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1.
Int Orthop ; 47(1): 175-186, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36401020

RESUMO

PURPOSE: This study aimed to evaluate the infection control rate of palliative arthroscopic debridement, antibiotics, and implant retention (DAIR) for the high mortality risk or terminal cancer stage patients. METHODS: From March 2018 to August 2021, 21 patients met the following inclusion criteria: old age of more than 80, diagnosed as a terminal stage of cancer, high risk of mortality and morbidity representing as Charlson comorbidity index (CCI) ≥ 5, low daily activity with disabled extremity, and re-infection after two-stage revision. Each patient underwent arthroscopic DAIR and additional continuous irrigation for 48 hours. The need for subsequent re-arthroscopic DAIR or two-stage revision was determined by the post-operative trends of C-reactive protein (CRP) levels. Infection control was defined as continuing controlled status of infection based on clinical and laboratory results by one or two times of arthroscopic DAIR within initial two months. Treatment failure was defined as more than three times arthroscopic debridement, two-stage revision surgery, or expired due to uncontrolled infection. RESULTS: Arthroscopic DAIR controlled the infection in 19 (90.5%) of the 21 cases. The other knee underwent a total of three times of re-arthroscopic DAIR and the other one underwent two-stage revision. Although five patients expired during the follow-up period due to worsening medical problems or terminal cancer, there were no deaths from uncontrolled infection, sepsis, or surgery-related complications. CONCLUSIONS: Arthroscopic debridement with continuous irrigation for the infection TKA with high mortality risk or terminal cancer patients showed a 90.5% infection control rate. For high-risk patients, arthroscopic debridement with continuous irrigation can be an alternative treatment to improve the quality of life during survival.


Assuntos
Artroplastia do Joelho , Infecções Relacionadas à Prótese , Humanos , Artroplastia do Joelho/efeitos adversos , Desbridamento/efeitos adversos , Desbridamento/métodos , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Antibacterianos/uso terapêutico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/cirurgia , Infecções Relacionadas à Prótese/diagnóstico
3.
Appl Health Econ Health Policy ; 21(1): 141-152, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36136263

RESUMO

OBJECTIVES: The aim of this study was to assess the cost effectiveness of allogeneic umbilical cord blood-derived mesenchymal stem cells with sodium hyaluronate (hUCB-MSC) compared with microfracture in patients with knee cartilage defects caused by osteoarthritis (OA) in South Korea. METHODS: A partitioned survival model approach was taken consisting of five mutually exclusive health states: excellent, good, fair, poor, and death over a 20-year time horizon. Utility values were obtained from a randomized clinical trial. Cost data were extracted from a database provided by the Health Insurance Review & Assessment Service, and the utilization of healthcare services was estimated from an expert panel of orthopedic surgeons using a structured questionnaire. The incremental cost-effectiveness ratio (ICER) in terms of quality-adjusted life-years (QALY) was calculated. Deterministic and probabilistic sensitivity analyses were performed. RESULTS: In the base case, the incremental costs of US$14,410 for hUCB-MSC therapy along with its associated QALY gain of 0.857 resulted in an ICER of US$16,812 (₩18,790,773) per QALY (95% confidence interval [CI] US$13,408-US$20,828) when compared with microfracture treatment from a healthcare payer perspective. From a societal perspective, the ICER was US$268 (₩299,255) per QALY (95% CI -US$2915 to US$3784). When using a willingness-to-pay threshold of US$22,367/QALY, the probability of hUCB being cost effectiveness compared with microfracture was 99% from the healthcare payer perspective and 100% from the societal perspective. CONCLUSIONS: The study demonstrated that hUCB-MSC therapy was cost effective compared with microfracture when treating patients with knee OA. These findings should inform health policy decision makers about considerations for cost-effective therapy for treating knee OA to ultimately enhance population health.


Assuntos
Fraturas de Estresse , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Análise de Custo-Efetividade , Sangue Fetal , Análise Custo-Benefício , Anos de Vida Ajustados por Qualidade de Vida
4.
Medicina (Kaunas) ; 58(9)2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36143903

RESUMO

Background and Objectives: Intraarticular injection of tranexamic acid (IA-TXA) plus drain-clamping is a preferred method of reducing bleeding after total knee arthroplasty (TKA). However, no consensus has been reached regarding the timing of the clamping. The purpose of this study was to determine the optimum duration of drain-clamping after TKA with IA-TXA. Materials and Methods: We retrospectively reviewed 151 patients that underwent unilateral TKA with IA-TXA plus drain-clamping for 30 min, 2 h, or 3 h. The total drained volume was reviewed as the primary outcome, and hematocrit (Hct) reductions, estimated blood loss (EBL), transfusion rates, and wound complications were reviewed as secondary outcomes. Results: The mean total drained volume, Hct reduction, and EBL were significantly less in the 3 h group than in the 30 min group. Between the 2 h and 3 h groups, there was no statistical difference in the mean total drained volume, Hct reduction, or EBL. The proportion of patients who drained lesser than 300 mL was high in the 3 h group. No significant intergroup difference was observed for transfusion volume, transfusion rate, and wound related complications. Conclusions: In comparison of the IA-TXA plus drain-clamping after TKA, there was no difference in EBL between the 2 h group and the 3 h group, but the amount of drainage volume was small in the 3 h group.


Assuntos
Antifibrinolíticos , Artroplastia do Joelho , Ácido Tranexâmico , Antifibrinolíticos/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Perda Sanguínea Cirúrgica , Constrição , Drenagem/métodos , Humanos , Injeções Intra-Articulares , Hemorragia Pós-Operatória/prevenção & controle , Estudos Retrospectivos , Ácido Tranexâmico/uso terapêutico
5.
J Int Med Res ; 50(4): 3000605221085062, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35387501

RESUMO

OBJECTIVE: To compare the clinical outcomes among three analgesic techniques, continuous femoral nerve block (CFNB), epidural patient-controlled analgesia (EPCA) and periarticular injection (PAI), in patients undergoing total knee arthroplasty (TKA). METHODS: This retrospective case-control study enrolled patients that underwent TKA. Visual analogue scale (VAS) pain scores, sleep disturbance, additional opioid consumption and incidence of opioid-related side-effects were assessed. RESULTS: A total of 120 patients were categorized into three groups: EPCA (group A, n = 40), PAI (group B, n = 40) and CFNB (group C, n = 40). Group C had significantly lower VAS pain scores than groups A and B at 8, 12 and 24 h after TKA. There were no significant differences in VAS pain scores among the three groups from 48 h after TKA. Sleep quality on the first day after surgery was significantly better in group C than in groups A and B. Additional opioid consumption was significantly lower in the group C than in the groups A and B. Group C showed a lower rate of opioid-related side-effects than groups A and B. CONCLUSION: CFNB was a more effective additional analgesic technique than EPCA or PAI for acute postoperative pain control within 24 h of TKA.


Assuntos
Artroplastia do Joelho , Bloqueio Nervoso , Analgesia Controlada pelo Paciente , Analgésicos/uso terapêutico , Analgésicos Opioides/uso terapêutico , Anestésicos Locais/uso terapêutico , Artroplastia do Joelho/efeitos adversos , Artroplastia do Joelho/métodos , Estudos de Casos e Controles , Nervo Femoral , Humanos , Injeções Intra-Articulares/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/etiologia , Estudos Retrospectivos
6.
Int J Mol Sci ; 23(3)2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-35163541

RESUMO

Osteoarthritis (OA) has generally been introduced as a degenerative disease; however, it has recently been understood as a low-grade chronic inflammatory process that could promote symptoms and accelerate the progression of OA. Current treatment strategies, including corticosteroid injections, have no impact on the OA disease progression. Mesenchymal stem cells (MSCs) based therapy seem to be in the spotlight as a disease-modifying treatment because this strategy provides enlarged anti-inflammatory and chondroprotective effects. Currently, bone marrow, adipose derived, synovium-derived, and Wharton's jelly-derived MSCs are the most widely used types of MSCs in the cartilage engineering. MSCs exert immunomodulatory, immunosuppressive, antiapoptotic, and chondrogenic effects mainly by paracrine effect. Because MSCs disappear from the tissue quickly after administration, recently, MSCs-derived exosomes received the focus for the next-generation treatment strategy for OA. MSCs-derived exosomes contain a variety of miRNAs. Exosomal miRNAs have a critical role in cartilage regeneration by immunomodulatory function such as promoting chondrocyte proliferation, matrix secretion, and subsiding inflammation. In the future, a personalized exosome can be packaged with ideal miRNA and proteins for chondrogenesis by enriching techniques. In addition, the target specific exosomes could be a gamechanger for OA. However, we should consider the off-target side effects due to multiple gene targets of miRNA.


Assuntos
Exossomos/transplante , Células-Tronco Mesenquimais/citologia , MicroRNAs/genética , Osteoartrite/terapia , Animais , Diferenciação Celular , Condrogênese , Progressão da Doença , Exossomos/genética , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/imunologia , Comunicação Parácrina , Regeneração
7.
J Med Internet Res ; 23(3): e20989, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33646133

RESUMO

BACKGROUND: With the development of health care-related mobile apps, attempts have been made to implement remote patient-reported outcome measures (PROMs). In order for remote PROMs to be widely used by mobile apps, the results should not be different depending on the location; that is, remote PROM results performed in locations other than hospitals should be able to obtain reliable results equivalent to those performed in hospitals, and this is very important. However, to our knowledge, there are no studies that have assessed the reliability of PROMs using mobile apps according to the location by comparing the results performed remotely from the hospital and performed at the outpatient visits. OBJECTIVE: The purpose of this study was to evaluate the reliability of remote PROMs using mobile apps compared to PROMs performed during outpatient follow-up visits after arthroscopic shoulder surgery. METHODS: A total of 174 patients who underwent arthroscopic rotator cuff repair completed questionnaires 2 days before visiting the clinic for the 1-, 2-, 3-, 6-, and 12-month follow-ups (test A). The patients completed the questionnaires at the clinic (test B) using the same mobile app and device for the 1-, 2-, 3-, 6-, and 12-month follow-ups. Test-retest comparisons were performed to analyze the differences and reliability of the PROMs according to the period. RESULTS: Comparisons of tests A and B showed statistically significant differences at 1, 2, and 3 months (all Ps<.05 except for the ASES function scale at 3-months) but not 6 or 12 months after surgery (all Ps>.05). The intraclass correlation values between the two groups were relatively low at the 1-, 2-, and 3-month follow-ups but were within the reliable range at 6 and 12 months after surgery. The rate of completion of tests A and B using the mobile app was significantly lower in the group older than 70 years than in the other groups for all postoperative periods (P<.001). CONCLUSIONS: PROMs using mobile apps with different locations differed soon after surgery but were reliably similar after 6 months. The remote PROMs using mobile apps could be used reliably for the patient more than 6 months after surgery. However, it is to be expected that the use of mobile app-based questionnaires is not as useful in the group older than 70 years as in other age groups.


Assuntos
Aplicativos Móveis , Seguimentos , Humanos , Pacientes Ambulatoriais , Medidas de Resultados Relatados pelo Paciente , Reprodutibilidade dos Testes , Manguito Rotador , Resultado do Tratamento
8.
Orthop J Sports Med ; 9(1): 2325967120973052, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33490296

RESUMO

BACKGROUND: There is currently no optimal method for cartilage restoration in large, full-thickness cartilage defects in older patients. PURPOSE: To determine whether implantation of a composite of allogeneic umbilical cord blood-derived mesenchymal stem cells and 4% hyaluronate (UCB-MSC-HA) will result in reliable cartilage restoration in patients with large, full-thickness cartilage defects and whether any clinical improvements can be maintained up to 5 years postoperatively. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A randomized controlled phase 3 clinical trial was conducted for 48 weeks, and the participants then underwent extended 5-year observational follow-up. Enrolled were patients with large, full-thickness cartilage defects (International Cartilage Repair Society [ICRS] grade 4) in a single compartment of the knee joint, as confirmed by arthroscopy. The defect was treated either with UCB-MSC-HA implantation through mini-arthrotomy or with microfracture. The primary outcome was proportion of participants who improved by ≥1 grade on the ICRS Macroscopic Cartilage Repair Assessment (blinded evaluation) at 48-week arthroscopy. Secondary outcomes included histologic assessment; changes in pain visual analog scale (VAS) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and International Knee Documentation Committee (IKDC) score from baseline; and adverse events. RESULTS: Among 114 randomized participants (mean age, 55.9 years; 67% female; body mass index, 26.2 kg/m2), 89 completed the phase 3 clinical trial and 73 were enrolled in the 5-year follow-up study. The mean defect size was 4.9 cm2 in the UCB-MSC-HA group and 4.0 cm2 in the microfracture group (P = .051). At 48 weeks, improvement by ≥1 ICRS grade was seen in 97.7% of the UCB-MSC-HA group versus 71.7% of the microfracture group (P = .001); the overall histologic assessment score was also superior in the UCB-MSC-HA group (P = .036). Improvement in VAS pain, WOMAC, and IKDC scores were not significantly different between the groups at 48 weeks, however the clinical results were significantly better in the UCB-MSC-HA group at 3- to 5-year follow-up (P < .05). There were no differences between the groups in adverse events. CONCLUSION: In older patients with symptomatic, large, full-thickness cartilage defects with or without osteoarthritis, UCB-MSC-HA implantation resulted in improved cartilage grade at second-look arthroscopy and provided more improvement in pain and function up to 5 years compared with microfracture. REGISTRATION: NCT01041001, NCT01626677 (ClinicalTrials.gov identifier).

9.
J Orthop Surg (Hong Kong) ; 28(3): 2309499020972204, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33258399

RESUMO

BACKGROUND: The best strategy for implant selection in midshaft clavicular fractures (MCF) remains controversial. The present study aims to determine the optimal strategy for implant selection by comparing plate and Titanium Elastic Nail (TEN) with respect to outcomes and related complications and analyze the results based on fracture patterns. METHODS: A total of 97 patients with MCF who underwent plate (48 patients) or TEN (49 patients) fixation were retrospectively reviewed. Both groups were divided into three subgroups by fracture type using the AO Foundation/Orthopaedic Trauma Association classification: simple fracture (type A), wedge fracture (type B), and multi-fragmentary fracture (type C). The observed outcome measures were bone union rate, related complications, functional scores, and patient satisfaction score. These outcomes were analyzed based on the fracture classification. RESULTS: Both groups demonstrated excellent union rates (p = 0.495) and similar functional scores (p > 0.05). Visual analog scale (VAS) for satisfaction was better in TEN than plate fixation (p < 0.001). In type A and B subgroups, there were no significant difference in functional scores between plate and TEN fixation (p > 0.05). In type C subgroup, however, both VAS for pain and DASH score in TEN fixation were significantly worse than in plate fixation at 2 and 6 weeks postoperatively (p < 0.05). The incidences of clavicle shortening and skin irritation are higher especially in type C subgroup of TEN fixation (p < 0.05). CONCLUSION: Patient satisfaction of TEN fixation was higher than that of plate fixation, but TEN fixation had a higher incidence of early postoperative pain and migration in type C fractures. Therefore, type A and B fractures can successfully be treated with plate or TEN fixation, but type C fractures should be treated with plate fixation.


Assuntos
Pinos Ortopédicos , Placas Ósseas , Clavícula/lesões , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Titânio , Adolescente , Adulto , Clavícula/diagnóstico por imagem , Clavícula/cirurgia , Feminino , Fraturas Ósseas/classificação , Fraturas Ósseas/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Satisfação do Paciente , Radiografia , Estudos Retrospectivos , Adulto Jovem
10.
PLoS One ; 15(9): e0238024, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991606

RESUMO

INTRODUCTION: At present, information about clinical efficacy and adverse events of controlled release (CR) form of pelubiprofen, a prodrug of 2-arylopropionic acid with relatively selective effects on cyclooxygenase-2 activity, remains scarce. In this study, we sought to determine non-inferiority of pelubiprofen CR 90 mg/day compared to aceclofenac 200 mg/day regarding clinical efficacy and adverse events after a 4-week course of medication in the patients with symptomatic knee osteoarthritis. MATERIALS AND METHODS: A total of 191 patients were randomly assigned to take either pelubiprofen CR 90 mg (n = 95) or aceclofenac 200 mg (n = 96). The primary outcome variable was non-inferiority of pain reduction between baseline and week 4 when assessed using a 100 mm pain visual analogue scale (VAS). Pelubiprofen was considered non-inferior to aceclofenac if the upper limit of the one-sided 97.5% confidence interval for the difference in terms of pain VAS was above 15 mm (the average change of pain VAS in the pelubiprofen group-pain VAS reduction in the aceclofenac group). Secondary outcome variables were the changes in 100 mm pain VAS at week 2 versus baseline, K-Western Ontario, and McMaster University Arthritis Index (K-WOMAC) changes at weeks 2 and 4 as compared to baseline, patient global assessment at weeks 2 and 4. The frequency and amount of rescue medicine usage at weeks 2 and 4 were also evaluated as the secondary outcome variable. For safety analysis, adverse events, clinical laboratory tests, vital signs, and physical examinations were assessed and conducted at each follow-up visit. RESULTS: At week 4, the pain VAS values were significantly reduced in both groups receiving either pelubiprofen CR 90 mg or aceclofenac 200 mg as compared to the baseline. However, the pelubiprofen group and the aceclofenac group respectively showed the pain VAS changes of -22 and -21.9 in the pre-protocol set and -20.8 and -21.7 in the full analysis set, confirming non-inferiority. The pelubiprofen CR 90 mg showed a reduced incidence of adverse events compared to the aceclofenac 200 mg (p = 0.005). CONCLUSIONS: Pelubiprofen CR 90 mg is as effective as aceclofenac 200 mg with reduced adverse events for the treatment of symptomatic knee osteoarthritis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/análogos & derivados , Osteoartrite do Joelho/tratamento farmacológico , Fenilpropionatos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diclofenaco/uso terapêutico , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Medição da Dor , Segurança do Paciente , Resultado do Tratamento
11.
Cell Transplant ; 29: 963689720943581, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32713192

RESUMO

Biological repair of cartilage lesions remains a significant clinical challenge. A wide variety of methods involving mesenchymal stem cells (MSCs) have been introduced. Because of the limitation of the results, most of the treatment methods have not yet been approved by the Food and Drug Administration (FDA). However, bone marrow aspirate concentrate (BMAC) and human umbilical cord blood derived mesenchymal stem cells (hUCB-MSCs) implantation were approved by Korea FDA. The aim of this study was to evaluate clinical and magnetic resonance imaging (MRI) outcomes after two different types of MSCs implantation in knee osteoarthritis. Fifty-two patients (52 knees) who underwent cartilage repair surgery using the BMAC (25 knees) and hUCB-MSCs (27 knees) were retrospectively evaluated for 2 years after surgery. Clinical outcomes were evaluated according to the score of visual analogue scale (VAS), the International Knee Documentation Committee (IKDC) subjective, and the Knee Injury and Osteoarthritis Outcome Score (KOOS). Cartilage repair was assessed according to the modified Magnetic Resonance Observation of Cartilage Repair Tissue (M-MOCART) score and the International Cartilage Repair Society (ICRS) cartilage repair scoring system. At 2-year follow-up, clinical outcomes including VAS, IKDC, and KOOS significantly improved (P < 0.05) in both groups; however, there were no differences between two groups. There was no significant difference in M-MOCART [1-year (P = 0.261), 2-year (P = 0.351)] and ICRS repair score (P = 0.655) between two groups. Both groups showed satisfactory clinical and MRI outcomes. Implantation of MSCs from BMAC or hUCB-MSCs is safe and effective for repairing cartilage lesion. However, large cases and a well-controlled prospective design with long-term follow-up studies are needed.


Assuntos
Células da Medula Óssea/citologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Sangue Fetal/citologia , Articulação do Joelho/patologia , Imageamento por Ressonância Magnética/métodos , Células-Tronco Mesenquimais/citologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
12.
Arthroscopy ; 36(6): 1612-1624, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31785390

RESUMO

PURPOSE: The purpose of this study was to evaluate the clinical efficacy and safety of treating patients with a cartilage defect of the knee with microfractures and porcine-derived collagen-augmented chondrogenesis technique (C-ACT). METHODS: One hundred participants were randomly assigned to the control group (n = 48, microfracture) or the investigational group (n = 52, C-ACT). Clinical and magnetic resonance imaging (MRI) outcomes were assessed 12 and 24 months postoperatively for efficacy and adverse events. Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) assessment was used to analyze cartilage tissue repair. MRI outcomes for 50% defect filling and repaired tissue/reference cartilage (RT/RC) ratio were quantified using T2 mapping. Clinical outcomes were assessed using the visual analogue scale (VAS) for pain and 20% improvement, minimal clinically important difference (MCID), and patient acceptable symptom state for Knee Injury and Osteoarthritis Outcome Score (KOOS) and the International Knee Documentation Committee score. RESULTS: MOCART scores in the investigation group showed improved defect repair and filling (P = .0201), integration with the border zone (P = .0062), and effusion (P = .0079). MRI outcomes showed that the odds ratio (OR) for ≥50% defect filling at 12 months was statistically higher in the investigation group (OR 3.984, P = .0377). Moreover, the likelihood of the RT/RC OR becoming ≥1 was significantly higher (OR 11.37, P = .0126) in the investigation group. At 24 months postoperatively, the OR for the VAS 20% improvement rate was significantly higher in the investigational group (OR 2.808, P = .047). Twenty-three patients (52.3%) in the control group and 35 (77.8%) in the investigation group demonstrated more than the MCID of KOOS pain from baseline to 1 year postoperatively, with a significant difference between groups (P = .0116). CONCLUSION: In this multicenter randomized trial, the addition of C-ACT resulted in better filling of cartilage defect of the knee joint. LEVEL OF EVIDENCE: Level Ⅰ, Multicenter Randomized Controlled Trial.


Assuntos
Doenças das Cartilagens/terapia , Cartilagem Articular/transplante , Condrogênese/fisiologia , Colágeno/farmacologia , Fraturas de Estresse/terapia , Articulação do Joelho/cirurgia , Animais , Doenças das Cartilagens/complicações , Doenças das Cartilagens/diagnóstico , Feminino , Seguimentos , Fraturas de Estresse/etiologia , Fraturas de Estresse/patologia , Humanos , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Suínos , Transplante Autólogo , Resultado do Tratamento
13.
Biomol Ther (Seoul) ; 28(2): 172-183, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31739383

RESUMO

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/ AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

14.
J Orthop Surg (Hong Kong) ; 28(1): 2309499019893509, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31876240

RESUMO

BACKGROUND: The purpose of this study was to evaluate clinical and radiological outcomes and to analyze the histological findings of repaired cartilage in patients more than 50 years old with underwent fibrin-matrix autologous chondrocyte implantation (ACI). METHODS: From January 2013 to February 2014, a prospective study was conducted on 16 patients (16 knees) who underwent fibrin-matrix ACI for International Cartilage Repair Society grade 3 or 4 chondral lesions of the knee. The major lesion was in the medial femoral condyle in all patients. The mean age of the patients was 58.1 ± 6.2 (range 51-66) years, and the minimum follow-up period was 2 years. All patients had clinical and radiological evaluations at 3 months, 6 months, 1 year, and 2 years after surgery. Twelve patients had second-look arthroscopies at 1 year after surgery, and implanted chondral biopsies were performed in 11 of these 12 patients for histological analysis. RESULTS: Functional disability assessment scales for the knee significantly improved after fibrin-matrix ACI (p < 0.05). The visual analog scale score significantly decreased from 6.7 ± 1.2 to 2.0 ± 1.8 (p < 0.001). The mean modified magnetic resonance observation of cartilage repair tissue score was 83.8 ± 17.3 at 1 year after surgery and 74.0 ± 19.2 at 2 years after surgery. Repair of the tissue with hyaline cartilage was confirmed histologically. CONCLUSIONS: Satisfactory clinical and radiological outcomes were obtained from gel-type fibrin-matrix ACI technique in older patients with a cartilage defect of the knee. Histological analysis confirmed that the new repaired tissue with hyaline cartilage filled the cartilage defect area. Therefore, fibrin-matrix ACI is believed to be an applicable treatment for older patients with chondral lesions of the knee. LEVEL OF EVIDENCE: Level IV.


Assuntos
Artroscopia/métodos , Doenças das Cartilagens/cirurgia , Cartilagem Articular/cirurgia , Condrócitos/transplante , Articulação do Joelho/cirurgia , Idoso , Doenças das Cartilagens/diagnóstico , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Radiografia , Fatores de Tempo , Transplante Autólogo
15.
J Orthop Surg Res ; 14(1): 281, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31462246

RESUMO

BACKGROUND: The guidelines to correct the mechanical axis in high tibial osteotomy (HTO) have changed recently, and some studies have suggested that the correction of the mechanical axis should be based on the severity of cartilage defect. The purpose of this study was (1) to evaluate the radiographic and clinical outcomes of HTO with concomitant cartilage procedures and (2) to compare our method with conventional method regarding the mechanical axis correction. METHODS: Sixty-six knees which underwent opening wedge HTO with cartilage procedures were evaluated retrospectively. The mean age was 56.0 ± 8.3 years, and the average follow-up period was 35.9 ± 22.0 months (range, 24-93 months) with a minimum follow-up of 2 years. All patients were divided into two groups regarding the method of mechanical axis correction; the postoperative mechanical axis was shifted to 50-55% of the tibial plateau width in group I (n = 46) and to 62-66% according to the conventional method in group II (n = 20). Concomitant cartilage procedures were performed, and each technique of those was determined according to the cartilage status. RESULTS: The functional scores and visual analog scale for pain in all patients showed a significant improvement at the final follow-up, but there was no significant difference between two groups. The postoperative mechanical axis was the valgus axis of 0.7° in group I with average mechanical axis deviation (MAD) of 51.7%, whereas the valgus axis of 4.2° in group II with average MAD of 64.0%. In patients who underwent second-look arthroscopy, the cartilaginous regeneration could be obtained by cartilage procedures. CONCLUSION: In HTO with concomitant cartilage procedures, the method to correct postoperative mechanical axis to the neutral or valgus axis less than 3° could be an effective and safe method to obtain reliable clinical outcomes without complications. Therefore, our method can be used as a selective technique to prevent complications related to the postoperative valgus alignment in patients who are needed much correction angle due to the preoperative severe varus alignment. STUDY DESIGN: Retrospective comparative study, level III.


Assuntos
Osteotomia/métodos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
16.
BMC Musculoskelet Disord ; 20(1): 185, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-31043170

RESUMO

BACKGROUND: Actinomycosis is a rare, chronic granulomatous disease caused by Gram-positive anaerobic bacteria that colonize the oral cavity. Cervicofacial actinomycosis is the most frequent clinical presentation of actinomycosis, but hematogenous osteomyelitis at distant sites can occur in rare instance in immunocompromised or pediatric patients, only a few cases have been reported in healthy patients. Here we described a new case of distal femur osteomyelitis caused by Actinomyces in an adult patient who was immunocompetent and had no predisposing factors. CASE PRESENTATION: A woman aged 52 years with no history of trauma presented with severe pain, swelling, and increased local heat in the proximal area of the right knee 3 weeks after she first noticed discomfort. Magnetic resonance imaging showed persistent osteomyelitis of the distal metaphysis and diaphysis of the femur with a multifocal intraosseous abscess pocket. An incision and drainage of the abscess were conducted. The tissue culture, fungus culture, acid fast bacillus (AFB) culture, AFB smear, and tuberculosis polymerase chain reaction test results were negative. A pathologic examination confirmed the presence of actinomycosis. The patient was successfully treated with intravenous penicillin G for 8 weeks followed by oral amoxicillin-clavulanate for 6 weeks with repeated surgical debridement and drainage. After a 5-year follow up, the patient had no signs of recurring infection or complications and she had full range of movement in the affected knee. CONCLUSIONS: Although rare, actinomycotic osteomyelitis can occur in healthy people. Furthermore, actinomycotic osteomyelitis is easily misdiagnosed as tuberculosis in areas with a high prevalence of tuberculosis. To detect and identify the bacteria accurately, pathologic examination should be performed as well as culture tests, because the probability for culture confirmation of actinomycosis is quite low. The initial treatment is vital to a successful outcome without ostectomy or amputation.


Assuntos
Actinomyces/isolamento & purificação , Actinomicose/complicações , Antibacterianos/administração & dosagem , Drenagem , Osteomielite/microbiologia , Actinomyces/imunologia , Actinomicose/imunologia , Actinomicose/microbiologia , Actinomicose/terapia , Biópsia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/microbiologia , Fêmur/patologia , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Osteomielite/diagnóstico por imagem , Osteomielite/imunologia , Osteomielite/terapia , Resultado do Tratamento
17.
Hum Gene Ther Clin Dev ; 29(1): 48-59, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29641281

RESUMO

The aim of this study was to test the clinical efficacy of TissueGene-C (TG-C), a cell and gene therapeutic for osteoarthritis consisting of non-transformed and transduced chondrocytes (3:1) retrovirally transduced to overexpress transforming growth factor-ß1. A total of 163 Kellgren-Lawrence grade 3 patients with knee osteoarthritis were randomly assigned to receive intra-articular TG-C or placebo. Primary efficacy measures included criteria for subjective assessment by International Knee Documentation Committee (IKDC) and pain severity by Visual Analog Scale (VAS) for 52 weeks. Secondary efficacy measures included IKDC and VAS at 26 and 39 weeks; pain, stiffness, and physical function by the Western Ontario and McMaster Universities Arthritis Index (WOMAC); and pain, symptoms, daily activities, function in sports and recreation, and quality of life by the Knee Injury and Osteoarthritis Outcome Score (KOOS), X-ray, magnetic resonance imaging, and soluble urine and blood biomarkers. TG-C was associated with statistically significant improvement over placebo in the total IKDC score and individual categories, and in the VAS score at 26, 39, and 52 weeks. WOMAC and KOOS scores also improved with TG-C over placebo. Patients treated with TG-C showed trends directed toward thicker cartilage and slower growing rates of subchondral bone surface area in the medial tibia, lateral tibia, lateral patella, and lateral patella femoral regions, although these were not statistically significant (p > 0.05). Serum C-terminal telopeptide of type I collagen (CTX-I) and urine CTX-II levels were lower over 1 year in TG-C than placebo-treated patients, with CTX-I level reaching statistical significance. These tendencies supported TG-C as holding great potential as a disease-modifying osteoarthritis drug. The most frequent adverse events in the TG-C group were peripheral edema (9%), arthralgia (8%), joint swelling (6%), and injection site pain (5%). TG-C was associated with statistically significant improvements in function and pain in patients with knee osteoarthritis. The unexpected adverse events were not observed.


Assuntos
Terapia Genética/efeitos adversos , Osteoartrite do Joelho/terapia , Idoso , Cartilagem/metabolismo , Cartilagem/fisiologia , Colágeno Tipo I/sangue , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Colágeno Tipo I/urina , Método Duplo-Cego , Feminino , Terapia Genética/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Regeneração
18.
Knee Surg Sports Traumatol Arthrosc ; 26(11): 3280-3289, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29450566

RESUMO

PURPOSE: Gait analysis is a valuable instrument for measuring function objectively after unicompartmental knee arthroplasty (UKA). However, most gait analysis studies have reported conflicting results for functional assessment after UKA. This meta-analysis compared the gait patterns of UKA patients and healthy controls during level walking. METHODS: Studies were included in the meta-analysis if they recorded vertical ground reaction force (GRF), flexion at initial contact, flexion at loading response, extension at mid-stance, flexion at swing, walking speed, cadence, and stride length in UKA patients or healthy controls. RESULTS: Seven studies met the criteria for inclusion in the meta-analysis. The UKA patients and healthy controls were similar in terms of vertical GRF (95% CI - 0.54 to 0.23; ns), flexion at initial contact (95% CI - 0.47 to 4.96; ns), flexion at loading response (95% CI - 1.29 to 3.69; ns), and flexion at swing (95% CI - 8.85 to 0.40; ns). In contrast, extension at mid-stance (95% CI 0.53 to 4.88; P = 0.01), walking speed (95% CI - 2.13 to - 0.15; P = 0.02), cadence (95% CI - 1.02 to - 0.25; P = 0.001), and stride length (95% CI - 2.02 to - 0.22; P = 0.01) differed significantly between groups. Subgroup analyses revealed that the pooled data were similar between groups: 1st maximum (heel strike), - 0.43 BW (ns); 1st minimum (mid-stance), 0.61 BW (ns); and 2nd maximum (toe off), - 0.46 BW (ns). CONCLUSIONS: There were no significant differences in vertical GRF or overall kinematics in the sagittal plane between UKA patients and healthy controls during level walking. However, the UKA group had a significantly slower walking speed and cadence and a shorter stride length than healthy controls. The current findings suggest that, clinically, UKA fails to completely restore normal gait patterns. LEVEL OF EVIDENCE: Level II, therapeutic study.


Assuntos
Artroplastia do Joelho , Marcha/fisiologia , Caminhada/fisiologia , Fenômenos Biomecânicos/fisiologia , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia
19.
Cartilage ; 9(4): 402-409, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-28393539

RESUMO

OBJECTIVE: The aim of this study was to evaluate the results of autologous bone marrow cell stimulation and allogenic chondrocyte implantation using 3-dimensional gel-type fibrin matrix in an animal model. DESIGN: Eighteen rabbits were divided into 2 treatment groups. One group was treated with a microfracture and covering of it with gel-type fibrin (AutoBMS; n = 9), and the other group was treated with allogenic chondrocytes mixed gel-type fibrin at the cartilage defect (AlloCI; n = 9). The control group was untreated cartilage defect at the other side knee of each object. Twelve weeks after treatment, the cartilage was evaluated using the International Cartilage Repair Society (ICRS) scoring system, immunohistochemical staining, and modified O'Driscoll grading system. RESULTS: The ICRS scores were similar in the AutoBMS (9.44 ± 2.44) and the AlloCI (9.33 ± 1.67) groups ( P < 0.05). Immunohistochemical staining confirmed higher expression of cartilaginous collagen for both groups. The average difference (AutoBMS, 31.89 ± 6.54; AlloCI, 32.89 ± 5.25) in the modified O'Driscoll scores appeared to be nonsignificant ( P > 0.05); however, both treatment groups showed significantly higher scores with respect to their control group (18.45 ± 1.65; 18.97 ± 1.58) ( P < 0.05). CONCLUSION: This experimental study suggests autologous bone marrow cells stimulation and implantation of allogenic chondrocytes are both useful methodologies for regenerating hyaline-like cartilage in full-thickness cartilage defects in animal model.


Assuntos
Células da Medula Óssea , Doenças das Cartilagens/terapia , Cartilagem Articular/citologia , Condrócitos/transplante , Transplante de Células-Tronco/métodos , Animais , Modelos Animais de Doenças , Coelhos , Transplante Autólogo , Transplante Homólogo
20.
J Orthop Surg (Hong Kong) ; 25(3): 2309499017731626, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28950794

RESUMO

INTRODUCTION: Although intraarticular tranexamic acid (IA-TXA) administration or drainage clamping are popular methods used to reduce blood loss after total knee replacement (TKR), the protocol remains controversial. We aimed (1) to establish new protocols through investigating whether two methods, that is, low-dose (500 mg) IA-TXA plus 30-min drain clamping and drainage clamping for the first 3 h without IA-TXA, can reduce blood loss and blood transfusion after unilateral TKR and (2) to make recommendations related to clinical application. MATERIALS AND METHODS: This study, conducted from September 2014 to June 2016 related to enrolled 95 patients with primary osteoarthritis who were to have a unilateral cemented TKR, was nonrandomized and retrospective. In group A, the drain was released following tourniquet deflation. In group B, 500-mg TXA was injected into the knee joint via a drain tube after fascia closure and the drain was clamped for the first 30 min to prevent leakage. In group C, the drain was clamped for the first 3-h postoperation. Demographic characteristics and clinical data were collected, including the levels of hematocrit (Hct), the total blood loss (TBL), drained blood volume (BV), the amount of blood transfused, and any complications that developed. RESULTS: We found a significantly lower postoperative TBL, drained BV, decreasing Hct level, and less transfused BV in the IA-TXA injection group (group B) and the 3-h drainage clamping group (group C) compared to the conventional negative drainage group (group A; p < 0.001). There was no significant difference between groups B and C ( p = 0.99). CONCLUSIONS: The drainage clamping method can be safer than IA-TXA administration in patients with risk factor of venous thromboembolic complication. Furthermore, the IA-TXA administration can be more optimal than drainage clamping in patients with high bleeding tendency or lateral retinacular release during TKR, who would be concerned about postoperative wound complication.


Assuntos
Antifibrinolíticos/administração & dosagem , Artroplastia do Joelho , Transfusão de Sangue , Drenagem/métodos , Hemorragia/prevenção & controle , Ácido Tranexâmico/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/prevenção & controle , Protocolos Clínicos/normas , Constrição , Feminino , Hemorragia/etiologia , Hemorragia/terapia , Humanos , Injeções Intra-Articulares , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/terapia , Estudos Retrospectivos
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