Comparison of tumor response and outcomes of patients with hepatocellular carcinoma after multimodal treatment including immune checkpoint inhibitors - a systematic review and meta-analysis.

BACKGROUND: The efficacy of immune checkpoint inhibitors (ICIs) combined with tyrosine kinase inhibitors (TKIs), trans-arterial chemoembolization (TACE), and radiotherapy to treat hepatocellular carcinoma (HCC) has not been well-defined. We performed a meta-analysis to characterize tumor response and survival associated with multimodal treatment of HCC. METHODS: PubMed, Embase, Medline, Scopus, and CINAHL databases were searched (1990-2022). Random-effect meta-analysis was conducted to compare efficacy of treatment modalities. Odds ratios (OR) and standardized mean difference (SMD) were reported. RESULTS: Thirty studies (4170 patients) met inclusion criteria. Triple therapy regimen (ICI + TKI + TACE) had the highest overall disease control rate (DCR) (87%, 95% CI 83-91), while ICI + radiotherapy had the highest objective response rate (ORR) (72%, 95% CI 54%-89%). Triple therapy had a higher DCR than ICI + TACE (OR 4.49, 95% CI 2.09-9.63), ICI + TKI (OR 3.08, 95% CI 1.63-5.82), and TKI + TACE (OR 2.90, 95% CI 1.61-5.20). Triple therapy demonstrated improved overall survival versus ICI + TKI (SMD 0.72, 95% CI 0.37-1.07) and TKI + TACE (SMD 1.13, 95% CI 0.70-1.48) (both p < 0.05). Triple therapy had a greater incidence of adverse events (AEs) compared with ICI + TKI (OR 0.59, 95% CI 0.29-0.91; p = 0.02), but no difference in AEs versus ICI + TACE or TKI + TACE (both p > 0.05). CONCLUSION: The combination of ICIs, TKIs and TACE demonstrated superior tumor response and survival and should be considered for select patients with advanced HCC.

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.

Predicting overall and recurrence-free survival in patients with intrahepatic cholangiocarcinoma using the MEGNA score: A multi-institutional analysis.

BACKGROUND AND OBJECTIVES: MEGNA is a prognostic scoring system for intrahepatic cholangiocarcinoma (ICC) based on tumor multifocality, extension, grade, lymph node positivity, and age. We sought to assess its predictive ability for overall survival (OS) and recurrence-free survival (RFS). METHODS: Patients who underwent curative-intent liver resection for ICC between 2000 and 2020 were identified using an international multi-institutional database. Multivariate Cox regression was utilized to identify prognostic factors. RESULTS: Among 800 patients with a median age of 58 years (interquartile range [IQR]: 50-68), the majority of patients were male (n = 467, 58.4%). 5-year OS was 40.5%, while 5-year RFS was 27.9%. The prognostic ability of MEGNA score (c-index = 0.60) was similar to AJCC (c-index = 0.58) and TBS (c-index = 0.58). MEGNA was an independent prognostic factor for OS (0: Reference; I: hazard ratio [HR]: 1.39, 95% confidence interval [CI]: 1.05-1.84; II: HR: 2.15, 95% CI: 1.57-2.96; ≥III: HR: 2.02, 95% CI: 1.33-3.06; all p < 0.05), alongside high CA 19-9, positive resection margins, and major vascular invasion (all p < 0.05). Furthermore, although MEGNA was not able to predict RFS, high CA 19-9 and microvascular invasion were independently associated with worse RFS. CONCLUSION: MEGNA score was an independent prognostic factor for OS. However, its prognostic ability was modest and comparable to existing systems such as AJCC eigth edition and TBS.

Association between the environmental quality index and textbook outcomes among Medicare beneficiaries undergoing surgery for colorectal cancer (CRC).

BACKGROUND: Quality of cancer care received by individuals may be influenced by environmental factors resulting in inequalities within the healthcare system. We sought to investigate the association between the Environmental Quality Index (EQI) and achievement of textbook outcomes (TOs) among Medicare beneficiaries who underwent surgical resection for colorectal cancer (CRC). METHODS: Patients diagnosed with CRC from 2004 to 2015 were identified using the Surveillance, Epidemiology, and End Results-Medicare database and merged with the US Environmental Protection Agency's EQI data. A high EQI category indicated poor environmental quality, whereas a low EQI indicated better environmental conditions. RESULTS: Among 40 939 patients, 33 699 (82.3%) were diagnosed with colon cancer, 7240 (17.7%) were diagnosed with rectal cancer, and 652 (1.6%) were diagnosed with both cancers. Median age was 76 years old (interquartile range: 70-82 years) with roughly half of patients being female (n = 22 033, 53.8%). Most patients self-reported as White (n = 32 404, 79.2%) and resided in the West region of the United States (n = 20 308, 49.6%). On multivariable analysis, patients residing in high EQI areas were less likely to achieve TO (referent: low EQI; odds ratio [OR]: 0.94, 95% confidence interval [95% CI]: 0.89-0.99; p = 0.02). Of note, Black patients living in moderate-to-high EQI counties had a 31% decreased likelihood of reaching a TO compared with White patients in low EQI counties (OR: 0.69, 95% CI: 0.55-0.87). CONCLUSION: Patients residing in high EQI counties and Black race were associated with a lower likelihood of TO following resection of CRC among Medicare patients. Environmental factors may be important contributors to health care disparities and affect postoperative outcomes following CRC resection.

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.

Prolonged length of stay after surgery for adult congenital heart disease: a single-centre study in a developing country.

BACKGROUND: With the growing number of adults requiring operations for CHD, prolonged length of stay adds an additional burden on healthcare systems, especially in developing countries. This study aimed to identify factors associated with prolonged length of stay in adult patients undergoing operations for CHD. METHODS: This retrospective study included all adult patients (≥18 years) who underwent cardiac surgery with cardiopulmonary bypass for their CHD from 2011 to 2016 at a tertiary-care private hospital in Pakistan. Prolonged length of stay was defined as hospital stay >75th percentile of the overall cohort (>8 days). RESULTS: This study included 166 patients (53.6% males) with a mean age of 32.05 ± 12.11 years. Comorbid disease was present in 59.0% of patients. Most patients underwent atrial septal defect repair (42.2%). A total of 38 (22.9%) patients had a prolonged length of stay. Post-operative complications occurred in 38.6% of patients. Multivariable analysis showed that pre-operative body mass index (odds ratio: 0.779; 95% confidence interval: 0.620-0.980), intraoperative aortic cross-clamp time (odds ratio: 1.035; 95% confidence interval: 1.009-1.062), and post-operative acute kidney injury (odds ratio: 7.392; 95% confidence interval: 1.036-52.755) were associated with prolonged length of stay. CONCLUSION: Predictors of prolonged length of stay include lower body mass index, longer aortic cross-clamp time, and development of post-operative acute kidney injury. Shorter operations, improved pre-operative nutritional optimisation, and timely management of post-operative complications could help prevent prolonged length of stay in patients undergoing operations for adult CHD.

Association of persistent poverty and U.S. News and World Report hospital rankings among patients undergoing major surgery.

BACKGROUND: We sought to determine the association of persistent poverty on patient outcomes relative to US News World Report (USNWR) rankings among individuals undergoing common major surgical procedures. METHODS: Medicare beneficiaries who underwent AAA repair, CABG, colectomy, or lung resection were identified. Multivariable logistic regression was used to evaluate the relationship between care at USNWR hospitals, county-level duration of poverty (never-high poverty (NHP); intermittent high poverty (IHP): persistent-poverty (PP)) and 30-day mortality. RESULTS: Among 916,164 beneficiaries, individuals residing in PP neighborhoods who received surgical care at ranked hospitals had lower risk-adjusted 30-day mortality (5.89% vs 8.89%; p â€‹< â€‹0.001). On multivariable analysis, 30-day mortality was lower at ranked hospitals across all poverty categories with greatest decrease among patients from PP regions (NHP: OR-0.91, 95%CI0.87-0.95; IHP: OR-0.78, 95%CI0.69-0.88; PP: OR-0.69, 95%CI0.57-0.83; p â€‹< â€‹0.001). CONCLUSION: Receipt of surgical care at top-ranked hospitals was associated with improvement in postoperative mortality, especially among patients residing in persistent poverty..

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.

Is surgical treatment of hepatocellular carcinoma at high-volume centers worth the additional cost?

BACKGROUND: Case volume has been associated with improved outcomes for patients undergoing treatment for hepatocellular carcinoma, often with higher hospital expenditures. We sought to define the cost-effectiveness of hepatocellular carcinoma treatment at high-volume centers. METHODS: Patients diagnosed with hepatocellular carcinoma from 2013 to 2017 were identified from Medicare Standard Analytic Files. High-volume centers were defined as the top decile of facilities performing hepatectomies in a year. A multivariable generalized linear model with gamma distribution and a restricted mean survival time model were used to estimate costs and survival differences relative to high-volume center status. The incremental cost-effectiveness ratio was used to define the additional cost incurred for a 1-year incremental gain in survival. RESULTS: Among 13,666 patients, 8,467 (62.0%) were treated at high-volume centers. Median expenditure was higher ($19,148, interquartile range $15,280-$29,128) among patients treated at high-volume centers versus low-volume centers ($18,209, interquartile range $14,959-$29,752). Despite similar median length-of-stay (6 days, interquartile range 4-9), a slightly higher proportion of patients were discharged to home from high-volume centers (n = 4,903, 57.9%) versus low-volume centers (n = 2,868, 55.2%) (P = .002). A 0.14-year (95% confidence interval 0.06-0.22) (1 month and 3 weeks) survival benefit was associated with an incremental cost of $1,070 (95% confidence interval $749-$1,392) among patients undergoing surgery at high-volume centers. The incremental cost-effectiveness ratio for treatment at a high-volume center was $7,951 (95% confidence interval $4,236-$21,217) for an additional year of survival, which was below the cost-effective threshold of $21,217. CONCLUSION: Surgical care at high-volume centers offers the potential to deliver cancer care in a more cost-effective and value-based manner.

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.

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.

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.

Association between the Environmental Quality Index and Textbook Outcomes Among Medicare Beneficiaries Undergoing Surgery for Early-Stage Pancreatic Adenocarcinoma.

BACKGROUND: Access to high-quality cancer care is affected by environmental exposures and structural inequities. This study sought to investigate the association between the environmental quality index (EQI) and achievement of textbook outcomes (TO) among Medicare beneficiaries over the age of 65 who underwent surgical resection for early-stage pancreatic adenocarcinoma (PDAC). METHODS: Patients diagnosed with early-stage PDAC from 2004 to 2015 were identified using the SEER-Medicare database and combined with the US Environmental Protection Agency's EQI data. High EQI category indicated poor environmental quality, whereas low EQI indicated better environmental conditions. RESULTS: A total of 5,310 patients were included, of which 45.0% (n = 2,387) patients achieved TO. Median age was 73 years and more than half were female (n = 2,807, 52.9%), married (n = 3,280, 61.8%), and resided in the Western region of the US (n = 2,712, 51.1%). On multivariable analysis, patients residing in moderate and high EQI counties were less likely to achieve a TO (referent: low EQI; moderate EQI: OR 0.66, 95% CI 0.46-0.95; high EQI: OR 0.65, 95% CI 0.45-0.94; p < 0.05). Increasing age (OR 0.98, 95%CI 0.97-0.99), racial minorities (OR 0.73, 95% CI 0.63-0.85), having a Charlson co-morbidity index > 2 (OR 0.54, 95%CI 0.47-0.61) and stage II disease (OR 0.82, 95%CI 0.71-0.96) were also associated with not achieving a TO (all p < 0.001). CONCLUSION: Older Medicare patients residing in moderate or high EQI counties were less likely to achieve an "optimal" TO after surgery. These results demonstrate that environmental factors may drive post-operative outcomes among patients with PDAC.

Utilization of Telemedicine among Medicare beneficiaries undergoing Hepatopancreatic Surgery during the COVID-19 Pandemic.

INTRODUCTION: Telemedicine may serve as an important avenue to address disparities in access to cancer care. We sought to define factors associated with telemedicine use among Medicare beneficiaries who underwent hepatopancreatic (HP) surgery, as well as characterize trends in telemedicine usage relative to community vulnerability based on the enactment of the Medicare telemedicine coverage waiver. METHODS: Patients who underwent HP surgery between 2013-2020 were identified from the Medicare Standard Analytic Files (SAF). Telemedicine utilization was assessed pre- versus post- implementation of the Medicare telemedicine coverage waiver; the county-level social vulnerability index (SVI) was obtained from the Center for Disease Control. Interrupted time series analysis with negative binomial and multivariable logistic regression methods were used to assess changes in telemedicine utilization after the implementation of the Medicare telemedicine coverage waiver relative to SVI. RESULTS: Pre-waiver telemedicine visits were scarce among 16,690 patients (0.2%, n = 28), while post-waiver telemedicine adoption was substantial among 3,301 patients (45.8%, n = 1,388). Post-waiver, the median patient age was 70 years (IQR, 66-74) with the majority of patients being age 65-69 (n = 994, 32.8%); 1,599 (52.8%) were female. Most patients self-identified as White (n = 2641, 87.1%), while a minority of patients self-identified as Black (n = 190, 6.3%), Asian (n = 18, 0.6%), Hispanic (n = 35, 1.2%), or Other/unknown (n = 147, 4.9%). On multivariable regression analysis, patients who lived in highly vulnerable counties (referent Low SVI; moderate SVI: OR 1.09, 95% CI 0.86-1.39, p = 0.449; high SVI: OR 0.72, 95% CI 0.55-0.94, p = 0.001) and individuals with advancing age (referent 18-64; 65-69, OR 0.68, 95%CI 0.54-0.86; 70-74, OR 0.56, 95%CI 0.44-0.71; 75-79, OR 0.57, 95%CI 0.44-0.75; 80-84, OR 0.43, 95%CI 0.30-0.61; 85 + , OR 0.25, 95%CI 0.13-0.49) had lower odds of utilizing telemedicine. In contrast, Black patients (referent White; OR 2.26, 95% CI 1.65-3.10) and patients with a higher CCI score > 2 (referent ≤ 2; OR 1.49, 95% CI 1.28-1.71) were more likely to use telemedicine (all p < 0.001). CONCLUSIONS: Medicare beneficiaries residing in counties with extreme vulnerability, as well as elderly individuals, were markedly less likely to use telemedicine services related to HP surgical episodes of care. The lower utilization of telemedicine in areas of high social vulnerability was attributable to concomitant lower rates of internet access in these areas.

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.