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.

Clinical and psychosocial factors associated with quality of life in patients with head and neck cancer: an analytical cross-sectional study from a lower-middle-income country.

INTRODUCTION: The disease course of head and neck (H&N) cancer can severely impair patients' quality of life (QoL). In Pakistan, a South Asian lower-middle-income country (LMIC), psychosocial factors may impact QoL. We aimed to assess QoL and associated factors amongst patients with H&N cancer in Pakistan. METHODS: An analytical cross-sectional study was conducted amongst adult (≥ 18 years) patients with H&N cancer who were ≥ 4 weeks post-initiation of treatment. The survey assessed QoL (European Organization for Research and Treatment of Cancer Quality of Life Questionnaires), anxiety and depression (Hospital Anxiety and Depression Scale), and social support (Enriched Social Support Instrument). Multivariable linear regression was performed for analysis. RESULTS: A total of 250 patients (mean age: 51.6 years) were included. The majority of patients were married (87%) and living with multigenerational/extended family households (53%). On multivariable linear regression, ongoing cancer treatment (beta coefficient: -13.93), having a tracheostomy (-10.02), and receiving adjuvant chemoradiotherapy (-8.17) were significantly associated with poorer global QoL. Additionally, poorer QoL was associated with depression (-24.37) and anxiety (-13.34). However, having more household family members was associated with better global QoL (0.34). CONCLUSION: The QoL of patients with H&N cancer in Pakistan is affected by both the nature of cancer treatment as well as sociocultural factors such the number of household family members. Given that poorer QoL is associated with worse mental health outcomes, there is a need to develop and implement psychosocial interventions to improve the QoL of patients with H&N cancer in Pakistan, particularly during active treatment.

Prolonging the zone 1 aortic occlusion time to 4 hours using a partial resuscitative endovascular balloon in a swine model.

BACKGROUND: The clinical usage of the resuscitative endovascular balloon occlusion of the aorta (REBOA) is limited by distal ischemia resulting from complete aortic occlusion. We hypothesized that animals would physiologically tolerate the prolonged partial occlusion using the novel partially occluding REBOA (pREBOA) with survivable downstream injuries. METHODS: This study used the pREBOA-PRO catheter in a previously established swine model. Female Yorkshire swine (n = 10) underwent a volume-controlled hemorrhage (40% estimated blood). After 1 hour of shock (mean arterial pressure, 28-32 mm Hg), animals were randomized to partial occlusion for either 2 hours or 4 hours. The pREBOA was inflated in zone 1 to achieve partial occlusion defined as a distal systolic blood pressure (SBP) of 20 ± 2 mm Hg. The balloon was deflated at the end of the occlusion period, and animals were resuscitated for 2 hours. Tissues were examined for gross and histologic injury. The primary endpoint was histologic organ injury, and secondary end points were hemodynamic variables and degree of distal organ ischemia. RESULTS: All animals survived to the endpoint. Both groups had similar proximal and distal SBP at baseline, with a divergence of pressures ranging from 55 mm Hg to 90 mm Hg on inflation. The lactate levels increased throughout the occlusion and decreased approximately 40% during the observation period. More animals required norepinephrine and fluid in the 4-hour group compared with the 2-hour group. There was no gross small bowel ischemia noted in the 2-hour animals. The 4-hour group had surgically resectable patchy short segment ischemia. Neither group showed nonsurvivable organ ischemia on pathology or laboratory values. CONCLUSION: This is the first study showing that the zone 1 aorta can be occluded for over 4 hours using a new pREBOA device without need for balloon titration. In conclusion, simple changes in balloon design offer reliable partial aortic occlusion, with potentially survivable and surgically manageable downstream injuries.

Colonoscopy, imaging, and carcinoembryonic antigen: Comparison of guideline adherence to surveillance strategies in patients who underwent resection of colorectal cancer - A systematic review and meta-analysis.

INTRODUCTION: Almost one-third of patients with colorectal cancer (CRC) experience recurrence after resection. Adherence to surveillance guidelines largely dictates efficacy in early detection of recurrence. We sought to assess and compare adherence to postoperative surveillance guidelines for colonoscopy, imaging, and Carcinoembryonic Antigen (CEA). METHODS: PubMed, Medline, Embase, Scopus, Cochrane, Web of Science, and CINAHL were systematically searched. Random-effects meta-analysis was performed and pooled adherence to each surveillance strategy was assessed for CEA, imaging, and colonoscopy. RESULTS: Overall 14 studies (55,895 patients) met the inclusion criteria. Adherence to colonoscopy guidelines was the highest (70%, 95%CI 67-73), followed by imaging (63%, 95%CI 47-80), and CEA (54%; 95%CI 42-66). Among 7 (50%) studies that examined adherence to the American Society of Clinical Oncology guidelines, compliance with colonoscopy was the highest (73%; 95% CI 70-76), followed by imaging (58%; 95% CI 37-78), and CEA (45%; 95%CI 37-52). Of note, guideline adherence to CEA testing was much lower than colonoscopy among patients with colon (OR 0.21; 95%CI 0.20-0.22) and rectal cancer (OR 0.25; 95%CI 0.23-0.28) (both p < 0.05). This was also noted when compared with imaging recommendations among older patients (OR = 0.62; 95%CI 0.42-0.93) and patients with stage II, (OR = 0.80; 95%CI 0.76-0.84) and stage III disease (OR = 0.88; 95%CI 0.82-0.94) (all p < 0.05). CONCLUSION: While guideline adherence to postoperative surveillance with colonoscopy was high, adherence to CEA testing and imaging surveillance strategies was markedly lower following CRC resection. Future studies should investigate avenues to improve compliance with surveillance guidelines among health care providers and patients to optimize postoperative follow-up for CRC.

Circulating Tumor DNA, Imaging, and Carcinoembryonic Antigen: Comparison of Surveillance Strategies Among Patients Who Underwent Resection of Colorectal Cancer-A Systematic Review and Meta-analysis.

BACKGROUND: Almost one-third of colorectal cancer (CRC) patients experience recurrence after resection; nevertheless, follow-up strategies remain controversial. We sought to systematically assess and compare the accuracy of carcinoembryonic antigen (CEA), imaging [positron emission tomography (PET) and computed tomography (CT) scans], and circulating tumor DNA (CtDNA) as surveillance strategies. PATIENTS AND METHODS: PubMed, Medline, Embase, Scopus, Cochrane, Web of Science, and CINAHL were systematically searched. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to assess methodological quality. We performed a bivariate random-effects meta-analysis and reported pooled sensitivity, specificity, and diagnostic odds ratio (DOR) values for each surveillance strategy. RESULTS: Thirty studies were included in the analysis. PET scans had the highest sensitivity to detect recurrence (0.95; 95%CI 0.91-0.97), followed by CT scans (0.77; 95%CI 0.67-0.85). CtDNA positivity had the highest specificity to detect recurrence (0.95; 95%CI 0.91-0.97), followed by increased CEA levels (0.88; 95%CI 0.82-0.92). Furthermore, PET scans had the highest DOR to detect recurrence (DOR 120.7; 95%CI 48.9-297.9) followed by CtDNA (DOR 37.6; 95%CI 20.8-68.0). CONCLUSION: PET scans had the highest sensitivity and DOR to detect recurrence, while CtDNA had the highest specificity and second highest DOR. Combinations of traditional cross-sectional/functional imaging and newer platforms such as CtDNA may result in optimized surveillance of patients following resection of CRC.

Health-related quality of life in adults with tetralogy of Fallot repair: a systematic review and meta-analysis.

BACKGROUND: With the advancement in diagnostics and clinical management, patients with Tetralogy of Fallot (ToF) are surviving till adulthood. Hence, assessing the impact of ToF repair on health-related quality of life (HRQOL) of these patients is becoming increasingly important. The objective of this paper is to conduct a systematic review and meta-analysis of the HRQOL in patients who have undergone ToF repair. METHODS: A systematic search was conducted using PubMed, CINAHL, Medline and Web of Science databases. Studies that compared the HRQOL of adult patients (mean age ≥ 18 years) who had previously undergone ToF repair with healthy controls were included. Analysis was done via Revman V5.3 using a random effects model. RESULTS: The 16 studies (15 using SF-36) included in the meta-analysis, comprised 1818 patients and 50,265 healthy controls. There was a higher proportion of males (59%). The mean ages at surgery and at HRQOL assessment were 5.37 years and 30.3 years, respectively. We found that repaired ToF patients had a statistically significantly lower score in the physical component summary (SMD = - 0.92 CI = - 1.54, - 0.30) and physical functioning (SMD = - 0.27 CI = - 0.50, - 0.03) compared to healthy controls. However, these patients had statistically significantly higher scores in the bodily pain domain (SMD = 0.35 CI = 0.12, 0.58) and social functioning (SMD = 0.23 CI = 0.01, 0.46), while there was no significant difference in other domains. CONCLUSION: Overall, physical domain of HRQOL was statistically significantly lower in repaired ToF patients compared to healthy controls. However, repaired ToF patients scored significantly higher on bodily pain and Social Functioning. There was additionally no difference in the HRQOL between the two groups in other domains of HRQOL.