Assessment of Intraoperative Liver Deformation During Hepatic Resection: Prospective Clinical Study

Background: The implementation of intraoperative navigation in liver surgery is handicapped by intraoperative organ shift, tissue deformation, the absence of external landmarks, and anatomical differences in the vascular tree. To investigate the impact of surgical manipulation on the liver surface and intrahepatic structures, we conducted a prospective clinical trial. Methods: Eleven consecutive patients [4 female and 7 male, median age=67years (range=54-80)] with malignant liver disease [colorectal metastasis (n=9) and hepatocellular cancer (n=2)] underwent hepatic resection. Pre- and intraoperatively, all patients were studied by CT-based 3D imaging and assessed for the potential value of computer-assisted planning. The degree of liver deformation was demonstrated by comparing pre- and intraoperative imaging. Results: Intraoperative CT imaging was successful in all patients. We found significant deformation of the liver. The deformation of the segmental structures is reflected by the observed variation of the displacements. There is no rigid alignment of the pre- and intraoperative organ positions due to overall deflection of the liver. Locally, a rigid alignment of the anatomical structure can be achieved with less than 0.5cm discrepancy relative to a segmental unit of the liver. Changes in total liver volume range from −13 to +24%, with an average absolute difference of 7%. Conclusions: These findings are fundamental for further development and optimization of intraoperative navigation in liver surgery. In particular, these data will play an important role in developing automation of intraoperative continuous registration. This automation compensates for liver shift during surgery and permits real-time 3D visualization of navigation imagin

Abschlussbericht der Evaluation des ESF-Programms "Schulverweigerung - Die 2. Chance"

Abschlussbericht der Evaluation des ESF-Programms "Schulverweigerung - Die 2. Chance". Zweitveröffentlichun

Ökonomische, ökologische und Tierwohlaspekte der Weidehaltung von Hochleistungskühen

Dieses Projekt zielte darauf ab, die Grünlandnutzung durch Weidehaltung für Milchkühe mit zu untersuchen. Vor dem Hintergrund, dass der Energiebedarf durch alleinige Weidehaltung in den Sommermonaten nicht gedeckt werden kann und Weidehaltung mit einem höheren Arbeits-aufwand verbunden sein kann, jedoch gleichwohl positive Effekte auf die Tiergesundheit dokumentiert wurden, war es das Ziel zu untersuchen, ob ein ökonomisch messbarer Weideeffekt besteht und welche Rolle das Tierwohl sowie die ökologischen Landschaftsfunktionen des Grünlandes spielen. Die Ergebnisse der on-farm Analyse zeigten, dass bei kombinierter Stall- und Weidehaltung ähnlich hohe Milchleistungen wie bei ganzjähriger Stallhaltung möglich sind. Auffälligkeiten am Integument der Tiere resultieren hauptsächlich aus Mängeln in der Haltungsumwelt und können das Tierwohl erheblich beeinträchtigen. Die Haltung auf der Weide bringt unter diesem Aspekt deutliche Vorteile, allerdings werden die Regenerationseffekte im folgenden Winter größtenteils wieder neutralisiert. Die Berücksichtigung dieser Aspekte in der Effizienzmessung zeigte, dass das mitunter größte Einsparpotential im Sinne einer Verbesserung der technischen Effizienz bei den Lahmheiten liegt. Es lässt sich kein Arbeitsmehraufwand bei den Weidebe-trieben im Saisonwechsel feststellen, da durch Einsparungen bei anderen Arbeitsvorgängen der Mehraufwand der Weidearbeiten ausgeglichen wurde. Das größte Potenzial bietet die Futterversorgung über die Weide. Hierfür ist ein eng aufeinander abgestimmtes Weide- und Herdemanagement essentiell, da unangepasstes Weidemanagement zu unterschiedlich ausgeprägten Trittschäden und in der Konsequenz zu Ertragsausfällen und Veränderungen der Futterqualität infolge von Verschieben der Artenzusammensetzung führt. Die Ergebnisse zeigten weiterhin, dass Grünlandnutzung als Weide zu einer erhöhten Humusspeicherung und somit zu einer echten klimawirksamen Kohlenstoffsequestrierung führt

The Effects of 5-Hydroxytryptophan in Combination with Different Fatty Acids on Gastrointestinal Functions: A Pilot Experiment

Background. Fat affects gastric emptying (GE). 5-Hydroxythryptophan (5-HTP) is involved in central and peripheral satiety mechanisms. Influence of 5-HTP in addition to saturated or monounsaturated fatty acids (FA) on GE and hormone release was investigated. Subjects/Methods. 24 healthy individuals (12f : 12m, 22-29 years, BMI 19-25.7 kg/m(2)) were tested on 4 days with either 5-HTP + short-chain saturated FA (butter), placebo + butter, 5-HTP + monounsaturated FA (olive oil), or placebo + olive oil in double-blinded randomized order. Two hours after FA/5-HTP or placebo intake, a C-13 octanoid acid test was conducted. Cortisol, serotonin, cholecystokinin (CCK), and ghrelin were measured, as were mood and GE. Results. GE was delayed with butter and was normal with olive (P < 0.05) but not affected by 5-HTP. 5-HTP supplementation did not affect serotonin levels. Food intake increased plasma CCK (F = 6.136; P < 0.05) irrespective of the FA. Ghrelin levels significantly decreased with oil/5-HTP (F = 9.166; P < 0.001). The diurnal cortisol profile was unaffected by FA or 5-HTP, as were ratings of mood, hunger, and stool urgency. Conclusion. Diverse FAs have different effects on GE and secretion of orexigenic and anorexigenic hormones. Supplementation of 5-HTP had no effect on plasma serotonin and central functions. Further studies are needed to explain the complex interplay

Polymorphisms within Novel Risk Loci for Type 2 Diabetes Determine β-Cell Function

BACKGROUND: Type 2 diabetes arises when insulin resistance-induced compensatory insulin secretion exhausts. Insulin resistance and/or beta-cell dysfunction result from the interaction of environmental factors (high-caloric diet and reduced physical activity) with a predisposing polygenic background. Very recently, genetic variations within four novel genetic loci (SLC30A8, HHEX, EXT2, and LOC387761) were reported to be more frequent in subjects with type 2 diabetes than in healthy controls. However, associations of these variations with insulin resistance and/or beta-cell dysfunction were not assessed. METHODOLOGY/PRINCIPAL FINDINGS: By genotyping of 921 metabolically characterized German subjects for the reported candidate single nucleotide polymorphisms (SNPs), we show that the major alleles of the SLC30A8 SNP rs13266634 and the HHEX SNP rs7923837 associate with reduced insulin secretion stimulated by orally or intravenously administered glucose, but not with insulin resistance. In contrast, the other reported type 2 diabetes candidate SNPs within the EXT2 and LOC387761 loci did not associate with insulin resistance or beta-cell dysfunction, respectively. CONCLUSIONS/SIGNIFICANCE: The HHEX and SLC30A8 genes encode for proteins that were shown to be required for organogenesis of the ventral pancreas and for insulin maturation/storage, respectively. Therefore, the major alleles of type 2 diabetes candidate SNPs within these genetic loci represent crucial alleles for beta-cell dysfunction and, thus, might confer increased susceptibility of beta-cells towards adverse environmental factors

Environmental Sustainability Post-COVID-19: Scrutinizing Popular Hypotheses from a Social Science Perspective

There is an increasingly vocal debate on potential long-term changes in environmental sustainability spurred by the global COVID-19 pandemic. This article scrutinizes the social science basis of selected popular hypotheses regarding the nexus between the COVID-19 pandemic and the societal transitions towards environmental sustainability. It presents results that were derived through an interdisciplinary dialogue among social scientists. First, it is confirmed that the COVID-19 crisis has likely created a potential window of opportunity for societal change. Yet, to ensure that societal change is enduring and actually supporting the transition towards environmental sustainability, a clear and well-targeted political framework guiding private investments and behavior is required. Second, it is emphasized that there are important structural differences between the COVID-19 crisis and environmental crises, like time scales. Consequently, many strategies used to address the COVID-19 crisis are hardly suitable for long-term transitions towards environmental sustainability. Third, it is argued that transitions towards environmental sustainability—building both on reducing environmental degradation and building socio-techno-ecological resilience—may create co-benefits in terms of preventing and coping with potential future pandemics. However, research still needs to explore how big these synergies are (and whether trade-offs are also possible), and what type of governance framework they require to materialize

Extended hypothermic oxygenated machine perfusion enables ex situ preservation of porcine livers for up to 24 hours

Background & Aims: End-ischemic hypothermic oxygenated machine perfusion (HOPE) of the donor liver for 1-2 h mitigates ischemia-reperfusion injury during subsequent liver transplantation. Extended preservation time may be preferred to facilitate difficult recipient hepatectomy or to optimize logistics. We therefore investigated whether end-ischemic dual HOPE (DHOPE) could extend preservation time for up to 24 h using a porcine liver reperfusion model. Methods: Following 30 min warm ischemia, porcine livers were subjected to 2 h static cold storage (SCS), followed by 2 h, 6 h, or 24 h DHOPE (n = 6 per group). Subsequent normothermic reperfusion was performed for 4 h using autologous blood. Two livers preserved by 24 h SCS served as additional controls. A proof of principle confirmation was carried out in 2 discarded human livers subjected to extended DHOPE. Hepatocellular and cholangiocyte injury and function were assessed. Oxidative stress levels and histology were compared between groups. Results: Perfusion flows remained stable during DHOPE, regardless of duration. After normothermic reperfusion, livers perfused for 24 h by DHOPE had similar lactate clearance, blood pH, glucose, and alanine aminotransferase levels, and biliary pH, bicarbonate, and LDH levels, as livers perfused for 2 h and 6 h. Levels of malondialdehyde and high-mobility group box 1 in serum and liver parenchyma were similar for all groups. Histological analysis of bile ducts and liver parenchyma revealed no differences between the groups. Extended DHOPE in discarded human livers preserved hepatocellular and cholangiocyte function and histology after reperfusion. In contrast, livers preserved by 24 h SCS were non-functioning. Conclusion: Extended end-ischemic DHOPE enabled successful preservation of porcine and discarded human donor livers for up to 24 h. Extended DHOPE enables safe extension of preservation time, which may facilitate allocation and transplantation from a logistical perspective, and further expand the donor pool. Lay summary: It has been suggested that preserving liver grafts with a technique called (dual) hypothermic oxygenated machine perfusion ([D]HOPE) leads to better outcomes after transplantation than if livers are stored on ice, especially if an organ is of lesser quality. In this study, we showed that DHOPE could be used to preserve liver grafts for up to 24 h. This extended procedure could be used globally to facilitate transplantation and expand the donor pool

Restoration of Bile Duct Injury of Donor Livers During Ex Situ Normothermic Machine Perfusion

BACKGROUND: End-ischemic ex situ normothermic machine perfusion (NMP) enables assessment of donor livers prior to transplantation. The objective of this study was to provide support for bile composition as a marker of biliary viability and to investigate whether bile ducts of high-risk human donor livers already undergo repair during NMP.METHODS: Forty-two livers that were initially declined for transplantation were included in our NMP clinical trial. After NMP, livers were either secondary declined (n = 17) or accepted for transplantation (n = 25) based on the chemical composition of bile and perfusate samples. Bile duct biopsies were taken before and after NMP and assessed using an established histological injury severity scoring system and a comprehensive immunohistochemical assessment focusing on peribiliary glands (PBGs), vascular damage, and regeneration.RESULTS: Bile ducts of livers that were transplanted after viability testing during NMP showed better preservation of PBGs, (micro)vasculature, and increased cholangiocyte proliferation, compared with declined livers. Biliary bicarbonate, glucose, and pH were confirmed as accurate biomarkers of bile duct vitality. In addition, we found evidence of PBG-based progenitor cell differentiation toward mature cholangiocytes during NMP.CONCLUSIONS: Favorable bile chemistry during NMP correlates well with better-preserved biliary microvasculature and PBGs, with a preserved capacity for biliary regeneration. During NMP, biliary tree progenitor cells start to differentiate toward mature cholangiocytes, facilitating restoration of the ischemically damaged surface epithelium.</p