Cerebral metabolic effects of exogenous lactate supplementation on the injured human brain

Purpose: Experimental evidence suggests that lactate is neuroprotective after acute brain injury; however, data in humans are lacking. We examined whether exogenous lactate supplementation improves cerebral energy metabolism in humans with traumatic brain injury (TBI). Methods: We prospectively studied 15 consecutive patients with severe TBI monitored with cerebral microdialysis (CMD), brain tissue PO2 (PbtO2), and intracranial pressure (ICP). Intervention consisted of a 3-h intravenous infusion of hypertonic sodium lactate (aiming to increase systemic lactate to ca. 5mmol/L), administered in the early phase following TBI. We examined the effect of sodium lactate on neurochemistry (CMD lactate, pyruvate, glucose, and glutamate), PbtO2, and ICP. Results: Treatment was started on average 33±16h after TBI. A mixed-effects multilevel regression model revealed that sodium lactate therapy was associated with a significant increase in CMD concentrations of lactate [coefficient 0.47mmol/L, 95% confidence interval (CI) 0.31-0.63mmol/L], pyruvate [13.1 (8.78-17.4)μmol/L], and glucose [0.1 (0.04-0.16) mmol/L; all p<0.01]. A concomitant reduction of CMD glutamate [−0.95 (−1.94 to 0.06) mmol/L, p=0.06] and ICP [−0.86 (−1.47 to −0.24) mmHg, p<0.01] was also observed. Conclusions: Exogenous supplemental lactate can be utilized aerobically as a preferential energy substrate by the injured human brain, with sparing of cerebral glucose. Increased availability of cerebral extracellular pyruvate and glucose, coupled with a reduction of brain glutamate and ICP, suggests that hypertonic lactate therapy has beneficial cerebral metabolic and hemodynamic effects after TBI

Neck-MRI experience for investigation of survived strangulation victims

For the medicolegal evaluation of victims of survived strangulation, a neck-magnetic resonance imaging (MRI) can be performed for assessing lesions in the inner soft tissues (fat, muscles or lymph nodes, for example). In our institute, such MRI examinations have been performed for a test period of 4 years with the aim of evaluating the use of this tool by forensic pathologists and identifying medicolegal indicators for the performance of neck-MRI in surviving victims of strangulation. We retrospectively reviewed medicolegal reports from all victims examined during the test period. We extracted objective lesions (e.g. petechiae, bruising and abrasions) and reported clinical symptoms (e.g. vision disorder, dysphasia) from the reports. These findings were compared to those reported from the neck-MRI. In total, 112 victims were clinically examined after suspected strangulation. Eleven of these victims underwent an MRI examination of the neck. Eighty-four of the victims presented objective lesions during the clinical examination, with eight showing signs of both petechiae and bruising. Neck-MRI was performed in four of these eight victims and three of them showed lesions visible in MRI. Of 76 victims with bruising as the only objective finding, 66 victims described clinical symptoms. Of those 66 victims, seven were examined by MRI and two demonstrated lesions in MRI. When MRI was performed, relevant findings were detected in 45% of the cases. This leads to the suspicion that many more findings could have been detected in the other victims, if an MRI had been performed in those cases. Our results lead us to the conclusion that an MRI examination of victims of suspected strangulation is useful, and strict indications for its application should be established

Bedside cerebral microdialysis monitoring of delayed cerebral hypoperfusion in comatose patients with poor grade aneurysmal subarachnoid haemorrhage.

BACKGROUND Delayed cerebral ischaemia (DCI) is frequent after poor grade aneurysmal subarachnoid haemorrhage (SAH). Owing to the limited accuracy of clinical examination, DCI diagnosis is often based on multimodal monitoring. We examined the value of cerebral microdialysis (CMD) in this setting. METHODS 20 comatose SAH participants underwent CMD monitoring-for hourly sampling of cerebral extracellular lactate/pyruvate ratio (LPR) and glucose-and brain perfusion CT (PCT). Patients were categorised as DCI when PCT (8±3 days after SAH) showed cerebral hypoperfusion, defined as cerebral blood flow 5.7 s. Clinicians were blinded to CMD data; for the purpose of the study, only patients who developed cerebral hypoperfusion in anterior and/or middle cerebral arteries were analysed. RESULTS DCI (n=9/20 patients) was associated with higher CMD LPR (51±36 vs 31±10 in patients without DCI, p=0.0007) and lower CMD glucose (0.64±0.34 vs 1.22±1.05, p=0.0005). In patients with DCI, CMD changes over the 18 hours preceding PCT diagnosis revealed a pattern of CMD LPR increase (coefficient +2.96 (95% CI 0.13 to 5.79), p=0.04) with simultaneous CMD glucose decrease (coefficient -0.06 (95% CI -0.08 to -0.01), p=0.03, mixed-effects multilevel regression model). No significant CMD changes were noted in patients without DCI. CONCLUSIONS In comatose patients with SAH, delayed cerebral hypoperfusion correlates with a CMD pattern of lactate increase and simultaneous glucose decrease. CMD abnormalities became apparent in the hours preceding PCT, thereby suggesting that CMD monitoring may anticipate targeted therapeutic interventions

Effect of general anaesthesia on functional outcome in patients with anterior circulation ischaemic stroke having endovascular thrombectomy versus standard care: a meta-analysis of individual patient data

Background: General anaesthesia (GA) during endovascular thrombectomy has been associated with worse patient outcomes in observational studies compared with patients treated without GA. We assessed functional outcome in ischaemic stroke patients with large vessel anterior circulation occlusion undergoing endovascular thrombectomy under GA, versus thrombectomy not under GA (with or without sedation) versus standard care (ie, no thrombectomy), stratified by the use of GA versus standard care. Methods: For this meta-analysis, patient-level data were pooled from all patients included in randomised trials in PuMed published between Jan 1, 2010, and May 31, 2017, that compared endovascular thrombectomy predominantly done with stent retrievers with standard care in anterior circulation ischaemic stroke patients (HERMES Collaboration). The primary outcome was functional outcome assessed by ordinal analysis of the modified Rankin scale (mRS) at 90 days in the GA and non-GA subgroups of patients treated with endovascular therapy versus those patients treated with standard care, adjusted for baseline prognostic variables. To account for between-trial variance we used mixed-effects modelling with a random effect for trials incorporated in all models. Bias was assessed using the Cochrane method. The meta-analysis was prospectively designed, but not registered. Findings: Seven trials were identified by our search; of 1764 patients included in these trials, 871 were allocated to endovascular thrombectomy and 893 were assigned standard care. After exclusion of 74 patients (72 did not undergo the procedure and two had missing data on anaesthetic strategy), 236 (30%) of 797 patients who had endovascular procedures were treated under GA. At baseline, patients receiving GA were younger and had a shorter delay between stroke onset and randomisation but they had similar pre-treatment clinical severity compared with patients who did not have GA. Endovascular thrombectomy improved functional outcome at 3 months both in patients who had GA (adjusted common odds ratio (cOR) 1·52, 95% CI 1·09–2·11, p=0·014) and in those who did not have GA (adjusted cOR 2·33, 95% CI 1·75–3·10, p&lt;0·0001) versus standard care. However, outcomes were significantly better for patients who did not receive GA versus those who received GA (covariate-adjusted cOR 1·53, 95% CI 1·14–2·04, p=0·0044). The risk of bias and variability between studies was assessed to be low. Interpretation: Worse outcomes after endovascular thrombectomy were associated with GA, after adjustment for baseline prognostic variables. These data support avoidance of GA whenever possible. The procedure did, however, remain effective versus standard care in patients treated under GA, indicating that treatment should not be withheld in those who require anaesthesia for medical reasons

FCC Physics Opportunities: Future Circular Collider Conceptual Design Report Volume 1

We review the physics opportunities of the Future Circular Collider, covering its e+e-, pp, ep and heavy ion programmes. We describe the measurement capabilities of each FCC component, addressing the study of electroweak, Higgs and strong interactions, the top quark and flavour, as well as phenomena beyond the Standard Model. We highlight the synergy and complementarity of the different colliders, which will contribute to a uniquely coherent and ambitious research programme, providing an unmatchable combination of precision and sensitivity to new physics