A genetic cause of Alzheimer disease: mechanistic insights from Down syndrome

Down syndrome, caused by an extra copy of chromosome 21, is associated with a greatly increased risk of early onset Alzheimer disease. It is thought that this risk is conferred by the presence of three copies of the gene encoding amyloid precursor protein (APP), an Alzheimer risk factor, although the possession of extra copies of other chromosome 21 genes may also play a role. Further study of the mechanisms underlying the development of Alzheimer disease in Down syndrome could provide insights into the mechanisms that cause dementia in the general population

Implementing the WHO Safe Childbirth Checklist: lessons from a global collaboration.

The WHO Safe Childbirth Checklist (SCC) was developed to ensure the delivery of essential maternal and perinatal care practices around the time of childbirth. A research collaboration was subsequently established to explore factors that influence use of the Checklist in a range of settings around the world. This analysis article presents an overview of the WHO SCC Collaboration and the lessons garnered from implementing the Checklist across a diverse range of settings. Project leads from each collaboration site were asked to distribute two surveys. The first was given to end users, and the second to implementation teams to describe their respective experiences using the Checklist. A total of 134 end users and 38 implementation teams responded to the surveys, from 19 countries across all levels of income. End users were willing to adopt the SCC and found it easy to use. Training and the provision of supervision while using the Checklist, alongside leadership engagement and local ownership, were important factors which helped facilitate initial implementation and successful uptake of the Checklist. Teams identified several challenges, but more importantly successfully implemented the WHO SCC. A critical step in all settings was the adaptation of the Checklist to reflect local context and national protocols and standards. These findings were invaluable in developing the final version of the WHO SCC and its associated implementation guide. Our experience will provide useful insights for any institution wishing to implement the Checklist

Sexual dysfunction following surgery for rectal cancer: a single-institution experience.

Although much focus is placed on oncological outcomes for rectal cancer, it is important to assess quality of life after surgery of which sexual function is an important component. This study set about to describe the prevalence of sexual dysfunction by resection type and gender among patients undergoing surgery for rectal cancer, usingretrospective analysis. All English-speaking living patients who underwent surgery for stage I-III rectal cancer with curative intent between 2012 and 2016 were identified from a prospectively maintained database at our institution. Eligible patients were invited to complete either the Female Sexual Function Index (FSFI) or the International Index of Erectile Function (IIEF). Primary outcomes were overall rates of sexual dysfunction, defined as more than one standard deviation below the mean of the normal population for each tool. A total of 147 patients responded, yielding a response rate of 38%. The overall sexual dysfunction rate was 70% at a median time from surgery of 38 months. Sixty-two men (62%) and 41 women (87%) reported overall scores that fell below one standard deviation of the population mean. There was no significant difference in sexual dysfunction for both male and female patients between low anterior resection, coloanal anastomosis, or abdominoperineal resection.. The present study revealed a high rate of sexual dysfunction after rectal cancer surgery, particularly in female patients. This study serves as a reminder to surgeons and their teams to openly discuss the impact of surgery on sexual function and ensure adequate consent and appropriate peri-operative management strategies. The retrospective nature of the analysis is the limitation of this study

The extent of colorectal resection and short-term outcomes in patients with ulcerative colitis.

There is limited literature on the impact of the extent of resection on short-term outcomes in patients with ulcerative colitis (UC) in an elective setting. The aim of this study was to better understand the impact of approach and extent of resection on short-term outcomes for patients undergoing total proctocolectomy (TPC) and subtotal colectomy (STC) for UC. Patients with UC who underwent elective TPC or STC were captured from the ACS-NSQIP® 2011-2018 database and divided into four cohorts: Open TPC (O-TPC), Laparoscopic TPC (L-STC), Open STC (O-STC), and Laparoscopic STC (L-STC). Baseline and perioperative variables were compared between the four groups alongside 30-day mortality and 30-day complication rates. Of 3387 patients, 368 (10.9%) underwent O-STC, 406 (12%) underwent O-TPC, 1958 (58%) underwent L-STC, and 655 (19%) underwent L-TPC. Overall rate of prolonged length of stay (LOS) was 27% and 9% needed a blood transfusion. There was no difference in the risk of complications between open TPC and open STC. Those who had open surgery had a higher risk of complications and prolonged LOS. Patients who had L-TPC had prolonged LOS compared to patients who had L-STC, but less compared to those who had O-STC. Elective surgery for UC is associated with high rates of prolonged LOS and blood transfusion despite MIS approaches. Short-term outcomes and LOS are more impacted by the operative approach than the extent of resection. Despite this laparoscopic TPC has higher rates of prolonged LOS when compared to laparoscopic STC

Re-resection of Microscopically Positive Margins Found on Intra-Operative Frozen Section Analysis Does Not Result in a Survival Benefit in Patients Undergoing Surgery and Intraoperative Radiation Therapy for Locally Recurrent Rectal Cancer.

Intraoperative frozen section analysis provides real-time margin resection status which can guide intraoperative decisions made by the surgeon and radiation oncologist. For patients with locally recurrent rectal cancer undergoing surgery and intraoperative radiation therapy, intraoperative re-resection of positive margins to achieve negative margins is common practice. To assess if re-resection of positive margins found on intraoperative frozen section analysis improves oncological outcomes. This is a retrospective cohort study. This study was an analysis of a prospectively maintained multicenter database. All patients who underwent surgical resection of locally recurrent rectal cancer with intraoperative radiation therapy between 2000 and 2015 were included and followed for 5 years. Three groups were compared: initial R0 resection (IR0), initial R1 converted to R0 after re-resection (IR1-R0) and initial R1 that remained R1 after re-resection (IR1-R1). Grossly positive margin resections (R2) were excluded. The primary outcome measures were 5-year overall survival, recurrence-free survival, and local re-recurrence. A total of 267 patients were analyzed (initial R0 resection n=94, initial R1 converted to R0 after re-resection n=95, initial R1 that remained R1 after re-resection n=78). Overall survival was 4.4 years for initial R0 resection, 2.7 years for initial R1 converted to R0 after re-resection and 2.9 years for initial R1 that remained R1 after re-resection (p=0.01). Recurrence free survival was 3.0 years for initial R0 resection and 1.8 years for both initial R1 converted to R0 after re-resection and initial R1 that remained R1 after re-resection (p<=0.01). Overall survival did not differ for patients with R1 and re-resection R1 or R0 (p=0.62). Recurrence-free survival and freedom from local re-recurrence did not differ between groups. Heterogeneous patient population, restricted to those receiving intraoperative radiation therapy. Re-resection of microscopically positive margins to obtain R0 status does not appear to provide a significant survival advantage or prevent local re-recurrence in patients undergoing surgery and intraoperative radiation therapy for locally recurrent rectal cancer. See Video Abstract at http://links.lww.com/DCR/B886