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OBJECTIVE: To conduct a systematic review and meta-analysis of case-control and cohort human studies evaluating metabolite markers identified using high-throughput metabolomics techniques on esophageal cancer (EC), cancer of the gastroesophageal junction (GEJ), and gastric cancer (GC) in blood and tissue. BACKGROUND: Upper gastrointestinal cancers (UGC), predominantly EC, GEJ, and GC, are malignant tumour types with high morbidity and mortality rates. Numerous studies have focused on metabolomic profiling of UGC in recent years. In this systematic review and meta-analysis, we have provided a collective summary of previous findings on metabolites and metabolomic profiling associated with EC, GEJ and GC. METHODS: Following the PRISMA procedure, a systematic search of four databases (Embase, PubMed, MEDLINE, and Web of Science) for molecular epidemiologic studies on the metabolomic profiles of EC, GEJ and GC was conducted and registered at PROSPERO (CRD42023486631). The Newcastle-Ottawa Scale (NOS) was used to benchmark the risk of bias for case-controlled and cohort studies. QUADOMICS, an adaptation of the QUADAS-2 (Quality Assessment of Diagnostic Accuracy) tool, was used to rate diagnostic accuracy studies. Original articles comparing metabolite patterns between patients with and without UGC were included. Two investigators independently completed title and abstract screening, data extraction, and quality evaluation. Meta-analysis was conducted whenever possible. We used a random effects model to investigate the association between metabolite levels and UGC. RESULTS: A total of 66 original studies involving 7267 patients that met the required criteria were included for review. 169 metabolites were differentially distributed in patients with UGC compared to healthy patients among 44 GC, 9 GEJ, and 25 EC studies including metabolites involved in glycolysis, anaerobic respiration, tricarboxylic acid cycle, and lipid metabolism. Phosphatidylcholines, eicosanoids, and adenosine triphosphate were among the most frequently reported lipids and metabolites of cellular respiration, while BCAA, lysine, and asparagine were among the most commonly reported amino acids. Previously identified lipid metabolites included saturated and unsaturated free fatty acids and ketones. However, the key findings across studies have been inconsistent, possibly due to limited sample sizes and the majority being hospital-based case-control analyses lacking an independent replication group. CONCLUSION: Thus far, metabolomic studies have provided new opportunities for screening, etiological factors, and biomarkers for UGC, supporting the potential of applying metabolomic profiling in early cancer diagnosis. According to the results of our meta-analysis especially BCAA and TMAO as well as certain phosphatidylcholines should be implicated into the diagnostic procedure of patients with UGC. We envision that metabolomics will significantly enhance our understanding of the carcinogenesis and progression process of UGC and may eventually facilitate precise oncological and patient-tailored management of UGC.
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Metabolômica , Humanos , Metabolômica/métodos , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/metabolismo , Neoplasias Gástricas/sangue , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/diagnóstico , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/metabolismo , Neoplasias Gastrointestinais/diagnóstico , Metaboloma/fisiologia , Estudos de Casos e Controles , Junção Esofagogástrica/patologia , Junção Esofagogástrica/metabolismoRESUMO
PURPOSE: Beside many advantages, disadvantages such as reduced degrees of freedom and poorer depth perception are still apparent in laparoscopic surgery. 3D visualization and the development of complex instruments are intended to counteract the disadvantages. We want to find out whether the use of complex instruments and 3D visualization has an influence on the performance of novices. METHODS: 48 medical students with no experience in laparoscopic surgery or simulator-based laparoscopy training were included. They were randomized in four groups according to a stratification assessment. During a structured training period they completed the FLS-Tasks "PEG Transfer", "Pattern Cut" and "Intracorporeal Suture" and a transfer task based on these three. Two groups used conventional laparoscopic instruments with 3D or 2D visualization, two groups used complex curved instruments. The groups were compared in terms of their performance. RESULTS: In 2D laparoscopy there was a better performance with straight instruments vs. curved instruments in PEG Transfer and Intracorporeal Suture. In the transfer task, fewer errors were made with straight instruments. In 2D vs. 3D laparoscopy when using complex curved instruments there was an advantage in Intracorporeal Suture and PEG Transfer for 3D visualization. Regarding the transfer exercise, a better performance was observed and fewer errors were made in 3D group. CONCLUSION: We could show that learning laparoscopic techniques with complex curved instruments is more difficult with standard 2D visualization and can be overcome using 3D optics. The use of curved instruments under 3D vision seems to be advantageous when working on more difficult tasks.
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Laparoscopia , Treinamento por Simulação , Humanos , Competência Clínica , Imageamento Tridimensional/métodos , Laparoscopia/métodos , Curva de Aprendizado , Treinamento por Simulação/métodosRESUMO
RATIONALE: Colorectal Cancer (CRC) represents the third most common type of cancer in Germany and the second most common cancer-related cause of death worldwide. Distant metastases are still the main limit for patient survival. While liver metastases as well as peritoneal carcinomatosis can often either be resected or treated with systemic therapy, little options remain for brain metastases. Additionally, a number of studies has already investigated hepatic, peritoneal, pulmonary as well as continuing distant metastases in colorectal cancer. Yet, with respect to tumor biology and brain metastases, little is known so far. MATERIAL AND METHODS: Two cohorts, M0 without distant spread and BRA with brain metastases were build. RNA was isolated from paraffin embedded specimen. Gene expression was performed by an RNA NanoString-Analysis using the nCounter® PanCancer Progression Panel by NanoString-Technologies (Hamburg, Germany). Results were analysed by principal component analysis, gene expression and pathway analysis using commonly available databases such as KEGG as benchmark for comparison. RESULTS: We were able to determine a gene signature that provides a sophisticated group separation between M0 and BRA using principal component analysis. All genes with strong loading characteristics on principal component 1 were cross-referenced with the subsequently performed accurate gene set enrichment analysis (GSEA). The GSEA revealed a clear dysregulation of the TGFß pathway in compared cohorts M0 and BRA. Interestingly, the targeted pathways analysis of the identified genes confirmed that in fact almost all strong loading genes of PC1 play a role in the TGFß pathway. CONCLUSION: Our results suggest the TGFß pathway as a crucial player in the development of brain metastases in primary CRC. In some types of colorectal cancer, downregulation of the TGFß pathway might hinder primary colorectal cancer to metastasize to the nervous system. While the paradoxical functioning of the TGFß pathway is still not fully understood, these shed light on yet another clinical implication of this complex pathway.
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Variants of garnet-type Li7La3Zr2O12 are being intensively studied as separator materials in solid-state battery research. The material-specific transport properties, such as bulk and grain boundary conductivity, are of prime interest and are mostly investigated by impedance spectroscopy. Data evaluation is usually based on the one-dimensional (1D) brick layer model, which assumes a homogeneous microstructure of identical grains. Real samples show microstructural inhomogeneities in grain size and porosity due to the complex behavior of grain growth in garnets that is very sensitive to the sintering protocol. However, the true microstructure is often omitted in impedance data analysis, hindering the interlaboratory reproducibility and comparability of results reported in the literature. Here, we use a combinatorial approach of structural analysis and three-dimensional (3D) transport modeling to explore the effects of microstructure on the derived material-specific properties of garnet-type ceramics. For this purpose, Al-doped Li7La3Zr2O12 pellets with different microstructures are fabricated and electrochemically characterized. A machine learning-assisted image segmentation approach is used for statistical analysis and quantification of the microstructural changes during sintering. A detailed analysis of transport through statistically modeled twin microstructures demonstrates that the transport parameters derived from a 1D brick layer model approach show uncertainties up to 150%, only due to variations in grain size. These uncertainties can be even larger in the presence of porosity. This study helps to better understand the role of the microstructure of polycrystalline electroceramics and its influence on experimental results.
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The unique architecture of ordered mesoporous oxides makes them a promising class of materials for various electrochemical applications, such as gas sensing or energy storage and conversion. The high accessibility of the internal surface allows tailoring of their electrochemical properties, e.g., by adjusting the pore size or surface functionalization, resulting in superior device performance compared to nanoparticles or disordered mesoporous counterparts. However, optimization of the mesoporous architecture requires reliable electrochemical characterization of the system. Unfortunately, the interplay between nanocrystalline grains, grain boundaries, and the open pore framework hinders a simple estimation of material-specific transport quantities by using impedance spectroscopy. Here, we use a 3D electric network model to elucidate the impact of the pore structure on the electrical transport properties of mesoporous thin films. It is demonstrated that the impedance response is dominated only by the geometric current constriction effect arising from the regular pore network. Estimating the effective conductivity from the total resistance and the electrode geometry, thus, differs by more than 1 order of magnitude from the material-specific conductivity of the solid mesoporous framework. A detailed analysis of computed impedances for varying pore size allows for the correlation of the effective conductivity with the material-specific conductivity. We derive an empirical expression that accounts for the porous structure of the thin films and allows a reliable determination of the material-specific conductivity with an error of less than 8%.
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Introduction: This study compares five augmented reality (AR) vasculature visualization techniques in a mixed-reality laparoscopy simulator with 50 medical professionals and analyzes their impact on the surgeon. Material and methods: ââThe different visualization techniques' abilities to convey depth were measured using the participant's accuracy in an objective depth sorting task. Demographic data and subjective measures, such as the preference of each AR visualization technique and potential application areas, were collected with questionnaires. Results: Despite measuring differences in objective measurements across the visualization techniques, they were not statistically significant. In the subjective measures, however, 55% of the participants rated visualization technique II, 'Opaque with single-color Fresnel highlights', as their favorite. Participants felt that AR could be useful for various surgeries, especially complex surgeries (100%). Almost all participants agreed that AR could potentially improve surgical parameters, such as patient safety (88%), complication rate (84%), and identifying risk structures (96%). Conclusions: More studies are needed on the effect of different visualizations on task performance, as well as more sophisticated and effective visualization techniques for the operating room. With the findings of this study, we encourage the development of new study setups to advance surgical AR.
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Realidade Aumentada , Laparoscopia , Cirurgiões , Cirurgia Assistida por Computador , Humanos , Laparoscopia/métodos , Cirurgia Assistida por Computador/métodosRESUMO
BACKGROUND: Analysis of surgical instrument motion is applicable in surgical skill assessment and monitoring of the learning progress in laparoscopy. Current commercial instrument tracking technology (optical or electromagnetic) has specific limitations and is expensive. Therefore, in this study, we apply inexpensive, off-the-shelf inertial sensors to track laparoscopic instruments in a training scenario. METHODS: We calibrated two laparoscopic instruments to the inertial sensor and investigated its accuracy on a 3D-printed phantom. In a user study during a one-week laparoscopy training course with medical students and physicians, we then documented and compared the training effect in laparoscopic tasks on a commercially available laparoscopy trainer (Laparo Analytic, Laparo Medical Simulators, Wilcza, Poland) and the newly developed tracking setup. RESULTS: Eighteen participants (twelve medical students and six physicians) participated in the study. The student subgroup showed significantly poorer results for the count of swings (CS) and count of rotations (CR) at the beginning of the training compared to the physician subgroup (p = 0.012 and p = 0.042). After training, the student subgroup showed significant improvements in the rotatory angle sum, CS, and CR (p = 0.025, p = 0.004 and p = 0.024). After training, there were no significant differences between medical students and physicians. There was a strong correlation between the measured learning success (LS) from the data of our inertial measurement unit system (LSIMU) and the Laparo Analytic (LSLap) (Pearson's r = 0.79). CONCLUSION: In the current study, we observed a good and valid performance of inertial measurement units as a possible tool for instrument tracking and surgical skill assessment. Moreover, we conclude that the sensor can meaningfully examine the learning progress of medical students in an ex-vivo setting.
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Laparoscopia , Médicos , Humanos , Competência Clínica , Laparoscopia/métodos , Destreza Motora , AprendizagemRESUMO
Venous-only perfusion flaps have not been used widely because of the associated high failure rate. Tissue conditioning offers a broad scope of techniques that can be applied pre-, peri-, or postoperatively to promote the adaptation of the affected tissue to any subsequent stress. This study aimed to assess the survival rates associated with a pure venous perfusion flap and investigate whether the timing of the vascular conditioning can affect free flap survival. Forty-four rats were included in the experiment. Group I underwent veno-arterial anastomoses with epigastric graft with pure venous perfusion without tissue conditioning. Groups II and III were pretreated for 7 or 14 days with ischemic conditioning. These groups were compared with a control group (group IV) of conventionally perfused flaps. After the initial surgery, all flaps were assessed clinically, photometrically, and by indocyanine green videoangiography. The flap success rates were 0% in group I, 49.97% ± 24.34% in group II, and 64.95% ± 20.36% in group III. The control group showed an overall survival of 89.3% ± 6.51%. With suitable conditioning, pure venous blood supply can provide adequate perfusion in the rat epigastric flap model. The timing of vascular conditioning appears to be critical for flap survival.
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Retalhos de Tecido Biológico , Veias , Ratos , Animais , Procedimentos Cirúrgicos Vasculares , Artérias , Angiofluoresceinografia , Sobrevivência de EnxertoRESUMO
PURPOSE: Only a few studies have evaluated Augmented Reality (AR) in in vivo simulations compared to traditional laparoscopy; further research is especially needed regarding the most effective AR visualization technique. This pilot study aims to determine, under controlled conditions on a 3D-printed phantom, whether an AR laparoscope improves surgical outcomes over conventional laparoscopy without augmentation. METHODS: We selected six surgical residents at a similar level of training and had them perform a laparoscopic task. The participants repeated the experiment three times, using different 3D phantoms and visualizations: Floating AR, Occlusion AR, and without any AR visualization (Control). Surgical performance was determined using objective measurements. Subjective measures, such as task load and potential application areas, were collected with questionnaires. RESULTS: Differences in operative time, total touching time, and SurgTLX scores showed no statistical significance ([Formula: see text]). However, when assessing the invasiveness of the simulated intervention, the comparison revealed a statistically significant difference ([Formula: see text]). Participants felt AR could be useful for various surgeries, especially for liver, sigmoid, and pancreatic resections (100%). Almost all participants agreed that AR could potentially lead to improved surgical parameters, such as operative time (83%), complication rate (83%), and identifying risk structures (83%). CONCLUSION: According to our results, AR may have great potential in visceral surgery and based on the objective measures of the study, may improve surgeons' performance in terms of an atraumatic approach. In this pilot study, participants consistently took more time to complete the task, had more contact with the vascular tree, were significantly more invasive, and scored higher on the SurgTLX survey than with AR.
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Realidade Aumentada , Laparoscopia , Cirurgia Assistida por Computador , Humanos , Cirurgia Assistida por Computador/métodos , Projetos Piloto , Laparoscopia/métodos , Imagens de FantasmasRESUMO
BACKGROUND: The "digital era" in the field of medicine is the new "here and now". Artificial intelligence has entered many fields of medicine and is recently emerging in the field of organ transplantation. Solid organs remain a scarce resource. Being able to predict the outcome after liver transplantation promises to solve one of the long-standing problems within organ transplantation. What is the perfect donor recipient match? Within this work we developed and validated a novel deep-learning-based donor-recipient allocation system for liver transplantation. METHOD: In this study we used data collected from all liver transplant patients between 2004 and 2019 at the university transplantation centre in Munich. We aimed to design a transparent and interpretable deep learning framework to predict the outcome after liver transplantation. An individually designed neural network was developed to meet the unique requirements of transplantation data. The metrics used to determine the model quality and its level of performance are accuracy, cross-entropy loss, and F1 score as well as AUC score. RESULTS: A total of 529 transplantations with a total of 1058 matching donor and recipient observations were added into the database. The combined prediction of all outcome parameters was 95.8% accurate (cross-entropy loss of 0.042). The prediction of death within the hospital was 94.3% accurate (cross-entropy loss of 0.057). The overall F1 score was 0.899 on average, whereas the overall AUC score was 0.940. CONCLUSION: With the achieved results, the network serves as a reliable tool to predict survival. It adds new insight into the potential of deep learning to assist medical decisions. Especially in the field of transplantation, an AUC Score of 94% is very valuable. This neuronal network is unique as it utilizes transparent and easily interpretable data to predict the outcome after liver transplantation. Further validation must be performed prior to utilization in a clinical context.
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Image registration is a commonly required task in computer assisted surgical procedures. Existing registration methods in laparoscopic navigation systems suffer from several constraints, such as lack of deformation compensation. The proposed algorithm aims to provide the surgeons with updated navigational information about the deep-seated anatomy, which considers the continuous deformations in the operating environment. We extended an initial rigid registration to a shape-preserving deformable registration pathway by incorporating user interaction and an iterative mesh editing scheme which preserves local details. The proposed deformable registration workflow was tested with phantom and animal trial datasets. A qualitative evaluation based on expert feedback demonstrated satisfactory outcome, and an commensurate execution efficiency was achieved. The improvements offered by the method, couples with its relatively easy implementation, makes it an attractive method for adoption in future pre-clinical and clinical applications of augmented reality assisted surgeries.
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Realidade Aumentada , Laparoscopia , Cirurgiões , Cirurgia Assistida por Computador , Algoritmos , Animais , HumanosRESUMO
A non-ideal contact at the electrode/solid electrolyte interface of a solid-state battery arising due to pores (voids) or inclusions results in a geometric constriction effect that severely deteriorates the electric transport properties of the battery cell. The lack of understanding of this phenomenon hinders the optimization process of novel components, such as reversible and high-rate metal anodes. Deeper insight into the constriction phenomenon is necessary to correctly monitor interface degradation and to accelerate the successful use of metal anodes in solid-state batteries. Here, we use a 3D electric network model to study the fundamentals of the constriction effect. Our findings suggest that dynamic constriction as a non-local effect cannot be captured by conventional 1D equivalent circuit models and that its electric behavior is not ad hoc predictable. It strongly depends on the interplay of the geometry of the interface causing the constriction and the microscopic transport processes in the adjacent phases. In the presence of constriction, the contribution from the non-ideal electrode/solid electrolyte interface to the impedance spectrum may exhibit two signals that cannot be explained when the porous interface is described by a physical-based (effective medium theory) 1D equivalent circuit model. In consequence, the widespread assumption of a single interface contribution to the experimental impedance spectrum may be entirely misleading and can cause serious misinterpretation.
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In an all-solid-state battery, the electrical contact between its individual components is of key relevance in addition to the electrochemical stability of its interfaces. Impedance spectroscopy is particularly suited for the non-destructive investigation of interfaces and of their stability under load. Establishing a valid correlation between microscopic processes and the macroscopic impedance signal, however, is challenging and prone to errors. Here, we use a 3D electric network model to systematically investigate the effect of various electrode/sample interface morphologies on the impedance spectrum. It is demonstrated that the interface impedance generally results from a charge transfer step and a geometric constriction contribution. The weights of both signals depend strongly on the material parameters as well as on the interface morphology. Dynamic constriction results from a non-ideal local contact, e.g., from pores or voids, which reduce the electrochemical active surface area only in a certain frequency range. Constriction effects dominate the interface behavior for systems with small charge transfer resistance like garnet-type solid electrolytes in contact with a lithium metal electrode. An in-depth analysis of the origin and the characteristics of the constriction phenomenon and their dependence on the interface morphology is conducted. The discussion of the constriction effect provides further insight into the processes at the microscopic level, which are, e.g., relevant in the case of reversible metal anodes.
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Disorder effects in alloys are usually modeled by averaging various supercell calculations considering different positions of the alloy atoms. This approach, however, is only possible as long as the portion of the individual components of the alloy is sufficiently large. Herein, we present anab initiostudy considering the lithium insertion material Li1-x[Ni0.33Co0.33Mn0.33]O2as model system to demonstrate the power of the coherent potential approximation within the Korringa-Kohn-Rostoker Green's function method. This approach enables the description of disorder effects within alloy systems of any composition. It is applied in this study to describe the (de-)intercalation of arbitrary amounts of lithium from the cathode active material. Moreover, we highlight that using either fully optimized structures or experimental lattice parameters and atomic positions both lead to comparable results. Our findings suggest that this approach is also suitable for modeling the electronic structure of state-of-the-art materials such as high-nickel alloys.
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BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. Laparoscopic lower rectal resections in accordance with the oncological principles are recommended as the gold standard for CRC surgical management. However, the learning curve for adopting these techniques is quite steep and the incomplete resections are predictive of local recurrence. This study was conducted in an attempt to find a way to help surgeons to overcome some of these difficulties and define the right resection margins. MATERIAL AND METHODS: As such, we carried out two laparoscopic lower rectal resections in porcine models. The first resection was performed following the ligation and selective infusion of Indocyanine Green (ICG) into the inferior mesenteric artery (IMA), and the second after the ligation of both inferior mesenteric artery and vein (IMV) and systemic intravenous infusion of ICG. Fluorescence was detected in real time by means of an infrared imaging system. RESULTS: Sharp resection margins were defined after intra-arterial infusion, and all the tissues in the IMA basin were colored in the first case. In the second model every organ and tissue was colored except the rectum, urinary bladder and ductus deferens. CONCLUSIONS: Although systemic intra-venous application of ICG and negative-staining of the rectum including the mesorectum is much easier compared to laparoscopic inter-arterial perfusion through IMA, image results of selevtive IMA-perfusion appear in sharper discrimination of the several layers. Further investigation should focus on simplifying this technique.
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Laparoscopia , Neoplasias Retais , Animais , Estudos de Viabilidade , Verde de Indocianina , Neoplasias Retais/cirurgia , Reto/diagnóstico por imagem , Reto/cirurgia , Coloração e Rotulagem , SuínosRESUMO
Background: For centuries, surgeons have relied on surgical drains during postoperative care. Despite all advances in modern medicine and the area of digitalization, as of today, most if not all assessment of abdominal secretions excreted via surgical drains are carried out manually. We here introduce a novel integrated Smart Sensor System (Smart Drain) that allows for real-time characterization and digitalization of postoperative abdominal drain output at the patient's bedside. Methods: A prototype of the Smart Drain was developed using a sophisticated spectrometer for assessment of drain output. The prototype measures 10 × 6 × 6 cm and therefore easily fits at the bedside. At the time of measurement with our Smart Drain, the drain output was additionally sent off to be analyzed in our routine laboratory for typical markers of interest in abdominal surgery such as bilirubin, lipase, amylase, triglycerides, urea, protein, and red blood cells. A total of 45 samples from 19 patients were included. Results: The measurements generated were found to correlate with conventional laboratory measurements for bilirubin (r = .658, P = .000), lipase (r = .490, P = .002), amylase (r = .571, P = .000), triglycerides (r = .803, P = .000), urea (r = .326, P = .033), protein (r = .387, P = .012), and red blood cells (r = .904, P = .000). Conclusions: To our best knowledge, for the first time we describe a device using a sophisticated spectrometer that allows for real-time characterization and digitalization of postoperative abdominal drain output at the patient's bedside.