Modified immunoscore improves the prediction of progression-free survival in patients with non-muscle-invasive bladder cancer: A digital pathology study

Tumour-infiltrating lymphocytes (TIL), known to be of prognostic value in various solid tumours, have been in the focus of research in the last years. TIL are often quantified via IMMUNOSCORE ® (IS), a scoring system based on TIL cell densities. Recent studies were able to replicate these findings for muscle-invasive bladder cancer (MIBC), however data regarding non-muscle-invasive bladder cancer (NMIBC) are scarce. This study aimed to evaluate the value of a modified Immunoscore (mIS) as a predictive marker for NMIBC prognosis using tissue-micro-arrays (TMAs). We analysed two TMAs containing 316 samples from 158 patients with NMIBC, stained for CD3, CD8, CD45RO and FOXP3. Stained TIL were captured by digital pathology, cumulated, averaged, and reported as density (stained cells per mm²). The mIS was then constructed based on density of all four immune-cell types. Clinical, pathological and follow-up data were collected retrospectively. Univariable and multivariable cox regression analysis was performed to assess the potential value of mIS as a predictor for progression free survival (PFS) and recurrence-free-survival (RFS). Patients within "European Organisation for Research and Treatment of Cancer" (EORTC) risk groups were further substratified in high mIS and low mIS subgroups. Finally log-rank test was used to compare the different survival curves. The median age in our cohort was 68 years (Interquartile Range (IQR): 60 - 76), and 117 (74%) patients were male. A total of 26 patients (16.5%) were classified as EORTC low risk, 45 (28.5%) as intermediate risk and 87 (55.1%) as high risk. Patients in the EORTC high risk group with low mIS showed a shorter PFS in comparison to high mIS (HR 2.9, CI 0.79 - 11.0, p=0.082). In contrast, no predictive potential regarding PFS was observed in intermediate or low risk groups. Furthermore, mIS was not able to predict RFS in any EORTC risk group. mIS could be utilized to predict prognosis more accurately in high-risk patients with NMIBC by identifying those with higher or lower risk of progression. Therefore, mIS could be used to allocate these highrisk patients to more streamlined follow-up or more aggressive treatment strategies. Keywords: biomarker; bladder cancer; digital pathology; immunoscore; prognosis; progressio

Analysis of Multi-Cavity (Bladder, Intestinal and Vaginal) Microbiome in Bladder Cancer Patients: Protocol for a Systematic Review

The overall pathogenesis of bladder cancer is still unknown. The microbiota has been shown to play a critical role in the development of different types of cancer. Nevertheless, the role of the microbiota in the development of bladder cancer is still not fully discovered. This review aims to assess the urinary, vaginal, and intestinal microbiota analyzed from the bacterial, viral, and fungal compartments of bladder cancer patients compared with the microbiota of controls to reveal possible differences. A systematic review according to the PRISMA guidelines will be performed. The findings will be presented in narrative form as well as in tables and graphs

Analysis of Multi-Cavity (Bladder, Intestinal and Vaginal) Microbiome in Bladder Cancer Patients: Protocol for a Systematic Review

The overall pathogenesis of bladder cancer is still unknown. The microbiota has been shown to play a critical role in the development of different types of cancer. Nevertheless, the role of the microbiota in the development of bladder cancer is still not fully discovered. This review aims to assess the urinary, vaginal, and intestinal microbiota analyzed from the bacterial, viral, and fungal compartments of bladder cancer patients compared with the microbiota of controls to reveal possible differences. A systematic review according to the PRISMA guidelines will be performed. The findings will be presented in narrative form as well as in tables and graphs

Lipoconstruct surface topography grating size influences vascularization onset in the dorsal skinfold chamber model

After skin tissue injury or pathological removal, vascularization timing is paramount in graft survival. As full thickness skin grafts often fail to become perfused over larger surfaces, split-thickness grafts are preferred and can be used together with biomaterials, which themselves are non-angiogenic. One way of promoting vascular ingrowth is to “pre-vascularize” an engineered substitute by introducing endothelial cells (ECs). Since it has been previously demonstrated that surface structured biomaterials have an effect on wound healing, skin regeneration, and fibrosis reduction, we proposed that a microvascular-rich lipoconstruct with anisotropic topographical cues could be a clinically translatable vascularization approach. Murine lipofragments were formed with three polydimethylsiloxane molds (flat, 5 µm, and 50 µm parallel gratings) and implanted into the dorsal skinfold chamber of male C57BL/6 mice. Vascular ingrowth was observed through intravital microscopy over 21 days and further assessed by histology and protein identification. Our investigation revealed that topographical feature size influenced the commencement of neovascular ingrowth, with 5 µm gratings exhibiting early construct perfusion at 3 days post-operation, and 50 µm being delayed until day 5. We therefore postulate that surface structured lipoconstructs may serve as an easily obtained and produced construct suitable for providing soft tissue and ECs to tissue defects

Compensatory recruitment allows amphibian population persistence in anthropogenic habitats

International audienceHabitat anthropization is a major driver of global biodiversity decline. Although most species are negatively affected, some benefit from anthropogenic habitat modifications by showing intriguing life-history responses. For instance, increased recruitment through higher allocation to reproduction or improved performance during early-life stages could compensate for reduced adult survival, corresponding to “compensatory recruitment”. To date, evidence of compensatory recruitment in response to habitat modification is restricted to plants, limiting understanding of its importance as a response to global change. We used the yellow-bellied toad ( Bombina variegata ), an amphibian occupying a broad range of natural and anthropogenic habitats, as a model species to test for and to quantify compensatory recruitment. Using an exceptional capture–recapture dataset composed of 21,714 individuals from 67 populations across Europe, we showed that adult survival was lower, lifespan was shorter, and actuarial senescence was higher in anthropogenic habitats, especially those affected by intense human activities. Increased recruitment in anthropogenic habitats fully offset reductions in adult survival, with the consequence that population growth rate in both habitat types was similar. Our findings indicate that compensatory recruitment allows toad populations to remain viable in human-dominated habitats and might facilitate the persistence of other animal populations in such environments