Evaluation of trauma resources in rural northern Alberta identifies opportunities for improvement.

Background: The care of rural trauma patients in northern Alberta can be extremely challenging because of the vast geographic area, the limited access to health care facilities and the lack of adequate resources to manage severe injuries. Identifying gaps in equipment and personnel in rural centres can provide opportunities for improving the care of injured patients in these environments. We conducted a survey based on Canadian Accreditation Council quality indicators to evaluate trauma infrastructure and human resources in rural centres across northern Alberta. Methods: A standardized survey was developed to assess the availability of trauma-specific equipment and personnel across the prehospital and emergency department (ED) settings. The survey was distributed to 50 peripheral hospitals biannually from January 2017 to September 2018. Two-tailed paired t tests were used to evaluate changes in survey responses; a p value of less than 0.05 was considered statistically significant. Results: The survey response rate was 100%. By the end of the study period, there were significant improvements in the number of providers (p = 0.04), nurses (p = 0.01) and dedicated trauma resuscitation bays (p = 0.04) in the ED for managing injured patients. There were also significant increases in the availability of equipment, including advanced airway management tools (p = 0.02), rapid infusion devices (p = 0.02) and warmers (p = 0.04). Access to x-ray equipment (p = 0.03) and computed tomography (CT) scanners (p = 0.04) as well as equipment to support telehealth and teleconferencing (p = 0.04) increased during the study period. Access to, and supply of, blood products also increased significantly (p = 0.02) during the study period. Conclusion: Our study demonstrates that the trauma resources of rural health care centres may be evaluated in a standardized fashion centres, and the results point to opportunities to remedy gaps in equipment and personnel. Our methods may be applied to any trauma network that serves geographically large areas with a sparse distribution of health care facilities, to provide critical information for the optimization of resources in rural trauma.

Contexte: Les soins aux patients victimes de traumatismes en région rurale dans le nord de l'Alberta peuvent être très difficiles en raison de la superficie de la région, de l'accès limité aux établissements de santé et du manque de ressources pour soigner adéquatement les blessures graves. En repérant les lacunes en équipement et en personnel dans les établissements en région rurale, on peut créer des occasions d'améliorer les soins aux patients blessés dans ces milieux. Nous avons mené un sondage fondé sur les indicateurs de qualité du Conseil d'accréditation canadien pour évaluer les infrastructures et les ressources humaines en traumatologie dans les établissements des régions rurales du nord de l'Alberta. Méthodes: Un sondage standardisé a été créé pour évaluer la disponibilité des équipements et des ressources humaines en traumatologie en contexte préhospitalier et aux services d'urgence. Le sondage a été distribué 2 fois par année à 50 hôpitaux entre janvier 2017 et septembre 2018. Des tests t appariés ayant une hypothèse non nulle ont été utilisés pour évaluer les changements dans les réponses au sondage; les résultats ayant une valeur p < 0,05 étaient considérés comme statistiquement significatifs. Résultats: Le taux de participation au sondage était de 100 %. À la fin de la période étudiée, il y avait une amélioration significative du nombre de fournisseurs (p = 0,04), de personnel infirmier (p = 0,01) et d'espaces de réanimation réservés à la traumatologie (p = 0,04) dans les services d'urgence. Il y avait aussi une augmentation significative de la disponibilité de l'équipement, notamment des outils de prise en charge avancée des voies respiratoires (p = 0,02), des appareils de perfusion rapide (p = 0,02) et d'armoires chauffantes (p = 0,04). Les équipements de radiographie (p = 0,03) et de tomographie par ordinateur (p = 0,04) ainsi que les équipements facilitant la télémédecine et les téléconférences (p = 0,04) sont devenus plus accessibles pendant la période étudiée. Les réserves de produits sanguins et l'accès à ces produits a aussi augmenté de manière significative (p = 0,02). Conclusion: Notre étude montre que les ressources en traumatologie dans les établissements de santé en région rurale peuvent être évaluées de manière standardisée, et les résultats indiquent qu'il y a des occasions de combler les lacunes en équipement et en personnel. Notres méthodes peuvent être reproduites dans tout réseau de traumatologie couvrant un grand territoire où les établissements de santé sont dispersés, pour fournir des données critiques sur l'organisation des ressources de traumatologie en région rurale.

Activation of the pattern recognition receptor NOD1 augments colon cancer metastasis.

While emerging data suggest nucleotide oligomerization domain receptor 1 (NOD1), a cytoplasmic pattern recognition receptor, may play an important and complementary role in the immune response to bacterial infection, its role in cancer metastasis is entirely unknown. Hence, we sought to determine the effects of NOD1 on metastasis. NOD1 expression in paired human primary colon cancer, human and murine colon cancer cells were determined using immunohistochemistry and immunoblotting (WB). Clinical significance of NOD1 was assessed using TCGA survival data. A series of in vitro and in vivo functional assays, including adhesion, migration, and metastasis, was conducted to assess the effect of NOD1. C12-iE-DAP, a highly selective NOD1 ligand derived from gram-negative bacteria, was used to activate NOD1. ML130, a specific NOD1 inhibitor, was used to block C12-iE-DAP stimulation. Stable knockdown (KD) of NOD1 in human colon cancer cells (HT29) was constructed with shRNA lentiviral transduction and the functional assays were thus repeated. Lastly, the predominant signaling pathway of NOD1-activation was identified using WB and functional assays in the presence of specific kinase inhibitors. Our data demonstrate that NOD1 is highly expressed in human colorectal cancer (CRC) and human and murine CRC cell lines. Clinically, we demonstrate that this increased NOD1 expression negatively impacts survival in patients with CRC. Subsequently, we identify NOD1 activation by C12-iE-DAP augments CRC cell adhesion, migration and metastasis. These effects are predominantly mediated via the p38 mitogen activated protein kinase (MAPK) pathway. This is the first study implicating NOD1 in cancer metastasis, and thus identifying this receptor as a putative therapeutic target.

Gram-Negative Pneumonia Augments Non-Small Cell Lung Cancer Metastasis through Host Toll-like Receptor 4 Activation.

INTRODUCTION: Surgery is essential for cure of early-stage non-small cell lung cancer (NSCLC). Rates of postoperative bacterial pneumonias, however, remain high, and clinical data suggests that post-operative infectious complications confer an increased risk for metastasis. Toll-like receptors (TLRs) mediate the inflammatory response to infection by recognizing evolutionarily conserved bacterial structures at the surface of numerous pulmonary cell types; yet, little is known about how host TLR activation influences NSCLC metastasis. TLR4 recognizes gram-negative bacterium lipopolysaccharide activating the innate immune system. METHODS: C57BL/6 and TLR4 knockout murine airways were inoculated with Escherichia coli or lipopolysaccharide. Hepatic metastasis assays and intravital microscopy were performed. Bronchoepithelial conditioned media was generated through coincubation of bronchoepithelial cells with TLR4 activating Escherichia coli or lipopolysaccharide. Subsequently, H59 NSCLC were stimulated with conditioned media and subject to various adhesion assays. RESULTS: We demonstrate that gram-negative Escherichia coli pneumonia augments the formation of murine H59 NSCLC liver metastases in C57BL/6 mice through TLR4 activation. Additionally, infected C57BL/6 mice demonstrate increased H59 NSCLC in vivo hepatic sinusoidal adhesion compared with negative controls, a response that is significantly diminished in TLR4 knockout mice. Similarly, intratracheal injection of purified TLR4 activating lipopolysaccharide increases in vivo adhesion of H59 cells to murine hepatic sinusoids. Furthermore, H59 cells incubated with bronchoepithelial conditioned medium show increased cell adhesion to in vitro extracellular matrix proteins and in vivo hepatic sinusoids through a mechanism dependent on bronchoepithelial TLR4 activation and interleukin-6 secretion. CONCLUSION: TLR4 is a viable therapeutic target for NSCLC metastasis augmented by gram-negative pneumonia.

Predictive Power of the NSQIP Risk Calculator for Early Post-Operative Outcomes After Whipple: Experience from a Regional Center in Northern Ontario.

BACKGROUND: NSQIP Risk Calculator was developed to allow surgeons to inform their patients about their individual risks for surgery. Its ability to predict complication rates and length of stay (LOS) has made it an appealing tool for both patients and surgeons. However, the NSQIP Risk Calculator has been criticized for its generality and lack of detail towards surgical subspecialties, including the hepatopancreaticobiliary (HPB) surgery. We wish to determine whether the NSQIP Risk Calculator is predictive of post-operative complications and LOS with respect to Whipple's resections for our patient population. As well, we wish to identify strategies to optimize early surgical outcomes in patients with pancreatic cancer. METHODS: We conducted a retrospective review of patients who underwent elective Whipple's procedure for benign or malignant pancreatic head lesions at Health Sciences North (Sudbury, Ontario), a tertiary care center, from February 2014 to August 2016. Comparisons of LOS and post-operative complications between NSQIP-predicted and actual ones were carried out. NSQIP-predicted complications rates were obtained using the NSQIP Risk Calculator through pre-defined preoperative risk factors. Clinical outcomes examined, at 30 days post-operation, included pneumonia, cardiac events, surgical site infection (SSI), urinary tract infection (UTI), venous thromboembolism (VTE), renal failure, readmission, and reoperation for procedural complications. As well, mortality, disposition to nursing or rehabilitation facilities, and LOS were assessed. RESULTS: A total of 40 patients underwent Whipple's procedure at our center from February 2014 to August 2016. The average age was 68 (50-85), and there were 22 males and 18 females. The majority of patients had independent baseline functional status (39/40) with minimal pre-operative comorbidities. The overall post-operative morbidity was 47.5% (19/40). The rate of serious complication was 17.5% with four Clavien grade II, two grade III, and one grade V complications. One mortality occurred within 30 days after surgery. NSQIP Risk Calculator was predictive for the majority of post-surgical complication types, including pneumonia, SSI, VTE, reoperation, readmission, and disposition to rehabilitation or nursing home. Our center appears to have a higher rate of UTI than NSQIP predicted (O/E = 3.9), as well, the rate of cardiac complication (O/E = 3.1) also appears to be higher at our center. With respect to readmission rates (O/E = 0.6) and renal failure (O/E = 0), NSQIP provided overestimated rates. The average LOS was 11.9 ± 0.9 days, which was not significantly different from the average LOS of 11.5 ± 0.3 days predicted by NSQIP (p = 0.3). Overall, 80% of discharges occurred less than or within 3 days of that predicted by NSQIP. CONCLUSION: NSQIP Risk Calculator is predictive of post-operative complications and LOS for patients who have undergone Whipple's at our center. A more HPB-focused NSQIP calculator may accurately project post-operative complication in the pre-operative period. Nevertheless, the generic NSQIP has allowed us to examine our existing practice of post-operative care and has paved way to reduce cardiac and urinary complications in the future.

Outcomes of a Single Surgeon-Based Transanal-Total Mesorectal Excision (TATME) for Rectal Cancer.

BACKGROUND: Several studies have shown the transanal total mesorectal excision (TATME) is emerging as a safe and effective technique for proctectomy. The majority of these studies to date, however, is based on procedures done in centers with teams of two surgeons working simultaneously. Few were performed by single-surgeon teams with sizeable case load. The objective of our study was to identify the feasibility and safety of a single-surgeon TATME. METHODS: Chart review of prospectively collected data on 27 patients who underwent TATME at our institution from June 2015 to September 2016 were included in this study. Indications for TATME included mid and low rectal cancers. Only patients who underwent surgery for neoplastic lesions were included in the study. Outcomes assessed included mesorectal integrity, margin status, operative time, complications, morbidity, LOS, and 30-day readmission. RESULTS: A total of 27 cases were available for inclusion. A single surgeon performed all procedures. The average BMI was 27.2 ± 1.3 kg/m2. The average tumor distance from anal verge was 6.8 ± 0.6 cm. The median operative time was 283 min. No intraoperative complications, including injuries and conversions, occurred. Circumferential resection margin (CRM) and distal resection margin (DRM) were R0 in 96 and 100% of patients, respectively. Mesorectal integrity was "Complete" in 67% and "Near complete" in 33% of patients. There were no incomplete specimens. The total lymph node (LN) harvest was 26 ± 2. The average LOS was 4 days for 75% of all patients. There were no mortalities. The overall morbidity was 33% (9/27). There were 4/27 anastomotic leaks, one required a laparoscopic ileostomy, one had laparoscopic drainage of an abscess, and the other two were endoscopically washed and trans-rectal drains inserted. CONCLUSION: TATME performed by a one-surgeon team is oncologically adequate, and it is safe and feasible. Morbidities are comparable with existing literature data from two-surgeon teams. In addition, resection margins, mesorectal integrity, and LN harvests are also comparable or superior to some of the existing studies.

Transanal minimally invasive surgery for benign large rectal polyps and early malignant rectal cancers: experience and outcomes from the first Canadian centre to adopt the technique.

BACKGROUND: Transanal minimally invasive surgery (TAMIS) has emerged as a relatively new technique in treating early cancer and benign lesion of the rectum. The technique is likely to be widely adopted, surpassing other comparable techniques owing to its simple setup and cost-effectiveness. We assessed the outcomes of TAMIS at our centre. METHODS: We retrospectively reviewed prospectively collected data on 50 patients who underwent TAMIS for benign, malignant T1 or T2 cancers that were unfit for radical surgery over a 4-year period. Outcomes, including 30-day complications and recurrence, as well as our ability to implement and integrate this technique at our centre were assessed. RESULTS: All 50 TAMIS procedures were successful. The average lesion was 7 cm from the anal verge, the average tumour size was 2.5 cm, the average duration of surgery was 73 minutes, the average length of stay was 1.1 days, and the margin negativity was 84%. Major indications in our series included 25 lesions that were too large for endoscopic resection, 14 early cancers or high-grade dysplasia, 10 margin checks postpolypectomy, 6 cases of recurrent polyposis, and 4 medically unfit patients. There were no deaths. The rate of short-term complications, including rectal bleeding, reoperation and urinary retention, was 16%. The rate of long-term complications, including anal incontinence and stenosis, was 4%. Benign and malignant recurrence rates were 2% and 6%, respectively. Overall long-term requirement for invasive procedures, low anterior resection or abdominoperineal resection, was 12%. CONCLUSION: To our knowledge, this is the first Canadian study showing TAMIS to be an efficient and safe procedure for the treatment of well-selected patients with rectal lesions. Outcomes from our centre are comparable with those found in the literature.

CONTEXTE: La chirurgie transanale mini-invasive (TAMIS) s'est imposée comme une technique relativement nouvelle pour le traitement du cancer précoce et des lésions bénignes du rectum. La technique est en voie d'être adoptée à grande échelle, voire de supplanter d'autres techniques comparables, en raison de sa mise en place facile et de sa rentabilité. Nous avons évalué les résultats de la technique TAMIS dans notre centre. MÉTHODES: Nous avons fait une analyse rétrospective de données recueillies de façon prospective sur 50 patients traités par TAMIS pour cause de cancer T1 ou T2 malin ou bénin et non candidats à la chirurgie radicale, sur une période de 4 ans. Nous avons évalué les résultats, y compris les complications et la récidive sur 30 jours, ainsi que notre capacité d'adopter et d'intégrer cette technique dans notre centre. RÉSULTATS: Les 50 chirurgies TAMIS furent une réussite. La taille moyenne de la lésion était de 7 cm à partir de la marge anale, la taille moyenne de la tumeur était de 2,5 cm, la durée moyenne de la chirurgie était de 73 minutes, la durée moyenne d'hospitalisation était de 1,1 jour et le taux de marges négatives était de 84 %. Parmi les principales indications dans notre série, mentionnons 25 lésions trop grandes pour la résection endoscopique; 14 cancers précoces ou dysplasies de haut grade; 10 vérifications des marges post-polypectomie, 6 cas de récidive de la polypose et 4 patients non candidats au traitement médical. Il n'y a eu aucun décès. Le taux de complications à court terme, incluant le saignement rectal, les interventions répétées et la rétention urinaire, était de 16 %. Le taux de complications à long terme, incluant l'incontinence anale et la sténose anale, était de 4 %. Les taux de récidive bénigne et maligne étaient respectivement de 2 % et de 6 %. Le taux global de besoin à long terme d'une intervention effractive, d'une résection antérieure basse ou d'une résection abdominopérinéale était de 12 %. CONCLUSION: À notre connaissance, notre étude est la première au Canada qui démontre que la technique TAMIS est une intervention efficace et sécuritaire pour le traitement de patients soigneusement choisis atteints de lésions rectales. Les résultats de notre centre sont comparables à ceux trouvés dans la littérature.

Gram-positive pneumonia augments non-small cell lung cancer metastasis via host toll-like receptor 2 activation.

Surgical resection of early stage nonsmall cell lung cancer (NSCLC) is necessary for cure. However, rates of postoperative bacterial pneumonias remain high and may confer an increased risk for metastasis. Toll-like receptors (TLRs) mediate the inflammatory cascade by recognizing microbial products at the surface of numerous cell types in the lung; however, little is known about how host TLRs influence NSCLC metastasis. TLR2 recognizes gram-positive bacterial cell wall components activating innate immunity. We demonstrate that lower respiratory tract infection with Streptococcus pneumonia augments the formation of murine H59 NSCLC liver metastases in C57BL/6 mice through host TLR2 activation. Infected mice demonstrate increased H59 and human A549 NSCLC adhesion to hepatic sinusoids in vivo compared with noninfected controls, a response that is significantly diminished in TLR2 knock-out mice. Intra-tracheal injection of purified TLR2 ligand lipoteichoic acid into mice similarly augments in vivo adhesion of H59 cells to hepatic sinusoids. Additionally, H59 and A549 NSCLC cells incubated with bronchoepithelial conditioned media show increased cell adhesion to extracellular matrix components in vitro and hepatic sinusoids in vivo in a manner that is dependent on bronchoepithelial TLR2 activation and interleukin-6 secretion. TLR2 is therefore a potential therapeutic target for gram-positive pneumonia-driven NSCLC metastasis.

Heterogeneous effects of fructose on blood lipids in individuals with type 2 diabetes: systematic review and meta-analysis of experimental trials in humans.

OBJECTIVE: Because of blood lipid concerns, diabetes associations discourage fructose at high intakes. To quantify the effect of fructose on blood lipids in diabetes, we conducted a systematic review and meta-analysis of experimental clinical trials investigating the effect of isocaloric fructose exchange for carbohydrate on triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol in type 1 and 2 diabetes. RESEARCH DESIGN AND METHODS: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library for relevant trials of > or =7 days. Data were pooled by the generic inverse variance method and expressed as standardized mean differences with 95% CI. Heterogeneity was assessed by chi(2) tests and quantified by I(2). Meta-regression models identified dose threshold and independent predictors of effects. RESULTS: Sixteen trials (236 subjects) met the eligibility criteria. Isocaloric fructose exchange for carbohydrate raised triglycerides and lowered total cholesterol under specific conditions without affecting LDL cholesterol or HDL cholesterol. A triglyceride-raising effect without heterogeneity was seen only in type 2 diabetes when the reference carbohydrate was starch (mean difference 0.24 [95% CI 0.05-0.44]), dose was >60 g/day (0.18 [0.00-0.37]), or follow-up was < or =4 weeks (0.18 [0.00-0.35]). Piecewise meta-regression confirmed a dose threshold of 60 g/day (R(2) = 0.13)/10% energy (R(2) = 0.36). A total cholesterol-lowering effect without heterogeneity was seen only in type 2 diabetes under the following conditions: no randomization and poor study quality (-0.19 [-0.34 to -0.05]), dietary fat >30% energy (-0.33 [-0.52 to -0.15]), or crystalline fructose (-0.28 [-0.47 to -0.09]). Multivariate meta-regression analyses were largely in agreement. CONCLUSIONS: Pooled analyses demonstrated conditional triglyceride-raising and total cholesterol-lowering effects of isocaloric fructose exchange for carbohydrate in type 2 diabetes. Recommendations and large-scale future trials need to address the heterogeneity in the data.