Clinical Research Directory

Natural History and Genotype-Phenotype Correlations in Mitochondrial Leukoencephalopathies

Mitochondrial disorders (MDs) are among the most common inherited metabolic diseases, caused by genetic defects in mitochondrial or nuclear DNA that impair cellular energy production. The central nervous system (CNS) is frequently affected, due to its high energy demands. Within the broad clinical spectrum of MDs, mitochondrial leukoencephalopathies (MLs) have emerged as a distinct subgroup characterized by CNS white matter involvement. MLs are clinically and genetically heterogeneous, with onset ranging from infancy to adulthood. Patients may experience episodes of neurological regression, often triggered by stressors such as febrile illnesses, alongside variable motor, cognitive, and occasionally extraneurological involvement. Neuroimaging typically reveals diffuse or focal white matter abnormalities, including cavitation and rarefaction, with additional involvement of deep gray matter structures. Certain ML subtypes exhibit characteristic MRI patterns that may aid in diagnosis. Despite recent advancements in the genetic and neuroradiological characterization of MLs, significant knowledge gaps persist. Although the number of disease-causing genes has increased over the last decades, a comprehensive understanding of genotype-phenotype correlations is still lacking. Additionally, knowledge on the natural history of these disorders is limited. Existing data often focus on imaging findings with insufficient integration of clinical, biochemical, and molecular features, limiting the understanding of disease mechanisms, progression, and therapeutic responses. In light of these gaps, this multicenter, observational, retrospective study aims to systematically collect and analyze clinical, biochemical, neuroradiological, and genetic data from individuals with MLs, assessed at international reference centers for MDs. The study seeks to better elucidate the phenotypic variability and genotype-phenotype correlations of MLs. This work is expected to enhance diagnostic accuracy, inform management strategies, support prognostic counseling, and ultimately contribute to the better overall management of affected individuals

Intermittent Versus Continuous Surface O2 During HMP of DCD Kidneys

The aim of the study is to evaluate the feasibility of this bubble and surface oxygenation and to determine the optimal timing of surface oxygenation (continuous versus intermittent) as alternative for membrane-oxygenated kidneys, originating from DCD donors, during HMP on early graft function in clinical practice.

Mitochondrial Function in the Peri-operative Setting: an Observational Study

Complications after surgery are common and a burden for patients and health services. Therefore it is important that clinicians improve surgical outcomes. Mitochondria are the part of the body's cells that manage energy. Research has already shown that how our body's mitochondria behave can predict who survives in intensive care patients. The investigators think this could also predict who is more likely to develop complications after surgery. Therefore a study has been designed to find out if changes in mitochondria are related to postoperative complications. This will help doctors improve how they prepare patients for surgery and potentially how they manage their treatment, and result in improving outcomes for patients after surgery. This study will recruit patients scheduled for major abdominal surgery as part of their treatment. The investigators will take samples of breath, blood and muscle to measure changes in mitochondria from the day before surgery to 7 days postoperatively. The muscle samples will only be taken when the patient is asleep having their operation. These samples will be used to analyse mitochondria. This study will be in two phases. Phase 1 is a pilot of up to 10 patients focussed on feasibility. Following this there will be an interim data analysis. The results may allow further optimisation to reduce the patient burden, eg reduction in sampling frequency, or avoiding need for muscle biopsy. The second phase will be a full cohort study of up to 40 patients, focussed on association of mitochondrial markers with clinical outcomes, such as postoperative complications, oxygen levels, pain, confusion and length of intensive care stay. The results of this study could improve how doctors select and prepare patients for surgery. It may also affect how doctors manage their treatment during and after operations. This could result in reducing complications and illness burden for patients after surgery.