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INTRODUCTION: Aseptic loosening and periprosthetic fractures are main reasons for revision after THA. Quite different from most other stem systems, Corail cementless hip stems show better survival rates than their cemented counterpart, which can possibly be explained by the use of a collar. The study aimed to investigate primary stability with standard and undersized hip stems both collared and collarless. MATERIALS AND METHODS: Primary stability of cementless, collared and collarless, femoral stems was measured in artificial bones using both undersized and standard size. After preconditioning, 3D micromotion was measured under cyclic loading at the bone-implant interface. RESULTS: The use of a collar resulted in higher micromotion within the same stem size but showed no statistically significant difference for both standard and undersized hip stems. The collared and collarless undersized stems showed no significant differences in 3D micromotion at the upper measuring positions compared to the standard stem size. Micromotion was significantly higher in the distal measuring positions, with and without collar, for the undersized stems (vs. standard collarless stem size). CONCLUSION: The key finding is that the collarless and collared Corail hip stems, within one stem size, showed no significant differences in primary stability. Undersized stems showed significantly higher micromotion in the distal area both with and without collar.
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Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Diseño de Prótesis , Fenómenos Biomecánicos , Artroplastia de Reemplazo de Cadera/métodos , Artroplastia de Reemplazo de Cadera/instrumentación , Humanos , Falla de PrótesisRESUMEN
Clonal hematopoiesis (CH) is an age-related condition predisposing to blood cancer and cardiovascular disease (CVD). Murine models demonstrate CH-mediated altered immune function and proinflammation. Low-grade inflammation has been implicated in the pathogenesis of osteoarthritis (OA), the main indication for total hip arthroplasty (THA). THA-derived hip bones serve as a major source of healthy hematopoietic cells in experimental hematology. We prospectively investigated frequency and clinical associations of CH in 200 patients without known hematologic disease who were undergoing THA. Prevalence of CH was 50%, including 77 patients with CH of indeterminate potential (CHIP, defined as somatic variant allele frequencies [VAFs] ≥2%), and 23 patients harboring CH with lower mutation burden (VAF, 1% to 2%). Most commonly mutated genes were DNMT3A (29.5%), TET2 (15.0%), and ASXL1 (3.5%). CHIP is significantly associated with lower hemoglobin, higher mean corpuscular volume, previous or present malignant disease, and CVD. Strikingly, we observed a previously unreported association of CHIP with autoimmune diseases (AIDs; multivariable adjusted odds ratio, 6.6; 95% confidence interval, 1.7-30; P = .0081). These findings underscore the association between CH and inflammatory diseases. Our results have considerable relevance for managing patients with OA and AIDs or mild anemia and question the use of hip bone-derived cells as healthy experimental controls.
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Artroplastia de Reemplazo de Cadera , Enfermedades Autoinmunes/genética , Hematopoyesis Clonal , Frecuencia de los Genes , Mutación , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/complicaciones , Células Cultivadas , ADN Metiltransferasa 3A/genética , Proteínas de Unión al ADN/genética , Dioxigenasas/genética , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
PURPOSE: The purpose of this study was to quantify changes in rotation of the lower limb between image pairs based on patellar position. Additionally, we investigated the differences in alignment between centralized patellar and orthograde-positioned condyles. METHODS: Three-dimensional models of 30 paired legs were aligned in neutral position with condyles orthogonal to the sagittal axis and then rotated internally and externally in 1° increments up to 15°. For each rotation, the deviation of the patella and the subsequent changes in alignment parameters were calculated and plotted using a linear regression model. Differences between neutral position and patellar centralization were analysed qualitatively. RESULTS: A linear relationship between lower limb rotation and patellar position can be postulated. The regression model (R2 = 0.99) calculated a change of the patellar position of - 0.9 mm per degree rotation and alignment parameters showed small changes due to rotation. The physiological lateralization of the patella at neutral position was on average - 8.3 mm (SD: ± 5.4 mm). From neutral position, internal rotation that led to a centralized patella was on average - 9.8° (SD: ± 5.2°). CONCLUSION: The approximately linear dependence of the patellar position on rotation allows an inverse estimation of the rotation during image acquisition and its influence on the alignment parameters. As there is still no absolute consensus about lower limb positioning during image acquisition, data about the impact of a centralized patella compared to an orthograde condyle positioning on alignment parameters was provided. LEVEL OF EVIDENCE: IV.
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Artroplastia de Reemplazo de Rodilla , Rótula , Humanos , Rótula/cirugía , Fémur/cirugía , Artroplastia de Reemplazo de Rodilla/métodos , Extremidad Inferior/diagnóstico por imagen , Pierna , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/fisiologíaRESUMEN
Tranexamic acid (TXA) can reduce blood loss and transfusion rates in orthopaedic surgery. In this regard, a new viscoelastometric test (TPA-test, ClotPro), enables the monitoring of TXA effects. This prospective observational study evaluated and correlated TXA plasma concentrations (cTXA) following intravenous and oral administration in patients undergoing elective orthopaedic surgery with lysis variables of TPA-test. Blood samples of 42 patients were evaluated before TXA application and 2, 6, 12, 24 and 48 h afterwards. TPA-test was used to determine lysis time (LT) as well as maximum lysis (ML) and cTXA was measured using Ultra-High-Performance-Liquid-Chromatography/Mass-Spectrometry. Data are presented as median (min-max). LTTPA-test and MLTPA-test correlated with cTXA (r = 0.9456/r = 0.5362; p < 0.0001). 2 h after intravenous TXA administration all samples showed complete lysis inhibition (LTTPA-test prolongation: T1: 217 s (161-529) vs. T2: 4500 s (4500-4500);p < 0.0001), whereas after oral application high intraindividual variability was observed as some samples showed only moderate changes in LTTPA-test (T1: 236 s (180-360) vs. T2: 4500 s (460-4500); p < 0.0001). Nevertheless, statistically LTTPA-test did not differ between groups. MLTPA-test differed 2 h after application (i.v.: 9.0% (5-14) vs. oral: 31% (8-97); p = 0.0081). In 17/21 samples after oral and 0/21 samples after intravenous administration cTXA was < 10 µg ml-1 2 h after application. TPA-test correlated with cTXA. MLTPA-test differed between intravenous and oral application 2 h after application. Most patients with oral application had TXA plasma concentration < 10 µg ml-1. The duration of action did not differ between intravenous and oral application. Additional studies evaluating clinical outcomes and side-effects based on individualized TXA prophylaxis/therapy are required.
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Antifibrinolíticos , Procedimientos Ortopédicos , Ácido Tranexámico , Administración Intravenosa , Pérdida de Sangre Quirúrgica , Transfusión Sanguínea , HumanosRESUMEN
BACKGROUND: German social legislation gives patients the right to obtain a second opinion before elective surgery and defines quality criteria for reimbursement by statutory health insurances. However, the effects of second opinions before elective surgery are largely unknown. The aim of this study was to evaluate the effects of a second opinion programme in patients recommended for knee arthroplasty. METHODS: The largest statutory health insurance funds in Bavaria offered patients who had been recommended to have knee arthroplasty the opportunity to partake in a second opinion programme which consisted of an in person presentation to an experienced knee surgeon. In this cohort study, consecutive patients from this second opinion programme who signed informed consent were included from 07/10/2016 to 14/02/2020. Data were collected before and after the second opinion visit. RESULTS: A total of 141 (66%) of 215 patients who presented for a second opinion participated in the evaluation study. The second opinion physician recommended knee arthroplasty to 40% of the patients, later knee arthroplasty if the conditions worsened to 40%, and no knee arthroplasty to 20%. After receiving the second opinion 28 of 56 (41%) undecided patients preferred knee arthroplasty, 14 no knee arthroplasty, 14 remained undecided. Four of 46 patients with a preference for "arthroplasty" changed their decision to "no arthroplasty", five of 35 patients from "no arthroplasty" to "arthroplasty". The patients were more confident in their decision according to the decision confidence scale (before: 5.4 ± 3.0; after: 7.8 ± 2.5; p < 0.001). They rated their satisfaction with the second opinion programme with a mean grade of 1.35 (± 0.60) (best:1; worst:6). Logistic regression analyses showed that the recommendation of the second opinion physician for joint arthroplasty was associated with the guideline criteria radiological severity of osteoarthritis (p = 0.001) and knee-joint-specific quality of life (p = 0.041). CONCLUSION: The second opinion of an experienced knee surgeon frequently deviates from the initial recommendation for knee arthroplasty. The association of guideline criteria to the second recommendation suggests a high quality of the second opinion. From the patient perspective, the second opinion reduces uncertainties in their treatment decision.
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Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios de Cohortes , Humanos , Osteoartritis de la Rodilla/cirugía , Satisfacción del Paciente , Satisfacción Personal , Calidad de Vida , Derivación y ConsultaRESUMEN
BACKGROUND: Borrelia bavariensis is one of the agents of Lyme Borreliosis (or Lyme disease) in Eurasia. The genome of the Borrelia burgdorferi sensu lato species complex, that includes B. bavariensis, is known to be very complex and fragmented making the assembly of whole genomes with next-generation sequencing data a challenge. RESULTS: We present a genome reconstruction for 33 B. bavariensis isolates from Eurasia based on long-read (Pacific Bioscience, for three isolates) and short-read (Illumina) data. We show that the combination of both sequencing techniques allows proper genome reconstruction of all plasmids in most cases but use of a very close reference is necessary when only short-read sequencing data is available. B. bavariensis genomes combine a high degree of genetic conservation with high plasticity: all isolates share the main chromosome and five plasmids, but the repertoire of other plasmids is highly variable. In addition to plasmid losses and gains through horizontal transfer, we also observe several fusions between plasmids. Although European isolates of B. bavariensis have little diversity in genome content, there is some geographic structure to this variation. In contrast, each Asian isolate has a unique plasmid repertoire and we observe no geographically based differences between Japanese and Russian isolates. Comparing the genomes of Asian and European populations of B. bavariensis suggests that some genes which are markedly different between the two populations may be good candidates for adaptation to the tick vector, (Ixodes ricinus in Europe and I. persulcatus in Asia). CONCLUSIONS: We present the characterization of genomes of a large sample of B. bavariensis isolates and show that their plasmid content is highly variable. This study opens the way for genomic studies seeking to understand host and vector adaptation as well as human pathogenicity in Eurasian Lyme Borreliosis agents.
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Secuencia Conservada , Genoma Bacteriano , Ixodes , Filogenia , Spirochaetales , Animales , Asia , Grupo Borrelia Burgdorferi , Secuencia Conservada/genética , Europa (Continente) , Genoma Bacteriano/genética , Genómica , Humanos , Enfermedad de Lyme/microbiología , Plásmidos/genética , Federación de Rusia , Spirochaetales/clasificación , Spirochaetales/genéticaRESUMEN
BACKGROUND: It is still controversial whether the combination of anterior cruciate ligament (ACL) reconstruction and extra-articular reconstruction (EAR) have good clinical efficacy. This meta-analysis aims systematically to compare the clinical effectiveness of ACL reconstruction and combined reconstruction. METHODS: Electronic databases, including Medline/PubMed, Embase and the Cochrane Library, were systematically searched to identify targeted studies. A meta-analysis were performed to pool the outcome estimates of interest, such as the Lysholm, International Knee Documentation Committee (IKDC) and Tegner scores and the results from the KT-1000/2000 arthrometer test, the Lachman test and the pivot shift test. RESULTS: Twelve studies involving 1146 knees were identified. Compared with single ACL reconstruction, combined reconstruction had better results for a pivot shift of grade 1 (relative ratio [RR] = 0.88, 95% CI: 0.83-0.94) and grade 2 (RR = 0.95, 95% CI: 0.91-0.99) rather than grade 3 (RR = 0.98, 95% CI: 0.90-1.06) and no statistically significant difference for both Lachman grade 1 (RR = 0.96, 95% CI: 0.89-1.05) and grade 2 (RR = 0.96, 95% CI: 0.90-1.03). Combined reconstruction resulted in significant improvements on the instrumented joint laxity test when considering a failure standard of more than 5 mm (a side-to-side arthrometric difference) (RR = 0.94, 95% CI: 0.89-0.98) rather than 3 mm (RR = 0.94, 95% CI: 0.86-1.03). Moreover, combined reconstruction increased the IKDC score at the 12-month (weighted mean difference [WMD] = - 6.38, 95% CI: - 9.66 to - 3.10), 24-month (WMD = - 5.60, 95% CI: - 8.54 to - 2.66) and 36-month follow-ups (WMD = - 4.71, 95% CI: - 7.59 to - 1.83) and the Tegner score at the 36-month follow-up (WMD = - 0.53, 95% CI: - 0.97 to - 0.09), but it did not increase the Lysholm score at the 36-month follow-up (WMD = - 0.84, 95% CI: - 2.02 to 0.34). CONCLUSION: With the advances in reconstruction techniques, combined reconstructions were found to be effective in improving rotational stability and to lead to good functional scores. However, obviously, the combined reconstruction technique is more time-consuming and requires an additional incision, which is not suitable for all ACL-deficient patients. Therefore, programs should be personalized and customized for the specific situation of each patient.
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Reconstrucción del Ligamento Cruzado Anterior/métodos , Ligamento Cruzado Anterior/cirugía , Inestabilidad de la Articulación/cirugía , Traumatismos de la Rodilla/cirugía , Articulación de la Rodilla/cirugía , Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior/efectos adversos , Humanos , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/fisiopatología , Traumatismos de la Rodilla/diagnóstico , Traumatismos de la Rodilla/fisiopatología , Articulación de la Rodilla/fisiopatología , Ensayos Clínicos Controlados Aleatorios como Asunto , Recuperación de la Función , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: Higher revision rates were shown in varus- or valgus-positioned tibias in unicompartmental knee arthroplasty (UKA), but more than 15% of UKA prostheses are implanted with more than 5° of varus or valgus. This study aimed to analyze the wear rate in UKA when implanting the tibial component in either varus or valgus position versus a neutral placement at 90° to the tibial anatomical axis. The study hypothesized that a 5° varus or valgus positioning of the tibial plateau will generate less wear compared to a neutral alignment. METHODS: Wear was experimentally analyzed on a medial anatomical fixed-bearing unicompartmental knee prosthesis (Univation, Aesculap, Germany) in vitro with a customized, four-station, servohydraulic knee wear simulator, reproducing the walking cycle. The forces, loading and range of motion were applied as specified in the ISO 14243-1:2002, 5 million cycles were analyzed. The tibial components of the medial prostheses were inserted in a neutral position, with 5° varus, and 5° valgus (n = 3, each group). RESULTS: The wear rate decreased significantly with a 5° varus positioning (6.30 ± 1.38 mg/million cycles) and a 5° valgus positioning (4.96 ± 2.47 mg/million cycles) compared to the neutral position (12.16 ± 1.26 mg/million cycles) (p < 0.01 for the varus and the valgus position). The wear area on the inlay was slightly reduced in the varus and valgus group. CONCLUSION: A varus or valgus "malpositioning" up to 5° will not lead to an increased wear. Wear was even less because of the reduced articulating contact area between the inlay and the femur. A slight varus positioning of the tibial component (parallel to the anatomical joint line) positioning can be advocated from a point of wear. LEVEL OF EVIDENCE: Experimental study.
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Artroplastia de Reemplazo de Rodilla/instrumentación , Prótesis de la Rodilla , Ensayo de Materiales , Falla de Prótesis , Ajuste de Prótesis , HumanosRESUMEN
PURPOSE: To analyze the ability of ropivacaine, bupivacaine, and triamcinolone to induce apoptosis and necrosis in fibroblasts, tenocytes, and human mesenchymal stem cells. METHODS: Human dermal fibroblasts, adipose-derived human mesenchymal stem cells (hMSCs), and tenocytes gained from the rotator cuff tendon were seeded with a cell density of 0.5 × 104/cm2. One specimen of ropivacaine, bupivacaine, and triamcinolone was tested separately on the cells with separate concentrations of 0.5%, 0.25%, and 0.125% for each specimen. The negative control received no agent, only a change of medium. The incubation period for each agent was 30 minutes. After a change of medium and 1 hour, 24 hours, and 7 days of incubation, 104 cells were harvested and analyzed via fluorescence-activated cell sorting with double-staining with annexin V and propidium iodide. Statistical analysis to determine significant difference (P < .05) between the groups with SPSS statistics 23 through one-way analysis of variance with a univariate general linear model was performed. RESULTS: Bupivacaine showed necrosis-inducing effects on fibroblasts and tenocytes, with the necrotic effect peaking at 0.5% and 0.25%. Ropivacaine and triamcinolone caused no significant necrosis. Compared with fibroblasts and tenocytes, hMSCs did not show significant necrotic or apoptotic effects after exposure to bupivacaine. Overall, no significant differences in apoptosis were detected between different cell lines, varying concentrations, or time measurements. CONCLUSIONS: Bupivacaine 0.5% and 0.25% have the most necrosis-inducing effects on fibroblasts and tenocytes. Ropivacaine caused less necrosis than bupivaine. Compared with fibroblasts and tenocytes, hMSCs were not affected by necrosis using any of the tested agents. A significant apoptosis-inducing effect could not be detected for the different cell lines. CLINICAL RELEVANCE: Possible cell toxicity raises questions of concern for intra-articular injections using local anesthetics and corticosteroids. The present study demonstrates the necrotic and apoptotic effects of ropivacaine, bupivacaine, and triamcinolone and may give recommendations for intra-articular use of local anesthetics and corticosteroids.
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Amidas/toxicidad , Bupivacaína/toxicidad , Fibroblastos/efectos de los fármacos , Células Madre Mesenquimatosas/efectos de los fármacos , Tenocitos/efectos de los fármacos , Triamcinolona/toxicidad , Adulto , Amidas/administración & dosificación , Anestésicos Locales/farmacología , Apoptosis/efectos de los fármacos , Bupivacaína/administración & dosificación , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/patología , Citometría de Flujo , Glucocorticoides/administración & dosificación , Glucocorticoides/toxicidad , Humanos , Células Madre Mesenquimatosas/patología , Necrosis , Ropivacaína , Manguito de los Rotadores/citología , Piel/citología , Tenocitos/patología , Triamcinolona/administración & dosificaciónRESUMEN
BACKGROUND: In patients undergoing general anaesthesia, intraoperative hypotension occurs frequently and is associated with adverse outcomes such as postoperative acute kidney failure, myocardial infarction or stroke. A history of chronic hypertension renders patients more susceptible to a decrease in blood pressure (BP) after induction of general anaesthesia. As a patient's BP is generally monitored intermittently via an upper arm cuff, there may be a delay in the detection of hypotension by the anaesthetist. OBJECTIVE: The current study investigates whether the presence of continuous BP monitoring leads to improved BP stability. DESIGN: Randomised, controlled and single-centre study. PATIENTS: A total of 160 orthopaedic patients undergoing general anaesthesia with a history of chronic hypertension. INTERVENTION: The patients were randomised to either a study group (nâ=â77) that received continuous non-invasive BP monitoring in addition to oscillometric intermittent monitoring, or a control group (nâ=â83) whose BP was monitored intermittently only. The interval for oscillometric measurements in both groups was set to 3âmin. After induction of general anaesthesia, oscillometric BP values of the two groups were compared for the first hour of the procedure. Anaesthetists were blinded to the purpose of the study. MAIN OUTCOME MEASURE: BP stability and hypotensive events. RESULTS: There was no difference in baseline BP between the groups. After adjustment for multiple testing, mean arterial BP in the study group was significantly higher than in the control group at 12 and 15âmin. Meanâ±âSD for study and control group, respectively were: 12âmin, 102â±â24 vs. 90â±â26âmmHg (Pâ=â0.039) and 15âmin, 102â±â21 vs. 90â±â23âmmHg (Pâ=â0.023). Hypotensive readings below a mean pressure of 55âmmHg occurred more often in the control group (25 vs. 7, Pâ=â0.047). CONCLUSION: Continuous monitoring contributes to BP stability in the studied population. TRIAL REGISTRATION: NCT02519101.
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Anestesia General/métodos , Determinación de la Presión Sanguínea/métodos , Presión Sanguínea/fisiología , Monitoreo Intraoperatorio/métodos , Procedimientos Ortopédicos/métodos , Anciano , Anestesia General/efectos adversos , Anestesia General/tendencias , Determinación de la Presión Sanguínea/tendencias , Femenino , Humanos , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/tendencias , Procedimientos Ortopédicos/efectos adversos , Procedimientos Ortopédicos/tendencias , Estudios ProspectivosRESUMEN
PURPOSE: Short stem total hip arthroplasty (SHA) has gained increasing popularity as it conserves bone stock and is supposed to allow revision with a conventional stem. However, no study has evaluated whether the revision of a SHA with a standard total hip arthroplasty (THA) stem provides sufficient primary stability to allow osseous integration. METHODS: A neck preserving SHA (Metha) and a standard THA (CLS) stem were implanted into six composite femurs respectively and dynamically loaded (300-1700 N, 1 Hz). Primary stability was evaluated by three dimensional-micromotions (3D micro motion) at five points of the interface. Then, a revision scenario was created by removing the SHA and using the same CLS stem as a revision implant (CLS-revision group), with subsequent evaluation of the 3D micro motion according to the primary CLS stem. RESULTS: The 3D micro motion pattern significantly differed in the primary situation between the short and the standard stem. The highest 3D micro motion were registered proximally for the Metha and distally for the CLS stem. Revising the Metha with a CLS stem revealed a bony defect at the calcar. However, the 3D micro motion of the CLS-revision group were not significant higher compared to those of the primary CLS stem. CONCLUSION: Our results show, that SHA (Metha) and standard THA (CLS) provide a good primary stability, however with different pattern of anchorage. The CLS stem reached a similar stability in this revision scenario as the CLS in the primary situation, wherefore it can be assumed that in uncomplicated revisions the Metha short stem can safely be revised with a CLS standard stem.
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Artroplastia de Reemplazo de Cadera/instrumentación , Articulación de la Cadera/cirugía , Prótesis de Cadera/efectos adversos , Reoperación/instrumentación , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Fenómenos Biomecánicos , Fémur/cirugía , Articulación de la Cadera/fisiopatología , Humanos , Movimiento (Física) , Diseño de Prótesis/efectos adversos , Diseño de Prótesis/métodos , Reoperación/métodosRESUMEN
PURPOSE: The aim of this study was to assess the reliability of preoperative MRI for the staging of osteochondritis dissecans (OCD) lesions of the knee and the talus in juvenile patients, using arthroscopy as the gold standard of diagnosis. METHODS: Sixty-three juvenile patients (range 8-16 years) with an OCD of the knee or the talus underwent arthroscopy after MRI. In 54/9 out of 63 cases, 1.5/3 T MR scanners were used. The OCD stage was classified according the staging criteria of Dipaola et al. Arthroscopic findings were compared with MRI reports in each patient. RESULTS: From the 63 juvenile patients, MRI/arthroscopy revealed a stage I OCD in 4/19 patients, stage II in 31/22 patients, stage III in 22/9 patients and stage IV in 6/6 patients. No osteochondral pathology was evident in arthroscopy in seven out of 63 patients. The overall accuracy of preoperative MRI in staging an OCD lesion of the knee or the talus was 41.3%. In 33 out of 63 patients (52.4%), arthroscopy revealed a lower OCD stage than in the preoperative MRI grading, and in four out of 63 cases (6.4%), the intraoperative arthroscopic grading was worse than in preoperative MRI prior to surgery. The utilization of the 3 T MRI provided a correct diagnosis with 44.4%. CONCLUSIONS: Even with today's modern MRI scanners, it is not possible to predict an accurate OCD stage in children. The children's orthopaedist should not solely rely on the MRI when it comes to the decision to further conservative or surgical treatment of a juvenile OCD, but rather should take surgical therapy in consideration within persisting symptoms despite a low OCD stage provided by MRI. LEVEL OF EVIDENCE: III.
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Artroscopía , Imagen por Resonancia Magnética , Osteocondritis Disecante/clasificación , Osteocondritis Disecante/diagnóstico por imagen , Adolescente , Niño , Femenino , Humanos , Masculino , Osteocondritis Disecante/cirugía , Estudios RetrospectivosRESUMEN
Chimeric antigen receptor (CAR)-modified T cells emerged as effective tools in the immunotherapy of cancer but can produce severe on-target off-tissue toxicities. This risk can conceivably be overcome, at least partially, by transient transfection. The design of CARs, however, has so far not been optimized for use in non-permanent T cell modification. Here we compared the performance of T cells modified with three different first- and second-generation CARs, each specific for MCSP (HMW-MAA) which is commonly expressed by melanoma cells. Upon RNA transfer, the expression of all receptors was limited in time. The second-generation CARs, which combined CD28-CD3ζ signaling, were expressed at higher levels and more prolonged than first-generation CARs with CD3ζ only. The CD28 domain increased the cytokine production, but had only an indirect effect on the lytic capacity, by prolonging the CAR expression. Especially for the second-generation CARs, the scFv clearly impacted the level and duration of CAR expression and the T cell performance. Thus, we identified a CAR high in both expression and anti-tumor cell reactivity. T cells transfected with this CAR increased the mean survival time of mice after challenge with melanoma cells. To facilitate clinical application, this CAR was used to redirect T cells from late-stage melanoma patients by RNA transfection. These T cells mediated effective antigen-specific tumor cell lysis and release of pro-inflammatory cytokines, even after cryoconservation of the transfected T cells. Taken together, the analysis identified a CAR with superior anti-melanoma performance after RNA transfer which is a promising candidate for clinical exploration.
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Proteínas Mitocondriales/inmunología , Receptores de Antígenos de Linfocitos T/inmunología , Animales , Proteínas Portadoras/inmunología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Melanoma/inmunología , Melanoma/fisiopatología , Ratones , Proteínas Mitocondriales/genética , Estabilidad Proteica , Estructura Terciaria de Proteína , Receptores de Antígenos de Linfocitos T/genética , Receptores de Antígenos de Linfocitos T/metabolismo , Anticuerpos de Cadena Única/metabolismoRESUMEN
Aseptic implant loosening due to inflammatory reactions to wear debris is the main reason for the revision of total knee replacements (TKR). Hence, the decrease in polyethylene wear particle generation from the articulating surfaces is aimed at improving implant design and material. For preclinical testing of new TKR systems standardized wear tests are required. However, these wear tests do not reproduce the entire in vivo situation, since the pattern and amount of wear and subsequent implant failure are underestimated. Therefore, daily activity, kinematics, implant aging and position, third-body-wear and surface properties have to be considered to estimate the wear of implant components in vivo. Hence, severe test conditions are in demand for a better reproduction of the in vivo situation of TKR. In the present article an overview of different experimental wear test scenarios considering clinically relevant polyethylene wear situations using severe test conditions is presented.
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Artroplastia de Reemplazo de Rodilla , Ensayo de Materiales , Polietilenos , Fenómenos Biomecánicos , HumanosRESUMEN
STUDY DESIGN: Retrospective study. OBJECTIVE: The purpose of this study was to investigate the question whether surgical treatment of patients with spondylodiscitis and neurological deficits caused by a spinal epidural abscess (SEA) is a predictor of clinical outcome. SUMMARY OF BACKGROUND DATA: Spondylodiscitis with an accompanying SEA is a serious medical condition that is associated with potentially high risk for long-term neurological morbidity. In the literature, up to 75% of patients suffer from neurological deficits related to SEA in spondylodiscitis. Independent of treatment, residual neurology persists at a high rate. METHODS: A retrospective analysis of 135 patients admitted to our department due to a diagnosis of spondylodiscitis was performed. Presence of SEA was evaluated based on computed tomography and magnetic resonance imaging. Neurological status was documented on admission and at discharge according to the Frankel Score. In addition, our patient population was separated into group I without neurological deficits (Frankel E) and group II with abnormal Frankel A-D. Surgical and nonsurgical therapy was retrospectively evaluated. Data were statistically analyzed using the 2-sided Fisher exact test. RESULTS: On admission, 102 patients were graded as Frankel E in group I. In group II, 15 were Frankel D, 8 Frankel C, 8 Frankel B, and 2 Frankel A. After treatment, 105 patients were Frankel E, 19 Frankel D, 4 Frankel C, 3 Frankel B, and none Frankel A. Four patients died because of severe comorbidities. In group II, 13 of 33 patients had a SEA. Twelve patients showed improvement in Frankel grade, 1 remained unchanged. Of the 20 patients in group II without a SEA, 11 improved and 9 remained unchanged. Twenty-eight of the 33 patients in group II were treated surgically. Patients in both groups with improved neurology showed an upgrade by 1 or 2 Frankel scores. There was no deterioration of neurology. The correlation between surgically treated patients with SEA in comparison with patients without SEA is considered to be statistically significant. CONCLUSION: Surgical treatment of patients with spondylodiscitis and neurological deficits caused by SEA is a predictor of clinical outcome.
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Discitis/complicaciones , Discitis/cirugía , Absceso Epidural/complicaciones , Absceso Epidural/cirugía , Enfermedades de la Médula Espinal/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Discitis/diagnóstico , Absceso Epidural/diagnóstico , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/etiología , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Enfermedades de la Médula Espinal/diagnóstico , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
Background: Periprosthetic joint infection (PJI) following total knee arthroplasty is a serious complication lacking evidence-based diagnostic and treatment protocols, particularly in ruling out persisting infection before reimplantation. Methods: This retrospective analysis assessed the mid-term outcomes of 66 patients undergoing septic two-stage knee revision surgeries from 2007 to 2013, diagnosed as per the Musculoskeletal Infection Society criteria. After implant removal and antibiotic treatment, reimplantation decisions were based on either joint aspiration, blood counts, and clinical examination (group A) or an open biopsy (group B). Both groups underwent meticulous debridement and spacer exchange during the interim period. Results: Late re-infection occurred in 12.1% of all patients. In group A, 13.8% experienced late re-infection, with 14.3% in subgroup A1 and 13.3% in subgroup A2. In group B, 10% had a late re-infection. No significant difference in re-infection or complication rates was found between the groups. Conclusions: The study did not demonstrate the superiority of group B's approach of open biopsy over group A's joint aspiration, clinical examination, and blood counts in preventing re-infection or reducing complications.
RESUMEN
OBJECTIVE: The objective of this study was to determine the impact of obtaining a second opinion consultation on time to knee arthroplasty (KA). We further examined the frequency of KA and the determinants of KA following the second opinion. DESIGN: Prospective cohort study. SETTING: The second opinion programme was implemented at the Ludwig Maximilian University Hospital in Munich. PARTICIPANTS: Participants comprised patients with knee osteoarthritis who were insured with one of the largest statutory health insurance Allgemeine Ortskrankenkasse Bayern (mean age 64.3±9.6 years). Patients participated in a second-opinion programme and completed questionnaires on site before and after personal presentation for the second opinion consultation. Follow-up questionnaires were delivered by post at 3 and 12 months after the second opinion consultation. Of the 142 patients included in the study, 47 (33.1%) underwent KA within 12 months after obtaining the second opinion. PRIMARY OUTCOME MEASURES: Primary outcome measure was time until patients received KA. Cox proportional hazard modelling was used to calculate the associations between the selected predictors and time that elapsed between receipt of the second opinion to KA. RESULTS: Mean time until KA was 17 weeks. Kaplan-Meier curves showed significant differences in time to KA according to the recommendation given at second opinion consultation, knee-related quality of life and Kellgren-Lawrence grade. In multivariate Cox proportional hazard modelling, second opinion recommendation (HR 5.33, 95% CI 1.16, 24.41) and knee-related quality of life (HR 1.03, 95% CI 1.01, 1.06) were significant predictors of time from second opinion to KA. CONCLUSIONS: Obtaining a second opinion had significant impact on time to knee replacement. Those who were recommended immediate surgery also underwent surgery more quickly after the second opinion. The effect of knee-related quality of life supports the importance of patient-reported outcome measures in the decision for or against KA.
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Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Persona de Mediana Edad , Anciano , Estudios Prospectivos , Calidad de Vida , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugíaRESUMEN
CLINICAL ISSUE: To assess postoperative imaging of the hip joint regarding possible complications, it is indispensable to have in-depth knowledge of commonly used surgical techniques, access routes, and the implanted materials. STANDARD RADIOLOGICAL METHODS: While radiography is used to evaluate the position of foreign material and to rule out periprosthetic fractures that have occurred intraoperatively, follow-up examinations might show signs of material failure, aseptic loosening, prosthesis infections, or the occurrence of heterotopic ossifications. If radiographic findings are ambiguous, computed tomography (CT) may be used to clarify findings, whereas magnetic resonance imaging (MRI) is helpful to identify intra- and periarticular soft tissue pathologies such as surgery-associated cartilage and ligament damage, muscle insufficiency, or metallosis. METHODOLOGICAL INNOVATION AND EVALUATION: To guide clinical decision making in common postoperative complications, various classification systems are available, e.g., for periprosthetic fractures, aseptic loosening, or heterotopic ossification. However, the differentiation between aseptic material loosening and septic endoprosthesis infection remains challenging if based on imaging alone. PRACTICAL RECOMMENDATIONS: The assessment of postoperative hip imaging should be closely linked to the respective surgical technique and the implanted foreign material, whereby different probabilities of specific complications can be derived.
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Artroplastia de Reemplazo de Cadera , Prótesis de Cadera , Osificación Heterotópica , Fracturas Periprotésicas , Artroplastia de Reemplazo de Cadera/efectos adversos , Articulación de la Cadera/diagnóstico por imagen , Prótesis de Cadera/efectos adversos , Humanos , Osificación Heterotópica/patología , Fracturas Periprotésicas/patología , Falla de PrótesisRESUMEN
BACKGROUND: Surgical decompression is the intervention of choice for lumbar spinal stenosis (LSS) when non-operative treatment has failed. Apart from acute complications such as hematoma and infections, same-level recurrent lumbar stenosis and adjacent-segment disease (ASD) are factors that can occur after index lumbar spine surgery. OBJECTIVE: The aim of this retrospective case series was to evaluate the outcome of surgery and the odds of necessary revisions. METHODS: Patients who had undergone either decompressive lumbar laminotomy or laminotomy and spinal fusion due to lumbar spinal stenosis (LSS) between 2000 and 2011 were included in this analysis. Demographic, perioperative and radiographic data were collected. Clinical outcome was evaluated using numeric rating scale (NRS), the symptom subscale of the adapted version of the german Spinal Stenosis Measure (SSM) and patient-sreported ability to walk. RESULTS: Within the LSS- cohort of 438 patients, 338 patients underwent decompression surgery only, while instrumentation in addition to decompression was performed in 100 cases (22.3%). 38 patients had prior spinal operations (decompression, disc herniation, fusion) either at our hospital or elsewhere. Thirty-five intraoperative complications were documented with dural tear with CSF leak being the most common (33/35; 94.3%). Postoperative complications were defined as complications that needed surgery and differentiated between immediate postoperative complications (⩽ 3 weeks post operation) and complications that needed revisions surgery at a later date. Within all patients 51 revisions were classified as immediate complications of the index operation with infections, neurological deficits and hematoma being the most common. Within this group only 22 patients had fusion surgery in the first place, while 29 were treated by decompression. Revision surgery was indicated by 53 patients at a later date. While 4 patients decided against surgery, 49 revision surgeries were planned. 28 were performed at the same level, 10 at the same level plus an adjacent level, and 10 were executed at index level with indications of adjacent level spinal stenosis, adjacent level spinal stenosis plus instability and stand-alone instability. Pre- operative VAS score and ability to walk improved significantly in all patients. CONCLUSIONS: While looking for predictors of revision surgery due to re-stenosis, instability or same/adjacent segment disease none of these were found. Within our cohort no significant differences concerning demographic, peri-operative and radiographic data of patients with or without revision wer noted. Patients, who needed revision surgery were older but slightly healthier while more likely to be male and smoking. Surprisingly, significant differences were noted regarding the distribution of intraoperative and early postoperative complications among the 6 main surgeons while these weren't obious within the intial index group of late revisions.
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Enfermedades de la Columna Vertebral , Fusión Vertebral , Estenosis Espinal , Cirujanos , Humanos , Masculino , Femenino , Estenosis Espinal/cirugía , Reoperación , Vértebras Lumbares/cirugía , Estudios Retrospectivos , Descompresión Quirúrgica , Constricción Patológica/cirugía , Enfermedades de la Columna Vertebral/cirugía , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Hematoma/cirugíaRESUMEN
To date, the exact role of specific Toll-like receptors (TLRs) in regulating immune reactivity to metallic byproducts of orthopedic implants has not been fully clarified. In light of the situation, our objective in this investigation was to assess the expression levels of surface TLRs after metallic particle and ion exposure in an established animal model. Ten female BALB/c mice in each group received intra-articular injections of phosphate buffer (PBS) (control), metallic particles (MP), and metallic ions (MI), respectively. Seven days later, immunohistochemical staining was undertaken in the synovial layer of the murine knee joints using anti-TLR 1, 2, 4, 5, and 6 polyclonal antibodies. In addition to increased cellular infiltrates and a hyperplastic synovial membrane, the MP group showed significantly elevated TLR expression compared to the control group and had higher TLR 1-, 4-, and 6-positive cells than the MI group (p < 0.0167). TLR 4- and TLR 6-positive cells were significantly augmented for the MI group compared to the control group (p < 0.0167). Additionally, greenish corrosion particles found in the necrotic tissue suggested that metallic particles might release a certain level of locally toxic metallic ions in vivo.