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Objective: To measure the rate of LTS in resected PDAC and determine the association between predictors of OS and LTS., Summary Background Data: Long-term survival (>5 y, LTS) remains rare in pancreatic ductal adenocarcinoma (PDAC). Multiple predictors of overall survival (OS) are known but their association with LTS remains unclear., Methods: An international, multicenter retrospective study was conducted. Included were patients from 2012-2019 with resected PDAC. Excluded were those with metastases at diagnosis or resection, R2 resections, and 90-day mortality. Predictors of OS were identified using multivariable Cox regression and their prevalence in patients with LTS assessed. LTS was calculated by excluding patients with shorter follow-up and predictors of LTS were identified using multivariable logistic regression., Results: 3,003 patients were included (27.4% received neoadjuvant chemotherapy). Elevated baseline CA19-9, high tumor grade, nodal disease, and perineural and lymphovascular invasion were negative independent predictors of OS, while receipt of adjuvant chemotherapy predicted improved OS (all P<0.05). LTS was observed in 220/2,436 patients (9.0%), of whom 198 (90%) harbored poor prognostic factors: elevated baseline CA19-9 (58.1%), poor tumor differentiation (51.0%), nodal disease (46.8%), and perineural invasion (76.0%). Of those without any of these four features, 50.0% achieved LTS as compared to 21.3%, 13.3%, 5.2%, and 3.5% in those with 1, 2, 3, or 4 features., Conclusions: This bi-national cohort demonstrates a true LTS rate of 9.0% in resected PDAC. Clinicians should remain aware that presence of poor prognostic factors does not preclude LTS., Competing Interests: Conflicts of Interest: The authors declare that there are no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Systematic collection and analysis of surgical outcomes data is a cornerstone of surgical quality improvement. Unfortunately, there remains a dearth of surgical outcomes data from low- and middle-income countries (LMICs). To improve surgical outcomes in LMICs, it is essential to have the ability to collect, analyze, and report risk-adjusted postoperative morbidity and mortality data. This study aimed to review the barriers and challenges to developing perioperative registries in LMIC settings., Methods: We conducted a scoping review of all published literature on barriers to conducting surgical outcomes research in LMICs using PubMed, Embase, Scopus, and GoogleScholar. Keywords included 'surgery', 'outcomes research', 'registries', 'barriers', and synonymous Medical Subject Headings derivatives. Articles found were subsequently reference-mined. All relevant original research and reviews published between 2000 and 2021 were included. The performance of routine information system management framework was used to organize identified barriers into technical, organizational, or behavioral factors., Results: Twelve articles were identified in our search. Ten articles focused specifically on the creation, success, and obstacles faced during the implementation of trauma registries. Technical factors reported by 50% of the articles included limited access to a digital platform for data entry, lack of standardization of forms, and complexity of said forms. 91.7% articles mentioned organizational factors, including the availability of resources, financial constraints, human resources, and lack of consistent electricity. Behavioral factors highlighted by 66.6% of the studies included lack of team commitment, job constraints, and clinical burden, which contributed to poor compliance and dwindling data collection over time., Conclusions: There is a paucity of published literature on barriers to developing and maintaining perioperative registries in LMICs. There is an immediate need to study and understand barriers and facilitators to the continuous collection of surgical outcomes in LMICs., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Contributors: EA participated in the literature search and writing and editing the article. NAM participated in writing and editing the article and sourced the patient photographs. FP participated in writing and editing the article. PAC participated in the literature search and editing the article and was responsible for overall supervision of the study; he is guarantor for the study. Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: PAC received travel expenses from Bayer to present on peripheral arterial disease to a general audience of primary and secondary care at the RCP.

Background: Complex abdominal aortic aneurysm (AAA) is a relatively common presentation to the vascular specialist. Despite this there is little consensus on how to manage the often comorbid group of patients. Recent advances in endovascular technology have led to the availability of multiple devices, many of which could be used to treat the same aneurysm. The aim of this study was to quantify this potential variability across vascular specialists from multiple countries., Methods: An online survey was emailed to members of the Vascular Society for Great Britain and Ireland (VSGBI), the Canadian Society for Vascular Surgery (CSVS) and the Australian and New Zealand Society for Vascular Surgery (ANZSVS). The survey presented a vignette of a 63-year-old woman with significant respiratory comorbidity and a 54 mm juxtarenal AAA (7 mm neck). There were no other adverse morphological features for endovascular repair. The survey included images and questions related to management of the aneurysm., Results: The survey received 238 responses; 61 from ANZSVS, 65 from CSVS and 112 from VSGBI. VSGBI specialists were significantly more likely to continue surveillance than both ANZSVS (odds ratio [OR] 3.41, 95% confidence interval [CI] 1.61-7.65; P<0.001) and CSVS counterparts (OR 2.61, 95% CI: 1.29-5.47; P<0.01). ANZSVS specialists were significantly more likely to perform an endovascular repair than those from CSVS (OR 3.28, 95% CI: 1.50-7.40; P<0.01) and VSGBI (OR 3.65, 95% CI: 1.81-7.59; P<0.001). CSVS specialists were significantly more likely to manage the aneurysm with open surgery than colleagues from the VSGBI (OR 6.57, 95% CI: 2.58-18.46; P<0.001) and ANZSVS (OR 7.18, 95% CI: 2.22-30.79; P<0.001)., Conclusions: Significant variation in the management of a juxtarenal AAA between countries was observed. The same patient would be more likely to have an endovascular repair in Australia and New Zealand, open surgery in Canada and continuing surveillance in the UK and Ireland. This variation reflects the lack of long-term evidence and international consensus on the optimal management of complex AAA.

Background: M-learning is education using personal mobile electronic devices. Given the prevalence of these in society and amongst healthcare professionals, we aimed to assess their use and feasibility in improving the educational programme of a single vascular institution., Methods: A weekly vascular departmental teaching programme was initiated with registrars giving 30-min presentations on a defined book chapter. Two multiple-choice questions (MCQ) per session were devised by a supervising consultant utilising the smartphone response system application, Polltogo. A separate investigator disseminated one pre-teaching and one post-teaching MCQ to the attending trainees via a WhatsApp group. Instant feedback of the correct answer was provided by the application. Participants' satisfaction was judged through a survey after 13 sessions., Results: 11 junior doctors of varying seniority participated in the trial. The median number of session attendees was 5. 129 MCQ responses were received. The mobile engagement score (number of answers received divided by total possible answers) was 97.7%. The average correct score for pre-teaching MCQs was 39.4% and post-teaching MCQs 73.0% (p < 0.001). Satisfaction with the concept was high; 80% of responders agreed that it was a useful adjunct to the teaching programme whilst 90% found the system highly user-friendly., Conclusions: Smartphones can be utilised effectively and with high user satisfaction in assessing knowledge transfer throughout a departmental education programme. Trainees' responses to MCQs significantly improved after 30-min teaching sessions. This concept of m-learning could be developed further to assist with postgraduate examination revision or Deanery teaching programmes in larger cohorts.

Scavenger receptors (SRs) are a 'superfamily' of membrane-bound receptors that were initially thought to bind and internalize modified low-density lipoprotein (LDL), though it is currently known to bind to a variety of ligands including endogenous proteins and pathogens. New family of SRs and their properties have been identified in recent years, and have now been classified into 10 eukaryote families, defined as Classes A-J. These receptors are classified according to their sequences, although in each class they are further classified based in the variations of the sequence. Their ability to bind a range of ligands is reflected on the biological functions such as clearance of modified lipoproteins and pathogens. SR members regulate pathophysiological states including atherosclerosis, pathogen infections, immune surveillance, and cancer. Here, we review our current understanding of SR structure and function implicated in health and disease.

Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular physiology. VEGF-A stimulates signal transduction pathways that modulate endothelial outputs such as cell migration, proliferation, tubulogenesis, and cell-cell interactions. Multiple VEGF-A isoforms exist, but the biological significance of this is unclear. Here we analyzed VEGF-A isoform-specific stimulation of VCAM-1 gene expression, which controls endothelial-leukocyte interactions, and show that this is dependent on both ERK1/2 and activating transcription factor-2 (ATF-2). VEGF-A isoforms showed differential ERK1/2 and p38 MAPK phosphorylation kinetics. A key feature of VEGF-A isoform-specific ERK1/2 activation and nuclear translocation was increased phosphorylation of ATF-2 on threonine residue 71 (T71). Using reverse genetics, we showed ATF-2 to be functionally required for VEGF-A-stimulated endothelial VCAM-1 gene expression. ATF-2 knockdown blocked VEGF-A-stimulated VCAM-1 expression and endothelial-leukocyte interactions. ATF-2 was also required for other endothelial cell outputs, such as cell migration and tubulogenesis. In contrast, VCAM-1 was essential only for promoting endothelial-leukocyte interactions. This work presents a new paradigm for understanding how soluble growth factor isoforms program complex cellular outputs and responses by modulating signal transduction pathways., (© 2014 Fearnley et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).)

Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Peripheral arterial disease remains a significant global health burden despite revolutionary improvements in endovascular techniques over the past decade. The durability of intervention for critical limb ischaemia is poor, and the condition is associated with high morbidity and mortality rates. To address this deficiency, alternative therapeutic options are being explored. Advances in the fields of gene therapy and therapeutic angiogenesis have led to these being advocated as potential future treatments., Methods: Relevant medical literature from PubMed, Embase, the Cochrane Library and Google Scholar from the inception of these databases to June 2011 was reviewed., Results: Encouraging outcomes in preclinical trials using a variety of proangiogenic growth factors have led to numerous efficacy and safety studies. However, no clinical study has shown significant benefit for gene therapy over placebo., Conclusion: Identifying the optimal site for gene delivery, choice of vector and duration of treatment is needed if gene therapy is to become a credible therapeutic option for peripheral arterial disease., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)