Cervical Spine Reconstruction with Chest Tube Technique After Metastasis Resection: A Single-Center Experience.

BACKGROUND: The silastic tube technique, in which a chest tube is placed into the vertebral body defect and impregnated with polymethyl methacrylate, showed good results in patients with lumbar and thoracic neoplastic diseases. There has been only 1 study about the effectiveness and safety of this technique in patients with cervical metastases. We aimed to report our experience in using this technique to reconstruct the spine after corpectomy for cervical metastasis. METHODS: All patients with cervical spinal metastasis who underwent surgical treatment using a chest tube impregnated with polymethyl methacrylate in conjunction with anterior cervical plate stabilization were retrospectively recruited. Demographics, tumor histology, revised Tokuhashi score, preoperative and postoperative American Spinal Injury Association score, preoperative and postoperative ambulatory status, perioperative complications, and survival time were collected. RESULTS: This study included 16 patients. The most common primary tumor site was the lung (6 patients; 37.5%). The mean (SD) survival time was 408 (795) days (range, 1-2797 days), and the median survival time was 72 days (95% confidence interval 28-116 days). Four patients (25%) died within 30 postoperative days. There was no surgical site infection or instrument failure after the surgery. Five patients (31.2%) lived >180 days, and 3 patients (18.8%) lived >360 days. One patient (6.2%) was still alive at the end of the study. CONCLUSIONS: The silastic tube technique in conjunction with anterior cervical plate stabilization might be safe, effective, and cost-effective for patients with cervical spine metastasis.

The Masquelet Technique: Can Disposable Polypropylene Syringes be an Alternative to Standard PMMA Spacers? A Rat Bone Defect Model.

BACKGROUND: Usually, the two-stage Masquelet induced-membrane technique for extremity reconstruction begins with a polymethylmethacrylate (PMMA) cement spacer-driven membrane, followed by an autologous cancellous bone graft implanted into the membrane cavity to promote healing of large bone defects. In exceptional cases, spacers made of polypropylene disposable syringes were successfully used instead of the usual PMMA spacers because of a PMMA cement shortage caused by a lack of resources. However, this approach lacks clinical evidence and requires experimental validation before being recommended as an alternative to the conventional technique. QUESTIONS/PURPOSES: To (1) develop and (2) validate a critical-sized femoral defect model in rats for two stages of the Masquelet technique and to (3) compare the biological and bone healing properties of polypropylene-induced membranes and PMMA-induced membranes in this model. METHODS: Fifty male Sprague Dawley rats aged 8 weeks old received a 6-mm femur defect, which was stabilized with an external fixator that was converted into an internal device. In the development phase, the defect was filled with PMMA in 16 rats to determine the most favorable timing for bone grafting. Two rats were excluded since they died of anesthetic complications. The other 14 were successively euthanized after 2 weeks (n = 3), 4 weeks (n = 4), 6 weeks (n = 4), and 8 weeks (n = 3) for induced membrane analyses. In the validation phase, 12 rats underwent both stages of the procedure using a PMMA spacer and were randomly assigned to two groups, whether the induced membrane was preserved or removed before grafting. To address our final objective, we implanted either polypropylene or PMMA spacers into the defect (Masquelet technique Stage 1; n = 11 rats per group) for the period established by the development phase. In each group, 6 of 11 rats were euthanized to compare the biological properties of polypropylene-induced membranes and PMMA-induced membranes using histological qualitative analysis, semiquantitative assessment of the bone morphogenic protein-2 content by immunostaining, and qualitative assessment of the mesenchymal stromal cell (MSC; CD31-, CD45-, CD90+, and CD73+ phenotypes) content by flow cytometry. Quantitative measurements from serum bone turnover markers were also performed. The five remaining rats of each group were used for Masquelet technique Stage 2, in which rat bone allografts were implanted in the induced membrane cavity after the polypropylene or PMMA spacers were removed. These rats recovered for 10 weeks before being euthanized for microCT quantitative measurements and bone histology qualitative assessment to evaluate and compare the extent of bone regeneration between groups. RESULTS: Induced membrane analyses together with serum bone turnover measurements indicated that a 4-week interval time between stages was the most favorable. Removal of the induced membrane before grafting led to almost constant early implant failures with poor bone formation. Four-week-old rats with polypropylene-triggered induced membranes displayed similar histologic organization as rats with PMMA-driven induced membranes, without any difference in the cell density of the extracellular matrix (4933 ± 916 cells per mm2 for polypropylene versus 4923 ± 1284 cells per mm2 for PMMA; p = 0.98). Induced membrane-derived MSCs were found in both groups with no difference (4 of 5 with polypropylene versus 3 of 3 with PMMA; p > 0.99). Induced membrane bone morphogenic protein-2 immunolabeling and serum bone turnover marker levels were comparable between the polypropylene and PMMA groups. MicroCT analysis found that bone regeneration in the polypropylene group seemed comparable with that in the PMMA group (29 ± 26 mm3 for polypropylene versus 24 ± 18 mm3 for PMMA; p > 0.99). Finally, qualitative histological assessment revealed a satisfactory endochondral ossification maturation in both groups. CONCLUSION: Using a critical-sized femoral defect model in rats, we demonstrated that polypropylene spacers could induce membrane encapsulation with histologic characteristics and bone regenerative capacities that seem like those of PMMA spacers. CLINICAL RELEVANCE: In a same bone site, polymers with close physical properties seem to lead to similar foreign body reactions and induce encapsulating membranes with comparable bone healing properties. Polypropylene spacers made from disposable syringes could be a valuable alternative to PMMA. These results support the possibility of a cementless Masquelet technique in cases of PMMA shortage caused by a lack of resources.

PMMA-Based Continuous Hemofiltration Modulated Complement Activation and Renal Dysfunction in LPS-Induced Acute Kidney Injury.

Sepsis-induced acute kidney injury (AKI) is a frequent complication in critically ill patients, refractory to conventional treatments. Aberrant activation of innate immune system may affect organ damage with poor prognosis for septic patients. Here, we investigated the efficacy of polymethyl methacrylate membrane (PMMA)-based continuous hemofiltration (CVVH) in modulating systemic and tissue immune activation in a swine model of LPS-induced AKI. After 3 h from LPS infusion, animals underwent to PMMA-CVVH or polysulfone (PS)-CVVH. Renal deposition of terminal complement mediator C5b-9 and of Pentraxin-3 (PTX3) deposits were evaluated on biopsies whereas systemic Complement activation was assessed by ELISA assay. Gene expression profile was performed from isolated peripheral blood mononuclear cells (PBMC) by microarrays and the results validated by Real-time PCR. Endotoxemic pigs presented oliguric AKI with increased tubulo-interstitial infiltrate, extensive collagen deposition, and glomerular thrombi; local PTX-3 and C5b-9 renal deposits and increased serum activation of classical and alternative Complement pathways were found in endotoxemic animals. PMMA-CVVH treatment significantly reduced tissue and systemic Complement activation limiting renal damage and fibrosis. By microarray analysis, we identified 711 and 913 differentially expressed genes with a fold change >2 and a false discovery rate <0.05 in endotoxemic pigs and PMMA-CVVH treated-animals, respectively. The most modulated genes were Granzyme B, Complement Factor B, Complement Component 4 Binding Protein Alpha, IL-12, and SERPINB-1 that were closely related to sepsis-induced immunological process. Our data suggest that PMMA-based CVVH can efficiently modulate immunological dysfunction in LPS-induced AKI.

Nonsurgical Methods for Penile Augmentation: A Systematic Review.

BACKGROUND: There is no standardized approach for nonsurgical techniques for penile augmentation despite the increase of demand for this intervention. OBJECTIVE: To compare the efficacy and safety between different injection techniques. MATERIALS AND METHODS: On October 8, 2019, a literature search was performed on PubMed, Embase, Ovid, and Cochrane database. All articles describing penile augmentation were included. RESULTS: Thirteen studies were included in this article with a total of 1,311 patients. Five studies were prospective cohort. The most commonly described technique was hyaluronic acid fillers with a total of 4 articles and 205 patients. The mean injected volume ranged from 20 to 40 mL. In all included studies, a minority of patients had side effects, but some had disabling complications. CONCLUSION: There are no defined clinical guidelines for penile augmentation techniques implemented yet. Hyaluronic acid seems to be safe, efficient, and with a high satisfaction score. Further randomized control trials are warranted. EBM LEVEL OF EVIDENCEBASED MEDICINE: 2a.

A 12-Month Study to Evaluate Safety and Efficacy of Polymethylmethacrylate-Collagen Gel for Correction of Midface Volume Loss Using a Blunt Cannula as Measured by 3-D Imaging.

BACKGROUND: Although polymethylmethacrylate (PMMA)-collagen gel is approved for correction of nasolabial folds, there are no reports characterizing safety and efficacy in the midface, an area where fillers are often used in clinical practice. OBJECTIVE: To determine the safety and efficacy of PMMA-collagen gel for long-term volume restoration in the midface. METHODS: In this prospective, single-center, 12-month study, 23 subjects with a pretreatment Midface Volume Deficit Scale (MFVDS) grade of 3, 4, or 5 were treated with PMMA-collagen gel. Efficacy was measured by the investigator and blinded reviewers using the MFVDS at 3, 6, and 12 months. Subject Global Aesthetic Improvement Scale (SGAIS) and physician GAIS (PGAIS) ratings were collected at 3, 6, and 12 months. RESULTS: Improvement in the MFVDS score from baseline was significant at all post-treatment time points (p < .0001). All subjects with baseline MFVDS grades of 5 (severe) or 4 (significant) had a grade of 0 (none) or 1 (minimal) at 12 months. Subject GAIS (SGAIS) and PGAIS ratings of improved or much improved were 100% at Month 3 and were maintained at 12 months (PGAIS = 100%, SGAIS = 91.3%). All adverse events were minor. CONCLUSION: Polymethylmethacrylate-collagen gel is safe and effective for long-lasting correction of midface volume deficit.

Cement-augmented screw fixation for calcaneal fracture treatment: a biomechanical study comparing two injectable bone substitutes.

BACKGROUND: The role of cement-augmented screw fixation for calcaneal fracture treatment remains unclear. Therefore, this study was performed to biomechanically analyze screw osteosynthesis by reinforcement with either a calcium phosphate (CP)-based or polymethylmethacrylate (PMMA)-based injectable bone cement. METHODS: A calcaneal fracture (Sanders type IIA) including a central cancellous bone defect was generated in 27 synthetic bones, and the specimens were assigned to 3 groups. The first group was fixed with four screws (3.5 mm and 6.5 mm), the second group with screws and CP-based cement (Graftys® QuickSet; Graftys, Aix-en-Provence, France), and the third group with screws and PMMA-based cement (Traumacem™ V+; DePuy Synthes, Warsaw, IN, USA). Biomechanical testing was conducted to analyze peak-to-peak displacement, total displacement, and stiffness in following a standardized protocol. RESULTS: The peak-to-peak displacement under a 200-N load was not significantly different among the groups; however, peak-to-peak displacement under a 600- and 1000-N load as well as total displacement exhibited better stability in PMMA-augmented screw osteosynthesis compared to screw fixation without augmentation. The stiffness of the construct was increased by both CP- and PMMA-based cements. CONCLUSION: Addition of an injectable bone cement to screw osteosynthesis is able to increase fixation strength in a biomechanical calcaneal fracture model with synthetic bones. In such cases, PMMA-based cements are more effective than CP-based cements because of their inherently higher compressive strength. However, whether this high strength is required in the clinical setting for early weight-bearing remains controversial, and the non-degradable properties of PMMA might cause difficulties during subsequent interventions in younger patients.

Minimally invasive spinal fixation in an aging population with osteoporosis: clinical and radiological outcomes and safety of expandable screws versus fenestrated screws augmented with polymethylmethacrylate.

OBJECTIVE: The goal of this study was to compare the clinical and radiological outcomes between fenestrated pedicle screws augmented with cement and expandable pedicle screws in percutaneous vertebral fixation surgical procedures for the treatment of degenerative and traumatic spinal diseases in aging patients with osteoporosis. METHODS: This was a prospective, single-center study. Twenty patients each in the expandable and cement-augmented screw groups were recruited. Clinical outcomes included visual analog scale (VAS), Oswestry Disability Index (ODI), and satisfaction rates. Radiographic outcomes comprised radiological measurements on the vertebral motion segment of the treated levels. Intraoperative data including complications were collected. All patients completed the clinical and radiological outcomes. Outcomes were compared preoperatively and postoperatively. RESULTS: An average shorter operative time was found in procedures in which expandable screws were used versus those in which cement-augmented screws were used (p < 0.001). No differences resulted in perioperative blood loss between the 2 groups. VAS and ODI scores were significantly improved in both groups after surgery. There was no significant difference between the 2 groups with respect to baseline VAS or ODI scores. The satisfaction rate of both groups was more than 85%. Radiographic outcomes also showed no significant difference in segment stability between the 2 groups. No major complications after surgery were seen. There were 4 cases (20%) of approach-related complications, all in fenestrated screw procedures in which asymptomatic cement extravasations were observed. In 1 case the authors detected a radiologically evident osteolysis around a cement-augmented screw 36 months after surgery. In another case they identified a minor loosening of an expandable screw causing local back discomfort at the 3-year follow-up. CONCLUSIONS: Expandable pedicle screws and polymethylmethacrylate augmentation of fenestrated screws are both safe and effective techniques to increase the pullout strength of screws placed in osteoporotic spine. In this series, clinical and radiological outcomes were equivalent between the 2 groups. To the authors' knowledge, this is the first report comparing the cement augmentation technique versus expandable screws in the treatment of aging patients with osteoporosis.

Design and development of polymethylmethacrylate-grafted gellan gum (PMMA-g-GG)-based pH-sensitive novel drug delivery system for antidiabetic therapy.

The objective of the present study was to develop a pH-sensitive drug delivery system by using polymethylmethacrylate-grafted gellan gum (PMMA-g-GG). PMMA-g-GG was synthesized by free radical polymerization reaction by using redox initiator ceric ammonium nitrate (CAN), and a series of graft copolymers were prepared with varying concentrations of methylmethacrylate (MMA) and CAN. Grafting parameters such as the percentage and efficiency of grafting were calculated, and the effect of monomer as well as initiator concentration was studied on the grafting yield. Optimization was done by one optimal response surface methodology. The batch with a better percentage grafting and grafting efficiency was selected and characterized by elemental analysis (CHN), FT-IR, DSC, PXRD, 1H-NMR, and SEM. Furthermore, acute oral toxicity study and histopathological analysis suggested non-toxic and biocompatible nature of the grafted gum. Metformin hydrochloride pellets were prepared using PMMA-g-GG, characterized in detail, and assessed for biocompatibility and efficacy. PMMA-g-GG-based formulation (M4) exhibited a pH-sensitive as well as sustained release of the drug over the period of 12 h and the release profile followed Peppas model. In vivo efficacy studies indicated a promising antidiabetic potential of the prepared formulation. Thus, PMMA-g-GG-based formulations can be implicated as novel drug delivery systems for facilitated antidiabetic therapy in the near future. Graphical abstract.

Additional Injection Laryngoplasty for Patients With Unilateral Vocal Fold Paralysis.

OBJECTIVES: In case of insufficient voice improvement after injection laryngoplasty (IL), additional IL will be one of the next option of treatments. However, little is known about the voice outcomes regarding an additional IL. STUDY DESIGN: Retrospective comparative study in single institution. METHODS: We enrolled the patients of unilateral vocal fold paralysis (UVFP), who received IL (N = 76) twice because of insufficient voice improvement. The etiologies of UVFP were related with thoracic and esophageal surgery (51.3%), neck surgery (30.3%), skull base surgery (7.9%), or unknown (10.5%). The subjective and objective voice parameters were collected before and after (mean: 5.3 months) each IL. RESULTS: Aspiration, maximum phonation time (MPT), jitter percentage, shimmer percentage, and noise to harmonic ratio (NHR) were significantly improved after both the first and second rounds of IL (P < .05). Voice handicap index (VHI)-30 was also significantly improved after both the first and second rounds of IL (P < .001). Regarding GRBAS score, overall grade of dysphonia (G), roughness (R), and breathiness (B) were significantly improved after the first IL, but only G and R after the second IL (P < .05). In comparison between postprocedural voice parameters of the first and second ILs, MPT was significantly improved from 5.5 ± 3.5 seconds to 7.3 ± 7.5 seconds (P = .001). Grade of dysphonia (1.9 ± 0.8) and breathiness (1.7 ± 0.9) of post-first IL were significantly (P < .001) improved to those of post-second IL (1.3 ± 0.7 and 1.2 ± 0.7, respectively). VHI-30 of post-first IL (72.0 ± 20) was significantly improved (P < .001) to those of the second IL (57.2 ± 23.7). CONCLUSIONS: In selected patients, additional IL could provide further improvement of voice in patient who had unsatisfactory voice results despite of initial IL. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

Glutathione and Reactive Oxygen Species Dual-Responsive Block Copolymer Prodrugs for Boosting Tumor Site-Specific Drug Release and Enhanced Antitumor Efficacy.

A remarkable hallmark of cancer cells is the heterogeneous coexistence of overproduced intracellular glutathione (GSH) and a high level of reactive oxygen species (ROS) compared with those in normal cells, which have been frequently used as the stimuli to trigger drug release from the nanocarriers. Most of the stimuli-responsive delivery vehicles have been designed to respond to only one redox stimulus (e.g., GSH or ROS). Herein, we develop a GSH and ROS dual-responsive amphiphilic diblock copolymer prodrug (BCP) (GR-BCP) consisting of poly(ethylene glycol) (PEG)- and camptothecin (CPT)-conjugated poly(methacrylate) in the side chains via thioether bonds. In comparison, GSH or ROS single-responsive BCPs (G-BCPs or R-BCPs) were prepared, where CPT drugs were linked by disulfide or thioketal bonds, respectively. The three BCPs can form well-defined spherical micellar nanoparticles in an aqueous solution with a diameter of ∼50 nm. Compared with G-BCP and R-BCP, GR-BCP realized the highest cytotoxicity against HeLa cells with the half-inhibitory concentration (IC50) of 6.3 µM, which is much lower than 17.8 µM for G-BCP and 28.9 µM for R-BCP. Moreover, for in vivo antitumor performance, G-BCP, R-BCP, and GR-BCP showed similar efficiencies in blood circulation and tumor accumulation after intravenous injection. However, GR-BCP realized the most efficient tumor suppression with few side effects. Our findings demonstrate that intracellular GSH and ROS dual-responsive BCPs show a more efficient responsive drug release inside tumor cells for boosting the antitumor efficacy as compared with GSH or ROS single-responsive BCPs, which provides novel strategies for designing redox-responsive BCPs.

Effectiveness of percutaneous cement injection on proximal junctional failure after posterior lumbar interbody fusion: Preliminary study.

Proximal junctional failure (PJF) is the greatest challenge after posterior lumbar interbody fusion (PLIF). The aim of this study was to evaluate the effectiveness of percutaneous cement injection (PCI) for PJF after PLIF patients requiring surgical revision.In this retrospective clinical study, we reviewed 7 patients requiring surgical revision for PJF after PLIF with 18 months follow-up. They received PCI at the collapsed vertebral body and supra-adjacent vertebra, with or without intervertebral disc intervention. The outcome measures were radiographic findings and revision surgery. Two different radiographic parameters (wedging rate (%) of the fractured vertebral body and local kyphosis angle) were used, and were performed before and immediately after PCI, and 18 month after the PCI.In our study, we showed that 5 of 7 patients who experienced PJF after PLIF did not receive any revision surgery after PCI. Immediately after cement injection, the anterior wedging rate (%) and the local kyphosis angle were significantly improved (P = .018, P = .028). The anterior wedging rates (%) and local kyphosis angle, at pre-PCI, immediate after PCI, and at final follow-up, were not significantly different between the non-revision surgery and revision surgery groups.Five of 7 patients who experienced PJF after PLIF did not receive revision surgery after PCI. Considering that general anesthesia and open surgery are high-risk procedures for geriatric patients, our results suggest that non-surgical PCI could be a viable alternative treatment option for PJF.SMC2017-01-011-001. Retrospectively registered 18 January 2017.

Successful use of percutaneous interspinous spacers and adjunctive spinoplasty in a 9 year cohort of patients.

PURPOSE: Lumbar spinal canal stenosis and lumbar spinal foraminal stenosis are common, degenerative pathologies which can result in neurogenic claudication and have a negative impact on function and quality of life. Percutaneous interspinous devices (PIDs) are a recently-developed, minimally-invasive, alternative treatment option. This study details a 9 year single-centre experience with PIDs and examines the complementary use of spinous process augmentation (spinoplasty) to reduce failure rates. METHODS: A retrospective cohort assessment of 800 consecutive patients who presented to a specialized spine hospital was performed with 688 receiving treatment. Inclusion was based on high-grade stenosis, failure of conservative management and electromyography. 256 had a PID alone while 432 had concurrent polymethyl methacrylate (PMMA) augmentation of the adjacent spinous processes. The patients were followed up at 3 and 12 months using the Zurich Claudication Questionnaire (ZCQ) and Oswestry Disability Index (ODI). RESULTS: Both groups showed marked improvement in the patients' ZCQ scores (3.2 to 1.3) and ODI scores (32 to 21), with strong satisfaction results (1.7). The symptom recurrence rate from complications for the group which received concurrent spinous process augmentation was reduced when compared with the PID alone cohort (<1% vs 11.3%). CONCLUSION: This study demonstrates the efficacy of percutaneous interspinous devices in treating lumbar spinal stenosis. It also provides evidence that concurrent spinous process augmentation reduces the rate of symptom recurrence.

Balloon Kyphoplasty Is a Safe and Effective Option for the Treatment of Vertebral Compression Fractures in Solid-Organ Transplant Recipients.

OBJECTIVES: Solid-organ transplant recipients are at great risk for osteoporotic vertebral compression fractures because of both underlying pretransplant bone diseases and posttransplant immunosuppressive treatments. Balloon kyphoplasty is a minimally invasive procedure that is used to treat painful osteoporotic vertebral compression fractures. It involves injection of polymethylmethacrylate into the vertebral body to stabilize the fracture and to alleviate the pain immediately. In this study, we report the results of balloon kyphoplasty for treatment of vertebral compression fractures in solid-organ transplant recipients. MATERIALS AND METHODS: We retrospectively reviewed 512 liver transplant and 2248 kidney transplant procedures that were performed in our center between 1985 and 2015. Seven transplant recipients with a total of 10 acute, symptomatic vertebral compression fractures who were unresponsive to conservative treatment for 3 weeks underwent balloon kyphoplasty. Clinical outcome was graded using the visual analog scale. Radiographic evaluation included measurement of the segmental kyphosis by the Cobb method. RESULTS: There were 4 female and 3 male patients in our study group. Ages of patients ranged from 56 to 63 years with an average age of 58.8 years. The affected vertebral levels varied from T12 to L4. Mean follow-up after balloon kyphoplasty was 3.4 years, and mean time interval from transplant to balloon kyphoplasty was 8.6 years. Statistically significant difference is evident 3 years after transplant surgery (P < .05). Sagittal alignment improved (> 5 degrees) in 2 of 7 patients (28%). CONCLUSIONS: Transplant recipients are at great risk in terms of vertebral compression fracture development, especially within 1 year after transplant. Although conservative treatment has been the first treatment choice for vertebral compression fracture, long treatment time and high costs may be needed to achieve cure. Experience with our small patient population showed that balloon kyphoplasty was effective and safe for obtaining rapid pain relief and earlier mobilization with fewer complications.

Combination Antibiotic Delivery in PMMA Provides Sustained Broad-Spectrum Antimicrobial Activity and Allows for Postimplantation Refilling.

Antibiotics are commonly added to poly(methyl methacrylate) (PMMA) by surgeons to locally treat infections such as in bone cement for joint replacement surgeries, as well as implantable antimicrobial "beads". However, this strategy is of limited value in high-risk patients where infections can be recurrent or chronic and otherwise hard to treat. Also, when only one drug is incorporated and applied toward polymicrobial infections (multiple bacterial species), there is a high risk that bacteria can develop antibiotic resistance. To combat these limitations, we developed a combination antibiotic PMMA composite system composed of rifampicin-filled ß-cyclodextrin (ß-CD) microparticles added into PMMA filled with a second drug. Different formulations were evaluated through zone of inhibition, drug activity, antibiotic release, and refilling, as well as mechanical studies. Our combination antibiotic PMMA composite system achieved up to an 8-fold increase in the duration of antimicrobial activity in comparison to clinically used antibiotic-filled PMMA. Inclusion of CD microparticles also allowed for refilling of additional antibiotics after simulated implantation, resulting in additional windows of therapeutic efficacy. Mechanical testing showed that our tested formulations did have a small, but significant decrease in mechanical properties when compared to unmodified controls. While further studies are needed to determine whether the tested formulations are still suitable for load-bearing applications (e.g., bone cement), our composites are certainly amenable for a variety of nonload-bearing applications (e.g., antimicrobial "beads" and temporary spacer in two-stage arthroscopic revisions).

Does the induced membrane have antibacterial properties? An experimental rat model of a chronic infected nonunion.

INTRODUCTION: The Masquelet procedure proved its efficiency in treating infected nonunion filling bony gaps up to 25 cm. Yet the use of local antibiotics is still questionable in the daily practice with lack of evidence regarding its usefulness in controlling infection. An experimental rat model is put in place to study the antibacterial properties of the induced membrane produced during the first stage of Masquelet. METHOD: Twenty-three-month-old wistar male rats are inoculated with a 0.5 mL solution of 10^8 CFU/mL MRSA over a critical fracture done on the right femur. Six weeks later, remaining 11 rats exhibiting signs of a chronic infection with a sinus tract and oozing pus along with radiological nonunion are used for a first stage Masquelet procedure. They are randomly divided into two groups with six rats having no local antibiotic in the cement mixture and five rats having 3 g of vancomycin mixed with gentamycin loaded cement. Six weeks later (twelve weeks from baseline), all eleven rats are euthanized and blood samples for C-reactive protein are withdrawn. The induced membrane is identified and resected along with bone fragments and sent for cultures and pathology. RESULTS: MRSA is isolated in the cultures of all six rats in the first group where no local antibiotic was added. Altered polymorphonuclears with abscess and pus are noted on four of six pathology samples. However in the second group where local antibiotics were added, three out of five rats exhibited eradication of MRSA (p = 0.034) and all samples did not exhibit clear infection signs on pathology. A pyo-epithelioid over a foreign body reaction is seen predominantly in this group demonstrating a regenerative process. DISCUSSION: The induced membrane does not have antimicrobial properties capable of overcoming an infected nonunion on its own. When local antibiotics were added during the first stage of the Masquelet procedure, new bone formation occurred indicating the need to control an infection in order for bone union to occur. CONCLUSION: Local antibiotics use in adjunction to extensive debridement is advisable during the first stage of a Masquelet procedure for an infected nonunion.

Síntese, Caracterização e propriedades mecânicas de nanofibras utilizadas para reforço de restaurações protéticas / Synthesis, characterization and mechanical properties of nanofibers used for reinforcement of prosthetic restorations

Este estudo visou sintetizar e caracterizar mantas não tecidas de nanofibras (NFs) do acrilonitrila butadieno estireno (ABS), poliamida 6 (PA6) e poliestireno (PS), e avaliar sua capacidade de ser utilizada como reforço no polimetilmetacrilato (PMMA). O ABS foi dissolvido em diclorometano e acetona, a PA6 pelo 1,1,1,3,3,3- Hexafluoro-2-propanol e o PS pela dimetilformamida, em uma concentração definida em estudo piloto. Após determinados os melhores parâmetros de eletrofiação (tensão contínua, razão de fluxo e distância agulha/anteparo) as amostras de cada grupo foram analisadas em microscopia eletrônica de varredura, análise de molhabilidade, análise de difratometria de raios X, espectroscopia de infravermelho por transformada de Fourier, diâmetro das fibras e resistência a tração. As NFs produzidas foram incluídas na área de tração dos corpos de prova em resina acrílica ativada termicamente (RAAT) conforme ISO1567, perfazendo 4 grupos (n=20), 1 controle (Grupo 1) e 3 experimentais (Grupo 2, RAAT+NF/ABS; Grupo 2, RAAT+NF/PA6; Grupo 4, RAAT+NF/PS), para ensaio de flexão três pontos para analisar suas propriedades mecânicas, como: módulos de elasticidade e resistência a flexão. De acordo com os testes de caracterização, as mantas se apresentaram hidrofóbicas, não houve mudança de sua estrutura polimérica, concluindo-se então que a técnica da eletrofiação foi promissora na síntese de mantas de NFs. A variação dos parâmetros afetou diretamente a morfologia, resultando em fibras uniformes, volumosas e sem defeitos (beads). Os Grupos 3 e 4 (RAAT+NF/PA6 e RAAT+NF F/PS) apresentaram um maior módulo elástico, conferindo maior rigidez ao material (AU)

This study aimed to synthesize and characterize non-woven blankets of acrylonitrile butadiene styrene (ABS), polyamide 6 (PA6) and polystyrene (PS) nanofibers (NFs), and to evaluate their ability to be used as reinforcement in polymethyl methacrylate (PMMA). ABS was dissolved in dichloromethane and acetone, PA6 by 1,1,1,3,3,3- hexafluoro-2-propanol and PS by dimethylformamide at a concentration defined in a pilot study. After determining the best electrospun parameters (continuous voltage, flow rate and needle/shield distance) the samples from each group were analyzed by scanning electron microscopy, wettability analysis, X-ray diffraction analysis, Fourier transform infrared spectroscopy, fiber diameter and tensile strength. The NFs produced were included in the tensile area of the thermally activated acrylic resin (RAAT) specimens according to ISO1567, making up 4 groups (n = 20), 1 control (Group 1) and 3 experimental (Group 2, RAAT+NF/ABS; Group 3, RAAT+NF/PA6 and Group 4 (RAAT+NF/PS), for three point bending test to analyze their mechanical properties, as: modules of elasticity and flexural strength. According to the characterization tests, the blankets were hydrophobic, there was no change in their polymeric structure, concluding that the electrospinning technique was promising in the synthesis of NFs blankets. The parameters variation affected directly in the morphology, resulting in uniform, bulky and without defects (beads) NFs blankets. The Groups 3 and 4 (NF/PA6+RAAT and NF/PS+RAAT) presented a superior elastic modulus, therefore a superior rigidity(AU)

Eficacia y seguridad a largo plazo del polimetilmetacrilato (PMMA) en pacientes osteoporóticos tratados mediante vertebroplastia percutánea / Long-term efficacy and safety of polymethylmethacrylate (PMMA) in osteoporotic patients treated by percutaneous vertebroplasty

OBJETIVO: Actualmente, existen pocos datos sobre la influencia a largo plazo del polimetilmetacrilato (PMMA) en la integridad de los cuerpos vertebrales tras la vertebroplastia percutánea (VP). Resulta de interés investigar la posible relación entre esta técnica y la aparición con el tiempo de fenómenos de osteólisis o la fragmentación del cemento en las vértebras intervenidas. El objetivo de este trabajo fue investigar si, a largo plazo, existe una pérdida de efectividad y/o seguridad de la VP con PMMA. MATERIAL Y MÉTODOS: Se analizaron radiografías de pacientes intervenidos correspondientes al post-operatorio inmediato y al estudio radiológico más reciente (VP hace más de 15 años). Con ambos estudios radiológicos, describimos: la altura del cuerpo vertebral, la angulación de platillos y la presencia de osteólisis alrededor del cemento en el tiempo. RESULTADOS: Un total de 7 pacientes intervenidos mediante VP con PMMA hace 15 o más años accedieron a realizarse una nueva radiografía en nuestro Centro. Tras el análisis de sus imágenes post-operatorias (inmediatas y a 15 ó más años de la cirugía), no se observó en ninguna de las vértebras intervenidas pérdida de altura del cuerpo vertebral cementado, diferencias de angulación en los platillos, presencia de osteólisis alrededor del cemento o fragmentación del PMMA inyectado. CONCLUSIÓN: El PMMA inyectado en el cuerpo vertebral mantiene una situación estable en el tiempo (más de 15 años). No se observan cambios en la interfaz hueso-PMMA, osteólisis y/o cambios en la altura de los cuerpos vertebrales en los casos analizados

OBJETIVE: Currently, there are limited data on the long-term influence of polymethylmethacrylate (PMMA) on the integrity of vertebral bodies after percutaneous vertebroplasty (PVP). Interesting investigation is being carried out into the possible relationship between this technique and the appearance over time of osteolytic phenomena or cement fragmentation in the intervened vertebrae. The objective of our study was to investigate whether there is a loss of effectiveness and/or safety of PVP with PMMA in the long term. MATERIAL AND METHOD: X-rays were analyzed of intervened patients corresponding to the immediate post-operative and the most recent radiological study (PVP more than 15 years previous). With both radiological studies, we describe: the height of the vertebral body, the angulation of lamellar plates and osteolytic presence around the cement over time. RESULTS: A total of 7 patients operated by PVP with PMMA 15 or more years earlier agreed to have a new radiograph in our center. After the analysis of their post-operative images (immediate and 15 or more years after surgery), no loss of height of the cemented vertebral body, differences in angulation in the lamellar plates, presence of osteolysis around the vertebrae was observed in any of the involved vertebrae cement or fragmentation of the injected PMMA. CONCLUSIONS: PMMA injected into the vertebral body remains stable over time (more than 15 years). There are no changes in the bone-PMMA interface, osteolysis and/or changes in the height of the vertebral bodies in the cases analyzed

Histologic Characterization of Polymethylmethacrylate Dermal Filler Biostimulatory Properties in Human Skin.

BACKGROUND: Little literature exits on the mechanism of action of implanted polymethylmethacrylate (PMMA) filler. OBJECTIVE: To characterize PMMA-induced dermal extracellular matrix production in the skin. MATERIALS AND METHODS: Single-center, open-label prospective study in healthy volunteers undergoing removal of redundant skin was injected intradermally and subdermally with PMMA dermal filler (Bellafill). Punch biopsies were harvested over a time course and evaluated for the deposition of collagen-3 and procollagen-1, proteoglycans and elastin using immunohistochemistry. Blinded histopathologic readings were performed by a dermatopathologist to characterize the nature of the dermal extracellular matrix findings. RESULTS: Normal inflammatory infiltrate was exhibited at all timepoints after PMMA injection with an influx of fibroblasts and new vasculature. Tissue proteoglycans were noted within the injectate beginning at Week 1 and persisted through the study end point. Increased collagen Type 3 was evident following the first week after injection, peaked at Month 2 and diminished through Months 3 through 6. Procollagen-1 was noted at Month 1 and continued to increase in intensity and organization through the study end point (6 months). Elastin staining was inconclusive. Polymethylmethacrylate microspheres remained within the initial injection area and became encapsulated within new collagen fibers. The growth and pattern of new connective tissue mimicked a normal wound healing response. CONCLUSION: Polymethylmethacrylate-collagen gel filler stimulates collagen-3 and procollagen-1 when injected into human skin. This combination of neocollagenesis followed by microencapsulation of PMMA microspheres in the new tissue provides for long-lasting results.

Vancomycin-laden calcium phosphate-calcium sulfate composite allows bone formation in a rat infection model.

OBJECTIVE: Local antibiotic delivery systems with differing chemical and mechanical properties have been developed to assist in the management of osteomyelitis. We investigated the bone conductive and resorptive capabilities of a calcium phosphate-calcium sulfate (CaP/CaS) composite compared with commercially available polymethylmethacrylate (PMMA). In addition, we compared the in vivo preventative and treatment efficacies of both biomaterials in a proven osteomyelitis model. METHODS: Sixty-four, male Sprague-Dawley rats were inoculated with 10 µl of 1.5 x 108 CFU/ml of Staphylococcus aureus in a surgically drilled defect in the right proximal tibia. Infected animals were randomly allocated into prevention and treatment groups with 32 rats each. In the prevention group, the defect was filled with a plug containing either PMMA or CaP/CaS immediately after the inoculation. In the treatment group, the infected defects were irrigated, debrided, and filled with either a PMMA or CaP/CaS plug. Both CaP/CaS and PMMA were impregnated with 10% weight of vancomycin. Rats were sacrificed 6 weeks after cement insertion. Infection was detected by bacterial culture and histological analysis. Bone formation in the defect was assessed with micro-computed tomography and histology. RESULTS: No bacteria were detected in any group. Both the prevention and treatment groups using CaP/CaS had significantly more bone volume fraction, bone area, and cartilage area than the PMMA groups. CONCLUSIONS: When loaded with 10% of vancomycin, CaP/CaS and PMMA have the same efficacy for treatment and prevention of osteomyelitis. CaP/CaS enhances bone defect healing through improved bone remodeling in our osteomyelitis rat model.