The Impact of Indocyanine Green Fluorescence Angiography on Intraoperative Decision Making in Right Hemicolectomy: A Case-Control Study.

INTRODUCTION: Anastomotic leak (AL) after right hemicolectomy remains a significant clinical challenge with an incidence of 4.2% to 8.2% in European series. Near infrared imaging with indocyanine green (NIR-ICG) allows real-time assessment of bowel perfusion. However, there is a lack of published data assessing the clinical utility of this new technology in right sided colonic resection. MATERIALS AND METHODS: Data from electronic records were retrospectively analyzed for consecutive patients undergoing right hemicolectomy in a single center between March 1, 2016 and October 31, 2019. Primary outcomes were the incidence of AL and the frequency with which ICG-NIR imaging altered the intraoperative course. RESULTS: Our study included 127 patients, with 65 in the NIR-ICG group and 62 in the control group. Median length of follow-up was 24 months. There was no significant difference in demographic or pathologic characteristics between the 2 cohorts. There was no significant difference in operation length between the NIR-ICG and control groups (164.7 vs. 162.9 min, P=0.88). The use of NIR-ICG altered the intraoperative course in 4/65 (6.2%) patients. The rate of AL was lower in the NIR-ICG group (1.5% vs. 4.8%), although this did not reach statistical significance. CONCLUSION: The use of NIR-ICG altered the intraoperative course for notable subset of patients undergoing right hemicolectomy without prolonging operative time. Larger prospective studies are required to evaluate the potential for the routine use of this technology to reduce AL rate in right hemicolectomy.

Evaluating outcomes following emergency laparotomy in the North of England and the impact of the National Emergency Laparotomy Audit - A retrospective cohort study.

BACKGROUND: Emergency laparotomy is associated with high morbidity and mortality. Current trends suggest improvements have been made in recent years, with increased survival and shorter lengths of stay in hospital. The National Emergency Laparotomy Audit (NELA) has evaluated participating hospitals in England and Wales and their individual outcomes since 2013. This study aims to establish temporal trends for patients undergoing emergency laparotomy and evaluate the influence of NELA. METHODS: Data for emergency laparotomies admitted to NHS hospitals in the Northern Deanery between 2001 and 2016 were collected, including demographics, co-morbidities, diagnoses, operations undertaken and outcomes. The primary outcome of interest was in-hospital death within 30 days of admission. Cox-regression analysis was undertaken with adjustment for covariates. RESULTS: There were 2828 in-hospital deaths from 24,291 laparotomies within 30 days of admission (11.6%). Overall 30-day mortality significantly reduced during the 15-year period studied from 16.3% (2001-04), to 8.1% during 2013-16 (p < 0.001). After multivariate adjustment, laparotomies undertaken in more recent years were associated with a lower mortality risk compared to earlier years (2013-16: HR 0.73, p < 0.001). There was a significant improvement in 30-day postoperative mortality year-on-year during the NELA period (from 9.1 to 7.1%, p = 0.039). However, there was no difference in postoperative mortality for patients who underwent laparotomy during NELA (2013-16) compared with the preceding three years (both 8.1%, p = 0.526). DISCUSSION: 30 day postoperative mortality for emergency laparotomy has improved over the past 15-years, with significantly reduced mortality risk in recent years. However, it is unclear if NELA has yet had a measurable effect on 30-day post-operative mortality.

Evaluating the effects of surgical subspecialisation on patient outcomes following emergency laparotomy: A retrospective cohort study.

BACKGROUND: General surgeons have become increasingly subspecialised in their elective practice. Emergency laparotomies, however, are performed by a range of subspecialists who may or may not have an interest in the affected area of gastrointestinal tract. This retrospective cohort study evaluates the impact of surgical subspecialisation on patient outcomes following emergency laparotomy. METHODS: Data was collected for patients who underwent an emergency abdominal procedure on the gastrointestinal tract in the North of England from 2001 to 2016. This included demographics, co-morbidities, diagnoses and procedures undertaken. Patients were grouped according to consultants' subspecialist interest. The primary outcome of interest was 30-day postoperative mortality. RESULTS: 24,291 emergency laparotomies were performed with an associated 30-day postoperative mortality of 11.7%. Laparotomies undertaken by upper gastrointestinal (UGI) or colorectal surgeons have significantly lower mortality (10.1%) when compared with other subspecialities (13.5%). More specifically, mortality was decreased for UGI (7.9% vs. 12.9%) and colorectal procedures (10.9% vs. 14.2%) when performed by surgeons with a specialist interest in the relevant area of the gastrointestinal tract (both p < 0.001). The utilisation of laparoscopic surgery is higher, in both UGI (21.8% vs. 9.0%) and colorectal procedures (7.2% vs. 3.5%), when the causative pathology is relevant to the surgeon's subspeciality (both p < 0.001). CONCLUSION: Mortality following emergency laparotomy is improved when performed under the care of gastrointestinal surgeons. Both UGI and colorectal emergency procedures have improved outcomes, with lower mortality and higher rates of laparoscopy, when under the care of a surgeon with a subspecialist interest in the affected area of the gastrointestinal tract.

Use of Flutemetamol F 18-Labeled Positron Emission Tomography and Other Biomarkers to Assess Risk of Clinical Progression in Patients With Amnestic Mild Cognitive Impairment.

Importance: Patients with amnestic mild cognitive impairment (aMCI) may progress to clinical Alzheimer disease (AD), remain stable, or revert to normal. Earlier progression to AD among patients who were ß-amyloid positive vs those who were ß-amyloid negative has been previously observed. Current research now accepts that a combination of biomarkers could provide greater refinement in the assessment of risk for clinical progression. Objective: To evaluate the ability of flutemetamol F 18 and other biomarkers to assess the risk of progression from aMCI to probable AD. Design, Setting, and Participants: In this multicenter cohort study, from November 11, 2009, to January 16, 2014, patients with aMCI underwent positron emission tomography (PET) at baseline followed by local clinical assessments every 6 months for up to 3 years. Patients with aMCI (365 screened; 232 were eligible) were recruited from 28 clinical centers in Europe and the United States. Physicians remained strictly blinded to the results of PET, and the standard of truth was an independent clinical adjudication committee that confirmed or refuted local assessments. Flutemetamol F 18-labeled PET scans were read centrally as either negative or positive by 5 blinded readers with no knowledge of clinical status. Statistical analysis was conducted from February 19, 2014, to January 26, 2018. Interventions: Flutemetamol F 18-labeled PET at baseline followed by up to 6 clinical visits every 6 months, as well as magnetic resonance imaging and multiple cognitive measures. Main Outcomes and Measures: Time from PET to probable AD or last follow-up was plotted as a Kaplan-Meier survival curve; PET scan results, age, hippocampal volume, and aMCI stage were entered into Cox proportional hazards logistic regression analyses to identify variables associated with progression to probable AD. Results: Of 232 patients with aMCI (118 women and 114 men; mean [SD] age, 71.1 [8.6] years), 98 (42.2%) had positive results detected on PET scan. By 36 months, the rates of progression to probable AD were 36.2% overall (81 of 224 patients), 53.6% (52 of 97) for patients with positive results detected on PET scan, and 22.8% (29 of 127) for patients with negative results detected on PET scan. Hazard ratios for association with progression were 2.51 (95% CI, 1.57-3.99; P < .001) for a positive ß-amyloid scan alone (primary outcome measure), 5.60 (95% CI, 3.14-9.98; P < .001) with additional low hippocampal volume, and 8.45 (95% CI, 4.40-16.24; P < .001) when poorer cognitive status was added to the model. Conclusions and Relevance: A combination of positive results of flutemetamol F 18-labeled PET, low hippocampal volume, and cognitive status corresponded with a high probability of risk of progression from aMCI to probable AD within 36 months.

The novel appearance of low rectal anastomosis on contrast enema following laparoscopic anterior resection: discriminating anastomotic leaks from "dog-ears" on water-soluble contrast enema and flexible sigmoidoscopy.

PURPOSE: Interpretation of water-soluble contrast enema following laparoscopic low anterior resection can be very challenging for both radiologists and colorectal surgeons. Discriminating the radiological appearances secondary to anastomotic configuration from those caused by actual anastomotic dehiscence is a common problem and may be made worse with the advent of laparoscopic surgery. The aim of this study is to identify potential novel appearances of the water-soluble contrast enema (WSCE) images of rectal anastomosis following laparoscopic low anterior resection to radiologists and surgeons. METHODS: We enrolled 45 patients who underwent laparoscopic low anterior resection with proximal de-functioning loop ileostomy within a specialized colorectal unit. The water-soluble contrast enema reports were reviewed. Two blinded colorectal radiologists independently reviewed the images of patients suspected of anastomotic leak. All of these patients also underwent a flexible sigmoidoscopy to confirm or exclude anastomotic leak before reversal of loop ileostomy. Inter-observer concordance was calculated. RESULTS: Seven out of eighteen patients (38.9%) were found to have true anastomotic leaks on flexible sigmoidoscopy (15% overall leak rate). In the remaining eleven patients the image appearances were attributed to the appearance of the anastomotic 'dog-ear effect', created by the anastomotic configuration due to multiple firing of the intra-corporeal laparoscopic stapling device. Radiologist inter-observer concordance was 83%. Sensitivity was 100%, specificity 71%, positive-predictive value (38.9%) and negative-predictive value (100%). CONCLUSIONS: The novel appearances of laparoscopic-stapled rectal anastomoses in WSCE can be mistaken for anastomotic leak. To avoid delay in reversal of ileostomy, a flexible sigmoidoscopy can be used to confirm or exclude a leak.

Protocol for a multicentre, prospective, observational cohort study of variation in practice in perioperative analgesic strategies in elective laparoscopic colorectal surgery: the LapCoGesic Study.

INTRODUCTION: Laparoscopic surgery combined with enhanced recovery programmes has become the gold standard in the elective management of colorectal disease. However, there is no consensus with regard to the optimal perioperative analgesic regime in this cohort of patients, with a number of options available, including thoracic epidural spinal analgesia, patient-controlled analgesia, subcutaneous and/or intraperitoneal local anaesthetics, local anaesthetic wound infiltration catheters and transversus abdominis plane blocks. This study aims to explore any differences in analgesic strategies employed across the North East of England and to assess whether any variation in practice has an impact on clinical outcomes. METHODS AND ANALYSIS: All North East Colorectal units will be recruited for participation by the Northern Surgical Trainees Research Association (NoSTRA). Data will be collected over a consecutive 2-month period. Outcome measures will include postoperative pain score, postoperative opioid analgesic use and side effects, length of stay, 30-day complication rates, 30-day reoperative rates and 30-day readmission rates. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the National Research Ethics Service. The protocol will be disseminated through NoSTRA. Individual unit data will be presented at local meetings. Overall collective data will be published in peer-reviewed journals and presented at relevant surgical meetings.

Protecting patient privacy when sharing patient-level data from clinical trials.

BACKGROUND: Greater transparency and, in particular, sharing of patient-level data for further scientific research is an increasingly important topic for the pharmaceutical industry and other organisations who sponsor and conduct clinical trials as well as generally in the interests of patients participating in studies. A concern remains, however, over how to appropriately prepare and share clinical trial data with third party researchers, whilst maintaining patient confidentiality. Clinical trial datasets contain very detailed information on each participant. Risk to patient privacy can be mitigated by data reduction techniques. However, retention of data utility is important in order to allow meaningful scientific research. In addition, for clinical trial data, an excessive application of such techniques may pose a public health risk if misleading results are produced. After considering existing guidance, this article makes recommendations with the aim of promoting an approach that balances data utility and privacy risk and is applicable across clinical trial data holders. DISCUSSION: Our key recommendations are as follows: 1. Data anonymisation/de-identification: Data holders are responsible for generating de-identified datasets which are intended to offer increased protection for patient privacy through masking or generalisation of direct and some indirect identifiers. 2. Controlled access to data, including use of a data sharing agreement: A legally binding data sharing agreement should be in place, including agreements not to download or further share data and not to attempt to seek to identify patients. Appropriate levels of security should be used for transferring data or providing access; one solution is use of a secure 'locked box' system which provides additional safeguards. This article provides recommendations on best practices to de-identify/anonymise clinical trial data for sharing with third-party researchers, as well as controlled access to data and data sharing agreements. The recommendations are applicable to all clinical trial data holders. Further work will be needed to identify and evaluate competing possibilities as regulations, attitudes to risk and technologies evolve.

A 15-year retrospective analysis of the epidemiology and outcomes for elderly emergency general surgical admissions in the North East of England: A case for multidisciplinary geriatric input.

INTRODUCTION: Life expectancies in the UK are increasing and with this there is an increasing elderly population with more complex co-morbidity. Emergency surgery in the elderly is challenging in terms of decision making, managing co-morbidity and post-operative rehabilitation with high morbidity and mortality. To optimise service design and development, it is important to understand the changing pattern of emergency surgical care for this group. METHODS: After obtaining necessary approvals, we approached each hospital trust in the North of England for details of every emergency admission under a general surgeon from 2000 to 2014. Data for each admission included demographics, co-morbidities, diagnoses, procedures undertaken and outcomes. RESULTS: There were 105 002 elderly (≥70 years) emergency general surgical admissions, and mean age and co-morbidity (defined by Charlson index scores) increased (both p < 0.001). Operative intervention was undertaken in a similar proportion of patients in all age groups (13%), with more patients undergoing operations over time (p < 0.001), of which 50% were within 48 h of admission. Overall in-hospital mortality decreased significantly as did length of hospital stay (both p < 0.001). Factors associated with increased 30 day in-hospital mortality were increasing age and Charlson score, admissions directly from clinic, operations undertaken at the weekend and patients admitted earlier in the study period. CONCLUSION: The workload of emergency general surgery in the elderly is becoming more complex. This challenge is already being addressed with improvements in outcomes. The data presented here reinforces the need for new models of care with increased multidisciplinary geriatric care input into elderly surgical patient care in the perioperative period.

A double-blind randomized placebo-controlled withdrawal trial comparing memantine and antipsychotics for the long-term treatment of function and neuropsychiatric symptoms in people with Alzheimer's disease (MAIN-AD).

BACKGROUND: Neuropsychiatric symptoms in Alzheimer disease (AD) cause significant distress and present a complex clinical challenge for treatment. Pharmacological treatment options are limited to antipsychotics, which carry extensive safety issues. There is emerging evidence to support the potential benefits of memantine, currently licensed for moderate to severe AD, in the prophylaxis of neuropsychiatric symptoms. METHODS: The MAIN-AD study is a double-blind randomized placebo-controlled withdrawal trial comparing memantine with antipsychotics for the treatment of neuropsychiatric symptoms over 24 weeks. A total of 199 people with probable AD living in care homes already receiving an antipsychotic were randomized to receive either memantine or to continue an antipsychotic. The primary outcomes were function (Bristol Activities of Daily Living Scale [BADLS]) and agitation (Cohen-Mansfield Agitation Inventory [CMAI]). Secondary outcomes were Neuropsychiatric Inventory (NPI), Mini-Mental State Examination (MMSE), and mortality. RESULTS: There was no significant difference between groups on the BADLS or CMAI. At 24 weeks, there was a nonsignificant adjusted difference in favor of memantine on the BADLS of 0.23 (95% CI -1.80-2.27; P = .82) and in favor of antipsychotic on the CMAI of 0.09 (95% CI -0.35-8.53; P = .07). Although there were no significant differences in total NPI, there were 5.01 (95% CI -1.68-11.70; P = .05) and 3.63 (95% CI -1.40-8.67; P = .16) point advantages favoring antipsychotics at weeks 12 and 24, respectively. In addition, in an exploratory analysis, individuals allocated to antipsychotics were significantly less likely to experience relapse of neuropsychiatric symptoms at all time points. The group receiving memantine had a nonsignificant 1.3-point advantage on the MMSE at 24 weeks. DISCUSSION: This study indicates no benefits for memantine in the long-term treatment and prophylaxis of clinically significant neuropsychiatric symptoms. The results did indicate some benefits for antipsychotic medications in reducing the relapse of neuropsychiatric symptoms, but this must be balanced against increased mortality risk.