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Purpose Minimally invasive en-bloc esophagectomy is associated with a reduction of postoperative morbidity. This was demonstrated for both total minimally invasive and hybrid esophagectomy. However, little is known about any benefits of robotic assistance compared to the conventional minimally invasive technique, especially in hybrid procedures. Methods For this retrospective study, all consecutive patients who had undergone elective esophagectomy with circular stapled intrathoracic anastomosis using the open and the minimally invasive hybrid technique at the University Hospital Magdeburg, from January 2010 to March 2021 were considered for analysis. Results In total, 137 patients (60.4%) had undergone open esophagectomy. In 45 patients (19.8%), the laparoscopic hybrid technique and in 45 patients (19.8%), the robot-assisted hybrid technique were applied. In propensity score matching analysis comparing the open with the robotic hybrid technique, significant differences were found in favor of the robotic technique (postoperative morbidity, p p p = 0.048). In propensity score matching analysis comparing the laparoscopic with the robotic hybrid technique, a significant reduction of the rate of postoperative delayed gastric emptying (p = 0.02) was found for patients who had undergone robotic esophagectomy. However, the operation time was significantly longer (p Conclusions En-bloc esophagectomy using the robotic hybrid technique is associated with a significant reduction of postoperative morbidity and of the hospital length of stay when compared to the open approach. However, when compared to the laparoscopic hybrid technique, only few advantages could be demonstrated.

Introduction: Study: International Multicentric Minimally Invasive Liver Resection for Colorectal Liver Metastases (SIMMILR-CRLM) was a propensity score matched (PSM) study that reported short-term outcomes of patients with CRLM who met the Milan criteria and underwent either open (OLR), laparoscopic (LLR) or robotic liver resection (RLR). This study, designated as SIMMILR-2, reports the long-term outcomes from that initial study, now referred to as SIMMILR-1. Methods: Data regarding neoadjuvant chemotherapeutic (NC) and neoadjuvant biological (NB) treatments received were collected, and Kaplan–Meier curves reporting the 5-year overall (OS) and recurrence-free survival (RFS) for OLR, LLR and RLR were created for patients who presented with synchronous lesions only, as there was insufficient follow-up for patients with metachronous lesions. Results: A total of 73% of patients received NC and 38% received NB in the OLR group compared to 70% and 28% in the LLR group, respectively (p = 0.5 and p = 0.08). A total of 82% of patients received NC and 40% received NB in the OLR group compared to 86% and 32% in the RLR group, respectively (p > 0.05). A total of 71% of patients received NC and 53% received NB in the LLR group compared to 71% and 47% in the RLR group, respectively (p > 0.05). OS at 5 years was 34.8% after OLR compared to 37.1% after LLR (p = 0.4), 34.3% after OLR compared to 46.9% after RLR (p = 0.4) and 30.3% after LLR compared to 46.9% after RLR (p = 0.9). RFS at 5 years was 12.1% after OLR compared to 20.7% after LLR (p = 0.6), 33.3% after OLR compared to 26.3% after RLR (p = 0.6) and 22.7% after LLR compared to 34.6% after RLR (p = 0.6). Conclusions: When comparing OLR, LLR and RLR, the OS and RFS were all similar after utilization of the Milan criteria and PSM. Biological agents tended to be utilized more in the OLR group when compared to the LLR group, suggesting that highly aggressive tumors are still managed through an open approach.

BACKGROUND: Incisional hernias with apertures measuring less than 7 cm can generally be treated adequately with the laparoscopic intraperitoneal onlay-mesh (IPOM) technique. The wearing of an abdominal binder after surgery is often recommended in order to promote wound healing and prevent recurrent herniation. We carried out a multicenter, randomized pilot trial to evaluate the utility of abdominal binders. METHODS: The trial was conducted from May 2019 to December 2020. Persons with a laparoscopic IPOM procedure for treatment of an incisional hernia were included in the trial and randomized preoperatively (1:1). The patients in the abdominal binder group wore an abdominal binder during the day for 14 days after surgery, while those in the control group wore no binder. The primary endpoint was pain at rest on postoperative days 1, 2, and 14, as measured on a visual analog scale. The secondary endpoints were overall subjective well-being, the rates of wound infection, recurrence, and complications, mobility, and the rate and size of postoperative seromas (on postoperative days 1, 2, and 14). RESULTS: Forty patients were included. Three were excluded because of conversion to an open surgical technique. The biometric and perioperative data of the abdominal binder group (n = 18) and the control group (n = 19) did not differ to any statistically significant extent. The patients in the binder group had significantly less postoperative pain (F [df(n), df(d)]) 4.44, 95% confidence interval [1; 35]; p = 0.042).The patients in the binder group also had better overall subjective well-being and a higher rate of postoperative seroma formation, but these differences did not reach statistical significance. There was less limitation of mobility than in the control group; however, this difference also did not attain statistical significance. CONCLUSION: An abdominal binder may reduce pain after incisional hernia repair with the IPOM technique. The postoperative use of analgesic medication was not measured.

Background: The implementation of robotics in liver surgery offers several advantages compared to conventional open and laparoscopic techniques. One major advantage is the enhanced degree of freedom at the tip of the robotic tools compared to laparoscopic instruments. This enables excellent vessel control during inflow and outflow dissection of the liver. Parenchymal transection remains the most challenging part during robotic liver resection because currently available robotic instruments for parenchymal transection have several limitations and there is no standardized technique as of yet. We established a new strategy and share our experience. Methods: We present a novel technique for the transection of liver parenchyma during robotic surgery, using three devices (3D) simultaneously: monopolar scissors and bipolar Maryland forceps of the robot and laparoscopic-guided waterjet. We collected the perioperative data of twenty-eight patients who underwent this procedure for minor and major liver resections between February 2019 and December 2020 from the Magdeburg Registry of minimally invasive liver surgery (MD-MILS). Results: Twenty-eight patients underwent robotic-assisted 3D parenchyma dissection within the investigation period. Twelve cases of major and sixteen cases of minor hepatectomy for malignant and non-malignant cases were performed. Operative time for major liver resections (≥ 3 liver segments) was 381.7 (SD 80.6) min vs. 252.0 (70.4) min for minor resections (p &lt, 0.01). Intraoperative measured blood loss was 495.8 (SD 508.8) ml for major and 256.3 (170.2) ml for minor liver resections (p = 0.090). The mean postoperative stay was 13.3 (SD 11.1) days for all cases. Liver surgery-related morbidity was 10.7%, no mortalities occurred. We achieved an R0 resection in all malignant cases. Conclusions: The 3D technique for parenchyma dissection in robotic liver surgery is a safe and feasible procedure. This novel method offers an advanced locally controlled preparation of intrahepatic vessels and bile ducts. The combination of precise extrahepatic vessel handling with the 3D technique of parenchyma dissection is a fundamental step forward to the standardization of robotic liver surgery for teaching purposing and the wider adoption of robotic hepatectomy into routine patient care.

The application of oleaginous yeast cells as feed supplement, for instance in aqua culture, can be a meaningful alternative for fish meal and oil additives. Therefore, a two-stage fed-batch process split into growth and lipogenesis phase was systematically developed to enrich the oleaginous yeast Rhodotorula glutinis Rh-00301 with high amounts of lipids at industrial relevant biomasses. Thereby, the different carbon sources glucose, sucrose and glycerol were investigated concerning their abilities to serve as a suited raw material for growth and/or lipid accumulation. With the background of economic efficiency C/N ratios of 40, 50 and 70 were investigated as well. It became apparent that glycerol is an improper carbon source most likely because of the passive diffusion of this compound caused by absence of active transporters. The opposite was observed for sucrose, which is the main carbon source in molasses. Finally, an industrially applicable process was successfully established that ensures biomasses of 106±2gL-1 combined with an attractive lipid content of 63±6% and a high lipid-substrate yield (YL/S) of 0.18±0.02gg-1 in a short period of time (84h). Furthermore, during these studies a non-negligible formation of the by-product glycerol was detected. This characteristic of R. glutinis is discussed related to other oleaginous yeasts, where glycerol formation is absent. Nevertheless, due to modifications in the feeding procedure, the formation of glycerol could have been reduced but not avoided.

Chronic stress could promote tumour growth and reduce survival of pancreatic cancer patients via beta-adrenergic receptors of tumour cells. We have tested the impact of chronic acoustic and restraint stress on tumour development in an orthotopic syngeneic murine model of pancreatic cancer.Tumour-bearing C57BL/6 mice exposed to chronic stress had 45% (p = 0.0138) higher circulating steroid and 111% (p = 0.0052) higher adrenal tyrosine hydroxylase levels. Their immune response was significantly suppressed: The in vitro LPS response of splenocytes was significantly reduced regarding Th1- and Th2-cytokines including IFN-gamma, IL-6, IL-10 and MCP-1 (0.0011 p 0.043). Also, tumours of stressed mice showed a tendency towards fewer total CD4 cells, more regulatory T cells (Treg), less T cell/tumour cell contacts and a reduction of CTLA-4 in CD4 cells (p 0.05). TGF-beta in vitro was increased by 23.4% using catecholamines (p 0.012) and in vivo employing chronic stress (p 0.001). After 5 weeks tumour volumes were 130% (p = 0.0061) larger and median survival reduced by 13.5% (p = 0.0058). Tumours expressed more VEGF (p = 0.0334), had greater microvessel densities (p = 0.047), and an increased MMP-9 expression (p = 0.0456). Beta-catecholamines increased proliferation in tumour cells by 18% (p 0.0001) and migration by 78% (p = 0.0348) whereas the beta-blocker propranolol reduced these effects by 25% (p 0.0001) and 53% (p = 0.045), respectively. When stressed tumour-bearing animals were treated with propranolol tumour volumes were reduced by 69% (p = 0.0088) and survival improved by 14% (p 0.0058).The potential treatment with beta-blockers of patients with pancreatic cancer or other malignancies should be further evaluated as an adjuvant anti-neoplastic agent in clinical trials.

Inherently complex problems from many scientific disciplines require a multiscale modeling approach. Yet its practical contents remain unclear and inconsistent. Moreover, multiscale models can be very computationally expensive, and may have potential to be executed on distributed infrastructure. In this paper we propose firm foundations for multiscale modeling and distributed multiscale computing. Useful interaction patterns of multiscale models are made predictable with a submodel execution loop (SEL), four coupling templates, and coupling topology properties. We enhance a high-level and well-defined Multiscale Modeling Language (MML) that describes and specifies multiscale models and their computational architecture in a modular way. The architecture is analyzed using directed acyclic task graphs, facilitating validity checking, scheduling distributed computing resources, estimating computational costs, and predicting deadlocks. Distributed execution using the multiscale coupling library and environment (MUSCLE) is outlined. The methodology is applied to two selected applications in nanotechnology and biophysics, showing its capabilities.

Glutathione (GSH) is a non-coding tripeptide thiol with several important regulative and protective functions in eukaryotes and in most prokaryotes. The primary function of GSH is to maintain the redox potential of the cell, which is directly connected to GSH concentration, and to prevent cellular damages caused by reactive oxygen species or toxic heavy metals. Due to its antioxidant character, it is widely used in pharmaceutical, cosmetic and food industry. There have been different strategies to optimize GSH yield and productivity in bacteria and yeasts by means of metabolic and evolutionary engineering, media optimization and bioprocess engineering. The fed-batch procedure with yeasts of the genera Saccharomyces and Candida is still common method for industrial production. However, for an economic bioprocess production of GSH key factors like media costs, strain performance and process scalability are essential. Beside the extraction and purification of GSH as bulk product, GSH-enriched yeast cells are used for food and beverage applications, as well. This review outlines current applications of microbially produced GSH and illustrates current developments and strategies for its production.

Nature is observed at all scales; with multiscale modeling, scientists bring together several scales for a holistic analysis of a phenomenon. The models on these different scales may require significant but also heterogeneous computational resources, creating the need for distributed multiscale computing. A particularly demanding type of multiscale models, tightly coupled, brings with it a number of theoretical and practical issues. In this contribution, a tightly coupled model of in-stent restenosis is first theoretically examined for its multiscale merits using the Multiscale Modeling Language (MML); this is aided by a toolchain consisting of MAPPER Memory (MaMe), the Multiscale Application Designer (MAD), and Gridspace Experiment Workbench. It is implemented and executed with the general Multiscale Coupling Library and Environment (MUSCLE). Finally, it is scheduled amongst heterogeneous infrastructures using the QCG-Broker. This marks the first occasion that a tightly coupled application uses distributed multiscale computing in such a general way.

† Abstract. The macroscopically emergent rheology of suspensions is dictated by details of fluid-particle and particle-particle interactions. For systems where the typical spatial scale on the particle level is much smaller than that of macroscopic properties, the scales can be split. We present a heterogeneous multiscale method (HMM) approach to modeling suspension flow in which at the macroscale the suspension is treated as a non-Newtonian fluid. The local shear-rate and particle volume fraction are input to a simulation of fully re- solved suspensionmicrodynamics. With the help of these simulations, the apparent viscosity and shear-induced diffusivities can be computed for a given shear-rate and volume fraction, and are then used to complete the information needed in the constitutional relations on the macroscopic level. On both levels, the lattice-Boltzmann method (LBM) is applied to model the fluid phase and coupled to a Lagrangian model for the advection-diffusion of the solid phase. Down and upward mapping of viscosity and diffusivity related quantities will be discussed, as well as information exchanged between the phases on both scales. Temporal scale splitting between viscous and diffusive dynamics has also been exploited to accelerate the macroscopic equilibration dynamics. Additionionally, Galileian and rotational symmetries allow us to make very efficient use of a database where the results of previous simulations can be stored, again reducing the computational effort by factors of several orders of magnitude. The HMM suspension model is applied to the simulation of a 2-dimensional flow through a straight channel of macroscopic width. The equilibration dynamics of flow and volume fraction profiles and equilibrium profiles of volume fraction, diffusivity, velocity, shear-rate, and viscosity are discussed. We show that the proposed HMM model not only reproduces experimental findings for low Reynolds numbers but also predicts additional dependencies introduced by shear-thickening effects not covered by existing macroscopic suspension flow models.

In-stent restenosis, the maladaptive response of a blood vessel to injury caused by the deployment of a stent, is a multiscale system involving a large number of biological and physical processes. We describe a Complex Automata model for in-stent restenosis, coupling bulk flow, drug diffusion, and smooth muscle cell models, all operating on different time scales. Details of the single scale models and of the coupling interfaces are described, together with first simulation results, obtained with a dedicated software environment for Complex Automata simulations. Preliminary results show that the model can reproduce growth trends observed in experimental studies and facilitate testing of hypotheses concerning the interaction of key factors.

In several disciplines, a multiscale approach is being used to model complex natural processes yet a principled background to multiscale modeling is not clear. Additionally, some multiscale models requiring distributed resources to be computed in an acceptable timeframe, while no standard framework for distributed multiscale computing is place. In this paper a principled approach to distributed multiscale computing is taken, formalizing multiscale modeling based on natural processes. Based on these foundations, the Multiscale Modeling Language (MML) is extended as a clear, general, formal, and high-level means to specify scales and interactions in, and as a guide to a uniform approach to crystalize, communicate, develop and execute a multiscale model. With an MML specification, a multiscale model can be analyzed for scheduling or deadlock detection using a task graph. The potential of this method is shown by applying it to two selected applications in nano materials and biophysics.

This paper considers a multiscale description of thrombus formation and its simplified numerical implementation in the case of cerebral aneurysms. In particular, we extend previously introduced generic 2D models towards 3D patient specific aneurysm geometries. The multiscale amplification method contributes to considerably reducing simulation time. This allows us to achieve a mesh resolution high enough to resolve details of the stent geometry which is triggering flow conditions to induce clotting. Simulation results presented in this paper are qualitatively in a good agreement with clinical observations.