the use of SAVES V2 capture system as a first-line tool to face the problem.

Correlation Between Sagittal Balance and Mechanical Distal Junctional Failure in Degenerative Pathology of the Spine: A Retrospective Analysis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: This study aimed to investigate the failure of the caudal end of lumbar posterior fixation in terms of pre-operative and post-operative spinopelvic parameters, correction performed, demographic and clinical data. METHODS: The lumbar, thoraco-lumbar and lumbo-sacral posterior fixations performed with pedicle screws and rods in 2017-2019 were retrospectively analyzed. As 81% failures occurred within 4 years, an observational period of 4 years was chosen. The revision surgeries due to the failure in the caudal end were collected in the junctional group. Fixations which have not failed were gathered in the control group. The main spinopelvic parameters were measured for each patient on standing lateral radiographs with the software Surgimap. Demographic and clinical data were extracted for both groups. RESULTS: Among the 457 patients who met the inclusion criteria, the junctional group included 101 patients, who required a revision surgery. The control group collected 356 primary fixations. The two most common causes of revision surgeries were screws pullout (57 cases) and rod breakage (53 cases). SVA, PT, LL, PI-LL and TPA differed significantly between the two groups (P = .021 for LL, P < .0001 for all the others). The interaction between the two groups and the pre-operative and post-operative conditions was significant for PT, SS, LL, TK, PI-LL and TPA (P < .005). Sex and BMI did not affect the failure onset. CONCLUSIONS: Mechanical failure is more likely to occur in patients older than 40 years with a thoraco-lumbar fixation where PT, PI-LL and TPA were not properly restored.

Gender-Specific Differences in Human Vertebral Bone Marrow Clot.

Recently, our group described the application of vertebral bone marrow (vBMA) clot as a cell therapy strategy for spinal fusion. Its beneficial effects were confirmed in aging-associated processes, but the influence of gender is unknown. In this study, we compared the biological properties of vBMA clots and derived vertebral mesenchymal stem cells (MSCs) from female and male patients undergoing spinal fusion procedures and treated with vBMA clot. We analyzed the expression of growth factors (GFs) in vBMA clots and MSCs as well as morphology, viability, doubling time, markers expression, clonogenicity, differentiation ability, senescence factors, Klotho expression, and HOX and TALE gene profiles from female and male donors. Our findings indicate that vBMA clots and derived MSCs from males had higher expression of GFs and greater osteogenic and chondrogenic potential compared to female patients. Additionally, vBMA-clot-derived MSCs from female and male donors exhibited distinct levels of HOX and TALE gene expression. Specifically, HOXA1, HOXB8, HOXD9, HOXA11, and PBX1 genes were upregulated in MSCs derived from clotted vBMA from male donors. These results demonstrate that vBMA clots can be effectively used for spinal fusion procedures; however, gender-related differences should be taken into consideration when utilizing vBMA-clot-based studies to optimize the design and implementation of this cell therapy strategy in clinical trials.

Carbon Fiber-Reinforced PolyEtherEtherKetone (CFR-PEEK) Instrumentation in Degenerative Disease of Lumbar Spine: A Pilot Study.

CFR-PEEK is gaining popularity in spinal oncological applications due to its reduction of imaging artifacts and radiation scattering compared with titanium, which allows for better oncological follow-up and efficacy of radiotherapy. We evaluated the use of these materials for the treatment of lumbar degenerative diseases (DDs) and considered the biomechanical potential of the carbon fiber in relation to its modulus of elasticity being similar to that of bone. Twenty-eight patients with DDs were treated using CRF-PEEK instrumentation. The clinical and radiographic outcomes were collected at a 12-month FU. Spinal fusion was evaluated in the CT scans using Brantigan scores, while the clinical outcomes were evaluated using VAS, SF-12, and EQ-5D scores. Out of the patients evaluated at the 12-month FU, 89% showed complete or almost certain fusion (Brantigan score D and E) and presented a significant improvement in all clinical parameters; the patients also presented VAS scores ranging from 6.81 ± 2.01 to 0.85 ± 1.32, EQ-5D scores ranging from 53.4 ± 19.3 to 85.0 ± 13.7, SF-12 physical component scores (PCSs) ranging from 29.35 ± 7.04 to 51.36 ± 9.75, and SF-12 mental component scores (MCSs) ranging from 39.89 ± 11.70 to 53.24 ± 9.24. No mechanical complications related to the implant were detected, and the patients reported a better tolerance of the instrumentation compared with titanium. No other series of patients affected by DD that was stabilized using carbon fiber implants have been reported in the literature. The results of this pilot study indicate the efficacy and safety of these implants and support their use also for spinal degenerative diseases.

Indications and Limits of Surgery for Spinal Metastases Derived from Lung Cancer: A Single-Center Experience.

Lung cancer is the second most frequently diagnosed cancer in the world, and surgery is an integral part of the treatment for spinal metastases. The aims of this retrospective study were to assess the overall survival of surgically treated patients affected by lung cancer spinal metastases and identify any factors related to a better survival rate. We recruited 56 consecutive patients (34 male and 22 female) surgically treated for metastatic lung cancer in the spine from 2009 to 2019. Surgical indications were based on a previously published and validated flow chart following a multidisciplinary evaluation. We assessed the localization of vertebral metastases, the presence of other bone or visceral metastases, neurological status according to the Frankel score, ambulatory autonomy, and general status, measured with the Karnofsky performance scale. The expected prognosis was retrospectively assessed according to the revised Tokuhashi score. The median survival was 8.1 months, with over a third of patients surviving more than 1 year. We observed a global improvement in all clinical parameters after surgical treatment. The Tokuhashi predictive score did not correlate with survival after surgery. The results of this study suggest that the surgical treatment of symptomatic spinal metastases from lung cancer can improve quality of life, even in patients with a shorter life expectancy, by controlling pain and improving autonomy.

Safety and efficacy of autologous bone marrow clot as a multifunctional bioscaffold for instrumental posterior lumbar fusion: a 1-year follow-up pilot study.

Background: Bone marrow aspirate (BMA), when combined with graft substitutes, has long been introduced as a promising alternative to iliac crest bone graft in spinal fusion. However, the use of BMA is limited by the absence of a standardized procedure, a structural texture, and the potential for diffusion away from the implant site. Recently, the potential use of a new formulation of BMA, named BMA clot, has been preclinically described. In this report, we present the results of a prospective pilot clinical study aimed at evaluating the safety and efficacy of autologous vertebral BMA (vBMA) clot as a three-dimensional and multifunctional bioscaffold in instrumented posterior lumbar fusion. Methods: Ten consecutive patients with an indication of multilevel (≤5) posterior spinal fusion due to lumbar spine degenerative diseases were included in the study and treated with vBMA. Clinical outcomes were assessed using the Visual Analog Scale (VAS), Oswestry Disability Index (ODI), and EuroQoL-5L (EQ-5L) preoperatively and at 3 months and 12 months after spinal fusion. Bone fusion quality was evaluated at the 12-month follow-up using the Brantigan classification on radiography (XR) imaging. Bone density was measured on computed tomography (CT) scans at 6 and 12 months of follow-up visits at the intervertebral arches and intervertebral joint areas and expressed in Hounsfield unit (HU). Results: The results indicate a successful posterolateral fusion rate of approximately 100% (considering levels with C, D, and E grades according to the Brantigan classification) at the 12-month follow-up, along with an increase in bone density from 6 to 12 months of follow-up. An improvement in the quality of life and health status following surgery, as assessed by clinical scores (ODI, VAS, and EQ-5L), was also observed as early as 3 months postsurgery. No adverse events related to the vBMA clot were reported. Conclusion: This prospective pilot study demonstrates the effectiveness and safety profile of vBMA clot as an advanced bioscaffold capable of achieving posterior lumbar fusion in the treatment of degenerative spine diseases. This lays the groundwork for a larger randomized clinical study.

Ceramic bone graft substitute (Mg-HA) in spinal fusion: A prospective pilot study.

Background: Iliac crest bone graft (ICBG) is considered the gold standard for spine surgical procedures to achieve a successful fusion due to its known osteoinductive and osteoconductive properties. However, complications related to harvesting procedure and donor site morbidity have been largely reported in the literature, favoring the development of a wide range of alternative products to be used as bone graft extenders or substitutes for spine fusion. Among all, ceramic-based biomaterials have been widely studied and employed in the last years as bone graft substitutes. Methods: We report here the results of a prospective pilot study aimed to evaluating the grade of ossification obtained by the use of an Mg-doped hydroxyapatite (HA) product to achieve postero-lateral fusion in degenerative spine diseases. Results: Results show a successful degree of fusion of about 62% at the 12-month follow-up and an improvement of quality of life and health status following surgery, as evaluated by clinical scores (ODI, VAS, and EQ-5L). No adverse events related to the material were reported. Conclusion: The present pilot study shows the effectiveness and the safety profile of an Mg-doped HA bone graft substitute used to achieve postero-lateral fusion in the treatment of degenerative spine diseases, laying down the basis for further larger clinical investigations.

Complications in Spinal Fusion Surgery: A Systematic Review of Clinically Used Cages.

Spinal fusion (SF) comprises surgical procedures for several pathologies that affect different spinal levels, and different cages are employed in SF surgery. Few clinical studies highlight the role of cages in complications beyond the outcomes. The aim of this systematic review is to collect the last 10 years' worth of clinical studies that include cages in SF surgery, focusing on complications. Three databases are employed, and 21 clinical studies are included. The most-performed SF procedure was anterior cervical discectomy and fusion (ACDF), followed by lumbar SF. The polyetheretherketone (PEEK) cage was the most-used, and it was usually associated with autograft or calcium phosphate ceramics (hydroxyapatite (HA) and tricalcium phosphate (ßTCP)). For lumbar SF procedures, the highest percentages of subsidence and pseudoarthrosis were observed with PEEK filled with bone morphogenetic protein 2 (BMP2) and ßTCP. For ACDF procedures, PEEK filled with autograft showed the highest percentages of subsidence and pseudoarthrosis. Most studies highlighted the role of surgical techniques in patient complications. There are many interacting events that contextually affect the rate of clinical success or failure. Therefore, in future clinical studies, attention should focus on cages to improve knowledge of chemical, biological and topographical characteristics to improve bone growth and to counteract complications such as cage loosening or breaking and infections.

Complications and Risk Factors in En Bloc Resection of Spinal Tumors: A Retrospective Analysis on 298 Patients Treated in a Single Institution.

En bloc resection consists in the surgical removal of a vertebral tumor in a single piece with a sufficient margin, to improve survival and reduce recurrence rate. This procedure is technically demanding and correlates with a high complication rate. The purpose of this study is to investigate the risk factors for complications in en bloc resection and evaluate if benefits overcome the risks in term of overall survival. We retrospectively analyzed prospectively collected data of patients treated with en bloc resection between 1980 and 2021. Complications were classified according to SAVES-V2. Overall Survival was estimated using Kaplan-Meier method. A total of 149 patients out of 298 (50%) suffered from at least one complication. Moreover, 220 adverse events were collected (67 intraoperative, 82 early post-operative, 71 late post-operative), 54% of these were classified as grade 3 (in a severity scale from 1 to 6). Ten years overall survival was 67% (95% CI 59-74). The occurrence of relapses was associated to an increased risk of mortality with OR 3.4 (95% CI 2.1-5.5), while complications did not affect the overall survival. Despite a high complication rate, en bloc resection allows for a better control of disease and should be performed in selected patients by specialized surgeons.

Clear Cell Renal Cell Carcinoma Spinal Metastases: Which Factors Matter to the Overall Survival? A 10-Year Experience of a High-Volume Tumor Spine Center.

Clear cell renal cell carcinoma (ccRCC) usually spreads in the spinal region causing instability or spinal cord compression leading to neurological deficits. Therefore, surgical treatment is required for improving the outcome of patients. The aim of this study is to identify which prognostic factors could affect overall survival in patients affected by ccRCC. Methods: Retrospective cohort study of patients with ccRCC spinal metastases, surgically treated from November 2009 to April 2019. Demographic and clinical data were collected. The Kaplan−Meier method was used to estimate overall survival, and the log-rank test was used to evaluate differences in survival among potentially prognostic factors. Results: A total of 69 patients were surgically treated and followed up for a median period of 65 months. The average age at the time of surgery was 62.6 years old. The median overall survival (OS) was 34.7 months (95% CI 20.8−51.9) and 5-year OS was 31.2% (95% CI 19.2−44.1). A high Tokuhashi score (p = 0.0217), the presence of visceral metastases (p < 0.001), other bone metastases (p = 0.02012) and the kind of surgical treatment (p = 0.0395) are the main prognostic factors that influence the OS. Moreover, 3-year progression-free survival (PFS) was analyzed: the median PFS was 53.1 months and the % 3-year PFS was 62.9% (45.2−76.3). In the multivariate analysis, only pre-operative radiation therapy had a significant impact on 3-year PFS (95% CI 0.929−12.994, p = 0.0643). Conclusion: The results of this study suggest that the absence of visceral metastases and an aggressive surgery as en-bloc, when feasible, could prolong the survival rate and improve quality of life for patients.

A Novel Quantitative Computer-Assisted Score Can Improve Repeatability in the Estimate of Vascular Calcifications at the Abdominal Aorta.

In CKD and in the elderly, Vascular Calcifications (VC) are associated to cardiovascular events and bone fractures. VC scores at the abdominal aorta (AA) from lateral spine radiographs are widely applied (the 0-24 semiquantitative discrete visual score (SV) being the most used). We hypothesised that a novel continuum score based on quantitative computer-assisted tracking of calcifications (QC score) can improve the precision of the SV score. This study tested the repeatability and reproducibility of QC score and SV score. In forty-four patients with VC from an earlier study, five experts from four specialties evaluated the data twice using a dedicated software. Test-retest was performed on eight subjects. QC results were reported in a 0-24 scale to readily compare with SV. The QC score showed higher intra-operator repeatability: the 95% CI of Bland-Altman differences was almost halved in QC; intra-operator R2 improved from 0.67 for SV to 0.79 for QC. Inter-observer repeatability was higher for QC score in the first (Intraclass Correlation Coefficient 0.78 vs. 0.64), but not in the second evaluation (0.84 vs. 0.82), indicating a possible heavier learning artefact for SV. The Minimum Detectable Difference (MDD) was smaller for QC (2.98 vs. 4 for SV, in the 0-24 range). Both scores were insensitive to test-retest procedure. Notably, QC and SV scores were discordant: SV showed generally higher values, and an increasing trend of differences with VC severity. In summary, the new QC score improved the precision of lateral spine radiograph scores in estimating VC. We reported for the first time an estimate of MDD in VC assessment that was 25% lower for the new QC score with respect to the usual SV score. An ongoing study will determine whether this lower MDD may reduce follow-up times to check for VC progression.

Custom-Made 3D-Printed Implants for Anterior Column Reconstruction in the Upper Cervical Spine after Intralesional Extracapsular Excision-Report of 2 Cases and Literature Review.

The use of three-dimensional (3D)-printed custom-made implants is spreading in the orthopedics field for the reconstruction of bone losses or for joint replacement, thanks to their unparalleled versatility. In particular, this novel technology opens new perspectives to formulate custom-made fixation strategies for the upper cervical region, sacrum and pelvis, where reconstruction is challenging. We report and analyze the literature concerning upper cervical reconstruction with 3D-printed personalized implants after tumor surgery, and discuss two cases of patients where this technology was used to reconstruct the anterior column after extracapsular debulking of C2 recurrent chordoma at our institution.

An inter- and intra-rater agreement assessment of a novel classification of pyogenic spinal infections.

PURPOSE: Pola et al. described a clinical-radiological classification of pyogenic spinal infections (PSI) based on magnetic resonance imaging (MRI) features including vertebral destruction, soft tissue involvement, and epidural abscess, along with the neurological status. We performed an inter- and intra-observer agreement evaluation of this classification. METHODS: Complete MRI studies of 80 patients with PSI were selected and classified using the scheme described by Pola et al. by seven evaluators. After a four-week interval, all cases were presented to the same assessors in a random sequence for repeat assessment. We used the weighted kappa statistics (wκ) to establish the inter- and intra-observer agreement. RESULTS: The inter-observer agreement was substantial considering the main categories (wκ = 0.77; 0.71-0.82), but moderate considering the subtypes (wκ = 0.51; 0.45-0.58). The intra-observer agreement was substantial considering the main types (wκ = 0.65; 0.59-0.71), and moderate considering the subtypes (wκ = 0.58; 0.54-0.63). CONCLUSION: The agreement at the main type level indicates that this classification allows adequate communication and may be used in clinical practice; at the subtypes level, the agreement is only moderate.

Autologous mesenchymal stem cells in the treatment of spinal aneurysmal bone cyst.

PURPOSE: We retrospectively analyzed a cohort of patients treated at our Centre with bone marrow concentrated (BMC) injection for aneurysmal bone cyst (ABC) of the spine, in order to propose this treatment as a valid alternative for the management of ABCs. METHODS: Fourteen patients (6 male, 8 female) were treated between June 2014 to December 2019 with BMC injection for ABC of the spine. The mean age was 15.5 years. The mean follow up was 37.4 months (range 12-60 months). The dimension of the cyst and the degree of ossification were measured by Computed Tomography (CT) scans before the treatment and during follow-up visits. RESULTS: Six patients received a single dose of BMC, five patients received two doses and in three patients three doses of BMC were administered. The mean ossification of the cyst (expressed in Hounsfield units) increased statistically from 43.48 ± 2.36 HU to 161.71 ± 23.48 HU during follow-up time and the ossification was associated to an improvement of the clinical outcomes. The mean ossification over time was significantly higher in patients treated with a single injection compared to patients treated with multiple injections. No significant difference in ossification was found between cervical and non-cervical localization of the cyst. Moreover, the initial size of the cyst was not statistically associated with the degree of ossification during follow-up CONCLUSIONS: Results of this paper reinforce our previous evidence on the use of BMC as a valid alternative for spinal ABC management when SAE treatment is contraindicated or ineffective.

Type, size, and position of metastatic lesions explain the deformation of the vertebrae under complex loading conditions.

BACKGROUND: Bone metastases may lead to spine instability and increase the risk of fracture. Scoring systems are available to assess critical metastases, but they lack specificity, and provide uncertain indications over a wide range, where most cases fall. The aim of this work was to use a novel biomechanical approach to evaluate the effect of lesion type, size, and location on the deformation of the metastatic vertebra. METHOD: Vertebrae with metastases were identified from 16 human spines from a donation programme. The size and position of the metastases, and the Spine Instability Neoplastic Score (SINS) were evaluated from clinical Quantitative Computed Tomography images. Thirty-five spine segments consisting of metastatic vertebrae and adjacent healthy controls were biomechanically tested in four different loading conditions. The strain distribution over the entire vertebral bodies was measured with Digital Image Correlation. Correlations between the features of the metastasis (type, size, position and SINS) and the deformation of the metastatic vertebrae were statistically explored. RESULTS: The metastatic type (lytic, blastic, mixed) characterizes the vertebral behaviour (Kruskal-Wallis, p = 0.04). In fact, the lytic metastases showed more critical deformation compared to the control vertebrae (average: 2-fold increase, with peaks of 14-fold increase). By contrast, the vertebrae with mixed or blastic metastases did not show a clear trend, with deformations similar or lower than the controls. Once the position of the lytic lesion with respect to the loading direction was taken into account, the size of the lesion was significantly correlated with the perturbation to the strain distribution (r2 = 0.72, p < 0.001). Conversely, the SINS poorly correlated with the mechanical evidence, and only in case of lytic lesions (r2 = 0.25, p < 0.0001). CONCLUSION: These results highlight the relevance of the size and location of the lytic lesion, which are marginally considered in the current clinical scoring systems, in driving the spinal biomechanical instability. The strong correlation with the biomechanical evidence indicates that these parameters are representative of the mechanical competence of the vertebra. The improved explanatory power compared to the SINS suggests including them in future guidelines for the clinical practice.

Two Hits for Bone Regeneration in Aged Patients: Vertebral Bone Marrow Clot as a Biological Scaffold and Powerful Source of Mesenchymal Stem Cells.

Recently, the use of a new formulation of bone marrow aspirate (BMA), the BMA clot, has been described. This product entails a naturally formed clot from the harvested bone marrow, which retains all the BMA components preserved in a matrix biologically molded by the clot. Even though its beneficial effects were demonstrated by some studies, the impact of aging and aging-associated processes on biological properties and the effect of BMA cell-based therapy are currently unknown. The purpose of our study was to compare selected parameters and properties of clotted BMA and BMA-derived mesenchymal stem cells (MSCs) from younger (<45 years) and older (>65 years) female donors. Clotted BMA growth factors (GFs) expression, MSCs morphology and viability, doubling time, surface marker expression, clonogenic potential, three-lineage differentiation, senescence-associated factors, and Klotho synthesis from younger and older donors were analyzed. Results indicated that donor age does not affect tissue-specific BMA clot regenerative properties such as GFs expression and MSCs morphology, viability, doubling time, surface antigens expression, colony-forming units, osteogenic and adipogenic differentiation, and Klotho and senescence-associated gene expression. Only few differences, i.e., increased platelet-derived growth factor-AB (PDGF-AB) synthesis and MSCs Aggrecan (ACAN) expression, were detected in younger donors in comparison with older ones. However, these differences do not interfere with all the other BMA clot biological properties. These results demonstrated that BMA clot can be applied easily, without any sample processing and avoiding potential contamination risks as well as losing cell viability, proliferation, and differentiation ability, for autologous transplantation in aged patients. The vertebral BMA clot showed two successful hits since it works as a biological scaffold and as a powerful source of mesenchymal stem cells, thus representing a novel and advanced therapeutic alternative for the treatment of orthopedic injuries.

Breast cancer spinal metastases: Prognostic factors affecting survival after surgery. A retrospective study.

Breast cancer spinal metastases (BCSM) are common and require proper treatment that leads to an improvement of the quality of life and contributes to the quod vitam prognosis. Surgical treatment is often required for intractable pain, spinal cord compression or spinal instability. The aim of this retrospective study is to identify which prognostic factors could affect postoperative overall survival in patients affected by BCSM. We report a retrospective cohort study of patients with BCSM, surgically treated from September 2009 to May 2018. Demographic and clinical data were collected. Kaplan-Meier method was used to estimate overall survival, and the log-rank test was used to compare survival curves. A total of 77 patients were studied. The median age at the time of surgery was 54 years. The median follow-up was 49 months. The 3-year and 5-year overall survival rates were 61% (95%CI: 47.5-72.1) and 43.3% (95%CI: 28.8-57.1). Metastatic bone disease (p = 0.0196), preoperative neurological impairment (p = 0.0029), Karnofsky status <70 (p = 0.0241) reduce survival. With multivariate analysis, the effect of Karnofsky score loses statistical significance. The presence of concurrent bone metastases and a preoperative neurological deficit are independent prognostic factors. Therapeutic choices are based on a multidisciplinary assessment that takes into consideration several factors, including an accurate study of prognostic factors.

Assessing the Mechanical Weakness of Vertebrae Affected by Primary Tumors: A Feasibility Study.

Patients spend months between the primary spinal tumor diagnosis and the surgical treatment, due to the need for performing chemotherapy and/or radiotherapy. During this period, they are exposed to an unknown risk of fracture. The aim of this study was to assess if it is possible to measure the mechanical strain in vertebrae affected by primary tumors, so as to open the way to an evidence-based scoring or prediction tool. We performed biomechanical tests on three vertebrae with bone tumor removed from patients. The tests were designed so as not to compromise the standard surgical and diagnostic procedures. Non-destructive mechanical tests in combination with state-of-the-art digital image correlation allowed to measure the distribution of strain on the surface of the vertebra. Our study has shown that the strains in the tumor region is circa 3 times higher than in the healthy bones, with principal strain peaks of 40,000/-20,000 microstrain, indicating a stress concentration potentially triggering vertebral fracture. This study has proven it is possible to analyze the mechanical behavior of primary tumor vertebrae as part of the clinical treatment protocol. This will allow building a tool for quantifying the risk of fracture and improving decision making in spine tumors.

Enhanced Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by a Hybrid Hydroxylapatite/Collagen Scaffold.

Human bone marrow-derived mesenchymal stem cells (hBMSCs) and their derivative enhanced green fluorescent protein (eGFP)-hBMSCs were employed to evaluate an innovative hybrid scaffold composed of granular hydroxylapatite and collagen hemostat (Coll/HA). The cellular morphology/cytoskeleton organization and cell viability were investigated by immunohistochemistry (IHC) and AlamarBlue metabolic assay, respectively. The expression of osteopontin and osteocalcin proteins was analyzed by IHC and ELISA, whereas osteogenic genes were investigated by quantitative PCR (Q-PCR). Cell morphology of eGFP-hBMSCs was indistinguishable from that of parental hBMSCs. The cytoskeleton architecture of hBMSCs grown on the scaffold appeared to be well organized, whereas its integrity remained uninfluenced by the scaffold during the time course. Metabolic activity measured in hBMSCs grown on a biomaterial was increased during the experiments, up to day 21 (p < 0.05). The biomaterial induced the matrix mineralization in hBMSCs. The scaffold favored the expression of osteogenic proteins, such as osteocalcin and osteopontin. In hBMSC cultures, the scaffold induced up-regulation in specific genes that are involved in ossification process (BMP2/3, SPP1, SMAD3, and SP7), whereas they showed an up-regulation of MMP9 and MMP10, which play a central role during the skeletal development. hBMSCs were induced to chondrogenic differentiation through up-regulation of COL2A1 gene. Our experiments suggest that the innovative scaffold tested herein provides a good microenvironment for hBMSC adhesion, viability, and osteoinduction. hBMSCs are an excellent in vitro cellular model to assay scaffolds, which can be employed for bone repair and bone tissue engineering.