ABSTRACT
BACKGROUND: This targeted chart review study reports the first ever detailed global account of clinical approaches adopted to detect and manage anastomotic leaks identified during surgery in routine clinical practice. METHOD: 156 surgeons from eight countries retrospectively extracted data from surgical records of 458 patients who underwent colorectal surgery with an identified intraoperative leak at the circular anastomosis. Demographic details, procedures, and outcomes were analyzed descriptively, by country. RESULTS: Most surgeries were performed laparoscopically (57.6%), followed by open surgeries (35.8%). The burden of intraoperative leaks on the healthcare system is driven in large part by the additional interventions such as using a sealant, recreating the anastomosis, and diverting the anastomosis to a colostomy bag, undertaken to manage the leak. The mean duration of hospitalization was 19.9 days. Postoperative anastomotic leaks occurred in 62 patients (13.5%), most frequently 4 to 7 days after surgery. Overall, country-specific differences were observed in patient characteristics, surgical procedures, method of diagnosis of intraoperative leak, interventions, and length of hospital stay. CONCLUSION: The potential cost of time and material needed to repair intraoperative leaks during surgery is substantial and often hidden to the healthcare system, potentially leading to an underestimation of the impact of this complication.
ABSTRACT
The 2.0 A crystal structure of the N6-adenine DNA methyltransferase M.TaqI in complex with specific DNA and a nonreactive cofactor analog reveals a previously unrecognized stabilization of the extrahelical target base. To catalyze the transfer of the methyl group from the cofactor S-adenosyl-l-methionine to the 6-amino group of adenine within the double-stranded DNA sequence 5'-TCGA-3', the target nucleoside is rotated out of the DNA helix. Stabilization of the extrahelical conformation is achieved by DNA compression perpendicular to the DNA helix axis at the target base pair position and relocation of the partner base thymine in an interstrand pi-stacked position, where it would sterically overlap with an innerhelical target adenine. The extrahelical target adenine is specifically recognized in the active site, and the 6-amino group of adenine donates two hydrogen bonds to Asn 105 and Pro 106, which both belong to the conserved catalytic motif IV of N6-adenine DNA methyltransferases. These hydrogen bonds appear to increase the partial negative charge of the N6 atom of adenine and activate it for direct nucleophilic attack on the methyl group of the cofactor.
