Two patients with a complete proximal rupture of the hamstring

Two men visited our Emergency Room because of a water-ski-accident. At physical examination, there was hematoma at the upper leg with loss of strength at extension of the hip and flexion of the knee. Both patients had a palpable gap just distal of the ischial tuberosity. Further imaging by sonography and MR-scan showed a rupture of the proximal hamstring tendon. Treatment was operative refixation of the hamstring tendons at the ischial tuberosity. Aftertreatment consisted of brace for 4 weeks after operation. Both patients returned to their pre-operatively sports, though at a lower level. Surgical treatment of a complete proximal rupture of the hamstrings is recommended in case of sportive patients

Associations with photoreceptor thickness measures in the UK Biobank

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40–69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

Switch of anti-VEGF agents is an option for nonresponders in the treatment of AMD

BACKGROUND: Although anti-VEGF therapy of exudative AMD with bevacizumab and ranibizumab proved efficacious in the majority of patients, CNV activity does not respond to continued treatment after repeated injections in a considerable amount of patients. These are referred to as nonresponders. A change of the drug to bevacizumab or ranibizumab could possibly offer an alternative option for the treatment of nonresponding exudative AMD. METHODS AND MATERIALS: A total of 138 nonresponders who switched therapy from bevacizumab to ranibizumab (n=114) or vice versa (n=24) were included in a retrospective study. Visual acuity (VA) and foveal thickness before and after the switch of therapy were compared. By means of linear regression analysis, we analyzed possible prognostic factors associated with a favorable outcome for visual acuity. RESULTS: Linear regression analysis revealed a statistically significant benefit for nonresponders when treatment was changed to a different anti-VEGF drug (bevacizumab or ranibizumab). VA at the time of the switch was positively correlated with a beneficial development of VA after changing the drug. There was no significant correlation with age, macular thickness, number of injections before the switch, or the development of VA under treatment before the switch. Both patients switching to Avastin and Lucentis benefitted without statistically significant differences. CONCLUSIONS: An exchange of bevacizumab with ranibizumab or vice versa should be considered in nonresponders in the treatment of exudative AMD. Further prognostic factors may help to identify patients who might benefit from a switch. These factors should be investigated in further studies

Abstract 297: Innovation in delivering synthetically challenging bicyclic arginase inhibitors to enhance immunotherapy

Abstract Arginase overexpression has been associated with poor survival rates in advanced cancer patients treated with Keytruda. High levels of Arginase may lead to a depletion of arginine within the tumor microenvironment, inhibiting the immune response. Thus, arginase inhibition has the potential to greatly enhance immunotherapy treatment. Discovering novel arginase inhibitors was met with several challenges including analyzing/purifying extremely polar chemical matter without chromophores, synthetically challenging space, and poor bioavailability of compounds with ClogP less than minus two. Cross-functional collaborations and innovations rapidly overcame these challenges. Structural chemistry and modeling guided the design of novel arginase inhibitors. Analytical and purification groups developed innovative analytical/purification methods. Novel technologies including ReatIR and Vapourtec flow system, provided key intermediates to enable chartering into synthetically challenging space. Through creative cyclization strategies and active transport strategy to improve bioavailability, the team ultimately delivered a diverse set of potent and extremely synthetically challenging arginase inhibitors to study the potential of arginase inhibition. Preliminary in vivo evaluation showed single agent efficacy in an EMT6 model. These arginase inhibitors have the potential to enhance immunotherapy. Citation Format: Derun Li, Hongjun Zhang, Thomas W. Lyons, Theodore A. Martinot, Abdelghani Achab, Min lu, Lisa M. Nogle, Spencer McMinn, Matthew J. Mitcheltree, Matthew Childers, Qinglin Pu, Symon Gathiaka, Anand Palani, Kalyan Chakravarthy, Amy D. DeCastro, Jennifer O'Neil, Roshi Afshar, Nicole C. Walsh, Peter W. Fan, Mangeng Cheng, Richard Miller, Amy Doty, Rachel Palte, Hai-Young Kim, Josep Saurí, Adam Beard, Christopher Brynczka, Christian Fischer. Innovation in delivering synthetically challenging bicyclic arginase inhibitors to enhance immunotherapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 297.</jats:p