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The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 106 GXCPC1, N = 5) and high dose (4 × 107 GXCPC1, N = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = -7.773 to -2.561t at 12 weeks compared to baseline) and knee function (95% CI = -24.297 to -10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study.
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Células Madre Mesenquimatosas , Osteoartritis de la Rodilla , Humanos , Inyecciones Intraarticulares , Osteoartritis de la Rodilla/terapia , Dolor , Proyectos PilotoRESUMEN
BACKGROUND: The cryoablation efficacy of semisolid freezing nitrogen ethanol composite (FNEC) has been demonstrated. We aimed to investigate the feasibility of adjuvant FNEC-assisted cryoablation in different bone cavity types by assessing the perioperative complication rates. METHODS: The medical charts of patients who received intraoperative adjuvant cryoablation using semisolid FNEC for bone tumors from December 2013 to January 2018 were reviewed. The bone cavities were categorized into three types according to liquid spill potential (type 1, able to hold liquid without limb manipulation; type 2, required extensive limb manipulation to retain liquid; type 3, unable to retain liquid). The overall complication rate and the complication rates stratified by bone cavity type were determined. RESULTS: Among the 76 patients, 30.3%, 57.9%, and 11.8% had type 1, 2, and 3 bone cavities, respectively. The mean follow-up time for perioperative complications was 43.5 ± 24.1 days. Five patients experienced complications, including two cases of skin damage, two cases of skin infection, and one case of fracture, yielding an overall perioperative complication rate of 6.4%. All cases of skin damage and skin infection were superficial and manageable by oral antibiotics. The patient with a pathologic fracture recovered well after being treated with open reduction and plate fixation. No neuropraxia was noted within the first few days postsurgery in any patient. The complication rates in type 1, 2, and 3 bone cavities were 13%, 4.6%, and 0%, respectively. CONCLUSION: All bone cavity types had a low incidence of perioperative complications after treatment with adjuvant FNEC-assisted cryoablation. Semisolid FNEC-assisted cryoablation is a feasible alternative to overcome the liquid spill potential in bone cavities resulting from tumor resection and intralesional curettage.
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Neoplasias Óseas , Criocirugía , Humanos , Congelación , Nitrógeno/uso terapéutico , Etanol/efectos adversos , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Criocirugía/efectos adversos , Criocirugía/métodos , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
The development of treatments for critical-sized bone defects has been considered an important topic in the biomedical field because of the high demand for transplantable bone grafts. Following the concept of tissue engineering, implantation of biocompatible porous scaffolds carrying cells and regulating factors is the most efficient strategy to stimulate clinical bone regeneration. With the advancement in the development of 3D-printing techniques, scaffolds with highly controllable architectures can be fabricated to further improve healing efficacies. However, challenges such as the limited biocompatibility of resin materials and poor cell-carrying capacities still exist in the application of current scaffolds. In this study, a novel biodegradable polymer, poly (ethylene glycol)-co-poly (glycerol sebacate) acrylate (PEGSA), was synthesized and blended with hydroxyapatite (HAP) nanoparticles to produce osteoinductive and photocurable resins for 3D printing. The composites were optimized and applied in the fabrication of gyroid scaffolds with biomimetic characteristics and high permeability, followed by the combination of bioactive hydrogels containing Wharton's jelly-derived mesenchymal stem cells (WJMSC) to increase the efficiency of cell delivery. The promotion of osteogenesis from 3D-printed scaffolds was confirmed in-vivo while the hybrid scaffolds were proven to be great platforms for WJMSC culture and differentiation in-vitro. These results indicate that the proposed hybrid systems, combining osteoinductive 3D-printed scaffolds and cell-laden hydrogels, have great potential for bone tissue engineering and are expected to be applied in the treatment of bone defects based on active tissue regeneration.
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Ingeniería de Tejidos , Andamios del Tejido , Ingeniería de Tejidos/métodos , Hidrogeles/farmacología , Huesos , PolímerosRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The treatment of osteoarthritis (OA) patients is a challenging problem. Mesenchymal stem cells (MSCs) are multipotent cells and play key roles in regenerative medicine for cartilage degeneration. GuiLu-ErXian Glue (GLEXG) is an herbal remedy widely used in traditional Chinese medicine to treat joint pain and disability in elderly OA patients. However, the mechanisms of how GLEXG affects MSCs-induced chondrogensis remains to be elucidated. AIM OF THE STUDY: The aim of this study was to investigate the effects of GLEXG on MSC-derived chondrogenesis, both in vitro and in vivo and its potential mechanisms. METHODS: Using human MSC (hMSCs) as in vitro model, the effects of HPLC-profiled GLEXG water extract on chondrogenic differentiation were investigated by 3D spheroid cultures under chondrogenesis-inducing medium (CIM) condition. The chondrogenesis process was evaluated by measuring the sphere sizes, chondrogenesis-related genes expression by reverse transcription real-time PCR that targeted type II/X collagens, SOX9, aggrecan, and protein expression by immunostaining. Anti-TGF-ß1 neutralization antibody was used for mechanistic study. Mono-iodoacetate (MIA) induced OA joint was used to evaluate the effects of GLEXG on in vivo model. MSCs-derived exosomes were purified for proteomics study and senescence process was evaluated by cumulative population doublings and senescence-associated ß-Galactosidase staining. RESULTS: The results showed that GLEXG enhanced hMSCs chondrogenesis and upregulated RNA expression of type II/X collagen, SOX9 and aggrecan at 0.1 µg/mL, 0.3 µg/mL in vitro. In vivo, GLEXG at the dose of 0.3 µg intraarticular (i.a.) injection rescued the MIA-induced cartilage defect. Proteomics and ingenuity pathway analysis obtained from MSCs-released exosomes suggested that senescence pathway was less activated in GLEXG group than in vehicle group. Besides, GLEXG was able to increase cumulative population doubling and delayed hMSCs senescence process after four passages in cultures. CONCLUSION: we conclude that GLEXG promotes in vitro MSC-induced chondrogenesis possibly via exosomes release and delays aging in the MSC senescence process and that treatment with GLEXG (0.3 µg, i.a.) rescued cartilage defects in rat OA knee model.
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Exosomas , Células Madre Mesenquimatosas , Osteoartritis , Humanos , Ratas , Animales , Anciano , Agrecanos/genética , Agrecanos/metabolismo , Agrecanos/farmacología , Condrogénesis/genética , Exosomas/metabolismo , Diferenciación Celular , Colágeno Tipo II/metabolismo , Colágeno Tipo X/metabolismo , Envejecimiento , Células CultivadasRESUMEN
BACKGROUND: Implant-associated infection remains a major complication of orthopedic surgery. The treatment of such infection is complicated by bacterial biofilm formation on the metal surfaces of implants. Biofilm surrounds and protects the bacteria against the organism's endogenous defense system and from external agents such as antibiotics and mechanical debridement. This study aims to evaluate whether freezing nitrogen ethanol composite (FNEC), the combination of liquid nitrogen and 95% ethanol in a 3 to 1 ratio, used frequently in bone tumor surgery, is capable of disinfecting Staphylococcus aureus contaminated implants. METHODS: The femurs of six New Zealand white rabbits were implanted with S. aureus-contaminated screws, half of which were treated with FNEC before implantation. The femurs were harvested 14 days after implantation. Histological analysis and TUNEL assay were conducted. The autoclaved screw, contaminated screw, and FNEC-treated contaminated screw were investigated using scanning electron microscopy to evaluate the biofilm structure. RESULTS: The FNEC-treated group had significantly lower relative C-reactive protein levels. An obvious periosteal reaction at the implant site was observed in all rabbits in the non-FNEC group but none was observed in the FNEC-treated group. The FNEC-treated group exhibited fewer empty lacunae, less inflammatory infiltration, and less bone necrosis. Immunohistochemical analysis showed no S. aureus in bone tissue from the FNEC-treated group. Scanning electron microscopy showed disruption of the biofilm on the contaminated screw treated with FNEC. CONCLUSION: FNEC showed potential in disinfecting S.aureus-contaminated implants. Further investigation is warranted, such as the effect on the implant-cement-bone interface, for FNEC to be used clinically in treating implant-associated infection.
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Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Conejos , Congelación , Etanol/farmacología , Nitrógeno/farmacología , Infecciones Estafilocócicas/etiología , Infecciones Estafilocócicas/microbiología , Biopelículas , Antibacterianos/farmacología , Complicaciones Posoperatorias , Tornillos Óseos/efectos adversosRESUMEN
Angiogenesis plays an important role in the development of bone and bone regeneration to provide the required molecules. Mesenchymal stem cells (MSCs) are pluripotent, self-renewing, and spindle-shaped cells, which can differentiate into multiple lineages such as chondrocytes, osteocytes, and adipocytes. MSCs derived from bone marrow (BMMSCs), adipose tissue (ADMSCs), and Wharton's jelly (UCMSCs) are popular in the field of tissue regeneration. MSCs have been proposed that can promote bone regeneration by enhancing vascularization. In this study, the angiogenic potential of secretomes of undifferentiated and osteo-differentiated BMMSCs, ADMSCs, and UCMSCs seeded on human decellularized allogeneic bone were compared. Human umbilical vein endothelial cells (HUVECs) were treated with MSC secretomes. Cell growth, cell migration, and angiogenesis of HUVECs were analyzed by MTT, wound healing, and tube formation assays. Angiogenic gene expression levels of MSCs were evaluated using real-time quantitative PCR. Antibody neutralization was performed to validate the candidate target. Our study demonstrates that the angiogenic gene expression profile is tissue-dependent and the angiogenic ability of secretomes is independent of the state of differentiation. We also explore that IL-1b is important for MSC angiogenic potential. Taken together, this study proves that IL-1b in the secretomes plays a vital role in angiogenesis.
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Células Madre Mesenquimatosas , Gelatina de Wharton , Humanos , Células Madre Mesenquimatosas/metabolismo , Diferenciación Celular , Regeneración Ósea , Proliferación Celular , Células Endoteliales de la Vena Umbilical Humana , Neovascularización FisiológicaRESUMEN
OBJECTIVE: We designed a highly adhesive cryoprotectant-gel composite (CGC), based on regular liquid-form cryoprotectant base (CB), aiming to protect cartilage tissue during frozen osteoarticular autograft reconstruction for high-grade sarcoma around the joint. This study aimed to evaluate its effectiveness in rat and porcine distal femur models. DESIGN: Fresh articular cartilage samples harvested from distal rat and porcine femurs were divided into 4 test groups: untreated control group, liquid nitrogen (LN) freezing group, LN freezing group pretreated with CB (CB group), and LN freezing group pretreated with CGC (CGC group). Microscopic and macroscopic evaluation of cartilage condition, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay, and apoptotic protein analysis of chondrocytes were performed to confirm our results. RESULTS: In the rat model, CGC could prevent articular cartilage from roughness and preserve more proteoglycans when compared with the LN freezing and CB groups. Western blot analysis showed CGC could prevent cartilage from LN-induced apoptosis supported by caspase-3/8 apoptotic signaling cascade. Macroscopically, we observed CGC could reduce both articular clefting and loss of articular luminance after freezing in the porcine model. In both models, CGC could reduce articular chondrocytes from degeneration. Fewer TUNEL-positive apoptotic and more viable chondrocytes in cartilage tissue were observed in the CGC group in our animal models. CONCLUSION: Our study proved that CGC could effectively prevent cartilage surface and chondrocytes from cryoinjury after LN freezing. Freezing articular cartilage surrounded with high concentration of CGC can be a better alternative to preserve articular cartilage during limb salvage surgery for malignant bone tumor.
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Neoplasias Óseas , Cartílago Articular , Animales , Autoinjertos/metabolismo , Neoplasias Óseas/metabolismo , Neoplasias Óseas/cirugía , Cartílago Articular/metabolismo , Criopreservación/métodos , Crioprotectores/metabolismo , Crioprotectores/farmacología , Congelación , Ratas , PorcinosRESUMEN
In the last few decades, biological reconstruction techniques have improved greatly for treating high-grade osteosarcoma patients. To conserve the limb, and its function the affected tumor-bearing bones have been treated using liquid nitrogen and irradiation processes that enable the removal of entire tumors from the bone, and these treated autografts can be reconstructed for the patients. Here, we focus on the expressions of the growth factor family proteins from the untreated and treated autografts that play a crucial role in bone union, remodeling, and regeneration. In this proteomic study, we identify several important cytoskeletal, transcriptional, and growth factor family proteins that showed substantially low levels in untreated autografts. Interestingly, these protein expressions were elevated after treating the tumor-bearing bones using liquid nitrogen and irradiation. Therefore, from our preliminary findings, we chose to determine the expressions of BMP2, TGF-Beta, and FGFR proteins by the target proteomics approach. Using a newly recruited validation set, we successfully validate the expressions of the selected proteins. Furthermore, the increased growth factor protein expression after treatment with liquid nitrogen may contribute to bone regeneration healing, assist in faster recovery, and reduce local recurrence and metastatic spread in high-grade sarcoma patients.
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Neoplasias Óseas , Osteosarcoma , Autoinjertos , Proteína Morfogenética Ósea 2/genética , Neoplasias Óseas/genética , Neoplasias Óseas/patología , Neoplasias Óseas/terapia , Trasplante Óseo/métodos , Humanos , Nitrógeno , Osteosarcoma/genética , Osteosarcoma/terapia , Proteómica , Factor de Crecimiento Transformador beta/genéticaRESUMEN
BACKGROUND: Liquid nitrogen (LN) has been used as an adjuvant cryotherapy for bone tumors including giant-cell tumor of the bone (GCTB) to remove residual tumor cells after curettage. This study evaluated variables related to the efficacy of LN-based cryoablation in the context of adjuvant treatment of GCTB using porcine femur bone model. METHODS: A porcine femur bone model was adopted to simulate intralesional cryotherapy. A LN-holding cavity (point 1, nadir) in the medial epicondyle, 4 holes (points 2-5) in the shaft situated 5, 10, 15, and 20 mm away from the proximal edge of the cavity, and 2 more holes (points 6 and 7) in the condyle cartilage (10 and 20 mm away from the distal edge of the cavity) were made. The cooling rate was compared between the 5 points. The cellular morphological changes and DNA damage in the GCTB tissue attributable to LN-based cryotherapy were determined by H&E stain and TUNEL assay. Cartilage tissue at points 6 and 7 was examined for the extent of tissue injury after cryotherapy. RESULTS: The temperature kinetics at points 1, 2 reached the reference target and were found to be significantly better than the reference (both p < 0.05). The target temperature kinetics were not achieved at points 4 and 5, which showed a significantly lower cooling rate than the reference (both p < 0.001) without reaching the -60°C target. Compared with untreated samples, significantly higher proportion of shrunken or apoptotic cells were found at points 1-3; very small proportion were observed at points 4, 5. Significantly increased chondrocyte degeneration was observed at point 6, and was absent at point 7. CONCLUSION: The cryotherapy effective range was within 5 mm from nadir. Complications were restricted to within this distance. The cooling rate was unchanged after three repeated cycles of cryotherapy.
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Neoplasias Óseas , Tumor Óseo de Células Gigantes , Animales , Neoplasias Óseas/patología , Crioterapia , Legrado , Tumor Óseo de Células Gigantes/patología , Tumor Óseo de Células Gigantes/cirugía , Nitrógeno , PorcinosRESUMEN
BACKGROUNDS: We designed a patella cryo-free method to protect patella from cryoinjury during recycled frozen bone-prosthesis-composite reconstruction for proximal tibial malignancy. This study aimed to use animal model to ensure safety and efficacy of this method and reported our clinical outcomes. METHODS: Six swine proximal tibias along with patella and patellar tendon were harvested and dived into group A (n = 3, traditional patella freezing) and group B (n = 3, patella cryo-free). Temperature curve measurement, histological analysis, and TUNEL assay were performed in both groups. Clinically, we retrospectively reviewed 23 patients with proximal tibia malignant bone tumor (13: traditional patella freezing method; 10: patella cryo-free method). The clinical and functional outcomes were reported and compared in both groups. RESULTS: Temperature curve of the group B showed that ideal therapeutic temperature (<-60°C) required to kill tumor cells can be achieved in the proximal tibia while the innocent patella can be kept in room temperature at all time. Histological analysis showed better preservation of the cartilage tissue in patella of group B. TUNEL assay showed significantly more apoptotic cells in the frozen tibia of both groups and frozen patella of group A. When reviewing our clinical results, less complication of the patella as well as better functional preservation were found in patients subjecting to patella cryo-free method. No local recurrence was observed in either group. CONCLUSION: Patellar cryo-free technique could protect patella from cryoinjury during freezing and therefore preserve more extensor functions for patients with proximal tibial malignant bone tumors.
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Neoplasias Óseas , Tibia , Animales , Autoinjertos , Neoplasias Óseas/cirugía , Congelación , Humanos , Rótula/cirugía , Estudios Retrospectivos , Porcinos , Tibia/cirugíaRESUMEN
Osteosarcoma is a highly malignant musculoskeletal tumor that is commonly noticed in adolescent children, young children, and elderly adults. Due to advances in surgery, chemotherapy and imaging technology, survival rates have improved to 70-80%, but chemical treatments do not enhance patient survival; in addition, the survival rate after chemical treatments is still low. The most obvious clinical feature of osteosarcoma is new bone formation, which is called "sun burst". Estrogen receptor alpha (ERα) is an essential feature of osteogenesis and regulates cell growth in various tumors, including osteosarcoma. In this study, we sought to investigate the role of ERα in osteosarcoma and to determine if ERα can be used as a target to facilitate the chemosensitivity of osteosarcoma to current treatments. The growth rate of each cell clone was assayed by MTT and trypan blue cell counting, and cell cycle analysis was conducted by flow cytometry. Osteogenic differentiation was induced by osteogenic induction medium and quantified by ARS staining. The effects of ERα on the chemoresponse of OS cells treated with doxorubicin were evaluated by colony formation assay. Mechanistic studies were conducted by examining the levels of proteins by Western blot. The role of ERα on OS prognosis was investigated by an immunohistochemical analysis of OS tissue array. The results showed an impaired growth rate and a decreased osteogenesis ability in the ERα-silenced P53(+) OS cell line U2OS, but not in P53(-) SAOS2 cells, compared with the parental cell line. Cotreatment with tamoxifen, an estrogen receptor inhibitor, increased the sensitivity to doxorubicin, which decreased the colony formation of P53(+) U2OS cells. Cell cycle arrest in the S phase was observed in P53(+) U2OS cells cotreated with low doses of doxorubicin and tamoxifen, while increased levels of apoptosis factors indicated cell death. Moreover, patients with ER-/P53(+) U2OS showed better chemoresponse rates (necrosis rate > 90%) and impaired tumor sizes, which were compatible with the findings of basic research. Taken together, ERα may be a potential target of the current treatments for osteosarcoma that can control tumor growth and improve chemosensitivity. In addition, the expression of ERα in osteosarcoma can be a prognostic factor to predict the response to chemotherapy.
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Neoplasias Óseas/tratamiento farmacológico , Resistencia a Antineoplásicos , Receptor alfa de Estrógeno/antagonistas & inhibidores , Regulación Neoplásica de la Expresión Génica , Osteosarcoma/tratamiento farmacológico , Tamoxifeno/farmacología , Proteína p53 Supresora de Tumor/metabolismo , Apoptosis , Neoplasias Óseas/genética , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Ciclo Celular , Proliferación Celular , Antagonistas de Estrógenos/farmacología , Humanos , Osteosarcoma/genética , Osteosarcoma/metabolismo , Osteosarcoma/patología , Células Tumorales Cultivadas , Proteína p53 Supresora de Tumor/genéticaRESUMEN
Allogeneic bone grafts are a promising material for bone implantation due to reduced operative trauma, reduced blood loss, and no donor-site morbidity. Although human decellularized allogeneic bone (hDCB) can be used to fill bone defects, the research of revitalizing hDCB blocks with human mesenchymal stem cells (hMSCs) for osteochondral regeneration is missing. The hMSCs derived from bone marrow, adipose tissue, and Wharton's jelly (BMMSCs, ADMSCs, and UMSCs, respectively) are potential candidates for bone regeneration. This study characterized the potential of hDCB as a scaffold for osteogenesis and chondrogenesis of BMMSCs, ADMSCs, and UMSCs. The pore sizes and mechanical strength of hDCB were characterized. Cell survival and adhesion of hMSCs were investigated using MTT assay and F-actin staining. Alizarin Red S and Safranin O staining were conducted to demonstrate calcium deposition and proteoglycan production of hMSCs after osteogenic and chondrogenic differentiation, respectively. A RT-qPCR was performed to analyze the expression levels of osteogenic and chondrogenic markers in hMSCs. Results indicated that BMMSCs and ADMSCs exhibited higher osteogenic potential than UMSCs. Furthermore, ADMSCs and UMSCs had higher chondrogenic potential than BMMSCs. This study demonstrated that chondrogenic ADMSCs- or UMSCs-seeded hDCB might be potential osteochondral constructs for osteochondral regeneration.
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Condrogénesis/fisiología , Células Madre Mesenquimatosas/metabolismo , Osteogénesis/fisiología , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Médula Ósea/metabolismo , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Huesos/metabolismo , Diferenciación Celular , Supervivencia Celular , Células Cultivadas , Trasplante de Células Madre Hematopoyéticas , Humanos , Células Madre Mesenquimatosas/fisiología , Gelatina de Wharton/citología , Gelatina de Wharton/metabolismoRESUMEN
PURPOSE: This retrospective, single-centre study compares the clinical and radiographic outcomes of limb reconstruction using recycled autografts to that using allografts. METHODS: Patients with histopathologically verified high-grade osteosarcoma treated with wide bone resection and limb reconstruction using allografts or recycled autografts from January 1998 through December 2012 were retrospectively screened for enrolment eligibility. The final study cohort included 255 patients (allograft, 91; recycled autograft, 164). Data regarding post-operative complications, salvage treatment, and graft survival were collected. A modified International Society of Limb Salvage classification system was used to evaluate the radiographic findings. RESULTS: The time to graft-host union did not differ significantly between the two graft types. Patients receiving recycled autografts had fewer complications compared than did those receiving allografts (recycled autografts vs. allograft: structural failure, 4.3 vs. 13.2%; late infection, 2.4 vs. 7.7%; all p < 0.05). Complications occurred most frequently during the first three years after surgery, and the majority were manageable. The five year limb survival rate did not differ significantly between the two graft types (91.3 vs. 94.0%; p = 0.752). No local oncological recurrence was observed within the recycled autografts. CONCLUSION: Recycled autografts and allografts are feasible options for biological limb reconstructions in terms of complications and graft survival after wide resection of osteosarcoma.
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Neoplasias Óseas , Osteosarcoma , Aloinjertos , Autoinjertos , Neoplasias Óseas/epidemiología , Neoplasias Óseas/cirugía , Trasplante Óseo , Humanos , Recurrencia Local de Neoplasia , Osteosarcoma/epidemiología , Osteosarcoma/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: The administration of an intra-articular injection (IAI) of tranexamic acid (TXA) has been demonstrated to be effective in reducing both blood loss and transfusion rate during total knee arthroplasty (TKA); however, few studies have reported the efficiency of a peri-articular injection (PAI) of TXA. We studied the efficiency of a PAI of TXA in reducing blood loss during TKA. METHODS: Fifty patients undergoing primary simultaneous bilateral TKA were enrolled in this retrospective study. The right knee received a PAI of 1 g of TXA (Group I), and the left knee received an IAI of 1 g of TXA (Group II). The clinical outcome measures were a change in blood loss from Hemovac drains and surgical time. RESULTS: The decrease in blood loss from the Hemovac was significantly lower in Group I (460.1 ± 36.79 vs. 576.0 ± 34.01, P < 0.001) than in Group II, and no significant difference in surgical times was observed. The blood transfusion rate in the present study was 16 %. CONCLUSIONS: A PAI of TXA may reduce blood loss more efficiently than an IAI of TXA during TKA without increased complications such as surgical site infection, poor wound healing, skin necrosis, pulmonary embolism, and deep vein thrombosis.
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Antifibrinolíticos , Artroplastia de Reemplazo de Rodilla , Ácido Tranexámico , Administración Intravenosa , Antifibrinolíticos/uso terapéutico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Pérdida de Sangre Quirúrgica/prevención & control , Humanos , Inyecciones Intraarticulares , Hemorragia Posoperatoria/inducido químicamente , Hemorragia Posoperatoria/prevención & control , Estudios RetrospectivosRESUMEN
PURPOSE: The recycled autograft in biological reconstruction for osteosarcoma has satisfactory outcome. There are few studies about its efficacy in pathological fracture. The aim of the study is to compare the clinical results of recycled autograft to those of allograft in patients with high-grade osteosarcoma with pathological fracture. PATIENTS AND METHODS: Between October 2010 and March 2018, 30 patients with osteosarcoma combining pathological fracture underwent biological reconstruction. Eleven patients received recycled autograft via extracorporeal irradiation or freezing nitrogen and nineteen patients restored bone defect via allograft to accomplish biological reconstruction. RESULTS: The mean follow-up was 58.1 months (range 12-120). The mean time to graft-host union of limbs reconstructed using recycled autografts and allografts was 17.45 ± 13.54 and 12.63 ± 12.62 months, respectively, with no significant difference observed between groups (p = 0.176). The five year probability of graft failure therefore did not significantly differ between groups (p = 0.245). The patient five year survival rate was similar (p = 0.229). Post-operative complication rates were similar for the recycled autograft group (54.5%) and the allograft group (57.9%). CONCLUSION: The recycled autograft showed comparable clinical results, graft-host union time, complication rate, and graft survival to allograft in biological reconstruction for osteosarcoma with pathological fracture.
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Neoplasias Óseas , Fracturas Espontáneas , Osteosarcoma , Aloinjertos , Autoinjertos , Neoplasias Óseas/cirugía , Fracturas Espontáneas/etiología , Fracturas Espontáneas/cirugía , Humanos , Osteosarcoma/cirugíaRESUMEN
The use of cryoablation/cryosurgery in treating solid tumors has been proven as a unique technique that uses lethal temperatures to destroy the tumors and impart better functions for the affected organs. This novel technique recently demonstrated the best clinical results in chondrosarcoma (CSA) with faster recovery, less recurrence, and metastasis. Due to the resistant nature of CSA to chemo and radiation therapy, cryoablation comes to light as the best alternative approach. Therefore, for the first time, we aimed to compare CSA-untreated with cryoablation treated samples to discover some potential markers that may provide various clues in terms of diagnosis and pathophysiology and may facilitate the development of novel methods to treat sarcoma efficiently. To find the altered proteins among both groups, a mass-based label-free approach was employed and identified a total of 160 significantly altered proteins. Among these, 138 proteins were dysregulated with <1- to -0.1-fold, 18 proteins were up-regulated with >3 folds, and four proteins were similarly expressed in the untreated group compared to the treated. Interestingly, the differential expressions of proteins from the untreated group showed contrast expressions in the treated group. Furthermore, the functional enrichment analysis revealed that most of the identified proteins from this study were associated with various significant pathways such as glycolysis, MAPK activation, PI3K-Akt signaling, extracellular matrix degradation, etc. In addition, two protein expressions, such as fibronectin and annexin-1, were validated by immunoblot analysis. Therefore, this study signifies the most comprehensive discovery of altered protein expressions to date and the first large-scale detection of protein profiles from CSA-cryoablation treated compared to untreated. This work may serve as the basis for future research to open novel treatment options for chondrosarcoma.
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Neoplasias Óseas/cirugía , Condrosarcoma/cirugía , Criocirugía , Proteínas/metabolismo , Proteómica/métodos , Adulto , Anciano , Western Blotting , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Condrosarcoma/metabolismo , Condrosarcoma/patología , Cromatografía Liquida/métodos , Femenino , Fibronectinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Mapas de Interacción de Proteínas , Proteínas/análisis , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en Tándem/métodosRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) posed a major threat to the clinical practice of orthopedic surgeons, especially in the emergency department. We aim to present: (1) the criteria established by the Surgery Management Committee of Taipei Veterans General Hospital in response to COVID-19 and (2) the impact of COVID-19 screening on orthopedic trauma patients in the emergency department. METHODS: From April 1 to April 30, 2020, all orthopedic trauma patients in the emergency department were screened for COVID-19 if they fulfilled any of the following: (1) travel from abroad within 14 days, (2) high-risk occupation, (3) contact or cluster history with a COVID-19-positive patient, and (4) any associated symptom, including fever up to 38°C, cough, sore throat, rhinorrhea, loss of taste or smell, muscle soreness, malaise, or shortness of breath. We recorded details on the injury, fever, management, and associated outcomes. RESULTS: Of the 163 orthopedic trauma patients presenting to the emergency department, 24 were screened for COVID-19; of these, 22 received surgery. Sixty-two patients received surgery without screening for COVID-19. Fever was the most common reason to screen for COVID-19 (N = 20; 83.3%). No patients were COVID-19 positive. Screened patients had a significantly longer mean interval from presentation to the emergency department to surgery (2.7 ± 2.5 vs. 1.5 ± 0.8 days, p = 0.037). Of the 20 patients screened because of fever, the focus was not identified in 12 (60.0%) patients. The other eight had urinary tract infection (N = 6; 27.2%), septic hip (N = 1; 4.6%), and concomitant pneumonia and urinary tract infection (N = 1; 4.6%). The mean duration of fever and hospital stay was 4.3 ± 4.6 and 8.7 ± 4.9 days, respectively. There were no thromboembolic events, surgical complications, or in-hospital mortality. CONCLUSION: We developed safe and reliable screening criteria for this COVID-19 pandemic. The delay in surgery was reasonable and did not adversely affect in-patient outcomes.
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COVID-19/diagnóstico , Servicio de Urgencia en Hospital/estadística & datos numéricos , Fracturas Óseas , Ortopedia , Centros Traumatológicos/estadística & datos numéricos , Adulto , Anciano , Niño , Femenino , Fiebre , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Pandemias , Estudios Retrospectivos , Taiwán , Adulto JovenRESUMEN
Cementation of a highly cross-linked polyethylene liner into a well-fixed acetabular shell provided a good durability for liner wear. However, its efficacy in treating recurrent instability due to malposition cup is less reported. The aim of this study is to evaluate the outcome of this surgical technique to treat hip instability. From 2009 to 2019, we have identified 38 patients who had been surgically treated for recurrent instability, including cementation liner (N = 20) and revision cup (N = 18) procedures. Patients were followed for a mean of 45.66 months. We have recorded and analyzed all causes of implant failure including recurrent instability. Clinical outcomes were assessed including complication and Harris Hip Score (HHS) preoperatively and at the latest follow-up. Revision-free survivorship for any cause was 95.0% at 1 year, and 84.4% at 5 years in cementation liner group and 88.9% at 1 year and 5 years in revision cup group. Mean Harris hip score improved from 48.3 points preoperatively to 79.5 points at the last follow-up in cementation liner group and mean HHS improved from 43.3 points preoperatively to 77.2 points in revision cup group. There were two implant failures in each group, including one is due to persistent hip instability and the other is due to periprosthetic joint infection in the cementation liner group and two implant failure are due to persistent hip instability in the revision cup group. Functional scores and implant survival were similar in both groups. We demonstrated that orientation correction via the cementation of the polyethylene liner into well-fixed acetabular shell is a promising option to treat and prevent instability. Level of Evidence: Therapeutic Level IV.
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Artroplastia de Reemplazo de Cadera/efectos adversos , Cementos para Huesos/uso terapéutico , Cementación/métodos , Luxaciones Articulares/terapia , Falla de Prótesis/efectos adversos , Acetábulo/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/instrumentación , Femenino , Estudios de Seguimiento , Prótesis de Cadera/efectos adversos , Humanos , Luxaciones Articulares/etiología , Masculino , Persona de Mediana Edad , Polietileno , Reoperación/estadística & datos numéricos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Giant cell tumors of bone (GCT) are benign tumors that show a locally aggressive nature and affect bones' architecture. Recently, cryoablation and irradiation treatments have shown promising results in GCT patients with faster recovery and less recurrence and metastasis. Therefore, it became a gold standard surgical treatment for patients. Hence, we have compared GCT-untreated, cryoablation, and irradiation-treated samples to identify protein alterations using high-frequency liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Our label-free quantification analysis revealed a total of 107 proteins (p < 0.01) with 26 up-regulated (< 2-folds to 5-fold), and 81 down-regulated (> 0.1 to 0.5 folds) proteins were identified from GCT-untreated and treated groups. Based on pathway analysis, most of the identified up-regulated proteins involved in critical metabolic functions associated with tumor proliferation, angiogenesis, and metastasis. On the other hand, the down-regulated proteins involved in glycolysis, tumor microenvironment, and apoptosis. The observed higher expressions of matrix metalloproteinase 9 (MMP9) and TGF-beta in the GCT-untreated group associated with bones' osteolytic process. Interestingly, both the proteins showed reduced expressions after cryoablation treatment, and contrast expressions identified in the irradiation treated group. Therefore, these expressions were confirmed by immunoblot analysis. In addition to these, several glycolytic enzymes, immune markers, extracellular matrix (ECM), and heat shock proteins showed adverse expressions in the GCT-untreated group were identified with favorable regulations after treatment. Therefore, the identified expression profiles will provide a better picture of treatment efficacy and effect on the molecular environment of GCT.
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Criocirugía , Tumor Óseo de Células Gigantes/metabolismo , Tumor Óseo de Células Gigantes/terapia , Proteómica , Espectrometría de Masas en Tándem , Adolescente , Niño , Preescolar , Cromatografía Liquida , Regulación hacia Abajo , Femenino , Ontología de Genes , Tumor Óseo de Células Gigantes/radioterapia , Tumor Óseo de Células Gigantes/cirugía , Humanos , Masculino , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Mapas de Interacción de Proteínas , Reproducibilidad de los Resultados , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: Bone tumors are often treated with intralesional curettage. High-speed burring, an adjuvant therapy, was performed to maximize the tumor cell killing; however, tumor recurrence might still occur, which may be caused by residual tumor or local tumor spread during surgery. METHODS: A porcine cadaver (femur) was utilized to determine whether the use of a high-speed burr causes bone cement spray. To mimic residual tumor after curettage, luminescent cement was smeared on two locations of the bone cavity, the wall and the bottom. The cavity in the femoral bone was then placed in the middle of a sheet of drawing paper featuring 10 cm, 20 cm, and 30 cm concentric circles. The luminescent cement was then burred totally with a high-speed burr. RESULTS: The intensity of the area in the wall in circle I was 72.6% ± 5.8%; within circle II, it was 22.1% ± 4.2%; and within circle III, it was 5.4% ± 1.5%. The intensity of the area within the bottom of the femoral bone within circle I was 66.5% ± 6.1%, within circle II was 28.1 ± 4.8%, and within circle III, it was 5.4% ± 1.4%. The amount of luminescent cement seeding decreased with distance, but there was no difference while burring at different locations of the bone cavity. Under the handpiece cover, a greater amount of cement spray was retained in circle I during burring of the cement in the bottom of the cavity and less was sprayed out in circle III. CONCLUSIONS: High-speed burring may cause explosive bone cement spray, which could extend to 20 cm. The intensities of spray did not decrease, even when the handpiece cover was used. The wide range of bone cement spray caused by high-speed burr was inspected in this pilot study, which may lead to tumor seeding. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.