A precise performance-based reimbursement model for the multi-centre NAPKON cohorts - development and evaluation.

Fair allocation of funding in multi-centre clinical studies is challenging. Models commonly used in Germany - the case fees ("fixed-rate model", FRM) and up-front staffing and consumables ("up-front allocation model", UFAM) lack transparency and fail to suitably accommodate variations in centre performance. We developed a performance-based reimbursement model (PBRM) with automated calculation of conducted activities and applied it to the cohorts of the National Pandemic Cohort Network (NAPKON) within the Network of University Medicine (NUM).

Artificial intelligence and neoantigens: paving the path for precision cancer immunotherapy.

Cancer immunotherapy has witnessed rapid advancement in recent years, with a particular focus on neoantigens as promising targets for personalized treatments. The convergence of immunogenomics, bioinformatics, and artificial intelligence (AI) has propelled the development of innovative neoantigen discovery tools and pipelines. These tools have revolutionized our ability to identify tumor-specific antigens, providing the foundation for precision cancer immunotherapy.

Prediction of tumor-specific splicing from somatic mutations as a source of neoantigen candidates.

Motivation: Neoantigens are promising targets for cancer immunotherapies and might arise from alternative splicing. However, detecting tumor-specific splicing is challenging because many non-canonical splice junctions identified in tumors also appear in healthy tissues. To increase tumor-specificity, we focused on splicing caused by somatic mutations as a source for neoantigen candidates in individual patients.

PARP-1 selectively impairs -driven phenotypic and molecular features in intrahepatic cholangiocarcinoma.

Objective: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer with limited therapeutic options. mutations are among the most abundant genetic alterations in iCCA associated with poor clinical outcome and treatment response. Recent findings indicate that Poly(ADP-ribose)polymerase1 (PARP-1) is implicated in -driven cancers, but its exact role in cholangiocarcinogenesis remains undefined.

Relevance of Positive Surgical Margins in Localized Renal Cell Carcinoma After Surgical Resection: Predictive Factors and Survival Implications.

Introduction: The implications of positive surgical margins (PSM) after surgery for renal cell carcinoma (RCC) remain subject of discussion. This study aimed to identify risk factors for PSM, assess its effect on overall survival (OS), and determine predictors of OS.

Patients And Methods: Data from RCC surgeries at Mannheim University Medical Center between 2010 and 2023 was analyzed.

Quality-of-life outcomes of the ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial.

Objectives: To comprehensively compare quality-of-life (QoL) outcomes between open partial nephrectomy (OPN) and robot-assisted PN (RAPN) from the randomised ROBOtic-assisted versus Conventional Open Partial nephrectomy (ROBOCOP) II trial, as QoL data comparing OPN and RAPN are virtually non-existent, especially not from randomised controlled trials (RCTs).

Patients And Methods: The ROBOCOP II was a single-centre, open-label RCT between OPN and RAPN. The pre-planned analyses of QoL outcomes are presented.

The radiomorphological appearance of the invasive margin in pancreatic cancer is associated with tumor budding.

Purpose: Pancreatic cancer (PDAC) is characterized by infiltrative, spiculated tumor growth into the surrounding non-neoplastic tissue. Clinically, its diagnosis is often established by magnetic resonance imaging (MRI). At the invasive margin, tumor buds can be detected by histology, an established marker associated with poor prognosis in different types of tumors.

L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial.

The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part of GLORIA (NCT04121455), a phase I/II trial combining RT and the CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD), recommended phase II dose (RP2D), NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life (QOL), median progression-free survival (PFS), 6-months PFS and overall survival (OS).

Hematologic Toxicity and Bone Marrow-Sparing Strategies in Chemoradiation for Locally Advanced Cervical Cancer: A Systematic Review.

The standard treatment for locally advanced cervical cancer typically includes concomitant chemoradiation, a regimen known to induce severe hematologic toxicity (HT). Particularly, pelvic bone marrow dose exposure has been identified as a contributing factor to this hematologic toxicity. Chemotherapy further increases bone marrow suppression, often necessitating treatment interruptions or dose reductions.

Preclinical efficacy and pharmacokinetics of an RNA-encoded T cell-engaging bispecific antibody targeting human claudin 6.

We present the preclinical pharmacology of BNT142, a lipid nanoparticle (LNP)-formulated RNA (RNA-LNP) encoding a T cell-engaging bispecific antibody that monovalently binds the T cell marker CD3 and bivalently binds claudin 6 (CLDN6), an oncofetal antigen that is absent from normal adult tissue but expressed on various solid tumors. Upon BNT142 RNA-LNP delivery in cell culture, mice, and cynomolgus monkeys, RNA is translated, followed by self-assembly into and secretion of the functional bispecific antibody RiboMab02.1.

Validation of the standardization framework SSTR-RADS 1.0 for neuroendocrine tumors using the novel SSTR‑targeting peptide [F]SiTATE.

Objectives: Somatostatin receptor positron emission tomography/computed tomography (SSTR-PET/CT) using [Ga]-labeled tracers is a widely used imaging modality for neuroendocrine tumors (NET). Recently, [F]SiTATE, a SiFAlin tagged [Tyr3]-octreotate (TATE) PET tracer, has shown great potential due to favorable clinical characteristics. We aimed to evaluate the reproducibility of Somatostatin Receptor-Reporting and Data System 1.

A systematic review of diagnostic and interventional techniques in non-occlusive hepatic artery hypoperfusion syndrome.

Objective: This systematic review aims to elucidate the diagnostic capabilities of imaging techniques in identifying Non-Occlusive Hepatic Artery Hypoperfusion Syndrome (NOHAH) and to evaluate the efficacy and outcomes of splenic artery embolization (SAE), including the choice and placement of embolic agents.

Materials And Methods: A comprehensive literature search was conducted using PubMed, CINAHL, and Scopus databases, adhering to PRISMA guidelines. Fifteen studies encompassing 240 patients treated with embolization (using coils or Amplatzer Vascular Plugs (AVP)) were analyzed.

Trans-Amplifying RNA: A Journey from Alphavirus Research to Future Vaccines.

Replicating RNA, including self-amplifying RNA (saRNA) and trans-amplifying RNA (taRNA), holds great potential for advancing the next generation of RNA-based vaccines. Unlike transcribed mRNA found in most current RNA vaccines, saRNA or taRNA can be massively replicated within cells in the presence of RNA-amplifying enzymes known as replicases. We recently demonstrated that this property could enhance immune responses with minimal injected RNA amounts.

Percutaneous Balloon-Expandable Stent Implantation to Treat Transverse Aortic Arch Obstruction: Medium- to Long-Term Outcomes of a Retrospective Multicenter Study.

Background: Transverse aortic arch obstruction is a challenging lesion for which stent implantation provides a potentially important alternate therapy. The objectives were to evaluate the technical, procedural, and medium-to-long-term clinical outcomes of percutaneous stent implantation of transverse aortic arch obstruction.

Methods: This is a retrospective, multicenter study of transverse aortic arch stent implantation.

The atypical IκB family member Bcl3 determines differentiation and fate of intestinal RORγt regulatory T-cell subsets.

Peripherally-induced regulatory T cells (pTregs) expressing the retinoic acid receptor-related orphan-receptor gamma t (RORγt) are indispensable for intestinal immune homeostasis. Nuclear factor kappa family members regulate the differentiation of thymic Tregs and promote their survival in the periphery. However, the Treg intrinsic molecular mechanisms controlling the size of the pTregs in the intestine and associated lymphoid organs remain unclear.

Influence of motivational interviewing on postoperative mobilization in the enhanced recovery after surgery (ERAS®) pathway in elective colorectal surgery - a randomized patient-blinded pilot study.

Purpose: Early mobilization is an essential component of the Enhanced Recovery after Surgery (ERAS®)-pathway. However, a large percentage of patients fail to achieve the ERAS® recommended goal (360 min out of bed from post-operative day 1/POD1). Motivational Interviewing (MI) is an evidence-based type of patient-centered consultation to promote intrinsic motivation.

The contribution of sensory information asymmetry and bias of attribution to egocentric tendencies in effort comparison tasks.

When comparing themselves with others, people often evaluate their own behaviors more favorably. This egocentric tendency is often categorized as a bias of attribution, with favorable self-evaluation resulting from differing explanations of one's own behavior and that of others. However, studies on information availability in social contexts offer an alternative explanation, ascribing egocentric biases to the inherent informational asymmetries between performing an action and merely observing it.

Mobocertinib in Patients with EGFR Exon 20 Insertion-Positive Non-Small Cell Lung Cancer (MOON): An International Real-World Safety and Efficacy Analysis.

EGFR exon 20 (EGFR Ex20) insertion mutations in non-small cell lung cancer (NSCLC) are insensitive to traditional EGFR tyrosine kinase inhibitors (TKIs). Mobocertinib is the only approved TKI specifically designed to target EGFR Ex20. We performed an international, real-world safety and efficacy analysis on patients with EGFR Ex20-positive NSCLC enrolled in a mobocertinib early access program.