Ethical, legal, and social issues in the Earth BioGenome Project.

The Earth BioGenome Project (EBP) is an audacious endeavor to obtain whole-genome sequences of representatives from all eukaryotic species on Earth. In addition to the project's technical and organizational challenges, it also faces complicated ethical, legal, and social issues. This paper, from members of the EBP's Ethical, Legal, and Social Issues (ELSI) Committee, catalogs these ELSI concerns arising from EBP. These include legal issues, such as sample collection and permitting; the applicability of international treaties, such as the Convention on Biological Diversity and the Nagoya Protocol; intellectual property; sample accessioning; and biosecurity and ethical issues, such as sampling from the territories of Indigenous peoples and local communities, the protection of endangered species, and cross-border collections, among several others. We also comment on the intersection of digital sequence information and data rights. More broadly, this list of ethical, legal, and social issues for large-scale genomic sequencing projects may be useful in the consideration of ethical frameworks for future projects. While we do not-and cannot-provide simple, overarching solutions for all the issues raised here, we conclude our perspective by beginning to chart a path forward for EBP's work.

C-reactive protein can predict anastomotic leak in colorectal surgery: a systematic review and meta-analysis.

BACKGROUND: Anastomotic leakage (AL) is one of the most significant complications after colorectal surgery, affecting length of stay, patient morbidity, mortality, and long-term oncological outcome. Serum C-reactive protein (CRP) level rises in infective and inflammatory states. Elevated CRP has been shown to be associated with anastomotic leak. OBJECTIVE: Perform a meta-analysis of current CRP data in AL after colorectal surgery. DATA SOURCES: MEDLINE, EMBASE, CINAHL, CENTRAL databases STUDY SELECTION: Comparative studies studying serum CRP levels in adult patients with and without AL after colorectal surgery. INTERVENTION(S): Elective and emergency open, laparoscopic or robotic colorectal excisions for cancer and benign pathology. MAIN OUTCOME MEASURES: Mean serum CRP measurements between post-operative days (POD) 1 through 7 in patients with and without AL. Perform ROC analysis to determine cut-off CRP values to indicate AL. RESULTS: Twenty-three studies with 6647 patients (482 AL). Pooled mean time to diagnosis of AL was 7.70 days. AL associated with higher CRP on POD1 (mean difference (MD) 15.19, 95% CI 5.88-24.50, p = 0.001), POD2 (MD 51.98, 05% CI 37.36-66.60, p < 0.00001), POD3 (MD 96.92, 95% CI 67.96-125.89, p < 0.00001), POD4 (MD 93.15, 95% CI 69.47-116.84, p < 0.00001), POD5 (MD 112.10, 95% CI 89.74-134.45, p < 0.00001), POD6 (MD 98.38, 95% CI 80.29-116.46, p < 0.00001), and POD7 (MD 106.41, 95% CI 75.48-137.35, p < 0.00001) compared with no AL. ROC analysis identified a cut-off CRP of 148 mg/l on POD3 with sensitivity and specificity of 95%. On POD4 through POD7, cut-off levels were 123 mg/l, 115 mg/l, 105 mg/l, and 96 mg/l, respectively, with sensitivity and specificity of 100%. LIMITATIONS: Study heterogeneity, some characteristics unreported, no RCT CONCLUSIONS: AL is associated with higher CRP levels on each post-operative day compared to no AL after colorectal surgery. The cut-off CRP values can be used to predict AL to expedite investigation and treatment.

Meta-analysis of transanal total mesorectal excision versus laparoscopic total mesorectal excision in management of rectal cancer.

OBJECTIVES: To evaluate comparative outcomes of transanal total mesorectal excision (TaTME) and laparoscopic TME (LaTME) in patients with rectal cancer. METHODS: We systematically searched multiple databases and bibliographic reference lists. A combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators, and limits were applied. Overall intraoperative complications, overall postoperative complications, anastomotic leak, surgical site infections (SSIs), completeness of mesorectal excision, R0 resection, distal (DRM) and circumferential resection margin (CRM), number of harvested lymph nodes, and procedure time were the evaluated outcome parameters. RESULTS: We identified 18 comparative studies reporting a total of 2048 patients evaluating outcomes of TaTME (n = 1000) and LaTME (n = 1048) in patients with rectal cancer. TaTME was associated with significantly higher number of R0 resection (OR 1.67, P = 0.01) and harvested lymph nodes (MD 1.08, P = 0.01), and lower rate of positive CRM (OR 0.67, P = 0.04) and conversion to an open procedure (OR 0.17, P < 0.00001) compared with LaTME. However, there was no significant difference in intraoperative complications (OR 1.18, P = 0.54), postoperative complications (OR 0.89, P = 0.24), anastomotic leak (OR 0.88, P = 0.42), SSIs (OR 0.64, P = 0.26), completeness of mesorectal excision (OR 1.43, P = 0.19), DRM (MD 1.87, P = 0.16), CRM (MD 0.36, P = 0.58), and procedure time (MD - 10.87, P = 0.18) between TaTME and LaTME. Moreover, for low rectal tumours, TaTME was associated with significantly lower rate of anastomotic leak and higher number of lymph nodes (MD 2.06, P = 0.002). CONCLUSIONS: Although the meta-analysis of best available evidence (level 2) demonstrated that TaTME may be associated with better short-term oncological outcomes and similar clinical outcomes compared with LaTME, the differences between the two groups were small questioning their clinical relevance. No solid conclusions can be made due to lack of high quality randomised studies.

User innovation: a novel framework for studying animal innovation within a comparative context.

Much work has been dedicated to defining and describing animal innovation. Despite this, efforts to compare human and animal innovation have been hindered by perceived fundamental differences between how, and why, humans and animals innovate. Furthermore, there is not a useful framework for comparisons across different taxa. Here, we provide an overview of the current understanding of human 'user' innovation, provide some examples of user innovation, and highlight the parallels between animal innovation and user innovation by humans. User innovation, put simply, is the process by which people invent to satisfy their own needs, not necessarily with the aim of distributing their invention, or marketing it for profit. Thus, it is much more closely aligned to the manner in which nonhuman animals innovate. Our intention is that this discussion will help to re-frame how we consider animal innovation and foster more direct comparisons between human and animal innovation, while propagating new avenues for research, both experimental and observational.

Meta-analysis of medial-to-lateral versus lateral-to-medial colorectal mobilisation during laparoscopic colorectal surgery.

OBJECTIVES: To evaluate comparative outcomes of medial-to-lateral and lateral-to-medial colorectal mobilisation in patients undergoing laparoscopic colorectal surgery. METHODS: We conducted a systematic search of electronic databases and bibliographic reference lists. Perioperative mortality and morbidity, procedure time, length of hospital stay, rate of conversion to open procedure, and number of harvested lymph nodes were the outcome parameters. Combined overall effect sizes were calculated using fixed-effects or random-effects models. RESULTS: We identified eight comparative studies reporting a total of 1477 patients evaluating outcomes of medial-to-lateral (n = 626) and lateral-to-medial (n = 851) approaches in laparoscopic colorectal resection. The medial-to-lateral approach was associated with significantly lower rate of conversion to open (odds ratio (OR) 0.43, P = 0.001), shorter procedure time (mean difference (MD) - 32.25, P = 0.003) and length of hospital stay (MD - 1.54, P = 0.02) compared to the lateral-to-medial approach. However, there was no significant difference in mortality (risk difference (RD) 0.00, P = 0.96), overall complications (OR 0.78, P = 0.11), wound infection (OR 0.84, P = 0.60), anastomotic leak (OR 0.70, P = 0.26), bleeding (OR 0.60, P = 0.50), and number of harvested lymph nodes (MD - 1.54, P = 0.02) between two groups. Sub-group analysis demonstrated that the lateral-to-medial approach may harvest more lymph nodes in left-sided colectomy (MD - 1.29, P = 0.0009). The sensitivity analysis showed that overall complications were lower in the medial-to-lateral group (OR 0.72, P = 0.49). CONCLUSIONS: Our meta-analysis (level 2 evidence) showed that medial-to-lateral approach during laparoscopic colorectal resection may reduce procedure time, length of hospital stay and conversion to open procedure rate. Moreover, it may probably reduce overall perioperative morbidity. However, both approaches carry similar risk of mortality, and have comparable ability to harvest lymph nodes. Future high-quality randomised trials are required.

Meta-analysis of temporary loop ileostomy closure during or after adjuvant chemotherapy following rectal cancer resection: the dilemma remains.

OBJECTIVE: To evaluate comparative outcomes of temporary loop ileostomy closure during or after adjuvant chemotherapy following rectal cancer resection. METHODS: We systematic searched MEDLINE, EMBASE, CINAHL, CENTRAL, the World Health Organization International Clinical Trials Registry, ClinicalTrials.gov , ISRCTN Register and bibliographic reference lists. Overall perioperative complications, anastomotic leak, surgical site infection, ileus and length of hospital stay were the evaluated outcome parameters. Combined overall effect sizes were calculated using fixed effects or random effects models. RESULTS: We identified 4 studies reporting a total of 436 patients comparing outcomes of temporary loop ileostomy closure during (n = 185) or after (n = 251) adjuvant chemotherapy following colorectal cancer resection. There was no significant difference in overall perioperative complications (OR 1.39; 95% CI 0.82-2.36, p = 0.22), anastomotic leak (OR 2.80; 95% CI 0.47-16.56, p = 0.26), surgical site infection (OR 1.97; 95% CI 0.80-4.90, p = 0.14), ileus (OR 1.22; 95% CI 0.50-2.96, p = 0.66) or length of hospital stay (MD 0.02; 95% CI - 0.85-0.89, p = 0.97) between two groups. Between-study heterogeneity was low in all analyses. CONCLUSIONS: The meta-analysis of the best, albeit limited, available evidence suggests that temporary loop ileostomy closure during adjuvant chemotherapy following rectal cancer resection may be associated with comparable outcomes to the closure of ileostomy after adjuvant chemotherapy. We encourage future research to concentrate on the completeness of chemotherapy and quality of life which can determine the appropriateness of either approach.

Has integrated 18F FDG PET/CT improved staging, reduced early recurrence or increased survival in oesophageal cancer?

BACKGROUND: Survival in oesophageal cancer remains poor with high post-operative recurrence rates. PET/CT was introduced to the Three-Counties Cancer Network (3CCN) in 2006 to detect 'occult' metastatic disease not seen with conventional staging modalities. This study aims to determine whether the introduction of Integrated fluorodeoxyglucose (18F) Positron Emission Tomography (PET/CT) has changed the management, improved survival or reduced the rate of early post-operative recurrence in patients with operable oesophageal cancer. METHODS: A retrospective review was undertaken of all patients diagnosed with oesophageal cancer in the 3CCN from 2005 to 2009. Early recurrence was defined as proven recurrence locally or at a distant site within one year of resection. RESULTS: 725 patients were identified. 200 (27.6%) patients underwent staging PET/CT. PET/CT altered treatment intent in 19 (9.5%) patients. 128 (17.7%) patients underwent oesophageal resection, 90 (70.3%) of which had a staging PET/CT. No significant difference was noted in post-operative mortality (4.4% Vs 5.3%, p = 0.8) or early recurrence where PET/CT was performed when adjusted for age, sex, stage or neo-adjuvant chemotherapy (p = 0.761, OR 1.136[95% CI 0.499-2.585]). PET/CT had no significant effect on survival (log-rank test; Chi-square 0.710, p = 0.4). CONCLUSION: PET/CT has improved the accuracy of oesophageal cancer staging avoiding potentially unnecessary surgery. Ultimately however, its use has had no effect on early recurrence or survival rates. Inaccurate identification of occult metastatic disease prior to the introduction of staging PET/CT does not appear to be the primary cause of early recurrence in patients with oesophageal cancer.

The impact of timing of cholecystectomy following gallstone pancreatitis.

INTRODUCTION: Current guidelines for the management of acute gallstone pancreatitis recommend cholecystectomy as definitive treatment during primary admission or within 2 weeks of discharge, with the aim of preventing recurrent pancreatitis. However, cholecystectomy during the inflammatory phase may increase surgical complication rates. This study aimed to determine whether adherence to the guidelines prevents recurrent pancreatitis while minimising surgical complications. METHODS: Multi-centre review of seven UK hospitals, indentifying patients presenting with their first episode of gallstone pancreatitis between 2006 and 2008. RESULTS: A total of 523 patients with gallstone pancreatitis were identified, of which 363 (69%) underwent cholecystectomy (72 during the primary admission or within 2 weeks of discharge; 291 following this). Overall, 7% of patients had a complication related to cholecystectomy of which a greater proportion occurred when cholecystectomy was performed within guideline parameters (13% vs 6%; p = 0.07). 11% of patients were readmitted with recurrent pancreatitis prior to surgery, with those undergoing cholecystectomy outside guideline parameters being most at risk (p = 0.006). CONCLUSION: This study suggests cholecystectomy within guideline parameters significantly reduces recurrence of pancreatitis but may increase the risk of surgical complications. A prospective randomised study to assess the associated morbidity is required to inform future guidelines.

The carbon emissions of writing and illustrating are lower for AI than for humans.

As AI systems proliferate, their greenhouse gas emissions are an increasingly important concern for human societies. In this article, we present a comparative analysis of the carbon emissions associated with AI systems (ChatGPT, BLOOM, DALL-E2, Midjourney) and human individuals performing equivalent writing and illustrating tasks. Our findings reveal that AI systems emit between 130 and 1500 times less CO2e per page of text generated compared to human writers, while AI illustration systems emit between 310 and 2900 times less CO2e per image than their human counterparts. Emissions analyses do not account for social impacts such as professional displacement, legality, and rebound effects. In addition, AI is not a substitute for all human tasks. Nevertheless, at present, the use of AI holds the potential to carry out several major activities at much lower emission levels than can humans.

Characteristics Of Key Patents Covering Recent FDA-Approved Drugs.

New drugs are protected by patents that block generic competition and allow manufacturers to charge high prices. To examine the breadth and characteristics of the key patents covering recently approved brand-name drugs, we extracted patents from the list maintained by the Food and Drug Administration (FDA) and evaluated the timing of patent filings, features of the drugs covered by patents, and whether similar patents were sought in other countries. Among seventy-eight qualifying drug approvals in 2019 and 2020, ten had zero patents, and the remaining sixty-eight drugs listed 322 different patents (the median number was 4). The most common category of patents, based on the nature of the invention being protected, was chemical compound (201; 62 percent), followed by method of use (195; 61 percent). The median time from originator drug approval to the expiration date of the final patent listed on our date of data collection was 10.3 years. About one in five patents had no counterparts in other major jurisdictions around the world, suggesting either a different manufacturer strategy or a differing application of patent standards in the US than in other comparable settings. Patents covering newly approved drugs largely protect the product and its uses; this shows that patent reform, rather than changes to nonpatent exclusivities, is the key to ensuring timely generic entry.

Incorporating Ethically Relevant Empirical Data From Systematic Review of Reasons: A Case Study of Sudden Unexpected Death in Epilepsy.

In this report we use a case study of risk of sudden unexpected death in epilepsy (SUDEP) to illustrate the contribution of systematic literature reviews of disease-specific ethical issues (DSEI). In particular, we show how ethically-relevant empirical data from such reviews can be used in the examination of the reasons for and against a particular normative approach to our DSEI. That is, we have attempted to offer a normative recommendation in response to the question of whether or not the risk of SUDEP should be disclosed to all patients. This case study functions as a form of empirical bioethics by providing a means of assessing empirical claims underlying reasons. As a result of this process, we are then able to provide clear and transparent, if not definitive, justification for a normative recommendation in response to a question of interest.

Optimized immunocytochemistry using leukocyte and tissue markers on Romanowsky-stained slides from dogs and cats.

BACKGROUND: Romanowsky staining is often the initial method used to stain hematologic and cytologic materials. While immunocytochemistry (ICC) is a well-established method on air-dried smears, there are rare veterinary reports of ICC involving Romanowsky-stained slides. OBJECTIVES: This study aimed to compare immunoreactivity of unstained vs Romanowsky-stained specimens, evaluate reactions over time, and assess ICC associations with confirmatory tests of 50 lymphoma cases. Another goal aimed to optimize manual ICC protocols with cellular and tissue immunomarkers to detect CD3ε, CD20, Pax5, MHCII, lysozyme, MUM1, vimentin, cytokeratin, and Melan-A antigens on Romanowsky-stained specimens. MATERIALS AND METHODS: Cytologic specimens from cases of lymphoid and nonlymphoid neoplasms were stained with a methanolic Romanowsky method. Additional unstained slides from these cases were used for comparison with the stained materials. Antigen retrieval involved a citrate buffer pH6 or Tris/EDTA pH9 at 95°C for 25 minutes in a decloaking chamber. Immunocytochemistry used known positive and secondary antibody-only negative cytologic controls. Immunoreactivity of unstained and prestained lymphoma slides was graded by the intensity and percent of stained cells. Signal grading was monitored over time for diagnostic differences. RESULTS: Unstained and Romanowsky-stained slides had similar membrane/cytoplasm graded reactions, but unstained slides produced stronger signals. Romanowsky-stained blood films from B-cell and T-cell leukemias showed minimal loss of signal when monitored over 20 weeks. Signal differences did not change the diagnosis. There was a significant association between ICC and confirmatory tests. Optimization involved antibody dilution and antigen retrieval methodology for each antibody tested. CONCLUSIONS: Immunocytochemistry of Romanowsky-stained material can be successfully performed using antibodies against CD3ε, CD20, cytokeratin, lysozyme, Melan-A, MHCII, MUM1, Pax5, and vimentin.

Three wound-dressing strategies to reduce surgical site infection after abdominal surgery: the Bluebelle feasibility study and pilot RCT.

BACKGROUND: Surgical site infection (SSI) affects up to 20% of people with a primary closed wound after surgery. Wound dressings may reduce SSI. OBJECTIVE: To assess the feasibility of a multicentre randomised controlled trial (RCT) to evaluate the effectiveness and cost-effectiveness of dressing types or no dressing to reduce SSI in primary surgical wounds. DESIGN: Phase A - semistructured interviews, outcome measure development, practice survey, literature reviews and value-of-information analysis. Phase B - pilot RCT with qualitative research and questionnaire validation. Patients and the public were involved. SETTING: Usual NHS care. PARTICIPANTS: Patients undergoing elective/non-elective abdominal surgery, including caesarean section. INTERVENTIONS: Phase A - none. Phase B - simple dressing, glue-as-a-dressing (tissue adhesive) or 'no dressing'. MAIN OUTCOME MEASURES: Phase A - pilot RCT design; SSI, patient experience and wound management questionnaires; dressing practices; and value-of-information of a RCT. Phase B - participants screened, proportions consented/randomised; acceptability of interventions; adherence; retention; validity and reliability of SSI measure; and cost drivers. DATA SOURCES: Phase A - interviews with patients and health-care professionals (HCPs), narrative data from published RCTs and data about dressing practices. Phase B - participants and HCPs in five hospitals. RESULTS: Phase A - we interviewed 102 participants. HCPs interpreted 'dressing' variably and reported using available products. HCPs suggested practical/clinical reasons for dressing use, acknowledged the weak evidence base and felt that a RCT including a 'no dressing' group was acceptable. A survey showed that 68% of 1769 wounds (727 participants) had simple dressings and 27% had glue-as-a-dressing. Dressings were used similarly in elective and non-elective surgery. The SSI questionnaire was developed from a content analysis of existing SSI tools and interviews, yielding 19 domains and 16 items. A main RCT would be valuable to the NHS at a willingness to pay of £20,000 per quality-adjusted life-year. Phase B - from 4 March 2016 to 30 November 2016, we approached 862 patients for the pilot RCT; 81.1% were eligible, 59.4% consented and 394 were randomised (simple, n = 133; glue, n = 129; no dressing, n = 132); non-adherence was 3 out of 133, 8 out of 129 and 20 out of 132, respectively. SSI occurred in 51 out of 281 participants. We interviewed 55 participants. All dressing strategies were acceptable to stakeholders, with no indication that adherence was problematic. Adherence aids and patients' understanding of their allocated dressing appeared to be key. The SSI questionnaire response rate overall was 67.2%. Items in the SSI questionnaire fitted a single scale, which had good reliability (test-retest and Cronbach's alpha of > 0.7) and diagnostic accuracy (c-statistic = 0.906). The key cost drivers were hospital appointments, dressings and redressings, use of new medicines and primary care appointments. LIMITATIONS: Multiple activities, often in parallel, were challenging to co-ordinate. An amendment took 4 months, restricting recruitment to the pilot RCT. Only 67% of participants completed the SSI questionnaire. We could not implement photography in theatres. CONCLUSIONS: A main RCT of dressing strategies is feasible and would be valuable to the NHS. The SSI questionnaire is sufficiently accurate to be used as the primary outcome. A main trial with three groups (as in the pilot) would be valuable to the NHS, using a primary outcome of SSI at discharge and patient-reported SSI symptoms at 4-8 weeks. TRIAL REGISTRATION: Phase A - Current Controlled Trials ISRCTN06792113; Phase B - Current Controlled Trials ISRCTN49328913. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 39. See the NIHR Journals Library website for further project information. Funding was also provided by the Medical Research Council ConDuCT-II Hub (reference number MR/K025643/1).

Wound infections are common after surgery. Some are cured with simple treatment, but others may lead to serious problems. Reducing the risk of a wound infection is important. We do not know if the type of dressing, or not using a dressing, influences the risk of infection. A study that allocated patients to receive different dressings (or no dressing) would answer this question. We did preliminary research to explore whether or not such a study is possible. We interviewed doctors, nurses and patients about their views on dressings and a future study. We also described dressings currently being used in the NHS and found that simple dressings and tissue adhesive (glue) 'as-a-dressing' are used most frequently. We studied existing evidence and interviewed experts to develop a questionnaire, completed by patients, to identify wound infections after patients leave hospital and tested its accuracy. We also explored taking photographs of wounds. We investigated whether or not a major study would be worth the cost and designed a pilot study to test its feasibility. The pilot study recruited 394 patients undergoing abdominal operations in five NHS hospitals. These patients were allocated to have a simple dressing, glue-as-a-dressing or no dressing, and 92% received the allocated dressing method. Patients and their doctors and nurses found the dressing methods to be acceptable. We showed that the new patient questionnaire accurately identified infections. Patients or their carers also found it acceptable to photograph their wounds. Our research suggests that a future large study would be worth the investment and is possible.

Impact of medial-to-lateral vs lateral-to-medial approach on short-term and cancer-related outcomes in laparoscopic colorectal surgery: A retrospective cohort study.

BACKGROUND: Laparoscopic surgery is the favoured method of colorectal cancer resections. It is surgeon expertise and discretion to choose whether to mobilize colon lateral-to-medial or medial-to-lateral. We aim to identify the advantage of one approach over the other in short-term and cancerrelated outcomes. METHODS: A retrospective review of a prospectively maintained database of all laparoscopic colorectal resections with curative-intent, in a single unit, from March 2013 to October 2014. Data was collected on patient demographics, method of laparoscopic mobilisation, operating time, length-of-stay, post-operative complications, clearance of circumferential resection margins lymph node harvest and follow-up. RESULTS: 137 patients with comparable patient demographics had laparoscopic colorectal cancer resection. 76 (60.3%) male and 50 (39.7%) female patients. 58(46.0%) of resections were performed using medial-to-lateral approach, while 68(54.0%) lateral-to-medial. Lateral group had on average 14(0-38) lymph nodes with specimen compared to 17 (6-45) in medial group. There was a statistically significant difference in the major complication rate (Clavien-Dindo IV) between the groups with 1(1.7%) in the medial-to-lateral group compared to 7 (10.2%) in the lateral-to-medial group, (p .035). Patients in the medial-to-lateral group had median length-of-stay of 7 days (range 2-55) compared to 7 days (range 2-75) in the lateral-to-medial group. There was no statistically significant difference in survival between both groups up-to 1334 days p=.413. CONCLUSION: Our study shows that mobilising the colon medially in laparoscopic colorectal cancer resection increases the lymph node harvest, gives comparable CRM clearance, similar length of hospital stay and complications. It makes no statistically significant difference in the overall patient survival.

Oncological outcomes of abdominoperineal resection for the treatment of low rectal cancer: A retrospective review of a single UK tertiary centre experience.

BACKGROUND: The use of abdominoperineal resection (APR) in the management of low rectal cancer has received criticism over high rates of incomplete resection due to tumour involvement at the circumferential resection margin. Extralevator abdominoperineal resection has been advocated as a means of improving complete resection. However, Extralevator abdominoperineal resection can result in increased cost, morbidity and reduced quality of life.This study aims to assess the histological features and long-term outcomes of patients undergoing standard abdominoperineal resection and discusses the potential role of Extralevator abdominoperineal resection in this cohort. METHOD: A retrospective review of a prospectively maintained database of rectal cancer patients at a single centre. Patients undergoing standard APR were included from 01/06/2007 to 31/05/2012 to allow a minimum 2-year follow-up. Data was collected on age, gender, co-morbidity, pre-operative stage, neo-adjuvant therapy, histology, recurrence and mortality. RESULTS: Seventy patients were identified (45 (64%) male, median age 67; (range 36-85)). 12 (17.1%) patients had a positive circumferential resection margin; 4 (6.1%) tumours were located anteriorly, 8 (11%) were located posteriorly or laterally and may potentially have been completely resected with extralevator abdomino-perineal resection, Number-needed to treat = 9. Positive circumferential resection margin was more common in advanced tumours (p < 0.001). Local recurrence was more common with positive circumferential resection margins (16.7% Vs 0%, p = 0.027), with no statistically significant difference in 5-year survival, although there was a tendency towards worse survival in these patients. CONCLUSION: Positive circumferential resection margin following APR resulted in significantly increased local recurrence with a trend towards poorer survival outcomes. Extralevator abdomino-perineal resection may have benefited some of these patients with locally advanced tumours and postero-lateral recurrences. However, this has to be balanced against exposing patients to increased risk of adverse events. We would recommend selective use of Extralevator abdominoperineal resection for locally advanced and node-positive tumours although further studies to help refine selection criteria are required with long-term follow-up.

CRISPR Becomes Clearer.

In this pivotal year for gene editing, the breakthrough molecular system CRISPR-Cas9 has advanced on three fronts. In under seven months, an influential scientific body-the National Academies of Sciences, Engineering, and Medicine the National Academies of Sciences, Engineering, and Medicine-cracked open the door to human germline gene editing, ownership of patents covering CRISPR-Cas9 came into much sharper focus as a result of a dispute between two parties, and experiments showing proof of concept of the most controversial of uses-altering germlines of humans-were revealed as having been successfully performed by a mainstream laboratory. Given the vast spoils that await the patent owners, final results of all patent disputes over CRISPR-Cas9 patents may stretch on for years. Meanwhile, bioethical considerations of CRISPR-Cas9 have also been contentious as the United States and other countries grapple with how best to regulate gene editing.

A mixed-methods feasibility and external pilot study to inform a large pragmatic randomised controlled trial of the effects of surgical wound dressing strategies on surgical site infections (Bluebelle Phase B): study protocol for a randomised controlled trial.

BACKGROUND: Surgical site infections (SSIs) are common, occurring in up to 25% of > 4 million operations performed in England each year. Previous trials of the effect of wound dressings on the risk of developing a SSI are of poor quality and underpowered. METHODS/DESIGN: This study is a feasibility and pilot trial to examine the feasibility of a full trial that will compare simple dressings, no dressing and tissue-glue as a dressing. It is examining the overall acceptability of trial participation, identifying opportunities for refinement, testing the feasibility of and validating new outcome tools to assess SSI, wound management issues and patients' wound symptom experiences. It is also exploring methods for avoiding performance bias and blinding outcome assessors by testing the feasibility of collecting wound photographs taken in theatre immediately after wound closure and, at 4-8 weeks after surgery, taken by participants themselves or their carers. Finally, it is identifying the main cost drivers for an economic evaluation of dressing types. Integrated qualitative research is exploring acceptability and reasons for non-adherence to allocation. Adults undergoing primary elective or unplanned abdominal general surgery or Caesarean section are eligible. The main exclusion criteria are abdominal or other major surgery less than three months before the index operation or contraindication to dressing allocation. The trial is scheduled to recruit for nine months. The findings will be used to inform the design of a main trial. DISCUSSION: This pilot trial is the first pragmatic study to randomise participants to no dressing or tissue-glue as a dressing versus a simple dressing. Early evidence from the ongoing pilot shows that recruitment is proceeding well and that the interventions are acceptable to participants. Combined with the qualitative findings, the findings will inform whether a main, large trial is feasible and, if so, how it should be designed. TRIAL REGISTRATION: ISRCTN49328913 . Registered on 20 October 2015.

Emergency surgery in the elderly: challenges and solutions.

Elderly patients frequently present with surgical emergencies to health care providers, and outcomes in this group of patients remain poor. Contributing factors include frailty, preexisting comorbidity, polypharmacy, delayed diagnosis, and lack of timely and consultant-led treatment. In this review, we address common emergency surgical presentations in the elderly and highlight the specific challenges in caring for these patients. We summarize 20 years of reports by various medical bodies that have aimed to improve the care of these patients. To improve morbidity and mortality, several aspects of care need to be addressed. These include accurate and timely preoperative assessment to identify treatable pathology and, where possible, to consider and correct age-specific disease processes. Identification of patients in whom treatment would be futile or associated with high risk is needed to avoid unnecessary interventions and to give patients and carers realistic expectations. The use of multidisciplinary teams to identify common postoperative complications and age-specific syndromes is paramount. Prevention of complications is preferable to rescue treatment due to the high proportion of patients who fail to recover from adverse events. Even with successful surgical treatment, long-term functional decline and increased dependency are common. More research into emergency surgery in the elderly is needed to improve care for this growing group of vulnerable patients.