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Legal requirements, certification specifications, as well as the demand for real world data on cancer research and treatment led to the decision to establish the University Clinical Cancer Registry Regensburg. The first organizational step in the implementation process of this oncological data registry was the evaluation and acquisition of suitable tumor documentation and database software. For this purpose, an evaluation matrix comprising required database software criteria was designed and consented by a multidisciplinary group of experts. Next, a yearly report of the Institute for Cancer Center Certification (OnkoZert 2019) was considered to identify database software already in use. The identified systems were rated according to the established criteria matrix and other relevant aspects. Onkostar was the system considered most suited for building up an oncological data repository. In the second step, the central IT department implemented Onkostar on-premise and migrated digitally available data after an adaptation and verification process. In parallel, a uniformed process for handling emerging oncological research questions was established. For research requirements, a data analysis concept was established comprising a proposal for data extraction, procedural instructions, and statistical training materials. In the final step, the implemented software and the process for handling research requirements in practice were evaluated by using two exemplary use cases with the focus on clinic-wide analyses and currently relevant scientific topics. A 2-month test phase conducted by various user groups showed a preference for Onkostar tumor documentation software from IT-Choice, mainly because of its adjustability to support research and treatment. Newly added and migrated data can be used for certification and research purposes. This software also provides support in current tumor documentation by displaying the course of cancer disease for individual patients over time. Such oncological data registries can be a powerful tool for legally required cancer registration, the certification of medical centers, as well as for additional oncological research. Tumor databases can be helpful in projects on cancer treatment and scientific aims. The experiences made at the University Hospital Regensburg may be used as a guidance for implementing clinical databases in similar settings with interdisciplinary responsibilities.
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Neoplasias , Programas Informáticos , Humanos , Sistema de Registros , Neoplasias/diagnóstico , Neoplasias/terapiaRESUMEN
BACKGROUND: Semipermeable gloves might be an alternative to cotton gloves in management of hand dermatoses. OBJECTIVES: To compare acceptance and tolerability of gloves made of cotton or a semipermeable Sympatex membrane in patients with hand dermatoses and their effect on skin lesions when worn overnight. METHODS: A total of 199 patients with work-related symmetrical hand dermatoses were asked to wear a cotton glove (COT) on one hand and a Sympatex glove underneath a cotton glove (SYM/COT) on the other hand for 19 consecutive nights. The severity of skin lesions was regularly examined. A questionnaire on acceptance and tolerability was used in a subset of 126 patients. RESULTS: Data on skin lesions were available for 183 participating patients (92%). The severity did not differ substantially between hands covered with SYM/COT or COT over time. Questionnaire data were available for 120 patients (95%). SYM/COT received better ratings regarding climate conditions while COT showed superiority in wearing comfort, practicality and appearance. CONCLUSIONS: Both SYM/COT and COT were well tolerated and accepted in patients with hand dermatoses. Hence, SYM/COT may serve as suitable alternative for COT as comfort gloves supporting therapeutic efforts. The observed slight differences may influence the decision when selecting the glove type.
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Dermatitis Alérgica por Contacto , Dermatosis de la Mano , Dermatitis Alérgica por Contacto/etiología , Guantes Protectores/efectos adversos , Mano , Dermatosis de la Mano/etiología , Humanos , TextilesRESUMEN
BACKGROUND: Penetrating keratoplasty can commonly restore vision in corneal blindness. However, immunological graft reactions may induce irreversible graft failure in a substantial percentage. Repeat keratoplasties in turn are associated with increased risk of graft failure and possibly irreversible blindness. Topical as well as systemic immunosuppressants are administered for prophylaxis. However, severe adverse effects limit long-term usage. By contrast, matching for transplantation antigens might be effective for a long time. METHODS: FANCY is a prospective, controlled, randomised, double-blind, multi-centre clinical trial with two parallel arms. The primary objective is to evaluate superiority of the proposed HLA matching strategy in comparison to random graft assignment with respect to the primary endpoint 'time to first endothelial graft rejection'. Relevant inclusion criteria are age over 18 years and waiting for penetrating or endothelial lamellar keratoplasty. The most important exclusion criteria are abuse of medication and/or drugs and an anticipated waiting time for an HLA match longer than 6 months. After randomisation, patients either receive a HLA-matched graft (experimental intervention) or a random graft (control intervention). The calculated sample size is 620 patients. The trial started in 2009 with a recruitment period of 24 months. A total of 654 patients were included during this time. DISCUSSION: The primary goal of FANCY is to assess whether histocompatibility matching is feasible and effective in the broad clinical routine. However, during the course of the trial, the landscape of keratoplasty changed due to the rise of Descemet Membrane Endothelial Keratoplasty (DMEK). Nowadays, immune reactions are confined mostly to the 'high-risk' subgroups. If we would design FANCY in 2014, we would narrow down the inclusion criteria to include only the high risk patients and accept longer waiting times for a matching donor here. TRIAL REGISTRATION: The unique identifying number of the FANCY trial is NCT00810472.
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Córnea/inmunología , Supervivencia de Injerto/inmunología , Antígenos HLA-A/inmunología , Antígenos HLA-B/inmunología , Cadenas HLA-DRB1/inmunología , Prueba de Histocompatibilidad , Queratoplastia Penetrante , Protocolos Clínicos , Método Doble Ciego , Rechazo de Injerto/inmunología , Rechazo de Injerto/prevención & control , Antígenos de Histocompatibilidad , Humanos , Inmunosupresores/administración & dosificación , Estudios Prospectivos , Proyectos de Investigación , Tolerancia al Trasplante/inmunologíaRESUMEN
OBJECTIVES: The aim of this cross-sectional study was to evaluate the value of prostate-specific antigen (PSA) testing as a tool for early detection of prostate cancer (PCa) applied by general practitioners (GPs) and internal specialists (ISs) as well as to assess criteria leading to the application of PSA-based early PCa detection. METHODS: Between May and December 2012, a questionnaire containing 16 items was sent to 600 GPs and ISs in the federal state Brandenburg and in Berlin (Germany). The independent influence of several criteria on the decision of GPs and ISs to apply PSA-based early PCa detection was assessed by multivariate logistic regression analysis (MLRA). RESULTS: 392 evaluable questionnaires were collected (return rate 65%). 81% of the physicians declared that they apply PSA testing for early PCa detection; of these, 58 and 15% would screen patients until the age of 80 and 90 years, respectively. In case of a pathological PSA level, 77% would immediately refer the patient to a urologist, while 13% would re-assess elevated PSA levels after 3-12 months. Based on MLRA, the following criteria were independently associated with a positive attitude towards PSA-based early PCa detection: specialisation (application of early detection more frequent for GPs and hospital-based ISs) (OR 3.12; p < 0.001), physicians who use exclusively GP or IS education (OR 3.95; p = 0.002), and physicians who recommend yearly PSA assessment after the age of 50 (OR 6.85; p < 0.001). CONCLUSIONS: GPs and ISs frequently apply PSA-based early PCa detection. In doing so, 13% would initiate specific referral to a urologist in case of pathological PSA values too late. Improvement of this situation could possibly result from specific educational activities for non-urological physicians active in fields of urological core capabilities, which should be guided by joint boards of the national associations of urology and general medicine.
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Detección Precoz del Cáncer/métodos , Médicos Generales , Medicina Interna , Calicreínas/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata/sangre , Especialización , Urología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Educación Médica Continua , Médicos Generales/educación , Alemania , Adhesión a Directriz , Humanos , Capacitación en Servicio , Medicina Interna/educación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Valor Predictivo de las Pruebas , Pronóstico , Neoplasias de la Próstata/patología , Derivación y Consulta , Encuestas y Cuestionarios , Urología/educación , Recursos HumanosRESUMEN
Malaria remains one of the highest causes of morbidity and mortality, with 249 million cases and over 608,000 deaths in 2022. Insecticides, which target the Anopheles mosquito vector, are the primary method to control malaria. The widespread nature of resistance to the most important insecticide class, the pyrethroids, threatens the control of this disease. To reverse the stall in malaria control there is urgent need for new vector control tools, which necessitates understanding the molecular basis of pyrethroid resistance. In this study we utilised multi-omics data to identify uridine-diphosphate (UDP)-glycosyltransferases (UGTs) potentially involved in resistance across multiple Anopheles species. Phylogenetic analysis identifies sequence similarities between Anopheline UGTs and those involved in agricultural pesticide resistance to pyrethroids, pyrroles and spinosyns. Expression of five UGTs was characterised in An. gambiae and An. coluzzii to determine constitutive over-expression, induction, and tissue specificity. Furthermore, a UGT inhibitor, sulfinpyrazone, restored susceptibility to pyrethroids and DDT in An. gambiae, An. coluzzii, An. arabiensis and An. funestus, the major African malaria vectors. Taken together, this study provides clear association of UGTs with pyrethroid resistance as well as highlighting the potential use of sulfinpyrazone as a novel synergist for vector control.
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Anopheles , Resistencia a los Insecticidas , Insecticidas , Malaria , Mosquitos Vectores , Animales , Anopheles/genética , Anopheles/efectos de los fármacos , Anopheles/enzimología , Resistencia a los Insecticidas/genética , Mosquitos Vectores/genética , Mosquitos Vectores/efectos de los fármacos , Mosquitos Vectores/enzimología , Insecticidas/farmacología , Malaria/transmisión , Filogenia , Glicosiltransferasas/genética , Glicosiltransferasas/metabolismo , Piretrinas/farmacología , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismoRESUMEN
BACKGROUND: There are few adequate randomized clinical trials directly comparing the therapeutic options of primary laryngectomy (pLE) vs. primary radio(system)therapy (pR(S)T) in patients with locally advanced laryngeal and hypopharyngeal carcinoma and thus little clear scientific evidence to decide which patients will benefit most from which procedure. AIMS/OBJECTIVES: Aim was to compare survival between the therapeutic options and to learn from the limitations of this study, especially in the context of improved clinical assessment. MATERIAL AND METHODS: The clinical data of patients treated between January 2010 and February 2022 were obtained from the electronic database of the University Hospital Regensburg. Overall survival (OS) and progression-free survival (PFS) were compared between the treatment groups. RESULTS: The study included 193 patients (pLE n = 68, pR(S)T, n = 125). Median OS was 31.2 months and median PFS was 24.7 months with no significant difference between the treatment groups (p > .050). Patients who did not receive complete treatment as recommended by the tumor conference (n = 47, 24.4%) had a higher risk of death (p = .024). CONCLUSIONS AND SIGNIFICANCE: The results of our study are consistent with the survival data reported in the literature. More detailed systematic data in clinical routine (e.g. relevant comorbidities) are required to ensure guideline-based recommended therapy.
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Neoplasias Hipofaríngeas , Neoplasias Laríngeas , Laringectomía , Humanos , Laringectomía/métodos , Neoplasias Hipofaríngeas/terapia , Neoplasias Hipofaríngeas/mortalidad , Neoplasias Hipofaríngeas/patología , Neoplasias Hipofaríngeas/cirugía , Masculino , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/terapia , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/cirugía , Persona de Mediana Edad , Femenino , Anciano , Sistema de Registros , Adulto , Estudios Retrospectivos , Anciano de 80 o más AñosRESUMEN
The widespread adoption of renewable energy hinges on the efficient transportation of hydrogen. Reciprocating piston compressor technology in non-lubricated operation will play a key role, ensuring high flow rates and compression ratios. These systems rely on advanced high-strength sealing solutions for piston and rod packing rings utilizing advanced fiber-reinforced polymers. Polyphenylene sulfide (PPS) polymer matrix composites have seen use in tribological applications and promise high mechanical strength and wear resistance. The presented work describes carbon and glass fiber-reinforced PPS matrix polymers in comparison, which are characterized by complementary methods to investigate their properties and potential for application in reciprocating compressor under non-lubricated operation. Thermo-mechanical and tribological testing was supported by microstructure analysis utilizing advanced X-ray and electron imaging techniques. New insights in micromechanical deformation behavior in regard to fiber materials, interface strength and orientation in fiber-reinforced polymers are given. Conclusions on the suitability of different PPS matrix composites for high-pressure hydrogen compression applications were obtained.
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BACKGROUND: While health data sharing for research purposes is strongly supported in principle, it can be challenging to implement in practice. Little is known about the actual bottlenecks to health data sharing in Switzerland. AIMS OF THE STUDY: This study aimed to assess the obstacles to Swiss health data sharing, including legal, ethical and logistical bottlenecks. METHODS: We identified 37 key stakeholders in data sharing via the Swiss Personalised Health Network ecosystem, defined as being an expert on sharing sensitive health data for research purposes at a Swiss university hospital (or a Swiss disease cohort) or being a stakeholder in data sharing at a public or private institution that uses such data. We conducted semi-structured interviews, which were transcribed, translated when necessary, and de-identified. The entire research team discussed the transcripts and notes taken during each interview before an inductive coding process occurred. RESULTS: Eleven semi-structured interviews were conducted (primarily in English) with 17 individuals representing lawyers, data protection officers, ethics committee members, scientists, project managers, bioinformaticians, clinical trials unit members, and biobank stakeholders. Most respondents felt that it was not the actual data transfer that was the bottleneck but rather the processes and systems around it, which were considered time-intensive and confusing. The templates developed by the Swiss Personalised Health Network and the Swiss General Consent process were generally felt to have streamlined processes significantly. However, these logistics and data quality issues remain practical bottlenecks in Swiss health data sharing. Areas of legal uncertainty include privacy laws when sharing data internationally, questions of "who owns the data", inconsistencies created because the Swiss general consent is perceived as being implemented differently across different institutions, and definitions and operationalisation of anonymisation and pseudo-anonymisation. Many participants desired to create a "culture of data sharing" and to recognise that data sharing is a process with many steps, not an event, that requires sustainability efforts and personnel. Some participants also stressed a desire to move away from data sharing and the current privacy focus towards processes that facilitate data access. CONCLUSIONS: Facilitating a data access culture in Switzerland may require legal clarifications, further education about the process and resources to support data sharing, and further investment in sustainable infrastructureby funders and institutions.
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Privacidad , Humanos , Difusión de la Información , Investigación Cualitativa , SuizaRESUMEN
PURPOSE: Providing patient access to precision oncology (PO) is a major challenge of clinical oncologists. Here, we provide an easily transferable model from strategic management science to assess the outreach of a cancer center. METHODS: As members of the German WERA alliance, the cancer centers in Würzburg, Erlangen, Regensburg and Augsburg merged care data regarding their geographical impact. Specifically, we examined the provenance of patients from WERA´s molecular tumor boards (MTBs) between 2020 and 2022 (n = 2243). As second dimension, we added the provenance of patients receiving general cancer care by WERA. Clustering our catchment area along these two dimensions set up a four-quadrant matrix consisting of postal code areas with referrals towards WERA. These areas were re-identified on a map of the Federal State of Bavaria. RESULTS: The WERA matrix overlooked an active screening area of 821 postal code areas - representing about 50 % of Bavaria´s spatial expansion and more than six million inhabitants. The WERA matrix identified regions successfully connected to our outreach structures in terms of subsidiarity - with general cancer care mainly performed locally but PO performed in collaboration with WERA. We also detected postal code areas with a potential PO backlog - characterized by high levels of cancer care performed by WERA and low levels or no MTB representation. CONCLUSIONS: The WERA matrix provided a transparent portfolio of postal code areas, which helped assessing the geographical impact of our PO program. We believe that its intuitive principle can easily be transferred to other cancer centers.
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Accesibilidad a los Servicios de Salud , Oncología Médica , Neoplasias , Medicina de Precisión , Humanos , Alemania , Accesibilidad a los Servicios de Salud/organización & administración , Neoplasias/terapia , Oncología Médica/organización & administración , Instituciones Oncológicas/organización & administración , Población RuralRESUMEN
PURPOSE: Given the concerns about the effects of the COVID-19 pandemic on cancer care, we analyzed the treatment quality of the head and neck cancer center Regensburg before and throughout 2 years of the pandemic. We included data of 3 years to reflect the extended pandemic period as new developments continued to influence its course. METHODS: This retrospective review included all patients diagnosed with head and neck cancer in 2019, 2020, and 2021 who had not started treatment elsewhere prior to being referred to the head and neck cancer center. We compared tumor characteristics and times to therapy of patients diagnosed before COVID-19 in 2019 (n = 253), during COVID-19 in 2020 (n = 206), and in a phase of partial normalization in a persistent pandemic situation in 2021 (n = 247). RESULTS: Our data revealed no decrease in diagnoses or drift in stages toward more advanced stages. There was an increased percentage of diagnoses confirmed at the head and neck cancer center from 2019 (57.3%) to 2020 (68.0%) and to 2021 (65.6%) compared to confirmation at other institutions (2019, 42.7%; 2020, 32.0%; 2021, 34.4%; P = 0.041). Surgery and radiotherapy were performed with the same frequency. The median days between diagnosis and surgery were decreased in 2020 (19.5 days; P = 0.049) and 2021 (20.0 days; P = 0.026) in comparison to 2019 (23 days). The days to radiotherapy were not affected. CONCLUSION: The data indicate a consistent oncological performance for head and neck cancer patients in all waves of the pandemic and thereafter without a decrease in diagnoses or shift in stages.
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COVID-19 , Neoplasias de Cabeza y Cuello , Humanos , COVID-19/epidemiología , Pandemias , Neoplasias de Cabeza y Cuello/epidemiología , Neoplasias de Cabeza y Cuello/terapia , Oncología Médica , Estudios RetrospectivosRESUMEN
Introduction: Ensuring that the health data infrastructure and governance permits an efficient secondary use of data for research is a policy priority for many countries. Switzerland is no exception and many initiatives have been launched to improve its health data landscape. The country now stands at an important crossroad, debating the right way forward. We aimed to explore which specific elements of data governance can facilitate - from ethico-legal and socio-cultural perspectives - the sharing and reuse of data for research purposes in Switzerland. Methods: A modified Delphi methodology was used to collect and structure input from a panel of experts via successive rounds of mediated interaction on the topic of health data governance in Switzerland. Results: First, we suggested techniques to facilitate data sharing practices, especially when data are shared between researchers or from healthcare institutions to researchers. Second, we identified ways to improve the interaction between data protection law and the reuse of data for research, and the ways of implementing informed consent in this context. Third, we put forth ideas on policy changes, such as the steps necessary to improve coordination between different actors of the data landscape and to win the defensive and risk-adverse attitudes widespread when it comes to health data. Conclusions: After having engaged with these topics, we highlighted the importance of focusing on non-technical aspects to improve the data-readiness of a country (e.g., attitudes of stakeholders involved) and of having a pro-active debate between the different institutional actors, ethico-legal experts and society at large.
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Composite filament co-extrusion (CFC) additive manufacturing (AM) is a bi-matrix rapid fabrication technique that is used to produce highly customisable composite parts. By this method, pre-cured, thermoset-based composite carbon fibre (CCF) is simultaneously extruded along with thermoplastic (TP) binding melt as the matrix. Like additive manufacturing, CFC technology also has inherent challenges which include voids, defects and a reduction in CCF's volume in the fabricated parts. Nevertheless, CFC AM is an emerging composite processing technology, a highly customisable and user-oriented manufacturing unit. A new TP-based composites processing technique has the potential to be synergised with conventional processing techniques such as injection moulding to produce lightweight composite parts. Thus, CFC AM can be a credible technology to replace unsustainable subtractive manufacturing, if only the defects are minimised and processing reliability is achieved. The main objective of this research is to investigate and reduce internal voids and defects by utilising compression pressing as a rapid consolidation post-processing technique. Post-processing techniques are known to reduce the internal voids in AM-manufactured parts, depending on the TP matrices. Accordingly, the rapid consolidated neat polylactic acid (PLA) TP matrix showed the highest reduction in internal voids, approximately 92%. The PLA and polyamide 6 (PA6) binding matrix were reinforced with short carbon fibre (SCF) and long carbon fibre (LCF), respectively, to compensate for the CCF's fibre volume reduction. An increase in tensile strength (ca. 12%) and modulus (ca. 30%) was observed in SCF-filled PLA. Furthermore, an approximately 53% increase in tensile strength and a 76% increase in modulus for LCF-reinforced PA6 as the binding matrix was observed. Similar trends were observed in CFC and rapidly consolidated CFC specimens' flexural properties, resulting due to reduced internal voids.
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BACKGROUND: In the past, xerostomia was considered one of the most important determining factors of quality of life (QoL) after radiotherapy (RT) of the head and neck region. In addition, more recent studies have shown that RT-induced dysphagia has an essential influence on the QoL. PATIENTS AND METHODS: Between September 2005 and August 2007, 35 patients with locally advanced squamous cell carcinoma of the head and neck region were included in the prospective study. Patients were treated by IMAT (intensity-modulated arc therapy) or IMRT (intensity-modulated radiotherapy) planned on 3D imaging. A total of 28 patients (80%) received concomitant chemotherapy. The evaluation of QoL (EORTC QLQ-C30, H&N C-35) and toxicities (CTC 2.0) were assessed at the beginning of, during, and after RT as well as up to 12 months after the end of therapy. RESULTS: At the end of therapy, 86% of the patients experienced difficulties in swallowing (62% CTC II-III°). Twelve months after the end of treatment, 15% still suffered from dysphagia CTC II-III°. Concomitant chemotherapy exacerbated the incidence and gravity of dysphagia, resulting in increasing dietary problems. QoL (EORTC) was significantly affected by dysphagia. In particular, the global state of health and QoL were influenced at the end of treatment (p=0.033) and at a later stage (p=0.050). CONCLUSION: The findings of this study suggest that more emphasis should be placed on structured clinical diagnostics, therapy, and rehabilitation of deglutition problems. This means in particular to not only spare the parotids while planning the irradiation, but also to take into consideration the important structures for deglutition, like the retropharyngeal muscles.
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Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Trastornos de Deglución/psicología , Neoplasias de Oído, Nariz y Garganta/tratamiento farmacológico , Neoplasias de Oído, Nariz y Garganta/radioterapia , Calidad de Vida/psicología , Traumatismos por Radiación/psicología , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/psicología , Quimioradioterapia Adyuvante/efectos adversos , Trastornos de Deglución/rehabilitación , Estudios de Seguimiento , Humanos , Imagenología Tridimensional , Estadificación de Neoplasias , Neoplasias de Oído, Nariz y Garganta/patología , Neoplasias de Oído, Nariz y Garganta/psicología , Estudios Prospectivos , Traumatismos por Radiación/rehabilitación , Dosificación Radioterapéutica , Planificación de la Radioterapia Asistida por Computador , Radioterapia de Intensidad Modulada , Encuestas y CuestionariosRESUMEN
BACKGROUND: According to the Swiss Law on Research in Humans, the reuse of routinely collected genetic and non-genetic data and samples from patients for research purposes requires the consent of patients. Unfortunately, the so far established paper-based processes are intrinsically linked to the hospital admission process, labour intensive and not yielding the targeted return rates. Therefore, the overall goal of the presented SPHN project is to increase patient reach by providing hospitals with a patient-centric, user-friendly and admission-independent electronic general consent pathway. As part of the project, feasibility of different digital pathways was evaluated in a usability testing. METHODS: Based on a nationwide harmonised template, a mobile centric progressive web application was developed by the Department of Clinical Research Basel. Usability of the application and according user journeys were evaluated at all partner hospitals. Two options of giving consent were explored using 1) patients' smartphones without any involvement of hospital personnel and 2) a hospital device (tablet) with explicit confirmation of patient identity by hospital personnel. Participant signatures were captured as a picture of a handwritten signature on paper taken with the camera of the smartphone or tablet. Usability issues and feedback of participants were documented directly after usability testing. RESULTS: In total, 122 users agreed to participate in the usability testing using a tablet or smartphone. The general consent request workflow on the smartphone or tablet was regarded as user friendly and easy to navigate by 96% of all participants. However, capturing a picture of a handwritten signature resulted in usability issues in multiple cases, i.e. due to missing pen or paper. CONCLUSION: Usability testing of our prototype application showed a broad acceptance of participants regarding the use of mobile electronic devices to give general consent. Therefore, we believe that easy-to-use digital general consent processes provide effective means to increase the patient pool for health-related research. Further discussions with legislative bodies are required to find patient centric, feasible and legally acceptable solutions in the specific case of electronic general consent for the near future.
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Interfaz Usuario-Computador , Electrónica , Humanos , Consentimiento Informado , Aplicaciones Móviles , Teléfono InteligenteRESUMEN
Hepatocyte growth factor (HGF) is a multifunctional growth factor affecting cell proliferation and differentiation. Due to its mitogenic potential, HGF plays an important role in tubular repair and regeneration after acute renal injury. However, recent reports have shown that HGF also acts as an anti-inflammatory and anti-fibrotic factor, affecting various cell types such as renal fibroblasts and triggering tubulointerstitial fibrosis of the kidney. The present study provides evidence that HGF stimulation of renal fibroblasts results in the activation of both the Erk1/2 and the Akt pathways. As previously shown, Erk1/2 phosphorylation results in Smad-linker phosphorylation, thereby antagonizing cellular signals induced by TGFbeta. By siRNA mediated silencing of the Erk1/2-Smad linkage, however, we now demonstrate that Akt signaling acts as an auxiliary pathway responsible for the anti-fibrotic effects of HGF. In order to define the anti-fibrotic function of HGF we performed comprehensive expression profiling of HGF-stimulated renal fibroblasts by microarray hybridization. Functional cluster analyses and quantitative PCR assays indicate that the HGF-stimulated pathways transfer the anti-fibrotic effects in renal interstitial fibroblasts by reducing expression of extracellular matrix proteins, various chemokines, and members of the CCN family.
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Fibroblastos/metabolismo , Regulación de la Expresión Génica , Factor de Crecimiento de Hepatocito/fisiología , Riñón/metabolismo , Animales , Proteínas CCN de Señalización Intercelular/genética , Colágeno Tipo I/genética , Fibroblastos/efectos de los fármacos , Fibroblastos/patología , Fibrosis , Perfilación de la Expresión Génica , Factor de Crecimiento de Hepatocito/genética , Factor de Crecimiento de Hepatocito/farmacología , Humanos , Riñón/efectos de los fármacos , Riñón/patología , Metaloproteinasas de la Matriz/genética , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Conejos , Transducción de Señal/genética , Proteínas Smad/genéticaRESUMEN
Myofibroblasts are the main cell types producing extracellular matrix proteins in a variety of fibrotic diseases. Therefore, they are useful targets for studies of intracellular communication and gene therapeutical approaches in scarring diseases. An artificial promoter containing the -702 bp regulatory sequence of the alpha-smooth muscle actin (SMA) gene linked to the first intron enhancer sequence of the beta-actin gene and the beta-globin intron-exon junction was constructed and tested for myofibroblast-dependent gene expression using the green fluorescent protein as a reporter. Reporter expression revealed myofibroblast-specific function in hepatic and renal myofibroblasts, in vitro. In addition, differentiation-dependent activation of the SMA-beta-actin promoter hybrid was shown after induction of myofibroblastic features in mesangial cells by stretching treatment. Furthermore, wound healing experiments with SMA-beta-actin promoter reporter mice demonstrated myofibroblast-specific action, in vivo. In conclusion, the -702 bp regulatory region of the SMA promoter linked to enhancing beta-actin and beta-globin sequences benefits from its small size and is suggested as a promising tool to target myofibroblasts as the crucial cell type in various scarring processes.
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Actinas/genética , Actinas/metabolismo , Modelos Animales de Enfermedad , Fibrosis/genética , Fibrosis/metabolismo , Marcación de Gen/métodos , Mioblastos/metabolismo , Animales , Línea Celular , Ratones , Ratones Transgénicos , Regiones Promotoras Genéticas/genética , Ingeniería de Proteínas/métodos , Transfección/métodosRESUMEN
PURPOSE: This study was aimed to determine the impact of bioregenerative operations in case of degenerative cartilage lesions within the media knee compartment. MATERIAL AND METHODS: The CartilageRegistry DGOU was founded in 2013. At the deadline August 2016 a total of 1847 patients were included. A total of 23.3% (n = 432) was suffering from a degenerative cartilage lesion in the medial compartment. Follow-up was performed after 6, 12, and 24 months (online evaluation). The patients were asked for their subject feeling as well as the KOOS (Knee injury and Osteoarthritis Outcome Score) was determined. RESULTS: Most of the patients (n = 358) suffered from a single femoral lesion. In 25 cases single tibial and in 49 cases combined defects ("kissing lesions") were addressed by different treatment options: 39.9% autologous chondrocyte transplantation, in 8.1% in combination with a spongiosa plasty. Other treatments were drilling, microfracturing with or without matrix. In 17.9% the surgeons had chosen combined methods. The bioregenerative treatment was combined with a concomitant operation in 39.7% in patients with medial, in 56.0% in patients with a tibial, and in 67.9% in patients with combined defects. The mostly performed additional operations were osteotomies. There were no gender differences at baseline or during follow-up. The history of patients with femoral defects was shorter than in the other groups. The patients with medial defects judged the subjective outcome significant more frequently better after 6, 12, or 24 months compared with the other groups. The KOOS raised from baseline (median 52 points) to a median of 75 after 6, to 78 points after 12, and to 80 points after 24 months. Patients with femoral defects had a better KOOS-outcome in tendency. Revision operations were required in 7.1%. CONCLUSIONS: The treatment of degenerative cartilage lesions (respective early OA) by bioregenerative procedures are well-established measures. These treatments are sufficient to produce high patients' satisfaction and acceptable short/midterm results.
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Enfermedades de los Cartílagos/cirugía , Cartílago Articular/cirugía , Articulación de la Rodilla/cirugía , Osteoartritis de la Rodilla/cirugía , Adolescente , Adulto , Anciano , Enfermedades de los Cartílagos/fisiopatología , Cartílago Articular/patología , Cartílago Articular/fisiología , Femenino , Fémur/fisiopatología , Fémur/cirugía , Humanos , Articulación de la Rodilla/patología , Articulación de la Rodilla/fisiología , Masculino , Persona de Mediana Edad , Osteoartritis de la Rodilla/fisiopatología , Regeneración , Sistema de Registros , Tibia/fisiopatología , Tibia/cirugía , Adulto JovenRESUMEN
BACKGROUND: The need for documentation in cartilage defects is as obvious as in other medical specialties. Cartilage defects can cause significant pain, and lead to reduced quality of life and loss of function of the affected joint. The risk of developing osteoarthritis is high. Therefore, the socioeconomic burden of cartilage defects should not be underestimated. OBJECTIVE: The objective of our study was to implement and maintain a registry of all patients undergoing surgical treatment of cartilage defects. METHODS: We designed this multicenter registry for adults whose cartilage defects of a knee, ankle, or hip joint are treated surgically. The registry consists of two parts: one for the physician and one for the patient. Data for both parts will be gathered at baseline and at 6-, 12-, 24-, 36-, 60-, and 120-month follow-ups. RESULTS: To date, a wide range of German, Swiss, and Austrian trial sites are taking part in the German Cartilage Registry, soon to be followed by further sites. More than 2124 (as of January 31, 2016) cases are already documented and the first publications have been released. CONCLUSIONS: The German Cartilage Registry addresses fundamental issues regarding the current medical care situation of patients with cartilage defects of knee, ankle, and hip joints. In addition, the registry will help to identify various procedure-specific complications, along with putative advantages and disadvantages of different chondrocyte products. It provides an expanding large-scale, unselected, standardized database for cost and care research for further retrospective studies. TRIAL REGISTRATION: German Clinical Trials Register: DRKS00005617; https://drks-neu.uniklinik-freiburg.de/ drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00005617 (Archived by WebCite at http://www.webcitation.org/6hbFqSws0).
RESUMEN
INTRODUCTION: Optic neuritis leads to degeneration of retinal ganglion cells whose axons form the optic nerve. The standard treatment is a methylprednisolone pulse therapy. This treatment slightly shortens the time of recovery but does not prevent neurodegeneration and persistent visual impairment. In a phase II trial performed in preparation of this study, we have shown that erythropoietin protects global retinal nerve fibre layer thickness (RNFLT-G) in acute optic neuritis; however, the preparatory trial was not powered to show effects on visual function. METHODS AND ANALYSIS: Treatment of Optic Neuritis with Erythropoietin (TONE) is a national, randomised, double-blind, placebo-controlled, multicentre trial with two parallel arms. The primary objective is to determine the efficacy of erythropoietin compared to placebo given add-on to methylprednisolone as assessed by measurements of RNFLT-G and low-contrast visual acuity in the affected eye 6 months after randomisation. Inclusion criteria are a first episode of optic neuritis with decreased visual acuity to ≤ 0.5 (decimal system) and an onset of symptoms within 10 days prior to inclusion. The most important exclusion criteria are history of optic neuritis or multiple sclerosis or any ocular disease (affected or non-affected eye), significant hyperopia, myopia or astigmatism, elevated blood pressure, thrombotic events or malignancy. After randomisation, patients either receive 33,000 international units human recombinant erythropoietin intravenously for 3 consecutive days or placebo (0.9% saline) administered intravenously. With an estimated power of 80%, the calculated sample size is 100 patients. The trial started in September 2014 with a planned recruitment period of 30 months. ETHICS AND DISSEMINATION: TONE has been approved by the Central Ethics Commission in Freiburg (194/14) and the German Federal Institute for Drugs and Medical Devices (61-3910-4039831). It complies with the Declaration of Helsinki, local laws and ICH-GCP. TRIAL REGISTRATION NUMBER: NCT01962571.
Asunto(s)
Protocolos Clínicos , Eritropoyetina/administración & dosificación , Neuritis Óptica/tratamiento farmacológico , Retina/fisiopatología , Agudeza Visual , Adolescente , Adulto , Método Doble Ciego , Eritropoyetina/efectos adversos , Femenino , Alemania , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Resultado del Tratamiento , Adulto JovenRESUMEN
Reduction kinetics of cytochrome f, plastocyanin (PC) and P(700) ('high-potential chain') in thylakoids from spinach were followed after pre-oxidation by a saturating light pulse. We describe a novel approach to follow PC redox kinetics from deconvolution of 810-860 nm absorption changes. The equilibration between the redox-components was analyzed by plotting the redox state of cytochrome f and PC against that of P(700). In thylakoids with (1) diminished electron transport rate (adjusted with a cytochrome bf inhibitor) or (2) de-stacked grana, cytochrome f and PC relaxed close to their thermodynamic equilibriums with P(700). In stacked thylakoids with non-inhibited electron transport, the equilibration plots were complex and non-hyperbolic, suggesting that during fast electron flux, the 'high-potential chain' does not homogeneously equilibrate throughout the membrane. Apparent equilibrium constants <5 were calculated, which are below the thermodynamic equilibrium known for the 'high potential chain'. The disequilibrium found in stacked thylakoids with high electron fluxes is explained by restricted long-range PC diffusion. We develop a model assuming that about 30% of Photosystem I mainly located in grana end-membranes and margins rapidly equilibrate with cytochrome f via short-distance transluminal PC diffusion, while long-range lateral PC migration between grana cores and distant stroma lamellae is restricted. Implications for the electron flux control are discussed.