Clinical Research Directory

Mechanisms of Brain-Heart Injury of Post-Intracranial Hemorrhage

Intracranial hemorrhage is a condition characterized by high mortality rates and suboptimal functional outcomes. It precipitates both direct brain injury and subsequent secondary injuries, including delayed cerebral ischemia, brain edema, and hydrocephalus. Complications such as cardiac injury may also arise, categorizing them within the cerebrocardiac syndrome (CCS). The clinical spectrum of CCS encompasses acute myocardial injury, acute coronary syndrome, left ventricular systolic and diastolic dysfunction, cardiac arrhythmias, and sudden cardiac death, all of which are associated with increased mortality and deterioration in patient status. The precise pathophysiological mechanisms underlying both cerebral and cardiac injuries remain enigmatic, and the implications for diagnosis and therapeutic strategies are yet to be fully explored. In this study, we propose to enroll patients with intracranial hemorrhage who will undergo conventional treatment and comprehensive multidisciplinary evaluations. Our observational research is grounded in a multimodal omics and imaging approach, aimed at investigating both local and systemic injuries subsequent to intracranial hemorrhage. This comprehensive strategy is intended to facilitate precise diagnosis, risk stratification, and clinical decision-making, while also shedding light on the pathophysiological mechanisms involved. The primary objectives of this research are to address the following key questions: * \[Question 1\] What are the pathophysiological mechanisms underlying cardiac injury in patients with intracranial hemorrhage? * \[Question 2\] What are the pathophysiological mechanisms responsible for early and delayed brain injuries following intracranial hemorrhage?\"

Oncometabolome and MALDI-MSI in Upper GI Carcinomas - Chemosensitivity in Esophageal Carcinoma

Locally advanced adenocarcinoma of the esophagus is a leading cause of death from malignant disease in Germany and has been characterized on a molecular level in recent years. This retrospective observational study deals with patients after esophagectomy with different risk constellations of esophageal carcinoma. An early and individualized therapy of this tumor in an approach of precision oncology significantly improves the prognosis. The metabolomic profile plays a central role in tumor plasticity and oncological outcome. At the same time, these factors affect the efficacy of chemotherapy and need to be investigated in more detail at the molecular level. A central element of this study is the investigation of phospholipid metabolism locally in tumor tissue, in adjacent normal tissue in terms of the tumor microenvironment and systemically in blood plasma. The focus lies on the validation of known oncometabolites that significantly influence tumor sensitivity to chemotherapy. By combining mass spectrometry imaging using matrix-assisted laser desorption ionization - mass spectrometry imaging (MALDI-MSI) with metabolomics using liquid chromatography tandem mass spectrometry (LC-MS/MS), the metabolic profile of tumors can be analyzed in detail, allowing conclusions to be drawn about chemo-insensitive and therapeutically challenging tumors. Both mass spectrometric methods are used to understand the heterogeneous metabolism of the tumors and to describe possible constellations that are associated with increasing chemoresistance. For precise investigation, the cohort under investigation is divided into two patient collectives. Patients with a regression grade 1 after four sessions of FLOT chemotherapy are compared with a regression grade 3 according to Becker in the postoperative pathological assessment. This facilitates the development of personalized therapeutic approaches tailored to the individual oncological profiles of the tumors. The study is complemented by conventional HE microscopic examinations of the tumor itself and the tumor microenvironment, which allow to analyze the morphology and its correlation with metabolic alterations in the tissue. We hypothesize that adenocarcinoma of the esophagus with regression grade 1 encompasses a fundamentally distinct metabolic profile than adenocarcinoma of the esophagus with regression grade 3. Consequently, a stratification parameter within the local tumor metabolism and the tumor microenvironment exists, which correlates with the systemic response to neoadjuvant chemotherapy in blood plasma. The primary aim of the study is to create a comprehensive metabolic profile that clearly identifies tumors with a regression grade 1 versus a regression grade 3 according to Becker. This will be used to improve diagnostics and develop personalized treatment strategies that increase treatment efficiency and patients' chances of survival. This is ultimately carried out with the intention of achieving an improved survival rate and a higher quality of life for patients with locally advanced esophageal cancer. The comprehensive analysis of the tumor microenvironment and the morphological and metabolic profiles should provide new insights into the mechanisms of tumor progression and resistance, which in turn will form the basis for future translational research and treatment approaches. The findings from this study have the potential to change the way esophageal cancer is treated by contributing to the development of stratified therapeutic approaches tailored to the molecular subtype of esophageal cancer.