[Prospective Cohort Study of In-Hospital Patients Undergoing Ophthalmic Surgery for the Validation of ClassIntra: Classification of Intraoperative Adverse Events]. / Prospektive Kohortenstudie bei stationären augenchirurgischen Patienten für die Validierung der ClassIntra-Klassifikation für unerwünschte intraoperative Ereignisse.

BACKGROUND: To the best of our knowledge, there is no validated classification to assess intraoperative adverse events (iAEs) in ophthalmic surgery. ClassIntra is a newly developed classification for surgery- and anaesthesia-related iAEs that has been recently validated in various surgical disciplines, but not in ophthalmic surgery. We aim to assess the validity and practicability of ClassIntra in patients undergoing ophthalmic surgery. METHODS: A consecutive sample of in-hospital patients undergoing any type of ophthalmic surgery was included in this single-centre prospective cohort study. iAEs were classified using ClassIntra, consisting of 5 severity grades according to the symptoms of the patient and the required treatment. All patients were followed for two weeks to record all postoperative adverse events according to Clavien-Dindo. The primary endpoint was the risk-adjusted association between the most severe iAE and the weighted sum of all postoperative adverse events within the two-week follow-up using the Comprehensive Complication Index (CCI). In addition, ophthalmologists and anaesthesiologists were asked to complete an online survey assessing the severity of iAEs for 10 fictitious clinical case scenarios. Reliability was assessed by comparing the clinicians' ratings to the prespecified benchmark rating of the study team. RESULTS: In this study, 100 in-hospital patients with an average age of 64 years (SD 15) were included. The majority of all patients were ASA II (n = 53, 53%) or III (n = 42, 42%). Thirty-two iAEs were recorded in 22 patients (17 grade I, 12 grade II, 3 grade III). Ninety-four postoperative adverse events occurred in 50 patients (44 grade I, 36 grade II, 14 grade IIIa). We found a mean difference in CCI of 2,1 (95% confidence interval [CI] - 2,5 to 6,8) per one unit increase in severity grades of ClassIntra. Fifty ophthalmologists and anaesthesiologists completed the online survey (response rate 54%). The intraclass correlation coefficient was 0,79 (95% CI 0,64 to 0,94). CONCLUSIONS: The application of ClassIntra during daily routine in ophthalmic surgery showed the usefulness and practicability of this classification for the standardised assessment of intraoperative adverse events. Although construct validity could not be demonstrated, the good reliability in the survey's rating underlines the criterion validity of this newly developed classification in ophthalmic surgery.

Argon Mediates Anti-Apoptotic Signaling and Neuroprotection via Inhibition of Toll-Like Receptor 2 and 4.

PURPOSE: Recently, 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. METHODS: Apoptosis 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. RESULTS: Argon 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. CONCLUSION: These findings suggest that argon-mediated anti-apoptotic and neuroprotective effects are mediated via inhibition of TLR2 and TLR4.