Are trauma centers penalized for improved prehospital resuscitation?: The effect of prehospital transfusion on arrival vitals and predicted mortality.

BACKGROUND: Prediction models for survival in trauma rely on arrival vital signs to generate survival probabilities. Hospitals are benchmarked on expected and observed outcomes. Prehospital blood (PB) transfusion has been shown to improve mortality, which may affect survival prediction modeling. We hypothesize that the use of PB increases the predicted survival derived from probability models compared with non-blood-based resuscitation. METHODS: All adult trauma patients presenting to a level 1 trauma center requiring emergency release blood transfusion from January 2017 to December 2021 were reviewed. Patients were grouped into those receiving PB or those who did not (no PB). Prehospital Trauma and Injury Severity Score (TRISS) and shock index were compared with those at presentation to hospital. Univariate and multivariate regressions were performed to identify factors associated with changes in survival probability at presentation. RESULTS: In total, 2117 patients were reviewed (PB, 1,011; no PB, 1,106). Patients receiving PB were younger (35 vs. 40 years, p < 0.001), more likely to have blunt mechanism (71% vs. 65%, p = 0.002), and more severely injured (Injury Severity Score, 27 vs. 25; p < 0.001) and had higher rates of prehospital hypotension (44% vs. 19%, p < 0.001) and shock index (1.10 vs. 0.87, p < 0.001). Upon arrival, PB patients had lower rates of ED hypotension (34% vs. 39%, p = 0.01), and significant improvements in arrival TRISS scores (+0.09 vs. -0.02, p < 0.001) and shock index (+0.10 vs. -0.07, p < 0.001) compared with prehospital. On multivariate analysis, PB was associated with a threefold increase in unexpected survivors (odds ratio, 3.28; 95% confidence interval, 2.23-4.60). CONCLUSION: The use of PB was associated with improved probability of survival and an increase in unexpected survivors. Applying TRISS and shock index at hospital arrival does not account for en route hemostatic resuscitation, causing patients to arrive with improved vitals despite severity of injury. Caution should be used when implementing survival probability calculations using arrival vitals in centers with prehospital transfusion capability. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

'Door-to-prophylaxis' as a novel quality improvement metric in prevention of venous thromboembolism following traumatic injury.

Objective: Venous thromboembolism (VTE) risk reduction strategies include early initiation of chemoprophylaxis, reducing missed doses, weight-based dosing and dose adjustment using anti-Xa levels. We hypothesized that time to initiation of chemoprophylaxis would be the strongest modifiable risk for VTE, even after adjusting for competing risk factors. Methods: A prospectively maintained trauma registry was queried for patients admitted July 2017-October 2021 who were 18 years and older and received emergency release blood products. Patients with deep vein thrombosis or pulmonary embolism (VTE) were compared to those without (no VTE). Door-to-prophylaxis was defined as time from hospital arrival to first dose of VTE chemoprophylaxis (hours). Univariate and multivariate analyses were then performed between the two groups. Results: 2047 patients met inclusion (106 VTE, 1941 no VTE). There were no differences in baseline or demographic data. VTE patients had higher injury severity score (29 vs 24), more evidence of shock by arrival lactate (4.6 vs 3.9) and received more post-ED transfusions (8 vs 2 units); all p<0.05. While there was no difference in need for enoxaparin dose adjustment or missed doses, door-to-prophylaxis time was longer in the VTE group (35 vs 25 hours; p=0.009). On multivariate logistic regression analysis, every hour delay from time of arrival increased likelihood of VTE by 1.5% (OR 1.015, 95% CI 1.004 to 1.023, p=0.004). Conclusion: The current retrospective study of severely injured patients with trauma who required emergency release blood products found that increased door-to-prophylaxis time was significantly associated with an increased likelihood for VTE. Chemoprophylaxis initiation is one of the few modifiable risk factors available to combat VTE, therefore early initiation is paramount. Similar to door-to-balloon time in treating myocardial infarction and door-to-tPA time in stroke, "door-to-prophylaxis time" should be considered as a hospital metric for prevention of VTE in trauma. Level of evidence: Level III, retrospective study with up to two negative criteria.

Empiric Cryoprecipitate Transfusion in Patients with Severe Hemorrhage: Results from the US Experience in the International CRYOSTAT-2 Trial.

BACKGROUND: Hypofibrinogenemia has been shown to predict massive transfusion and is associated with higher mortality in severely injured patients. However, the role of empiric fibrinogen replacement in bleeding trauma patients remains controversial. We sought to determine the effect of empiric cryoprecipitate as an adjunct to a balanced transfusion strategy (1:1:1). STUDY DESIGN: This study is a subanalysis of patients treated at the single US trauma center in a multicenter randomized controlled trial. Trauma patients (more than 15 years) were eligible if they had evidence of active hemorrhage requiring emergent surgery or interventional radiology, massive transfusion protocol (MTP) activation, and received at least 1 unit of blood. Transfer patients, those with injuries incompatible with life, or those injured more than 3 hours earlier were excluded. Patients were randomized to standard MTP (STANDARD) or MTP plus 3 pools of cryoprecipitate (CRYO). Primary outcomes included all-cause mortality at 28 days. Secondary outcomes were transfusion requirements, intraoperative and postoperative coagulation laboratory values, and quality-of-life measures (Glasgow outcome score-extended). RESULTS: Forty-nine patients (23 in the CRYO group and 26 in the STANDARD group) were enrolled between May 2021 and October 2021. Time to randomization was similar between groups (14 vs 24 minutes, p = 0.676). Median time to cryoprecipitate was 41 minutes (interquartile range 37 to 48). There were no differences in demographics, arrival physiology, laboratory values, or injury severity. Intraoperative and ICU thrombelastography values, including functional fibrinogen, were similar between groups. There was no benefit to CRYO with respect to post-emergency department transfusions (intraoperative and ICU through 24 hours), complications, Glasgow outcome score, or mortality. CONCLUSIONS: In this study of severely injured, bleeding trauma patients, empiric cryoprecipitate did not improve survival or reduce transfusion requirements. Cryoprecipitate should continue as an "on-demand" addition to a balanced transfusion strategy, guided by laboratory values and should not be given empirically.

The reports of my death are greatly exaggerated: An evaluation of futility cut points in massive transfusion.

BACKGROUND: Following COVID and the subsequent blood shortage, several investigators evaluated futility cut points in massive transfusion. We hypothesized that early aggressive use of damage-control resuscitation, including whole blood (WB), would demonstrate that these cut points of futility were significantly underestimating potential survival among patients receiving >50 U of blood in the first 4 hours. METHODS: Adult trauma patients admitted from November 2017 to October 2021 who received emergency-release blood products in prehospital or emergency department setting were included. Deaths within 30 minutes of arrival were excluded. Total blood products were defined as total red blood cell, plasma, and WB in the field and in the first 4 hours after arrival. Patients were first divided into those receiving ≤50 or >50 U of blood in the first 4 hours. We then evaluated patients by whether they received any WB or received only component therapy. Thirty-day survival was evaluated for all included patients. RESULTS: A total of 2,299 patients met the inclusion criteria (2,043 in ≤50 U, 256 in >50 U groups). While there were no differences in age or sex, the >50 U group was more likely to sustain penetrating injury (47% vs. 30%, p < 0.05). Patients receiving >50 U of blood had lower field and arrival blood pressure and larger prehospital and emergency department resuscitation volumes ( p < 0.05). Patients in the >50 U group had lower survival than those in the ≤50 cohort (31% vs. 79%; p < 0.05). Patients who received WB (n = 1,291) had 43% increased odds of survival compared with those who received only component therapy (n = 1,008) (1.09-1.87, p = 0.009) and higher 30-day survival at transfusion volumes >50 U. CONCLUSION: Patient survival rates in patients receiving >50 U of blood in the first 4 hours of care are as high as 50% to 60%, with survival still at 15% to 25% after 100 U. While responsible blood stewardship is critical, futility should not be declared based on high transfusion volumes alone. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Is the use of nonsteroidal anti-inflammatories after bowel anastomosis in trauma safe?

BACKGROUND: With an increasing interest in multimodal and opioid-reducing pain strategies, nonsteroidal anti-inflammatory drugs (NSAIDs) have become common place in the care of injured patients. Long-standing concerns of increased anastomotic leak (AL) rate with the use of NSAIDs, however, have persisted. We hypothesized that there would be no significant risk associated with NSAID use after bowel anastomosis in trauma patients. METHODS: All patients presenting to a level 1 trauma center who required intestinal resection and anastomosis from 2011 to 2017 were reviewed. Patients receiving NSAIDs were compared with those managed without NSAIDs. Primary outcome of interest was anastomosis-related complications (AL, intra-abdominal abscess, anastomotic bleed, fascial dehiscence, fascial dehiscence, and enterocutaneous fistula). Multivariable logistic regression analyses were performed with propensity adjustment for inverse probability of NSAID treatment weights. RESULTS: A total of 295 patients met the inclusion criteria with 192 receiving NSAIDs. Patients receiving NSAIDs had lower abdominal Abbreviated Injury Scale and Injury Severity Score ( p < 0.046). Arrival systolic blood pressure, diastolic blood pressure, and Glasgow Coma Scale were higher in the NSAID group ( p < 0.013). After propensity weighting, NSAID use was not a major predictor of anastomotic complication ( p = 0.39). There was an increased risk of AL with perioperative vasopressor exposure (odds ratio [OR], 3.33; 95% confidence interval [CI], 1.17-9.05; p < 0.001). Increasing red blood cell transfusions in the first 24 hours were associated with intra-abdominal complications (OR, 1.02; 95% CI, 1.00-1.04; p = 0.05). Nonsteroidal anti-inflammatory drug exposure demonstrated a weak association with AL (OR, 1.92; 95% CI, 0.97-3.90; p = 0.06). CONCLUSION: Consistent with previous studies, perioperative vasopressor exposure and increased number of red blood cell transfusions are risk factors for ALs and intra-abdominal complications, respectively. Nonsteroidal anti-inflammatory drug use in trauma patients with multiple risk factors may be associated with an increased risk of AL and should be used with caution in the setting of other established risk factors. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Simultaneous versus rapid serial interventions in a hybrid operating suite for severely injured patients: a prospective evaluation of differences in RAPTOR techniques and outcomes.

BACKGROUND: Open surgical and percutaneous endovascular procedures aimed at arresting traumatic life-threatening hemorrhage are usually performed in rapid serial fashion by surgeons and interventional radiologists; truly simultaneous procedures require modifications in technique, workflow and team collaboration. The primary objective of this study was to prospectively audit outcomes in patients with ongoing hemorrhage who underwent truly simultaneous open and percutaneous procedures. METHODS: We prospectively evaluated the cases of all severely injured patients who required an open and percutaneous procedure within the hybrid RAPTOR (resuscitation with angiography, percutaneous techniques and operative repair) suite at the Foothills Medical Centre, Calgary, Alberta, Canada, between Apr. 4, 2013, and Dec. 5, 2019. We compared outcomes between the truly simultaneous and rapid serial cases. RESULTS: Thirty-five patients (31 [89%] male, median age 46 yr, median Injury Severity Score 30, blunt mechanism in 26 cases [74%]) underwent a hybrid intervention in the RAPTOR suite to stop ongoing hemorrhage during the study period. Twenty-three patients (66%) had a rapid serial procedure, and 12 (34%) had a truly simultaneous procedure. Demographic characteristics were similar between the 2 groups. Compared to the rapid serial group, a higher proportion of patients in the truly simultaneous group were hemodynamically unstable (11 [92%] v. 13 [56%], p = 0.03) and required damage-control procedures (10 [83%] v. 12 [52%], p = 0.03). The time from hospital arrival to procedure initiation was shorter for the truly simultaneous group (mean 31 min v. 59 min, p = 0.02), and a lower proportion had initial radiologic studies (3 [25%] v. 16 [70%], p = 0.01). The median hospital length of stay, intensive care unit stay and mortality rate were similar between the 2 groups. CONCLUSION: Truly simultaneous open and percutaneous procedures to stop ongoing hemorrhage were unique in both patient and procedural details. For the most severely injured patients, the provision of truly simultaneous modalities is necessary to achieve clinical outcomes equivalent to those of less ill patients.

Penetrating renal injuries: an observational study of non-operative management and the impact of opening Gerota's fascia.

BACKGROUND: Non-operative management has become increasingly popular in the treatment of renal trauma. While data are robust in blunt mechanisms, the role of non-operative management in penetrating trauma is less clear. Additionally, there is a paucity of data comparing gunshot and stab wounds. METHODS: A retrospective review of patients admitted to a high-volume level 1 trauma center (Groote Schuur Hospital, Cape Town) with penetrating abdominal trauma was performed. Patients with renal injuries were identified and compared based on mechanism [gunshot (GSW) vs. stab] and management strategy (operative vs. non-operative). Primary outcomes of interest were mortality and failure of non-operative management. Secondary outcomes of interest were nephrectomy rates, Clavien-Dindo complication rate, hospital length of stay, and overall morbidity rate. RESULTS: A total of 150 patients with renal injuries were identified (82 GSW, 68 stab). Overall, 55.2% of patients required emergent/urgent laparotomy. GSWs were more likely to cause grade V injury and concurrent intra-abdominal injuries (p > 0.05). The success rate of non-operative management was 91.6% (89.9% GSW, 92.8% stab, p = 0.64). The absence of hematuria on point of care testing demonstrated a negative predictive value of 98.4% (95% CI 96.8-99.2%). All but 1 patient who failed non-operative management had associated intra-abdominal injuries requiring surgical intervention. Opening of Gerota's fascia resulted in nephrectomy in 55.6% of cases. There were no statistically significant risk factors for failure of non-operative management identified on univariate logistic regression. CONCLUSIONS: NOM of penetrating renal injuries can be safely and effectively instituted in both gunshot and stab wounds with a very low number of patients progressing to laparotomy. Most patients fail NOM for associated injuries. During laparotomy, the opening of Gerota's fascia may lead to increased risk of nephrectomy. Ongoing study with larger populations is required to develop effective predictive models of patients who will fail NOM.

Is the Pringle manoeuvre becoming a lost art? Contemporary use for both severe liver trauma with ongoing hemorrhage and elective partial hepatectomy.

The Pringle manoeuvre (vascular inflow occlusion) has been a mainstay technique in trauma surgery and hepato-pancreato-biliary surgery since it was first described in the early 1900s. We sought to determine how frequently the manoeuvre is used today for both elective and emergent cases in these disciplines. To reflect on its evolution, we evaluated the Pringle manoeuvre over a recent 10-year period (2010-2020). We found it is used less frequently owing to more frequent nonoperative management and more advanced elective hepatic resection techniques. Continuing educational collaboration is critical to ensure continued insight into the impact of hepatic vascular inflow occlusion among trainees who observe this procedure less frequently.

Inviting a friend to evaluate potential grade III pancreatic injuries: Are they truly occult, or simply missed on CT?

Traumatic inuries to the pancreas are notoriously challenging to diagnose and treat. Detecting a main pancreatic ductal injury can be particularly difficult on screening computed tomography (CT). Twenty-four blinded faculty clinicians from 4 differing specialties and 6 institutions reviewed 9 video CT cases of potential pancreatic ductal injuries. Clinician performance in detection of confirmed grade III pancreatic injuries varied widely among specialties. This heterogeneity confirms the critical need for multidisciplinary care and image interpretation for even "minor" (i.e., not grade IV or V) potential pancreatic injuries to optimize outcomes for injured patients. The ubiquitous availability of electronic devices allows real-time collegial second opinions to be easily available.

Topography of occult pneumothoraces: its importance for efficiency in diagnosis and avoiding sono-paralysis during POCUS.

Traumatic pneumothoraces remain a life-threatening problem that may be resolved quickly with timely diagnosis. Unfortunately, they are still not optimally managed. The most critically injured patients with hemodynamic instability require immediate diagnoses of potentially correctible conditions in the primary survey. Point-of-care ultrasonography (POCUS) performed by the responsible physician can be a tremendous adjunct to expediting diagnoses in the primary surgery and can typically be done in seconds rather than minutes. If more detailed sonographic examination is required, the secondary survey of the hemodynamically unstable patient is more appropriate. All involved in bedside care need to be conscious to efficiently integrate POCUS into resuscitation with the right intentions and goals to avoid sono-paralysis of the resuscitation sequence. Sono-paralysis has recently been described as critical situations wherein action is delayed through unnecessary imaging after a critical diagnosis has been made or unnecessary imaging details are sought despite an urgent diagnosis being made.

OPTICC: A multicentre trial of Occult Pneumothoraces subjected to mechanical ventilation: The final report.

INTRODUCTION: Patients with occult pneumothorax (OPTX) requiring positive-pressure ventilation (PPV) face uncertain risks of tension pneumothorax or chest drainage complications. METHODS: Adults with traumatic OPTXs requiring PPV were randomized to drainage/observation, with the primary outcome of composite "respiratory distress" (RD)). RESULTS: Seventy-five (75) patients were randomized to observation, 67 to drainage. RD occurred in 38% observed and 25% drained (p = 0.14; Power = 0.38), with no mortality differences. One-quarter of observed patients failed, reaching 40% when ventilated >5 days. Twenty-three percent randomized to drainage had complications or ineffectual drains. CONCLUSION: RD was not significantly different with observation. Thus, OPTXs may be cautiously observed in stable patients undergoing short-term PPV when prompt "rescue drainage" is immediately available. As 40% of patients undergoing prolonged (≥5 days) ventilation (PPPV) require drainage, we suggest consideration of chest drainage performed with expert guidance to reduce risk of chest tube complications. LEVEL OF EVIDENCE: Therapeutic study, level II.

The prehospital use of younger age whole blood is associated with an improved arrival coagulation profile.

INTRODUCTION: Recent in vitro data have shown that the hemostatic profile of whole blood (WB) degrades significantly after 14 days, yet the optimal storage remains debated. We hypothesized that arrival coagulation studies would be improved in patients receiving younger WB in the prehospital setting. METHODS: This study was approved by our institutional institutional review board. We evaluated all trauma patients who received prehospital blood products by our helicopter service between July 2017 and July 2019. "Young" WB was defined as 14 days or less. Patients who received at least 1 U of young WB were classified as YOUNG, while the remainder was classified as OLD. Continuous data are presented as medians (25th-75th interquartile range) with comparisons performed using Wilcoxon rank sum. Assessments of clinical hemostatic potential included arrival platelet cell count and rapid thrombelastography. Multivariate regression analysis was also performed (Stata 12.1; College Station, TX). RESULTS: A total of 220 patients received prehospital WB during the study period. Of these, 153 patients received YOUNG WB, while 67 were transfused only OLD WB units. There were no differences in demographics, prehospital or arrival physiology, or Injury Severity Score among the two groups. The measures of clot initiation (activated clotting time) and kinetics (k time) were improved, as were the measures of clot acceleration/fibrinogen function (angle) and platelet function (maximum amplitude). As well, arrival platelet count was higher in the YOUNG cohort. No significant differences in postarrival transfusion were noted (p = 0.220). Multivariate analysis showed the greatest differences in maximum amplitude and α angle but failed to reach significance. CONCLUSION: Previous in vitro data have suggested deterioration of platelet function in cold-stored WB after 14 days. The current study demonstrated decreased global hemostasis by clinically available laboratory tests, especially related to fibrinogen and platelet interactions on univariate, but not multivariate analysis. This did not translate into increased transfusion requirements. Further studies are needed to determine the optimal storage duration for cold-stored WB for transfusion in the bleeding trauma patient, as well as rule out the presence of confounding variables. LEVEL OF EVIDENCE: Therapeutic, level IV.

A Guide to COVID-19: a global pandemic caused by the novel coronavirus SARS-CoV-2.

The emergence of the SARS-CoV-2 strain of the human coronavirus has thrown the world into the midst of a new pandemic. In the human body, the virus causes COVID-19, a disease characterized by shortness of breath, fever, and pneumonia, which can be fatal in vulnerable individuals. SARS-CoV-2 has characteristics of past human coronaviruses, with close genomic similarities to SARS-CoV, the virus that causes the disease SARS. Like these related coronaviruses, SARS-CoV-2 is transmitted through the inhalation of droplets and interaction with contaminated surfaces. Across the world, laboratories are developing candidate vaccines for the virus - with vaccine trials underway in the United States and the United Kingdom - and considering various drugs for possible treatments and prophylaxis. Here, we provide an overview of SARS-CoV-2 by analyzing its virology, epidemiology, and modes of transmission while examining the current progress of testing procedures and possible treatments through drugs and vaccines.

AIBP-mediated cholesterol efflux instructs hematopoietic stem and progenitor cell fate.

Hypercholesterolemia, the driving force of atherosclerosis, accelerates the expansion and mobilization of hematopoietic stem and progenitor cells (HSPCs). The molecular determinants connecting hypercholesterolemia with hematopoiesis are unclear. Here, we report that a somite-derived prohematopoietic cue, AIBP, orchestrates HSPC emergence from the hemogenic endothelium, a type of specialized endothelium manifesting hematopoietic potential. Mechanistically, AIBP-mediated cholesterol efflux activates endothelial Srebp2, the master transcription factor for cholesterol biosynthesis, which in turn transactivates Notch and promotes HSPC emergence. Srebp2 inhibition impairs hypercholesterolemia-induced HSPC expansion. Srebp2 activation and Notch up-regulation are associated with HSPC expansion in hypercholesterolemic human subjects. Genome-wide chromatin immunoprecipitation followed by sequencing (ChIP-seq), RNA sequencing (RNA-seq), and assay for transposase-accessible chromatin using sequencing (ATAC-seq) indicate that Srebp2 transregulates Notch pathway genes required for hematopoiesis. Our studies outline an AIBP-regulated Srebp2-dependent paradigm for HSPC emergence in development and HPSC expansion in atherosclerotic cardiovascular disease.

Synchronous colorectal liver metastases: a national survey of surgeon opinions on simultaneous resection and multidisciplinary cooperation.

BACKGROUND: The management of patients with synchronous colorectal liver metastases (sCRLM) has evolved significantly (improved chemotherapy, hepatic surgery advancements, colonic stenting, consultation synergies). We sought to better understand surgeon viewpoints on optimal referral patterns and the delivery of simultaneous resections. METHODS: A 40 question on-line survey was offered to members of the Canadian surgical community. Statistical analysis was descriptive. RESULTS: A total of 52 surgeons responded. Most colorectal surgeons (CRS) had access to and a good working relationship with regional hepatobiliary (HPB) surgeons (86%) and medical oncologists (100%). The majority (92%) believed there was a role for simultaneous resection of sCRLM, with 69% having first hand experience. Many CRS (62%) discussed all cases of known hepatic metastases with HPB prior to any resection. When a lesion was asymptomatic/minimally symptomatic, most CRS (92%) discussed them with medical oncology/HPB prior to resection (8%). Bilobar metastases (58%), patient comorbidities (35%), portal lymphadenopathy (35%), and patient age (15%) restricted CRS from obtaining HPB consultations. Many CRS (46%) did not believe that resecting hepatic metastases prior to the primary lesion might be beneficial. Most CRS (60%) reported they could not accurately predict hepatic resectability, with only 27% familiarity with evidence-based guidelines. Despite working in smaller hospitals with less access to HPB and less experience with simultaneous resections, non-CR general surgeons more commonly supported a 'liver-first' approach. CONCLUSIONS: There was general agreement between CRS and general surgeons on numerous topics, but additional education is required with regard to HPB surgical capabilities and to provide truly individualized patient-centered care.

Neurocognitive assessment in patients with a minor traumatic brain injury and an abnormal initial CT scan: Can cognitive evaluation assist in identifying patients who require surveillance CT brain imaging?

BACKGROUND: Evidence for repeat computed tomography (CT) in minor traumatic brain injury (mTBI) patients with intracranial pathology is scarce. The aim of this study was to investigate the utility of clinical cognitive assessment (COG) in defining the need for repeat imaging. METHODS: COG performance was compared with findings on subsequent CT, and need for neurosurgery in mTBI patients (GCS 13-15 and positive CT findings). RESULTS: Of 152 patients, 65.8% received a COG (53.0% passed). Patients with passed COG underwent fewer repeat CT (43.4% vs. 78.7%; p = .001) and had shorter LOS (8.7 vs. 19.5; p < .05). Only 1 patient required neurosurgery after a passed COG. The negative predictive value of a normal COG was 90.6% (95%CI = 81.8%-95.4%). CONCLUSION: mTBI patients with an abnormal index CT who pass COG are less likely to undergo repeat CT head, and rarely require neurosurgery. The COG warrants further investigation to determine its role in omitting repeat head CT.

Neuropilin 1 balances ß8 integrin-activated TGFß signaling to control sprouting angiogenesis in the brain.

Angiogenesis in the developing central nervous system (CNS) is regulated by neuroepithelial cells, although the genes and pathways that couple these cells to blood vessels remain largely uncharacterized. Here, we have used biochemical, cell biological and molecular genetic approaches to demonstrate that ß8 integrin (Itgb8) and neuropilin 1 (Nrp1) cooperatively promote CNS angiogenesis by mediating adhesion and signaling events between neuroepithelial cells and vascular endothelial cells. ß8 integrin in the neuroepithelium promotes the activation of extracellular matrix (ECM)-bound latent transforming growth factor ß (TGFß) ligands and stimulates TGFß receptor signaling in endothelial cells. Nrp1 in endothelial cells suppresses TGFß activation and signaling by forming intercellular protein complexes with ß8 integrin. Cell type-specific ablation of ß8 integrin, Nrp1, or canonical TGFß receptors results in pathological angiogenesis caused by defective neuroepithelial cell-endothelial cell adhesion and imbalances in canonical TGFß signaling. Collectively, these data identify a paracrine signaling pathway that links the neuroepithelium to blood vessels and precisely balances TGFß signaling during cerebral angiogenesis.