Nonterpenoid Chemical Diversity of Cannabis Phenotypes Predicts Differentiated Aroma Characteristics.

The recent increase in legality of Cannabis Sativa L. has led to interest in developing new varieties with unique aromatic or effect-driven traits. Selectively breeding plants for the genetic stability and consistency of their secondary metabolite profiles is one application of phenotyping. While this horticultural process is used extensively in the cannabis industry, few studies exist examining the chemical data that may differentiate phenotypes aromatically. To gain insight into the diversity of secondary metabolite profiles between progeny, we analyzed five ice water hash rosin extracts created from five different phenotypes of the same crossing using comprehensive 2-dimensional gas chromatography coupled to time-of-flight mass spectrometry, flame ionization detection, and sulfur chemiluminescence detection. These results were then correlated to results from a human sensory panel, which revealed specific low-concentration compounds that strongly influence sensory perception. We found aroma differences between certain phenotypes that are driven by key minor, nonterpenoid compounds, including the newly reported 3-mercaptohexyl hexanoate. We further report the identification of octanoic and decanoic acids, which are implicated in the production of cheese-like aromas in cannabis. These results establish that even genetically similar phenotypes can possess diverse and distinct aromas arising not from the dominant terpenes, but rather from key minor volatile compounds. Moreover, our study underscores the value of detailed chemical analyses in enhancing cannabis selective breeding practices, offering insights into the chemical basis of aroma and sensory differences.

Evaluation of pain related behaviors and disease related outcomes in an immunocompetent mouse model of prostate cancer induced bone pain.

Cancer-induced bone pain (CIBP) is the most common and devastating symptom of bone metastatic cancer that substantially disrupts patients' quality of life. Currently, there are few effective analgesic treatments for CIBP other than opioids which come with severe side effects. In order to better understand the factors and mechanisms responsible for CIBP it is essential to have clinically relevant animal models that mirror pain-related symptoms and disease progression observed in patients with bone metastatic cancer. In the current study, we characterize a syngeneic mouse model of prostate cancer induced bone pain. We transfected a prostate cancer cell line (RM1) with green fluorescent protein (GFP) and luciferase reporters in order to visualize tumor growth longitudinally in vivo and to assess the relationship between sensory neurons and tumor cells within the bone microenvironment. Following intra-femoral injection of the RM1 prostate cancer cell line into male C57BL/6 mice, we observed a progressive increase in spontaneous guarding of the inoculated limb between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. Daily running wheel performance was evaluated as a measure of functional impairment and potentially movement evoked pain. We observed a progressive reduction in the distance traveled and percentage of time at optimal velocity between 12 and 21 days post inoculation in tumor bearing compared to sham operated mice. We utilized histological, radiographic and µCT analysis to examine tumor induced bone remodeling and observed osteolytic lesions as well as extra-periosteal aberrant bone formation in the tumor bearing femur, similar to clinical findings in patients with bone metastatic prostate cancer. Within the tumor bearing femur, we observed reorganization of blood vessels, macrophage and nerve fibers within the intramedullary space and periosteum adjacent to tumor cells. Tumor bearing mice displayed significant increases in the injury marker ATF3 and upregulation of the neuropeptides SP and CGRP in the ipsilateral DRG as well as increased measures of central sensitization and glial activation in the ipsilateral spinal cord. This immunocompetent mouse model will be useful when combined with cell type selective transgenic mice to examine tumor, immune cell and sensory neuron interactions in the bone microenvironment and their role in pain and disease progression associated with bone metastatic prostate cancer.

Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of Exotic Cannabis.

Cannabis sativa L. produces a wide variety of volatile secondary metabolites that contribute to its unique aroma. The major volatile constituents include monoterpenes, sesquiterpenes, and their oxygenated derivates. In particular, the compounds ß-myrcene, D-(+)-limonene, ß-caryophyllene, and terpinolene are often found in greatest amounts, which has led to their use in chemotaxonomic classification schemes and legal Cannabis sativa L. product labeling. While these compounds contribute to the characteristic aroma of Cannabis sativa L. and may help differentiate varieties on a broad level, their importance in producing specific aromas is not well understood. Here, we show that across Cannabis sativa L. varieties with divergent aromas, terpene expression remains remarkably similar, indicating their benign contribution to these unique, specific scents. Instead, we found that many minor, nonterpenoid compounds correlate strongly with nonprototypical sweet or savory aromas produced by Cannabis sativa L. Coupling sensory studies to our chemical analysis, we derive correlations between groups of compounds, or in some cases, individual compounds, that produce many of these diverse scents. In particular, we identified a new class of volatile sulfur compounds (VSCs) containing the 3-mercaptohexyl functional group responsible for the distinct citrus aromas in certain varieties and skatole (3-methylindole) as the key source of the chemical aroma in others. Our results provide not only a rich understanding of the chemistry of Cannabis sativa L. but also highlight how the importance of terpenes in the context of the aroma of Cannabis sativa L. has been overemphasized.

Perioperative Considerations for Patients Exposed to Psychostimulants.

Concerns regarding the perioperative management of acute psychostimulant intoxication have been recognized for decades, but novel and diverse substances in this class continue to be developed. Despite the similarities in mechanisms of action among psychostimulants, each subclass within this broad category has unique receptor specificity and different mechanisms that play a role in patient clinical presentation. These issues present challenges to anesthesia providers when caring for patients with either acute or chronic exposure to psychostimulants during the perioperative period. Challenges result from both physiological and psychological effects that influence the action of the primary anesthetic agent, adjuvant anesthetics, and analgesics used for perioperative management of pain. The epidemiology, pharmacology, and perioperative implications of psychostimulant use are presented for amphetamines and similar acting nonamphetamines, cocaine, and, finally, the mixed-action drugs known as entactogens that share stimulant and psychedelic properties. This information is then used as the foundation for safe and effective perioperative management of patients exposed to psychostimulants.

Cannabidiol and cannabis-inspired terpene blends have acute prosocial effects in the BTBR mouse model of autism spectrum disorder.

Introduction: Cannabidiol (CBD) is a non-intoxicating phytocannabinoid with increasing popularity due to its purported therapeutic efficacy for numerous off-label conditions including anxiety and autism spectrum disorder (ASD). Those with ASD are commonly deficient in endogenous cannabinoid signaling and GABAergic tone. CBD has a complex pharmacodynamic profile that includes enhancing GABA and endocannabinoid signaling. Thus, there is mechanistic justification for investigating CBD's potential to improve social interaction and related symptoms in ASD. Recent clinical trials in children with ASD support CBD's beneficial effects in numerous comorbid symptoms, but its impact on social behavior is understudied. Methods: Here, we tested the prosocial and general anxiolytic efficacy of a commercially available CBD-rich broad spectrum hemp oil delivered by repeated puff vaporization and consumed via passive inhalation in the female cohort of the BTBR strain, a common inbred mouse line for preclinical assessment of ASD-like behaviors. Results: We observed that CBD enhanced prosocial behaviors using the 3-Chamber Test with a different vapor dose-response relationship between prosocial behavior and anxiety-related behavior on the elevated plus maze. We also identified that inhalation of a vaporized terpene blend from the popular OG Kush cannabis strain increased prosocial behavior independently of CBD and acted together with CBD to promote a robust prosocial effect. We observed similar prosocial effects with two additional cannabis terpene blends from the Do-Si-Dos and Blue Dream strains, and further reveal that these prosocial benefits rely on the combination of multiple terpenes that comprise the blends. Discussion: Our results illustrate the added benefit of cannabis terpene blends for CBD-based treatment of ASD.

Comparison of surgical stabilization of rib fractures vs epidural analgesia on in-hospital outcomes.

INTRODUCTION: Surgical stabilization of rib fractures (SSRF) improves functional outcomes compared to controls, partly due to reduction in pain. We investigated the impact of early SSRF on pulmonary complications, mortality, and length of stay compared to non-operative analgesia with epidural analgesia (EA). METHODS: Retrospective cohort study of the Trauma Quality Improvement Program (TQIP) 2017 dataset for adults with rib fractures, excluding those with traumatic brain injury or death within twenty-four hours. Early SSRF and EA occurred within 72 h, and we excluded those who received both or neither intervention. Our primary outcome was a composite of pulmonary complications including acute respiratory distress syndrome (ARDS) or ventilator-associated pneumonia (VAP). Additional outcomes included unplanned endotracheal intubation, in-hospital mortality, and hospital and intensive care unit (ICU) length of stay (LOS) for those surviving to discharge. Multiple logistic and linear regressions were controlled for variables including age, sex, flail chest (FC), injury severity, additional procedures, and medical comorbidities. RESULTS: We included 1,024 and 1,109 patients undergoing early SSRF and EA, respectively. SSRF patients were more severely injured with higher rates of FC (42.8 vs 13.3%, p<0.001), Injury Severity Score (ISS) > 16 (56.9 vs 36.1%, p<0.001), and Abbreviated Injury Scale (AIS) Thorax > 3 (33.3 vs 12.2%, p<0.001). Overall, 49 (2.3%) of patients developed ARDS or VAP, 111 (5.2%) required unplanned intubation, and 58 (2.7%) expired prior to discharge. On multivariable analysis, SSRF was not associated with the primary composite outcome (OR: 1.65, 95%CI: 0.85-3.21). Early SSRF significantly predicted decreased risk of unplanned intubation (OR:0.59, 95%CI: 0.38-0.92) compared with early EA alone, however, was not a significant predictor of in-hospital mortality (OR: 1.27, 95%CI: 0.68-2.39). SSRF was associated with significantly longer hospital (Exp(ß): 1.06, 95%CI: 1.00-1.12, p = 0.047) and ICU LOS (Exp(ß): 1.17, 95%CI: 1.08-1.27, p<0.001). CONCLUSIONS: Aside from unplanned intubation, we observed no statistically significant difference in the adjusted odds of in-hospital pulmonary morbidity or mortality for patients undergoing early SSRF compared with early EA. Chest wall injury patients may benefit from referral to trauma centers where both interventions are available and appropriate surgical candidates may receive timely intervention.

Safety and Feasibility of Ultra-Restrictive Transfusion Protocol as a Blood-Preservation Strategy During Shortage Crises.

BACKGROUND: We hypothesized that implementation of new ultra-restrictive transfusion protocol in adult surgical intensive care units (SICU) was safe and feasible during pandemic-associated shortage crises. METHODS: Retrospective analysis two months pre- and post-implementation of ultra-restrictive transfusion protocol in March 2020 with hemoglobin cutoff of 6 g/dL (6.5 g/dL if ≥ 65 years old) for patients without COVID, active bleeding, or myocardial ischemia. RESULTS: We identified 16/93 and 27/168 patients PRE and POST meeting standard transfusion threshold (7 g/dL); within POST, 12 patients met ultra-restrictive cutoffs. There was no significant difference between PRE and POST in the rate of mortality, ischemic complications, or the number of transfusions per patient, however, the overall incidence of transfusion was lower in the POST group (7.1 vs 17.2%, p = 0.02). Patients received a mean (SD) of 4(3.8) and 2.4(1.5) PRBC transfusions pre- and post-implementation. Odds ratio of mortality in POST group was 0.62 (95%CI: 0.08-5.12) adjusted for age, sex, and SOFA score. CONCLUSIONS: Implementation of an ultra-restrictive transfusion protocol was feasible and effective as a blood- preservation strategy.

Lucky number 13: Association between center-specific chest wall stabilization volumes and patient outcomes.

BACKGROUND: Chest wall stabilization (CWS) improves outcomes for patients with chest wall injury (CWI). We hypothesized that patients treated at centers with higher annual CWS volumes experience superior outcomes. METHODS: A retrospective study of adults with acute CWI undergoing surgical stabilization of rib or sternal fractures within the 2019 Trauma Quality Improvement Program database, excluding those with 24-hour mortality or any Abbreviated Injury Scale body region of six, was conducted. Hospitals were grouped in quartiles by annual CWS volume. Our primary outcome was a composite of in-hospital mortality, ventilator-associated pneumonia, acute respiratory distress syndrome, sepsis, and unplanned intubation or intensive care unit readmission. Regression was controlled for age, sex, Injury Severity Scale, flail chest, medical comorbidities, and Abbreviated Injury Scale chest. We performed cut-point analysis and compared patient outcomes from high- and low-volume centers. RESULTS: We included 3,207 patients undergoing CWS at 430 hospitals with annual volumes ranging from 1 to 66. There were no differences between groups in age, sex, or Injury Severity Scale. Patients in the highest volume quartile (Q4) experienced significantly lower rates of the primary outcome (Q4, 14%; Q3, 18.4%; Q2, 17.4%; Q1, 22.1%) and significantly shorter hospital and intensive care unit lengths of stay. Q4 versus Q1 had lower adjusted odds of the primary outcome (odds ratio, 0.58; 95% confidence interval, 0.43-0.80). An optimal cut point of 12.5 procedures annually was used to define high- and low-volume centers. Patients treated at high-volume centers experienced significantly lower rates of the primary composite outcome, in-hospital mortality, and deep venous thrombosis with shorter lengths of stay and higher rates of home discharge. CONCLUSION: Center-specific CWS volume is associated with superior in-hospital patient outcomes. These findings support efforts to establish CWI centers of excellence. Further investigation should explore the impact of center-specific volume on patient-reported outcomes including pain and postdischarge quality of life. LEVEL OF EVIDENCE: Prognostic and Epidemiologic; Level III.

Integrated multi-omic characterization of congenital heart disease.

The heart, the first organ to develop in the embryo, undergoes complex morphogenesis that when defective results in congenital heart disease (CHD). With current therapies, more than 90% of patients with CHD survive into adulthood, but many suffer premature death from heart failure and non-cardiac causes1. Here, to gain insight into this disease progression, we performed single-nucleus RNA sequencing on 157,273 nuclei from control hearts and hearts from patients with CHD, including those with hypoplastic left heart syndrome (HLHS) and tetralogy of Fallot, two common forms of cyanotic CHD lesions, as well as dilated and hypertrophic cardiomyopathies. We observed CHD-specific cell states in cardiomyocytes, which showed evidence of insulin resistance and increased expression of genes associated with FOXO signalling and CRIM1. Cardiac fibroblasts in HLHS were enriched in a low-Hippo and high-YAP cell state characteristic of activated cardiac fibroblasts. Imaging mass cytometry uncovered a spatially resolved perivascular microenvironment consistent with an immunodeficient state in CHD. Peripheral immune cell profiling suggested deficient monocytic immunity in CHD, in agreement with the predilection in CHD to infection and cancer2. Our comprehensive phenotyping of CHD provides a roadmap towards future personalized treatments for CHD.

Low-dose methylprednisolone treatment in critically ill patients with severe community-acquired pneumonia.

PURPOSE: Severe community-acquired pneumonia (CAP) requiring intensive care unit admission is associated with significant acute and long-term morbidity and mortality. We hypothesized that downregulation of systemic and pulmonary inflammation with prolonged low-dose methylprednisolone treatment would accelerate pneumonia resolution and improve clinical outcomes. METHODS: This double-blind, randomized, placebo-controlled clinical trial recruited adult patients within 72-96 h of hospital presentation. Patients were randomized in 1:1 ratio; an intravenous 40 mg loading bolus was followed by 40 mg/day through day 7 and progressive tapering during the 20-day treatment course. Randomization was stratified by site and need for mechanical ventilation (MV) at the time of randomization. Outcomes included a primary endpoint of 60-day all-cause mortality and secondary endpoints of morbidity and mortality up to 1 year of follow-up. RESULTS: Between January 2012 and April 2016, 586 patients from 42 Veterans Affairs Medical Centers were randomized, short of the 1420 target sample size because of low recruitment. 584 patients were included in the analysis. There was no significant difference in 60-day mortality between the methylprednisolone and placebo arms (16% vs. 18%; adjusted odds ratio 0.90, 95% CI 0.57-1.40). There were no significant differences in secondary outcomes or complications. CONCLUSIONS: In patients with severe CAP, prolonged low-dose methylprednisolone treatment did not significantly reduce 60-day mortality. Treatment was not associated with increased complications.

Comparison of Infectious Complications after Surgical Fixation versus Epidural Analgesia for Acute Rib Fractures.

Background: Surgical stabilization of rib fractures (SSRF) is associated with decreased mortality and respiratory complications. Patients who are not offered SSRF are often treated with epidural analgesia (EA) to reduce pain and improve pulmonary mechanics. We sought to compare infectious complications in patients undergoing either SSRF or EA. We hypothesized that infectious complications are equivalent between the two treatment groups. Patients and Methods: We performed a retrospective cohort study of adult trauma patients with acute rib fractures within the Trauma Quality Improvement Program (TQIP) 2017 dataset and used International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes to identify patients who underwent SSRF or EA. We excluded patients who received both treatments in the same admission. Our primary outcome was the development of sepsis. Secondary outcomes were specific infections including ventilator-associated pneumonia (VAP), catheter-associated urinary tract infection (CAUTI), and central line-associated blood stream infections (CLABSI). Multiple logistic regression analyses were used to adjust for age, injury severity score (ISS), chest Abbreviated Injury Scale (AIS), flail chest, traumatic brain injury (TBI), and comorbidities. Results: We identified 2,252 and 1,299 patients who underwent SSRF and EA, respectively. Patients with SSRF were younger with higher ISS and longer length of stay (LOS). There was no difference in mortality, however, SSRF had higher rate of sepsis (1.6% vs. 0.5%; p = 0.001), VAP (5.1% vs. 0.9%; p < 0.001), CAUTI (1.7% vs. 0.5%; p = 0.001), and CLABSI (0.2% vs. 0%; p = 0.05). On multiple regression, SSRF was associated with higher odds of sepsis (odds ratio [OR], 2.63; 95% confidence interval [CI], 1.04-6.63), CAUTI (OR, 2.96; 95% CI, 1.11-7.88), and VAP (OR, 3.24; 95% CI, 1.73-6.06). Among those who developed sepsis, there was no significant difference in mortality or LOS between groups. Conclusions: Despite no difference in mortality, SSRF was associated with increased risk of septic complications in patients with rib fractures compared to epidural analgesia. Identifying, and addressing, risk factors of sepsis in this patient population is a critical performance improvement process to optimize outcomes without increased adverse events.

Surgical Infection Society: Chest Wall Injury Society Recommendations for Antibiotic Use during Surgical Stabilization of Traumatic Rib or Sternal Fractures to Reduce Risk of Implant Infection.

Background: Surgical stabilization of rib fractures is recommended in patients with flail chest or multiple displaced rib fractures with physiologic compromise. Surgical stabilization of rib fractures (SSRF) and surgical stabilization of sternal fractures (SSSF) involve open reduction and internal fixation of fractures with a plate construct to restore anatomic alignment. Most plate constructs are composed of titanium and presence of this foreign, non-absorbable material presents opportunity for implant infection. Although implant infection rates after SSRF and SSSF are low, they present a challenging clinical entity often requiring prolonged antibiotic therapy, debridement, and potentially implant removal. Methods: The Surgical Infection Society's Therapeutics and Guidelines Committee and Chest Wall Injury Society's Publication Committee convened to develop recommendations for antibiotic use during and after surgical stabilization of traumatic rib and sternal fractures. Clinical scenarios included patients with concomitant infectious processes (sepsis, pneumonia, empyema, cellulitis) or sources of contamination (open chest, gross contamination) incurred as a result of their trauma and present at the time of their surgical stabilization. PubMed, Embase, and Cochrane databases were searched for pertinent studies. Using a process of iterative consensus, all committee members voted to accept or reject each recommendation. Results: For patients undergoing SSRF or SSSF in the absence of pre-existing infectious process, there is insufficient evidence to suggest existing peri-operative guidelines or recommendations are inadequate. For patients undergoing SSRF or SSSF in the presence of sepsis, pneumonia, or an empyema, there is insufficient evidence to provide recommendations on duration and choice of antibiotic. This decision may be informed by existing guidelines for the concomitant infection. For patients undergoing SSRF or SSSF with an open or contaminated chest there is insufficient evidence to provide specific antibiotic recommendations. Conclusions: This guideline document summarizes the current Surgical Infection Society and Chest Wall Injury Society recommendations regarding antibiotic use during and after surgical stabilization of traumatic rib or sternal fractures. Limited evidence exists in the chest wall surgical stabilization literature and further studies should be performed to delineate risk of implant infection among patients undergoing SSSRF or SSSF with concomitant infectious processes.

Initial Evaluations of the Microtubule-Based PET Radiotracer, [11C]MPC-6827 in a Rodent Model of Cocaine Abuse.

Purpose: Microtubules (MTs) are structural units made of α and ß tubulin subunits in the cytoskeleton responsible for axonal transport, information processing, and signaling mechanisms-critical for healthy brain function. Chronic cocaine exposure affects the function, organization, and stability of MTs in the brain, thereby impairing overall neurochemical and cognitive processes. At present, we have no reliable, non-invasive methods to image MTs for cocaine use disorder (CUD). Recently we reported the effect of cocaine in patient-derived neuroblastoma SH-SY5Y cells. Here we report preliminary results of a potential imaging biomarker of CUD using the brain penetrant MT-based radiotracer, [11C]MPC-6827, in an established rodent model of cocaine self-administration (SA). Methods: Cell uptake studies were performed with [11C]MPC-6827 in SH-SY5Y cells, treated with or without cocaine (n = 6/group) at 30 and 60 min incubations. MicroPET/CT brain scans were performed in rats at baseline and 35 days after cocaine self-administration and compared with saline-treated rats as controls (n = 4/sex). Whole-body post-PET biodistribution, plasma metabolite assay, and brain autoradiography were performed in the same rats from imaging. Results: Cocaine-treated SH-SY5Y cells demonstrated a ∼26(±4)% decrease in radioactive uptake compared to non-treated controls. Both microPET/CT imaging and biodistribution results showed lower (∼35 ± 3%) [11C]MPC-6827 brain uptake in rats that had a history of cocaine self-administration compared to the saline-treated controls. Plasma metabolite assays demonstrate the stability (≥95%) of the radiotracer in both groups. In vitro autoradiography also demonstrated lower radioactive uptake in cocaine rats compared to the control rats. [11C]MPC-6827's in vitro SH-SY5Y neuronal cell uptake, in vivo positron emission tomography (PET) imaging, ex vivo biodistribution, and in vitro autoradiography results corroborated well with each other, demonstrating decreased radioactive brain uptake in cocaine self-administered rats versus controls. There were no significant differences either in cocaine intake or in [11C]MPC-6827 uptake between the male and female rats. Conclusions: This project is the first to validate in vivo imaging of the MT-associations with CUD in a rodent model. Our initial observations suggest that [11C]MPC-6827 uptake decreases in cocaine self-administered rats and that it may selectively bind to destabilized tubulin units in the brain. Further longitudinal studies correlating cocaine intake with [11C]MPC-6827 PET brain measures could potentially establish the MT scaffold as an imaging biomarker for CUD, providing researchers and clinicians with a sensitive tool to better understand the biological underpinnings of CUD and tailor new treatments.

Identification of a New Family of Prenylated Volatile Sulfur Compounds in Cannabis Revealed by Comprehensive Two-Dimensional Gas Chromatography.

Cannabis sativa L. produces over 200 known secondary metabolites that contribute to its distinctive aroma. Studies on compounds traditionally associated with the scent of this plant have focused on those within the terpenoid class. These isoprene-derived compounds are ubiquitous in nature and are the major source of many plant odors. Nonetheless, there is little evidence that they provide the characteristic "skunk-like" aroma of cannabis. To uncover the chemical origins of this scent, we measured the aromatic properties of cannabis flowers and concentrated extracts using comprehensive two-dimensional gas chromatography equipped with time-of-flight mass spectrometry, flame ionization detection, and sulfur chemiluminescence. We discovered a new family of volatile sulfur compounds (VSCs) containing the prenyl (3-methylbut-2-en-1-yl) functional group that is responsible for this scent. In particular, the compound 3-methyl-2-butene-1-thiol was identified as the primary odorant. We then conducted an indoor greenhouse experiment to monitor the evolution of these compounds during the plant's lifecycle and throughout the curing process. We found that the concentrations of these compounds increase substantially during the last weeks of the flowering stage, reach a maximum during curing, and then drop after just one week of storage. These results shed light on the chemical origins of the characteristic aroma of cannabis and how volatile sulfur compound production evolves during plant growth. Furthermore, the chemical similarity between this new family of VSCs and those found in garlic (allium sativum) suggests an opportunity to also investigate their potential health benefits.

Impact of Direct Transport vs. Transfer on Out-of-Hospital Traumatic Cardiac Arrest.

BACKGROUND: Injured patients benefit from direct transport to a trauma center; however, it is unknown whether patients with traumatic out-of-hospital cardiac arrest (OHCA) benefit from initial resuscitation at the nearest emergency department (ED) if a trauma center is farther away. We hypothesized that patients with traumatic OHCA transported directly to a trauma center have less in-hospital mortality after initial resuscitation compared to those transferred from non-trauma centers. METHODS: We examined patients presenting with traumatic OHCA within our institutional trauma registry and the National Trauma Data Bank (NTDB) and excluded patients with ED mortality. Our primary outcome was all-cause mortality during index hospitalization; multiple logistic regression controlled for age, sex, injury severity score, mechanism of injury, signs of life, emergency surgery, and level I trauma center designation. RESULTS: We identified 271 and 1,138 adult patients with traumatic OHCA in our registry and the NTDB; 28% and 16% were transferred from another facility, respectively. Following initial resuscitation, patients transferred to a trauma center had higher in-hospital mortality than those transported directly in both our local and national cohorts (aOR: 2.27, 95%CI: 1.03-4.98, and aOR: 2.66, 95%CI: 1.35 - 5.26, respectively). DISCUSSION: Patients with traumatic OHCA transported directly to a trauma center may have increased survival to discharge compared to those transferred from another facility, even accounting for initial resuscitation. Further investigation should examine the impact of both physiologic and logistic factors including distance to trauma center, traffic, and weather patterns that may impact prehospital decision-making and destination selection.

Application of pie-crusting technique to facilitate closure of open abdomen after decompressive laparotomy.

We present the case of a 23-year-old man who developed abdominal compartment syndrome secondary to severe pancreatitis and required decompressive laparotomy and pancreatic necrosectomy. Despite application of a temporary abdominal closure system (ABThera Open Abdomen Negative Pressure Therapy), extensive retroperitoneal oedema and inflammation continued to contribute to loss of domain and prevented primary closure of the skin and fascia. The usual course of action would have involved reapplication of ABThera system until primary closure could be achieved or sufficient granulation tissue permitted split-thickness skin grafting. Though a safe option for abdominal closure, application of a skin graft would delay return to baseline functional status and require eventual graft excision with abdominal wall reconstruction for this active labourer. Thus, we achieved primary closure of the skin through the novel application of abdominal wall 'pie-crusting', or tension-releasing multiple skin incisions, technique.

A Painful Beginning: Early Life Surgery Produces Long-Term Behavioral Disruption in the Rat.

Early life surgery produces peripheral nociceptive activation, inflammation, and stress. Early life nociceptive input and inflammation have been shown to produce long-term processing changes that are not restricted to the dermatome of injury. Additionally stress has shown long-term effects on anxiety, depression, learning, and maladaptive behaviors including substance abuse disorder and we hypothesized that early life surgery would have long-term effects on theses complex behaviors in later life. In this study surgery in the rat hindpaw was performed to determine if there are long-term effects on anxiety, depression, audiovisual attention, and opioid reward behaviors. Male animals received paw incision surgery and anesthesia or anesthesia alone (sham) at postnatal day 6. At 10 weeks after surgery, open field center zone entries were decreased, a measure of anxiety (n = 20) (P = 0.03) (effect size, Cohen's d = 0.80). No difference was found in the tail suspension test as a measure of depression. At 16-20 weeks, attentional performance in an operant task was similar between groups at baseline and decreased with audiovisual distraction in both groups (P < 0.001) (effect size, η2 = 0.25), but distraction revealed a persistent impairment in performance in the surgery group (n = 8) (P = 0.04) (effect size, η2 = 0.13). Opioid reward was measured using heroin self-administration at 16-24 weeks. Heroin intake increased over time in both groups during 24-h free access (P < 0.001), but was greater in the surgery group (P = 0.045), with a significant interaction between time and treatment (P < 0.001) (effect size, Cohen f 2 = 0.36). These results demonstrate long-term disruptions in complex behaviors from surgical incision under anesthesia. Future studies to explore sex differences in early life surgery and the attendant peripheral neuronal input, stress, and inflammation will be valuable to understand emerging learning deficits, anxiety, attentional dysfunction, and opioid reward and their mechanisms. This will be valuable to develop optimal approaches to mitigate the long-term effects of surgery in early life.

Optimizing surgical stabilization of rib fractures using intraoperative ultrasound localization.

BACKGROUND: Surgical stabilization of rib fractures (SSRF) significantly improve the outcomes of patients with rib fractures. Ultrasound is a specific modality for localizing rib fractures. We hypothesized that use of perioperative ultrasound localization of fracture sites optimizes surgical approach and clinical outcomes. METHODS: We performed a retrospective cohort study of adult patients undergoing SSRF and compared those with and without adjunctive perioperative ultrasound fracture localization. Our primary outcome was improved surgical efficiency as measured by incision length and total operative time. Secondary clinical outcomes included numeric pain score on follow-up visit and daily morphine milligram equivalent prescribed within 30 days from discharge. RESULTS: We performed 49 surgical rib fixations between 2015 and 2020; of which, 13 (26.5%) additionally underwent ultrasound localization (26.5%). There were no significant differences between groups in age, sex, number of ribs repaired, or days till surgery. More patients in the ultrasound group had nonflail chest wall injury (76.9% vs. 27.8%, p = 0.003). Use of perioperative ultrasound was associated with shorter incision length (median, 9 vs. 15.5 cm; p = 0.0001), shorter operative time (median, 120 vs. 174 minutes; p = 0.003), less daily morphine milligram equivalent (25 vs. 68 mg, p = 0.009), and reduced numeric pain score on follow up (median, 4 vs. 7, p = 0.05). CONCLUSION: Use of perioperative ultrasound localization of rib fractures to optimize surgical approach for SSRF was associated with reduced incision length, operative time, and opioid requirements on patient discharge. We recommend considering routine perioperative localization to improve surgical approach and efficiency during SSRF. LEVEL OF EVIDENCE: Therapeutic, level IV.