A development study of drain fluid gastrografin as a biomarker of anastomotic leak

Purpose@#Anastomotic leakage (AL) is the anathema of colorectal surgery. Its occurrence leads to increased morbidity and mortality and a prolonged hospital stay. Much work has gone into studying various biomarkers in drain fluid to facilitate early detection of AL. This stage 2a development study aims to assess the safety and feasibility of reliably detecting the iodine in Gastrografin (GG; Bayer Australia Ltd.) in drain fluid and stool samples by dual-energy computed tomography (DECT). @*Methods@#This is a prospective, observational, controlled, consecutive cohort study establishing the safety and feasibility of the detection of GG in surgical drain fluid and stool as a biomarker of AL when patients with a low pelvic colorectal anastomosis undergo luminal flushing of the rectal tube with GG. @*Results@#Ten consecutive patients were allocated to the saline flush group and the following 10 to the GG flush group. Three patients in the saline flush group developed an AL. One patient in the GG flush group developed an AL. An elevation in the drain fluid GG was detected using DECT on the day of clinical deterioration. None of the patients in the control group were found to have a positive result on DECT. @*Conclusion@#This study demonstrates the safety of a novel approach to the early detection of AL from extraperitoneal colorectal anastomoses. The technique requires validation in a larger cohort and a multicenter study is planned to investigate the efficacy of GG rectal tube flushes as an early biomarker of AL in low pelvic anastomoses.

Intelligent Resolution: Integrating Cryo-EM with AI-driven Multi-resolution Simulations to Observe the SARS-CoV-2 Replication-Transcription Machinery in Action

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) replication transcription complex (RTC) is a multi-domain protein responsible for replicating and transcribing the viral mRNA inside a human cell. Attacking RTC function with pharmaceutical compounds is a pathway to treating COVID-19. Conventional tools, e.g., cryo-electron microscopy and all-atom molecular dynamics (AAMD), do not provide sufficiently high resolution or timescale to capture important dynamics of this molecular machine. Consequently, we develop an innovative workflow that bridges the gap between these resolutions, using mesoscale fluctuating finite element analysis (FFEA) continuum simulations and a hierarchy of AI-methods that continually learn and infer features for maintaining consistency between AAMD and FFEA simulations. We leverage a multi-site distributed workflow manager to orchestrate AI, FFEA, and AAMD jobs, providing optimal resource utilization across HPC centers. Our study provides unprecedented access to study the SARS-CoV-2 RTC machinery, while providing general capability for AI-enabled multi-resolution simulations at scale.

Ileal Pouch-Anal Anastomosis for Ulcerative Colitis: An Australian Institution’s Experience

Purpose@#We report outcomes and evaluate patient factors and the impact of surgical evolution on outcomes in consecutive ulcerative colitis patients who had restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) at an Australian institution over 26 years. @*Methods@#Data including clinical characteristics, preoperative medical therapy, and surgical outcomes were collected. We divided eligible patients into 3 period arms (period 1, 1990 to 1999; period 2, 2000 to 2009; period 3, 2010 to 2016). Outcomes of interest were IPAA leak and pouch failure. @*Results@#A total of 212 patients were included. Median follow-up was 50 (interquartile range, 17 to 120) months. Rates of early and late complications were 34.9% and 52.0%, respectively. Early complications included wound infection (9.4%), pelvic sepsis (8.0%), and small bowel obstruction (6.6%) while late complications included small bowel obstruction (18.9%), anal stenosis (16.8%), and pouch fistula (13.3%). Overall, IPAA leak rate was 6.1% and pouch failure rate was 4.8%. Eighty-three patients (42.3%) experienced pouchitis. Over time, we observed an increase in patient exposure to thiopurine (P=0.0025), cyclosporin (P=0.0002), and anti-tumor necrosis factor (P<0.00001) coupled with a shift to laparoscopic technique (P<0.00001), stapled IPAA (P<0.00001), J pouch configuration (P<0.00001), a modified 2-stage procedure (P=0.00012), and a decline in defunctioning ileostomy rate at time of IPAA (P=0.00002). Apart from pouchitis, there was no significant difference in surgical and chronic inflammatory pouch outcomes with time. @*Conclusion@#Despite greater patient exposure to immunomodulatory and biologic therapy before surgery coupled with a significant change in surgical techniques, surgical and chronic inflammatory pouch outcome rates have remained stable.

Geographical Variation in the Use of Diverting Loop Ileostomy in Australia and New Zealand Colorectal Surgeons

Purpose@#Anastomotic leak (AL) after a low pelvic anastomosis is a devastating complication, with short- and long-term morbidity and increased mortality. Surgeons may employ various adjuncts in an attempt to reduce AL rates or mitigate their impact. These include the use of temporary diverting ileostomy (TDI), transanal or rectal tubes and pelvic drains. This questionnaire evaluates the preferences and routine use of these adjuncts in Australasian colorectal surgeons. @*Methods@#A cross-sectional survey was administered to Australian and New Zealand colorectal surgeons on September 20, 2018. The study survey consisted of 15 questions exploring basic demographics and the number of rectal resections and ileal pouches performed in 12 months, along with the surgeon’s preference for the use of diverting stomas, rectal tubes, and pelvic drains. @*Results@#There were 90 respondents to the survey (31.6%). Surgeons in Western Australia (71.4%) were more likely to use a mandatory TDI in colorectal extraperitoneal anastomoses than surgeons in Queensland (14.3%). South Australian surgeons are more likely to employ a mandatory TDI (100%) for ileal pouches than Queensland surgeons (42.9%). Rectal tubes are not commonly utilized (40.0% never use them), and pelvic drains are (45.6% in all cases). Surgeons consider a median AL rate of 15% was felt to justify the use of a TDI in low pelvic anastomoses and a median AL rate of 10% for ileal pouches @*Conclusion@#There is considerable geographical variation in colorectal surgical practice throughout Australia and New Zealand. While surgeons interrogate the same literature, there are presumably other factors that see translation into variations in clinical practice.