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1.
Chirurgie (Heidelb) ; 95(7): 539-545, 2024 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-38864879

RESUMO

BACKGROUND: Even now the further training in surgery faces considerable challenges. The planned hospital structural reform will result in new bureaucratic and organizational hurdles, which could lead to a considerable loss of quality in advanced surgical training across all disciplines. OBJECTIVE: The aim of this position paper is to describe the current and future challenges for advanced surgical training and to identify possible approaches and opportunities for the further development against the background of the planned hospital structural reform. MATERIAL AND METHODS: For the development of this position paper a committee of representatives of the Young Forums of the German surgical societies identified and critically discussed current problems and challenges of the present residency training system and formulated a list of demands for a sustainable residency training concept. RESULTS: The planned shift to outpatient treatment and centralization were identified as central challenges for surgical residency training. Surgical training must be considered consistently and from the outset in all political reform efforts. In addition to a transparent and cost-appropriate financing of residency training, we call for the involvement of all German surgical societies in the reform process. Furthermore, the social framework conditions for junior surgeons should be considered. CONCLUSION: The structural change in the hospital landscape in Germany, which is being forced by politicians, harbors the risk of a further loss of quality and experience in surgical treatment and training. At the same time, the planned hospital reform offers a unique opportunity to address existing problems and challenges in surgical training and to consider them as a starting point for structural changes which are fit for the future.


Assuntos
Reforma dos Serviços de Saúde , Internato e Residência , Alemanha , Humanos , Cirurgia Geral/educação , Educação de Pós-Graduação em Medicina , Previsões
2.
Langenbecks Arch Surg ; 409(1): 193, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38900254

RESUMO

BACKGROUND: Emergencies and emergency surgeries are a central part of everyday surgical care in Germany. However, it is unclear how emergency surgery is practically trained in clinics on a daily basis and what training concept is underlying. Therefore, the aim of this survey study was to capture the status quo of emergency surgical training of German general and visceral surgeons. METHODS: The members of the German Society for General and Visceral Surgery were surveyed online (n = 5281). The questionnaire included demographic data and expertise in surgery and assistance in emergency surgery regarding common emergency surgical operations. In addition, further training measures in emergency surgery and their support by employers were queried. RESULTS: Only complete questionnaires (n = 184, response rate 3.5%) were included in the analysis. Most participants were in training (n = 69; 38%), followed by senior physicians (n = 52; 29%), specialists (n = 31; 17%) and chief physicians (n = 30; 17%). 64% of the participants were employed at university hospitals or maximum care hospitals. Regarding further training opportunities, in-clinic shock room training was most frequently used. Outside of their own clinic, the ATLS course was most frequently mentioned. Operations for cholecystitis and appendicitis as well as emergency stoma procedures are the most common emergency procedures. There was a strong difference in the frequency of operated cases depending on the level of training. For operations to treat acute abdominal traumas (hemostasis of liver and spleen, packing) as well as outside of visceral surgery, only low competence was reported. Over 90% of survey participants consider emergency surgery to be an indispensable core competence. Neither in the old (76%) nor in the new training regulations (47%) is emergency surgery adequately represented according to the participants' assessment. There was a significantly lower prevalence of the "sub-steps concept" in emergency surgery at 38% compared to elective surgery (44%). Important elements of imparting skills in emergency surgery are simulation and courses as well as operative sub-steps, according to the majority of survey participants. CONCLUSION: The results show that general and visceral surgeons in Germany are introduced to emergency surgery too little structured during further training and at specialist level. The survey participants had, as expected, hardly any experience in emergency surgery outside of visceral surgery but surprisingly also little experience in visceral surgical trauma care. There is a need to discuss the future organization of emergency surgical training. Adequate simulation structures and extracurricular courses could contribute to an improvement in this respect.


Assuntos
Competência Clínica , Humanos , Alemanha , Inquéritos e Questionários , Feminino , Masculino , Adulto , Emergências , Pessoa de Meia-Idade , Cirurgia Geral/educação
3.
Nat Med ; 30(6): 1622-1635, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38760585

RESUMO

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is limited. We present an epigenetically defined neural signature of glioblastoma that independently predicts patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals a high abundance of malignant stemcell-like cells in high-neural glioblastoma, primarily of the neural lineage. These cells are further classified as neural-progenitor-cell-like, astrocyte-like and oligodendrocyte-progenitor-like, alongside oligodendrocytes and excitatory neurons. In line with these findings, high-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature is associated with decreased overall and progression-free survival. High-neural tumors also exhibit increased functional connectivity in magnetencephalography and resting-state magnet resonance imaging and can be detected via DNA analytes and brain-derived neurotrophic factor in patients' plasma. The prognostic importance of the neural signature was further validated in patients diagnosed with diffuse midline glioma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant. High-neural gliomas likely require a maximized surgical resection approach for improved outcomes.


Assuntos
Neoplasias Encefálicas , Epigênese Genética , Glioma , Humanos , Prognóstico , Glioma/genética , Glioma/patologia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Metilação de DNA/genética , Animais , Camundongos , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Glioblastoma/genética , Glioblastoma/patologia , Pessoa de Meia-Idade , Neurônios/patologia , Neurônios/metabolismo , Adulto , Análise de Célula Única , Linhagem Celular Tumoral , Transcriptoma , Gradação de Tumores
4.
Chirurgie (Heidelb) ; 95(7): 563-577, 2024 Jul.
Artigo em Alemão | MEDLINE | ID: mdl-38671250

RESUMO

BACKGROUND: The new competency-based further training regulations (nWBO) for surgical training have been adopted by all German state medical associations. METHODS: From May to June 2023 the Young Surgeons' Working Group (CAJC) conducted an anonymous online survey among the 5896 members of the German Society for General and Visceral Surgery (DGAV). OBJECTIVE: The survey aimed to assess expectations regarding the nWBO and to develop strategies for enhancing surgical training. RESULTS: With 488 participants (response rate 8.3%) the study is representative. The respondents consisted of 107 continuing education assistants (WBA 21.9%), 69 specialist physicians, and 188 senior physicians (specialist physicians 14.1% and senior physicians 38.5%), as well as 107 chief physicians (21.9%). The majority worked in regular care providers (44%), followed by maximum care providers (26.8%) and university clinics (20.1%). Only 22% considered the required operative spectrum of the new medical specialist training regulations (nWBO) to be realistic. Half of the respondents believed that full training in their clinic according to the new catalog will no longer be possible and 54.6% considered achieving the target numbers in 6 years to be impossible or state that they can no longer train the same number of continuing education assistants (WBAs) in the same time frame. Endoscopy (17.1-18.8%), fundoplication (15.4-17.7%) and head and neck procedures (12.1-17.1%) were consistently mentioned as bottlenecks across all levels of care. Rotations for balance were reported to be already established or not necessary in 64.7%. In 48% it was stated that the department had established the partial steps concept. The importance of a structured training concept was considered important by 85% of WBAs, compared to 53.3% of chief physicians (CÄ). If a structured training concept was present in the department, the achievability of the target numbers was significantly assessed more positively in the univariate analysis. In the multivariate analysis, male gender and the status of "habilitated/professor" were independent factors for a more positive assessment of the nWBO. Objective certification of training was considered important by 51.5%. CONCLUSION: Concerns surround the nWBO and the sentiment is pessimistic. Additional requirements and hospital reforms could exacerbate the situation. Collaboration and rotations are crucial but still insufficiently implemented. Quality-oriented certification could enhance the quality of training.


Assuntos
Educação Médica Continuada , Humanos , Inquéritos e Questionários , Alemanha , Masculino , Feminino , Adulto , Competência Clínica/legislação & jurisprudência , Sociedades Médicas , Cirurgia Geral/educação , Cirurgiões/educação , Pessoa de Meia-Idade
5.
Int J Mol Sci ; 25(6)2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38542491

RESUMO

Effective management of glomerular kidney disease, one of the main categories of chronic kidney disease (CKD), requires accurate diagnosis, prognosis of progression, assessment of therapeutic efficacy, and, ideally, prediction of drug response. Multiple biomarkers and algorithms for the assessment of specific aspects of glomerular diseases have been reported in the literature. Though, the vast majority of these have not been implemented in clinical practice or are not available on a global scale due to limited access, missing medical infrastructure, or economical as well as political reasons. The aim of this review is to compile all currently available information on the diagnostic, prognostic, and predictive biomarkers currently available for the management of glomerular diseases, and provide guidance on the application of these biomarkers. As a result of the compiled evidence for the different biomarkers available, we present a decision tree for a non-invasive, biomarker-guided diagnostic path. The data currently available demonstrate that for the large majority of patients with glomerular diseases, valid biomarkers are available. However, despite the obvious disadvantages of kidney biopsy, being invasive and not applicable for monitoring, especially in the context of rare CKD etiologies, kidney biopsy still cannot be replaced by non-invasive strategies.


Assuntos
Rim , Insuficiência Renal Crônica , Humanos , Progressão da Doença , Rim/patologia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/terapia , Insuficiência Renal Crônica/patologia , Glomérulos Renais/patologia , Biomarcadores , Taxa de Filtração Glomerular
6.
Int J Mol Sci ; 25(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38473806

RESUMO

Cisplatin nephrotoxicity is a critical limitation of solid cancer treatment. Until now, the complex interplay of various pathophysiological mechanisms leading to proximal tubular cell apoptosis after cisplatin exposure has not been fully understood. In our study, we assessed the role of the autophagy-related protein BECLIN1 (ATG6) in cisplatin-induced acute renal injury (AKI)-a candidate protein involved in autophagy and with putative impact on apoptosis by harboring a B-cell lymphoma 2 (BCL2) interaction site of unknown significance. By using mice with heterozygous deletion of Becn1, we demonstrate that reduced intracellular content of BECLIN1 does not impact renal function or autophagy within 12 months. However, these mice were significantly sensitized towards cisplatin-induced AKI, and by using Becn1+/-;Sglt2-Cre;Tomato/EGFP mice with subsequent primary cell analysis, we confirmed that nephrotoxicity depends on proximal tubular BECLIN1 content. Mechanistically, BECLIN1 did not impact autophagy or primarily the apoptotic pathway. In fact, a lack of BECLIN1 sensitized mice towards cisplatin-induced ER stress. Accordingly, the ER stress inhibitor tauroursodeoxycholic acid (TUDCA) blunted cisplatin-induced cell death in Becn1 heterozygosity. In conclusion, our data first highlight a novel role of BECLIN1 in protecting against cellular ER stress independent from autophagy. These novel findings open new therapeutic avenues to intervene in this important intracellular stress response pathway with a promising impact on future AKI management.


Assuntos
Injúria Renal Aguda , Cisplatino , Camundongos , Animais , Cisplatino/farmacologia , Proteína Beclina-1/metabolismo , Injúria Renal Aguda/metabolismo , Autofagia , Apoptose
8.
Acta Neuropathol ; 147(1): 21, 2024 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-38244080

RESUMO

The longitudinal transition of phenotypes is pivotal in glioblastoma treatment resistance and DNA methylation emerged as an important tool for classifying glioblastoma phenotypes. We aimed to characterize DNA methylation subclass heterogeneity during progression and assess its clinical impact. Matched tissues from 47 glioblastoma patients were subjected to DNA methylation profiling, including CpG-site alterations, tissue and serum deconvolution, mass spectrometry, and immunoassay. Effects of clinical characteristics on temporal changes and outcomes were studied. Among 47 patients, 8 (17.0%) had non-matching classifications at recurrence. In the remaining 39 cases, 28.2% showed dominant DNA methylation subclass transitions, with 72.7% being a mesenchymal subclass. In general, glioblastomas with a subclass transition showed upregulated metabolic processes. Newly diagnosed glioblastomas with mesenchymal transition displayed increased stem cell-like states and decreased immune components at diagnosis and exhibited elevated immune signatures and cytokine levels in serum. In contrast, tissue of recurrent glioblastomas with mesenchymal transition showed increased immune components but decreased stem cell-like states. Survival analyses revealed comparable outcomes for patients with and without subclass transitions. This study demonstrates a temporal heterogeneity of DNA methylation subclasses in 28.2% of glioblastomas, not impacting patient survival. Changes in cell state composition associated with subclass transition may be crucial for recurrent glioblastoma targeted therapies.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/genética , Glioblastoma/terapia , Metilação de DNA , Recidiva Local de Neoplasia/genética , Análise de Sobrevida
10.
Nephrol Dial Transplant ; 39(3): 453-462, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-37697716

RESUMO

BACKGROUND AND HYPOTHESIS: Specific urinary peptides hold information on disease pathophysiology, which, in combination with artificial intelligence, could enable non-invasive assessment of chronic kidney disease (CKD) aetiology. Existing approaches are generally specific for the diagnosis of single aetiologies. We present the development of models able to simultaneously distinguish and spatially visualize multiple CKD aetiologies. METHODS: The urinary peptide data of 1850 healthy control (HC) and CKD [diabetic kidney disease (DKD), immunoglobulin A nephropathy (IgAN) and vasculitis] participants were extracted from the Human Urinary Proteome Database. Uniform manifold approximation and projection (UMAP) coupled to a support vector machine algorithm was used to generate multi-peptide models to perform binary (DKD, HC) and multiclass (DKD, HC, IgAN, vasculitis) classifications. This pipeline was compared with the current state-of-the-art single-aetiology CKD urinary peptide models. RESULTS: In an independent test set, the developed models achieved 90.35% and 70.13% overall predictive accuracies, respectively, for the binary and the multiclass classifications. Omitting the UMAP step led to improved predictive accuracies (96.14% and 85.06%, respectively). As expected, the HC class was distinguished with the highest accuracy. The different classes displayed a tendency to form distinct clusters in the 3D space based on their disease state. CONCLUSION: Urinary peptide data present an effective basis for CKD aetiology differentiation using machine learning models. Although adding the UMAP step to the models did not improve prediction accuracy, it may provide a unique visualization advantage. Additional studies are warranted to further validate the pipeline's clinical potential as well as to expand it to other CKD aetiologies and also other diseases.


Assuntos
Glomerulonefrite por IGA , Insuficiência Renal Crônica , Vasculite , Humanos , Biomarcadores , Diagnóstico Diferencial , Inteligência Artificial , Glomerulonefrite por IGA/complicações , Biópsia Líquida/efeitos adversos , Peptídeos , Proteômica
11.
RMD Open ; 9(4)2023 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-38101819

RESUMO

OBJECTIVE: Refractory autoimmune diseases remain a significant challenge in clinical practice and new therapeutic options are needed. This systematic review evaluates the existing reported data on the CD38-targeting antibody daratumumab as a new therapeutic approach in autoantibody-mediated autoimmune diseases. METHODS: A protocolised systematic literature review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was performed. Two databases (Medline and Embase) were searched for suitable studies. Usage of daratumumab in non-oncological or non-transplantation associated diseases with autoimmune pathophysiology was analysed including patient characteristics, therapeutic regimen, adverse events and patient outcome. RESULTS: 38 publications reporting the clinical course of 83 patients met the inclusion criteria. Daratumumab usage was reported in therapy-refractory cases (median of 5 different previous therapies) in 24 different autoimmune diseases. The median number of applications of daratumumab was 4, mainly via intravenous applications (87%). Concomitant treatment included glucocorticoids in 64% of patients, intravenous immunoglobulins (33%) and rituximab (17%). Remission or improvement of disease was reported in 81% of patients. Autoantibody depletion or reduction was stated in 52% of patients. Death occurred in three patients (3%). Adverse events were reported in 45% of patients including application-associated reaction (20%), infection (19%) and hypogammaglobulinaemia (33%). CONCLUSION: Targeting CD38 via daratumumab is a new promising therapeutic option in therapy refractory autoimmune diseases. Efficacy as well as optimal therapeutic regimen and management or prevention of adverse events require further investigation. Therefore, systematic clinical trials of this therapeutic approach are needed.


Assuntos
Anticorpos Monoclonais , Doenças Autoimunes , Humanos , Anticorpos Monoclonais/efeitos adversos , Rituximab , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/induzido quimicamente , Autoanticorpos
12.
Ann Transl Med ; 11(10): 346, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37675318

RESUMO

Background: Liver surgery is the standard of care for primary and many secondary liver tumors. Due to variability and complexity in liver anatomy preoperative imaging is necessary to determine resectability and for planning the surgical strategy. In the last few years, computer-assisted resection planning has been introduced in liver surgery. Aim of this trial was the evaluation of computer-assisted three-dimensional (3D)-navigation for liver surgery. Methods: This study was a prospective randomized-controlled pilot trial and patients were randomized in navigated or non-navigated group. Primary end point was the quotient of intraoperative resected volume and planned resection volume. Secondary end points included operation time, resection margin and postoperative complications. 3D reconstructions were performed with MeVis Distant Services (MeVis AG, Bremen, Germany). The navigation system CAS-One Liver (CAScination AG, Bern, Switzerland) was used for intraoperative computer-assisted 3D-navigation. Results: The data of 16 patients with 20 liver tumors were used in this analysis. Of these, 8 liver tumors were resected with the utilization of intraoperative navigation. Two postoperative complications were classified grade IIIa or higher. There was no difference in duration of operation (189 vs. 180 min, P=0.970), rate of postoperative complications (n=1 vs. n=1, P=0.696) and length of hospital stay (9 vs. 7 days, P=0.368) between the two groups. Minimal resection margin (0.15 vs. 0.40 cm, P=0.384) and quotient of planned to intraoperative resection volume (0.94 vs. 1.11, P=0.305) were also similar. Conclusions: Intraoperative navigation is a technology that can be safely used during liver resection. Surgical accuracy is not yet superior to the current standard of intraoperative orientation. Further technological advances with suitable deformation algorithms and augmented reality systems will enable a further improvement of the technical feasibility.

13.
Neurooncol Pract ; 10(5): 462-471, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37720395

RESUMO

Background: 5-aminolevulinic acid (5-ALA) fluorescence-guided resection increases the percentage of complete CNS tumor resections and improves the progression-free survival of IDH-wildtype glioblastoma patients. A small subset of IDH-wildtype glioblastoma shows no 5-ALA fluorescence. An explanation for these cases is missing. In this study, we used DNA methylation profiling to further characterize non-fluorescent glioblastomas. Methods: Patients with newly diagnosed and recurrent IDH-wildtype glioblastoma that underwent surgery were analyzed. The intensity of intraoperative 5-ALA fluorescence was categorized as non-visible or visible. DNA was extracted from tumors and genome-wide DNA methylation patterns were analyzed using Illumina EPIC (850k) arrays. Furthermore, 5-ALA intensity was measured by flow cytometry on human gliomasphere lines (BT112 and BT145). Results: Of 74 included patients, 12 (16.2%) patients had a non-fluorescent glioblastoma, which were compared to 62 glioblastomas with 5-ALA fluorescence. Clinical characteristics were equally distributed between both groups. We did not find significant differences between DNA methylation subclasses and 5-ALA fluorescence (P = .24). The distribution of cells of the tumor microenvironment was not significantly different between the non-fluorescent and fluorescent tumors. Copy number variations in EGFR and simultaneous EGFRvIII expression were strongly associated with 5-ALA fluorescence since all non-fluorescent glioblastomas were EGFR-amplified (P < .01). This finding was also demonstrated in recurrent tumors. Similarly, EGFR-amplified glioblastoma cell lines showed no 5-ALA fluorescence after 24 h of incubation. Conclusions: Our study demonstrates an association between non-fluorescent IDH-wildtype glioblastomas and EGFR gene amplification which should be taken into consideration for recurrent surgery and future studies investigating EGFR-amplified gliomas.

14.
bioRxiv ; 2023 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-37609137

RESUMO

Neural-tumor interactions drive glioma growth as evidenced in preclinical models, but clinical validation is nascent. We present an epigenetically defined neural signature of glioblastoma that independently affects patients' survival. We use reference signatures of neural cells to deconvolve tumor DNA and classify samples into low- or high-neural tumors. High-neural glioblastomas exhibit hypomethylated CpG sites and upregulation of genes associated with synaptic integration. Single-cell transcriptomic analysis reveals high abundance of stem cell-like malignant cells classified as oligodendrocyte precursor and neural precursor cell-like in high-neural glioblastoma. High-neural glioblastoma cells engender neuron-to-glioma synapse formation in vitro and in vivo and show an unfavorable survival after xenografting. In patients, a high-neural signature associates with decreased survival as well as increased functional connectivity and can be detected via DNA analytes and brain-derived neurotrophic factor in plasma. Our study presents an epigenetically defined malignant neural signature in high-grade gliomas that is prognostically relevant.

15.
Kidney Int ; 104(5): 916-928, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37598854

RESUMO

The phospholipase A2 receptor 1 (PLA2R1) is the major target antigen in patients with membranous nephropathy (MN), an antibody-mediated autoimmune glomerular disease. Investigation of MN pathogenesis has been hampered by the lack of reliable animal models. Here, we overcome this issue by generating a transgenic mouse line expressing a chimeric PLA2R1 (chPLA2R1) consisting of three human PLA2R1 domains (cysteine-rich, fibronectin type-II and CTLD1) and seven murine PLA2R1 domains (CTLD2-8) specifically in podocytes. Mice expressing the chPLA2R1 were healthy at birth and showed no major glomerular alterations when compared to mice with a wild-type PLA2R1 status. Upon active immunization with human PLA2R1 (hPLA2R1), chPLA2R1-positive mice developed anti-hPLA2R1 antibodies, a nephrotic syndrome, and all major histological features of MN, including granular deposition of mouse IgG and complement components in immunofluorescence and subepithelial electron-dense deposits and podocyte foot process effacement in electron microscopy. In order to investigate the role of the complement system in this model, we further crossed chPLA2R1-positive mice with mice lacking the central complement component C3 (C3-/- mice). Upon immunization with hPLA2R1, chPLA2R1-positive C3-/- mice had substantially less severe albuminuria and nephrotic syndrome when compared to chPLA2R1-positive mice with a wild-type C3 status. In conclusion, we introduce a novel active immunization model of PLA2R1-associated MN and demonstrate a pathogenic role of the complement system in this model.


Assuntos
Doenças Autoimunes , Glomerulonefrite Membranosa , Síndrome Nefrótica , Humanos , Camundongos , Animais , Receptores da Fosfolipase A2/genética , Autoanticorpos , Camundongos Transgênicos , Vacinação , Complemento C3 , Modelos Animais de Doenças
16.
Nat Commun ; 14(1): 4903, 2023 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-37580326

RESUMO

Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of their functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration and upon exposure to TNFα, a cytokine stressor. Older organoids increase deposition of extracellular matrix but decrease expression of glomerular proteins. Single cell transcriptome integration reveals that most proteome changes localize to podocytes, tubular and stromal cells. TNFα treatment of organoids results in 322 differentially expressed proteins, including cytokines and complement components. Transcript expression of these 322 proteins is significantly higher in individuals with poorer clinical outcomes in proteinuric kidney disease. Key TNFα-associated protein (C3 and VCAM1) expression is increased in both human tubular and organoid kidney cell populations, highlighting the potential for organoids to advance biomarker development. By integrating kidney organoid omic layers, incorporating a disease-relevant cytokine stressor and comparing with human data, we provide crucial evidence for the functional relevance of the kidney organoid model to human kidney disease.


Assuntos
Nefropatias , Fator de Necrose Tumoral alfa , Humanos , Fator de Necrose Tumoral alfa/metabolismo , Proteoma/metabolismo , Rim , Nefropatias/genética , Nefropatias/metabolismo , Organoides/metabolismo
17.
Zentralbl Chir ; 148(4): 337-346, 2023 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-37562395

RESUMO

Practice makes perfect - a saying that everyone has certainly heard. Surgeons of all levels of training can demonstrably practice to some extent on simulators. This training outside the operating theatre and independent of patients makes sense, both ethically and financially. Although the effectiveness of simulation in surgery has been proven several times, simulation training is not a mandatory part of surgical specialist training in Germany. Simulation covers a very wide range in terms of application, effort and costs. This review is intended to give an overview of the systems and their areas of application and the target group. The focus lies on the commonly available systems and possible advantages and disadvantages. Practical skills are in the foreground and all three pillars of general and visceral surgery - conventional techniques, laparoscopy and robotics - are taken into account. However, simulators alone do not achieve cost-benefit effectiveness. The full potential of such an investment can only be exploited with a site-specific, structured training concept in which simulation training according to the post-graduate year and appropriate allocation to surgeries in the operating room are closely interlinked. It should always be possible to train basic skills on site. The significant additional costs for complex simulation systems are possible, depending on the financial resources, or should be purchased in a network or for national courses. The techniques of immersive virtual reality in combination with artificial intelligence and deformation algorithms will certainly play a decisive role for the future of simulation, whereby the use of the available systems must be a primary goal. The integration of simulation into specialist training should be striven for, not least in order to justify the costs.


Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Cirurgia Geral , Laparoscopia , Treinamento por Simulação , Cirurgiões , Humanos , Inteligência Artificial , Simulação por Computador , Laparoscopia/educação , Competência Clínica , Cirurgia Geral/educação
18.
J Cancer Res Clin Oncol ; 149(12): 10075-10084, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37261525

RESUMO

PURPOSE: Modern, personalized treatment concepts in oncology require an interdisciplinary and multiprofessional collaboration. In addition to its relevance in patient care, interdisciplinary collaboration is also becoming increasingly important in clinical research as well as medical education and resident training in oncology. METHODS: Between November 2021 and March 2022, an online survey was conducted among German early career research groups, represented by Young Oncologists United (YOU). The aim was to identify the status and need for interdisciplinarity at clinic, educational, and research levels. RESULTS: A total of 294 participants completed the questionnaire in full. 90.7% of the respondents fully or predominantly agreed with the statement that interdisciplinary work plays a major role in their daily clinical work. 78.9% wished for more interdisciplinary collaboration. Of the 49.7% of participants who have never participated in an interdisciplinary research project, 80.1% said they would like to participate in such a study project in the future. Lack of time resources, too much organizational effort, and possible political conflicts between institutions were identified as factors that make practical implementation difficult. 74.1% declared their willingness to become active in an oncology early career research group. CONCLUSION: Interdisciplinary collaboration has become increasingly important in oncology. Networks that span different disciplines could help to promote interdisciplinary research projects among young scientists and improve exchange in professional practice and education with the implication of improved patient care.


Assuntos
Oncologia , Oncologistas , Humanos , Inquéritos e Questionários
19.
Zentralbl Chir ; 148(5): 415-424, 2023 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-37339662

RESUMO

The requirements and challenges for the university hospitals in Germany are changing. Especially in surgical subjects, it is more and more difficult to adequately serve these three pillars of university medicine - clinic, research and education. This survey was intended to determine the status quo of general and visceral surgery at universities, in order to provide a basis for proposed solutions.For this online survey, 1505 visceral surgeons at the 38 university clinics were contacted. The questionnaire contained 29 questions on the structure of the clinic, scientific motivation, opportunities for time-off and the appreciation of academic achievements. The type and scope of student courses and the preparation for them were also determined. With regard to patient care, the type and number of services and the course of surgical training were examined. Based on the data published on the websites of the individual clinics on the number, gender, position and academic title of the doctors, a demographic analysis of university visceral surgeons could also be created.Of 1505 surgeons successfully contacted, 352 took part in the survey, which corresponds to a response rate of 23.4%. Of the participants, 93.5% were scientifically active, the majority being in the field of clinical data collection. Many indicated that they were also active in translational and/or experimental research, while educational research was rarely named. 45% confirmed that they could perform scientific work during their normal working hours. The reward for this activity was mostly in the form of time-off for congresses and clinical appreciation. Most participants stated that they were involved in 3-4 student courses per week, with 24.4% reporting that they were not adequately prepared for them.The compatibility of the classic three pillars of clinic, research and teaching continues to be of great relevance. There is a high level of motivation among the participating visceral surgeons not to neglect research and teaching, despite increasing economic pressure in the field of patient care. However, arrangements must be created in order to reward and promote commitment in research and teaching in a structured way.

20.
J Am Coll Surg ; 237(2): 292-300, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-37042553

RESUMO

BACKGROUND: We developed an interactive augmented reality tool (HoloPointer) that enables real-time annotation on a laparoscopy monitor for intraoperative guidance. This application operates exclusively via verbal commands and head movements to ensure a sterile workflow. STUDY DESIGN: Purpose of this randomized controlled clinical trial was to evaluate the integration of this new technology into the operating room. This prospective single-center study included 32 elective laparoscopic cholecystectomies (29 surgical teams, 15 trainees, and 13 trainers). The primary objective and assessment measure was the HoloPointer's influence on surgical performance (subjective assessment, global operative assessment of laparoscopic skills [GOALS] and critical view of safety [CVS]). The secondary objectives and outcome variables were its influence on operation time, quality of assistance (5-point Likert scale), and user-friendliness (system usability scale, 0 to 100 points). RESULTS: Gestural corrections were reduced by 59.4% (4.6 SD 8.1 vs 1.9 SD 4.7, p > 0.05) and verbal corrections by 36.1% (17.8 SD 12.9 vs 11.4 SD 8.1, p > 0.05). Subjective surgical performance could be improved by 84.6% of participants. No statistically significant differences were observed for objective parameters GOALS, CVS, and operation time. In the system usability scale, the application achieved an average score of 72.5 SD 16.3 (good user-friendliness). Of the participants, 69.2% wanted to use the HoloPointer more frequently. CONCLUSIONS: The majority of trainees improved their surgical performance using the HoloPointer in elective laparoscopic cholecystectomies, and the rate of classic but potentially misleading corrections was noticeably reduced. The HoloPointer has the potential to improve education in minimally invasive surgery.


Assuntos
Realidade Aumentada , Colecistectomia Laparoscópica , Laparoscopia , Humanos , Estudos Prospectivos , Competência Clínica , Laparoscopia/educação , Colecistectomia Laparoscópica/educação
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