Post-Cancer Treatment Reflections by Patients Concerning the Provisions and Support Required for a Prehabilitation Programme.

BACKGROUND: Evidence suggests that physical fitness interventions, mental health support and nutritional advice before surgery (prehabilitation) could reduce hospital stay and improve quality of life of patients with cancer. In this study we captured the opinions of a group of patients with cancer undergoing these interventions after treatment to discover what a prehabilitation programme should encompass. METHODS: Patients from the Cancer and Rehabilitation Exercise (CARE) programme based in Nottingham took part in a 26-point online questionnaire about the design of prehabilitation programmes. RESULTS: The questionnaire was completed over a 2-week period in December 2021 by 54 patients from the CARE programme. Their responses were as follows: 44 (81.5%) participants would have participated in prehabilitation had it been available to them and 28 (51.9%) ranked physical exercise as the most important component. Forty (74.1%) participants believed the counselling aspect of prehabilitation would have contributed to a successful outcome and 35 (64.8%) thought dietary advice would have benefitted them before surgery. Thirty-one (57.4%) participants preferred the programme to take place in a fitness centre, rather than at home or hospital and 43 (79.6%) would have liked to have known about prehabilitation from their doctor at the time of diagnosis. CONCLUSIONS: Patients are interested in prehabilitation to become more physically fit and mentally prepared for surgery. They expressed the need for a focus on physical exercise, counselling to improve mental health and personalised nutritional advice. Tailoring a prehabilitation programme, with input from patients, could contribute to improving patient outcomes following cancer treatments.

Adapting Patient and Public Involvement processes in response to the Covid-19 pandemic.

BACKGROUND: The COVID-19 pandemic brought rapid and major changes to research, and those wishing to carry out Patient and Public Involvement (PPI) activities faced challenges, such as restrictions on movement and contact, illness, bereavement and risks to potential participants. Some researchers moved PPI to online settings during this time but remote consultations raise, as well as address, a number of challenges. It is important to learn from PPI undertaken in this period as face-to-face consultation may no longer be the dominant method for PPI. METHODS: UK stay-at-home measures announced in March 2020 necessitated immediate revisions to the intended face-to-face methods of PPI consultation for the ESORT Study, which evaluated emergency surgery for patients with common acute conditions. PPI plans and methods were modified to all components being online. We describe and reflect on: initial plans and adaptation; recruitment; training and preparation; implementation, contextualisation and interpretation. Through first-hand accounts we show how the PPI processes were developed, experienced and viewed by different partners in the process. DISCUSSION AND CONCLUSIONS: While concerns have been expressed about the possible limiting effects of forgoing face-to-face contact with PPI partners, we found important benefits from the altered dynamic of the online PPI environment. There were increased opportunities for participation which might encourage the involvement of a broader demographic, and unexpected benefits in that the online platform seemed to have a 'democratising' effect on the meetings, to the benefit of the PPI processes and outcomes. Other studies may however find that their particular research context raises particular challenges for the use of online methods, especially in relation to representation and inclusion, as new barriers to participation may be raised. It is important that methodological challenges are addressed, and researchers provide detailed examples of novel methods for discussion and empirical study. PATIENT AND PUBLIC CONTRIBUTION: We report a process which involved people with lived experience of emergency conditions and members of the public. A patient member was involved in the design and implementation, and two patients with lived experience contributed to the manuscript.

Impact of the first wave of COVID-19 on outcomes following emergency admissions for common acute surgical conditions: analysis of a national database in England.

BACKGROUND: This study assessed the impact of the first COVID-19 wave in England on outcomes for acute appendicitis, gallstone disease, intestinal obstruction, diverticular disease, and abdominal wall hernia. METHODS: Emergency surgical admissions for patients aged 18 years and older to 124 NHS Trust hospitals between January and June in 2019 and 2020 were extracted from Hospital Episode Statistics. The risk of 90-day mortality after admission during weeks 11-19 in 2020 (national lockdown) and 2019 (pre-COVID-19) was estimated using multilevel logistic regression with case-mix adjustment. The primary outcome was all-cause mortality at 90 days. RESULTS: There were 12 231 emergency admissions and 564 deaths within 90 days during weeks 11-19 in 2020, compared with 18 428 admissions and 542 deaths in the same interval in 2019. Overall, 90-day mortality was higher in 2020 versus 2019, with an adjusted OR of 1.95 (95 per cent c.i. 0.78 to 4.89) for appendicitis, 2.66 (1.81 to 3.92) for gallstone disease, 1.99 (1.44 to 2.74) for diverticular disease, 1.70 (1.13 to 2.55) for hernia, and 1.22 (1.01 to 1.47) for intestinal obstruction. After emergency surgery, 90-day mortality was higher in 2020 versus 2019 for gallstone disease (OR 3.37, 1.26 to 9.02), diverticular disease (OR 2.35, 1.16 to 4.73), and hernia (OR 2.34, 1.23 to 4.45). For intestinal obstruction, the corresponding OR was 0.91 (0.59 to 1.41). For admissions not leading to emergency surgery, mortality was higher in 2020 versus 2019 for gallstone disease (OR 2.55, 1.67 to 3.88), diverticular disease (1.90, 1.32 to 2.73), and intestinal obstruction (OR 1.30, 1.06 to 1.60). CONCLUSION: Emergency admission was reduced during the first lockdown in England and this was associated with higher 90-day mortality.

Identifying a core symptom set triggering radiological and endoscopic investigations for suspected recurrent esophago-gastric cancer: a modified Delphi consensus process.

BACKGROUND: There is currently a lack of evidence-based guidelines regarding surveillance for recurrence after esophageal and gastric (OG) cancer surgical resection, and which symptoms should prompt endoscopic or radiological investigations for recurrence. The aim of this study was to develop a core symptom set using a modified Delphi consensus process that should guide clinicians to carry out investigations to look for suspected recurrent OG cancer in previously asymptomatic patients. METHODS: A web-based survey of 42 questions was sent to surgeons performing OG cancer resections at high volume centers. The first section evaluated the structure of follow-up and the second, determinants of follow-up. Two rounds of a modified Delphi consensus process and a further consensus workshop were used to determine symptoms warranting further investigations. Symptoms with a 75% consensus agreement as suggestive of recurrent cancer were included in the core symptom set. RESULTS: 27 surgeons completed the questionnaires. A total of 70.3% of centers reported standardized surveillance protocols, whereas 3.7% of surgeons did not undertake any surveillance in asymptomatic patients after OG cancer resection. In asymptomatic patients, 40.1% and 25.9% of centers performed routine imaging and endoscopy, respectively. The core set that reached consensus, consisted of eight symptoms that warranted further investigations included; dysphagia to solid food, dysphagia to liquids, vomiting, abdominal pain, chest pain, regurgitation of foods, unexpected weight loss and progressive hoarseness of voice. CONCLUSION: There is global variation in monitoring patients after OG cancer resection. Eight symptoms were identified by the consensus process as important in prompting radiological or endoscopic investigation for suspected recurrent malignancy. Further randomized controlled trials are necessary to link surveillance strategies to survival outcomes and evaluate prognostic value.

Outcomes Following an Index Emergency Admission With Cholecystitis: A National Cohort Study.

OBJECTIVE: The objective of this study was to evaluate the differences between patients who undergo cholecystectomy following index admission for cholecystitis, and those who are managed nonoperatively. SUMMARY BACKGROUND DATA: Index emergency cholecystectomy following acute cholecystitis is widely recommended by national guidelines, but its effect on clinical outcomes remains uncertain. METHODS: Data collected routinely from the Hospital Episode Statistics database (all admissions to National Health Service organizations in England and Wales) were extracted between April 1, 2002 and March 31, 2015. Analyses were limited to patients aged over 18 years with a primary diagnosis of cholecystitis. Exclusions included records with missing or invalid datasets, patients who had previously undergone a cholecystectomy, patients who had died without a cholecystectomy, and those undergoing cholecystectomy for malignancy, pancreatitis, or choledocholithiasis. Patients were grouped as either "no cholecystectomy" where they had never undergone a cholecystectomy following discharge, or "cholecystectomy." The latter group was then subdivided as "emergency cholecystectomy" when cholecystectomy was performed during their index emergency admission, or "interval cholecystectomy" when a cholecystectomy was performed within 12 months following a subsequent (emergency or elective) admission. Propensity Score Matching was used to match emergency and interval cholecystectomy groups. Main outcome measures included 1) One-year total length of hospital stay due to biliary causes following an index emergency admission with cholecystitis. 2) One-year mortality; defined as death occurring within 1 year following the index emergency admission with acute cholecystitis. RESULTS: Of the 99,139 patients admitted as an emergency with acute cholecystitis, 51.1% (47,626) did not undergo a cholecystectomy within 1 year of index admission. These patients were older, with more comorbidities (Charlson Comorbidity Score ≥ 5 in 23.5% vs. 8.1%, P < 0.001) when compared to patients who did have a cholecystectomy. While all-cause 1-year mortality was higher in the nonoperated versus the operated group (12.2% vs. 2.0%, P < 0.001), gallbladder-related deaths were significantly lower than all other causes of death in the non-operated group (3.3% vs. 8.9%, P < 0.001). Following matching, 1-year total hospital admission time was significantly higher following emergency compared with interval cholecystectomy (17.7 d vs. 13 d, P < 0.001). CONCLUSIONS: Over 50% of patients in England did not undergo cholecystectomy following index admission for acute cholecystitis. Mortality was higher in the nonoperated group, which was mostly due to non-gallbladder pathologies but total hospital admission time for biliary causes was lower over 12 months. Increasing the numbers of emergency cholecystectomy may risk over-treating patients with acute cholecystitis and increasing their time spent admitted to hospital.

Upper GI biopsies for adenocarcinoma - how many biopsies should endoscopists take?

AIMS: There is evidence that four or five gastric cancer biopsies are required for accurate HER2 interpretation. However, the number of biopsies that need to be taken to reach this number of viable cancer biopsies is without evidence. This study aimed to address this gap by assessing the number of biopsies required to gain at least four viable biopsies containing cancer. METHODS AND RESULTS: A total of 105 consecutive biopsy cases of gastric and oesophageal adenocarcinoma were retrieved from files. Only definite cancer diagnoses were included; missed cancers or unproven cases were not considered. The cases were reviewed and the number of biopsies taken, and the number containing viable tumour was recorded. In total, 667 biopsies were taken, of which 471 had viable tumour (70.6%). Seventy of 105 cases (67%) had four viable tumour biopsies, but only 47 of 105 (45%) had five viable tumour biopsies. In order to have a >90% chance of having four viable tumour biopsies, seven needed to be taken, while 10 or more were required for a >90% chance of five viable tumour biopsies. Mathematically, using a 0.7 probability for a single biopsy, eight biopsies would be required for a 94% chance of at least four viable tumour biopsies. CONCLUSION: In our large upper GI cancer centre, many biopsy cases do not contain sufficient material for adequate HER2 assessment. In order to meet the four-biopsy requirement for adequate HER2 assessment in >90% of cases, at least eight biopsies need to be taken, while 10 biopsies would be required for the 5-cancer biopsy threshold.

Comparison of Outcomes with Semi-mechanical and Circular Stapled Intrathoracic Esophagogastric Anastomosis following Esophagectomy.

BACKGROUND: Several techniques have been described for esophagogastric anastomosis following esophagectomy. This study compared the outcomes of circular stapled anastomoses with semi-mechanical technique using a linear stapler. METHODS: Perioperative data were extracted from a contemporaneously collected database of all consecutive esophagectomies for cancer with intrathoracic anastomoses performed in the Trent Oesophago-Gastric Unit between January 2015 and April 2018. Anastomotic techniques: circular stapled versus semi-mechanical, were evaluated and outcomes were compared. The primary outcome was anastomotic leak rate. Secondary outcomes included anastomotic stricture, overall complication rates, length of stay (LOS) and 30 day all-cause mortality. RESULTS: One hundred and fifty-nine consecutive esophagectomies with intrathoracic anastomosis were performed during the study period. There were no significant differences between the two groups in terms of age, American Society of Anaesthesiologists score, Charlson comorbidity index and neoadjuvant therapies received. Circular stapled anastomoses were performed in 85 patients, while 74 patients received a semi-mechanical anastomosis. Clavien-Dindo complications II or more were higher in the circular stapled group (p = 0.02). There were 16 (10%) anastomotic leaks overall, three (4%) in semi-mechanical group versus 13 (15%) in the circular stapled group (p < 0.019). There was no statistically significant difference between the two groups in terms of LOS, 30-day mortality or the need for endoscopic dilatation of the anastomosis at 3 months follow-up. CONCLUSION: The move from a circular stapled to a semi-mechanical intrathoracic anastomosis has been associated with a reduced postoperative anastomotic leak rate following esophagectomy for esophageal cancer.

Survival After Neoadjuvant and Adjuvant Treatments Compared to Surgery Alone for Resectable Esophageal Carcinoma: A Network Meta-analysis.

OBJECTIVE: This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach. SUMMARY BACKGROUND DATA: The optimal treatment for resectable esophageal cancer is unknown. METHODS: A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival. RESULTS: In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87). CONCLUSIONS: This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.

A Comparison of Mortality Following Emergency Laparotomy Between Populations From New York State and England.

OBJECTIVE: The aim of this study was to compare mortality following emergency laparotomy between populations from New York State and England. SUMMARY OF BACKGROUND DATA: Mortality following emergency surgery is a key quality improvement metric in both the United States and UK. Comparison of the all-cause 30-day mortality following emergency laparotomy between populations from New York State and England might identify factors that could improve care. METHODS: Patient demographics, in-hospital, and 30-day outcomes data were extracted from Hospital Episode Statistics (HES) in England and the New York Statewide Planning and Research Cooperative System (SPARCS) administrative databases for all patients older than 18 years undergoing laparotomy for emergency open bowel surgery between April 2009 and March 2014. The primary outcome measure was all-cause mortality within 30 days of the index laparotomy. Mixed-effects logistic regression was performed to model independent demographic variables against mortality. A one-to-one propensity score matched dataset was created to compare the odd ratios of mortality between the 2 populations. RESULTS: Overall, 137,869 patient records, 85,286 (61.9%) from England and 52,583 (38.1%) from New York State, were extracted. Crude 30-day mortality for patients was significantly higher in the England compared with New York State [11,604 (13.6%) vs 3633 (6.9%) patients, P < 0.001]. Patients undergoing emergency laparotomy in England had significantly higher risk of mortality compared with those in New York State (odds ratio 2.35, confidence interval 2.24-2.46, P < 0.001). CONCLUSION: The risk of mortality at 30 days is higher following emergency laparotomy in England as compared with New York State despite similar patient groups.

Effectiveness of Antibiotic Prophylaxis in Non-emergency Cholecystectomy Using Data from a Population-Based Cohort Study.

BACKGROUND: There is a variation in the administration of antibiotics prophylaxis to reduce the perceived risk of SSI in patients undergoing non-emergency cholecystectomy. The aim of this study was to determine the effectiveness of antibiotic prophylaxis following non-emergency cholecystectomy to prevent 30-day superficial surgical site infections (SSIs) using non-selected, nationally collected, prospective data. METHODS: Data were extracted from the CholeS study, which examined and independently validated the outcomes on consecutive patients following non-emergency cholecystectomy across 166 hospitals in the UK and Ireland. Patients who received antibiotic prophylaxis were exact matched to those who did not on variables associated with antibiotic prophylaxis. The primary outcome of interest was superficial SSI, and secondary outcomes included deep SSI, readmissions, complications and re-interventions within 30 days. RESULTS: Out of a total of 7327 patients included in the study, 4468 (61%) received antibiotic prophylaxis. These were matched to patients who did not receive antibiotic prophylaxis on a range of demographic and surgical factors, leaving 1269 pairs of patients for analysis. Within this cohort, patients receiving antibiotic prophylaxis had significantly lower rates of superficial SSI (0.7% vs. 2.3%, p = 0.001) and all-cause complications (5.8 vs. 8.0%, p = 0.031), but similar rates of deep SSI (1.0 vs. 1.4%, p = 0.473), readmissions (5.2 vs. 6.2%, p = 0.302) and re-interventions (2.6 vs. 3.7%, p = 0.093). The number needed to treat to prevent one superficial SSI was 45 (95% confidence interval 24-662). CONCLUSIONS: Antibiotics appear effective at reducing SSI after non-emergency cholecystectomy. However, due to the high number needed to treat it is unclear whether they provide a worthwhile clinical benefit to patients.

A Population-Based Cohort Study of Emergency Appendectomy Performed in England and New York State.

BACKGROUND: To compare selected outcomes (30-day reoperation and total length of hospital stay) following emergency appendectomy between populations from New York State and England. METHODS: This retrospective cohort study used demographic and in-hospital outcome data from Hospital Episode Statistics (HES) and the New York Statewide Planning and Research Cooperative System (SPARCS) administrative databases for all patients aged 18+ years undergoing appendectomy between April 2009 and March 2014. Univariate and adjusted multivariable logistic regression were used to test significant factors. A one-to-one propensity score matched dataset was created to compare odd ratios (OR) of reoperations between the two populations. RESULTS: A total of 188,418 patient records, 121,428 (64.4%) from England and 66,990 (35.6%) from NYS, were extracted. Appendectomy was completed laparoscopically in 77.7% of patients in New York State compared to 53.6% in England (P < 0.001). The median lengths of hospital stay for patients undergoing appendectomy were 3 (interquartile range, IQR 2-4) days versus 2 (IQR 1-3) days (P < 0.001) in England and New York State, respectively. All 30-day reoperation rates were higher in England compared to New York State (1.2 vs. 0.6%, P < 0.001), representing nearly a twofold higher risk of 30-day reoperation (OR 1.88, 95% CI 1.64-2.14, P < 0.001). As the proportion of appendectomy completed laparoscopically increased, there was a reduction in the reoperation rate in England (correlation coefficient -0.170, P = 0.036). CONCLUSIONS: Reoperations and total length of hospital stay is significantly higher following appendectomy in England compared to New York State. Increasing the numbers of appendectomy completed laparoscopically may decrease length of stay and reoperations.

Diaphragmatic herniation following esophagogastric resectional surgery: an increasing problem with minimally invasive techniques? : Post-operative diaphragmatic hernias.

BACKGROUND: Post-operative diaphragmatic hernias (PODHs) are serious complications following esophagectomy or total gastrectomy. The aim of this study was to describe and compare the incidence of PODHs at a high volume center over time and analyze the outcomes of patients who develop a PODH. METHODS: A prospective database of all resectional esophagogastric operations performed for cancer between January 2001 and December 2015 was analyzed. Patients diagnosed with PODH were identified and data extracted regarding demographics, details of initial resection, pathology, PODH symptoms, diagnosis and treatment. RESULTS: Out of 631 patients who had hiatal dissection for malignancy, 35 patients developed of PODH (5.5 % overall incidence). Median age was 66 (range 23-87) years. The incidence of PODH in each operation type was: 2 % (4/221) following an open 2 or 3 stage esophagectomy, 10 % (22/212) following laparoscopic hybrid esophagectomy, 7 % (5/73) following MIO, and 3 % (4/125) following total gastrectomy. The majority of patients had colon or small bowel in a left-sided hernia. Of the 35 patients who developed a PODH, 20 (57 %) patients required emergency surgery, whereas 15 (43 %) had non-urgent repair. The majority of the patients had had suture repair (n = 24) or mesh repair (n = 7) of the diaphragmatic defect. Four patients were treated non-operatively. In hospital post-operative mortality was 20 % (4/20) in the emergency group and 0 % (0/15) in the elective group. Further hernia recurrence affected seven patients (n = 7/27, 26 %) and 4 of these patients (15 %) presented with multiple recurrences. CONCLUSION: PODH is a common complication following hybrid esophagectomy and MIO. Given the high mortality from emergency repair, careful thought is needed to identify surgical techniques to prevent PODH forming when minimal access esophagectomy are performed. Upper GI surgeons need to have a low index of suspicion to investigate and treat patients for this complication.

Outcomes Following Extended Surgery for Retroperitoneal Sarcomas: Results From a UK Referral Centre.

BACKGROUND: Primary extended resection has been proposed as the initial treatment for patients with retroperitoneal sarcoma. This approach comprises an extended en-bloc resection of the directly infiltrated organs and adjacent uninvolved organs. The results of such radical surgery have yet to be validated. This retrospective study aims to investigate this practice in a contemporary series from a referral center in the UK. METHODS: We extracted data from consecutive patients who underwent extended resectional surgery between 2009 and 2013, and investigated the type of resection performed, the effectiveness of extended surgery in providing negative microscopic margins, and the occurrence of post-surgical adverse events. RESULTS: A total of 69 patients were included. Fifty-two patients had a primary tumor (75.4 %), and in 55 patients (79.7 %) the tumor was resected en bloc with adjacent organs or structures. Colonic resection (N = 35, 50.7 %) and nephrectomy (N = 28, 40.6 %) were the most frequently performed organ resections. Organs were infiltrated in 22 patients (32 %), and there was no association between organ infiltration and patient variables and staging characteristics. Negative microscopic margins were achieved in 88.6 % of patients in this series. Postoperative complications occurred in 21 patients (30 %) and a reoperation was required in ten cases (14.5 %). No independent predictors of morbidity were identified and no 30-day postoperative deaths occurred. CONCLUSIONS: Four-fifths of patients in this series had organs removed in association with the retroperitoneal sarcoma. This approach in a specialist sarcoma unit results in negative microscopic tumor margins in up to 90 % of cases and can be performed safely.

Psychological Prehabilitation Before Cancer Surgery: A Systematic Review.

BACKGROUND: Cancer patients experience anxiety and depression after diagnosis and during treatment. A wide range of psychological interventions have been proposed to alleviate distress, but the evidence about the perioperative effectiveness of such interventions is not clear. This systematic review examined the effect of preoperative psychological interventions or prehabilitation on the postoperative outcomes of patients undergoing surgery for cancer. METHODS: A systematic review of the published data was performed using Embase, Medline, and PsycInfo for the period from 1946 to February 2014. A total of 951 publications (case series, single case reports, and reviews) were found. Only seven of these studies included patients undergoing an operation for cancer and a preoperative psychological intervention. RESULTS: Six of the seven studies were randomized controlled trials. Four were conducted with patients who had breast cancer (n = 356). The other studies included patients with gynecologic cancer (n = 30), colorectal cancer (n = 60), and prostate cancer (n = 159). Assessment of the studies showed four to be of good quality, two to be of moderate quality, and one to be of poor quality. Interventions did not affect traditional surgical outcomes (e.g., length of hospital stay, complications, analgesia use, or mortality) but positively affected patients' immunologic function. However, psychological interventions appeared to have an impact on patients' reported outcome measures including psychological outcomes, quality of life, and somatic symptoms. CONCLUSION: Available data suggested that preoperative psychological prehabilitation may have a role for cancer patients undergoing surgery. Further evidence is needed to evaluate its role.

The LOX-1 scavenger receptor cytoplasmic domain contains a transplantable endocytic motif.

Oxidized low-density lipoprotein particles is a pro-atherogenic factor implicated in atherosclerotic plaque formation. The LOX-1 scavenger receptor binds OxLDL and is linked to atherosclerotic plaque initiation and progression. We tested the hypothesis that the LOX-1 cytoplasmic domain contains a transplantable signal for membrane protein endocytosis. Structural modeling of the LOX-1 cytoplasmic domain reveals that a tripeptide motif (DDL) implicated in LOX-1 endocytosis is part of a curved beta-pleated sheet structure. The two aspartic acid residues within this structural model are highly solvent-accessible enabling recognition by cytosolic factor(s). A triple alanine substitution of the DDL motif within the LOX-1 scavenger receptor substantially reduced endocytosis of OxLDL. Transplantation of the LOX-1 cytoplasmic domain into a transferrin receptor reporter molecule conferred efficient endocytosis on this hybrid protein. Mutation of the DDL motif within the hybrid LOX-1-TfR protein also substantially reduced receptor-mediated endocytosis. Thus a transplantable endocytic motif within the LOX-1 cytoplasmic domain is needed to ensure efficient internalization of pro-atherogenic OxLDL particles.

The lectin-like oxidized low-density-lipoprotein receptor: a pro-inflammatory factor in vascular disease.

Scavenger receptors are membrane glycoproteins that bind diverse ligands including lipid particles, phospholipids, apoptotic cells and pathogens. LOX-1 (lectin-like oxidized low-density lipoprotein receptor-1) is increasingly linked to atherosclerotic plaque formation. Transgenic mouse models for LOX-1 overexpression or gene knockout suggests that LOX-1 contributes to atherosclerotic plaque formation and progression. LOX-1 activation by oxidized LDL (low-density lipoprotein) binding stimulates intracellular signalling, gene expression and production of superoxide radicals. A key question is the role of leucocyte LOX-1 in pro-atherogenic lipid particle trafficking, accumulation and signalling leading to differentiation into foam cells, necrosis and plaque development. LOX-1 expression is elevated within vascular lesions and a serum soluble LOX-1 fragment appears diagnostic of patients with acute coronary syndromes. LOX-1 is increasingly viewed as a vascular disease biomarker and a potential therapeutic target in heart attack and stroke prevention.

Atherosclerosis and the Lectin-like OXidized low-density lipoprotein scavenger receptor.

The Lectin-like OXidized low-density lipoprotein scavenger receptor (LOX-1) is implicated in vascular inflammation and atherosclerotic plaque initiation, progression, and destabilization. LOX-1 levels are elevated upon recognition of oxidized low-density lipoprotein, a key pro-atherogenic substance in the vasculature. Recent evidence indicates this gene product is a biomarker of inflammation and disease status. We review and assess the role of LOX-1 in atherosclerotic plaque formation, physiologic regulation, and as a biomarker and target in cardiovascular disease diagnosis and prevention.

Achieving long term survival in oesophagectomy patients aged over 75.

AIMS: Surgical resection is often the only curative treatment for oesophageal cancer. The aim of this retrospective cohort study was to analyse outcomes following oesophageal resection in patients aged 75 years and older and the impact of an Enhanced Recovery after Surgery (ERAS) program in this cohort. METHODS: Patients aged over 75 years undergoing oesophagectomy between 2003 and 2013 were identified from a single centre using an electronic database. Data on pre-operative comorbidity, tumour stage and length of hospital stay (LOS) were collected. Complications were classified according to the Clavien-Dindo system. Thirty day, 1- and 5-year mortality rates were calculated. RESULTS: 147 patients were identified with a median age of 78.5 (IQR 76.7-80.9). 33% (n = 44) had a grade 3 complication or higher. Median LOS in hospital was 16 days (IQR 13.0-22.0). Thirty-day mortality was 3.4%, 1-year and 5-year survival was 65% and 21% respectively. 45% of patients were enrolled into an Enhanced Recovery After Surgery program and they demonstrated a significantly reduced length of stay from 18 to 14 days (p = 0.005) and 30-day mortality from 6.2% to 0% (p = 0.04) compared to the time period before the program. CONCLUSION: Long-term survival is achievable in patients aged over 75 years.

A systematic review and meta-analysis of perioperative oral decontamination in patients undergoing major elective surgery.

BACKGROUND: Oral antiseptics reduce nosocomial infections and ventilator-associated pneumonia in critically ill medical and surgical patients intubated for prolonged periods. However, the role of oral antiseptics given before and after planned surgery is not clear. The aim of this systematic review and meta-analysis is to determine the effect of oral antiseptics (chlorhexidine or povidone-iodine) when administered before and after major elective surgery. METHODS: Searches were conducted of the MEDLINE, EMBASE and Cochrane databases. The analysis was performed using the random-effects method and the risk ratio (RR) with 95 % confidence interval (CI). RESULTS: Of 1114 unique identified articles, perioperative chlorhexidine was administered to patients undergoing elective surgery in four studies. This identified 2265 patients undergoing elective cardiac surgery, of whom 1093 (48.3 %) received perioperative chlorhexidine. Postoperative pneumonia and nosocomial infections were observed in 5.3 and 20.2 % who received chlorhexidine compared to 10.4 and 31.3 % who received a control preparation, respectively. Oral perioperative chlorhexidine significantly reduced the risk of postoperative pneumonia (RR = 0.52; 95 % CI 0.39-0.71; p < 0.01) and overall nosocomial infections (RR = 0.65; 95 % CI 0.52-0.81; p < 0.01), with no effect on in-hospital mortality (RR = 1.01; 95 % CI 0.49-2.09; p = 0.98). CONCLUSIONS: Perioperative oral chlorhexidine significantly decreases the incidence of nosocomial infection and postoperative pneumonia in patients undergoing elective cardiac surgery. There are no randomised controlled studies of this simple and cheap intervention in patients undergoing elective non-cardiac surgery. TRIAL REGISTRATION: This systematic review was registered with the International prospective register of systematic reviews (PROSPERO). The registration number is CRD42015016063.