Protein prenylation: unique fats make their mark on biology.

The modification of eukaryotic proteins by isoprenoid lipids, which is known as prenylation, controls the localization and activity of a range of proteins that have crucial functions in biological regulation. The roles of prenylated proteins in cells are well conserved across species, underscoring the biological and evolutionary importance of this lipid modification pathway. Genetic suppression and pharmacological inhibition of the protein prenylation machinery have provided insights into several cellular processes and into the aetiology of diseases in which prenylation is involved. The functional dependence of prenylation substrates, such as RAS proteins, on this modification and the therapeutic potential of targeting the prenylation process in pathological conditions accentuate the need to fully understand this form of post-translational modification.

GNA13 suppresses proliferation of ER+ breast cancer cells via ERα dependent upregulation of the MYC oncogene.

GNA13 (Gα13) is one of two alpha subunit members of the G12/13 family of heterotrimeric G-proteins which mediate signaling downstream of GPCRs. It is known to be essential for embryonic development and vasculogenesis and has been increasingly shown to be involved in mediating several steps of cancer progression. Recent studies found that Gα13 can function as an oncogene and contributes to progression and metastasis of multiple tumor types, including ovarian, head and neck and prostate cancers. In most cases, Gα12 and Gα13, as closely related α-subunits in the subfamily, have similar cellular roles. However, in recent years their differences in signaling and function have started to emerge. We previously identified that Gα13 drives invasion of Triple Negative Breast Cancer (TNBC) cells in vitro. As a highly heterogenous disease with various well-defined molecular subtypes (ER+ /Her2-, ER+ /Her2+, Her2+, TNBC) and subtype associated outcomes, the function(s) of Gα13 beyond TNBC should be explored. Here, we report the finding that low expression of GNA13 is predictive of poorer survival in breast cancer, which challenges the conventional idea of Gα12/13 being universal oncogenes in solid tumors. Consistently, we found that Gα13 suppresses the proliferation in multiple ER+ breast cancer cell lines (MCF-7, ZR-75-1 and T47D). Loss of GNA13 expression drives cell proliferation, soft-agar colony formation and in vivo tumor formation in an orthotopic xenograft model. To evaluate the mechanism of Gα13 action, we performed RNA-sequencing analysis on these cell lines and found that loss of GNA13 results in the upregulation of MYC signaling pathways in ER+ breast cancer cells. Simultaneous silencing of MYC reversed the proliferative effect from the loss of GNA13, validating the role of MYC in Gα13 regulation of proliferation. Further, we found Gα13 regulates the expression of MYC, at both the transcript and protein level in an ERα dependent manner. Taken together, our study provides the first evidence for a tumor suppressive role for Gα13 in breast cancer cells and demonstrates for the first time the direct involvement of Gα13 in ER-dependent regulation of MYC signaling. With a few exceptions, elevated Gα13 levels are generally considered to be oncogenic, similar to Gα12. This study demonstrates an unexpected tumor suppressive role for Gα13 in ER+ breast cancer via regulation of MYC, suggesting that Gα13 can have subtype-dependent tumor suppressive roles in breast cancer.

Local Anesthesia for Endovascular Repair of Abdominal Aortic Aneurysm Allows for Accurate Graft Deployment with Durable Results.

BACKGROUND: Local anesthesia (LA) is sparsely used in endovascular aneurysm repair (EVAR) despite short-term benefit, likely secondary to concerns over patient movement preventing accurate endograft deployment. The objective of this study is to examine the association between anesthesia type and endoleak, sac regression, reintervention, and mortality. METHODS: The Vascular Quality Initiative database was queried for all EVAR cases from 2014 to 2022. Patients were included if they underwent percutaneous elective EVAR with anatomical criteria within instructions for use of commercially approved endografts. Multivariable logistic regression with propensity score weighting was used to determine the association between anesthesia type on the risk of any endoleak noted by intraoperative completion angiogram and sac regression. Multivariable survival analysis with propensity score weighting was used to determine the association between anesthesia type and endoleak at 1 year, long-term reintervention, and mortality. RESULTS: Thirteen thousand nine hundred thirty two EVARs met inclusion criteria: 1,075 (8%) LA and 12,857 (92%) general anesthesia (GA). On completion angiogram, LA was associated with fewer rates of any endoleaks overall (16% vs. 24%, P < 0.001). On multivariable analysis with propensity score weighting, LA was associated with similar adjusted odds of any endoleak on intraoperative completion angiogram (odds ratio [OR] 0.56, 95% confidence interval [CI] 0.47-0.68) as well as combined type 1a and type 1b endoleaks (OR 0.72, 95% CI 0.47-1.09). Follow-up computed tomography imaging at 1 year was available for 4,892 patients, 377 (8%) LA and 4,515 (92%) GA. At 1 year, LA was associated with similar rate of freedom from any endoleaks compared to GA (0.66 [95% CI 0.63-0.69] vs. 0.71 [95% CI 0.70-0.72], P = 0.663) and increased rates of sac regression (50% vs. 45%, P = 0.040). On multivariable analysis with propensity score weighting, LA and GA were associated with similar adjusted odds of sac regression (OR 1.22, 95% CI 0.97-1.55). LA and GA had similar rates of endoleak at 1 year (hazard ratio [HR] 0.14, 95% CI 0.63-1.07); however, LA was associated with decreased hazards of combined type 1a and 1b endoleaks at 1 year (HR 0.87, 95% CI 0.80-0.96). LA and GA had similar adjusted long-term reintervention rate (HR 0.77, 95% CI 0.44-1.38) and long-term mortality (HR 1.100, 95% CI 079-1.25). CONCLUSIONS: LA is not associated with increased adjusted rates of any endoleak on completion angiogram or at 1-year follow-up compared to GA. LA is associated with decreased adjusted rates of type 1a and type 1b endoleak at 1 year, but similar rates of sac regression, long-term reintervention, and mortality. Concerns for accurate graft deployment should not preclude use of LA and LA should be increasingly considered when deciding on anesthetic type for standard elective EVAR.

Effect of after-hours presentation in ruptured abdominal aortic aneurysm.

OBJECTIVE: Ruptured abdominal aortic aneurysms (RAAAs) are surgical emergencies that require immediate and expert treatment. It has been unclear whether presentation during evenings and weekends, when "on call" teams are primarily responsible for patient care, is associated with worse outcomes. Our objective was to evaluate the outcomes of patients presenting with RAAAs after-hours vs during the workday. METHODS: A retrospective cohort study of all RAAAs in Nova Scotia between 2005 and 2015 was performed through linkage of administrative databases. Patients who had presented to the hospital with RAAAs during the workday (Monday through Friday, 6 am to 6 pm) were compared with those who had presented after-hours (6 pm to 6 am during the week and on weekends). The baseline and operative characteristics were identified for all patients through the available databases and a review of the medical records. Mortality before surgery, 30-day mortality, and operative mortality were compared between groups using multivariable logistic regression, adjusting for factors clinically significant on univariable analysis. RESULTS: A total of 390 patients with RAAAs were identified from 2005 to 2015, of whom 205 (53%) had presented during the workday and 185 (47%) after-hours. The overall chance of survival (OCS) was 45% overall, 49% if admitted to hospital, and 64% if surgery had been performed. During the workday, the OCS was 43% overall, 48% if admitted to hospital, and 67% if surgery had been performed. After-hours, the OCS was 46% overall, 49% if admitted to hospital, and 61% if surgery had been performed. Mortality before surgery was increased for patients who had presented to the hospital during the workday compared with after-hours (36% vs 26%; P = .04). The 30-day mortality (57% vs 54%; P = .62), rates of operative management (63% vs 72%; P = .06), and operative mortality (33% vs 39%; P = .33) were similar between the workday and after-hours groups (57% vs 54%; P = .06). After adjusting for significant clinical variables, the patients who had presented with RAAAs after-hours had had a similar odds of dying before surgery (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.41-1.03), operative management (OR, 1.47; 95% CI, 0.93-2.31), 30-day mortality (OR, 0.98; 95% CI, 0.63-1.51), and operative mortality (OR, 1.33; 95% CI, 0.78-2.26). In the subgroup of patients presenting to a hospital with endovascular capabilities, patients presenting after-hours had had similar odds of 30-day mortality (OR, 1.07; 95% CI, 0.57-2.02), and operative mortality (OR, 1.14; 95% CI, 0.58-2.23). CONCLUSIONS: We found that patients presenting to the hospital with RAAAs after-hours did not have increased adjusted odds of mortality before surgery, operative management, 30-day mortality, or operative mortality.

Trends in Incidence of Abdominal Aortic Aneurysm Rupture, Repair, and Mortality in Nova Scotia.

BACKGROUND: The purpose of this study was to examine sex-based trends in incidence of elective abdominal aortic aneurysm (AAA), ruptured AAA, ruptured AAA repair, and AAA-related mortality. METHODS: A retrospective analysis of patients presenting with AAA from 2005 to 2015 was conducted. Rates of elective AAA repair, ruptured AAA, ruptured AAA repair, and mortality were obtained from linking provincial administrative data using medical services insurance billing number. The age-adjusted incidence of elective AAA repair, overall rate of ruptured AAA, ruptured AAA repair, and AAA-related mortality was calculated for each sex based on Canadian census estimates, adjusted to the Canadian standard population. Weighted linear regression was performed to analyze trends in incidence over time. RESULTS: One thousand nine hundred eighty-six elective AAA repairs were identified, of which 1,098 were repaired open and 898 underwent endovascular abdominal aneurysm repair (EVAR). Five hundred and seventy ruptured AAAs were identified, of which 295 (52%) were repaired: 259 open and 36 EVAR. The proportion of ruptured AAA that was repaired did not change over time (P = 0.54). The proportion repairs performed using EVAR increased significantly in both elective (P < 0.001) and rupture repairs (P < 0.001). During the study period, 662 patients died of AAA-associated mortality. The average incidence of elective AAA repair in men was 29.3 (95% confidence interval (CI): 27.8 to 30.8) per 100,000 and decreased over time (P = 0.04), whereas the average incidence in women was 9.2 [8.3 to 10.0] and stable (P = 0.07). The incidence of open elective AAA repair was 10.5 [9.9-11.1] with a decreasing trend over time (P < 0.001) and EVAR was 9.0 (8.5-9.6) with an increasing trend over time (P < 0.001). A decreasing trend of overall ruptured AAA (5.4 [5.0-5.9], P < 0.001), ruptured AAA repair (2.9 [2.5-3.2], P = 0.02), and of AAA-related mortality (6.2 [5.8-6.8], P < 0.001) was found, with consistent trends in both sexes. The incidence of open ruptured AAA repair decreased over time (P = 0.001) whereas the incidence of ruptured EVAR remained stable (P = 0.23). CONCLUSIONS: The incidence of elective AAA repair is decreasing in males but not females, whereas the incidence of rupture has decreased in both sexes. This has translated into reduced incidence of AAA-related mortality. Increased adoption of EVAR for ruptured AAA should continue these trends.

Dying to Get There: Patients Who Reside at Increased Distance from Tertiary Center Experience Increased Mortality Following Abdominal Aortic Aneurysm Rupture.

BACKGROUND: Centralization of vascular surgery care for Ruptured Abdominal Aortic Aneurysms (RAAAs) to high-volume tertiary centers may hinder access to timely surgical intervention for patients in remote areas. The objective of this study was to determine the association between distance from vascular care and mortality from RAAAs in the province of Nova Scotia, Canada. METHODS: A retrospective cohort study of all RAAAs in Nova Scotia between 2005 and 2015 was performed through linkage of administrative databases. Patients were divided into groups by estimated travel time from their place of residence to the tertiary center (<1 hr and ≥1 hr) using geographic information software. Baseline and operative characteristics were identified for all patients through available databases and completed through chart review. Mortality at home, during transfer to the vascular center, and overall 30-day mortality were compared between groups using t-test and chi-squared test, as appropriate. Multivariable logistic regression analysis was used to calculate the independent effect of travel time on survival outcomes. RESULTS: A total of 567 patients with RAAA were identified from 2005-2015, of which 250 (44%) resided <1 hr travel time to the tertiary center and 317 (56%) resided ≥1 hr. On multivariable analysis, travel time ≥1 hr from vascular care was an independent predictor of mortality at home (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.07-2.63, P = 0.02), mortality prior to operation (OR 2.64, 95% CI 1.81-3.83, P < 0.001), and overall 30-day mortality (OR 1.61, 95% CI 1.10-2.37, P = 0.02). In patients who received an operation (n = 294), there was no association between increased travel time and mortality (OR 1.02, 95% CI 0.60-1.73, P = 0.94). CONCLUSIONS: Travel time ≥1 hr to the tertiary center is associated with significantly higher mortality from ruptured abdominal aortic aneurysm (AAA). However, there was no difference in overall chance of survival between groups for patients that underwent AAA repair. Therefore, strategies to facilitate early detection, and timely transfer to a vascular surgery center may improve outcomes for patients with RAAA.

Effect of socioeconomic status on patients undergoing elective abdominal aortic aneurysm repair in a publicly funded health care system.

BACKGROUND: The association between socioeconomic status (SES) and outcomes after abdominal aortic aneurysm (AAA) repair in publicly funded health care systems is poorly described. The purpose of this study was to determine the effect of SES on postoperative outcomes in patients who underwent AAA repair in Nova Scotia, Canada. METHODS: We performed a retrospective analysis of all elective AAA repairs in Nova Scotia between November 2005 and March 2015 using administrative data sources. We compared postoperative 30-day outcomes and long-term survival across socio-economic quintiles, defined as the Pampalon Material Deprivation Index (MDI) and Social Deprivation Index (SDI). We also compared the relation between baseline characteristics, MDI quintile, SDI quintile and 30-day mortality. We used multivariable logistic regression and survival analysis to calculate adjusted 30-day mortality and long-term survival, respectively. RESULTS: A total of 1913 patients underwent AAA repair during the study period. The overall 30-day mortality rate was 2.6% (50 patients). Thirty-day outcomes including death (p = 0.8), stroke (p = 0.7), myocardial infarction (p = 0.06), length of stay (p = 0.3) and discharge disposition other than home (p = 0.8) were similar across MDI quintiles. Similarly, there was no statistically significant association between SDI quintile and postoperative outcomes. Multivariable analysis showed that age greater than 70 years (odds ratio [OR] 3.06, 95% confidence interval [CI] 1.55-6.06) and open repair (OR 3.22, 95% CI 1.59-6.52) but not MDI quintile (p = NS) or SDI quintile (p = NS) were associated with increased 30-day mortality. There was no effect of MDI or SDI quintile on long-term survival on univariable or multivariable analysis. CONCLUSION: Socioeconomic status does not appear to affect short- or long-term mortality after AAA repair in a publicly funded health care system. Further research is needed to address any existing gaps in screening and referral before repair.

Cost-benefit analysis of home visiting to reduce infant mortality among preterm infants.

PURPOSE: The Following Baby Back Home (FBBH) visiting program, which is provided by nurse and social worker teams, supports families of low-birthweight preterm infants after discharge from a neonatal intensive care unit. Enrollment in the FBBH program has been documented to reduce the likelihood of infant death. In this study, we conducted a cost-benefit analysis of the FBBH program. DESIGN AND METHODS: Infants enrolled in the FBBH program (N = 416) were identified through administrative records. Infants in the FBBH program were propensity score matched with comparison infants to estimate the difference in healthcare costs in the first year of life. RESULTS: Infants enrolled in the FBBH program incurred similar medical care costs compared to a comparison group. Avoided deaths, program costs, healthcare costs resulted in net economic benefits of the FBBH program to avoid infant death estimate at $83,020, cost per life saved at $3080, and benefit-to-cost ratio at 27.95. CONCLUSIONS: The FBBH program's net economic benefits from avoided deaths suggest a substantial return on investment of resources, yielding benefits in excess of program and healthcare costs. PRACTICE IMPLICATIONS: It is economically beneficial to provide home visiting services to families of low-birthweight babies by a team comprised of a registered nurse and social worker.

RAB4A GTPase regulates epithelial-to-mesenchymal transition by modulating RAC1 activation.

Epithelial-to-mesenchymal transition (EMT) is a critical underpinning process for cancer progression, recurrence and resistance to drug treatment. Identification of new regulators of EMT could lead to the development of effective therapies to improve the outcome of advanced cancers. In the current study we discovered, using a variety of in vitro and in vivo approaches, that RAB4A function is essential for EMT and related manifestation of stemness and invasive properties. Consistently, RAB4A suppression abolished the cancer cells' self-renewal and tumor forming ability. In terms of downstream signaling, we found that RAB4A regulation of EMT is achieved through its control of activation of the RAC1 GTPase. Introducing activated RAC1 efficiently rescued EMT gene expression, invasion and tumor formation suppressed by RAB4A knockdown in both the in vitro and in vivo cancer models. In summary, this study identifies a RAB4A-RAC1 signaling axis as a key regulatory mechanism for the process of EMT and cancer progression and suggests a potential therapeutic approach to controlling these processes.

Frailty in Older Patients Undergoing Emergency Laparotomy: Results From the UK Observational Emergency Laparotomy and Frailty (ELF) Study.

OBJECTIVE: This study aimed to document the prevalence of frailty in older adults undergoing emergency laparotomy and to explore relationships between frailty and postoperative morbidity and mortality. SUMMARY BACKGROUND DATA: The majority of adults undergoing emergency laparotomy are older adults (≥65 y) that carry the highest mortality. Improved understanding is urgently needed to allow development of targeted interventions. METHODS: An observational multicenter (n=49) UK study was performed (March-June 2017). All older adults undergoing emergency laparotomy were included. Preoperative frailty score was calculated using the progressive Clinical Frailty Score (CFS): 1 (very fit) to 7 (severely frail). Primary outcome measures were the prevalence of frailty (CFS 5-7) and its association to mortality at 90 days postoperative. Secondary outcomes included 30-day mortality and morbidity, length of critical care, and overall hospital stay. RESULTS: A total of 937 older adults underwent emergency laparotomy: frailty was present in 20%. Ninety-day mortality was 19.5%. After age and sex adjustment, the risk of 90-day mortality was directly associated with frailty: CFS 5 adjusted odds ratio (aOR) 3.18 [95% confidence interval (CI), 1.24-8.14] and CFS 6/7 aOR 6·10 (95% CI, 2.26-16.45) compared with CFS 1. Similar associations were found for 30-day mortality. Increasing frailty was also associated with increased risk of complications, length of Intensive Care Unit, and overall hospital stay. CONCLUSIONS: A fifth of older adults undergoing emergency laparotomy are frail. The presence of frailty is associated with greater risks of postoperative mortality and morbidity and is independent of age. Frailty scoring should be integrated into acute surgical assessment practice to aid decision-making and development of novel postoperative strategies.

Early infant feeding effect on growth and body composition during the first 6 years and neurodevelopment at age 72 months.

BACKGROUND: This study longitudinally characterized the developmental status, growth, and body composition of children who were fed human milk (breastfed, BF), cow's milk-based (MF), or soy protein-based (SF) infant formula from 3 to 12 months. METHODS: Standardized anthropometrics and dual-energy X-ray absorptiometry were used to characterize growth and body composition at 3, 6, 9, 12, 24, 36, 48, 60, and 72 months (NCT00616395). Preschool Language Scale-3, Children's Memory Scale Index (CMS), and Wechsler Preschool and Primary Scale of Intelligence were administered at age 72 months. Mixed-effects models adjusting for gestational age, birth weight, child race and sex, parental education, and maternal IQ were performed. RESULTS: Body Mass index (BMI) was significantly lower between 24 and 72 months in BF children compared to SF children. At 3 and 6 months, BF infants had significantly higher fat mass (FM) than SF infants, whereas BF children had significantly lower FM at 36 and 48 months than SF children. Delayed Recognition Index of the CMS was higher for SF than for MF participants (p = 0.009). There was no other significant difference in developmental outcomes between groups. CONCLUSIONS: In conclusion, BF, MF, and SF support adequate growth and development up to age 6 years. IMPACT: Although soy protein-based infant formula is reported to support normal infant growth and development compared to cow's milk-based formula and human milk, there are limited data on the effect of these feeding methods in school-aged children. This study suggests a significant difference in body composition, specifically BMI, after 24 months between infant feeding methods during the first year of life and in early childhood; however, all diets provide adequate nutrients to maintain normal development up to 72 months.

COVID-19-induced sarcopenia and physical deconditioning may require reassessment of surgical risk for patients with cancer.

BACKGROUND: The long-term physiological consequences of SARS-CoV-2 (severe acute respiratory syndrome coronavirus) infection are not known. The ability of COVID-19 to cause chronic illness, sarcopenia, and physical deconditioning may be underestimated and go beyond the anticipated respiratory sequelae. Myalgia, lethargy, and anorexia are common symptoms even in mild to moderate cases and have the potential to exacerbate frailty. How this impacts on risk-stratification for patients requiring surgery for time-critical conditions, such as malignancy, requires further urgent investigation. MAIN BODY: The deleterious effect of sarcopenia and poor physical capacity are well recognised in cancer surgery. This review commentary highlights current evidence which suggests skeletal muscle as an under recognised cause of COVID-19-related functional deconditioning. The mechanisms behind this are via direct (viral induced myositis, nutritional decline, cytokine-mediated myopathy) and indirect mechanisms (social isolation, inactivity, and psychological consequences). CONCLUSION: Further mechanistic research is required to explore the processes behind the deconditioning effects of SARS-CoV-2 infection and how this impacts on treatment of malignant disease.

Gα-13 induces CXC motif chemokine ligand 5 expression in prostate cancer cells by transactivating NF-κB.

GNA13, the α subunit of a heterotrimeric G protein, mediates signaling through G-protein-coupled receptors (GPCRs). GNA13 is up-regulated in many solid tumors, including prostate cancer, where it contributes to tumor initiation, drug resistance, and metastasis. To better understand how GNA13 contributes to tumorigenesis and tumor progression, we compared the entire transcriptome of PC3 prostate cancer cells with those cells in which GNA13 expression had been silenced. This analysis revealed that GNA13 levels affected multiple CXC-family chemokines. Further investigation in three different prostate cancer cell lines singled out pro-tumorigenic CXC motif chemokine ligand 5 (CXCL5) as a target of GNA13 signaling. Elevation of GNA13 levels consistently induced CXCL5 RNA and protein expression in all three cell lines. Analysis of the CXCL5 promoter revealed that the -505/+62 region was both highly active and influenced by GNA13, and a single NF-κB site within this region of the promoter was critical for GNA13-dependent promoter activity. ChIP experiments revealed that, upon induction of GNA13 expression, occupancy at the CXCL5 promoter was significantly enriched for the p65 component of NF-κB. GNA13 knockdown suppressed both p65 phosphorylation and the activity of a specific NF-κB reporter, and p65 silencing impaired the GNA13-enhanced expression of CXCL5. Finally, blockade of Rho GTPase activity eliminated the impact of GNA13 on NF-κB transcriptional activity and CXCL5 expression. Together, these findings suggest that GNA13 drives CXCL5 expression by transactivating NF-κB in a Rho-dependent manner in prostate cancer cells.

A Bifidobacterial pilus-associated protein promotes colonic epithelial proliferation.

Development of the human gut microbiota commences at birth, with certain bifidobacterial species representing dominant and early colonisers of the newborn gastrointestinal tract. The molecular basis of Bifidobacterium colonisation, persistence and presumed communication with the host has remained obscure. We previously identified tight adherence (Tad) pili from Bifidobacterium breve UCC2003 as an essential colonisation factor. Here, we demonstrate that bifidobacterial Tad pili also promote in vivo colonic epithelial proliferation. A significant increase in cell proliferation was detectable 5 days postadministration of B. breve UCC2003. Using advanced functional genomic approaches, bacterial strains either (a) producing the Tad2003 pili or (b) lacking the TadE or TadF pseudopilins were created. Analysis of the ability of these mutant strains to promote epithelial cell proliferation in vivo demonstrated that the pilin subunit, TadE, is the bifidobacterial molecule responsible for this proliferation response. These findings were confirmed in vitro using purified TadE protein. Our data imply that bifidobacterial Tad pili may contribute to the maturation of the naïve gut in early life through the production of a specific scaffold of extracellular protein structures, which stimulate growth of the neonatal mucosa.

Safety and effectiveness of single ProGlide vascular access in patients undergoing endovascular aneurysm repair.

OBJECTIVE: The objective of this study was to evaluate the safety and effectiveness of single ProGlide use per bilateral access site for endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms. METHODS: A retrospective cohort study was performed for all elective percutaneous EVARs from November 2015 to December 2017 at the QEII Health Sciences Centre (Halifax, Nova Scotia, Canada). Exposure of interest was number of ProGlides used per access site, dichotomized into bilateral single ProGlide closure vs nonsingle ProGlide closure on at least one femoral arteriotomy. Outcomes included Valve Academic Research Consortium (VARC)-2 and Bleeding Academic Research Consortium (BARC) criteria. Groups were compared with Fisher exact test, analysis of variance, or Wilcoxon rank sum, as appropriate. Logistic regression was used to compare the effect of single ProGlide use on VARC-2 and BARC criteria. RESULTS: A total of 131 cases were included, of which 116 had bilateral single ProGlide use for access closure. Baseline characteristics including comorbidities and smoking status were compared between groups. Groups were similar for all characteristics except smoking status, with an increased proportion of former smokers in the nonsingle ProGlide group. There were 119 (90.8%) patients who had single ProGlide use on the right femoral artery and 121 (92.4%) on the left; 16 (12.2%) patients had ProGlide deployment issues. Median maximal right and left femoral sheath diameters were 16F (interquartile range [IQR], 16F-18F) and 14F (IQR, 14F-16F), respectively. Median length of stay was 1 day (IQR, 1-1 day). VARC-2 criteria occurred in 8 of 131 (6.11%) patients, 6 of 116 (5.17%) with bilateral single ProGlides and 2 of 15 (13.3%) with nonsingle ProGlides. BARC criteria occurred in 6 of 131 (4.58%) patients, 5 of 116 (4.31%) with bilateral single ProGlides and 1 of 15 (6.67%) with nonsingle ProGlides. Single ProGlide use was not associated with a difference in VARC-2 (odds ratio, 0.35; 95% confidence interval, 0.64-1.94) or BARC (odds ratio, 0.63; 95% confidence interval, 0.07-6.79) criteria. No patients developed pseudoaneurysms or required repeated intervention for bleeding. CONCLUSIONS: Single ProGlide use per vascular access site in patients undergoing EVAR is a safe and effective method for access closure with sheath diameters up to and including 16F.

Surgically positioned paravertebral catheters and postoperative analgesia after open abdominal aortic aneurysm repair.

OBJECTIVE: To compare postoperative morphine equivalent intake after open abdominal aortic aneurysm (AAA) repair among analgesic modalities: systemic analgesia (SA) only with no regional anesthesia, surgically positioned paravertebral catheter (PVC), and thoracic epidural analgesia (TEA). METHODS: This retrospective cohort study included patients undergoing elective open AAA at the Queen Elizabeth II Health Science Center, Halifax, Nova Scotia. Demographics, morphine equivalents, methods of analgesia administration, and outcomes data were collected on all patients from 2005 to 2016. Total morphine equivalent (MEQ) on postoperative days (PODs) 1, 2, and 3 were compared among patients with SA, PVC, and TEA. A multivariable zero-inflated log-linear regression was used to determine the association between analgesic modality and MEQ. Multivariable logistic regression models were used to determine associations between analgesic modality and postoperative pain, rates of discharge from intensive care within 1 day and opioid-related adverse events. RESULTS: The study cohort included 355 patients: 177 retroperitoneal and 178 transperitoneal repairs; 173 patients underwent SA, 117 PVC, and 65 TEA. On POD1, median MEQs were 984 (interquartile range [IQR], 342-1525) for SA, 89 (33-246) for PVC, and 49 (0-90) for TEA. On POD2, the median MEQs were 105 (IQR, 57-210) for SA, 45 (15-99) for PVC, and 30 (0-64) for TEA. On POD3, the median MEQs were 45 (IQR, 15-120) for SA, 30 (0-60) for PVC, and 10 (0-45) for TEA. On multivariable log-linear regression, compared with SA, PVC and TEA were associated with increased odds of receiving no opioids on POD1 (odds ratio [OR], 66.85; 95% confidence interval [CI], 17.49-255.57; and OR, 214.68; 95% CI, 60.20-766.38; respectively), POD 2 (OR, 6.97; 95% CI, 3.61-13.46; and OR, 28.73; 95% CI, 15.68-52.62; respectively), and POD 3 (OR, 3.93; 95% CI, 2.72-5.67; and OR, 4.68; 95% CI, 3.20-6.86; respectively). If patients did receive opioids, compared with SA, PVC and TEA were associated with decreased consumption on POD1 (RR, 0.22; 95% CI, 0.18-0.27; and RR, 0.16; 95% CI, 0.12-0.20; respectively), POD2 (RR, 0.50; 95% CI, 0.42-0.58; and RR, 0.46; 95% CI, 0.37-0.56; respectively), and POD3 (RR, 0.78; 95% CI, 0.66-0.93; and RR, 0.76; 95% CI, 0.63-0.93; respectively). Compared with SA, PVC was associated with earlier discharge from intensive care (OR, 2.75; 95% CI, 1.17-6.45) and TEA was not (OR, 1.12; 95% CI, 0.56-2.2). Compared with TEA, PVC was not associated with increased rate of opioid-related adverse events (OR, 0.44; 95% CI, 0.08-2.44). CONCLUSIONS: PVC and TEA are associated with decreased MEQ compared with SA. PVC is associated with earlier discharge from intensive care compared with SA and similar rates of opioid-related adverse events compared with TEA. Paravertebral analgesia appears to be a safe and effective analgesic modality in patients undergoing retroperitoneal approach for abdominal aneurysm repair.

Impact of food allergy on food insecurity and health literacy in a tertiary care pediatric allergy population.

BACKGROUND: Food insecurity (FI), limited availability of or access to nutritional foods, is linked to poor child/caregiver health. We examined FI in food-allergic and non-food-allergic children to determine whether dietary limitations associated with food allergy increases risk of FI. METHODS: Food-allergic and non-food-allergic children (1-17 years) were recruited from Arkansas Children's Hospital allergy/asthma clinics. The USDA Food Security Survey, the Newest Vital Sign Health Literacy (HL) questionnaire, and the Food Allergy Impact Scale QOL survey were administered. Logistic regression and analysis of covariance models were utilized for data analysis. RESULTS: Subjects (n = 650) included 325 food-allergic and 325 non-food-allergic children. Overall rate of FI was 21.5% (food allergic 22.2% and non-food allergic 20.9%) with no significant difference in the prevalence of FI between groups (OR = 1.30; 95% CI 0.86-1.96; P = 0.21). FI was increased in households of children with both milk and egg allergy when compared to those without food allergy and those with single food allergy (OR = 2.5; 95% CI 1.4-4.6; P = 0.003). Mean HL rates were higher in the food-secure vs food-insecure groups (mean diff = 0.31; 95% CI 0.03-0.59; P = 0.03). Among food-allergic children, QOL was better in the food-secure vs food-insecure group (mean diff = 0.61; 95% CI 0.002-1.23; P = 0.049). CONCLUSION: Food allergy to milk and egg was associated with increased risk of household FI. Food-insecure participants had lower HL than their food-secure counterparts. Further work is needed to define risks associated with FI among food-allergic children to improve screening and management strategies.

Long-Term Neurodevelopment of Low-Birthweight, Preterm Infants with Patent Ductus Arteriosus.

OBJECTIVE: To evaluate whether the presence of patent ductus arteriosus (PDA) in preterm infants worsens long-term neurodevelopmental outcomes. STUDY DESIGN: This was a secondary observational analysis of data from 1090 preterm low-birthweight infants in the Infant Health and Development Program (IHDP), a multicenter longitudinal cohort study of outcomes assessed from 3 to 18 years of age. Multivariable analysis was adjusted for IHDP treatment group (intervention or follow-up), birth weight, maternal race, maternal education, infant sex, maternal preconception weight, Home Observation Measurement of the Environment (HOME) total score at 12 months, neonatal health index, and gestational age. RESULTS: Of the 1090 patients (49% male) included in the analysis, 135 had a PDA. Mean birth weight (1322 g vs 1871 g; P < .0001) and gestational age (30.2 weeks vs 33.4 weeks, P < .0001) were lower and mean ventilator days (11.8 vs 1.3; P < .0001), vasopressor use (12.6% vs 1.2%; P < .0001), and congestive heart failure (8.9% vs 0.1%; P < .0001) were higher in the PDA group. There were no differences between the PDA and no-PDA groups in maternal education level and HOME total score at age 12 months. Multivariable analysis demonstrated no between-group differences in cognitive development or behavioral competence at age 3, 8, and 18 years. CONCLUSIONS: The presence of a PDA in moderately preterm, low-birthweight infants does not impact long-term neurodevelopmental outcomes.

GNA13 loss in germinal center B cells leads to impaired apoptosis and promotes lymphoma in vivo.

GNA13 is the most frequently mutated gene in germinal center (GC)-derived B-cell lymphomas, including nearly a quarter of Burkitt lymphoma and GC-derived diffuse large B-cell lymphoma. These mutations occur in a pattern consistent with loss of function. We have modeled the GNA13-deficient state exclusively in GC B cells by crossing the Gna13 conditional knockout mouse strain with the GC-specific AID-Cre transgenic strain. AID-Cre(+) GNA13-deficient mice demonstrate disordered GC architecture and dark zone/light zone distribution in vivo, and demonstrate altered migration behavior, decreased levels of filamentous actin, and attenuated RhoA activity in vitro. We also found that GNA13-deficient mice have increased numbers of GC B cells that display impaired caspase-mediated cell death and increased frequency of somatic hypermutation in the immunoglobulin VH locus. Lastly, GNA13 deficiency, combined with conditional MYC transgene expression in mouse GC B cells, promotes lymphomagenesis. Thus, GNA13 loss is associated with GC B-cell persistence, in which impaired apoptosis and ongoing somatic hypermutation may lead to an increased risk of lymphoma development.

Intraoperative insertion of paravertebral catheter for postoperative analgesia in retroperitoneal aortic aneurysm repair.

Paravertebral catheters are a well-established analgesic modality in thoracic surgery but have not been described in abdominal aortic surgery. We describe a simple, safe, and effective technique of paravertebral catheter insertion by the operative surgeon after a retroperitoneal abdominal aortic aneurysm repair. Once the aneurysm repair is complete, an extrapleural plane between the parietal pleura and the twelfth rib is created through blunt dissection. A catheter is advanced into the space percutaneously under direct vision, and a continuous infusion of local anesthetic is administered. Paravertebral catheters typically remain in place for 3 to 5 days and provide excellent postoperative non-narcotic analgesia.