At present, there are no proven pharmacological treatments demonstrated to improve long term functional outcomes following traumatic brain injury(TBI). In the setting of non-penetrating TBI, sterile brain inflammatory responses are associated with the development of cerebral edema, intracranial hypertension, and secondary neuronal injury. There is increasing evidence that endogenous apolipoprotein E(apoE) modifies the neuroinflammatory response through its role in downregulating glial activation, however, the intact apoE holoprotein does not cross the blood-brain barrier due to its size. To address this limitation, we developed a small 5 amino acid apoE mimetic peptide(CN-105) that mimics the polar face of the apoE helical domain involved in receptor interactions. The goal of this study was to investigate the therapeutic potential of CN-105 in a murine model of closed head injury. Treatment with CN-105 was associated with a durable improvement in functional outcomes as assessed by Rotarod and Morris Water Maze and a reduction in positive Fluoro-Jade B stained injured neurons and microglial activation. Administration of CN-105 was also associated with reduction in mRNA expression of a subset of inflammatory and immune-related genes.

Our study suggests that craniosynostosis patients who are non-White, have a non-English primary language, and have Medicaid insurance are at risk for delayed primary surgery, which may lead to increased 30-day readmission. Interventions are necessary to reduce craniosynostosis patients' barriers to care to minimize the sequelae associated with delayed surgery.

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Our study suggests that weakness, sensory deficits, and uncontrolled pain are the most common complications after resection of spinal metastases, with a relatively high associated 30-day readmission rate. Further studies are necessary to corroborate our findings and identify strategies to reduce complication and readmission rates after resection of spinal metastases.

Extracellular mitochondrial DNA levels are elevated early in patients' hospital courses in many acute illnesses and are higher in patients who develop inflammatory complications. Elevated mitochondrial DNA levels may be clinically useful in risk prediction and clinical decision support systems. Further research is needed to determine the role of extracellular N-formyl peptides in systemic inflammation and their possible clinical utility.

Background: Certain intrauterine risk factors are known to increase the risk of premature cranial suture fusion and may cause complications during birth. Some of these risk factors may be modifiable. Therefore, the authors sought to characterize the institutional patterns of prenatal risk factors and perinatal complications in nonsyndromic craniosynostosis patients compared to normal births from the surrounding area to identify areas for possible intervention or prevention. Methods: The medical records of all infants with nonsyndromic craniosynostosis and full birth records born at Duke University Health System from 2006 to 2017 were retrospectively reviewed. Maternal comorbidities, prenatal risk factors, and perinatal complications were collected. The North Carolina State Center for Health Statistics was queried for perinatal statistics from Durham county and the Northeastern Perinatal Care Region to represent a control cohort of normal births from the same time period and region. The primary outcome investigated was the incidence of prenatal risk factors and complications at birth associated with premature fusion of cranial sutures. Results: Eighty births with nonsyndromic craniosynostosis were included in this study. The majority of these patients were males (61.7%) and born via cesarean section (55.0%). Intrauterine growth restriction occurred in 10.0% and head trauma during delivery occurred in 2.5%. Twinning (14.8% vs 3.6%, P < 0.0001), cesarean births (55.5% vs 30.0%, P < 0.0001), and breech presentation (17.3% vs 3.2%, P < 0.0001) were significantly more common in craniosynostosis patients. Prenatally, mothers of craniosynostosis infants had higher incidence of gestational diabetes (13.5% vs 5.0%, P < 0.0001) and oligohydramnios (6.1% vs 1.3%, P < 0.0001) compared to regional controls. Conclusion: This study demonstrates that premature suture fusion is associated with prenatal risk factors such as gestational diabetes and oligohydramnios. Continued research into potentially modifiable prenatal risk factors and more refined prenatal diagnostic tools has the potential to reduce both the incidence of premature suture fusion and the sequelae of birth complications in this population.

BACKGROUND: The recent pandemic exposed a largely unrecognized threat to medical resources, including daily available blood products. Some of the most severely injured patients who arrive in extremis consume tremendous resources yet succumb shortly after arrival. We sought to identify cut points available early in the patient’s resuscitation that predicted 100% mortality. STUDY DESIGN: Cut points were developed from a previously collected data set of all level 1 trauma patients admitted January 2010 to December 2016. Objective values available on or shortly after arrival were evaluated. Once generated, we then validated these variables against (1) a prospective data set November 2017 to October 2021 of severely injured patients and (2) a multicenter, randomized trial of hemorrhagic shock patients. Analyses were conducted using STATA 17.0 (College Station, TX), generating positive predictive value (PPV), negative predictive value, sensitivity, and specificity. RESULTS: The development data set consisted of 9,509 patients (17% mortality), with 2,137 (24%) and 680 (24%) in the two validation data sets. Several combinations of arrival vitals and labs had 100% PPV. Patients undergoing CPR in the field or on arrival (with subsequent return of spontaneous circulation) required lower fibrinolysis LY-30 (30%) than those with systolic blood pressures of ≤50 (30 to 50%), ≤70 (80 to 90%), and ≤90 mmHg (90%). Using a combination of these validated variables, the Suspension of Transfusions and Other Procedures (STOP) criteria were developed, with each element predicting 100% mortality, allowing physicians to cease further resuscitative efforts. CONCLUSIONS: The use of evidence-based STOP criteria provides cut points of futility to help guide early decisions for discontinuing aggressive treatment of severely injured patients arriving in extremis.

Background: The hypoxia-inducible factor (HIF) pathway, regulated by prolyl hydroxylase, is central to tissue adaptation to ischemia. The authors tested whether the prolyl hydroxylase inhibitor dimethyloxalylglycine reduces skin flap necrosis. Methods: Dorsal skin flaps were raised on hairless rats, with dimethyloxalylglycine delivered intraperitoneally and/or topically for 7 days before and after surgery. After 14 treatment days, percentage of flap necrosis was compared grossly and tissue perfusion compared with an in vivo imaging system. Angiogenesis was compared using immunohistochemical CD31 staining and enzyme-linked immunosorbent assay for tissue vascular endothelial growth factor. Expression levels of HIF-1α and terminal deoxynucleotidyl transferase-mediated dUDP end-labeling were compared using immunohistochemical staining. Complete blood counts and gross necropsy specimens were obtained to assess systemic toxicity. Results: Dimethyloxalylglycine administration significantly improved postoperative flap viability, with combined topical and intraperitoneal dimethyloxalylglycine administration leading to reduced necrosis on postsurgical day 7 at 6 mg/kg/day, 12 mg/kg/day, 24 mg/kg/day, and 48 mg/kg/day versus controls (all p < 0.05). Compared with controls (unperfused, 39.9 ± 3.8 percent), dimethyloxalylglycine treatment led to a dose-dependent decrease in unperfused tissue at 6 mg/kg/day (11.4 ± 1.7 percent), 12 mg/kg/day (9.4 ± 4.2 percent), 24 mg/kg/day (4.7 ± 2.6 percent), and 48 mg/kg/day (1.4 ± 0.9 percent) (all p < 0.001). Topical dimethyloxalylglycine application alone administered at 48 mg/kg/day was sufficient to improve flap viability (p = 0.005). Dimethyloxalylglycine-treated flaps exhibited higher CD31 staining (p = 0.004), tissue vascular endothelial growth factor (p = 0.007), HIF-1α staining (p < 0.001), and reduced terminal deoxynucleotidyl transferase-mediated dUDP end-labeling staining (p = 0.045). There were no differences in hematocrit or macroscopic organ changes on gross necropsy. Conclusion: Topical and systemic targeting of the HIF-1 pathway may be a promising therapeutic approach to improve flap resistance to ischemia.