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Expansion of the glutamine tract (poly-Q) in the protein huntingtin (HTT) causes the neurodegenerative disorder Huntington's disease (HD). Emerging evidence suggests that mutant HTT (mHTT) disrupts brain development. To gain mechanistic insights into the neurodevelopmental impact of human mHTT, we engineered male induced pluripotent stem cells to introduce a biallelic or monoallelic mutant 70Q expansion or to remove the poly-Q tract of HTT. The introduction of a 70Q mutation caused aberrant development of cerebral organoids with loss of neural progenitor organization. The early neurodevelopmental signature of mHTT highlighted the dysregulation of the protein coiled-coil-helix-coiled-coil-helix domain containing 2 (CHCHD2), a transcription factor involved in mitochondrial integrated stress response. CHCHD2 repression was associated with abnormal mitochondrial morpho-dynamics that was reverted upon overexpression of CHCHD2. Removing the poly-Q tract from HTT normalized CHCHD2 levels and corrected key mitochondrial defects. Hence, mHTT-mediated disruption of human neurodevelopment is paralleled by aberrant neurometabolic programming mediated by dysregulation of CHCHD2, which could then serve as an early interventional target for HD.
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Encéfalo , Proteínas de Ligação a DNA , Proteína Huntingtina , Doença de Huntington , Células-Tronco Pluripotentes Induzidas , Mitocôndrias , Proteínas Mitocondriais , Organoides , Fatores de Transcrição , Humanos , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Proteína Huntingtina/genética , Proteína Huntingtina/metabolismo , Organoides/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Mitocondriais/genética , Encéfalo/metabolismo , Encéfalo/patologia , Doença de Huntington/metabolismo , Doença de Huntington/genética , Doença de Huntington/patologia , Células-Tronco Pluripotentes Induzidas/metabolismo , Masculino , Mitocôndrias/metabolismo , Mutação , Dinâmica Mitocondrial/genéticaRESUMO
BACKGROUND: Prehabilitation before knee joint replacement surgery is gaining increasing importance due to the rising prevalence of knee osteoarthritis. The aim is to optimize the preoperative condition to improve postoperative recovery and reduce complications. MATERIALS AND METHODS: This review is based on a systematic literature search in the databases Medline, Cochrane Library, and Web of Science on the topic of prehabilitation in knee joint replacement. RESULTS: The current evidence shows heterogeneous results regarding the effectiveness of prehabilitation before knee joint replacement; some studies report improved postoperative outcomes such as reduced pain, increased function, and shorter hospital stays through preoperative training measures, while others found no significant differences. Additional preoperatively modifiable risk factors such as reduced physical fitness, substance abuse, nutritional status, comorbidities, and psychological factors should already be addressed during prehabilitation. Digital therapy and education measures offer a promising solution for the implementation of prehabilitation programs and are well received by patients. CONCLUSION: Overall, the evidence for preoperative training before knee joint replacement remains heterogeneous. Despite positive indications, evidence on exercise content, duration, frequency, and setting remains incomplete, requiring a critical review of current meta-analyses and systematic reviews. Modern prehabilitation before knee joint replacement should include musculoskeletal training and address preoperative risk factors to improve postoperative outcomes.
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Artroplastia do Joelho , Osteoartrite do Joelho , Exercício Pré-Operatório , Humanos , Artroplastia do Joelho/reabilitação , Osteoartrite do Joelho/cirurgia , Resultado do Tratamento , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Cuidados Pré-Operatórios/métodosRESUMO
Intra-operative fractures in knee revision surgery are relatively rare and have not been well studied. They may occur during joint exposition, removal of the prosthesis or cement, or implantation of trial or original components. The fractures affect both the metaphyseal area and diaphysis of the tibia and femur. Tibial fractures are slightly more common than femur fractures. On the femur, the medial condyle is most frequently affected, followed by the femur diaphysis. The use of non-cemented stems is associated with a greater risk of intra-operative diaphyseal fractures than that of cemented stems. Overall, women and patients with an osteopenic bone structure have a higher risk of fractures. It is common that fractures are diagnosed post-operatively. In these cases, conservative therapy may be successful, depending on the stability of the prosthesis and bones. The most common surgical fixation options are cerclages and screws, followed by stem extensions for bridging the fracture. Plate fixation or use of strut grafts are also sensible therapy options. Overall, intraoperative fractures have a high healing potential with stable and good joint function. The revision rate is still 15%, which is most often caused by peri-prosthetic infection.
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Fraturas do Fêmur , Tíbia , Humanos , Feminino , Tíbia/cirurgia , Reoperação , Fêmur/cirurgia , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/cirurgia , Extremidade InferiorRESUMO
BACKGROUND: Aseptic loosening is one of the most common reasons for revision in knee arthroplasty. Its pathogenesis is multifactorial, and early diagnosis is necessary to initiate appropriate therapy and to avoid serious complications, such as substantial bone loss or even periprosthetic fractures. OBJECTIVES: This paper describes the current standard in the diagnosis of aseptic loosening in total knee arthroplasty. Sensitivity and specificity of the individual diagnostic procedures are presented, and other causes for differential diagnoses of painful total knee arthroplasty (TKA) are discussed. RESULTS: In the case of suspected loosening in TKA, infection diagnostics should be performed to rule out periprosthetic infection, as this is crucial in terms of surgical strategy. The gold standard in diagnosing aseptic loosening is conventional radiography. Radiolucent lines at the cement-bone or metal-cement interface of more than 2â¯mm or increasing in translucency, migration of components, and cement fractures are obvious signs of loosening. Artifact-reduced computed tomography can bring additional information regarding periprosthetic osteolysis. A single bone scan is not reliable in diagnosing aseptic loosening, especially in the first 2 years after surgery. Single photon emission computed tomography (SPECT-CT) could be a useful extension in loosening diagnosis in the future. CONCLUSIONS: The diagnosis of aseptic loosening poses a great challenge to the treating physician and requires a structured diagnostic algorithm. After exclusion of infection, conventional radiography is the basic examination, which should be supplemented by computed tomography and nuclear medicine examinations according to the clinical symptoms and the time course.
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Artroplastia do Joelho , Prótese do Joelho , Artroplastia do Joelho/efeitos adversos , Cimentos Ósseos , Humanos , Falha de Prótese , Radiografia , Reoperação , Sensibilidade e EspecificidadeRESUMO
PURPOSE: In contrast to total knee arthroplasty (TKA), unicompartmental knee arthroplasty (UKA) is a true resurfacing procedure, as none of the ligaments are replaced or released, and the pre-arthritic leg alignment is the major goal. As such, the alignment of the tibial component plays a crucial role in postoperative knee function and long-term survival. Pinless navigation has shown reliable results in total knee arthroplasty. To the best of our knowledge, the use of pinless navigation has not been investigated for UKA. Therefore, the present study investigated whether implantation of the tibial component in 3° varus, which is closer to the anatomical axis, is feasible with a pinless optical navigation system. METHODS: 60 patients with the diagnosis of an unicompartmental arthritis, were eligible for UKA and treated with implantation in 3° varus alignment of the tibial component. Two groups were established. In the treatment group the tibial component was aligned using a pinless navigation technique. In the control group, a conventional extramedullary alignment guide was used. A clinical and radiographic follow up took place within 1 year of operation. RESULTS: 57 Patients were eligible for analysis. No clinical incidents were noted in the follow up period. The desired target value, the position of the tibial component, was accurately achieved with an average of 3° medial inclination using the pinless navigation as well as using the conventional technique. Mean incision to suture time was negligible between the two techniques. The mean suture time was 43.2 min with pinless navigation and 42.7 min with the conventional technique. CONCLUSIONS: With pinless navigation in UKA, a method was presented that made it possible to achieve sled prosthesis alignment at the level of a high-volume surgeon. These results were achieved with an irrelevant increase of surgical time and without placement of pins.
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Skills training is important in an arthroplasty curriculum and can focus either on "part tasks" or on full procedures. The most commonly used simulations in orthopedics including arthroplasty are anatomic specimens, dry bone models, and virtual or other technology-enhanced systems. A course curriculum planning committee must identify the gaps to address, define what learners need to be able to do, and select the most appropriate simulation modality and assessment for delivery. Each simulation must have a clear structure with learning objectives, steps, and take-home messages. Feedback from learners and faculty must be integrated to improve processes and models for future learning.
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Artroplastia de Quadril/educação , Artroplastia do Joelho/educação , Competência Clínica , Currículo , Ortopedia/educação , Cadáver , Simulação por Computador , Humanos , Modelos AnatômicosRESUMO
With increasing life expectancy, the demand for knee replacement is continuously rising. Despite the use of antibiotic prophylaxis and improved aseptic surgical techniques, periprosthetic joint infection (PJI) still occurs in 1% to 5% of patients after primary arthroplasty. An open question is the influence of PJI and resulting surgical procedures on the occurrence of long-term complications such as aseptic loosening. Patients needing multiple revision surgeries are especially at risk for decreases in bone mass and damage to the medullary cavity. Thus, we theorized that prior surgeries on the affected knee increase the risk of aseptic loosening in patients with PJI. METHODS: We retrospectively analyzed the cases of 100 patients who underwent total knee replacement exchange surgery as a result of PJI. In addition to clinical, paraclinical, and radiographic examination, we assessed comorbidities and the number of prior surgeries. RESULTS: Prosthetic survival was drastically decreased after PJI-related revision arthroplasty: during the first 7.3 years after reimplantation, 22% and 16% of all patients had aseptic loosening and recurrent PJI, respectively. The prevalence of aseptic loosening was 27.8% for female and 15.2% for male patients. A significant association between increasing patients' American Society of Anesthesiologists (ASA) classification and prosthetic failure rates was found, as was a strong correlation between number of prior surgeries and aseptic loosening. CONCLUSIONS: In this study, we found notable rates of aseptic loosening and recurrent PJI following PJI-related revision arthroplasty. The difference in the rate of aseptic loosening among male and female patients supports theories of the role of bone metabolism in the development of aseptic loosening. The economic and clinical burdens of prosthetic failure make it paramount to gain a better understanding of bone metabolism in PJI. Additional research should address the need to optimize treatment strategies to increase prosthetic survival. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
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Surgical risk factors for periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) are the subjects of ongoing research. It is unclear if there are specific locations of the surgical area that might act as a pathogen source. Due to the fact that bacterial replication occurs preferably under humid conditions, it was our aim to investigate if irrigation fluid reservoirs on the surgical covers are subject to bacterial colonization. We prospectively observed 40 patients with scheduled aseptic 1-stage TKA revision. At time intervals of 30 min, irrigation samples were tested for microbiological colonization. Additionally, the suction tip was investigated at the end of surgery. Overall, a bacterial detection rate of 25% was found (57/232 samples). Analysis for any positive microbial detection revealed pathogen findings of irrigation fluid in 41.7% of samples after 30 min with a constant increase up to 77.8% after 90 min. Twenty-three percent of suction tips showed bacterial colonization. Coagulase-negative staphylococci, accounting for the majority of PJI, were the predominant pathogens. After an average follow-up of 17 months, no PJI was confirmed. Despite the substantial bacterial load of irrigation fluid, PJI rates were not elevated. Nevertheless, we recommend that irrigation fluid reservoirs should be prevented and not withdrawn by suction.
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We discuss the derivation and the solutions of integrodifferential equations (variable-order time-fractional diffusion equations) following as continuous limits for lattice continuous time random walk schemes with power-law waiting-time probability density functions whose parameters are position-dependent. We concentrate on subdiffusive cases and discuss two situations as examples: A system consisting of two parts with different exponents of subdiffusion, and a system in which the subdiffusion exponent changes linearly from one end of the interval to another one. In both cases we compare the numerical solutions of generalized master equations describing the process on the lattice to the corresponding solutions of the continuous equations, which follow by exact solution of the corresponding equations in the Laplace domain with subsequent numerical inversion using the Gaver-Stehfest algorithm.
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An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Prior to a surgical intervention, the examination of patient coagulation disorders is unfortunately often underestimated. While patients with a haemophilia A or B are usually aware of the congenital tendency to bleed, disorders of increased blood coagulation, thrombophilia, are frequently undetected. Therefore, complications caused by thromboses and embolisms after total hip arthroplasty are far more common than uncontrollable post-operative bleeding. Patients with liver cirrhosis are considered to be particularly complicated and their coagulation status can be difficult to manage. This article describes the most common pathological coagulation disorders and provides information to identify them preoperatively. Furthermore, surgical strategy considerations for the use of certain implant types in this patient group are discussed.
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Artroplastia de Quadril , Hemofilia A , Hemofilia B , Hemorragia , HumanosRESUMO
The knee joint center of rotation is altered in the absence of the anterior cruciate ligament, which leads to substantially higher variance in kinematic patterns. To overcome this, total knee arthroplasty (TKA) designs with a high congruency in the lateral compartment have been proposed. The purpose of this study was to analyze the influence of a lateral pivot TKA-design on in-vivo knee joint kinematics. Tibiofemoral motion was retrospectively addressed in 10 patients during unloaded flexion-extension and loaded lunge using single plane fluoroscopy. During the unloaded flexion-extension movement, the lateral condyle remained almost stationary with little rollback at maximum flexion. The medial condyle exhibited anterior translation during the whole flexion cycle. During the loaded lunge movement, a higher degree of rollback compared to the unloaded activity was observed on the lateral condyle, whereas the medial condyle remained almost stationary. The results showed a clear lateral pivot during the unloaded activity, reflective of the implant's geometric characteristics, and a change to a medial pivot and a higher lateral rollback during the weight-bearing conditions, revealing the impact of load and muscle force. It remains unclear if the kinematics with a lateral TKA design could be considered as physiological, due to the limited knowledge available on native knee joint kinematics.
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Artroplastia do Joelho , Articulação do Joelho/fisiologia , Articulação do Joelho/cirurgia , Amplitude de Movimento Articular , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Masculino , Estudos Retrospectivos , Suporte de CargaRESUMO
BACKGROUND: Patients with osteosynthetic implants around the hip and knee show higher infection rates after joint arthroplasty. Our aim was to evaluate the bacterial colonization of any osteosynthetic implants around the hip and knee in patients without clinical signs of infection. METHODS: Consecutive patients with osteosynthetic implant removal because of related soft tissue irritations or before elective total joint arthroplasty of the hip and knee were prospectively included. Patients with signs of infection were excluded. Based on sonication fluid cultures, implants were classified according to microbial growth as negative (no growth), contaminated (nonsignificant growth), or colonized (significant growth). RESULTS: Sonication cultures were positive in 54 of 203 implants (27%), including 8 of 34 (24%) after orthopedic and 46 of 169 (27%) after traumatological surgery. Of 203 sonication cultures, 22 (11%) grew significant bacterial counts. Most common microorganisms were coagulase-negative staphylococci (46%). Implants around the knee showed a significantly higher rate of positive sonication cultures compared with those around the hip (14% vs 2%, P = .017). CONCLUSIONS: We detected high bacterial implant colonization rates regardless of the initial type of surgery. Predominant pathogens were staphylococci, the most common causative agents of periprosthetic joint infections. Positive sonication results do not necessarily lead to postoperative surgical complications and thus do not equal infection. It remains unclear if patients with evidence of bacterial implant colonization show a higher risk of periprosthetic joint infection after adjacent subsequent total joint arthroplasty. Nevertheless, surgeons should be aware of a significantly higher colonization rate of implants around the knee and take this into consideration when total knee arthroplasty is scheduled in patients with osteosynthetic devices.
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Artrite Infecciosa/etiologia , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Articulação do Quadril/cirurgia , Articulação do Joelho/cirurgia , Próteses e Implantes/efeitos adversos , Infecções Relacionadas à Prótese/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Assintomáticas , Bactérias , Remoção de Dispositivo/efeitos adversos , Feminino , Fixação Interna de Fraturas/efeitos adversos , Articulação do Quadril/microbiologia , Humanos , Articulação do Joelho/microbiologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Estudos Prospectivos , Infecções Relacionadas à Prótese/microbiologia , Sonicação , Adulto JovemRESUMO
The percentage area of fast twitch fibres of a muscle is a major determinant of muscle mechanical power and, thus, an important biomarker for the evaluation of training processes. However, the invasive character of the assessment (muscle biopsy) limits the wide application of the biomarker in the training praxis. Our purpose was to develop a non-invasive method for the assessment of fast twitch fibre content in human soleus muscle. From a theoretical point of view, the maximum muscle mechanical power depends on the fibre composition, the muscle volume and muscle specific tension. Therefore, we hypothesised that the percentage area of type II fibres would show a correlation with the maximum muscle mechanical power normalised to muscle volume and specific muscle contractile strength (i.e., plantar flexion moment divided by muscle cross-sectional area). In 20 male adults, the percentage area of type II fibres, volume and maximum cross-sectional area of the soleus muscle as well as the maximum plantar flexion moment and the maximum mechanical power were measured using muscle biopsies, magnetic resonance imaging and dynamometry. The maximum mechanical power normalised to muscle volume and specific muscle contractile strength provided a significant relationship (r = 0.654, p = 0.002) with the percentage area of type II fibres. Although the proposed assessment parameter cannot fully replace histological measurements, the predictive power of 43% can provide a relevant contribution to performance diagnostics in the training praxis.
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INTRODUCTION:: The aim of this study was to analyse the relationship between bony joint orientation and the distribution of hip musculature. METHODS:: The bone anatomy of the hip (femoral antetorsion (AT), acetabular anteversion (AV), and combined anteversion (AV/AT)) and the muscle volume of the gluteal muscles and the tensor fasciae latae were analysed bilaterally using computed tomography data of 49 patients. Muscle force direction (MFD) was determined for each muscle. The total MFD of the hip musculature was calculated and then correlated with the bony anatomy. RESULTS:: The mean AV, AT, and AV/AT were 21.9° ± 5.9°, 7.22° ± 7.4°, and 29.2° ± 9°, respectively. We found the following mean muscle volumes: gluteus maximus: 780 ± 227 cm3, gluteus medius: 322 ± 82 cm3, gluteus minimus: 85 ± 20 cm3, and tensor fasciae latae: 68 ± 22 cm3. The mean MFD was 18.92° ± 1.29°. We found a uniform distribution of the musculature that was not correlated with the bone anatomy. CONCLUSION:: This study highlights the variability in native acetabular and femoral anatomy and that bone hip anatomy does not correlate with the distribution of hip musculature. Although native acetabular anteversion matches the suggested targets for cup insertion, native combined anteversion is not related to current implant insertion targets. Understanding native muscular anatomy and the alterations that occur with different surgical approaches can serve as an explanatory model for THAs that has become unstable despite the components being implanted within the safe zone.
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Acetábulo/diagnóstico por imagem , Artroplastia de Quadril/métodos , Fêmur/diagnóstico por imagem , Articulação do Quadril/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Acetábulo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/instrumentação , Pesos e Medidas Corporais , Nádegas , Feminino , Fêmur/cirurgia , Articulação do Quadril/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: A two-stage exchange is the standard treatment approach for chronic periprosthetic joint infection (PJI). While a 6-8 week interval is commonly used before reimplantation, the optimal length of the prosthesis-free interval has not yet been determined. We evaluated the influence of a short (< 4 weeks) and long (≥ 4 weeks) interval on reinfection rate and functional outcome of hip and knee PJI. METHODS: In this prospective cohort, patients undergoing two-stage revision for PJI were assigned to prosthesis reimplantation after a short (< 4 weeks) or long (≥ 4 weeks) interval. All patients received standardized antimicrobial therapy, which consisted of antibiogram-adapted, non-biofilm-active antibiotics during the interval and an antimicrobial combination therapy with biofilm-active antibiotics after reimplantation. Follow-up was performed for infection, joint function, pain, need for care and quality of life. RESULTS: Thirty-eight patients undergoing two-stage revision for PJI (18 hips and 20 knees) were included. Short interval was used in 19 patients having a mean interval of 17.9 days (range 7-27 days), long interval in 19 patients having a mean interval of 63.0 days (range 28-204 days). At a mean follow-up of 39.5 months (range 32-48 months), 37 of 38 patients (97.4%) were infection-free. One failure occurred among patients with long interval and none among patients with short interval. Functional results (ROM, HHS, KSS, VAS) and quality of life (SF-36) were similar in both groups. Patients treated with long interval required cumulatively additional 204 inpatient days for nursing care compared to patients with short interval. CONCLUSIONS: This study suggests that two-stage exchange with short interval has a similar outcome than with long interval, when highly active antibiotic therapy is used. Patient inconvenience and care costs due to immobilization were lower when strategies with a short interval were used.
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Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Infecções Relacionadas à Prótese , Antibacterianos/uso terapêutico , Biofilmes , Humanos , Estudos Prospectivos , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/terapia , Reoperação/estatística & dados numéricos , Resultado do TratamentoRESUMO
BACKGROUND: Local infiltration anaesthesia (LIA) was introduced as an innovative analgesic procedure for enhanced recovery after primary total knee arthroplasty (TKA). However, LIA has never been compared with analgesia based on an adductor canal catheter and a single-shot sciatic nerve block. OBJECTIVE: To evaluate two analgesic regimens for TKA comparing mobility, postoperative pain and patient satisfaction. DESIGN: Two-group randomised, controlled clinical trial. SETTING: Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Germany between April and August 2017. PATIENTS: Adults undergoing primary TKA under general anaesthesia were eligible for study participation. Exclusion criteria were heart insufficiency (New York Heart Association class >2), liver insufficiency (Child Pugh Score >B), evidence of diabetic polyneuropathy, severe obesity (BMIâ>â40âkgâm), chronic opioid therapy for more than 3 months before scheduled surgery and allergy to local anaesthetics. INTERVENTIONS: Nerve block patients group (n=20) underwent surgery with two ultrasound-guided regional anaesthesia blocks: a single-shot sciatic nerve block with 20âml of ropivacaine 0.75% combined with an adductor canal block with a catheter placed for less than 4 days with an infusion of ropivacaine 0.2% at a rate of 6âmlâh. LIA patients (LIA group, n=20) received LIA of the knee capsule at the end of surgery with 150âml of ropivacaine 0.2%. MAIN OUTCOME MEASURES: The primary endpoint was postoperative time to patient mobilisation (ability to walk) on the ward. RESULTS: Baseline characteristics were similar in each study group. Patients in both groups were mobilised to walk after TKA in similar time frames (LIA 24.0âh versus nerve block 27.1âh, 95% CI of difference -9.6 to 3.3âh). Maximum postoperative pain scores on exertion were higher in LIA patients with a mean 1.3 of 10 numerical rating scale points (95% CI 0.3 to 2.3, Pâ=â0.010) as were intra-operative opioid requirements (LIA median 107 [IQR 100 to 268]âmg versus nerve block median 78 [60 to 98]âmg, Pâ<â0.001). Patient satisfaction, postoperative oral morphine-equivalents and resting pain levels were comparable between groups. Anaesthesia induction time was reduced in LIA patients (LIA 10âmin versus nerve block 35âmin, 95% CI of difference 13 to 38âmin, Pâ<â0.001). CONCLUSION: Both analgesic regimens allow early mobilisation after TKA with high patient satisfaction. LIA shortened peri-operative time. Further research is required to optimise especially pain control during the later postoperative period with LIA. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT03114306.
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Anestesia Local , Artroplastia do Joelho/efeitos adversos , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Satisfação do Paciente , Idoso , Anestésicos Locais/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/etiologia , Nervo Isquiático/diagnóstico por imagem , Nervo Isquiático/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: No regenerative approach has thus far been shown to be effective in skeletal muscle injuries, despite their high frequency and associated functional deficits. We sought to address surgical trauma-related muscle injuries using local intraoperative application of allogeneic placenta-derived, mesenchymal-like adherent cells (PLX-PAD), using hip arthroplasty as a standardized injury model, because of the high regenerative and immunomodulatory potency of this cell type. METHODS: Our pilot phase I/IIa study was prospective, randomized, double blind, and placebo-controlled. Twenty patients undergoing hip arthroplasty via a direct lateral approach received an injection of 3.0 × 108 (300 M, n = 6) or 1.5 × 108 (150 M, n = 7) PLX-PAD or a placebo (n = 7) into the injured gluteus medius muscles. RESULTS: We did not observe any relevant PLX-PAD-related adverse events at the 2-year follow-up. Improved gluteus medius strength was noted as early as Week 6 in the treatment-groups. Surprisingly, until Week 26, the low-dose group outperformed the high-dose group and reached significantly improved strength compared with placebo [150 M vs. placebo: P = 0.007 (baseline adjusted; 95% confidence interval 7.6, 43.9); preoperative baseline values mean ± SE: placebo: 24.4 ± 6.7 Nm, 150 M: 27.3 ± 5.6 Nm], mirrored by an increase in muscle volume [150 M vs. placebo: P = 0.004 (baseline adjusted; 95% confidence interval 6.0, 30.0); preoperative baseline values GM volume: placebo: 211.9 ± 15.3 cm3 , 150 M: 237.4 ± 27.2 cm3 ]. Histology indicated accelerated healing after cell therapy. Biomarker studies revealed that low-dose treatment reduced the surgery-related immunological stress reaction more than high-dose treatment (exemplarily: CD16+ NK cells: Day 1 P = 0.06 vs. placebo, P = 0.07 vs. 150 M; CD4+ T-cells: Day 1 P = 0.04 vs. placebo, P = 0.08 vs. 150 M). Signs of late-onset immune reactivity after high-dose treatment corresponded to reduced functional improvement. CONCLUSIONS: Allogeneic PLX-PAD therapy improved strength and volume of injured skeletal muscle with a reasonable safety profile. Outcomes could be positively correlated with the modulation of early postoperative stress-related immunological reactions.
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Artroplastia de Quadril , Imunomodulação , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Músculo Esquelético/fisiologia , Placenta/citologia , Idoso , Biomarcadores , Fenômenos Biomecânicos , Feminino , Humanos , Imunidade , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Gravidez , RegeneraçãoRESUMO
PURPOSE: During surgical procedures, some amount of irrigation fluid leaks from the surgical site and accumulates on the sterile drapes. Whether these fluid collections show bacterial contamination over time in primary total knee arthroplasty remains unclear. METHODS: In this study, we included 100 patients. We collected the samples of irrigation fluid before skin incision and every 30 minutes after the start of surgery. In addition, at the end of surgery, we evaluated the suction tip for bacterial contamination. After 3 months, we clinically evaluated all patients for periprosthetic joint infection. RESULTS: Although the drapes were found to be sterile after 30 minutes, fluid residues on the surgical drapes show a contamination rate of 22% after 60 minutes and thus a marked correlation between advanced duration of surgery and bacterial contamination. The suction tip was contaminated with bacteria in 22% of cases. The spectrum of pathogens typical of periprosthetic joint infection could be demonstrated. CONCLUSION: Fluid surgical drape reservoirs were abacterial during the first 30 minutes but showed marked bacterial contamination over time. For total knee arthroplasty, we recommend regular replacement of the suction tip every 30 minutes. In addition, irrigation fluid reservoirs should not be withdrawn by suction 30 minutes after skin incision.