A ketogenic diet substantially reshapes the human metabolome.

BACKGROUND: Western dietary habits (WD) have been shown to promote chronic inflammation, which favors the development of many of today's non-communicable diseases. Recently, ketogenic diets (KD) have emerged as an immune-regulating countermeasure for WD-induced metaflammation. To date, beneficial effects of KD have been solely attributed to the production and metabolism of ketone bodies. Given the drastic change in nutrient composition during KD, it is reasonable to assume that there are widespread changes in the human metabolome also contributing to the impact of KD on human immunity. The current study was conducted to gain insight into the changes of the human metabolic fingerprint associated with KD. This could allow to identify metabolites that may contribute to the overall positive effects on human immunity, but also help to recognize potential health risks of KD. METHODS: We conducted a prospective nutritional intervention study enrolling 40 healthy volunteers to perform a three-week ad-libitum KD. Prior to the start and at the end of the nutritional intervention serum metabolites were quantified, untargeted mass spectrometric metabolome analyses and urine analyses of the tryptophan pathway were performed. RESULTS: KD led to a marked reduction of insulin (-21.45% ± 6.44%, p = 0.0038) and c-peptide levels (-19.29% ± 5.45%, p = 0.0002) without compromising fasting blood glucose. Serum triglyceride concentration decreased accordingly (-13.67% ± 5.77%, p = 0.0247), whereas cholesterol parameters remained unchanged. LC-MS/MS-based untargeted metabolomic analyses revealed a profound shift of the human metabolism towards mitochondrial fatty acid oxidation, comprising highly elevated levels of free fatty acids and acylcarnitines. The serum amino acid (AA) composition was rearranged with lower abundance of glucogenic AA and an increase of BCAA. Furthermore, an increase of anti-inflammatory fatty acids eicosatetraenoic acid (p < 0.0001) and docosahexaenoic acid (p = 0.0002) was detected. Urine analyses confirmed higher utilization of carnitines, indicated by lower carnitine excretion (-62.61% ± 18.11%, p = 0.0047) and revealed changes to the tryptophan pathway depicting reduced quinolinic acid (-13.46% ± 6.12%, p = 0.0478) and elevated kynurenic acid concentrations (+10.70% ± 4.25%, p = 0.0269). CONCLUSIONS: A KD fundamentally changes the human metabolome even after a short period of only three weeks. Besides a rapid metabolic switch to ketone body production and utilization, improved insulin and triglyceride levels and an increase in metabolites that mediate anti-inflammation and mitochondrial protection occurred. Importantly, no metabolic risk factors were identified. Thus, a ketogenic diet could be considered as a safe preventive and therapeutic immunometabolic tool in modern medicine. TRIAL REGISTRATION: German Clinical Trials Register; DRKS-ID: DRKS00027992 (www.drks.de).

Trends in Emergent Groin Hernia Repair-An Analysis From the Herniamed Registry.

Introduction: While the proportion of emergency groin hernia repairs in developed countries is 2.5-7.7%, the percentage in developing countries can be as high as 76.9%. The mortality rate for emergency groin hernia repair in developed countries is 1.7-7.0% and can rise to 6-25% if bowel resection is needed. In this present analysis of data from the Herniamed Registry, patients with emergency admission and operation within 24 h are analyzed. Methods: Between 2010 and 2019 a total of 13,028 patients with emergency admission and groin hernia repairs within 24 h were enrolled in the Herniamed Registry. The outcome results were assigned to the year of repair and summarized as curves. The total patient collective is broken down into the subgroups with pre-operative manual reduction (taxis) of the hernia content, operative reduction of the hernia content without bowel resection and with bowel resection. The explorative Fisher's exact test was used for statistical assessment of significant differences with Bonferroni adjustment for multiple testing. Results: The proportion of emergency admissions with groin hernia repair within 24 h was 2.7%. The percentage of women across the years was consistently 33%. The part of femoral hernias was 16%. The proportion of patients with pre-operative reduction (taxis) remained unchanged at around 21% and the share needing bowel resection was around 10%. The proportion of TAPP repairs rose from 21.9% in 2013 to 38.0% in 2019 (p < 0.001). Between the three groups with pre-operative taxis, without bowel resection and with bowel resection, highly significant differences were identified between the patients with regard to the rates of post-operative complications (4% vs. 6.5% vs. 22.7%; p < 0.0001), complication-related reoperations (1.9% vs. 3.8% vs. 17.7%; p < 0.0001), and mortality rate (0.3% vs. 0.9% vs. 7.5%; p < 0.001). In addition to emergency groin hernia repair subgroups female gender and age ≥66 years are unfavorable influencing factors for perioperative outcomes. Conclusion: For patients with emergency groin hernia repair the need for surgical reduction or bowel resection, female gender and age ≥66 years have a highly significantly unfavorable influence on the perioperative outcomes.

Computed tomographic assessment of lung weights in trauma patients with early posttraumatic lung dysfunction.

INTRODUCTION: Quantitative computed tomography (qCT)-based assessment of total lung weight (Mlung) has the potential to differentiate atelectasis from consolidation and could thus provide valuable information for managing trauma patients fulfilling commonly used criteria for acute lung injury (ALI). We hypothesized that qCT would identify atelectasis as a frequent mimic of early posttraumatic ALI. METHODS: In this prospective observational study, Mlung was calculated by qCT in 78 mechanically ventilated trauma patients fulfilling the ALI criteria at admission. A reference interval for Mlung was derived from 74 trauma patients with morphologically and functionally normal lungs (reference). Results are given as medians with interquartile ranges. RESULTS: The ratio of arterial partial pressure of oxygen to the fraction of inspired oxygen was 560 (506 to 616) mmHg in reference patients and 169 (95 to 240) mmHg in ALI patients. The median reference Mlung value was 885 (771 to 973) g, and the reference interval for Mlung was 584 to 1164 g, which matched that of previous reports. Despite the significantly greater median Mlung value (1088 (862 to 1,342) g) in the ALI group, 46 (59%) ALI patients had Mlung values within the reference interval and thus most likely had atelectasis. In only 17 patients (22%), Mlung was increased to the range previously reported for ALI patients and compatible with lung consolidation. Statistically significant differences between atelectasis and consolidation patients were found for age, Lung Injury Score, Glasgow Coma Scale score, total lung volume, mass of the nonaerated lung compartment, ventilator-free days and intensive care unit-free days. CONCLUSIONS: Atelectasis is a frequent cause of early posttraumatic lung dysfunction. Differentiation between atelectasis and consolidation from other causes of lung damage by using qCT may help to identify patients who could benefit from management strategies such as damage control surgery and lung-protective mechanical ventilation that focus on the prevention of pulmonary complications.