Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice

BACKGROUND: Stanniocalcin 2 (STC2) is a secreted protein activated by (PKR)-like Endoplasmic Reticulum Kinase (PERK) signalling under conditions of ER stress in vitro. Over-expression of STC2 in mice leads to a growth-restricted phenotype; however, the physiological function for STC2 has remained elusive. Given the relationship of STC2 to PERK signalling, the objective of this study was to examine the role of STC2 in PERK signalling in vivo. RESULTS: Since PERK signalling has both physiological and pathological roles in the pancreas, STC2 expression was assessed in mouse pancreata before and after induction of injury using a cerulein-induced pancreatitis (CIP) model. Increased Stc2 expression was identified within four hours of initiating pancreatic injury and correlated to increased activation of PERK signalling. To determine the effect of STC2 over-expression on PERK, mice systemically expressing human STC2 (STC2Tg) were examined. STC2Tg pancreatic tissue exhibited normal pancreatic morphology, but altered activation of PERK signalling, including increases in Activating Transcription Factor (ATF) 4 accumulation and autophagy. Upon induction of pancreatic injury, STC2Tg mice exhibited limited increases in circulating amylase levels and increased maintenance of cellular junctions. CONCLUSIONS: This study links STC2 to the pathological activation of PERK in vivo, and suggests involvement of STC2 in responding to pancreatic acinar cell injury

Biological Treatment and the Potential Risk of Adverse Postoperative Outcome in Patients With Inflammatory Bowel Disease: An Open-Source Expert Panel Review of the Current Literature and Future Perspectives

Abstract Background There is widespread concern that treatment with biologic agents may be associated with suboptimal postoperative outcome after surgery for inflammatory bowel diseases (IBD). Aim We aimed to search and analyze the literature regarding the potential association of biologic treatment on adverse postoperative outcome in patients with IBD. We used the subject as a case in point for surgical research. The aim was not to conduct a new systematic review. Method This is an updated narrative review written in a collaborative method by authors invited through Twitter via the following hashtags (#OpenSourceResearch and #SoMe4Surgery). The manuscript was presented as slides on Twitter to allow discussion of each section of the paper sequentially. A Google document was created, which was shared across social media, and comments and edits were verified by the primary author to ensure accuracy and consistency. Results Forty-one collaborators responded to the invitation, and a total of 106 studies were identified that investigated the potential association of preoperative biological treatment on postoperative outcome in patients with IBD. Most of these studies were retrospective observational cohorts: 3 were prospective, 4 experimental, and 3 population-based studies. These studies were previously analyzed in 10 systematic/narrative reviews and 14 meta-analyses. Type of biologic agents, dose, drug concentration, antidrug antibodies, interval between last dose, and types of surgery varied widely among the studies. Adjustment for confounders and bias control ranged from good to very poor. Only 10 studies reported postoperative outcome according to Clavien–Dindo classification. Conclusion Although a large number of studies investigated the potential effect of biological treatment on postoperative outcomes, many reported divergent results. There is a need for randomized controlled trials. Future studies should focus on the avoiding the weakness of prior studies we identified. Seeking collaborators and sharing information via Twitter was integral to widening the contributors/authors and peer review for this article and was an effective method of collaboration

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10 years; 78.2% included were male with a median age of 37 years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020

What Should We Recommend for Colorectal Cancer Screening in Adults Aged 75 and Older?

The current recommendation to stop colorectal cancer screening for older adults is based on a lack of evidence due to systematic exclusion of this population from trials. Older adults are a heterogenous population with many available strategies for patient-centered assessment and decision-making. Evolutions in management strategies for colorectal cancer have made safe and effective options available to older adults, and the rationale to screen for treatable disease more reasonably, especially given the aging Canadian population. In this commentary, we review the current screening guidelines and the evidence upon which they were built, the unique considerations for screening older adults, new treatment options, the risks and benefits of increased screening and potential considerations for the new guidelines

Stanniocalcin 2 alters PERK signalling and reduces cellular injury during cerulein induced pancreatitis in mice

Abstract Background Stanniocalcin 2 (STC2) is a secreted protein activated by (PKR)-like Endoplasmic Reticulum Kinase (PERK) signalling under conditions of ER stress in vitro. Over-expression of STC2 in mice leads to a growth-restricted phenotype; however, the physiological function for STC2 has remained elusive. Given the relationship of STC2 to PERK signalling, the objective of this study was to examine the role of STC2 in PERK signalling in vivo. Results Since PERK signalling has both physiological and pathological roles in the pancreas, STC2 expression was assessed in mouse pancreata before and after induction of injury using a cerulein-induced pancreatitis (CIP) model. Increased Stc2 expression was identified within four hours of initiating pancreatic injury and correlated to increased activation of PERK signalling. To determine the effect of STC2 over-expression on PERK, mice systemically expressing human STC2 (STC2Tg) were examined. STC2Tg pancreatic tissue exhibited normal pancreatic morphology, but altered activation of PERK signalling, including increases in Activating Transcription Factor (ATF) 4 accumulation and autophagy. Upon induction of pancreatic injury, STC2Tg mice exhibited limited increases in circulating amylase levels and increased maintenance of cellular junctions. Conclusions This study links STC2 to the pathological activation of PERK in vivo, and suggests involvement of STC2 in responding to pancreatic acinar cell injury.</p

Leveraging Videoconferencing Technology to Augment Surgical Training During a Pandemic

Objective:. Our objective was to review the use of videoconferencing as a practical tool for remote surgical education and to propose a model to overcome the impact of a pandemic on resident training. Summary Background Data:. In response to the coronavirus disease 2019 pandemic, most institutions and residency programs have been restructured to minimize the number of residents in the hospital as well as their interactions with patients and to promote physical distancing measures. This has resulted in decreased resident operative exposure, responsibility, and autonomy, hindering their educational goals and ability to achieve surgical expertise necessary for independent practice. Methods:. We conducted a narrative review to explore the use of videoconferencing for remote broadcasting of surgical procedures, telecoaching using surgical videos, telesimulation for surgical skills training, and establishing a didactic lecture series. Results and Conclusions:. We present a multimodal approach for using practical videoconferencing tools that provide the means for audiovisual communication to help augment residents’ operative experience and limit the impact of self-isolation, redeployment, and limited operative exposure on surgical training

Intraoperative Cystoscopic Evaluation of Ureteral Patency: A Randomized Controlled Trial.

OBJECTIVE: To compare different modalities to aid in the evaluation of intraoperative ureteral patency on cystoscopy in the postindigo carmine era. METHODS: In a randomized controlled trial, participants undergoing pelvic surgery were randomized into one of four groups: saline distention (control), 10% dextrose distention, oral phenazopyridine, or intravenous sodium fluorescein. Our primary outcome was visibility of the ureteral jets. Secondary outcomes included surgeon satisfaction; adverse reactions including allergies, urinary tract infections, urinary retention, cystoscopy times, and ureteral obstruction; and delayed diagnosis. Participants were followed for 6 weeks. A sample size of 176 participants was planned to demonstrate a 30% difference in the visibility scale. All analyses were performed in an intention-to-treat fashion. RESULTS: From February 25, 2015, through August 2015, 176 participants were enrolled; 174 completed the trial, and two did not undergo intervention. Forty-four participants were included in the phenazopyridine, dextrose, saline, and sodium fluorescein groups. Sodium fluorescein and 10% dextrose resulted in significantly improved visibility and satisfaction when compared with the control group (P CONCLUSION: Compared with the control, 10% dextrose and sodium fluorescein resulted in improved visibility and provided significantly more satisfaction in the evaluation for ureteral patency with no considerable increase in operative time or morbidity. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, https://clinicaltrials.gov, NCT02476448

A Snapshot of the International Views of the Treatment of Rectal Cancer Patients, a Multi-regional Survey:International Tendencies in Rectal Cancer

BACKGROUND: Management of rectal cancer has a number of potentially appropriate alternatives for each patient. Despite acceptance of standards, practices may vary among regions. There is significant paucity of data in this area. The objective was to create a snapshot of the regional differences. DESIGN: This online survey included 10 questions. Enquiries focused on controversial topics, on surgeon and hospital volume, surgical margins, appropriateness of surgical approaches and techniques, watch-and-wait strategies, and total neoadjuvant therapy. Major colorectal surgery societies around the world were asked to invite their members to complete the survey. OUTCOME MEASURES: Frequency of responses across regions within each question was compared by Fisher's exact test. RESULTS: Seven hundred and fifty-three participants from 60 countries responded. Eight regions were identified, and four had sufficient representation for comparisons. Similarities and differences in the therapies among these regions were identified. Robotic surgery penetrance is higher in North America, and watch and wait is more accepted in South America. Patients in Oceania are more likely to be diverted; Europe has more usage of taTME. DISCUSSION: This online survey was practical as a mean to provide a rapid assessment of the international picture on consistency and variability of rectal cancer patients' care, and to potentially identify opportunities to standardized care to patients. Medical surveys have inherent limitations; pertinence to our study is selection bias. CONCLUSIONS: The management of rectal cancer varies among different regions. Identification of differences is important when considering global efforts to improve management and interpret data