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1.
Haemophilia ; 30(4): 1025-1031, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38825768

RESUMO

INTRODUCTION/AIM: To evaluate whether patients with haemophilia (PwH) can be enabled to perform ultrasonography (US) of their knees without supervision according to the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) protocol and whether they would be able to recognize pathologies. METHODS: Five PwH (mean age 29.6 years, range 20-48 years) were taught the use of a portable US device and the HEAD-US protocol. Subsequently, the patients performed US unsupervised at home three times a week for a total of 6 weeks with a reteaching after 2 weeks. All images were checked for mapping of the landmarks defined in the HEAD-US protocol by a radiologist. In a final test after the completion of the self-sonography period, participants were asked to identify scanning plane and potential pathology from US images of other PwH. RESULTS: On the images of the self-performed scans, 82.7% of the possible anatomic landmarks could be identified and 67.5% of the requested images were unobjectionable, depicting 100% of the required landmarks. There was a highly significant improvement in image quality following reteaching after 2 weeks (74.80 ± 36.88% vs. 88.31 ± 19.87%, p < .001). In the final test, the participants identified the right scanning plane in 85.0% and they correctly identified pathology in 90.0% of images. CONCLUSION: Appropriately trained PwH can perform the HEAD-US protocol of their knee with high quality and are capable to identify pathologic findings on these standardized images. Asynchronous tele-sonography could enable early therapy adjustment and thereby possibly reduce costs.


Assuntos
Estudos de Viabilidade , Hemofilia A , Ultrassonografia , Humanos , Hemofilia A/complicações , Hemofilia A/diagnóstico por imagem , Ultrassonografia/métodos , Adulto , Pessoa de Meia-Idade , Masculino , Adulto Jovem , Articulação do Joelho/diagnóstico por imagem , Joelho/diagnóstico por imagem
2.
Arch Orthop Trauma Surg ; 143(3): 1301-1310, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34846590

RESUMO

INTRODUCTION: Acetabular defect recognition and classification remains a challenging field of practice for orthopedic surgeons. Recently, the Acetabular Defect Classification (ADC) has been introduced to provide a reliable, reproducible and intuitive classification system. In order to improve ease of use and efficiency of the ADC, a browser-based application has been created. We hypothesized that the ADC application can improve rating performance of non-specialists (medical students) to achieve good inter- and intra-rater agreement and will compare favorable to the results of specialists (experienced surgeons) without the help of the application. MATERIALS AND METHODS: The ADC is based on the integrity of the acetabular rim and the supporting structures. It consists of four main types of defects ascending in severity. These defects are further subdivided in A-C, narrowing down defect location. 80 randomized radiographs were graded according to ADC by three non-specialists (medical students) with help of the ADC application and by three specialists (orthopedic surgeons) without help of the application to evaluate the difference in inter-rater agreement between groups. To account for intra-rater agreement, the rating process was repeated after a reasonable wash-out period. RESULTS: Inter-rater and intra-rater agreement within the non-specialist group rated lower when compared to the specialist group while still falling into the good agreement range. The student group presented with k values of 0.61 for inter-rater agreement and 0.68 for intra-rater agreement, while the surgeon group displayed k values of 0.72 for inter-rater agreement and 0.83 for intra-rater agreement. CONCLUSION: The app-guided assessment of acetabular defects offers a promising innovative approach to simplify complex situations. It makes the challenging field of acetabular revision arthroplasty more approachable especially for less experienced surgeons and offers insight and guidance in the planning stage as well as intra-operative setting.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Reoperação , Acetábulo/cirurgia , Radiografia
3.
Eur J Orthop Surg Traumatol ; 33(8): 3597-3601, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37246990

RESUMO

PURPOSE: Pathologic fractures of the extremities due to carcinoma metastases require individual and patient prognosis-related stabilization procedures. Quick remobilization of the patient to restore the quality of life is of high importance, especially in the case of subtrochanteric and diaphyseal femoral fractures. In our retrospective cohort study, we evaluated intraoperative blood loss, length of operation, complication rate, and regain of lower extremity function in plate compound osteosynthesis (PCO) versus intramedullary nailing (IM) for subtrochanteric and diaphyseal pathologic fractures of the femur. METHODS: Between January 2010 and July 2021, we retrospectively reviewed 49 patients who were treated at our institution for pathologic fractures of the subtrochanteric and diaphyseal femurs for group differences in terms of blood loss, length of operation, implant survival, and Musculoskeletal Tumor Society (MSTS) score. RESULTS: We included 49 stabilization procedures of the lower extremity due to pathologic fractures of the proximal or diaphyseal femur, with a mean follow-up of 17.7 months. IM (n = 29) had a significantly shorter operation time than PCO (n = 20) (112.4 ± 9.4 and 163.3 ± 15.96 min, respectively). We did not detect any significant differences in terms of blood loss, complication rate, implant survival, or MSTS score. CONCLUSION: Based on our data, pathologic subtrochanteric and diaphyseal fractures of the femur can be stabilized with IM, which has a shorter operation time than PCO, but the complication rate, implant survival, and blood loss remain unaffected.


Assuntos
Fraturas do Fêmur , Fixação Intramedular de Fraturas , Fraturas Espontâneas , Doenças Musculoesqueléticas , Humanos , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/cirurgia , Fixação Intramedular de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/métodos , Estudos Retrospectivos , Qualidade de Vida , Fraturas do Fêmur/etiologia , Fraturas do Fêmur/cirurgia , Fraturas do Fêmur/patologia , Extremidade Inferior , Resultado do Tratamento , Pinos Ortopédicos/efeitos adversos
4.
Haemophilia ; 28(4): 663-670, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35420240

RESUMO

BACKGROUND: In patients with haemophilia (PwH), most frequently affected joints are the ankle, knee and elbow. Due to improved factor therapy in the last decades, these previous findings have to be verified in Germany. AIM: The aim of this study is to detect the most affected joint, evaluate the significance of the source of pain and determine the point prevalence of back pain in Germany today. PATIENTS AND METHODS: In a retrospective study, data of n = 300 patients with severe moderate and mild haemophilia were evaluated regarding the most affected joint, the most common source of pain, and the point prevalence of back pain. An anamnesis questionnaire and the German Pain Questionnaire were used for this assessment. RESULTS: The most affected joint in German PwH is still the ankle (41%), followed by the knee (27%) and the elbow (11%). The most common source of pain is also the ankle joint (32%). Back pain was also identified as one of the most common sources of pain, which is comparable to the elbow (elbow:15%; back:13%). The point prevalence in PwH for back pain was significantly higher compared to the general German population (P = .031). CONCLUSION: Our data showed that the ankle is still the most affected joint and the most common source of pain in Germany. These results also showed the relevance of back pain as a pain source. The evaluations also demonstrated the high point prevalence of back pain in PwH. Future therapies should also focus on the spine because joint changes affect posture.


Assuntos
Hemofilia A , Articulação do Tornozelo , Alemanha/epidemiologia , Hemofilia A/complicações , Hemofilia A/epidemiologia , Humanos , Dor , Estudos Retrospectivos
5.
Ultraschall Med ; 43(2): 177-180, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32722821

RESUMO

PURPOSE: In Middle Europe developmental dysplasia of the hip (DDH) has an incidence of up to 5.9 %. The rate of congenital hip dislocation as the worst complication of a growth disorder of the hip is between 1.5 % and 2.5 %. Among known risk factors of DDH are breech position, multiples, foot deformities and family history. The aim of this retrospective study was to investigate prematurity as a risk factor for developmental dysplasia of the hip (DDH). MATERIALS AND METHODS: The hips of 283 infants who were born before the 38th week of gestation or earlier, and those of 377 infants who were born after the 37th week of gestation, none of whom had other risk factors for DDH, were compared using the ultrasound technique according to Graf et al., within the first week after birth. Both hips of all infants were included in the study. RESULTS: Surprisingly, the difference in alpha angles between the two groups was statistically extremely significant, favoring the preterm infants. Moreover, we found a physiological curve of alpha angle development with a peak after the 31st week of gestation. The incidence of pathological dysplasia was not significantly different in the two groups. CONCLUSION: Our results suggest that prematurity is not a predisposing factor for DDH, but rather is protective for hip development.


Assuntos
Displasia do Desenvolvimento do Quadril , Luxação Congênita de Quadril , Feminino , Luxação Congênita de Quadril/diagnóstico por imagem , Luxação Congênita de Quadril/epidemiologia , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Fatores de Proteção , Estudos Retrospectivos , Fatores de Risco , Ultrassonografia/efeitos adversos
6.
J Mater Sci Mater Med ; 32(4): 41, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792782

RESUMO

The aim of this study is to compare biomechanical features of different devices used in clinical routine for temporary epiphysiodesis (eight-Plate® and FlexTackTM). The tested implants were divided into four different groups (eight-Plate® vs. FlexTackTM for lateral and anterior implantation) á 10 samples for testing implanted eight-Plate® vs. FlexTackTM in fresh frozen pig femora for maximum load forces (Fmax) and axial physis distance until implant failure (lmax). A servo hydraulic testing machine (858 Mini Bionix 2) was used to exert and measure reproducible forces. Statistical analyses tested for normal distribution and significant (p < 0.05) differences in primary outcome parameters. There were no significant differences between the eight-Plate® lateral group and the FlexTackTM lateral group for neither Fmax (p = 0.46) nor lmax (p = 0.65). There was a significant higher Fmax (p < 0.001) and lmax (p = 0.001) measured in the eight-Plate® group compared to the FlexTackTM group when implanted anteriorly. In anterior temporary ephiphysiodesis, eight-Plate® demonstrated superior biomechanical stability. At this stage of research, there is no clear advantage of either implant and the choice remains within the individual preference of the surgeon.


Assuntos
Substitutos Ósseos/química , Epífises/química , Fêmur/cirurgia , Próteses e Implantes , Desenho de Prótese , Animais , Fenômenos Biomecânicos , Placas Ósseas , Fêmur/efeitos dos fármacos , Teste de Materiais , Estresse Mecânico , Suínos , Distribuição Tecidual
7.
J Mater Sci Mater Med ; 30(11): 124, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31705395

RESUMO

OBJECTIVE: External fixators are important for correcting length discrepancies and axis deformities in pediatric or trauma orthopedic surgery. Pin loosening is a common pitfall during therapy that can lead to pain, infection, and necessary revisions. This study aims to present clinical data using calcium titanate (CaTiO3) Schanz screws and to measure the fixation strength. PATIENTS AND METHODS: 22 titanate screws were used for external fixators in 4 pediatric patients. Therapy was initiated to lengthen or correct axial deformities after congenital abnormalities. The maximum tightening torque was measured during implantation, and the loosening torque was measured during explantation. In addition, screws of the same type were used in a cadaver study and compared with stainless steel and hydroxyapatite-coated screws. 12 screws of each type were inserted in four tibias, and the loosening and tightening torque was documented. RESULTS: The fixation index in the in vivo measurement showed a significant increase between screw insertion and extraction in three of the four patients. The pins were in situ for 91 to 150 days, and the torque increased significantly (P = 0.0004) from insertion to extraction. The cadaveric study showed lower extraction torques than insertion torques, as expected in this setting. The calculated fixation index was significantly higher in the CaTiO3 group than in the other groups (P = 0.0208 vs. HA and P < 0.0001 vs. steel) and in the HA group vs. plain steel group (P = 0.0448). CONCLUSION: The calcium titanate screws showed favorable fixation strength compared to HA and stainless steel screws and should be considered in long-term therapy of external fixation.


Assuntos
Materiais Biocompatíveis , Parafusos Ósseos , Cálcio/química , Fixadores Externos , Teste de Materiais , Titânio/química , Adolescente , Braço/anormalidades , Fenômenos Biomecânicos , Cadáver , Criança , Pré-Escolar , Feminino , Fêmur/anormalidades , Humanos , Masculino , Tíbia
8.
Int Orthop ; 41(2): 423-428, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27830274

RESUMO

BACKGROUND AND OBJECTIVES: The aim of our study was to evaluate if there is an increased risk of periprosthetic infection (PJI) in patients following replacement of the proximal humerus by using a modular tumour prosthesis in combination with a trevira tube. METHODS: Thirty patients were treated by using a modular tumour endoprosthesis (MUTARS®) following intra-articular resection of the proximal humerus. Fifteen patients received treatment by using a trevira tube. In 15 further cases the use of a trevira tube was not necessary. The mean follow-up time was 26 months (range: 24 months to 84 months). Both, Enneking score and range of motion (ROM), was evaluated. Further radiographs were obtained in two planes. RESULTS: The survival rate one year after surgery was 83 % and 63 % after two years. We recorded a 96 % survival of the limb two years after surgery. We also observed only one case of periprosthetic joint infection (PJI) in the entire follow-up period in one patient who received treatment with a trevira tube. The mean Enneking score was 20 points (range 8 to 26 points). ROM was equal in both study groups. In total 20 % of the treated patients (n = 6) suffered complications. CONCLUSIONS: Replacement of the proximal humerus by using a trevira tube in combination with a modular tumour endoprosthesis is a safe and viable treatment option for both, bone tumours and metastases. There is no statistically significant increased risk of infection by using trevira tube even among immunosuppressed patients. LEVEL OF EVIDENCE: Level 3, retrospective comparative study.


Assuntos
Neoplasias Ósseas/cirurgia , Úmero/cirurgia , Implantação de Prótese/métodos , Infecções Relacionadas à Prótese/epidemiologia , Reimplante/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Implantação de Prótese/efeitos adversos , Amplitude de Movimento Articular , Estudos Retrospectivos , Medição de Risco , Prata/efeitos adversos , Prata/uso terapêutico , Taxa de Sobrevida , Adulto Jovem
9.
Biochim Biophys Acta ; 1853(7): 1551-63, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25764979

RESUMO

Mitochondrial membrane architecture is important for organelle function. Alterations thereof are linked to a number of human disorders including diabetes and cardiomyopathy. The MICOS complex was recently reported to be a central player determining cristae structure and formation of crista junctions. Here we investigated the functional role of MIC26, a lipoprotein formerly termed APOO. Its levels are increased in diabetic heart tissue and in blood plasma of patients suffering from acute coronary syndrome. We demonstrate that human MIC26 exists in three distinct forms: (1) a glycosylated and secreted 55kDa protein, (2) an ER/Golgi-resident form thereof, and (3) a non-glycosylated 22kDa mitochondrial protein. The latter isoform spans the mitochondrial inner membrane and physically interacts with several MICOS complex subunits such as MIC60, MIC27, and MIC10. We further demonstrate that MIC26 and MIC27, a homologous protein formerly termed APOOL, regulate their levels in an antagonistic manner. Both proteins are positively correlated with the levels of MIC10 as well as tafazzin, an enzyme required for cardiolipin remodeling. Overexpression of MIC26 induced fragmentation of mitochondria, promoted ROS formation and resulted in impaired mitochondrial respiration. Downregulation of MIC26 induced a decrease in mitochondrial oxygen consumption, whereas mitochondrial network morphology and ROS levels remained unaffected. MIC26 depletion led to alterations in mitochondrial ultrastructure and caused a significant reduction in the number of crista junctions. In summary, we show that the human apolipoprotein MIC26 is a bona fide subunit of the MICOS complex and that MIC26 is linked to cardiolipin metabolism and promotes crista junction formation.


Assuntos
Apolipoproteínas/metabolismo , Mamíferos/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/metabolismo , Complexos Multiproteicos/metabolismo , Aciltransferases , Animais , Linhagem Celular Tumoral , Respiração Celular , Espaço Extracelular/metabolismo , Técnicas de Silenciamento de Genes , Glicosilação , Humanos , Proteína Cofatora de Membrana/metabolismo , Mitocôndrias/ultraestrutura , Proteínas Mitocondriais/metabolismo , Peso Molecular , Ligação Proteica , Isoformas de Proteínas/metabolismo , Subunidades Proteicas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/metabolismo
10.
J Biol Chem ; 289(15): 10769-10784, 2014 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-24515116

RESUMO

The majority of amyotrophic lateral sclerosis (ALS) cases as well as many patients suffering from frontotemporal lobar dementia (FTLD) with ubiquitinated inclusion bodies show TDP-43 pathology, the protein encoded by the TAR DNA-binding protein (Tardbp) gene. We used recombinase-mediated cassette exchange to introduce an ALS patient cDNA into the mouse Tdp-43 locus. Expression levels of human A315T TDP-43 protein were 300% elevated in heterozygotes, whereas the endogenous mouse Tdp-43 was decreased to 20% of wild type levels as a result of disturbed feedback regulation. Heterozygous TDP-43(A315TKi) mutants lost 10% of their body weight and developed insoluble TDP-43 protein starting as early as 3 months after birth, a pathology that was exacerbated with age. We analyzed the splicing patterns of known Tdp-43 target genes as well as genome-wide gene expression levels in different tissues that indicated mitochondrial dysfunction. In heterozygous mutant animals, we observed a relative decrease in expression of Parkin (Park2) and the fatty acid transporter CD36 along with an increase in fatty acids, HDL cholesterol, and glucose in the blood. As seen in transmission electron microscopy, neuronal cells in motor cortices of TDP-43(A315TKi) animals had abnormal neuronal mitochondrial cristae formation. Motor neurons were reduced to 90%, but only slight motoric impairment was detected. The observed phenotype was interpreted as a predisease model, which might be valuable for the identification of further environmental or genetic triggers of neurodegeneration.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Proteínas de Ligação a DNA/genética , Regulação da Expressão Gênica , Mitocôndrias/patologia , Alelos , Esclerose Lateral Amiotrófica/genética , Animais , Comportamento Animal , Glicemia/metabolismo , Peso Corporal , Antígenos CD36/metabolismo , HDL-Colesterol/metabolismo , DNA Complementar/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células-Tronco Embrionárias/citologia , Ácidos Graxos/metabolismo , Feminino , Técnicas de Introdução de Genes , Genoma , Genótipo , Heterozigoto , Humanos , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Transgênicos , Neurônios Motores/metabolismo , Mutagênese Sítio-Dirigida , Mutação , Fenótipo , Ubiquitina-Proteína Ligases/metabolismo
11.
Hum Mol Genet ; 22(24): 4871-87, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-23851121

RESUMO

The caseinolytic peptidase P (CLPP) is conserved from bacteria to humans. In the mitochondrial matrix, it multimerizes and forms a macromolecular proteasome-like cylinder together with the chaperone CLPX. In spite of a known relevance for the mitochondrial unfolded protein response, its substrates and tissue-specific roles are unclear in mammals. Recessive CLPP mutations were recently observed in the human Perrault variant of ovarian failure and sensorineural hearing loss. Here, a first characterization of CLPP null mice demonstrated complete female and male infertility and auditory deficits. Disrupted spermatogenesis already at the spermatid stage and ovarian follicular differentiation failure were evident. Reduced pre-/post-natal survival and marked ubiquitous growth retardation contrasted with only light impairment of movement and respiratory activities. Interestingly, the mice showed resistance to ulcerative dermatitis. Systematic expression studies detected up-regulation of other mitochondrial chaperones, accumulation of CLPX and mtDNA as well as inflammatory factors throughout tissues. T-lymphocytes in the spleen were activated. Thus, murine Clpp deletion represents a faithful Perrault model. The disease mechanism probably involves deficient clearance of mitochondrial components and inflammatory tissue destruction.


Assuntos
DNA Mitocondrial/metabolismo , Endopeptidase Clp/genética , Endopeptidase Clp/metabolismo , Transtornos do Crescimento/genética , Perda Auditiva/genética , Infertilidade/genética , Mediadores da Inflamação/metabolismo , Animais , Respiração Celular/genética , Modelos Animais de Doenças , Feminino , Ordem dos Genes , Gônadas/metabolismo , Gônadas/patologia , Transtornos do Crescimento/metabolismo , Perda Auditiva/metabolismo , Infertilidade/metabolismo , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Mitocôndrias/metabolismo , Chaperonas Moleculares/metabolismo , Atividade Motora/genética , Mutação , Fenótipo , Baço/citologia , Baço/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
12.
Biol Chem ; 395(3): 285-96, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24391192

RESUMO

Mitochondria exist in a highly dynamic network that is constantly altered by fusion and fission events depending on various factors such as cellular bioenergetic state and cell cycle. Next to this dynamic nature of the organelle, its cristae membrane also undergoes drastic morphological changes upon physiological or pathological alterations. The Mitofilin/mitochondrial inner membrane organizing system (MINOS) complex was recently reported to ensure mitochondrial architecture and crista junction integrity. Several subunits of this complex are linked to a diverse set of neurological human disorders. Recently, two apolipoproteins, ApoO (APOO) and ApoO-like (APOOL) were suggested to represent constituents of the mammalian Mitofilin/MINOS complex. APOOL was shown to bind the mitochondrial phospholipid cardiolipin (CL) and to interact physically with this complex. In this review we highlight the current view on the mammalian Mitofilin/MINOS complex and focus on APOOL and the role of CL in determining cristae morphology. We will discuss possible functions of the Mitofilin/MINOS complex on lipid transport, on assembly of respiratory supercomplexes, on F1FO-ATP synthase organization, on contact site formation, and on trapping CL within the cristae subcompartment.


Assuntos
Apolipoproteínas/metabolismo , Mitocôndrias/metabolismo , Membranas Mitocondriais/química , Membranas Mitocondriais/metabolismo , Proteínas Mitocondriais/metabolismo , Proteínas Musculares/metabolismo , Animais , Apolipoproteínas/química , Humanos , Mitocôndrias/química , Proteínas Mitocondriais/química , Modelos Biológicos , Proteínas Musculares/química
13.
Biochim Biophys Acta ; 1823(12): 2297-310, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22917578

RESUMO

Mitochondrial dysfunction is linked to apoptosis, aging, cancer, and a number of neurodegenerative and muscular disorders. The interplay between mitophagy and mitochondrial dynamics has been linked to the removal of dysfunctional mitochondria ensuring mitochondrial quality control. An open question is what role mitochondrial fission plays in the removal of mitochondria after mild and transient oxidative stress; conditions reported to result in moderately elevated reactive oxygen species (ROS) levels comparable to physical activity. Here we show that applying such conditions led to fragmentation of mitochondria and induction of mitophagy in mouse and human cells. These conditions increased ROS levels only slightly and neither triggered cell death nor led to a detectable induction of non-selective autophagy. Starvation led to hyperfusion of mitochondria, to high ROS levels, and to the induction of both non-selective autophagy and to a lesser extent to mitophagy. We conclude that moderate levels of ROS specifically trigger mitophagy but are insufficient to trigger non-selective autophagy. Expression of a dominant-negative variant of the fission factor DRP1 blocked mitophagy induction by mild oxidative stress as well as by starvation. Taken together, we demonstrate that in mammalian cells under mild oxidative stress a DRP1-dependent type of mitophagy is triggered while a concomitant induction of non-selective autophagy was not observed. We propose that these mild oxidative conditions resembling well physiological situations are thus very helpful for studying the molecular pathways governing the selective removal of dysfunctional mitochondria.


Assuntos
Autofagia , Mitocôndrias/patologia , Dinâmica Mitocondrial/fisiologia , Mitofagia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Animais , Proteína 5 Relacionada à Autofagia , Western Blotting , Células Cultivadas , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Células HeLa , Humanos , Camundongos , Camundongos Knockout , Proteínas Associadas aos Microtúbulos/fisiologia , Mitocôndrias/metabolismo
14.
J Cancer Res Clin Oncol ; 149(8): 4877-4888, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36287264

RESUMO

BACKGROUND: Over the years, radiotherapy has been established as a tool to improve local control for high-grade sarcomas. Although the European Society for Medical Oncology guidelines has taken notice of a shift toward a neoadjuvant radiotherapy approach, the American Society for Radiation Oncology guidelines clearly favor a neoadjuvant approach, citing debilitating long-term adverse effects when radiotherapy is applied postoperatively. In this study, we examined these irradiation-associated adverse events for adjuvant radiotherapy and focused on the prognostic factors for disease outcome, including local control. METHODS: In this retrospective study, data for 106 patients with extremity soft-tissue sarcomas diagnosed between 1997 and 2021, of which 40 received adjuvant radiotherapy, were collected from the clinical and radiological information systems of a high-volume sarcoma treatment center. These data were then analyzed for radiation-associated side effects as well as predictive factors for overall survival, disease-free survival, local control, and surgical complications. RESULTS: Radiotherapy was beneficial to patients improving local control, especially for high-grade sarcomas, even when those were resected with negative margins. Side effects due to radiotherapy occurred in 87.5% of the patients, and these effects primarily included radiation dermatitis in 67.5%; however, only 40.0% had any adverse event of ≥ grade 2 according to Common Terminology Criteria for Adverse Events. Long-term function-limiting side effects occurred in 45.0% of the patients; 10% exhibited ≥ grade 2 function-limiting adverse events. Greater time between surgery and adjuvant radiotherapy was beneficial for the patients, whereas joint infiltrating sarcomas were associated with more severe long term, function-limiting adverse events. 28.3% of the patients experienced a recurrence at any location (median time 18.35 months) and in 16% the recurrence was local (median time 16.11 months), resulting in 1, 3, and 5 year disease-free survival rates of 74.1, 58.9, and 38.5% and local control rates of 78.7, 61.6, and 42.8% were observed, respectively. CONCLUSION: Recurrences may be avoided with high-dose radiation, especially for high-grade G2 and G3 sarcomas, even after complete R0 resection. This resulted in a low rate of severe long-term function-limiting adverse events. Thus, adjuvant radiotherapy should be seriously considered when planning patient treatment, especially when treating patients that present with high-grade sarcomas.


Assuntos
Sarcoma , Neoplasias de Tecidos Moles , Humanos , Radioterapia Adjuvante/efeitos adversos , Estudos Retrospectivos , Sarcoma/radioterapia , Sarcoma/cirurgia , Extremidades , Terapia Neoadjuvante/métodos , Neoplasias de Tecidos Moles/radioterapia , Neoplasias de Tecidos Moles/cirurgia , Recidiva Local de Neoplasia
15.
Hamostaseologie ; 43(3): 208-214, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36863396

RESUMO

INTRODUCTION: Patients with hemophilia (PWHs) suffer from an increased risk of osteoporosis. Multiple hemophilia and hemophilic arthropathy associated factors correlate with a low bone mineral density (BMD) in PWHs. The aim of this study was to assess the long-term development of BMD in PWH as well as to analyze potentially influencing factors. METHODS: A total of 33 adult PWHs were evaluated in a retrospective study. General medical history, specific-hemophilia-associated comorbidities, joint status using the Gilbert score, calcium level, and vitamin D level as well as at least two results of bone density measurements with a minimum range of 10 years per patient were taken into account. RESULTS: The BMD did not change significantly from one point of measurement to the other. A total of 7 (21.2%) cases of osteoporosis and 16 (48.5%) cases of osteopenia were identified. The two following significant correlations could be revealed: the higher the patients' body mass index, the higher their BMD (r = 0.41; p = 0.022). Moreover, a high Gilbert score came along with a low BMD (r = -0.546; p = 0.003). CONCLUSION: Even if PWHs frequently suffer from a reduced BMD, our data suggest that their BMD remains constant on a low level in the course of time. A risk factor of osteoporosis often found in PWHs is a vitamin D deficiency and joint destruction. Therefore, a standardized screening of PWHs on BMD reduction by collecting vitamin D blood level and assessing joint status seems appropriate.


Assuntos
Hemofilia A , Osteoporose , Adulto , Humanos , Hemofilia A/complicações , Hemofilia A/epidemiologia , Estudos Retrospectivos , Osteoporose/epidemiologia , Osteoporose/complicações , Osteoporose/diagnóstico , Densidade Óssea , Vitamina D
16.
Clin Exp Metastasis ; 40(1): 117-122, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36435893

RESUMO

PURPOSE: The effect of preoperative embolization of bone metastases prior to stabilization procedures in reducing intraoperative blood loss remains controversial. This study aimed to analyze the effect of preoperative embolization on orthopedic stabilization procedures of the extremities and spine in cases with bone metastases from renal cell carcinomas. In particular, do these patients suffer less blood loss during the operation and do they need lesser fluid replacements or packed red cell bags intra- and perioperatively? Does preoperative embolization reduce the duration of surgery? METHODS: We retrospectively reviewed stabilization procedures of the spine and extremities at our institution between 2011 and 2021 for group differences (embolization vs. no embolization) in terms of blood loss, fluid substitution, need for packed red cell transfusions, tumor size, and duration of surgery. RESULTS: We reviewed 79 stabilization procedures of the spine (n = 36) and extremities (n = 43), of which 30 included preoperative embolization procedures. Surprisingly, the embolization group showed a statistically significant increase in blood loss, the need for fluid substitution, and red cell transfusions. Subgroup analysis revealed a significant negative effect of preoperative embolization on stabilization procedures of the extremities. CONCLUSION: Based on our data, preoperative embolization of renal cell carcinoma metastases of the extremities had a negative effect on intraoperative blood loss and the need for fluid substitution and should therefore be avoided. Our data did not show an effect on stabilization procedures of the spine.


Assuntos
Neoplasias Ósseas , Carcinoma de Células Renais , Neoplasias Renais , Neoplasias da Coluna Vertebral , Humanos , Perda Sanguínea Cirúrgica/prevenção & controle , Neoplasias Ósseas/cirurgia , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/secundário , Resultado do Tratamento
17.
J Cancer Res Clin Oncol ; 149(9): 5573-5582, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36495329

RESUMO

BACKGROUND: Major demographical changes in Germany commenced in the 1960s. Ongoing humanitarian crises in the Ukraine with subsequent immigration will have also long-range effects on national provision of cancer treatment. Ensuring the best possible outcomes for each cancer patient undergoing radiotherapy requires the prediction and prevention of unfavorable side effects. Given that recent research has primarily focused on clinical outcome indicators solely, less is known regarding sociodemographic predictors of therapeutic outcomes, such as patient nationality. Here, we investigated whether the severity of early side effects after radiotherapy are associated with patient nationality and other sociodemographic and clinical characteristics. METHODS: Out of 9187 patients treated at a German university medical center between 2017 and 2021, 178 German and 178 non-German patients were selected for matched-pair analysis based on diagnostic and demographic criteria. For all 356 patients, data on side effects from follow-up care after radiotherapy were collected. RESULTS: Non-German patients were more likely to have severe side effects than German patients. Side effect severity was also associated with tumor entity, concomitant therapy, body mass index, and age. CONCLUSION: Foreign cancer patients are at higher risk of experiencing severe side effects of radiotherapy, suggesting a need to develop and implement targeted preventive measures for these patients. Further research investigating factors predicting the occurrence of radiotherapy side effects, including other sociodemographic characteristics, is needed to better personalize therapy regimens for cancer.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Neoplasias , Humanos , Etnicidade , Neoplasias/radioterapia , Neoplasias/etiologia , Pacientes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/etiologia , Alemanha/epidemiologia , Radioterapia/efeitos adversos
18.
Oper Orthop Traumatol ; 34(2): 141-152, 2022 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-34870725

RESUMO

OBJECTIVE: Supracondylar distal femoral osteotomy. Fixation with the contralateral TomoFix® (Fa. DePuy Synthes, Oberdorf, Switzerland) lateral distal femur plate. Use of the laterally reversed plate to improve the reconstruction of the sagittal anatomical axis of the leg. INDICATIONS: To correct knee flexion contractures with a deficiency of extension >20° at the age of 10 years. CONTRAINDICATIONS: Surgical site infections or tumors. SURGICAL TECHNIQUE: Ventral closed wedge osteotomy of the distal femur. Implantation of the locking compression TomoFix® lateral distal femur plate. POSTOPERATIVE MANAGEMENT: Full weight bearing. RESULTS: In all, 16 distal femoral osteotomies were performed in 9 patients. All patients had knee flexion contraction due to neurological disease. Patients with cerebral palsy showed a better GMFCS (gross motor function classification scale) level after surgery. Hardware was removed after 11.5 months (range: 9-18 months).


Assuntos
Fêmur , Osteotomia , Placas Ósseas , Criança , Fêmur/cirurgia , Humanos , Articulação do Joelho/cirurgia , Resultado do Tratamento
19.
Am J Clin Oncol ; 45(9): 379-380, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35983966

RESUMO

BACKGROUND AND OBJECTIVES: Pathologic fractures of the extremities due to carcinoma metastases require individual and patient prognosis-related stabilization procedures. Considering the anatomic features of the humerus, implant material stability is less critical than femoral fractures because of less weight-bearing stress. Therefore, operation length, blood loss, and quick recovery of function are of greater interest. In this retrospective cohort study, we evaluated and compared the outcomes of compound plate osteosynthesis and intramedullary (IM) nailing while managing diaphyseal pathologic fractures of the humerus. METHODS: We retrospectively reviewed patients treated at our institution for pathologic fractures of the diaphyseal humerus between 2010 and 2021 for group differences (plate osteosynthesis vs. IM nailing) in terms of blood loss, length of operation, implant survival, and upper extremity function. RESULTS: We reviewed 42 stabilization procedures due to pathologic diaphyseal humerus fractures, with a mean follow-up of 8.5±15.4  months. IM nailing (n=20) showed a significantly lower blood loss (266.7±23.7 mL) than plate osteosynthesis (n=22, 571.1±92.6 mL). We did not detect statistically significant differences in the complication rate, length of operation, or Musculoskeletal Tumor Society score. CONCLUSION: Our findings suggested that diaphyseal fractures of the humerus should be stabilized using an IM nail rather than plate osteosynthesis due to lower blood loss, while complication rate, implant survival, and length of operation remain indifferent.


Assuntos
Fixação Intramedular de Fraturas , Fraturas Espontâneas , Pinos Ortopédicos , Fixação Intramedular de Fraturas/efeitos adversos , Fixação Intramedular de Fraturas/métodos , Fraturas Espontâneas/etiologia , Fraturas Espontâneas/cirurgia , Humanos , Úmero/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
20.
Gait Posture ; 93: 26-31, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35051714

RESUMO

BACKGROUND: Patients with severe haemophilia suffer from bleeding-related joint changes in which the ankle joint is most frequently affected. In the resulting gait changes, the forefoot is involved by reducing the foot pressure. However, it is unclear which changes in foot pressure are present in the individual's foot zones. RESEARCH QUESTION: The aim of the study was to determine whether compensation mechanisms are present in the foot zones regarding the peak pressure under dynamic conditions and to identify possible underlying mechanisms for gait changes. METHODS: In a controlled cross-sectional study, a pedobarography was performed during gait with a standardized speed (3 km/h) in patients with haemophilia (PwH;n = 40) and healthy controls (Con;n = 40). Pressure pain thresholds (PPT) were detected, and Haemophilia Joint Health Score (HJHS) was performed to determine the current joint status. RESULTS: PwH showed a decreased peak pressure in metatarsals II-IV and heel compared to Con. Patients with major-affected ankle joints (determined with the HJHS) showed a decreased single-step length, stride-length and stride-time. Accordingly, the cadence was increased by 10 ± 11 steps/min in PwH compared to Con. Furthermore, PwH showed decreased ankle range of motion (ROM) in HJHS and an altered pain perception due to reduced PPT. SIGNIFICANCE: PwH showed a changed gait pattern in peak pressure compared to Con. A restricted rolling behavior, which might be caused by movement restrictions and pain sensation, leads to reduced pressure in the center forefoot, resulting in a shorter stride-length. Future therapies should focus on maintaining joint mobility for better rolling behavior and improving ankle joints' stability to achieve a balanced load between the midfoot, heel, and forefoot. The use of insoles adapted to our data, based on group differences between PwH and Con, could be supportive in this case.


Assuntos
Hemofilia A , Articulação do Tornozelo , Estudos Transversais , , Marcha , Hemofilia A/complicações , Humanos , Dor
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