Cornelius Wiedenmann

Abstract Purpose: Cell-to-cell variability in apoptosis signaling contributes to heterogenic responses to cytotoxic stress in clinically heterogeneous neoplasia, such as acute myeloid leukemia (AML). The BCL-2 proteins BAX and BAK can commit mammalian cells to apoptosis and are inhibited by retrotranslocation from the mitochondria into the cytosol. The subcellular localization of BAX and BAK could determine the cellular predisposition to apoptotic death. Experimental Design: The relative localization of BAX and BAK was determined by fractionation of AML cell lines and patient samples of a test cohort and a validation cohort. Results: This study shows that relative BAX localization determines the predisposition of different AML cell lines to apoptosis. Human AML displays a surprising variety of relative BAX localizations. In a test cohort of 48 patients with AML, mitochondria-shifted BAX correlated with improved patient survival, FLT3-ITD status, and leukocytosis. Analysis of a validation cohort of 80 elderly patients treated with myelosuppressive chemotherapy confirmed that relative BAX localization correlates with probability of disease progression, FLT3-ITD status, and leukocytosis. Relative BAX localization could therefore be helpful to identify elderly or frail patients who may benefit from cytotoxic therapy. Conclusions: In this retrospective analysis of two independent AML cohorts, our data suggest that Bax localization may predict prognosis of patients with AML and cellular predisposition to apoptosis, combining the actual contribution of known and unknown factors to a final “common path.” Clin Cancer Res; 23(16); 4805–16. ©2017 AACR.

Background: Fibrosis limits the success of filtering glaucoma surgery. We employed 2D and 3D in vitro models to assess the effects of fluid flow on human tenon fibroblasts (HTF). Methods: HTF were exposed to continuous or pulsatile fluid flow for 48 or 72 h, at rates expected at the transscleral outflow site after filtering surgery. In the 2D model, the F-actin cytoskeleton and fibronectin 1 (FN1) were visualized by confocal immunofluorescence microscopy. In the 3D model, mRNA and whole cell lysates were extracted to analyze the expression of fibrosis-associated genes by qPCR and Western blot. The effects of a small-molecule inhibitor of the TGF-β receptor ALK5 were studied. Results: Slow, continuous fluid flow induced fibrotic responses in the 2D and 3D models. It elicited changes in cell shape, the F-actin cytoskeleton, the deposition of FN1 and activated the intracellular TGF-β signaling pathway to induce expression of fibrosis-related genes, such as CTGF, FN1 and COL1A1. ALK5-inhibition reduced this effect. Intermittent fluid flow also induced fibrotic changes, which decreased with increasing pause duration. Conclusions: Slow interstitial fluid flow is sufficient to induce fibrosis, could underlie the intractable nature of fibrosis following filtering glaucoma surgery and might be a target for antifibrotic therapy.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic restricted face-to-face interactions of medical students and teachers. OBJECTIVE: To develop and evaluate an online course for ophthalmology examination techniques for medical students and to determine the impact of the course on the practical objective structured clinical examination (OSCE). MATERIAL AND METHODS: The online examination course was developed as a video-based tutorial according to the SMART (specific, measurable, activating, reasonable, time-bound) principle covering all topics of the National Competency-based Catalogue of Learning Objectives for Medical Education and made available to medical students in the ophthalmology course. At the end of the semester the students graded the online examination course on an ordinal scale from 1 (strongly agree) to 6 (strongly disagree) anonymously and were asked for comments. The grades of the OSCE (range 1-5) were compared with the OSCE results of the previous semester. RESULTS: Of the 164 students 67 participated in the online evaluation (41%). The students reported to be well-prepared for the OSCE (mean grade 2.0; SD 1.0). In the future, 70% of the students would prefer combined online and on-site teaching (47 out of 67 students). Among all 164 students, the mean OSCE results were excellent (mean grade 1.1; SD 0.2) and comparable to the previous semester (mean grade among 166 students, 1.1; SD 0.2; two-sided t-test, p = 0.86). CONCLUSION: The online course on ophthalmology examination techniques allowed medical students to prepare for the OSCE. Beyond the COVID-19 pandemic, online teaching options can support on-site teaching.

The occurrence of malignant glaucoma several years after cataract surgery is a very rare delayed complication. An increasing myopic shift can be an early hint for the formation. A surgical intervention is often inevitable; however, intraocular pressure can also be successfully managed with conservative treatment as in the case described. Therefore, treatment should be adapted to the situation and individually decided how invasive the treatment must be and whether a vitrectomy is absolutely necessary.

BACKGROUND: The occurrence of herpes zoster is rising globally. Future trends will be influenced by changes in population demographics and the growing number of patients at risk. Overall this poses a challenge for healthcare systems. METHODS: In our interdisciplinary, single-centre retrospective analysis, we aimed to assess the burden of the disease within the Department of Dermatology and the Eye Centre from the Medical Centre, University of Freiburg from 2009-2022. We obtained data from 3034 cases coded using the ICD-10 B02.x. Patients were characterised by sex, age, year of treatment, and type of treatment (inpatient vs. outpatient). RESULTS: Overall we observed a 200% increase in the number of herpes zoster patients over the 13-year period. Upon closer analysis, this was mainly due to a rise in inpatient treatment for herpes zoster ophthalmicus. CONCLUSIONS: If the incidence of herpes zoster ophthalmicus continues to increase at the current rate the number of hospitalisations of zoster ophthalmicus would double by 2040, assuming guideline-appropriate treatment. Overall, the results show a growing need for inpatient ophthalmological care.