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This paper contributes to the automatic detection of perioperative workflow by developing a binary endoscope localization. Automated situation recognition in the context of an intelligent operating room requires the automatic conversion of low level cues into more abstract high level information. Imagery from a laparoscope delivers rich content that is easy to obtain but hard to process. We introduce a system which detects if the endoscope's distal tip is inside or outsiede the patient based on the endoscope video. This information can be used as one parameter in a situation recognition pipeline. Our localization performs in real-time at a video resolution of 1280x720 and 5-fold cross validation yields mean F1-scores of up to 0,94 on videos of 7 laparoscopies.
The best fully automated analysis process achieves even better classification results than the established manual process. The best algorithms for the three analysis steps are (i) SGLTR (Savitzky-Golay Laplace operator filter thresholding regions) and LM (Local Maxima) for automated peak identification, (ii) EM clustering (Expectation Maximization) and DBSCAN (Density-Based Spatial Clustering of Applications with Noise) for the clustering step and (iii) RF (Random Forest) for multivariate classification. Thus, automated methods can replace the manual steps in the analysis process to enable an unbiased high throughput use of the technology.
Propofol in exhaled breath can be measured and may provide a real-time estimate of plasma concentration. However, propofol is absorbed in plastic tubing, thus estimates may fail to reflect lung/blood concentration if expired gas is not extracted directly from the endotracheal tube.We evaluated exhaled propofol in five ventilated ICU patients who were sedated with propofol. Exhaled propofol was measured once per minute using ion mobility spectrometry. Exhaled air was sampled directly from the endotracheal tube and at the ventilator end of the expiratory side of the anesthetic circuit. The circuit was disconnected from the patient and propofol was washed out with a separate clean ventilator. Propofol molecules, which discharged from the expiratory portion of the breathing circuit, were measured for up to 60 h.We also determined whether propofol passes through the plastic of breathing circuits. A total of 984 data pairs (presented as median values, with 95% confidence interval), consisting of both concentrations were collected. The concentration of propofol sampled near the patient was always substantially higher, at 10.4 [10.25–10.55] versus 5.73 [5.66–5.88] ppb (p<0.001). The reduction in concentration over the breathing circuit tubing was 4.58 [4.48–4.68] ppb, 3.46 [3.21–3.73] in the first hour, 4.05 [3.77–4.34] in the second hour, and 4.01 [3.36–4.40] in the third hour. Out-gassing propofol from the breathing circuit remained at 2.8 ppb after 60 h of washing out. Diffusion through the plastic was not observed. Volatile propofol binds or adsorbs to the plastic of a breathing circuit with saturation kinetics. The bond is reversible so propofol can be washed out from the plastic. Our data confirm earlier findings that accurate measurements of volatile propofol require exhaled air to be sampled as close as possible to the patient.
Purpose: Medical processes can be modeled using different methods and notations.Currently used modeling systems like Business Process Model and Notation (BPMN) are not capable of describing the highly flexible and variable medical processes in sufficient detail.
Methods: We combined two modeling systems, Business Process Management (BPM) and Adaptive Case Management (ACM), to be able to model non-deterministic medical processes. We used the new Standards Case Management Model and Notation (CMMN) and Decision Management Notation (DMN).
Results: First, we explain how CMMN, DMN and BPMN could be used to model non-deterministic medical processes. We applied this methodology to model 79 cataract operations provided by University Hospital Leipzig, Germany, and four cataract operations provided by University Eye Hospital Tuebingen, Germany. Our model consists of 85 tasks and about 20 decisions in BPMN. We were able to expand the system with more complex situations that might appear during an intervention.
Conclusion: An effective modeling of the cataract intervention is possible using the combination of BPM and ACM. The combination gives the possibility to depict complex processes with complex decisions. This combination allows a significant advantage for modeling perioperative processes.
Propofol is a commonly used intravenous general anesthetic. Multi-capillary column (MCC) coupled ion-mobility spectrometry (IMS) can be used to quantify exhaled propofol, and thus estimate plasma drug concentration. Here, we present results of the calibration and analytical validation of a MCC/IMS pre-market prototype for propofol quantification in exhaled air.
Knee osteoarthritis is a common complication and can lead to total loss of joint function in patients. Treatment by either partial or total knee replacement with appropriate UHMWPE based implantsis highly invasive, may cause complications and may show unsatisfying results. Alternatively, treatment may be done by insertion of an elastic interpositional knee spacer with optimized material characteristics.
We report the development of high performance polyurethane-based polymers modified with bioactive molecules for fabrication of such knee spacers. In order to tailor mechanical and tribological properties and to improve resist to enzymatic degradation we propose a core-shell model for the spacer with specifically adapted properties.
Propofol is an intravenous anesthetic. Currently, it is not possible to routinely measure blood concentration of the drug in real time. However, multi-capillary column ion-mobility spectrometry of exhaled gas can estimate blood propofol concentration.Unfortunately, adhesion of volatile propofol on plastic materials complicates measurements. Therefore, it is necessary to consider the extent to which volatile propofol adheres to various plastics used in sampling tubing. Perfluoralkoxy (PFA), polytetrafluorethylene (PTFE), polyurethane (PUR), silicone, and Tygon tubing were investigated in an experimental setting using a calibration gas generator (HovaCAL). Propofol gas was measured for one hour at 26 °C, 50 °C, and 90 °C tubing temperature. Test tubing segments were then flushed with N2 to quantify desorption. PUR and Tygon sample tubing absorbed all volatile propofol. The silicone tubing reached the maximum propofol concentration after 119 min which was 29 min after propofol gas exposure stopped. The use of PFAor PTFE tubing produced comparable and reasonably accurate propofol measurements. The desaturation time for the PFA was 10 min shorter at 26 °C than for PTFE. PFA tubing thus seems most suitable for measurement of volatile propofol,with PTFE as an alternative.
Purpose: Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods: VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results: We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p < 0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p < 0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r =−0.393, p = 0.013), %VC (r =−0.569, p < 0.001), FVC (r = −0.440, p = 0.004), %FVC (r =−0.539, p < 0.001), DLco (r =−0.394, p = 0.018), and %DLco (r =−0.413, p = 0.008) and a positive correlation with KL-6 (r = 0.432, p = 0.005) were found for p-cymene. Conclusion: We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.
In the last decades, several driving systems were developed to improve the driving behaviour in energy efficiency or safety. However, these driving systems cover either the area of energy-efficiency or safety. Furthermore, they do not consider the stress level of the driver when showing a recommendation, although stress can lead to an unsafe or inefficient driving behaviour. In this paper, an approach is presented to consider the driver stress level in a driving system for safe and energy-efficient driving behaviour. The driving system tries to suppress a recommendation when the driver is in stress in order not to stress the driver additionally with recommendations in a stressful driving situation. This can lead to an increase in the road safety and in the user acceptance of the driving system, as the driver is not getting bothered or stressed by the driving system.
The evaluation of the approach showed, that the driving system
is able to show recommendations to the driver, while also reacting
to a high stress level by suppressing recommendations in
order not to stress the driver additionally.
Tumorzellen on the move : mikrosystem-basierter Assay zur Untersuchung der Tumorzellen-Migration
(2016)
Die Invasion von Tumorzellen in umliegendes Gewebe und die Bildung von Metastasen transformieren einen lokal wachsenden Tumor in eine systemische und lebensbedrohliche Krankheit mit schlechter Prognose. Dabei spielt die aktive Migration der Tumorzellen eine entscheidende Rolle. Tumorzellen gelangen durch die aktive Zellbewegung in das Lymph- oder Blutsystem und breiten sich im Körper aus. Bei der Invasion in ein neues Organ migrieren die Zellen ebenfalls wieder in komplexer Weise durch das Gewebe und können schließlich dort Metastasen bilden. Auf Grund der enormen medizinischen Relevanz der Tumorzell-Invasion, wird die Bewegung von Tumorzellen seit Jahrzehnten unter Laborbedingungen umfassend untersucht und ist ein wichtiger Marker für die Aggressivität der Tumorzellen. Zur Bewegungsanalyse gibt es mehrere experimentelle und auch kommerziell erhältliche in-vitro Untersuchungsmethoden. Ziel des interdisziplinären Projektes „MigChip“ ist die Entwicklung, Herstellung und experimentelle Validierung eines Mikrofludik-Chips zur verbesserten, detailgenauen in-vitro Untersuchung der Tumorzellen-Migration.
New drugs serving unmet medical needs are one of the key value drivers of research-based pharmaceutical companies. The efficiency of research and development (R&D), defined as the successful approval and launch of new medicines (output) in the rate of the monetary investments required for R&D (input), has declined since decades. We aimed to identify, analyze and describe the factors that impact the R&D efficiency. Based on publicly available information, we reviewed the R&D models of major research-based pharmaceutical companies and analyzed the key challenges and success factors of a sustainable R&D output. We calculated that the R&D efficiencies of major research-based pharmaceutical companies were in the range of USD 3.2–32.3 billion (2006–2014). As these numbers challenge the model of an innovation-driven pharmaceutical industry, we analyzed the concepts that companies are following to increase their R&D efficiencies: (A) Activities to reduce portfolio and project risk, (B) activities to reduce R&D costs, and (C) activities to increase the innovation potential. While category A comprises measures such as portfolio management and licensing, measures grouped in category B are outsourcing and risk-sharing in late-stage development. Companies made diverse steps to increase their innovation potential and open innovation, exemplified by open source, innovation centers, or crowdsourcing, plays a key role in doing so. In conclusion, research-based pharmaceutical companies need to be aware of the key factors, which impact the rate of innovation, R&D cost and probability of success. Depending on their company strategy and their R&D set-up they can opt for one of the following open innovators: knowledge creator, knowledge integrator or knowledge leverager.
From raw ion mobility measurements to disease classification : a comparison of analysis processes
(2015)
Ion mobility spectrometry (IMS) is a technology for the detection of volatile compounds in the air of exhaled breath that is increasingly used in medical applications. One major goal is to classify patients into disease groups, for example diseased versus healthy, from simple breath samples. Raw IMS measurements are data matrices in which peak regions representing the compounds have to be identified and quantified. A typical analysis process consists of pre-processing and peak detection in single experiments, peak clustering to obtain consensus peaks across several experiments, and classification of samples based on the resulting multivariate peak intensities. Recently several automated algorithms for peak detection and peak clustering have been introduced, in order to overcome the current need for human-based analysis that is slow, subjective and sometimes not reproducible. We present an unbiased comparison of a multitude of combinations of peak processing and multivariate classification algorithms on a disease dataset. The specific combination of the algorithms for the different analysis steps determines the classification accuracy, with the encouraging result that certain fully-automated combinations perform even better than current manual approaches.
Background and purpose: Transapical aortic valve replacement (TAVR) is a recent minimally invasive surgical treatment technique for elderly and high-risk patients with severe aortic stenosis. In this paper,a simple and accurate image-based method is introduced to aid the intra-operative guidance of TAVR procedure under 2-D X-ray fluoroscopy.
Methods: The proposed method fuses a 3-D aortic mesh model and anatomical valve landmarks with live 2-D fluoroscopic images. The 3-D aortic mesh model and landmarks are reconstructed from interventional X-ray C-arm CT system, and a target area for valve implantation is automatically estimated using these aortic mesh models.Based on template-based tracking approach, the overlay of visualized 3-D aortic mesh model, land-marks and target area of implantation is updated onto fluoroscopic images by approximating the aortic root motion from a pigtail catheter motion without contrast agent. Also, a rigid intensity-based registration algorithm is used to track continuously the aortic root motion in the presence of contrast agent.Furthermore, a sensorless tracking of the aortic valve prosthesis is provided to guide the physician to perform the appropriate placement of prosthesis into the estimated target area of implantation.
Results: Retrospective experiments were carried out on fifteen patient datasets from the clinical routine of the TAVR. The maximum displacement errors were less than 2.0 mm for both the dynamic overlay of aortic mesh models and image-based tracking of the prosthesis, and within the clinically accepted ranges. Moreover, high success rates of the proposed method were obtained above 91.0% for all tested patient datasets.
Conclusion: The results showed that the proposed method for computer-aided TAVR is potentially a helpful tool for physicians by automatically defining the accurate placement position of the prosthesis during the surgical procedure.
Informationstechnische Systeme, die den Arbeitsablauf im klinischen Bereich unterstützen, sind aktuell auf organisatorische Abläufe beschränkt. Diese Arbeit stellt einen ersten Ansatz vor, wie solch ein System in den perioperativen Bereich eingebracht werden kann. Hierzu wurde eine Workflow Engine mit einer perioperativen Prozess-Visualisierung verknüpft. Das System wurde nach Modell-View-Controller-Prinzip implementiert. Als "Controller" kommt die Workflow Engine zum Einsatz; also "Modell" ein Prozessmodell, mit den erforderlichen klinischen Daten. Der "View" wurde durch eine abgekoppelte Anwendung realisiert, welche auf Web-Technologien basiert. Drei Visualisierungen, die Workflow Engine sowie die Anbindung beider über eine Datenbankschnittstelle, wurden erfolgreich umgesetzt. Bei den drei Visualisierungen wurden jeweils eine Ansicht für den OP-Koordinator, den Springer und eine Ansicht für die Übersicht einer OP erstellt.
An operating room is a stressful work environment. Nevertheless, all involved persons have to work safely as there is no space for mistakes. To ensure a high level of concentration and seamless interaction, all involved persons have to know their own tasks and the tasks of their colleagues. The entire team must work synchronously at all times. To optimize the overall workflow, a task manager supporting the team was developed. In parallel, a common conceptual design of a business process visualization was developed, which makes all relevant information accessible in real-time during a surgery. In this context an overview of all processes in the operating room was created and different concepts for the graphical representation of these user-dependent processes were developed. This paper describes the concept of the task manager as well as the general concept in the field of surgery.
Im Fokus der Arbeit steht die Unterstützung der Stentgraftauswahl bei endovaskulärer Versorgung eines infrarenalen Aortenaneurysmas. Im Rahmen der Arbeit wurde eine Methode zur Auswertung von Ergebnissen einer Finite Elemente-Analyse zum Stentgraftverhalten konzipiert, implementiert und im Rahmen einer deutschlandweiten Benutzerstudie mit 16 Chirurgen diskutiert. Die entwickelte Mensch-Maschine-Schnittstelle ermöglicht dem Gefäßmediziner eine interaktive Analyse berechneter Fixierungskräfte und Kontaktzustände mehrerer Stentgrafts im Kontext mit dem zu behandelnden Aortenabschnitt. Die entwickelte Methode ermöglicht eine tiefergehende Auseinandersetzung der Mediziner mit numerischen Simulationen und Stentgraftbewertungsgrößen. Hierdurch konnte im Rahmen der Benutzerstudie das Einsatzpotenzial numerischer Simulationen zur Unterstützung der Stentgraftauswahl ermittelt und eine Anforderungsspezifikation an ein System zur simulationsbasierten Stentgraftplanung definiert werden. Im Ergebnis wurde als wesentliches Einsatzpotenzial die Festlegung eines Mindestmaßes an Überdimensionierung, die Optimierung der Schenkellänge von bifurkativen Stentgrafts sowie der Vergleich unterschiedlicher Stentgraftdesigns ermittelt. Zu den wesentlichen Funktionen eines Systems zur simulationsbasierten Stentgraftauswahl gehören eine Übersichtskarte zu farbkodiertem Migrationsrisiko pro Stentgraft und Landungszone, die Visualisierung des Abdichtungszustandes der Stentkomponenten sowie die Darstellung von Stentgraft- und Gefäßdeformationen im 3D-Modell.
Die DGCH registriert vermehrt Klagen aus der klinischen Praxis hinsichtlich der nicht vollständigen Vernetzung bzw. Integration von Gerätesystemen im Chirurgischen OP. Die Anzahl, der Funktionsumfang und der Komplexitätsgrad der verwendeten Geräte nehmen ständig zu und machen die Bedienung immer aufwendiger und damit schwieriger und fehleranfälliger, sodass eine Verbesserung bei der Unterstützung im Ablauf wünschenswert ist. Die Sektion Computer- und telematikassistierte Chirurgie (CTAC) der DGCH hat es auf Veranlassung des Generalsekretärs deshalb übernommen, eine aktuelle Bestandsaufnahme vorzunehmen und mögliche Ansätze zur Verbesserung des derzeitigen Status zu bewerten.
An ongoing challenge in our days is to lower the impact on the quality of life caused by dysfunctionality through individual support. With the background of an aging society and continuous increases in costs for care, a holistic solution is needed. This solution must integrate individual needs and preferences, locally available possibilities, regional conditions, professional and informal caregivers and provide the flexibility to implement future requirements. The proposed model is a result of a common initiative to overcome the major obstacles and to center a solution on individual needs caused by dysfunctionality.
Methacrylated gelatin and mature adipocytes are promising components for adipose tissue engineering
(2016)
In vitro engineering of autologous fatty tissue constructs is still a major challenge for the treatment of congenital deformities, tumor resections or high-graded burns. In this study, we evaluated the suitability of photo-crosslinkable methacrylated gelatin (GM) and mature adipocytes as components for the composition of three-dimensional fatty tissue constructs. Cytocompatibility evaluations of the GM and the photoinitiator Lithium phenyl-2,4,6 trimethylbenzoylphosphinate (LAP) showed no cytotoxicity in the relevant range of concentrations. Matrix stiffness of cell-laden hydrogels was adjusted to native fatty tissue by tuning the degree of crosslinking and was shown to be comparable to that of native fatty tissue. Mature adipocytes were then cultured for 14 days within the GM resulting in a fatty tissue construct loaded with viable cells expressing cell markers perilipin A and laminin. This work demonstrates that mature adipocytes are a highly valuable cell source for the composition of fatty tissue equivalents in vitro. Photo-crosslinkable methacrylated gelatin is an excellent tissue scaffold and a promising bioink for new printing techniques due to its biocompatibility and tunable properties.
The physiology of vascular cells depends on stimulating mechanical forces caused by pulsatile flow. Thus, mechano-transduction processes and responses of primary human endothelial cells (ECs) and smooth muscle cells (SMCs) have been studied to reveal cell-type specific differences which may contribute to vascular tissue integrity. Here, we investigate the dynamic reorientation response of ECs and SMCs cultured on elastic membranes over a range of stretch frequencies from 0.01 to 1 Hz. ECs and SMCs show different cell shape adaptation responses (reorientation) dependent on the frequency. ECs reveal a specific threshold frequency (0.01 Hz) below which no responses is detectable while the threshold frequency for SMCs could not be determined and is speculated to be above 1 Hz. Interestingly, the reorganization of the actin cytoskeleton and focal adhesions system, as well as changes in the focal adhesion area, can be observed for both cell types and is dependent on the frequency. RhoA and Rac1 activities are increased for ECs but not for SMCs upon application of a uniaxial cyclic tensile strain. Analysis of membrane protrusions revealed that the spatial protrusion activity of ECs and SMCs is independent of the application of a uniaxial cyclic tensile strain of 1 Hz while the total number of protrusions is increased for ECs only. Our study indicates differences in the reorientation response and the reaction times of the two cell types in dependence of the stretching frequency, with matching data for actin cytoskeleton, focal adhesion realignment, RhoA/Rac1 activities, and membrane protrusion activity. These are promising results which may allow cell-type specific activation of vascular cells by frequency selective mechanical stretching. This specific activation of different vascular cell types might be helpful in improving strategies in regenerative medicine.