European Society of Anaesthesiology.

Mice expressing a transgene encoding the transcription factor NF-E2 in hematopoietic cells exhibit features of myeloproliferative neoplasms, including thrombocytosis, Epo-independent colony formation, stem and progenitor cell overabundance, leukocytosis, and progression to acute myeloid leukemia.

Retinal ischemia and reperfusion injuries (R-IRI) damage neuronal tissue permanently. Recently, we demonstrated that Argon exerts anti-apoptotic and protective properties. The molecular mechanism remains unclear. We hypothesized that Argon inhalation exert neuroprotective effects in rats retinal ganglion cells (RGC) via an ERK-1/2 dependent regulation of heat-shock proteins. Inhalation of Argon (75 Vol%) was performed after R-IRI on the rats 0 left eyes for 1 h immediately or with delay. Abbreviations used: ChAT, choline acetyltransferase; CO 2 , carbon dioxcide; DAPI, 4 0 , 6-diamino-2-phenylindole dihydrochloride hydrate; DMSO, dimethylsulfoxid; ERK, extracellular regulated protein kinase; FG, Fluorogold; GFAP, glial fibrillary acidic protein; HO-1, hemeoxygenase-1; HSP, heat-shock protein(s); Iba1, ionized calcium binding adaptor molecule 1; JNK, c-Jun N-terminale kinase; MAPK, mitogen activated protein kinases; NF-jB, nuclear factor j B; PBS, phosphate buffered saline; PD98059, ERK inhibitor; RGC, retinal ganglion cell(s); R-IRI, retinal ischemia/reperfusion injury.

Argon has recently come into scientific focus as a neuroprotective agent. The underlying neuroprotective mechanism remains unknown although toll-like receptors were recently suggested to play an important role. We hypothesized that TLR-associated downstream transcription factors are responsible for argon's effects, leading to anti-apoptotic and antiinflammatory properties. Apoptosis was induced in human neuroblastoma cells. Immediately afterwards, argon treatment (75 Vol% for 2 h) was initiated. Cells were analyzed, measuring mitochondrial membrane potential, reactive-oxygen-species, annexin-V/propidium iodide staining, transcription factor phosphorylation and binding activity as well as protein and mRNA expression of interleukins. Argon's in vivo effects were analyzed by quantification of retinal ganglion cell density, mRNA expression, serum cytokine analysis and immunohistochemistry after retinal ischemia reperfusion injury (IRI) in rats. Argon diminished rotenone-induced kappa-lightchain-enhancer' of activated B-cells (NF-jB) and signal transducer and activator of transcription 3 (STAT3) but not Cerebral ischemia and reperfusion injury -for example, stroke -is associated with destruction of neuronal tissue and subsequent increased mortality or functional disability. At a molecular level inflammation, oxidative stress and apoptosis play an important role in this detrimental process (Ahmad et al. 2014). As a result of the fact that neurons have a limited potential to regenerate, ischemia and reperfusion injury is a major cause of morbidity and mortality (Ng et al. 2011 Abbreviations used: DMSO, dimethylsulfoxid; ERK-1/2, extracellular regulated kinase-1/2; IL, interleukin; IRI, ischemia reperfusion injury; NF-jB, kappa-light-chain-enhancer' of activated B-cells; STAT3, signal transducer and activator of transcription 3.

The study was registered in the German Clinical Trials Register (DRKS 00006961). https://drks-neu.uniklinik-freiburg.de/drks_web/.

PurposeRecently, the noble gas argon attracted significant attention due to its neuroprotective properties. However, the underlying molecular mechanism is still poorly understood. There is growing evidence that the extracellular regulated kinase 1/2 (ERK1/2) is involved in Argon´s protective effect. We hypothesized that argon mediates its protective effects via the upstream located toll-like receptors (TLRs) 2 and 4.MethodsApoptosis in a human neuroblastoma cell line (SH-SY5Y) was induced using rotenone. Argon treatment was performed after induction of apoptosis with different concentrations (25, 50 and 75 Vol% in oxygen 21 Vol%, carbon dioxide and nitrogen) for 2 or 4 hours respectively. Apoptosis was analyzed using flow cytometry (annexin-V (AV)/propidiumiodide (PI)) staining, caspase-3 activity and caspase cleavage. TLR density on the cells’ surface was analyzed using FACS and immunohistochemistry. Inhibition of TLR signaling and extracellular regulated kinase 1/2 (ERK1/2) were assessed by western blot, activity assays and FACS analysis.ResultsArgon 75 Vol% treatment abolished rotenone-induced apoptosis. This effect was attenuated dose- and time-dependently. Argon treatment was accompanied with a significant reduction of TLR2 and TLR4 receptor density and protein expression. Moreover, argon mediated increase in ERK1/2 phosphorylation was attenuated after inhibition of TLR signaling. ERK1/2 and TLR signaling inhibitors abolished the anti-apoptotic and cytoprotective effects of argon. Immunohistochemistry results strengthened these findings.ConclusionThese findings suggest that argon-mediated anti-apoptotic and neuroprotective effects are mediated via inhibition of TLR2 and TLR4.

Objective: Post-operative pulmonary complications (PPCs) represent the most frequent complications after lung surgery. The aim of this study was to identify the modifiable risk factors for PPCs after video-assisted thoracoscopic surgery (VATS) in lung cancer patients.Methods: Data of this retrospective study were extracted from the German Thorax Registry, an interdisciplinary and multicenter database of the German Society of Anesthesiology and Intensive care medicine and the German Society of ThoracicSurgery. Univariate and multivariate stepwise logistic regression analysis of patientspecific and procedural risk factors for PPCs were conducted. Results:We analyzed 376 patients with lung cancer who underwent VATS bilobectomy (n = 2), lobectomy (n = 258) or segmentectomy (n = 116) in 2016 and 2017. Onehundred fourteen patients (114/376; 30%) developed PPCs. Two patients died within 30 days after surgery. In the univariate analysis, patients of the PPC group showed significantly more often a body mass index (BMI) ≤ 19 kg/m 2 ; a pre-operative forced expiratory volume in 1 second (FEV 1 ) ≤ 60%; a pre-operative arterial oxygen partial pressure (p a O 2 ) ≤ 60 mm Hg; a higher rate of prolonged duration of surgery (≥2 hours [h]) and a higher frequency of intraoperative blood loss ≥500 mL. The multivariate stepwise logistic regression analysis revealed 4 independent risk factors: FEV 1 ≤ 60%(1.9[1.1-3.4] OR [95% CI], P = 0.029); p a O 2 ≤ 60 mm Hg (4.6[1.7-12.8] OR [95% CI], P = 0.003; duration of surgery ≥2 hours (2.7[1.5-4.7] OR [95% CI], P = 0.001) and intraoperative crystalloids ≥6 mL/kg/h (2.9[1.2-7.5] OR [95% CI], P = 0.023). Conclusion:Intraoperative amount of crystalloid fluids should be kept below 6 mL/ kg/h and duration of surgery should be below 2 hours to avoid an increased risk for PPCs.

BackgroundPostoperative complications after lung surgery are frequent, having a detrimental effect on patients’ further course. Complications may lead to an increased length of hospital stay and cause additional costs. Several risk factors have been identified but it is still difficult to predict contemporary which patients are at risk. We hypothesized that patients who show an increased inflammatory response at the time of wound closure and 24 hours after surgery are at risk of postoperative complications within 30 days after surgery.MethodsPostoperative complications (pulmonary, cardiac, neurological and renal) of 96 patients scheduled for lung surgery at the Medical Center–University of Freiburg were analyzed in this prospective, clinical study. Blood samples for cytokine analysis (Interleukin (IL)-6, IL-8, IL-10, Tumor necrosis factor [TNF]-α, IL-1ß and IL12p70) were taken before surgery, at wound closure and 24 hours after surgery. Cytokine levels of patients with and without postoperative complications were analyzed by Receiver operating characteristic (ROC) curve analysis. To adjust the results according to existing covariates a multivariate logistic regression analysis was conducted.ResultsThe complication and non-complication group differed significantly according to nicotine dependency, Angiotensin-receptor-II blocker medication, rate of thoracotomy and preoperative lung function. The intraoperative hemodynamic parameters and therapy did not differ between the groups. Twenty-nine patients (30%) developed postoperative complications within 30 days after surgery. Plasma concentrations of IL-6, IL-10 and IL-8 at the time of wound closure and 24 hours after surgery were higher in the complication group. Multivariate regression analysis on postoperative complications revealed an Odds ratio of 56 for patients with IL-6 and IL-8 levels above the 3rd quartile measured on the first postoperative day.ConclusionsPerioperative detection of increased plasma concentrations of inflammatory cytokines in lung surgery may be used in addition to other clinical predictors to identify patients at risk for postoperative complications.Trial registrationGerman Clinical Trials Register 00006961.