THE NEUROENDOTHELIAL AXIS IN TRAUMATIC BRAIN INJURY: MECHANISMS OF MULTIORGAN DYSFUNCTION, NOVEL THERAPIES, AND FUTURE DIRECTIONS.

ABSTRACT: Severe traumatic brain injury (TBI) often initiates a systemic inflammatory response syndrome, which can potentially culminate into multiorgan dysfunction. A central player in this cascade is endotheliopathy, caused by perturbations in homeostatic mechanisms governed by endothelial cells due to injury-induced coagulopathy, heightened sympathoadrenal response, complement activation, and proinflammatory cytokine release. Unique to TBI is the potential disruption of the blood-brain barrier, which may expose neuronal antigens to the peripheral immune system and permit neuroinflammatory mediators to enter systemic circulation, propagating endotheliopathy systemically. This review aims to provide comprehensive insights into the "neuroendothelial axis" underlying endothelial dysfunction after TBI, identify potential diagnostic and prognostic biomarkers, and explore therapeutic strategies targeting these interactions, with the ultimate goal of improving patient outcomes after severe TBI.

Finding the Right Balance: Partial REBOA in a Swine Model of Uncontrolled Vascular Injury.

BACKGROUND: We have previously shown that partial REBOA (pREBOA) deployment in the thoracic aorta is safe for 2 to 4 hours, but it is unclear whether the distal blood flow after partial aortic occlusion would lead to ongoing hemorrhage. The objective of this study was to evaluate the hemostatic efficacy of pREBOA in a model of uncontrolled vascular injury. STUDY DESIGN: Female Yorkshire swine (n = 10, 40 to 45 kg) were anesthetized and instrumented. A through-and-through injury was created in the common iliac artery. The animals were randomly assigned to: (1) pREBOA-PRO deployment after 3 minutes and (2) control. Both groups were given normal saline resuscitation for hypotension. The pREBOA was adjusted to partial occlusion (distal mean arterial pressure of 30 mmHg), and then left without titration for 2 hours. Then, fresh frozen plasma was transfused and the vessel repaired. The balloon was deflated and the animals were monitored for 2 hours. In the critical care period, 2 L of normal saline was infused, norepinephrine was given for mean arterial pressure ≤55, and electrolytes and acidosis were corrected. Organs were examined for gross and histologic evidence of ischemic injuries. The primary endpoint was post-inflation blood loss. RESULTS: All the pREBOA animals survived until the end, whereas control animals had a mean survival time of 38.2 minutes (p < 0.05). The pREBOA group showed significantly less bleeding after balloon deployment (93.8 vs 1,980.0 mL, p < 0.05), and had appropriate lactate clearance, with minimal histologic distal organ ischemia. CONCLUSIONS: Partial aortic occlusion with the newly designed balloon can achieve the desired balance between effective hemorrhage control and adequate distal flow, without a need for ongoing balloon titration.

The impact of sleeve gastrectomy on renal function in patients with chronic kidney disease varies with severity of renal insufficiency.

BACKGROUND: Although laparoscopic sleeve gastrectomy is known, in general, to improve renal function in patients with obesity and chronic kidney disease (CKD), its effect on estimated glomerular filtration rate (eGFR) stratified by the stage of CKD is less clear. OBJECTIVES: We aimed to evaluate the impact of sleeve gastrectomy on renal function in a stratified cohort of patients with CKD. SETTING: University Hospital. METHODS: We performed a retrospective review of 1932 patients who met National Institutes of Health's guidelines for metabolic surgery and underwent laparoscopic sleeve gastrectomy performed by 1 of 3 surgeons. One hundred sixty-four patients with CKD stages 1 through 4 were identified. RESULTS: Mean follow-up period was 1.57 ± 1.0 years. Mean age was 56.4 ± 9.9 years with a preoperative body mass index of 47 ± 9 kg/m2, which decreased to 38.9 ± 8.7 kg/m2 at most recent follow-up (P < .001). In the cohort of patients with diabetes, significant decreases were observed in mean glycated hemoglobin level, daily number of oral hypoglycemics, and daily long acting insulin use (P < .001 each). Of 67 patients with diabetes, 34.3% (n = 24) achieved complete remission. In patients with hypertension, average daily number of antihypertensives decreased (P < .001) and 22.3% (n = 31) of 133 patients with hypertension discontinued all antihypertensives. Patients with CKD stages 2, 3a, and 3b showed significant improvement in eGFR. Reinforcing this evidence of improvement, patients with CKD 3a and 3b were more likely to downstage disease compared with those with CKD 4 (58.1% versus 73.1% versus 22.7%, respectively) (P < .001). CONCLUSION: Renal function, as measured by eGFR, in patients with stages 1 and 4 CKD did not improve after laparoscopic sleeve gastrectomy; in contrast, eGFR in patients with CKD stages 2 and 3 significantly improved. Early surgical referral and intervention may be important in achieving the greatest improvement in eGFR and possibly delaying or reversing progression to end-stage renal disease.