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1.
Artigo em Inglês | MEDLINE | ID: mdl-38815354

RESUMO

After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery. Adequate exposure of the administered antibiotic to the pathogen is of crucial importance during the treatment of any infection. Inadequately low concentrations are associated with an increase in antibiotic resistance, antibiotic related side effects, treatment failures and prolonged infections. While high concentrations may lead to serious adverse events and potential lasting damage. Despite the importance of optimal dosing, there is a lack of knowledge with respect to the correlation between the plasma concentrations and target site concentrations of the antibiotics. Two of the commonly administered antimicrobial agents during the arthroplasty exchange are cefuroxime and flucloxacillin. Therefore, an accurate, specific, and sensitive quantification method is required in order to assess pharmacokinetics of cefuroxime and flucloxacillin in synovial tissue and bone. The aim of this study is to develop and validate a quantification method for the measurement of cefuroxime and flucloxacillin in human synovial tissue and bone using the UPC2-MS/MS conform Food and Drug Administration guidelines. The method was found linear for both compounds in both matrices (r2 > 0.990) from 1 µg/g to 20 µg/g, except for cefuroxime in bone, which was validated from 1 µg/g to 15 µg/g. We developed and validated a quantification method for cefuroxime and flucloxacillin in synovial tissue and bone using a simple sample preparation and a short analysis run time of 5.0 min, which has been already successfully applied in a clinical study. To our knowledge, no methods have been described earlier for the simultaneous quantification of cefuroxime and flucloxacillin in synovial tissue and bone.


Assuntos
Cefuroxima , Floxacilina , Espectrometria de Massas em Tandem , Humanos , Espectrometria de Massas em Tandem/métodos , Cefuroxima/análise , Cefuroxima/farmacocinética , Cefuroxima/sangue , Cromatografia Líquida de Alta Pressão/métodos , Modelos Lineares , Reprodutibilidade dos Testes , Floxacilina/análise , Floxacilina/farmacocinética , Floxacilina/química , Antibacterianos/análise , Antibacterianos/sangue , Antibacterianos/farmacocinética , Osso e Ossos/química , Osso e Ossos/metabolismo , Membrana Sinovial/química , Membrana Sinovial/metabolismo , Limite de Detecção
2.
Bone Joint J ; 105-B(7): 775-782, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37394959

RESUMO

Aims: The aims of this study were to determine if an increasing serum cobalt (Co) and/or chromium (Cr) concentration is correlated with a decreasing Harris Hip Score (HHS) and Hip disability and Osteoarthritis Outcome Score (HOOS) in patients who received the Articular Surface Replacement (ASR) hip resurfacing arthroplasty (HRA), and to evaluate the ten-year revision rate and show if sex, inclination angle, and Co level influenced the revision rate. Methods: A total of 62 patients with an ASR-HRA were included and monitored yearly postoperatively. At follow-up, serum Co and Cr levels were measured and the HHS and the HOOS were scored. In addition, preoperative patient and implant variables and the need for revision surgery were recorded. We used a linear mixed model to relate the serum Co and Cr levels to different patient-reported outcome measures (PROMs). For the survival analyses we used the Kaplan-Meier and Cox regression model. Results: We found that an increase of one part per billion (ppb) in serum Co and Cr levels correlated significantly with worsening of the HHS in the following year. This significant correlation was also true for the HOOS-Pain and HOOS-quality of life sub scores. The overall ten-year survival rate in our cohort was 65% (95% confidence interval (CI) 52.5 to 77.6). Cox regression analysis showed a significant hazard ratio (HR) of 1.08 (95% CI 1.01 to 1.15; p = 0.028) for serum Co level. No significance was found with sex or inclination angle. Conclusion: This study shows that increasing serum Co and Cr levels measured in patients with an ASR-HRA are predictive for deterioration in HHS and HOOS subscales in the following year. Increasing serum Co and Cr should forewarn both surgeon and patient that there is a heightened risk of failure. Continued and regular review of patients with an ASR-HRA implant by measurement of serum Co/Cr levels and PROMs remains essential.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Cromo , Cobalto , Artroplastia de Quadril/efeitos adversos , Prótese de Quadril/efeitos adversos , Qualidade de Vida , Falha de Prótese , Desenho de Prótese , Reoperação , Medidas de Resultados Relatados pelo Paciente , Seguimentos
3.
Artigo em Inglês | MEDLINE | ID: mdl-36283258

RESUMO

Periprosthetic joint infection is a challenging infection involving the joint prosthesis and adjacent tissue, such as synovial fluid, synovial tissue, and bone tissue. The current treatment consists of multiple surgical revisions and long-term antibiotic therapy. Treatment failure can cause poor functional outcome and reduced quality of life. Further research on the extent of antibiotic penetration into the infected tissues is of great importance. Our work aimed to develop and validate a novel ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method for the determination of the commonly administered antibiotics vancomycin and clindamycin in plasma and synovial fluid. An extraction procedure consisting of zinc sulfate precipitation and dilution with eluent was used for both analytes. Chromatographic separation was performed on a Waters Acquity UPLC HSS T3 C18 column (1.8 µm, 2.1 × 100 mm), and quantification was carried out by a Waters Xevo TQ-S micro mass spectrometer. Stable isotope-labeled vancomycin-d10 served as internal standard. The method validation was performed based on the guidelines of the EMA and FDA. The calibration curves were linear over the range of 0.5-50 mg/L, with a coefficient of determination above 0.990. The validation results for precision and accuracy, specificity, matrix effects and stability were all within the acceptance range. An accurate and rapid method for the simultaneous quantification of vancomycin and clindamycin in human plasma and synovial fluid on the UPLC-MS/MS was developed, optimized and validated. The analysis has a run time of 5.2 min and 50 µL sample volume is needed. This developed method was successfully applied in eight patients with PJI and is suitable to determine the exposure of antibiotics in plasma and synovial fluid in patients during current PK/PD studies.


Assuntos
Espectrometria de Massas em Tandem , Vancomicina , Humanos , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida de Alta Pressão/métodos , Clindamicina , Líquido Sinovial , Qualidade de Vida , Limite de Detecção , Antibacterianos , Reprodutibilidade dos Testes
4.
Front Pharmacol ; 13: 900551, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35837288

RESUMO

Introduction: Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic literature review was to give an overview of the current knowledge of protein binding of cephalosporins in human body fluids as well as to describe patient characteristics influencing the level of protein binding. Method: A systematic literature search was performed in Embase, Medline ALL, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials with the following search terms: "protein binding," "beta-lactam antibiotic," and "body fluid." Only studies were included where protein binding was measured in humans in vivo. Results: The majority of studies reporting protein binding were performed in serum or plasma. Other fluids included pericardial fluid, blister fluid, bronchial secretion, pleural exudate, wound exudate, cerebrospinal fluid, dialysate, and peritoneal fluid. Protein binding differs between diverse cephalosporins and between different patient categories. For cefazolin, ceftriaxone, cefpiramide, and cefonicid a non-linear pattern in protein binding in serum or plasma was described. Several patient characteristics were associated with low serum albumin concentrations and were found to have lower protein binding compared to healthy volunteers. This was for critically ill patients, dialysis patients, and patients undergoing cardiopulmonary bypass during surgery. While mean/median percentages of protein binding are lower in these patient groups, individual values may vary considerably. Age is not likely to influence protein binding by itself, however limited data suggest that lower protein binding in newborns. Obesity was not correlated with altered protein binding. Discussion/Conclusion: Conclusions on protein binding in other body fluids than blood cannot be drawn due to the scarcity of data. In serum and plasma, there is a large variability in protein binding per cephalosporin and between different categories of patients. Several characteristics were identified which lead to a lower protein binding. The finding that some of the cephalosporins display a non-linear pattern of protein binding makes it even more difficult to predict the unbound concentrations in individual patients. Taken all these factors, it is recommended to measure unbound concentrations to optimize antibiotic exposure in individual patients. Systematic Review Registration: PROSPERO, identifier (CRD42021252776).

5.
Trials ; 23(1): 24, 2022 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-34998425

RESUMO

INTRODUCTION: Knee osteoarthritis is a common disease with pain as the most prevalent symptom. Previous cohort studies have shown genicular artery embolization to reduce pain symptoms in patients with mild to moderate knee osteoarthritis. Patients resistant to conservative therapy but not eligible yet for surgical treatment due to young age or comorbidities may profit from an effective and sustained pain reduction treatment. This study is a randomized sham-controlled trial to evaluate the efficacy of genicular artery embolization in patients with knee osteoarthritis. METHODS AND ANALYSIS: Fifty-eight patients with mild-to-moderate knee osteoarthritis will be recruited and randomly allocated to the treatment or control group in a 1:1 ratio. Participants in the treatment group will undergo genicular artery embolization. Patients in the control group will undergo sham treatment. Outcome measurements will be assessed at baseline and after 1, 4, 8, and 12 months with questionnaires, pressure pain threshold testing, and MR imaging. The MR imaging protocol is designed to (semi)quantitatively assess osteoarthritis in the knee joint. The primary outcome is the change from baseline of the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale after 4 months. Secondary outcomes include change in osteoarthritis-related questionnaires, pressure pain threshold, and OA-related MRI features, particularly synovitis and bone marrow lesions. ETHICS AND DISSEMINATION: This trial will determine the efficacy of genicular artery embolization compared to a sham treatment. This is of importance to assess before proceeding to larger-scale efficiency studies and, ultimately, implementing this treatment into day to day clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03884049. Registered on 21 March 2019.


Assuntos
Osteoartrite do Joelho , Artérias , Humanos , Articulação do Joelho , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/terapia , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
6.
Artigo em Inglês | MEDLINE | ID: mdl-33872930

RESUMO

Total hip- and knee arthroplasty generally result in successful outcomes. A small percentage of patients however suffer from periprosthetic joint infections (PJI) postoperatively, often with severe consequences. The standard treatment of chronic PJIs consists of a staged arthroplasty exchange during which antibiotic therapy plays a crucial role. For successful antibiotic treatment, adequate concentrations at the infection site are a prerequisite. Regarding the treatment of PJIs, knowledge is lacking with respect to the relationship between administered dosages and plasma- and infection site concentrations of the antibiotics. To gain insight into the antibiotic exposure at the infection site, validated analytical methods for analysis of the antibiotics in matrices at the site of the PJI are essential. We describe a validated ultra-performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS) method for quantification of the beta-lactam antibiotics cefuroxime and flucloxacillin in synovial fluid. This method was successfully validated for antibiotic quantification in synovial fluids according to the EMA guidelines and consists of a simple sample preparation. For both antibiotics, the accuracy and precision were within requirements (RSD < 15%). In addition, matrix effects and recovery were within the range of 80-120%. Carry over was less than 20% and stability in -80 °C was at least 2 months for standards and quality controls. The limits of quantification were adequate (1-100 mg/L) to cover potential cefuroxime and flucloxacillin concentrations in synovial fluid as described in literature (r > 0.995). The method has a run time of 4.5 min and 50 µL synovial fluid is needed and the validated method will be applied during a PK/PD study to determine the exposure of the study antibiotics in synovial fluid at the site of PJIs.

7.
BMC Musculoskelet Disord ; 20(1): 473, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31651318

RESUMO

BACKGROUND: Computer Assisted Surgery (CAS) has proven to improve the accuracy in several orthopedic procedures. Therefore we used this technique to evaluate femoral component positioning in Hip Resurfacing Arthroplasty (HRA). The aim of this study was to evaluate imageless CAS compared to manually implanted femoral components and subsequently evaluates Patient Related Outcome Measures (PROMs). We hypothesized that the use of CAS optimizes the position of the femoral component and improves PROMs. METHODS: This is a multicenter, single-blinded, randomized, controlled trial of two groups. In the CAS group guiding of the femoral component was done with imageless navigation. In the Conventional (control) group the femoral component was placed manually according to the preplanned position. The primary outcome measure consists of a maximum of 3 degrees difference between the postoperative Stem Shaft Angle (SSA) and preplanned SSA. Secondary outcome measures consist of the Hip disability and Osteoarthritis Outcome Scale (HOOS), the Harris Hip Score (HHS) and Visual Analogue Scale (VAS) pain score. RESULTS: A total of 122 patients were randomized, 61 in the CAS group and 61 in the conventional group. There was no significant differences in accuracy of femoral implant position. The mean difference between the postoperative- and preplanned SSA was - 2.26 and - 1.75 degrees (more varus) respectively in the CAS and Conventional group. After surgery both groups show significant improvement in all PROMs compared to the baseline measurements, with no significant differences between the groups. CONCLUSION: Our cohort indicates no benefit for the use of CAS in accuracy of placement of the femoral component in HRA compared to manual implantation. There are no clinical differences in PROMs after 1 year follow up. This study showed no added value and no justification for the use of CAS in femoral component positioning in HRA. TRIAL REGISTRATION: This trial is registered at ClinicalTrails.gov ( https://clinicaltrials.gov/ ) on the 25th of October 2006: NCT00391937. LEVEL OF INCIDENCE: Level IIb, multicenter randomized controlled trial.


Assuntos
Artroplastia de Quadril/métodos , Prótese de Quadril , Osteoartrite do Quadril/cirurgia , Medidas de Resultados Relatados pelo Paciente , Cirurgia Assistida por Computador/métodos , Adulto , Artroplastia de Quadril/instrumentação , Feminino , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Período Pós-Operatório , Radiografia , Método Simples-Cego , Cirurgia Assistida por Computador/instrumentação
8.
Arthritis Res Ther ; 21(1): 192, 2019 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-31443685

RESUMO

BACKGROUND: Predicting which patients with hip osteoarthritis are more likely to show disease progression is important for healthcare professionals. Therefore, the aim of this review was to assess which factors are predictive of progression in patients with hip osteoarthritis. METHODS: A literature search was made up until 14 March 2019. Included were cohort and case-control studies evaluating the association between factors and progression (either clinical, radiological, or THR). Excluded were studies with a follow-up < 1 year or specific underlying pathologies of osteoarthritis. Risk of bias was assessed using the QUIPS tool. A best-evidence synthesis was conducted. RESULTS: We included 57 articles describing 154 different factors. Of these, a best-evidence synthesis was possible for 103 factors, separately for clinical and radiological progression, and progression to total hip replacement. We found strong evidence for more clinical progression in patients with comorbidity and more progression to total hip replacement for a higher Kellgren and Lawrence grade, superior or (supero) lateral femoral head migration, and subchondral sclerosis. Strong evidence for no association was found regarding clinical progression for gender, social support, pain medication, quality of life, and limited range of motion of internal rotation or external rotation. Also, strong evidence for no association was found regarding radiological progression for the markers CTX-I, COMP, NTX-I, PINP, and PIIINP and regarding progression to total hip replacement for body mass index. CONCLUSION: Strong evidence suggested that 4 factors were predictive of progression of hip osteoarthritis, whereas 12 factors were not predictive of progression. Evidence for most of the reported factors was either limited or conflicting. PROTOCOL REGISTRATION: PROSPERO, CRD42015010757.


Assuntos
Índice de Massa Corporal , Osteoartrite do Quadril/diagnóstico , Qualidade de Vida , Radiografia/métodos , Progressão da Doença , Humanos , Prognóstico
9.
Eur Cell Mater ; 36: 218-230, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30398288

RESUMO

Mesenchymal stem cells (MSCs) represent a promising biological therapeutic option as an osteoarthritis (OA)-modifying treatment. MSCs secrete factors that can counteract inflammatory and catabolic processes and attract endogenous repair cells. The effects of intra-articular injection of MSC secretome on OA-related pain, cartilage damage, subchondral bone alterations and synovial inflammation were studied in a mouse collagenase-induced OA model. The MSC secretome was generated by stimulating human bone-marrow-derived MSCs with interferon gamma (IFNγ) and tumour necrosis factor alpha (TNFα). 54 mice were randomly assigned to injections with i) MSC secretome from 20,000 MSCs, ii) 20,000 MSCs or iii) medium (control). Pain was assessed by hind limb weight distribution. Cartilage damage, subchondral bone volume and synovial inflammation were evaluated by histology. MSC-secretome- and MSC-injected mice showed pain reduction at day 7 when compared to control mice. Cartilage damage was more abundant in the control group as compared to healthy knees, a difference which was not found in knees treated with MSC secretome or MSCs. No effects were observed regarding synovial inflammation, subchondral bone volume or the presence of different macrophage subtypes. Injection of MSC secretome, similarly to injection of MSCs, resulted in early pain reduction and had a protective effect on the development of cartilage damage in a murine OA model. By using the regenerative capacities of the MSC-secreted factors, it will be possible to greatly enhance the standardisation, affordability and clinical translatability of the approach. This way, this biological therapy could evolve towards a true disease-modifying anti-osteoarthritic drug.


Assuntos
Cartilagem Articular/patologia , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/complicações , Osteoartrite/patologia , Dor/complicações , Dor/prevenção & controle , Proteoma/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Membro Posterior/patologia , Humanos , Inflamação/patologia , Masculino , Transplante de Células-Tronco Mesenquimais , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Tamanho do Órgão , Dor/patologia , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
10.
Knee Surg Sports Traumatol Arthrosc ; 25(3): 895-901, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26026274

RESUMO

PURPOSE: Varus medial knee osteoarthritis (OA) can be treated with a closing-wedge (CW) or opening-wedge (OW) high tibial osteotomy (HTO). Little is known about the adverse event (AE) rate of these techniques. The purpose of this study was to examine the AE rate and survival rate of a consecutive series of 412 patients undergoing CW- or OW-HTO. METHODS: Medical records were retrospectively screened, and all patients who underwent HTO from 1993 to 2012 at the Erasmus University Medical Centre were assessed with a self-administered questionnaire. Patients filled in the intermittent and constant osteoarthritis pain score, knee injury and osteoarthritis outcome score, and a general questionnaire focusing on AE. RESULTS: Medical records of 412 patients (354 CW- and 112 OW-HTOs) were screened. Of the 358 eligible patients, 291 (81 %) returned their questionnaire. A total of 80 AE (17 %) were found in 466 osteotomies. In the CW-group, 47 (13 %) serious adverse events (SAE) and 2 (0.6 %) AE were found. In the OW-group, 17 (15 %) SAE and 14 (13 %) AE were found. The most common AE was in 14 (4 %) patients of the CW-group sensory palsy of the common peroneal nerve. The most common AE in the OW-group was persistent pain at the iliac crest [11 (9.8 %) patients]. Hardware was removed in 48 % of the CW-osteotomies and 71 % of the OW-osteotomies (p < 0.05). The probability of survival was 75 % after 10 years in the CW-group versus 90 % in the OW-group (p < 0.05). In both groups, an equal number of patients were "in need for prosthesis" according to OARSI criteria. CONCLUSION: OW-HTO was associated with more AE than CW-HTO. OW-HTO resulted in better survival than CW-HTO. However, in both groups an equal number of patients were in need for prosthesis. LEVEL OF EVIDENCE: Retrospective comparative study, Level III.


Assuntos
Osteoartrite do Joelho/cirurgia , Osteotomia/efeitos adversos , Complicações Pós-Operatórias , Tíbia/cirurgia , Adulto , Artroplastia do Joelho , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Osteotomia/métodos , Dor/etiologia , Neuropatias Fibulares/etiologia , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
11.
Osteoarthritis Cartilage ; 24(6): 1012-20, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26851449

RESUMO

OBJECTIVE: Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content. DESIGN: In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re-scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-µCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-µCT X-ray attenuation, sGAG content and collagen content was assessed. RESULTS: CTa X-ray attenuation correlated well with EPIC-µCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36). CONCLUSIONS: Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research.


Assuntos
Artrografia , Cartilagem Articular , Meios de Contraste , Glicosaminoglicanos , Humanos , Estudos Prospectivos
12.
Bone Joint J ; 97-B(2): 215-20, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25628285

RESUMO

A total of seven patients (six men and one woman) with a defect in the Achilles tendon and overlying soft tissue underwent reconstruction using either a composite radial forearm flap (n = 3) or an anterolateral thigh flap (n = 4). The Achilles tendons were reconstructed using chimeric palmaris longus (n = 2) or tensor fascia lata (n = 2) flaps or transfer of the flexor hallucis longus tendon (n = 3). Surgical parameters such as the rate of complications and the time between the initial repair and flap surgery were analysed. Function was measured objectively by recording the circumference of the calf, the isometric strength of the plantar flexors and the range of movement of the ankle. The Achilles tendon Total Rupture Score (ATRS) questionnaire was used as a patient-reported outcome measure. Most patients had undergone several previous operations to the Achilles tendon prior to flap surgery. The mean time to flap surgery was 14.3 months (2.1 to 40.7). At a mean follow-up of 32.3 months (12.1 to 59.6) the circumference of the calf on the operated lower limb was reduced by a mean of 1.9 cm (sd 0.74) compared with the contralateral limb (p = 0.042). The mean strength of the plantar flexors on the operated lower limb was reduced to 88.9% of that of the contralateral limb (p = 0.043). There was no significant difference in the range of movement between the two sides (p = 0.317). The mean ATRS score was 72 points (sd 20.0). One patient who had an initial successful reconstruction developed a skin defect of the composite flap 12 months after free flap surgery and this resulted in recurrent infections, culminating in transtibial amputation 44 months after reconstruction. These otherwise indicate that reconstruction of the Achilles tendon combined with flap cover results in a successful and functional reconstruction.


Assuntos
Tendão do Calcâneo/lesões , Tendão do Calcâneo/cirurgia , Retalhos de Tecido Biológico , Procedimentos de Cirurgia Plástica/métodos , Lesões dos Tecidos Moles/cirurgia , Infecção da Ferida Cirúrgica/cirurgia , Adulto , Idoso , Articulação do Tornozelo/fisiopatologia , Desbridamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Ruptura , Traumatismos dos Tendões/cirurgia , Resultado do Tratamento
13.
Osteoarthritis Cartilage ; 23(1): 57-62, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25205018

RESUMO

OBJECTIVES: To assess associations between uCTX-II or uCIIM and severity of hip pain in patients with mild-moderate hip osteoarthritis (OA) over a 2-year period, and establish whether the level of these biomarkers at baseline could estimate a specific trajectory of hip pain. DESIGN: A cohort study with a 2-year follow-up and 6-monthly measurements of urinary biomarkers (uCTX-II and uCIIM) and symptom severity. Patients were recruited from general practices. The primary outcome was hip pain, measured with the Western Ontario and McMasters University Osteoarthritis Index (WOMAC) subscale and the Visual Analog Scale (VAS). Associations between hip pain and biomarkers were assessed using linear mixed-model analysis for repeated measurements. Five previously identified pain trajectories were used as outcome to investigate whether the level of biomarkers at baseline could estimate membership in one of the trajectories using multinomial regression analysis. RESULTS: LoguCTX-II and loguCIIM were not associated with WOMAC pain or VAS pain during the 2-year follow-up. Patients in the highly progressive pain trajectory and the moderate pain trajectory were more likely to have a higher loguCTX-II at baseline (OR 6.7; 95% CI 1.6-28.2 and OR 4.8; 95% CI 1.0-22.8, respectively) than patients in the mild pain trajectory. CONCLUSION: This study shows that in patients with mild-moderate hip OA the urinary biochemical markers uCTX-II and uCIIM are not cross-sectionally associated with hip pain during the 2-year follow-up. Because the uCTX-II level estimated a progressive or moderate hip pain trajectory, this correlation needs to be confirmed in additional patients with hip OA.


Assuntos
Colágeno Tipo II/urina , Osteoartrite do Quadril/diagnóstico , Osteoartrite do Quadril/urina , Fragmentos de Peptídeos/urina , Biomarcadores/urina , Cartilagem Articular/metabolismo , Estudos de Coortes , Epitopos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
14.
J Bone Joint Surg Am ; 96(17): 1425-32, 2014 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-25187580

RESUMO

BACKGROUND: Varus deformity increases the risk of progression of medial compartment knee osteoarthritis. The aim of this study was to investigate the clinical and radiographic mid-term results of closing-wedge and opening-wedge high tibial osteotomy when used to treat this condition. METHODS: From January 2001 to April 2004, ninety-two patients were randomized to receive either a closing-wedge or an opening-wedge high tibial osteotomy. The clinical outcome and radiographic results were examined preoperatively; at one year; and, for the present study, at six years postoperatively. The outcomes that we reviewed included maintenance of the achieved correction, progression of osteoarthritis (based on the Kellgren and Lawrence classification), severity of pain (as assessed on a visual analog scale [VAS]), knee function (as measured with the Hospital for Special Surgery [HSS] score and Knee injury and Osteoarthritis Outcome Score [KOOS]), walking distance, complications, and survival with conversion to a total knee arthroplasty as the end point. The results were analyzed on the basis of the intention-to-treat principle. RESULTS: Six years postoperatively, the mean hip-knee-ankle (HKA) angle (and standard deviation) was 3.2° ± 4.1° of valgus after a closing-wedge high tibial osteotomy and 1.3° ± 5.0° of valgus after an opening-wedge high tibial osteotomy (p = 0.343). In both groups, the six-year postoperative HKA angles did not differ from the respective one-year postoperative angles. No difference in the severity of pain or in knee function was found between the two groups. Four complications (9%) occurred in the closing-wedge group and seventeen (38%), in the opening-wedge group. Ten (22%) of the patients in the closing-wedge group and three (8%) in the opening-wedge group needed conversion to a total knee arthroplasty within the six-year period (p = 0.05). The difference in the percentage of cases with conversion to total knee arthroplasty was 14% (95% confidence interval [CI] = 21.7 to 0.2). CONCLUSIONS: In the group of patients without conversion to a total knee arthroplasty, there was no difference between the high tibial closing-wedge and opening-wedge osteotomies in terms of clinical outcomes or radiographic alignment at six years postoperatively. Opening-wedge osteotomy was associated with more complications, but closing-wedge osteotomy was associated with more early conversions to total knee arthroplasty. LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Osteoartrite do Joelho/cirurgia , Osteotomia/métodos , Amplitude de Movimento Articular/fisiologia , Tíbia/cirurgia , Adulto , Idoso , Artroplastia do Joelho/métodos , Artroplastia do Joelho/estatística & dados numéricos , Intervalos de Confiança , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Osteotomia/efeitos adversos , Medição da Dor , Dor Pós-Operatória/fisiopatologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Radiografia , Reoperação/estatística & dados numéricos , Medição de Risco , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento
15.
J Biomech ; 47(12): 3107-14, 2014 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-25052137

RESUMO

Estimating the risk of osteoporotic fractures is an important diagnostic step that needs to be taken before medicinal treatment. Densitometry-based criteria are normally used in clinical practice for this purpose. However, densitometry-based techniques could not explain all low-energy fractures. As patient-specific finite element (FE) models allow for consideration of other parameters (e.g. load conditions) that are known to be associated with fracture, they are considered promising candidates for more accurate fracture risk estimation. Nevertheless, they are often time consuming, expensive, and complex to build and may need the type of expertise that is not normally available in clinical settings. In this study, we report the development of an automated platform for estimating proximal femur fracture loads using patient-specific 2D FE models generated using dual-energy x-ray absorptiometry (DXA) scans. First, a statistical shape and appearance model (SSAM) is built using DXA scans of patients screened for osteoporosis following a low energy fracture. SSAM is then used together with Active Appearance Models (AAM) for automated segmentation of the proximal femur from new unseen DXA scans. The mean point-to-curve error of the automated procedure, i.e. 1.2-1.4mm, is shown to be only slightly larger than the intra-observer variability of manual segmentation, i.e. 1.0mm. Moreover, the developed platform automatically meshes the segmented shape, assigns density-based mechanical properties, assigns loads and boundary conditions, submits the 2D FE model for solution, and performs post-processing of the 2D FE simulation data to determine fracture loads. The fracture loads predicted using the manually generated and automatically generated 2D FE models are shown to be very close with a mean difference of around 8.8%. Repeated measures ANOVA showed no significant differences between the fracture loads calculated using FE models manually generated by three independent observers and those calculated using the automatically generated FE models (p>0.05).


Assuntos
Fraturas do Fêmur/diagnóstico por imagem , Análise de Elementos Finitos , Absorciometria de Fóton , Automação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/diagnóstico por imagem , Modelagem Computacional Específica para o Paciente , Estresse Mecânico , Fatores de Tempo
16.
Ned Tijdschr Geneeskd ; 158(6): A6621, 2014.
Artigo em Holandês | MEDLINE | ID: mdl-24495368

RESUMO

UNLABELLED: A 19-year-old man was evaluated for medial knee pain 1.5 year after repeated distortion of the right knee. The medial side of his knee was swollen and painful upon running and playing soccer. An anteroposterior knee radiograph showed a calcification located at the proximal medial collateral ligament. He was diagnosed with Pellegrini-Stieda syndrome. Treatment of this syndrome includes rest, range of motion exercises, nonsteroidal anti-inflammatory drugs, local infiltration with corticosteroids or excision in refractory cases. DIAGNOSIS: Pellegrini-Stieda syndrome.


Assuntos
Instabilidade Articular/diagnóstico , Traumatismos do Joelho/diagnóstico , Ligamento Colateral Médio do Joelho/patologia , Futebol , Calcinose/diagnóstico , Calcinose/diagnóstico por imagem , Humanos , Instabilidade Articular/etiologia , Traumatismos do Joelho/diagnóstico por imagem , Masculino , Ligamento Colateral Médio do Joelho/diagnóstico por imagem , Radiografia , Amplitude de Movimento Articular , Descanso , Síndrome , Adulto Jovem
17.
Osteoarthritis Cartilage ; 21(10): 1465-73, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23831631

RESUMO

BACKGROUND: An important goal of stem cell research in orthopaedics is to develop clinically relevant techniques that could be applied to heal cartilage or joint pathology. Stem cell treatment in orthopaedics for joint pathology is promising since these cells have the ability to modulate different processes in the various tissues of the joint simultaneously. The non life-threatening nature of musculoskeletal system disorders makes safety of stem cell therapy a necessary prerequisite. OBJECTIVE: To systematically review the literature and provide an overview of reported adverse events (AEs) of intra-articular treatment with culture-expanded stem cells in humans. DESIGN: A systematic literature search was performed in Pubmed, EMBASE, Web of Science and CINAHL in February 2013. AEs were reported into three categories: local/systemic, serious adverse event or AE (SAE/AE), related/unrelated. RESULTS: 3039 Potentially eligible articles were identified of which eventually eight fulfilled our inclusion criteria. In total, 844 procedures with a mean follow-up of 21 months were analysed. Autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) were used for cartilage repair and osteoarthritis treatment in all included studies. Four SAEs were reported by the authors. One infection following bone marrow aspiration (BMA) was reported as probably related and resolved with antibiotics. One pulmonary embolism occurred 2 weeks after BMA and was reported as possibly related. Two tumours, both not at the site of injection, were reported as unrelated. Twenty-two other cases of possible procedure-related and seven of possible stem cell-product related adverse events (AEs) were documented. The main AEs related to the procedure were increased pain/swelling and dehydration after BMA. Increased pain and swelling was the only AE reported as related to the stem cell-product. CONCLUSIONS: Based on current literature review we conclude that application of cultured stem cells in joints appears to be safe. We believe that with continuous caution for potential side effects, it is reasonable to continue with the development of articular stem cell therapies.


Assuntos
Transplante de Células-Tronco Mesenquimais/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Osteoartrite/terapia , Técnicas de Cultura de Células , Células Cultivadas/transplante , Humanos , Injeções Intra-Articulares
18.
Knee ; 20(4): 226-31, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23566735

RESUMO

INTRODUCTION: The infrapatellar fat pad (IPFP) is often removed during total knee arthroplasty (TKA). No evidence based guidelines on changes in clinical outcome have yet been described. The aim of this review is to investigate whether regular removal of the IPFP during TKA should be performed. MATERIAL AND METHODS: Seven databases were systematically searched. Clinical studies, in which TKA with IPFP resection was compared with IPFP preservation, were included. Risk of bias was assessed using the Cochrane collaboration tool. Studies reporting anterior knee pain, patellar tendon length, range of motion, patellar vascularisation or functional outcome were included. RESULTS: The indication for TKA varied in the different studies: osteoarthritis (OA), rheumatic arthritis (RA) and multiple indications (OA, RA and osteonecrosis). After IPFP resection: 1. For OA, no differences in function, range of motion, and anterior knee pain were found. 2. In the RA study, there was a trend towards more discomfort and a decrease in function. 3. In OA and RA patients a decrease in patellar tendon length was observed. 4. One study reported no decrease in patellar vascularisation. DISCUSSION: Limitations of this review are the high risk of bias scores of the included studies, the varying outcome measures, follow up, number and type of participants. Randomised clinical trials are required to support or refute the results, contributing to a possible future evidence based guideline on IPFP resection during TKA.


Assuntos
Tecido Adiposo/cirurgia , Artroplastia do Joelho , Avaliação de Resultados da Assistência ao Paciente , Artralgia/etiologia , Artrite Reumatoide/cirurgia , Humanos , Osteoartrite do Joelho/cirurgia , Osteonecrose/cirurgia , Ligamento Patelar/anatomia & histologia , Complicações Pós-Operatórias , Amplitude de Movimento Articular
19.
Eur Radiol ; 23(2): 496-504, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22886535

RESUMO

OBJECTIVES: To assess the reproducibility of 3D delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 3 T in early stage knee osteoarthritis (OA) patients. METHODS: In 20 patients, 3D dGEMRIC at 3 T was acquired twice within 7 days. To correct for patient motion during acquisition, all images were rigidly registered in 3D. Eight anatomical cartilage ROIs were analysed on both images of each patient. Capability of dGEMRIC to yield T1 maps that reproducibly distinguish spatial differences in cartilage quality was assessed in two ROIs within a single slice in each patient. Reproducibility was assessed using ICCs and Bland-Altman plots. RESULTS: ICCs ranged from 0.87 to 0.95, indicating good reproducibility. T1 maps revealed reproducible spatial differences in cartilage quality (ICC 0.79). Based on the Bland-Altman plots, we defined a threshold of 95 ms to determine if a change in dGEMRIC outcome in longitudinal research was statistically significant. CONCLUSIONS: 3D knee dGEMRIC at 3 T combined with 3D image registration is a highly reproducible measure of cartilage quality in early stage OA. Therefore, dGEMRIC may be a valuable tool in the non-invasive evaluation of cartilage quality changes in longitudinal research in patients with early stage OA and focal cartilage defects.


Assuntos
Cartilagem Articular/patologia , Gadolínio DTPA , Imageamento Tridimensional , Imageamento por Ressonância Magnética/métodos , Osteoartrite do Joelho/diagnóstico , Adulto , Estudos de Coortes , Meios de Contraste , Feminino , Humanos , Aumento da Imagem/métodos , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença
20.
Osteoarthritis Cartilage ; 20(10): 1186-96, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22771777

RESUMO

OBJECTIVE: Mesenchymal stem cells (MSCs) are promising candidates for osteoarthritis (OA) therapies, although their mechanism of action remains unclear. MSCs have recently been discovered to secrete anti-inflammatory cytokines and growth factors. We studied the paracrine effects of MSCs on OA cartilage and synovial explants in vitro. DESIGN: MSC-conditioned medium was prepared by stimulating primary human MSCs with tumour necrosis factor alpha (TNFα) and (50ng/ml each). Human synovium and cartilage explants were cultured in MSC-conditioned medium or in control medium, containing the same amount of added TNFα and IFNγ but not incubated with MSCs. Explants were analyzed for gene expression and the production of nitric oxide (NO). The presence of the inhibitor of nuclear factor kappa B alpha (IκBa) was assessed by Western blot analysis. RESULTS: Synovial explants exposed to MSC-conditioned medium showed decreased gene expression of interleukin-1 beta (IL-1ß), matrix metalloproteinase (MMP)1 and MMP13, while suppressor of cytokine signaling (SOCS)1 was upregulated. In cartilage, expression of IL-1 receptor antagonist (IL-1RA) was upregulated, whereas a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)5 and collagen type II alpha 1 (COL2A1) were downregulated. MSC-conditioned medium reduced NO production in cartilage explants and the presence of IκBa was increased in synoviocytes and chondrocytes treated with MSC-conditioned medium. CONCLUSIONS: In an inflammatory environment, MSCs secrete factors which cause multiple anti-inflammatory effects and influence matrix turnover in synovium and cartilage explants. Thereby, the presented data encourage further study of MSCs as a treatment for joint diseases.


Assuntos
Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Condrogênese/fisiologia , Células-Tronco Mesenquimais/metabolismo , Osteoartrite/metabolismo , Membrana Sinovial/metabolismo , Biomarcadores/metabolismo , Cartilagem Articular/efeitos dos fármacos , Células Cultivadas , Condrócitos/efeitos dos fármacos , Técnicas de Cocultura , Meios de Cultivo Condicionados/farmacologia , Expressão Gênica/efeitos dos fármacos , Humanos , Proteínas I-kappa B/metabolismo , Interferon gama/farmacologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Inibidor de NF-kappaB alfa , Óxido Nítrico/metabolismo , Proteína 1 Supressora da Sinalização de Citocina , Proteínas Supressoras da Sinalização de Citocina/genética , Proteínas Supressoras da Sinalização de Citocina/metabolismo , Membrana Sinovial/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia
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