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BACKGROUND: Although sonication is a valuable diagnostic tool for periprosthetic joint infections (PJI), it is not commonly utilized. We analyzed sonicate and intraoperative tissue culture results obtained from three hospitals to define the microbial etiology of PJIs in Korea. Furthermore, we investigated necessity of conducting regular fungal and mycobacterial cultures. METHODS: We retrospectively analyzed data for patients with suspected orthopedic-related infections between 2017 and 2022, who had undergone prostheses removal surgery. We included 193 patients with suspected PJIs, and bacterial (n = 193), fungal (n = 193), and mycobacterial (n = 186) cultures were conducted on both sonicate and intraoperative tissue samples. The diagnosis of PJI was based on the European Bone and Joint Infection Society (EBJIS) criteria. RESULTS: Out of 193 patients, 121 (62.7%) had positive sonicate cultures, while 112 (58.0%) had positive periprosthetic tissue cultures. According to EBJIS criteria, a total of 181 patients were diagnosed with PJI, and 141 patients received microbiological confirmation through sonicate fluid culture or tissue culture. Of the 181 patients, 28 were classified with acute PJI (within 3 months of implantation) and 153 with chronic PJI. Among 141 patients, staphylococci were the most common organisms, accounting for 51.8% of cases, followed by Gram-negative organisms (15.6%), fungus (8.5%), and mycobacteria (3.5%). Nearly 91.7% of fungal isolates were Candida species, which also grew in bacterial cultures. In total, 11 cases cultured positive only in tissue culture, whereas 20 cases cultured positive only in sonicate culture. The antibiotic treatment plans were adjusted according to culture results. CONCLUSIONS: Utilizing sonicate culture has greatly assisted in identifying pathogens responsible for chronic indolent PJIs, allowing suitable antimicrobial treatment. Based on few cases involving non-Candida and mycobacterial infections, it appears that routine fungal and mycobacterial cultures may not be necessary.
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Hongos , Infecciones Relacionadas con Prótesis , Humanos , Infecciones Relacionadas con Prótesis/microbiología , Infecciones Relacionadas con Prótesis/diagnóstico , Masculino , Femenino , Anciano , República de Corea/epidemiología , Estudios Retrospectivos , Persona de Mediana Edad , Hongos/aislamiento & purificación , Sonicación , Mycobacterium/aislamiento & purificación , Mycobacterium/efectos de los fármacos , Adulto , Anciano de 80 o más AñosRESUMEN
PURPOSE: To compare the anterior and posterior trans-septal (TS) portal approaches in anterior cruciate ligament reconstruction (ACLR) by evaluating femoral tunnel positioning and passive anterior tibial subluxation (PATS). METHODS: A total of 205 patients who underwent primary ACLR using the outside-in technique between March 2018 and December 2021 were retrospectively enrolled. Patients were classified into two groups based on the viewing techniques: the anterior group was treated using anteromedial or anterolateral portals (n = 155), and the TS group was treated using posterior TS portal (n = 55). The relative locations of the femoral tunnel were evaluated using the deep-shallow planes (X-axis) and superior-inferior planes (Y-axis) with the quadrant method in the lateral femoral condyle on a 3-dimensional computed tomography image. Anterior tibial subluxation for the lateral and medial compartments relative to the femoral condyles was evaluated as measured on magnetic resonance imaging. Knee laxity was assessed using the pivot-shift test and stress radiography. RESULTS: In the posterior TS group, the femoral tunnel was usually located deeper on the X-axis and more superior on the Y-axis, which corresponds to a more proximal position, than in the anterior group (deeper on the X-axis and superior on the Y-axis). Moreover, the femoral tunnel locations in this group were more compactly distributed than those in the anterior group. The TS group showed significantly better reduction of postoperative PATS in the lateral compartments than the anterior group (anterior group vs. TS group: lateral compartment, 3.2 ± 3.1 vs. 4.5 ± 3.2 mm; p = .016). Significantly better results were found in the TS group for knee stability as assessed by the pivot-shift grade (p = .044); however, there were no significant differences between the two groups with respect to patient-reported outcome measures (p > .05) and other complications (p = .090). CONCLUSION: Our results suggest that positioning the femoral tunnel using the posterior TS portal approach may lead to better outcomes in terms of PATS and rotational stability compared to the anterior portal approach in ACLR.
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Osteoarthritis (OA) is a degenerative joint disorder that is distinguished by inflammation and chronic cartilage damage. Interleukin-1ß (IL-1ß) is a proinflammatory cytokine that plays an important role in the catabolic processes that underlie the pathogenesis of OA. In this study, we investigate the therapeutic efficacy of exosomes derived from untreated bone-marrow-derived mesenchymal stem cells (BMMSC-Exo) and those treated with cinnamaldehyde (BMMSC-CA-Exo) for preventing the in vitro catabolic effects of IL-1ß on chondrocytes. We stimulated chondrocytes with IL-1ß to mimic the inflammatory microenvironment of OA. We then treated these chondrocytes with BMMSC-Exo and BMMSC-CA-Exo isolated via an aqueous two-phase system and evaluated their effects on the key cellular processes using molecular techniques. Our findings revealed that treatment with BMMSC-Exo reduces the catabolic effects of IL-1ß on chondrocytes and alleviates inflammation. However, further studies directly comparing treatments with BMMSC-Exo and BMMSC-CA-Exo are needed to determine if CA preconditioning can provide additional anti-inflammatory benefits to the exosomes beyond those of CA preconditioning or treatment with regular BMMSC-Exo. Through a comprehensive molecular analysis, we elucidated the regulatory mechanisms underlying this protective effect. We found a significant downregulation of proinflammatory signaling pathways in exosome-infected chondrocytes, suggesting the potential modulation of the NF-κB and MAPK signaling cascades. Furthermore, our study identified the molecular cargo of BMMSC-Exo and BMMSC-CA-Exo, determining the key molecules, such as anti-inflammatory cytokines and cartilage-associated factors, that may contribute to their acquisition of chondroprotective properties. In summary, BMMSC-Exo and BMMSC-CA-Exo exhibit the potential as therapeutic agents for OA by antagonizing the in vitro catabolic effects of IL-1ß on chondrocytes. The regulation of the proinflammatory signaling pathways and bioactive molecules delivered by the exosomes suggests a multifaceted mechanism of action. These findings highlight the need for further investigation into exosome-based therapies for OA and joint-related diseases.
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Acroleína , Condrocitos , Exosomas , Inflamación , Interleucina-1beta , Células Madre Mesenquimatosas , Transducción de Señal , Exosomas/metabolismo , Interleucina-1beta/metabolismo , Acroleína/análogos & derivados , Acroleína/farmacología , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Inflamación/metabolismo , Animales , Osteoartritis/metabolismo , Osteoartritis/tratamiento farmacológico , Humanos , Células CultivadasRESUMEN
Background: The Coronal Plane Alignment of the Knee (CPAK) classification system has been developed as a comprehensive system that describes 9 coronal plane phenotypes based on constitutional limb alignment and joint line obliquity (JLO). Due to the characteristics of Asian populations, which show more varus and wider distribution in lower limb alignment than other populations, modification of the boundaries of the arithmetic hip-knee-ankle angle (aHKA) and JLO should be considered. The purpose of this study was to determine the knee phenotype in a Korean population based on the original CPAK and modified CPAK classification systems. Methods: We reviewed prospectively collected data of 500 healthy and 500 osteoarthritic knees between 2021 and 2023 using radiographic analysis and divided them based on the modified CPAK classification system by widening the neutral boundaries of the aHKA to 0° ± 3° and using the actual JLO as a new variable. Using long-leg standing weight-bearing radiographs, 6 radiographic parameters were measured to evaluate the CPAK type: the mechanical HKA angle, medial proximal tibial angle (MPTA), lateral distal femoral angle (LDFA), aHKA, JLO, and actual JLO. Results: From 2 cohorts of 1,000 knees, the frequency distribution representing all CPAK types was different between the healthy and arthritic groups. The most common categories were type II (38.2%) in the healthy group and type I (53.8%) in the arthritic group based on the original CPAK classification. The left and upward shift in the distribution of knee phenotypes in the original classification was corrected evenly after re-establishing the boundaries of a neutral aHKA and the actual JLO. According to the modified CPAK classification system, the most common categories were type II (35.2%) in the healthy group and type I (38.0%) in the arthritic group. Conclusions: Although the modified CPAK classification corrected the uneven distribution seen when applying the original classification system in a Korean population, the most common category was type I in Korean patients with osteoarthritic knees in both classification systems. Furthermore, there were different frequencies of knee phenotypes among healthy and arthritic knees.
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Articulación de la Rodilla , Osteoartritis de la Rodilla , Fenotipo , Radiografía , Humanos , República de Corea , Masculino , Femenino , Persona de Mediana Edad , Anciano , Articulación de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/clasificación , Adulto , Estudios Prospectivos , Pueblo AsiaticoRESUMEN
Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by cartilage degeneration and synovial inflammation. Paracrine interactions between chondrocytes and macrophages play an essential role in the onset and progression of OA. In this study, in replicating the inflammatory response during OA pathogenesis, chondrocytes were treated with interleukin-1ß (IL-1ß), and macrophages were treated with lipopolysaccharide and interferon-γ. In addition, a coculture system was developed to simulate the biological situation in the joint. In this study, we examined the impact of hyaluronic acid (HA) viscosupplement, particularly Hyruan Plus, on chondrocytes and macrophages. Notably, this viscosupplement has demonstrated promising outcomes in reducing inflammation; however, the underlying mechanism of action remains elusive. The viscosupplement attenuated inflammation, showing an inhibitory effect on nitric oxide production, downregulating proinflammatory cytokines such as matrix metalloproteinases (MMP13 and MMP3), and upregulating the expression levels of type II collagen and aggrecan in chondrocytes. HA also reduced the expression level of inflammatory cytokines such as IL-1ß, TNF-α, and IL-6 in macrophages, and HA exerted an overall protective effect by partially suppressing the MAPK pathway in chondrocytes and p65/NF-κB signaling in macrophages. Therefore, HA shows potential as a viscosupplement for treating arthritic joints.
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BACKGROUND: Although high tibial osteotomy (HTO) is an established treatment option for medial compartment osteoarthritis, predictive factors for HTO treatment success remain unclear. This study aimed to identify informative variables associated with HTO treatment success and to develop and internally validate machine learning algorithms to predict which patients will achieve HTO treatment success for medial compartmental osteoarthritis. METHODS: This study retrospectively reviewed patients who underwent medial opening-wedge HTO (MOWHTO) at our center between March 2010 and December 2015. The primary outcomes were a lack of conversion to total knee arthroplasty (TKA) and achievement of a minimal clinically important difference of improvement in the Knee Injury and Osteoarthritis Outcome Score (KOOS) at a minimum of five years postoperatively. Recursive feature selection was used to identify the combination of variables from an initial pool of 25 features that optimized model performance. Five machine learning algorithms (XGBoost, multilayer perception, support vector machine, elastic-net penalized logistic regression, and random forest) were trained using five-fold cross-validation three times and applied to an independent test set of patients. The performance of the model was evaluated by the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 231 patients were included, and 200 patients (86.6%) achieved treatment success at the mean of 9 years of follow-up. A combination of seven variables optimized algorithm performance, and the following specific cutoffs increased the likelihood of MOWHTO treatment success: body mass index (BMI) ≤ 26.8 kg/m2, preoperative KOOS for pain ≤ 46.0, preoperative KOOS for quality of life ≤ 33.0, preoperative International Knee Documentation Committee score ≤ 42.0, preoperative Short-Form 36 questionnaire (SF-36) score > 42.25, three-month postoperative hip-knee-ankle angle > 1.0°, and three-month postoperative medial proximal tibial angle (MPTA) > 91.5° and ≤ 94.7°. The random forest model demonstrated the best performance (F1 score: 0.93; AUC: 0.81) and was transformed into an online application as an educational tool to demonstrate the capabilities of machine learning. CONCLUSIONS: The random forest machine learning algorithm best predicted MOWHTO treatment success. Patients with a lower BMI, poor clinical status, slight valgus overcorrection, and postoperative MPTA < 94.7 more frequently achieved a greater likelihood of treatment success. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
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Aprendizaje Automático , Osteoartritis de la Rodilla , Osteotomía , Tibia , Humanos , Masculino , Femenino , Osteotomía/métodos , Estudios Retrospectivos , Persona de Mediana Edad , Osteoartritis de la Rodilla/cirugía , Tibia/cirugía , Anciano , Resultado del Tratamiento , Articulación de la Rodilla/cirugía , Artroplastia de Reemplazo de Rodilla/métodosRESUMEN
UPDATE: This article was updated on May 15, 2024 because of previous errors, which were discovered after the preliminary version of the article was posted online. On page 898, in the section entitled "Materials and Methods," the sentence that had read "The WBL ratio of the knee joint was defined as the point where the GA or MA passed through the width of the tibia and intersected a line from the center of the femoral head to the center of the calcaneus (for the GA) or talus (for the MA), with the medial edge defined as 0% and the lateral edge as 100%." now reads "The WBL ratio of the knee joint was defined as the point where the GA or MA passed through the width of the tibia and intersected a line from the center of the femoral head to the lowest point of the calcaneus (for the GA) or the center of the talus (for the MA), with the medial edge defined as 0% and the lateral edge as 100%." Likewise, in the legend for Figure 3 on page 899, the sentence that had read "Depiction of the ground mechanical axis (GA), defined as the line (represented by the solid red line) from the center of the femoral head to the ground reaction point at the center of the calcaneus, passing lateral to the traditional mechanical axis (MA; represented by the dashed red line)." now reads "Depiction of the ground mechanical axis (GA), defined as the line (represented by the solid red line) from the center of the femoral head to the ground reaction point at the lowest point of the calcaneus, passing lateral to the traditional mechanical axis (MA; represented by the dashed red line)." Finally, on page 903, "HKA" was changed to "HKA angle" in Table III. BACKGROUND: The hip-to-calcaneus axis, previously known as the ground mechanical axis (GA), ideally passes through the center of the knee joint in the native knee. The aim of this study was to elucidate, with use of hip-to-calcaneus radiographs, changes in knee and hindfoot alignment and changes in outcomes following high tibial osteotomy (HTO). METHODS: We reviewed the records for 128 patients who underwent HTO between 2018 and 2020. Patients were stratified into 2 groups, a hindfoot valgus group (n = 94) and a hindfoot varus group (n = 34), on the basis of their preoperative hindfoot alignment. The hindfoot alignment was evaluated with use of the hindfoot alignment angle (HAA). To evaluate lower-limb alignment, full-length standing posteroanterior hip-to-calcaneus radiographs were utilized to measure 4 radiographic parameters preoperatively and 2 years postoperatively: the hip-knee-ankle (HKA) angle, hip-knee-calcaneus (HKC) angle, and the weight-bearing line (WBL) ratios of the mechanical axis (MA) and GA. RESULTS: The mean HAA improved significantly from 5.1° valgus preoperatively to 1.9° valgus postoperatively in the hindfoot valgus group (p < 0.001). In contrast, in the hindfoot varus group, the HAA showed no meaningful improvement in the coronal alignment of the hindfoot following HTO (p = 0.236). The postoperative mean HKC angle in the hindfoot varus group was 2° more varus than that in the hindfoot valgus group (1.0° versus 3.0°; p = 0.001), and the GA in the hindfoot varus group passed across the knee 8.0% more medially than that in the hindfoot valgus group (55% versus 63% from the most medial to the most lateral part of the tibial plateau). The hindfoot varus group had worse postoperative clinical outcomes than the hindfoot valgus group in terms of the mean Knee injury and Osteoarthritis Outcome Score for pain and American Orthopaedic Foot & Ankle Society Ankle-Hindfoot Score. CONCLUSIONS: Although our findings did not provide sufficient evidence to establish clinically relevant differences between the groups, they indicated that the group with a preoperative fixed hindfoot varus deformity had a higher rate of undercorrection and worse clinical outcomes, especially pain, following HTO. Therefore, modification of the procedure to shift the GA more laterally may be required for these patients. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.
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Osteoartritis de la Rodilla , Osteotomía , Tibia , Humanos , Osteotomía/métodos , Tibia/cirugía , Tibia/diagnóstico por imagen , Osteoartritis de la Rodilla/cirugía , Osteoartritis de la Rodilla/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , AncianoRESUMEN
Osteoarthritis (OA) is a joint disorder caused by wear and tear of the cartilage that cushions the joints. It is a progressive condition that can cause significant pain and disability. Currently, there is no cure for OA, though there are treatments available to manage symptoms and slow the progression of the disease. A chondral defect is a common and devastating lesion that is challenging to treat due to its avascular and aneural nature. However, there are conventional therapies available, ranging from microfracture to cell-based therapy. Anyhow, its efficiency in cartilage defects is limited due to unclear cell viability. Exosomes have emerged as a potent therapeutic tool for chondral defects because they are a complicated complex containing cargo of proteins, DNA, and RNA as well as the ability to target cells due to their phospholipidic composition and the altering exosomal contents that boost regeneration potential. Exosomes are used in a variety of applications, including tissue healing and anti-inflammatory therapy. As in recent years, biomaterials-based bio fabrication has gained popularity among the many printable polymer-based hydrogels, tissue-specific decellularized extracellular matrix might boost the effects rather than an extracellular matrix imitating environment, a short note has been discussed. Exosomes are believed to be the greatest alternative option for current cell-based therapy, and future progress in exosome-based therapy could have a greater influence in the field of orthopaedics. The review focuses extensively on the insights of exosome use and scientific breakthroughs centered OA.
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Aims: Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy. Methods: We reviewed our institutional joint arthroplasty database and identified 41 patients diagnosed with fungal PJIs and treated with two-stage exchange arthroplasty after primary total knee arthroplasty (TKA) between January 2001 and December 2020, and compared them with those who had non-fungal PJIs during the same period. After propensity score matching based on age, sex, BMI, American Society of Anesthesiologists grade, and Charlson Comorbidity Index, 40 patients in each group were successfully matched. The surgical and antimicrobial treatment, patient demographic and clinical characteristics, recurrent infections, survival rates, and relevant risk factors that affected joint survivorship were analyzed. We defined treatment success as a well-functioning arthroplasty without any signs of a PJI, and without antimicrobial suppression, at a minimum follow-up of two years from the time of reimplantation. Results: The fungal PJI group demonstrated a significantly worse treatment success rate at the final follow-up than the non-fungal PJI group (65.0% (26/40) vs 85.0% (34/40); p < 0.001). The mean prosthesis-free interval was longer in the fungal PJI group than in the non-fungal PJI group (6.7 weeks (SD 5.8) vs 4.1 weeks (SD 2.5); p = 0.020). The rate of survivorship free from reinfection was worse in the fungal PJI group (83.4% (95% confidence interval (CI) 64.1 to 92.9) at one year and 76.4% (95% CI 52.4 to 89.4) at two years) than in the non-fungal PJI group (97.4% (95% CI 82.7 to 99.6) at one year and 90.3% (95% CI 72.2 to 96.9) at two years), but the differences were not significant (p = 0.270). Cox proportional hazard regression analysis identified the duration of the prosthesis-free interval as a potential risk factor for failure (hazard ratio 1.128 (95% CI 1.003 to 1.268); p = 0.043). Conclusion: Fungal PJIs had a lower treatment success rate than non-fungal PJIs despite two-stage revision arthroplasty and appropriate antifungal treatment. Our findings highlight the need for further developments in treating fungal PJIs.
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Antiinfecciosos , Artroplastia de Reemplazo de Rodilla , Micosis , Infecciones Relacionadas con Prótesis , Humanos , Antifúngicos/uso terapéutico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Articulación de la Rodilla/cirugía , Micosis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/etiología , Masculino , FemeninoRESUMEN
Orthopedic surgery is one of the first surgical specialties to apply surgical robotics in clinical practice, which has become an interesting field over the years with promising results. Surgical robotics can facilitate total joint arthroplasty by providing robotic support to accurately prepare the bone, improving the ability to reproduce alignment, and restoring normal kinematics. Various robotic systems are available on the market, each tailored to specific types of surgeries and characterized by a series of features with different requirements and/or modus operandi. Here, a narrative review of the current state of surgical robotic systems for total joint knee arthroplasty is presented, covering the different categories of robots, which are classified based on the operation, requirements, and level of interaction with the surgeon. The different robotic systems include closed/open platform, image-based/imageless, and passive/active/semi-active systems. The main goal of a robotic system is to increase the accuracy and precision of the operation regardless of the type of system. Despite the short history of surgical robots, they have shown clinical effectiveness compared to conventional techniques in orthopedic surgery. When considering which robotic system to use, surgeons should carefully evaluate the different benefits and drawbacks to select the surgical robot that fits their needs the best.
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BACKGROUND: The purpose of the current study was (1) to analyze various factors that may be associated with the outcomes of Legg-Calvé-Perthes disease (LCPD), and (2) to develop and internally validate machine learning algorithms capable of providing patient-specific predictions of which patients with LCPD will achieve relevant improvement in radiologic outcomes after proximal femoral varus osteotomy (PFVO). We examined several variables, previously identified as factors, that may influence the outcome of LCPD and developed a machine learning algorithm based on them. METHODS: In this retrospective study, we analyzed patients aged older than â6 years at the time of LCPD diagnosis who underwent PFVO at our institution between 1979 and 2015. Univariate and multivariate logistic regression analyses were used to examine the effects of variables on the sphericity of the femoral head at skeletal maturity, including age at onset, sex, stage at operation, extent of epiphyseal involvement and collapse, presence of specific epiphyseal, metaphyseal, and acetabular changes, and postoperative neck shaft angle (NSA). Recursive feature selection was used to identify the combination of variables from an initial pool of 13 features that optimized the model performance. Five machine learning algorithms [extreme gradient boosting (XGBoost), multilayer perception, support vector machine, elastic-net penalized logistic regression, and random forest) were trained using 5-fold cross-validation 3 times and applied to an independent testing set of patients. RESULTS: Ninety patients with LCPD who underwent PFVO were included in this study. The mean age at diagnosis was 7.93 (range, 6.0 to 12.33) years. The average follow-up period was 10.11 (range, 5.25 to 22.92) years. A combination of 8 variables, optimized algorithm performance, and specific cutoffs were found to decrease the likelihood of achieving the 1 or 2 Stulberg classification: age at onset ≤ 8.06, lateral classification ≤ B, 12.40 < preoperative migration percentage (MP) ≤ 22.85, Catterall classification ≤ 2, 117.4 < postoperative NSA ≤ 122.90, -10.8 < postoperative MP ≤ 6.5, 139.65 < preoperative NSA ≤ 144.67, and operation at stage 1. The XGBoost model demonstrated the best performance (F1 score: 0.78; area under the curve: 0.84). CONCLUSIONS: The XGBoost machine learning algorithm achieved the best performance in predicting the postoperative radiologic outcomes in patients with LCPD who underwent PFVO. In our population, age at onset ≤ 8.06, lateral classification ≤ B, 12.40 < preoperative MP ≤ 22.85, Catterall classification ≤ 2, 117.4 < postoperative NSA ≤ 122.90, -10.8 < postoperative MP ≤ 6.5, 139.65 < preoperative NSA ≤ 144.67, and operation at an early stage had the likelihood of achieving the spherical femoral head for the patients with LCPD that underwent PFVO. After external validation, the online application of this model may enhance shared decision-making. LEVEL OF EVIDENCE: Level III-retrospective cohort study.
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Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin-1ß (IL-1ß) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL-1ß induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.
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FN-kappa B , Osteoartritis , Animales , Humanos , Masculino , FN-kappa B/metabolismo , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 13 de la Matriz/metabolismo , Polinucleótidos/farmacología , Polinucleótidos/metabolismo , Polinucleótidos/uso terapéutico , Células Cultivadas , Semen/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Osteoartritis/metabolismo , Condrocitos/metabolismo , Antiinflamatorios/farmacología , Hipertrofia/metabolismo , Interleucina-1beta/metabolismoRESUMEN
PURPOSE: To demonstrate the clinical outcomes of patients with fungal periprosthetic joint infections (PJIs) after two-stage exchange arthroplasty combined with antifungal therapy. METHODS: We retrospectively reviewed the outcomes of 41 patients with fungal PJIs after primary total knee arthroplasty (TKA) in a single centre from January 1999 to October 2017. During the first stage of resection arthroplasty, antifungal-impregnated cement spacers (AICSs) were implanted in all patients. After systemic antifungal treatment during the interval between the two surgeries, delayed reimplantation as part of a two-stage exchange protocol was performed when patients were clinically stable. We defined treatment success as a well-functioning arthroplasty without any signs of PJI after a minimum follow-up of two years without antimicrobial suppression. Successful treatment was confirmed by repeat negative cultures as well as a return of inflammatory markers to normal levels. RESULTS: The treatment success rate was 63.4% at the final follow-up. Thirty-six of 41 patients (87.8%) met the criteria for second-stage revision after confirmation of complete infection control. The mean prosthesis-free interval was 6.6 months (range, 2.0-30.0 months). During follow-up after two-stage exchange arthroplasty, ten patients (27.7% of 36 patients) unfortunately experienced recurrence or relapse of infection after an average of 31.3 months (range, 2.7-135.6 months). The rate of survivorship free from reinfection was 94.4% at six months, 84.8% at one year, and 73.6% at two years. Cox proportional hazard regression analysis demonstrated that the prosthesis-free interval (HR = 1.016, p = 0.037) and mean length of antifungal treatment (HR = 0.226, p = 0.046) were potential risk factors for failure. CONCLUSION: Fungal PJIs led to devastating clinical outcomes despite even two-stage revision arthroplasty with the use of AICSs and antifungal medications.
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Artritis Infecciosa , Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Infecciones Relacionadas con Prótesis , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Artroplastia de Reemplazo de Rodilla/métodos , Antifúngicos/uso terapéutico , Infecciones Relacionadas con Prótesis/tratamiento farmacológico , Infecciones Relacionadas con Prótesis/epidemiología , Infecciones Relacionadas con Prótesis/etiología , Estudios Retrospectivos , Resultado del Tratamiento , Artritis Infecciosa/cirugía , Reoperación/efectos adversos , Articulación de la Rodilla/cirugía , Articulación de la Rodilla/microbiología , Prótesis de la Rodilla/efectos adversos , Antibacterianos/uso terapéuticoRESUMEN
Background: Revision total knee arthroplasty (RTKA) is a technically demanding procedure for failed primary TKA. Posterior-stabilized (PS) and constrained condylar knee (CCK) articulations are commonly used for RTKA, but comparison of these articulations in RTKA is scarce. The aim of this study was to compare survival rates and clinical outcomes of RTKAs using PS articulation and CCK articulation. Methods: This study conducted a retrospective analysis of 86 RTKAs (PS, n = 41; CCK, n = 45) with a mean follow-up of 9.15 ± 2.79 years. Clinical outcomes were evaluated using the Hospital for Special Surgery score, Knee Society Score, and The Western Ontario and McMaster Universities Osteoarthritis Index at final follow-up. The survival rate of each group was analyzed by Kaplan-Meier survival analysis and Cox-hazard progression model. Results: Clinical outcomes were improved in both groups without significant difference. Twelve patients had orthopedic complications (4 in PS group and 8 in CCK group). Eight of them underwent re-RTKA (3 in PS group and 5 in CCK group). The articulation design did not influence the failure. The estimated 10-year survival rate was 92.7% in the PS group and 88.2% in the CCK group with no significant difference (p = 0.60). Also in septic failure, there was no significant difference in survival rate (92.7% in PS group and 92.5% in CCK group, p = 0.87). The hazard ratio in the PS group was not significantly different (p = 0.607). Conclusions: In RTKA, both PS and CCK showed similar survival rates and clinical outcomes at a mean follow-up of 9.2 years. Implant articulation did not affect the outcomes when properly indicated.
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Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Tasa de Supervivencia , Prótesis de la Rodilla/efectos adversos , Estudios Retrospectivos , Estudios de Seguimiento , Falla de Prótesis , Reoperación , Diseño de Prótesis , Articulación de la Rodilla/cirugíaRESUMEN
Microfracture technique for treating articular cartilage defects usually has poor clinical outcomes due to critical heterogeneity and extremely limited in quality. To improve the effects of current surgical technique (i.e., microfracture technique), we propose the transplantable stem cell nanobridge scaffold, acting as a protective bridge between host tissue and defected cartilage as well as microfracture-derived cells. Nanobridge scaffolds have a sophisticated nanoaligned structure with freestanding and flexible shapes for imposing direct structural guidance to cells including transplanted stem cells and host cells, and it can induce not only chondrocyte migration but also stem cell differentiation, maturation, and growth factor secretion. The transplantable stem cell nanobridge scaffold is capable of reconstructing the defected cartilage with homogeneous architecture and highly enhanced adhesive stress similar with native cartilage tissue by the synergistic effects of stem cells-based chondro-induction and nanotopography-based chondro-conduction. Our findings demonstrate a significant advancement in the traditional treatment technique by using a nanoengineered tool for achieving successful cartilage regeneration.
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Cartílago Articular , Fracturas por Estrés , Humanos , Células Madre , Diferenciación Celular , RegeneraciónRESUMEN
Mesenchymal stem cells (MSCs) rely on chemokines and chemokine receptors to execute their biological and physiological functions. Stromal cell-derived factor-1 (SDF-1) is upregulated in injury sites, where it acts as a chemotactic agent, attracting CXCR4-expressing MSCs, which play a pivotal role in the healing and regeneration of tissue throughout the body. Furthermore, SDF-1 expression has been observed in regions experiencing inflammation-induced bone destruction and fracture sites. In this study, we identified a novel peptide called bone-forming peptide-5 (BFP-5), derived from SDF-1δ, which can promote the osteogenesis of MSCs as well as bone formation and healing. Multipotent bone marrow stromal cells treated with BFP-5 showed enhanced alizarin red S staining and higher alkaline phosphatase (ALP) activity. Moreover, ALP and osterix proteins were more abundantly expressed when cells were treated with BFP-5 than SDF-1α. Histology and microcomputed tomography data at 12 weeks demonstrated that both rabbit and goat models transplanted with polycaprolactone (PCL) scaffolds coated with BFP-5 showed significantly greater bone formation than animals transplanted with PCL scaffolds alone. These findings suggest that BFP-5 could be useful in the development of related therapies for conditions associated with bones.
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Células Madre Mesenquimatosas , Osteogénesis , Animales , Conejos , Microtomografía por Rayos X , Diferenciación Celular , Células del Estroma/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Quimiocina CXCL12/farmacología , Quimiocina CXCL12/metabolismo , Células de la Médula ÓseaRESUMEN
Background: Knee arthroscopy is frequently performed to improve joint function and relieve pain. However, there is no consensus regarding the effect of prior arthroscopy on outcomes following medial opening-wedge high tibial osteotomy (MOWHTO). Purpose: To compare midterm clinical outcomes and survival rates after MOWHTO between patients with and without a history of knee arthroscopy. Study Design: Cohort study; Level of evidence, 3. Methods: We enrolled patients who underwent MOWHTO between March 2008 and February 2017 and had ≥4 years of follow-up. Patients who had undergone knee arthroscopy were included in an arthroscopy group, and those who had not were included as controls. After propensity score matching based on age, sex, body mass index, and lesion size, 80 patients in each group were included. Clinical outcomes were assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), 36-Item Short Form Health Survey, and Tegner Activity Scale. Furthermore, survival rates and relevant risk factors that affected joint survivorship were analyzed, wherein conversion to total knee arthroplasty was considered the endpoint. Results: Although the pre- to postoperative improvement in clinical outcomes did not differ significantly between the groups, there were significant between-group differences in final postoperative scores on the KOOS-Activities of Daily Living (arthroscopy vs control, 78.1 ± 10.6 vs 81.0 ± 9.8; P = .031), KOOS-Sport and Recreation (45.4 ± 12.8 vs 48.7 ± 13.5; P = .045), 36-Item Short Form Health Survey Physical Component Summary (65.1 ± 12.7 vs 69.3 ± 11.8; P = .017), and Tegner Activity Scale (4.1 ± 1.1 vs 4.5 ± 1.0; P = .007). The survival rate was 96.8% at a mean follow-up of 8 years, and survival was not associated with a history of arthroscopy (P = .697; log-rank test). Conclusion: Although patients with prior arthroscopy had some inferior patient-reported outcome scores after MOWHTO, the overall clinical improvements were similar in the arthroscopy and control groups.
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This study aimed to assess the safety and effectiveness of the highly cross-linked hyaluronic acid-LBSA0103-in patients with knee osteoarthritis (OA) as per the prescribing information (PI) in South Korea. A total of 3,140 subjects aged ≥19 years were enrolled in this post-marketing surveillance (PMS) study from 2013 to 2019. The subjects received one or two injections of LBSA0103. The median duration of follow-up was 308 days. Adverse events (AEs), adverse drug reactions (ADRs), and serious AEs (SAEs) were monitored. Effectiveness was evaluated based on an index of effectiveness in accordance with the guidelines established by the Ministry of Food and Drug Safety and using a 100-mm visual analog scale (VAS) for weight-bearing pain. Overall, 250 subjects (7.96%) experienced 292 AEs and of these, unexpected AEs occurred in 114 subjects (3.63% [95% CI: 3.00-4.35]). Injection site pain was the most frequent AE reported by 81 subjects (2.58% [95% confidence intervals (CI): 2.05-3.20]). One hundred subjects experienced 108 ADRs (3.18% [95% CI: 2.60, 3.86]) and 15 unexpected ADRs were experienced by 13 subjects (0.41% [95% CI: 0.22-0.71]). Seventeen subjects experienced 22 SAEs (0.54% [95% CI: 0.32-0.87]) during the entire PMS period, and all were considered "unlikely" related to the study drug. Most AEs were mild in terms of severity and resolved during the study period. LBSA0103 was also effective in relieving symptomatic pain in knee OA patients. The condition in more than 80% of the subjects was considered to be improved when assessed by the investigators. LBSA0103 resulted in a significant reduction in the mean VAS score at 12 weeks after the first and second injections (24.79 (± 20.55) mm and 17.63 (±12.31) mm, respectively; p<0.0001). In conclusion, LBSA0103, used for the treatment of knee OA in a real-world setting, was well tolerated, with an acceptable safety profile and consistent therapeutic effect.
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Ácido Hialurónico , Osteoartritis de la Rodilla , Humanos , Ácido Hialurónico/efectos adversos , Inyecciones Intraarticulares , Osteoartritis de la Rodilla/terapia , República de Corea/epidemiología , Dolor/tratamiento farmacológico , Dolor/inducido químicamente , Vigilancia de Productos Comercializados , Resultado del TratamientoRESUMEN
PURPOSE: To analyze the effect of augmenting a hamstring autograft anterior cruciate ligament reconstruction (ACLR) with an anterolateral ligament reconstruction (ALLR) on a primary outcome of passive anterior tibial subluxation (PATS) and a secondary outcome of the clinical outcomes. METHODS: ACL-injured patients who underwent primary ACLR between March 2014 and February 2020 at our center were enrolled. Patients who underwent combined procedures (ACLR + ALLR) were matched in a 1:1 propensity ratio to patients who underwent ACLR only. We evaluated PATS, knee stability (side-to-side laxity difference, pivot-shift test), and patient-reported outcome measures (PROMs) after the procedure and documented complications. RESULTS: From an initial cohort of 252 patients with a minimum follow-up period of 2 years (48.4 ± 16.6 months), 35 matched pairs were included, and 17 patients (48.6%) in each group underwent second-look arthroscopy. The combined ACLR + ALLR group showed significantly better improvement of PATS in the lateral compartments than the isolated ACLR group (P = .034). There were no significant differences between the groups regarding knee stability (side-to-side laxity difference, pivot-shift test), PROMs, complications, and second-look arthroscopic findings (all P > .05). Moreover, the proportions of patients who achieved the minimal clinically important difference in PROMs were not different between groups. CONCLUSIONS: The combined ACLR + ALLR procedure was associated with a mean improvement in anterior tibial subluxation for the lateral compartment that was 1.2 mm better than an isolated ACLR procedure, despite its lack of clinical significance. LEVEL OF EVIDENCE: Level III, cohort study.
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Reconstrucción del Ligamento Cruzado Anterior , Luxaciones Articulares , Humanos , Ligamento Cruzado Anterior , Estudios de Cohortes , Tibia/cirugía , Articulación de la RodillaRESUMEN
Background: The number of revision total knee arthroplasty (TKA) has been increasing. Although many studies have analyzed the causes of revision TKA in Western countries, a limited number of studies have analyzed changes in causes of or trends in revision TKA in Asia. This study analyzed and determined the frequency and causes of failures after TKA in our hospital. We also analyzed the differences and trends over the past 17 years. Methods: A total of 296 revision TKAs performed in a single institution from 2003 to 2019 were analyzed. During the 17-year study period, patients who had undergone primary TKA between 2003 and 2011 were classified into a past group, while those who had undergone primary TKA from 2012 to 2019 were classified into a recent group. A revision performed within 2 years after primary TKA was defined as early revision. Further, differences in causes of revision TKA according to the interval from primary TKA to revision TKA were determined. The causes of revision TKA were analyzed through a comprehensive analysis of patients' medical records. Results: Overall, infection was the most common cause of failure (151/296 cases, 51.0%). Compared to the past group, the recent group had a relatively higher proportion of patients undergoing revision TKA for mechanical loosening (past group, 19.1% vs. recent group, 31.9%) and instability (11.2% vs. 13.5%) and a relatively lower proportion of patients undergoing revision TKA for infection (56.2% vs. 48.8%), polyethylene (PE) wear (9.0% vs. 2.9%), osteolysis (2.2% vs. 1.9%), and malalignment (2.2% vs. 1.0%). On comparison according to the interval from primary TKA to revision TKA, the rate of infection relatively decreased, whereas the rate of mechanical loosening and instability relatively increased in the late revision TKA compared to the early revision TKA. Conclusions: Infection and aseptic loosening were the most common reasons of revision TKA in both past and recent groups. Compared to the past, revision TKA due to PE wear has decreased significantly and revision TKA due to mechanical loosening has relatively increased recently. Orthopedic surgeons need to be aware of recent trends in mechanisms of failure and should try to recognize and address the probable causes in TKA.