Human iPS derived progenitors bioengineered into liver organoids using an inverted colloidal crystal poly (ethylene glycol) scaffold.

Generation of human organoids from induced pluripotent stem cells (iPSCs) offers exciting possibilities for developmental biology, disease modelling and cell therapy. Significant advances towards those goals have been hampered by dependence on animal derived matrices (e.g. Matrigel), immortalized cell lines and resultant structures that are difficult to control or scale. To address these challenges, we aimed to develop a fully defined liver organoid platform using inverted colloid crystal (ICC) whose 3-dimensional mechanical properties could be engineered to recapitulate the extracellular niche sensed by hepatic progenitors during human development. iPSC derived hepatic progenitors (IH) formed organoids most optimally in ICC scaffolds constructed with 140 μm diameter pores coated with type I collagen in a two-step process mimicking liver bud formation. The resultant organoids were closer to adult tissue, compared to 2D and 3D controls, with respect to morphology, gene expression, protein secretion, drug metabolism and viral infection and could integrate, vascularise and function following implantation into livers of immune-deficient mice. Preliminary interrogation of the underpinning mechanisms highlighted the importance of TGFβ and hedgehog signalling pathways. The combination of functional relevance with tuneable mechanical properties leads us to propose this bioengineered platform to be ideally suited for a range of future mechanistic and clinical organoid related applications

LHC Impedance Model: Experience with High Intensity Operation in the LHC

The CERN Large Hadron Collider (LHC) is now in luminosity production mode and has been pushing its performance in the past months by increasing the proton beam brightness, the collision energy and the machine availability. As a consequence, collective effects have started to become more and more visible and have effectively slowed down the performance increase of the machine. Among these collective effects, the interaction of brighter LHC bunches with the longitudinal and transverse impedance of the machine has been observed to generate beam induced heating, as well as longitudinal and transverse instabilities since 2010. This contribution reviews the current LHC impedance model obtained from theory, simulations and bench measurements as well as a selection of measured effects with the LHC beam

Update on Beam Induced RF Heating in the LHC

Since June 2011 the rapid increase of the luminosity performance of the LHC has come at the expense of both increased temperature and pressure of specific, near-beam, LHC equipment. In some cases, this beam induced heating has caused delays while equipment cool-down, beam dumps and even degradation of some devices. This contribution gathers the observations of beam induced heating, attributed to longitudinal beam coupling impedance, their current level of understanding and possible actions planned to be implemented during the 1st LHC Long Shutdown (LS1) in 2013-2014

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

Aim The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. Methods This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. Results Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. Conclusion One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Jitter Impact on Clock Distribution in LHC Experiments

The LHC Bunch Clock is one of the most important accelerator signals delivered to the experiments. Being directly derived from the Radio Frequency driving the beams in the accelerator by a simple division of its frequency by a factor of 10, the Bunch Clock signal represents the frequency at which the bunches are crossing each other at each experiment. It is thus used to synchronize all the electronics systems in charge of event detection. Its frequency is around 40.079 MHz, but varies with beam parameters (energy, particle type, etc) by a few hundreds of Hz. The present paper discusses the quality of this Bunch Clock signal in terms of jitter. It is in particular compared to typical requirements of electronic components of the LHC detectors and put in perspective with the intrinsic jitter of the beam itself, to which this signal is related

247 LAPAROSCOPIC INTRAGASTRIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC CANCER: A VIDEO OF THE OXFORD APPROACH

Abstract   Laparoscopic intragastric submucosal dissection (LISD) is a novel approach to the resection of early gastric cancers not amenable to conventional gastroscopic approaches. The technique permits favourable access to lesions situated high on the posterior wall or lesser curvature of the stomach, enables en-block resection of large areas of tissue, and can prevent the need for formal gastrectomy. Using intraoperative video capture, we demonstrate our approach to LISD, and describe our peri-operative and long-term outcomes. Methods Six cases were identified as suitable for LISD by multidisciplinary team panel following EUS assessment and employing locally developed inclusion criteria. As demonstrated by video tutorial, a 3-port laparoscopic approach to the stomach was undertaken and gastrotomies performed to enable port insertion into the stomach. Following establishment of stable pneumogastrium, the area of interest was circumferentially marked with cautery and submucosal colloid injection performed to provide a cushion in the plane of dissection. Resection was completed using cautery hook, and intracorporeal suture closure of gastrotomies performed. Measures were taken to ensure correct orientation of resected specimens prior to fixation. Results Four male and two female patients (median age 74.5 years) sequentially underwent LISD, with complete curative excision confirmed histologically in 5 cases. In one case, a positive deep margin necessitated completion total gastrectomy, later confirmed to be T0 resection. No immediate or late complications, including haemorrhage, perforation or stenosis, occurred in these cases. Conclusion In this, the largest United Kingdom case series, LISD is shown to be a safe and effective intervention for the treatment of early gastric cancers in selected patients having undergone appropriate mapping endoscopy and deemed not to be amenable for endoscopic mucosal resection. Its application can serve as route to avoid formal gastrectomy and the associated morbidity. Video https://www.dropbox.com/s/nqlp7b9v64z56z8/Low.mp4?dl=0 This video demonstrates a novel approach to the resection of early gastric cancers not amenable to conventional gastroscopic approaches. Laparoscopic intragastric submucosal dissection (LISD) involves 3-port laparoscopy and intragastric port passage via gastrotomies. Stable pneumogastrium is performed and the field circumferentially marked by cautery. Submucosal colloid injection aids dissection. Tumour resection is completed by cautery and specimens removed via ports. Of 6 cases performed in Oxford, complete curative excision was confirmed histologically in 5, with 1 necessitating completion gastrectomy later confirmed to be T0 resection. No immediate or late complications were encountered. LISD is a safe and effective intervention which permits favourable access to lesions situated high on the posterior wall or lesser curvature of the stomach, enables en-block resection of large areas, and can prevent the need for gastrectomy. </jats:sec

834 ENDOSCOPIC VACUUM THERAPY IN THE MANAGEMENT OF OESOPHAGEAL PERFORATIONS AND POST-OPERATIVE LEAKS

Abstract   Oesophageal perforations and post-oesophagectomy anastomotic leaks are associated with high morbidity and mortality. Endoscopic vacuum therapy (EVT) is a novel treatment strategy with the potential to promote healing and ameliorate sepsis. Few instances of the use of EVT have been reported in the UK, wioth only two cases published outside our centre representing a limited aetiological and demographic spectrum. Methods From May 2019 to November 2020 8 patients aged 27–85 years underwent EVT for disparate oesophageal wall defects. Data regarding technical success and feasibility were analysed. Video recordings of procedures were undertaken with patient consent. Results Complete defect resolution was achieved in cases (87%), requiring median of 13 days of treatment (range 6–23), and necessitating 3 replacement procedures (range 1–4). Significant improvement in C-reactive protein was achieved in all patients undergoing treatment (P = 0.015). Over an average follow up of 360 days, no severe complications resulted directly from sponge placement, however 2 individuals (25%) developed oesophageal stricture necessitating endoscopic balloon dilatation, and one died whilst undergoing treatment. Conclusion Here we provide a video demonstration of the application of EVT in patients with oesophageal perforation or post-operative leak. Our data demonstrate this approach to be a safe, valuable tool for the management of a spectrum of oesophageal wall defects, with the potential to reduce associated morbidity and mortality in selected patients. Video Video of safe application of EVT. https://www.dropbox.com/s/rgypt6o1z93iui5/EVT.mp4?dl=0. </jats:sec