Body composition, mitochondrial oxygen metabolism and metabolome of patients with obesity before and after bariatric surgery (COMMITMENT): protocol for a monocentric prospective cohort study.

INTRODUCTION: Obesity, defined as a body mass index ≥30 kg/m2, is one of the most prevalent health conditions worldwide. It is part of the metabolic syndrome, which encompasses arterial hypertension, dyslipoproteinaemia and diabetes. Obesity is viewed as a systemic disease with pathophysiological mechanisms on the molecular level. Dysfunction of the mitochondrion and systemic low-grade inflammation are among the proposed causes for the metabolic changes. In severe cases of obesity, laparoscopic sleeve gastrectomy, a bariatric operation, can achieve the desired weight loss and has been associated with clinical outcome improvement. Hitherto, the influence of patients' body composition on mitochondrial function and concomitant metabolic changes has not been fully understood. This study aims to quantify the patient's body composition before and after laparoscopic sleeve gastrectomy and to correlate these findings with changes in mitochondrial oxygen metabolism, metabolome and immune status. METHODS AND ANALYSIS: In this prospective monocentric cohort study, patients undergoing laparoscopic sleeve gastrectomy (n=30) at Jena University Hospital (Germany) will be assessed before surgery and at four time points during a 1-year follow-up. Body composition will be measured by bioimpedance analysis. Non-invasive assessment of mitochondrial oxygen metabolism using protoporphyrin IX-triplet state lifetime technique (PPIX-TSLT) and blood sampling for, among other, metabolomic and immunological analysis, will be performed. The primary outcome is the difference in relative fat mass between the preoperative time point and 6 months postoperatively. Further outcomes comprise longitudinal changes of PPIX-TSLT and metabolic and immunological variables. Outcomes will be assessed using paired t-tests, Wilcoxon signed-rank tests and regression analyses. ETHICS AND DISSEMINATION: The study was approved by the Ethics Committee of Friedrich Schiller University Jena (2018-1192-BO). Written informed consent will be obtained from all patients prior to enrolment in the study. The results will be published in peer-reviewed journals and presented at appropriate conferences. TRIAL REGISTRATION NUMBER: DRKS00015891.

Non-invasive Assessment of Mitochondrial Oxygen Metabolism in the Critically Ill Patient Using the Protoporphyrin IX-Triplet State Lifetime Technique-A Feasibility Study.

The imbalance of oxygen delivery and oxygen consumption resulting in insufficient tissue oxygenation is pathognomonic for all forms of shock. Mitochondrial function plays an important role in the cellular oxygen metabolism and has been shown to impact a variety of diseases in the intensive care setting, specifically sepsis. Clinical assessment of tissue oxygenation and mitochondrial function remains elusive. The in vivo protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) allows the direct, non-invasive measurement of mitochondrial oxygen tension (mitoPO2) in the human skin. Our recently established measurement protocol for the Cellular Oxygen Metabolism (COMET) Monitor, a novel device employing the PpIX-TSLT, additionally allows the evaluation of oxygen consumption (mitoVO2) and delivery (mitoDO2). In the intensive care setting, these variables might provide new insight into mitochondrial oxygen metabolism and especially mitoDO2 might be a surrogate parameter of microcirculatory function. However, the feasibility of the PpIX-TSLT in critically ill patients has not been analyzed systematically. In this interim study analysis, we evaluated PpIX-TSLT measurements of 40 patients during the acute phase of sepsis. We assessed (a) potential adverse side effects of the method, (b) the rate of analyzable measurements, (c) the stability of mitoPO2, mitoVO2, and mitoDO2, and (d) potential covariates. Due to excessive edema in patients with sepsis, we specifically analyzed the association of patients' hydration status, assessed by bioimpedance analysis (BIA), with the aforementioned variables. We observed no side effects and acquired analyzable measurements sessions in 92.5% of patients (n = 37/40). Different measures of stability indicated moderate to good repeatability of the PpIX-TSLT variables within one session of multiple measurements. The determined limits of agreement and minimum detectable differences may be helpful in identifying outlier measurements. In conjunction with signal quality they mark a first step in developing a previously unavailable standardized measurement quality protocol. Notably, higher levels of hydration were associated with lower mitochondrial oxygen tension. We conclude that COMET measurements are viable in patients with sepsis. To validate the clinical and diagnostic relevance of the PpIX-TSLT using the COMET in the intensive care setting, future studies in critically ill patients and healthy controls are needed.