Since the 1990’s attempts to favorably modulate nitric oxide (NO) have been unsuccessful. We hypothesized that because NO is lipophilic it would preferentially localize into intravascularly infused hydrophobic nanoparticles, thereby reducing its bioavailability and adverse effects without inhibiting its production. We aimed to determine the efficacy and safety of intravenous infusion of a fluid comprised of hydrophobic phospholipid nanoparticles (VBI-S) that reversibly absorb NO in the treatment of hypotension of patients in severe septic shock. This is a multicentre, open-label, repeated measures, phase 2a clinical pilot trial done at six hospital centers in the USA. Patients in severe septic shock were enrolled after intravenous fluid therapy had failed to raise mean arterial blood pressure (MAP) to at least the generally accepted level of 65 mmHg, requiring the use of vasopressors. The primary endpoint of this study is the proportion of patients in whom MAP increased by at least 10 mmHg. VBI-S was administered intravenously to patients as boluses of 100 ml, 200 ml, 400 ml, and 800 ml at 999 ml/min until the blood pressure goal was reached after which the infusion was stopped, and the MAP was recorded. All patients who received any volume of VBI-S were included in the primary and safety analysis. The study is registered with ClinicalTrials.gov, NCT04257136. Between February 17, 2020 and January 3, 2023, 20 eligible patients were enrolled in the study. In all 20 (100%) patients, the goal of increasing MAP by at least 10 mmHg using VBI-S was achieved (p = 0.0087, effect size = 0.654). Mean VBI-S volume required to meet the primary goal was 561.0 ± 372.3 ml. The goal of lowering vasopressor dose was also achieved (p = 0.0017). Within 48 h or less after VBI-S, there was a statistically significant improvement in oxygenation, serum creatinine, clotting variables, procalcitonin, lactic acid, and the sequential organ failure assessment (SOFA) score. At 24 h and 48 h following administration of VBI-S, 12/15 (80%) and 9/12 (75%) patients developed hyperlipidemia, respectively. No severe adverse events of VBI-S were observed, and there were no treatment-related deaths. These preliminary findings suggest the safety and efficacy of VBI-S in treating hypotension in patients with septic shock. However, a definitive mortality benefit cannot be demonstrated without a randomized controlled study. The Naval Medical Research Command—Naval Advanced Medical Development program via the 10.13039/100021976 Medical Technology Enterprise Consortium .

Background/Objectives: Exsanguination is a leading cause of preventable death in military and civilian settings due to extensive blood loss and hemorrhagic shock, which trigger systemic effects such as impaired tissue perfusion, hypoxia, inflammation, and multi-organ dysfunction. Standard resuscitation restores blood volume but fails to address critical aspects of hemorrhagic shock, including inflammation, coagulopathy, and reperfusion injury. To address these limitations, novel phospholipid nanoparticle (PNP)-based resuscitative fluids, VBI-S and VBI-1, were developed to modulate nitric oxide (NO) levels, improving hemodynamic stability, tissue oxygenation, and reducing inflammatory injury. This study assessed the potential of novel phospholipid nanoparticle fluids, VBI-S and VBI-1, as resuscitative agents for severe hemorrhagic shock by evaluating their ability to regulate nitric oxide, restore blood pressure, and mitigate ischemia–reperfusion injury. Methods: This study involved two phases with Sprague Dawley rats (n = 6 per group). Phase one, lasting 4 h, included four groups: blood, Ringer’s lactate, VBI-S, and VBI-1. Phase two, lasting 12 h, comprised sham, blood, and VBI-1 groups. Under anesthesia, one femoral artery was catheterized for blood pressure monitoring, and blood withdrawal from the other induced apnea. Reanimation was performed using an intra-arterial infusion of shed blood, Ringer’s lactate, VBI-S, or VBI-1. Tissue samples were analyzed histologically and for oxidative DNA damage via immunofluorescence. Chemiluminescence and rheology assessed nitric oxide interactions and viscosity. Data were analyzed using ANOVA. Results: VBI-1 and shed blood increased mean arterial pressure (MAP) from <10 mmHg to survivable levels sustained for 12 h, with VBI-1 showing significantly higher MAP at 3–4 h. Rats treated with Ringer’s lactate died within 30 min. Histology revealed reduced organ damage in VBI-1-treated rats compared to shed blood. Immunohistochemistry indicated significantly less oxidative DNA damage (p < 0.001) in VBI-1-treated rats. VBI-1 exhibited superior viscosity and nitric oxide binding. Conclusions: VBI-1 demonstrates strong potential as a resuscitative fluid, offering blood pressure restoration, reduced oxidative damage, and enhanced tissue perfusion, with significant implications for use in resource-limited and pre-hospital settings.

Background: Research on interpersonal violence typically focuses on urban areas. However, violence is also an issue in rural America, although knowledge gaps exist in this area. Our study aims to identify factors related to interpersonal violence in rural Missouri.Methods: For each rural county, we collected data on homicide and crime rates, along with multiple variables that may contribute to violent crime, based on a literature review. We used Pearson Correlations to determine statistically significant relationships between variables.Findings: We found a strong correlation between crimes committed by juvenile gangs and the homicide rate. We also found that juvenile gang crime correlated with the percentage of families below the poverty line. The homicide rate did not correlate with the crime rate; however, the crime rate did correlate with domestic violence and third-grade reading levels. Surprisingly, there was no correlation between the Gini index and the homicide rate, a known correlate to homicide rates worldwide. Interpretation: Crimes committed by juvenile gangs may be a better marker for the homicide rate within a smaller geographic region in which there is a small variation in the Gini Index. Correlates to the crime and homicide rates suggest family stress and dysfunction. Our findings are significant in directing focus to interventions that provide support for families to hopefully reduce the burden of interpersonal violence in rural Missouri communities.