Could exhaled methane be used as a possible indicator for hemodynamic changes in trauma induced hemorrhagic shock? Scientific basis supported by a case study.

INTRODUCTION: Identification of severe blood loss and hemorrhagic shock in polytrauma patients poses a key challenge for trauma teams across the world, as there are just a few objective parameters, on which clinicians can rely. We investigated the relationship between exhaled air methane (CH4) concentration and blood loss in a polytrauma patient. Decreased blood flow in the superior mesenteric artery (SMA) is one of the first compensatory responses to blood loss. Gases produced by the anaerobic flora of the intestinal segment supplied by the SMA are the primary source of exhaled CH4, which diffuses through the intestinal microvessels into the circulation and is finally eliminated through the lungs. We hypothesized that diminution of exhaled CH4 indicates blood loss and tested our theory in a severely injured patient. METHODS: Exhaled CH4 concentrations of a severely injured patient were measured using a photoacoustic spectroscope (PAS) attached to the exhalation side of the breathing circuit. The primary objective was to investigate the relationship between exhaled CH4 and conventional indicators of hemorrhage including hemoglobin (Hb) levels, base deficit (BD) values and vital parameters (heart rate and systolic blood pressure) in the early phase of in-hospital care (first 4 h). RESULTS: A severely injured patient was admitted with unstable hemodynamic parameters and incomplete left lower limb amputation, (Injury Severity Score: 38, 74/36 mmHg, 76 bpm). At the time of arrival, considerably lower CH4 levels were detected (22,800 PAU) in the exhaled air. During the first 4 h fluid and massive blood resuscitation, the exhaled CH4 levels were continuously rising in parallel with Htc and Hb values. Corresponding to these changes, BD values displayed a decreasing tendency. DISCUSSION: Our study was conducted to characterize the changes in exhaled air CH4 concentration in response to hemorrhagic shock and to provide data on a viable clinical use of an experimental technique. According to our results, the real-time detection of exhaled air CH4 concentration is an applicable and promising technique for the early detection of bleeding and hemorrhagic shock in severely injured patients. Further research on large sample size and refinement of the PAS technique is required.

Mitochondrial dysfunction in platelets from severe trauma patients - A prospective case-control study.

INTRODUCTION: Trauma-induced coagulopathy (TIC) refers to an abnormal coagulation process, an imbalance between coagulation and fibrinolysis due to several pathological factors, such as haemorrhage and tissue injury. Platelet activation and subsequent clot formation are associated with mitochondrial activity, suggesting a possible role for mitochondria in TIC. Comprehensive studies of mitochondrial dysfunction in platelets from severe trauma patients have not yet been performed. METHODS: In this prospective case-control study, patients with severe trauma (ISS≥16) had venous blood samples taken at arrival to the Emergency Unit of a Level 1 Trauma Centre. Mitochondrial functional measurements (Oxygraph-2k, Oroboros) were performed to determine oxygen consumption in different respiratory states, the H2O2 production and extramitochondrial Ca2+ movements. In addition, standard laboratory and coagulation tests, viscoelastometry (ClotPro) and aggregometry (Multiplate) were performed. Measurements data were compared with age and sex matched healthy control patients. RESULTS: Severe trauma patients (n = 113) with a median age of 38 years (IQR, 20-51), a median ISS of 28 (IQR, 20-48) met our inclusion criteria. Oxidative phosphorylation in platelet mitochondria from severe trauma patients significantly decreased compared to controls (34.7 ± 8.8 pmol/s/mL vs. 48.0 ± 19.7 pmol/s/mL). The mitochondrial H2O2 production significantly increased and greater endogenous Ca2+ release was found in the polytrauma group. Consistent with these results, clotting time (CT) increased while maximum clot firmness (MCF) decreased with the EX-test and FIB-test in severe trauma samples. Multiplate aggregometry showed significantly decreased ADP-test (38 ± 12 AUC vs. 112 ± 14 AUC) and ASPI test (78 ± 22 AUC vs. 84 ± 28 AUC) also tended to decrease in mitochondria of polytrauma patients as compared with controls. Significant strong correlation has been demonstrated between mitochondrial OxPhos and MCF while it was negatively correlated with ISS (R2=0.448, P˂0.05), INR, CT and lactate level of patients. CONCLUSIONS: The present study revealed that severe trauma is associated with platelet mitochondrial dysfunction resulting in reduced ATP synthesis and impaired extramitochondrial Ca2+ movement. These factors are required for platelet activation, recruitment and clot stability likely thus, platelet mitochondrial dysfunction contributes to the development of TIC.

Anterior cruciate ligament reconstruction in the elderly: 5-Year follow-up study.

BACKGROUND: Older adults remain active for longer and continue sports and activities that require rotation on one leg later in life. The rate of anterior cruciate ligament (ACL) tears is therefore increasing in those over 40 years old, with an associated increase in the rate of surgical reconstruction (ACLR), but there is limited literature on its effectiveness. Our aim was to compare the outcomes of elderly patients who have undergone ACLR with those of a younger group of patients. MATERIALS AND METHODS: Patients who underwent ACLR with bone-patella tendon-bone grafting (BPTB) at a level I trauma center between 2015 and 2017 were included in the study with a 5-year follow-up. Patients were divided into 4 groups: below 40 years, 40-49 years, 50-59 years and over 60 years. The graft function was evaluated by the International Knee Documentation Committee (IKDC) Objective Score, the anteroposterior (AP) displacement was measured by arthrometer (KT-1000; MEDMetric) and the Lysholm scale was used for subjective evaluation. RESULTS: 195 patients were included in the final analysis. The IKDC score showed significantly poorer scores in the 50-59 years and over 60 years group than in the younger groups, however in 83 % and 66 % of cases reached normal or nearly normal grades, respectively. A significant difference was found in the knee AP displacement (measured in mm) between the below 40 years group and 50-59 years as well as over 60 years old groups; however, the number of graft failure (laxity >5 mm) and elongation (>3 mm) did not increased in these senior groups. The patient-reported Lysholm scores in the 40-49 years, 50-59 years and 60 years groups was lower than in the below 40 years group, but the average score was "good". CONCLUSIONS: The long-term results of ACL reconstruction in older athletes are comparable to those of younger patients, both in terms of knee function and patient satisfaction. Furthermore, there is no difference in outcomes for older patients over the age of 40 compared to those in their 50 s or even 60 s. There is still insufficient published evidence to define an upper age limit for ACL reconstruction in older athletes.

Does Combined Reconstruction of the Medial Collateral and Anterior Cruciate Ligaments Provide Better Knee Function? A Systematic Review and Meta-Analysis.

Objective: This study aimed to determine if medial collateral ligament reconstruction (MCLR) alongside anterior cruciate ligament reconstruction (ACLR) preserves knee functionality better than isolated ACLR in combined ACL and MCL tears. Methods: MEDLINE, EMBASE, Scopus, CENTRAL, and Web of Science were searched systematically on 31 March 2023. Studies reporting post-operative function after ACLR and ACLR + MCLR in combined injuries were included. Outcomes included International Knee Documentation Committee (IKDC) score, side-to-side difference (SSD), Lysholm, and Tegner scale values. Results: Out of 2362 papers, 8 studies met the criteria. The analysis found no significant difference in outcomes (MD = 3.63, 95% CI: [-5.05, 12.3] for IKDC; MD = -0.64, 95% CI: [-3.24, 1.96] for SSD at 0° extension; MD = -1.79, 95% CI: [-4.61, 1.04] for SSD at 30° extension; MD = -1.48, 95% CI: [-16.35, 13.39] for Lysholm scale; MD = -0.21, 95% CI: [-4.29, 3.87] for Tegner scale) between treatments. Conclusions: This meta-analysis found no significant difference in outcomes between ACLR and ACLR + MCLR, suggesting that adding MCLR does not provide additional benefits. Due to the heterogeneity and quality of the included studies, further high-quality randomized controlled trials are needed to determine the optimal treatment for combined severe MCL-ACL injuries.

Impairment of Mesenteric Perfusion as a Marker of Major Bleeding in Trauma Patients.

The majority of potentially preventable mortality in trauma patients is related to bleeding; therefore, early recognition and effective treatment of hemorrhagic shock impose a cardinal challenge for trauma teams worldwide. The reduction in mesenteric perfusion (MP) is among the first compensatory responses to blood loss; however, there is no adequate tool for splanchnic hemodynamic monitoring in emergency patient care. In this narrative review, (i) methods based on flowmetry, CT imaging, video microscopy (VM), measurement of laboratory markers, spectroscopy, and tissue capnometry were critically analyzed with respect to their accessibility, and applicability, sensitivity, and specificity. (ii) Then, we demonstrated that derangement of MP is a promising diagnostic indicator of blood loss. (iii) Finally, we discussed a new diagnostic method for the evaluation of hemorrhage based on exhaled methane (CH4) measurement. Conclusions: Monitoring the MP is a feasible option for the evaluation of blood loss. There are a wide range of experimentally used methodologies; however, due to their practical limitations, only a fraction of them could be integrated into routine emergency trauma care. According to our comprehensive review, breath analysis, including exhaled CH4 measurement, would provide the possibility for continuous, non-invasive monitoring of blood loss.

Methane Admixture Protects Liver Mitochondria and Improves Graft Function after Static Cold Storage and Reperfusion.

Mitochondria are targets of cold ischemia-reperfusion (IR), the major cause of cell damage during static cold preservation of liver allografts. The bioactivity of methane (CH4) has recently been recognized in various hypoxic and IR conditions as having influence on many aspects of mitochondrial biology. We therefore hypothesized that cold storage of liver grafts in CH4-enriched preservation solution can provide an increased defence against organ dysfunction in a preclinical rat model of liver transplantation. Livers were preserved for 24 h in cold histidine-tryptophan-ketoglutarate (HTK) or CH4-enriched HTK solution (HTK-CH4) (n = 24 each); then, viability parameters were monitored for 60 min during normothermic isolated reperfusion and perfusate and liver tissue were collected. The oxidative phosphorylation capacity and extramitochondrial Ca2+ movement were measured by high resolution respirometry. Oxygen and glucose consumption increased significantly while hepatocellular damage was decreased in the HTK-CH4 grafts compared to the HTK group. Mitochondrial oxidative phosphorylation capacity was more preserved (128.8 ± 31.5 pmol/s/mL vs 201.3 ± 54.8 pmol/s/mL) and a significantly higher Ca2+ flux was detected in HTK-CH4 storage (2.9 ± 0.1 mV/s) compared to HTK (2.3 ± 0.09 mV/s). These results demonstrate the direct effect of CH4 on hepatic mitochondrial function and extramitochondrial Ca2+ fluxes, which may have contributed to improved graft functions and a preserved histomorphology after cold IR.

Mitochondrial Side Effects of Surgical Prophylactic Antibiotics Ceftriaxone and Rifaximin Lead to Bowel Mucosal Damage.

Despite their clinical effectiveness, a growing body of evidence has shown that many classes of antibiotics lead to mitochondrial dysfunction. Ceftriaxone and Rifaximin are first choice perioperative antibiotics in gastrointestinal surgery targeting fundamental processes of intestinal bacteria; however, may also have negative consequences for the host cells. In this study, we investigated their direct effect on mitochondrial functions in vitro, together with their impact on ileum, colon and liver tissue. Additionally, their impact on the gastrointestinal microbiome was studied in vivo, in a rat model. Rifaximin significantly impaired the oxidative phosphorylation capacity (OxPhos) and leak respiration in the ileal mucosa, in line with increased oxidative tissue damage and histological changes following treatment. Ceftriaxone prophylaxis led to similar changes in the colon mucosa. The composition and diversity of bacterial communities differed extensively in response to antibiotic pre-treatment. However, the relative abundances of the toxin producing species were not increased. We have confirmed the harmful effects of prophylactic doses of Rifaximin and Ceftriaxone on the intestinal mucosa and that these effects were related to the mitochondrial dysfunction. These experiments raise awareness of mitochondrial side effects of these antibiotics that may be of clinical importance when evaluating their adverse effects on bowel mucosa.