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1.
N Engl J Med ; 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39216093

RESUMO

BACKGROUND: Current treatment recommendations for patients with heart failure and secondary mitral regurgitation include transcatheter edge-to-edge repair and mitral-valve surgery. Data from randomized trials comparing these therapies are lacking in this patient population. METHODS: In this noninferiority trial conducted in Germany, patients with heart failure and secondary mitral regurgitation who continued to have symptoms despite guideline-directed medical therapy were randomly assigned, in a 1:1 ratio, to undergo either transcatheter edge-to-edge repair (intervention group) or surgical mitral-valve repair or replacement (surgery group). The primary efficacy end point was a composite of death, hospitalization for heart failure, mitral-valve reintervention, implantation of an assist device, or stroke within 1 year after the procedure. The primary safety end point was a composite of major adverse events within 30 days after the procedure. RESULTS: A total of 210 patients underwent randomization. The mean (±SD) age of the patients was 70.5±7.9 years, 39.9% were women, and the mean left ventricular ejection fraction was 43.0±11.7%. Within 1 year, at least one of the components of the primary efficacy end point occurred in 16 of the 96 patients with available data (16.7%) in the intervention group and in 20 of the 89 with available data (22.5%) in the surgery group (estimated mean difference, -6 percentage points; 95% confidence interval [CI], -17 to 6; P<0.001 for noninferiority). A primary safety end-point event occurred in 15 of the 101 patients with available data (14.9%) in the intervention group and in 51 of the 93 patients with available data (54.8%) in the surgery group (estimated mean difference, -40 percentage points; 95% CI, -51 to -27; P<0.001). CONCLUSIONS: Among patients with heart failure and secondary mitral regurgitation, transcatheter edge-to-edge repair was noninferior to mitral-valve surgery with respect to a composite of death, rehospitalization for heart failure, stroke, reintervention, or implantation of an assist device in the left ventricle at 1 year. (Funded by Abbott Vascular; MATTERHORN ClinicalTrials.gov number, NCT02371512.).

2.
Materials (Basel) ; 17(10)2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38793314

RESUMO

A phenomenological material model has been developed to facilitate the efficient numerical analysis of fiber-reinforced high-performance concrete (HPC). The formulation integrates an elasto-plastic phase-field model for simulating fractures within the HPC matrix, along with a superimposed one-dimensional elasto-plasticity model that represents the behavior of the embedded fibers. The Drucker-Prager plasticity and one-dimensional von-Mises plasticity formulations are incorporated to describe the nonlinear material behavior of both the HPC matrix and the fibers, respectively. Specific steps are undertaken during the development and calibration of the phenomenological material model. In the initial step, an experimental and numerical analysis of the pullout test of steel fibers embedded in an HPC matrix is conducted. This process is used to calibrate the micro-mechanical model based on the elasto-plastic phase-field formulation for fracture. In the subsequent step, virtual experiments based on an ellipsoidal unit cell, also with the resolution of fibers (used as a representative volume element, RVE), are simulated to analyze the impact of fiber-matrix interactions and their physical properties on the effective material behavior of fiber-reinforced HPC. In the final step, macroscopic boundary value problems (BVPs) based on a cuboid are simulated on a single scale using the developed phenomenological material model. The resulting macroscopic stress-strain characteristics obtained from both types of simulations, namely simulations of virtual experiments and macroscopic BVPs, are compared. This comparison is utilized for the calibration of material parameters to obtain a regularized solution and to assess the effectiveness of the presented phenomenological material model.

3.
J Clin Med ; 12(17)2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37685535

RESUMO

PURPOSE: Articular cartilage defects are a prevalent consequence of femoroacetabular impingement (FAI) in young active patients. In accordance with current guidelines, large chondral lesions of the hip joint over 2 cm2 are recommended to be treated with matrix-associated, autologous chondrocyte transplantation (MACT); however, the conditions in the hip joint are challenging for membrane-based MACT options. Injectable MACT products can solve this problem. The purpose of the trial was to assess clinical and radiological outcomes 24 months after injectable MACT of focal chondral lesions caused by FAI. METHODS: We present data of 21 patients with focal cartilage defects of the hip [3.0 ± 1.4 cm2 (mean ± SD)], ICRS Grade III and IV caused by CAM-type impingement, who underwent arthroscopic MACT (NOVOCART® Inject) and FAI correction. The outcome was evaluated with the patient-reported outcome instruments iHOT33 and EQ-5D-5L (index value and VAS), whilst graft morphology was assessed based on the MOCART score over a follow-up period of 24 months. RESULTS: The iHOT33 score increased significantly from 52.9 ± 21.1 (mean ± SD) preoperatively to 85.8 ± 14.8 (mean ± SD; p < 0.0001) 24 months postoperatively. The EQ-5D-5L index value (p = 0.0004) and EQ-5D VAS (p = 0.0006) showed a statistically significant improvement as well. MRI evaluation after 24 months showed successful integration of the implant in all patients with a complete defect filling in 11 of 14 patients. CONCLUSIONS: Injectable MACT for the treatment of full-thickness chondral lesions of the hip joint due to FAI in combination with FAI correction improved symptoms, function, and quality of life in the treated cohort. Alongside the treatment of the underlying pathology by the FAI correction, the developed cartilage defect can be successfully repaired by MACT, which is of considerable clinical relevance.

4.
Aktuelle Urol ; 54(3): 189-195, 2023 06.
Artigo em Alemão | MEDLINE | ID: mdl-37224856

RESUMO

The current cancer registry notification, which was introduced in Germany as a mandatory institution in 2015, has its starting point in the National Cancer Plan of 2008. Other milestones include the Federal Cancer Registry Data Act (2009), the Cancer Early Detection and Registry Act (2013), the Uniform Oncological Basic Data Set (2014/2021) with its modules (e.g. the module prostate carcinoma 2017) as well as the Cancer Registry Data Merger Act (2021). At the beginning of 2017, the German Society of Uro-Oncologists (d-uo) had the idea of designing a documentation platform that would enable d-uo members to report to the cancer registry and transfer data to d-uo's own database - without a double effort. The cancer registry reimburses the first notification of a tumour with € 18. As the only provider, d-uo reimburses its members for the documentation effort associated with the additional notification to d-uo with a further € 18. In addition to the basic oncological data set, further parameters were defined by d-uo. This data is collected, evaluated and interpreted as part of the VERSUS study. The realisation that the parameters of the basic data set are limited in their informative value led d-uo to establish the two national registries for urothelial carcinoma (UroNAT) and prostate carcinoma (ProNAT). This underscores d-uo's leading position in uro-oncological healthcare research in Germany.


Assuntos
Carcinoma de Células de Transição , Oncologistas , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Masculino , Humanos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Sistema de Registros
5.
Aktuelle Urol ; 54(3): 196-201, 2023 06.
Artigo em Alemão | MEDLINE | ID: mdl-37224857

RESUMO

At the beginning of 2017, the German Society of Uro-Oncologists (d-uo) had the idea of designing a documentation platform that would enable d-uo members to report cancer cases to the cancer registry and transfer data to d-uo's own database - without a double effort. The cancer registry reimburses the first notification of a tumour with €18. As the only provider, d-uo reimburses its members for the documentation effort associated with the additional notification to d-uo with a further €18. In addition to the basic oncological data set, further parameters were defined by d-uo. This data is collected, evaluated and interpreted as part of the VERSUS study. At the end of 2022, 14,834 patients with a newly diagnosed urological tumour were included in the VERSUS study. Almost two thirds of all patients had prostate cancer. About half of all patients with prostate cancer were diagnosed as part of an early detection measure. These patients then also had more favourable tumour stages. Overall, almost every eighth patient already had metastases at the time of initial diagnosis. Data from the VERSUS study are available for 2,167 operations on prostate cancer with tumour category T2 or T3. There were 1,360 operations in patients with a T2 tumour (62.8%) and 807 operations in patients with T3 tumours (37.2%). A positive margin was present in 25.5% of all operated-on patients. In relation to tumour categories T2 and T3, the proportion of a positive resection margin was 14.3% and 44.2%, respectively. The VERSUS study will continue to provide answers to many questions from the uro-oncological field with reference to the "real world" situation in Germany.


Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/cirurgia , Bases de Dados Factuais , Documentação , Alemanha , Oncologia
6.
Aktuelle Urol ; 54(3): 202-207, 2023 06.
Artigo em Alemão | MEDLINE | ID: mdl-37224858

RESUMO

The German Society of Uro-Oncologists ("Deutsche Uro-Onkologen e.V.", d-uo) provides a national registry for urothelial cancer (UroNat) and a national registry for prostate cancer (ProNAT). These registries aim to evaluate the standard of care for urothelial cancer of the bladder and the upper urinary tract as well as prostate cancer by office-based urologists, oncologists and outpatient hospital departments in Germany. This includes, but is not limited to, adherence to guidelines during the treatment of patients with urothelial cancer and prostate cancer. The registries aim to capture and analyse scientifically how patients with these two most frequent urological tumours are treated and how quality assurance is implemented to improve the quality of their outpatient treatment in Germany. Both registries may share basic patient data supplied by the non-interventional, prospective, multicentre VERSUS registry by d-uo, which has been ongoing since 2018 and today includes more than 15,000 patients with different urological malignancies. In the UroNAT and ProNAT registries, additional items and parameters are included to allow for more detailed analyses of outcomes of outpatient treatments in Germany, which have so far been unavailable from the German Cancer Registry. By documenting the current treatment landscape of urothelial and prostate cancer in the outpatient setting, the registries intend to identify potential improvements of patient care and to initiate their implementation into clinical practice. These non-interventional prospective registries only document daily routine diagnostics, clinical courses and procedures.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Próstata , Neoplasias da Bexiga Urinária , Masculino , Humanos , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/terapia , Sistema de Registros
7.
Aktuelle Urol ; 53(6): 517-525, 2022 12.
Artigo em Alemão | MEDLINE | ID: mdl-36423612

RESUMO

INTRODUCTION: Patients with prostate cancer often present with reduced bone mineral density. We herein present real-world data (RWD) regarding osteoprotection in patients with non-metastatic hormone-sensitive prostate cancer (nmHSPC) receiving androgen deprivation therapy (ADT) treated by German urologists in private practice. MATERIAL AND METHODS: This is a questionnaire-based study including members of d-uo ("Deutsche Uro-Onkologen", German uro-oncologists). Patients with nmHSPC between July 2019 and June 2020 were included. They were asked about start, type and duration of osteoprotection as well as supplementation with calcium and vitamin D. RESULTS: Between July 2019 and June 2020, a total of 3,692 patients with prostate cancer were seen at least once in one of the private practices of 15 urologists (all d-uo members). There were 844 patients (22.9%) with nmHSPC treated with ADT. Osteoprotection using denosumab or a bisphosphonate to prevent skeletal-related events (SRE) was applied in 183/844 patients (21.7%) with nmHSPC. In patients receiving osteoprotection, denosumab was chosen in 73.2% of patients and a bisphosphonate was chosen in 26.8% of patients. Supplementation with calcium and vitamin D was given in 84.7% of patients. CONCLUSION: Patients with nmHSPC received osteoprotection in 1/5 of patients. Of these, 3/4 received denosumab and 1/4 received a bisphosphonate. The majority of patients were additionally treated with calcium and vitamin D. In our study, osteoprotection in patients with nmHSPC was rather an exception.


Assuntos
Antagonistas de Androgênios , Neoplasias da Próstata , Masculino , Humanos , Antagonistas de Androgênios/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Androgênios , Denosumab/uso terapêutico , Cálcio , Alemanha , Vitamina D/uso terapêutico , Difosfonatos
8.
Aktuelle Urol ; 53(6): 526-534, 2022 12.
Artigo em Alemão | MEDLINE | ID: mdl-36423613

RESUMO

INTRODUCTION: Patients with bone metastasis due to prostate cancer often present allover reduced bone mineral density. Additionally, patients with bone metastatic castration-resistant prostate cancer (mCRPC) have a relevant risk for skeletal-related events (SRE). We herein present real-world data (RWD) regarding osteoprotection in mCRPC patients with bone metastasis treated by German urologists in private practice. MATERIAL AND METHODS: This is a questionnaire-based study including members of d-uo ("Deutsche Uro-Onkologen", German uro-oncologists). All patients with histologically confirmed prostate cancer seen at least once in the surveyed urology practice between July 2019 and June 2020 were included. Questions included start, type and duration of osteoprotection as well as supplementation with calcium and vitamin D. RESULTS: Between July 2019 and June 2020, a total of 3,692 patients with prostate cancer were seen at least once in 15 urology practices. There were 410 mCRPC patients (11.1%) with bone metastasis. Osteoprotection with denosumab or a bisphosphonate to prevent SRE was applied in 274/410 mCRPC patients (66.4%) with bone metastasis. In patients receiving osteoprotection, denosumab was chosen for 67.9% of patients and a bisphosphonate was chosen for 32.1%. Supplementation with calcium and vitamin D was performed in 93.4% of the patients. The median duration of treatment was 25.3 months for denosumab compared with 39.6 months for bisphosphonates. CONCLUSIONS: Patients with mCRPC with bone metastasis received osteoprotection in 2/3 of cases. Of these, 2/3 received denosumab and 1/3 received a bisphosphonate. The majority of patients were also treated with calcium and vitamin D. According to guideline recommendations regarding osteoprotection in mCRPC patients with bone metastasis, our RWD data showed some lack of guideline adherence.


Assuntos
Neoplasias Ósseas , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/patologia , Denosumab/uso terapêutico , Cálcio/uso terapêutico , Neoplasias Ósseas/secundário , Difosfonatos/uso terapêutico , Alemanha , Vitamina D/uso terapêutico
9.
Aktuelle Urol ; 53(6): 511-516, 2022 12.
Artigo em Alemão | MEDLINE | ID: mdl-36167310

RESUMO

During phase III study ERA-223, patients under combination therapy with radium-223 and abiraterone showed an increased risk of bone fractures and a possible higher risk of death. This observation led to a change in the German therapeutic guidelines in 2018. Radium-223 is now only allowed as a third-line monotherapy (besides ADT) in patients with metastatic castration resistant prostate cancer (mCRPC) with symptomatic bone lesions without known visceral metastases or for patients with mCRPC, for whom no other available systematic therapy is suitable. Since almost no data on practice-related care research on the use of radium-223 exist, we consulted members of d-uo (German Uro-Oncologists) over their therapy algorithms. This study analysed data of patients treated with radium-223 between 2014 and 2019. It could be shown that 50% of mCRPC-patients had received radium-223 in the past as third-line therapy. Half of these were treated in combination with new androgen receptor targeted therapies (ARTA) and no increase in bone fractures was observed. This was most likely due to the additional use of bone protecting agents. Despite the late cancer stage, treatment response was seen in almost half of the patients.


Assuntos
Neoplasias Ósseas , Fraturas Ósseas , Neoplasias de Próstata Resistentes à Castração , Rádio (Elemento) , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Neoplasias de Próstata Resistentes à Castração/radioterapia , Neoplasias de Próstata Resistentes à Castração/patologia , Estudos Retrospectivos , Neoplasias Ósseas/tratamento farmacológico , Rádio (Elemento)/efeitos adversos , Fraturas Ósseas/induzido quimicamente , Fraturas Ósseas/tratamento farmacológico
10.
Materials (Basel) ; 15(3)2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35161123

RESUMO

This contribution aims to analyze the deterioration behaviour of steel fibre-reinforced high-performance concrete (HPC) in both experiments as well as numerical simulations. For this purpose, flexural tensile tests are carried out on beams with different fibre contents and suitable damage indicators are established to describe and calibrate the damage behaviour numerically using a phase-field model approach. In addition to conventional measurement methods, the tests are equipped with acoustic emission sensors in order to obtain a more precise picture of crack evolution by observing acoustic events. It is shown that, in addition to classical damage indicators, such as stiffness degradation and absorbed energy, various acoustic indicators, such as the acoustic energy of individual crack events, can also provide information about the damage progress. For the efficient numerical analysis of the overall material behaviour of fibre-reinforced HPC, a phenomenological material model is developed. The data obtained in the experiments are used to calibrate and validate the numerical model for the simulation of three-point bending beam tests. To verify the efficiency of the presented numerical model, the numerical results are compared with the experimental data, e.g., load-CMOD curves and the degradation of residual stiffness.

11.
Cardiovasc Diabetol ; 21(1): 18, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-35123462

RESUMO

BACKGROUND: The gut incretin hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic peptide) are secreted by enteroendocrine cells following food intake leading to insulin secretion and glucose lowering. Beyond its metabolic function GIP has been found to exhibit direct cardio- and atheroprotective effects in mice and to be associated with cardiovascular prognosis in patients with myocardial infarction. The aim of this study was to characterize endogenous GIP levels in patients with acute myocardial infarction. METHODS AND RESULTS: Serum concentrations of GIP were assessed in 731 patients who presented with clinical indication of coronary angiography. Circulating GIP levels were significantly lower in patients with STEMI (ST-elevation myocardial infarction; n=100) compared to clinically stable patients without myocardial infarction (n=631) (216.82 pg/mL [Q1-Q3: 52.37-443.07] vs. 271.54 pg/mL [Q1-Q3: 70.12-542.41], p = 0.0266). To characterize endogenous GIP levels in patients with acute myocardial injury we enrolled 18 patients scheduled for cardiac surgery with cardiopulmonary bypass and requirement of extracorporeal circulation as a reproducible condition of myocardial injury. Blood samples were drawn directly before surgery (baseline), upon arrival at the intensive care unit (ICU), 6 h post arrival to the ICU and at the morning of the first and second postoperative days. Mean circulating GIP concentrations decreased in response to surgery from 45.3 ± 22.6 pg/mL at baseline to a minimum of 31.9 ± 19.8 pg/mL at the first postoperative day (p = 0.0384) and rose again at the second postoperative day (52.1 ± 28.0 pg/mL). CONCLUSIONS: Circulating GIP levels are downregulated in patients with myocardial infarction and following cardiac surgery. These results might suggest nutrition-independent regulation of GIP secretion following myocardial injury in humans.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Polipeptídeo Inibidor Gástrico/sangue , Cardiopatias/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Idoso , Biomarcadores/sangue , Ponte Cardiopulmonar/efeitos adversos , Estudos de Casos e Controles , Angiografia Coronária , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática , Feminino , Cardiopatias/diagnóstico , Cardiopatias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico por imagem
12.
Orthopade ; 51(3): 176-186, 2022 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-35190849

RESUMO

BACKGROUND: Properly performed high-quality imaging is critical in the diagnosis of femoroacetabular impingement syndrome (FAIS). Currently, conventional imaging in the form of an anteroposterior view of the pelvis and at least a second view is still the first step in the diagnosis of FAIS. Here, by determining the various parameters, the acetabular configuration should also be accurately assessed with regard to a combination with dysplasia or acetabular retroversion. MRI: MRI should also be demanded as standard before joint-preserving surgery. It allows for more precise detection of morphology, secondary chondrolabral damage, and thus helps identify outcome-relevant risk factors and cases that are too advanced in terms of degenerative aspects. OTHER IMAGING METHODS: Depending on the problem, MRI can be supplemented by intravenous or intra-articular application of contrast agents (indirect or direct MRA), determination of torsion, and, if necessary, even with the performance of a traction MRA. While the importance of invasive MRA has decreased due to the improvements of 3­Tesla scanners in clinical practice, rotational analysis has gained in importance. Computed tomography (CT), although associated with increased radiation exposure, allows high-resolution imaging of bony structures and extremely illustrative 3D planning of complex corrections, and is an alternative to MRI for this purpose or in contraindications. PROSPECTS: 4D simulations appear useful and may make diagnostics and therapy planning safer and easier in the future. Thus, a broad portfolio of imaging techniques is available today, the advances of which have contributed significantly to the development of differentiated joint-preserving surgery of the hip joint.


Assuntos
Impacto Femoroacetabular , Acetábulo/cirurgia , Impacto Femoroacetabular/diagnóstico por imagem , Impacto Femoroacetabular/cirurgia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Imageamento por Ressonância Magnética/métodos , Tomografia Computadorizada por Raios X/métodos
13.
J Clin Med ; 10(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34362116

RESUMO

Sleep disordered breathing (SDB) is common among patients with valvular heart disease, and successful valve surgery could reduce SDB severity. However, data about the effects of transcatheter mitral valve repair on SDB are scarce. Therefore, mitral regurgitation (MR) patients undergoing MitraClip-placement were prospectively enrolled. Before MitraClip-placement, daytime sleepiness and sleep quality were assessed using the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI), respectively; and all patients underwent SDB screening using five-channel respiratory polygraphy. After 3-6 months, patients had a similar reassessment including: ESS, PSQI, and respiratory polygraphy. 67 patients were included (77 ± 8years). Despite normal sleepiness scores, 41 patients (61%) had SDB with apnea-hypopnea-index (AHI) ≥ 15 h before MitraClip-placement, of whom only three patients had known SDB previously. Compared to patients without SDB, patients with SDB had similar sleepiness scores but higher NT-proBNP values at baseline (4325 vs. 1520 pg/mL, p < 0.001). At follow-up, there were significant AHI improvements among patients with SDB (p = 0.013). However, there were no significant sleepiness score changes. In conclusion, the prevalence of SDB among MitraClip candidates is very high even in those without daytime sleepiness. MR patients with SDB have higher NT-proBNP values, which may reflect a worse prognosis. MitraClip-placement may improve the underlying SDB, which could be an additional benefit of the procedure.

14.
Knee Surg Sports Traumatol Arthrosc ; 28(4): 1317-1324, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30993353

RESUMO

PURPOSE: Acetabular chondral lesions are common in patients with FAI. For large full-thickness cartilage defects, arthroscopic matrix-associated autologous chondrocyte transplantation (MACT) using an injectable in situ crosslinking product is an option. Aim of the study was to evaluate clinical and MRI results 12 months after MACT of acetabular cartilage defects in FAI patients. METHODS: We report data on 21 patients with a focal cartilage defect of the hip [2.97 ± 1.44 cm2 (mean ± SD)] caused by FAI treated with an arthroscopically conducted MACT combined with FAI surgery. The results were assessed with patient-reported outcome measures (iHOT33, EQ-5D) pre- as well as post-operatively and by MRI using MOCART scoring system 6 and 12 months post-operatively. RESULTS: The iHOT33 score improved from 52.9 ± 21.14 (mean ± SD) pre-operative to 81.08 ± 22.04 (mean ± SD; p = 0.0012) 12 months post-operatively. The lower the pre-operative iHOT33 score and the larger the defect size, the greater the observed improvement compared to pre-operative scores at 12 months. Patients showed a significant improvement in EQ-5D-5L index value (p = 0.0015) and EQ-5D VAS (p = 0.0006). MRI analysis after 12 months revealed a complete integration of the transplant in 16 of 20 patients. CONCLUSIONS: Injectable MACT is a promising minimally invasive treatment option for full-thickness cartilage defects of the hip caused by FAI. A significant improvement in symptoms and function associated with an increase in quality of life was detected in patients treated with injectable MACT combined with FAI surgery. This is of considerable clinical relevance, since, in addition to the elimination of the mechanical cause, MACT allows the successful therapy of consequential cartilage damage. LEVEL OF EVIDENCE: Level 4, case series.


Assuntos
Artroscopia/métodos , Doenças das Cartilagens/patologia , Cartilagem Articular/cirurgia , Condrócitos/transplante , Articulação do Quadril/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Qualidade de Vida , Adulto , Doenças das Cartilagens/cirurgia , Feminino , Articulação do Quadril/cirurgia , Humanos , Masculino , Transplante Autólogo
15.
Int J Cancer ; 143(6): 1416-1425, 2018 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-29659014

RESUMO

To evaluate the role of constitutive epigenetic changes in normal body cells of BRCA1/BRCA2-mutation negative patients, we have developed a deep bisulfite sequencing assay targeting the promoter regions of 8 tumor suppressor (TS) genes (BRCA1, BRCA2, RAD51C, ATM, PTEN, TP53, MLH1, RB1) and the estrogene receptor gene (ESR1), which plays a role in tumor progression. We analyzed blood samples of two breast cancer (BC) cohorts with early onset (EO) and high risk (HR) for a heterozygous mutation, respectively, along with age-matched controls. Methylation analysis of up to 50,000 individual DNA molecules per gene and sample allowed quantification of epimutations (alleles with >50% methylated CpGs), which are associated with epigenetic silencing. Compared to ESR1, which is representative for an average promoter, TS genes were characterized by a very low (< 1%) average methylation level and a very low mean epimutation rate (EMR; < 0.0001% to 0.1%). With exception of BRCA1, which showed an increased EMR in BC (0.31% vs. 0.06%), there was no significant difference between patients and controls. One of 36 HR BC patients exhibited a dramatically increased EMR (14.7%) in BRCA1, consistent with a disease-causing epimutation. Approximately one third (15 of 44) EO BC patients exhibited increased rates of single CpG methylation errors in multiple TS genes. Both EO and HR BC patients exhibited global underexpression of blood TS genes. We propose that epigenetic abnormalities in normal body cells are indicative of disturbed mechanisms for maintaining low methylation and appropriate expression levels and may be associated with an increased BC risk.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Ilhas de CpG/genética , Metilação de DNA , Epigênese Genética , Mutação , Proteínas Supressoras de Tumor/genética , Adulto , Alelos , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Humanos , Prognóstico , Regiões Promotoras Genéticas , Fatores de Risco
17.
Arch Orthop Trauma Surg ; 138(4): 471-477, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29282525

RESUMO

INTRODUCTION: Pigmented villonodular synovitis (PVNS) is a rare, destructive synovial disease that affects the hip joint the second most common after the knee. However, in contrast, joint preserving surgery in the hip joint is considered to be significantly more difficult or even impossible due to earlier occurrence of osteochondral dissemination and surgical difficulties. Today, earlier diagnosis due to the generous use of MRI and modern surgical strategies raise hope for improved outcomes. METHODS: Since 2005, six patients with PVNS of the hip and a minimal follow-up of 2 years underwent joint preserving surgery in our institution (mean age 20.5 years, range 14-27). After PVNS was suspected in the MRI and confirmed by arthroscopic biopsy (four diffuse, two focal forms), synovectomy was carried out in 5 patients via surgical hip dislocation and in one focal case via arthroscopy. In diffuse forms, adjuvant radiosynoviorthesis (RSO) was conducted 6-8 week postoperatively. MRI and clinical examinations were performed during follow-up. RESULTS: After a mean follow-up of 8 years (range 35-141 months), five of six patients did not show recurrence or secondary osteoarthritis. Clinical outcome evaluation resulted in a mean modified Harris Hip Score of 91 points (range 67-100 points). A 21-year-old patient with a diffuse form and advanced osteochondral involvement at the time of diagnosis was eventually treated by total hip arthroplasty. CONCLUSION: In cases without osteochondral involvement, recurrence-free long-term results without progression of joint degeneration can be achieved by joint preserving therapy.


Assuntos
Articulação do Quadril , Tratamentos com Preservação do Órgão , Sinovite Pigmentada Vilonodular , Adolescente , Adulto , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/fisiopatologia , Articulação do Quadril/cirurgia , Humanos , Sinovite Pigmentada Vilonodular/diagnóstico por imagem , Sinovite Pigmentada Vilonodular/fisiopatologia , Sinovite Pigmentada Vilonodular/cirurgia , Adulto Jovem
18.
Z Orthop Unfall ; 155(6): 670-682, 2017 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-28915523

RESUMO

Background Symptomatic pre-arthritic deformities such as femoroacetabular impingement (FAI) or hip dysplasia often lead to localised cartilage defects and subsequently to osteoarthritis. The present review of the working group "Clinical Tissue Regeneration" of the German Society of Orthopaedics and Trauma (DGOU) and the hip committee of the AGA (German speaking Society for Arthroscopy and Joint Surgery) provides an overview of current knowledge of the diagnosis and surgical treatment of cartilage defects, in order to infer appropriate therapy recommendations for the hip. Methods Review of FAI and resultant cartilage damage in the hip as reported in published study findings in the literature and discussion of the advantages and disadvantages of different surgical procedures to preserve the joint. Results Most published studies on the surgical treatment of cartilage damage in the hip report defects caused by cam-type FAI at the acetabulum. Development of these defects can be prevented by timely elimination of the relevant deformities. At present, current full-thickness cartilage defects are mostly treated with bone marrow-stimulating techniques such as microfracture (MFx), with or without a biomaterial, and matrix-assisted autologous chondrocyte transplantation (MACT). Osteochondral autologous transplantation (OAT) is not the treatment of choice for isolated full-thickness chondral defects at the hip, because of the unfavourable risk-benefit profile. Due to the relatively short history of cartilage repair surgery on the hip, the studies available on these procedures have low levels of evidence. However, it is already becoming obvious that the experience gained with the same procedures on the knee can be applied to the hip as well. For example, limited healing and regeneration of chondral defects after MFx can also be observed at the hip joint. Conclusions The cartilage surface of the acetabulum, where FAI-related chondral lesions appear, is considerably smaller than the weight-bearing cartilage surface of the knee joint. However, as in the knee joint, MACT is the therapy of choice for full-thickness cartilage defects of more than 1.5 - 2 cm2. Minimally invasive types of MACT (e.g. injectable chondrocyte implants) should be preferred in the hip joint. In cases where a single-stage procedure is indicated or there are other compelling reasons for not performing a MACT, a bone marrow-stimulating technique in combination with a biomaterial covering is preferable to standard MFx. For treatment of lesions smaller than 1.5 - 2 cm2 the indication for a single-stage procedure is wider. As with defects in the knee, it is not possible to determine a definite upper age limit for joint-preserving surgery or MACT in the hip, as the chronological age of patients does not necessarily correlate with their biological age or the condition of their joints. Advanced osteoarthritis of the hip is a contraindication for any kind of hip-preserving surgery. Long-term observations and prospective randomised studies like those carried out for other joints are necessary.


Assuntos
Cartilagem Articular/cirurgia , Condrócitos/transplante , Impacto Femoroacetabular/cirurgia , Luxação do Quadril/cirurgia , Articulação do Quadril/cirurgia , Proteínas Matrilinas/uso terapêutico , Osteoartrite do Quadril/cirurgia , Fatores Etários , Transplante de Células , Contraindicações , Impacto Femoroacetabular/diagnóstico , Regeneração Tecidual Guiada , Luxação do Quadril/diagnóstico , Humanos , Injeções Intra-Articulares , Procedimentos Cirúrgicos Minimamente Invasivos , Osteoartrite do Quadril/diagnóstico
19.
Z Orthop Unfall ; 155(4): 409-416, 2017 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-28423434

RESUMO

Background Besides the known intraarticular femoroacetabular impingement (FAI), recently forms of extra-articular impingement of the hip have been increasingly recognized. Recent studies have described an extra-articular impingement between a distal extension of the anterior inferior iliac spine (AIIS) and the femoral neck (AIIS or subspine impingement). Evidently, an association between this subspine impingement and an intraarticular FAI seems to exist. Little is known about the incidence of this impingement type and the value of its radiological diagnostics. The aim of this study was therefore to evaluate the correlation of a subspine impingement with intraarticular femoroacetabular impingement and radiological criteria of subspine impingement. Material and Methods In 2013 arthroscopic correction of intra-articular femoroacetabular impingement was performed in 80 cases. This collective was evaluated for simultaneous intraoperative findings of subspine impingement. In addition, the patients were evaluated for radiological signs of subspine impingement in conventional X-ray. A projection of the AIIS either below the acetabular sourcil or the anterior acetabular rim in an AP pelvis X-ray was considered as a radiological sign of low AIIS formation. These radiological findings were compared with the presence of intraoperative signs for subspine impingement, which are defined as a combination of focal capsule synovitis, labral ecchymosis close to the AIIS and a decreased offset between the acetabular rim and the AIIS. The specificity and sensitivity of the pre-operative radiological signs were calculated. Results A subspine impingement was found in 17 cases (21 %, 3 female, 14 male, mean age 28 years). A projection of the AIIS caudal to the acetabular sourcil in the AP pelvis X-ray was represented in 15 of the 17 cases detected (sensitivity 0.90, specificity 0.88). A projection below the anterior glenoid rim was detectable in 2 cases with symptomatic AIIS impingement (sensitivity 0.12, specificity 1). Conclusion A relevant proportion of patients with intraarticular FAI showed intraoperative signs for an additive extraarticular AIIS impingement. Preoperative pelvic X-rays are helpful with a sensitivity of 90 % in detecting the presence of a distal extension of the AIIS in FAI patients. Evaluation of the preoperative AP pelvis x-ray should include the projection of the AIIS. We recommend evaluation for subspine impingement during routine arthroscopy.


Assuntos
Impacto Femoroacetabular/diagnóstico por imagem , Colo do Fêmur/diagnóstico por imagem , Luxação do Quadril/diagnóstico por imagem , Ílio/diagnóstico por imagem , Adolescente , Adulto , Artroscopia , Diagnóstico Diferencial , Equimose/diagnóstico por imagem , Equimose/cirurgia , Feminino , Impacto Femoroacetabular/cirurgia , Colo do Fêmur/cirurgia , Seguimentos , Luxação do Quadril/cirurgia , Humanos , Ílio/cirurgia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estatística como Assunto , Sinovite/diagnóstico por imagem , Sinovite/cirurgia , Adulto Jovem
20.
J Am Soc Echocardiogr ; 30(3): 235-243.e1, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28259304

RESUMO

BACKGROUND: The effects of acute excessive alcohol ingestion on echocardiographic parameters of left ventricular (LV) function are unclear. METHODS: One hundred ninety-nine healthy subjects (44 ± 5 years, 71% male) were prospectively examined within 6 hours after excessive alcohol ingestion as well as after 4 weeks with strict alcohol abstinence. Echocardiography was performed at baseline and follow-up for conventional parameters (left ventricular ejection fraction [LVEF], transmitral E and A Doppler flow velocities, E/A ratio, tissue Doppler velocity lateral and septal (é), E/é ratio, deceleration time of E, and isovolumic relaxation time) and myocardial deformation data (such as global radial and global and layer-specific circumferential [endo and epi global CS] and longitudinal [endo and epi global LS] strain). Multivariate regression was used to assess the impact of independent variables on echocardiographic parameters. RESULTS: Alcohol levels were 1.2 ± 0.3 g/L at the time of drinking cessation. After alcohol ingestion endo CS (30% ± 2% vs 37% ± 3%, P = .008) and endo LS (27% ± 4% vs 33% ± 3%, P = .002) were significantly lower at baseline versus follow-up. Blood pressure, LVEF and heart rate, and other echocardiographic parameters did not differ between the two examinations. Alcohol levels were modestly, negatively associated with change in endo CS and endo LS (r = -0.54, 95% CI, -0.63 to -0.43, P < .001; and r = -0.26, 95% CI, -0.39 to -0.14; P < .003, respectively). Alcohol levels were the strongest predictor for endo CS (ß = -4.84; 95% CI, -6.31 to -3.37) and endo LS (ß = -2.50; 95% CI, -4.32 to -0.68). CONCLUSIONS: Acute alcohol ingestion effects endocardial CS and LS, suggesting an acute and transient toxic effect on myocardial deformation, an effect that remains undetected by conventional echocardiographic parameters. The current findings may help clinicians to gain more understanding into the mechanism of developing an alcohol cardiomyopathy and to detect early persistent alcohol-induced myocardial disturbances for an effective therapy in time to prevent harm.


Assuntos
Alcoolismo/complicações , Alcoolismo/diagnóstico por imagem , Ecocardiografia/métodos , Técnicas de Imagem por Elasticidade/métodos , Volume Sistólico , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Adulto , Alcoolismo/fisiopatologia , Módulo de Elasticidade , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estresse Mecânico , Disfunção Ventricular Esquerda/fisiopatologia
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