BACKGROUND:The greatest impact on the burden of CNS infections resulted from preventive measures, mainly vaccination programs, that have decreased the incidence of many CNS infections significantly. Here, we highlight the main cornerstones of vaccination programs on bacterial and viral CNS infections and point at future chances of upcoming vaccines. MAIN BODY:Vaccination programs have significantly decreased the number of cases due to Haemophilus influenzae type B and Neisseria meningitidis. For pneumococcal meningitis, new vaccines that prevent neuroinvasive serotypes have the potential to decrease numbers in the future. Whereas a vaccine is available for tick-borne encephalitis, prevention of neuroborreliosis is limited to contact precautions. However, vaccination rates against tick-borne encephalitis remain too low in many countries. Another neurotropic virus that can be prevented effectively by vaccination is varicella zoster virus (VZV). Interestingly, vaccination against VZV also seems to reduce the risk of dementia as recently shown. While vaccination is important in general, patients with immunosuppression benefit most from vaccinations. Finally, recent measles outbreaks impressively underline the efficacy of vaccination programs and demonstrate what can happens if vaccination rates decrease. CONCLUSION:Vaccination programs have shown to be effective in reducing the burden of CNS infections. As vaccination rates are generally still too low and as new vaccines are coming up, it is obvious that the potential of vaccines to prevent CNS infections is not maxed out yet.
Sowohl der operative Eingriff als auch die Narkose führen zu Veränderungen des intravasalen Volumenstatus des Patienten. Ziele der perioperativen Flüssigkeits- bzw. Volumentherapie sind die Aufrechterhaltung des zirkulierenden intravasalen Volumen (Normovolämie), einer adäquaten Gewebeperfusion und -oxygenierung, des Gleichgewichts im Elektrolythaushalt sowie die Aufrechterhaltung der Normoglykämie.
Abstract Background Long non-coding RNAs (lncRNAs) regulate multiple cellular processes and are involved in the development and progression of human cancers, including renal cell carcinoma (RCC). Methods Genome-wide DNA methylation profiling using Illumina EPIC arrays was performed to identify differentially methylated regions (DMR) associated with metastatic RCC. Candidate loci within LINC01354 and LINC01510 were validated by pyrosequencing in 145 primary RCC tissues, 124 paired tumor-adjacent normal tissues (adNs), and 194 metastatic tissue samples obtained from 101 patients with metastatic RCC. In addition, data from The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma Collection (TCGA-KIRC) were analyzed in silico to assess the clinical relevance of DNA methylation (DNAm) and its association with gene expression. Results Hypermethylation across all analyzed CpG sites at both loci was associated with high-stage (≥ T3; p = 0.001) and high-grade (≥ G3; p = 0.003) RCC and was markedly increased in metastatic tissues compared with localized primary tumors ( p < 0.001). In addition, primary tumors from patients with distant metastases (M+) showed significantly higher methylation at PS_307-CG1 within LINC01510 than tumors from patients without distant metastases (M0; p = 0.031). Analyses of TCGA-KIRC data confirmed associations of increased methylation with adverse clinicopathological features and reduced gene expression, supporting a potential role for epigenetic silencing. Conclusion Our data provide further insight into the epigenetic alterations associated with RCC progression by demonstrating tumor- and metastasis-associated hypermethylation at the LINC01354 and LINC01510 loci. The association of hypermethylation with advanced disease and metastatic tissues, together with the observed inverse relationship between methylation and expression, suggests that epigenetic inactivation of these lncRNAs may contribute to RCC progression. DNAm at these loci may therefore represent a potential biomarker of aggressive disease.
Background & Aims Tumour-infiltrating lymphocytes (TIL) therapy has shown durable efficacy in melanoma but remains largely ineffective in immunologically “cold” malignancies such as colorectal cancer (CRC) and prostate cancer (PC), which are characterized by poor intratumoural T-cell infiltration and limited responsiveness to immunotherapies.CytoPLY™ is a novel TIL manufacturing platform designed to overcome these limitations by enabling optimized ex vivo expansion and functional programming of tumour-reactive T cells, resulting in enhanced cellular fitness and persistence from cold tumours. Methodology ProbeTILity is a first-in-human, open-label phase I/IIa trial evaluating the safety, feasibility, and preliminary activity of repeated administrations of CytoPLY™-manufactured autologous TILs (CC-38) in patients with metastatic CRC or PC who have progressed after all available standard-of-care therapies.Eligible patients undergo tumour resection for TIL manufacturing using a GMP-compliant, two-phase expansion process. Following cyclophosphamide lymphodepletion, patients receive up to three intravenous CC-38 infusions at 4–6-week intervals with interleukin-2 support. Up to 12 patients will be enrolled. The primary endpoint is safety, tolerability and feasibility, of repeated CC-38 administrations without treatment-emergent adverse event (≥grade 3). Secondary endpoints include objective response rate (RECIST 1.1/iRECIST), progression-free survival, overall survival, and tumour-specific biomarkers. Exploratory analyses will assess TIL persistence, clonality, and tumour microenvironment modulation. Results Recruitment is ongoing. Safety, feasibility, and translational immunomonitoring data will be reported as they become available. Conclusion ProbeTILity represents the first clinical evaluation of repeated administrations of CytoPLY™-manufactured autologous TILs in metastatic colorectal and prostate cancer. This study will provide critical insights into the safety, feasibility, and immunological impact of next-generation TIL therapy in immunologically cold tumours and inform future clinical development strategies.EU CT number: 2025-521227-70-00, Clinical Trial: NCT07255664.
