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This cohort study examines the association between tumor-infiltrating lymphocyte classification and disease progression among patients with metastatic primary cutaneous melanoma receiving checkpoint inhibitor therapy.

Introduction Karl Popper’s hypothetico-deductive model contends that an assertion is true if it agrees with the facts, and that science progresses via paradigms held to be true until replaced by better approximations of reality. Our study aimed to estimate the half-life of surgical dogma. Methods The first 15 general surgery articles at 5-year intervals were extracted from the British Journal of Surgery since its inception in 1913. A statement summarising each article’s conclusion was formatted, and non-conducive articles were excluded (n=22). A total of 293 article statements were reviewed and marked as true or false by a cohort of 15 senior general surgeons, with a majority positive response denoting a true statement. Regression analysis of the relationship between perceived truth and time was performed. Results Median reviewer positive response rate was 49.5% (range 35.8–64.2%), with over 80% of responders in total agreement regarding 151 statements (51.5%) and deeming 137 (46.8%) currently true. Publication year correlated with percentage of true responses (rho 0.647, p=0.002). Linear modelling of true responses related to 5-year intervals (R2=0.398, p=0.002) estimated the annual rate of loss of truth to be 0.25%, equating to a half-life of 200.0 years. Conclusions Contrary to popular belief, it appears THAT surgical dogma does not lose its lustre for some seven generations. Regression line extrapolation is contentious but would suggest that the current era of surgical knowledge extends from 1769 – the days of John Hunter, the ‘father of modern surgery’ – to 2176, although relative rates of innovation may accelerate and move the nexus point.

Background Little is known regarding the impact of acute kidney injury (AKI) on renal transplant outcome. Our aim was to define the incidence and outcome of AKI in renal transplant patients using data collected from a national AKI electronic alert system Methods The study represents a prospective national cohort study collecting data on 1224 renal transplants recipients with a functioning renal transplant, between April 2015 and March 2019. Results Four hundred forty patients experienced at least one episode of AKI giving an incidence rate of 35.4%. Sixty-four point seven% of episodes were AKI stage 1, 7.3% AKI stage 2 and 28% AKI stage 3. Only 6.2% of episodes occurred in the context of rejection. Forty-three point five% of AKI episodes were associated with sepsis. AKI was associated with pre-existing renal dysfunction, and a primary renal diagnosis of diabetic nephropathy. AKI was more prevalent in recipients from a donor after cardiac death (26.4% vs. 21.4%, p Conclusion The study provides a detailed characterisation of AKI in renal transplant recipients highlighting its significant negative impact on patient and graft survival.

Introduction\ud3C, a study comparing alemtuzumab versus basiliximab induction immunosuppression in kidney transplants has shown lower acute rejection rate with alemtuzumab but same graft survival. Aim of the current study is to examine the effect of induction immunosuppression (thymoglobulin, alemtuzumab, basiliximab) on the outcome of kidneys after circulatory death (DCD).\udMethods\udData of the 274 DCD patients of the 3C obtained from the sponsor was compounded with the 140 DCD patients who received thymoglobulin in a single centre with the same entry criteria as the 3C, giving 414 patients on three induction regimes.\udResults\udThere were more male donors (p

Background Co-production of research into public health services has yet to demonstrate tangible benefits. Few studies have reported the impact of co-production on research outcomes. The previous studies of organ donation have identified challenges in engaging with public organizations responsible, gaining ethical approval for sensitive studies with the recently bereaved and difficulty in recruiting bereaved family members who were approached about organ donation. Objective To address these challenges, we designed the first large co-productive observational study to evaluate implementation of a new system of organ donation in Wales. This paper outlines the co-productive strategies that were designed to overcome known methodological challenges and reports what impact they had on resolving these challenges. Design Two-year co-produced study with multiple stakeholders with the specific intention of maximizing engagement with the National Health Service arm in Wales responsible for organ donation, and recruitment of bereaved family members whose perspectives are essential but commonly absent from studies. Setting and participants NHS Blood and Transplant, Welsh Government and multiple patient and public representatives who served as co-productive partners with the research team. Results Co-productive strategies enabled a smooth passage through four different ethics processes within the 10-week time frame, family member recruitment targets to be surpassed, sharing of routinely collected data on 100% of potential organ donor cases and development of further research capacity and capability in a critically under researched area. Discussion and conclusion Although expensive and time consuming, co-production was effective and added value to research processes and study outcomes.

Following the advice [1] released by the Medical School Council in March 2020 in response to the COVID-19 pandemic, medical schools in the UK suspended all remaining clinical placements. Reasonably...

BACKGROUND AND OBJECTIVES Timely access to pediatric dermatology care remains a challenge. While awaiting appointments, many patients and families utilize so-called health care touchpoints outside of the dermatology clinic such as primary care or emergency department visits to address dermatologic concerns. Long waiting periods also factor into nonattendance rates at pediatric dermatology appointments. This observational retrospective study investigated wait times, relevant health care touchpoints, and factors related to nonattendance at a pediatric dermatology clinic. METHODS We reviewed demographic, health care touchpoint, and nonattendance data for patients referred by a primary care affiliate to the Children's Hospital of Philadelphia (CHOP) pediatric dermatology clinic from February 2016 to May 2017. Descriptive statistics were used to identify trends among analyzed variables. RESULTS We reviewed 250 patient records. The average number of touchpoints per patient was 0.56, and factors that significantly correlated with increased numbers of touchpoints included younger patient age and longer wait time while payer, primary diagnosis, and time of year were not associated. The nonattendance rate was 26%, and factors significantly associated with increased nonattendance rate included longer wait times and winter and spring appointments. CONCLUSION Long wait times impact numbers of touchpoints and appointment attendance rate when referring to pediatric dermatology. A platform such as teledermatology may represent an opportunity to improve access to care by allowing for earlier input from the pediatric dermatologist.

ObjectivesTo determine the short-term impact of a soft opt-out organ donation system on consent rates and donor numbers.DesignBefore and after observational study using bespoke routinely collected data.SettingNational Health Service Blood and Transplant.Participants205 potential organ donor cases in Wales.InterventionsThe Act and implementation strategy.Primary and secondary outcomesConsent rates at 18 months post implementation compared with 3 previous years, and organ donor numbers 21 months before and after implementation. Changes in organ donor register activity post implementation for 18 months.ResultsThe consent rate for all modes of consent was 61.0% (125/205), showing a recovery from the dip to 45.8% in 2014/2015. 22.4% (46/205) were deemed consented donors: consent rate 60.8% (28/46). Compared with the 3 years before the switch there was a significant difference in Welsh consent rates (χ2 p value=0.009). Over the same time period, rest of the UK consent rates also significantly increased from 58.6% (5256/8969) to 63.1% (2913/4614) (χ2 p valueConclusionThis is the first rigorous initial evaluation with bespoke data collected on all cases. The longer-term impact on consent rates and donor numbers is unclear. Concerns about a potential backlash and mass opting out were not realised. The move to a soft opt-out system has not resulted in a step change in organ donation behaviour, but can be seen as the first step of a longer journey. Policymakers should not assume that soft opt-out systems by themselves simply need more time to have a meaningful effect. Ongoing interventions to further enhance implementation and the public’s understanding of organ donation are needed to reach the 2020 target of 80% consent rates. Further longitudinal monitoring is required.

Establishing a patient with a functioning arteriovenous fistula (AVF) remains a challenge for vascular access surgeons. The presence of venous branches directing flow away from the main outflow vein in a brachiocephalic fistula may be one of the reasons for their failure to mature, and often these are ligated. When not ligated, “retrograde flow” may occur and develop into an “unorthodox” fistula. At the Cardiff & Vale University Health Board, 331 brachiocephalic fistulas were created for hemodialysis access over a 3-year period. Five male patients were identified, with a median age of 69 years, who had, as a result of proximal cephalic vein stenosis/occlusion, developed a functioning mature fistula within a distal branch/forearm vein that eventually drains via the basilic vein. Moreover, the flow rates within these new fistula outflow veins were comparable to functioning conventional brachiocephalic fistulas. These retrograde brachiocephalic fistulas that have been inadvertently/accidentally created appear to be successful in providing stable vascular access for hemodialysis. These cases are an interesting find, as such branches often would have been ligated at the time of fistula creation. When creating an AVF between the brachial artery and the median cubital vein, consideration should be given to not ligating the below elbow cephalic vein.

Organ donation is an often contentious subject, with deep-rooted cultural and religious implications. Despite this, Wales became the first country in the UK to adopt an opt-out system for deceased organ donation, in December 2015. Michael Stephens discusses how taking a proactive approach helped the opt-out programme come to pass, and reflects on the results of the system's implementation so far.

Introduction Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases including diabetes and renal failure, and often poorer outcomes for patients with such conditions. The influence of deprivation on outcomes following vascular access surgery has not previously been reported. Methods The Welsh Index of Multiple Deprivation was used to assess the influence of socioeconomic deprivation on outcomes following 507 consecutive first upper limb arteriovenous (AV) fistulas from a single institution in the United Kingdom, performed between 2011 and 2014. The primary outcome measures were early failure and maturation into a working fistula. Results Four hundred and five (80%) patients had a patent AV fistula at the 2-week follow-up clinic. Three hundred and fifty-nine (71%) patients developed a functionally mature AV fistula as determined by clinical assessment and a Doppler scan. There were no differences in either early failure rates ( p = 0.95) or maturation rates ( p = 0.77) between the least and most deprived groups of patients. Conclusions In conclusion, this study has shown that socioeconomic deprivation does not influence outcomes following vascular access surgery.

Socioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases including diabetes and renal failure, with poorer outcomes of their treatments. The influence of deprivation on outcomes following pancreas transplantation has not previously been reported. The Welsh Index of Multiple Deprivation was used to assess the influence of socioeconomic deprivation on outcomes for 119 consecutive pancreas transplant recipients from a single center in the United Kingdom, transplanted between 2004 and 2013. Outcomes measured were rate of acute rejection and graft survival. Thirty-five (29.4%) patients experienced at least one episode of acute rejection following their transplant. Rejection rates in least deprived were 37% and most deprived 24% (p = 0.29). Within the individual domains, rejection rate was higher for the “physical environment” domain (least deprived 40% vs. most deprived 17% (p = 0.053). Five-year graft survival for least and most deprived groups was 75% and 88%, respectively (log-rank test p-value 0.24). This study has not demonstrated any significant differences in outcomes following pancreas transplantation in Wales in relation to socioeconomic deprivation with the exception possibly of the “physical environment” domain. Further studies with larger patient population or concentrating on physical environment deprivation would be of interest.

IntroductionThe Human Transplantation (Wales) Act 2013 (the Act) introduced a ‘soft opt-out’ system of organ donation on 1 December 2015. Citizens are encouraged to make their organ donation decision known during their lifetime. In order to work, the Act and media campaign need to create a context, whereby organ donation becomes the norm, and create a mechanism for people to behave as intended (formally register their decision; consider appointing a representative; convey their donation decision to their families and friends or do nothing—deemed consent). In addition, family members/appointed representatives need to be able to put their own views aside to support the decision of their loved one. The aim of this study is to evaluate initial implementation, outcomes and impact on families and appointed representatives who were approached about organ donation during the first 18 months.Methods and analysisProspective mixed-method coproductive study undertaken with National Health Service Blood and Transplant (NHSBT), and multiple patient/public representatives. The study is designed to collect information on all cases who meet specified criteria (≥18 years, deceased person voluntarily resident in Wales and died in Wales or England) whose family were approached between 1 December 2015 and 31 June 2017). Data for analysis include: NHSBT routinely collected anonymised audit data on all cases; Specialist Nurse in Organ Donation (SNOD) completed anonymised form for all cases documenting their perception of the families’ understanding of the Act, media campaign and outcome of the donation approach; questionnaires and depth interviews with any family member or appointed representative (minimum 50 cases). Additional focus groups and interviews with SNODs. Anonymised donation outcomes and registration activity reports for Wales provide additional context.Ethics and disseminationApproved by NHSBT Research, Innovation and Technology Advisory Group on 23 October 2015; Wales Research Ethics Committee 5 (IRAS190066; Rec Reference 15/WA/0414) on 25 November 2015 and NHSBT R&D Committee (NHSBT ID: AP-15–02) on 24 November 2015.RegistrationThe protocol is registered on the Health and Care Research Wales Clinical Research Portfolio. Study ID number 34396, www.ukctg.nihr.ac.uk

BackgroundSocioeconomic deprivation is an important factor in determining poor health and is associated with a higher prevalence of many chronic diseases, including renal failure, and often poorer outcomes for patients with such conditions. The aim of this study was to investigate the effect of deprivation on peritonitis episodes following peritoneal dialysis (PD)-catheter insertion.MethodsThe Welsh Index of Multiple Deprivation (WIMD) was used to assess the influence of socioeconomic deprivation on outcomes following 233 consecutive first PD-catheter insertions from a single institution in the United Kingdom, performed between 2010 and 2015. The primary outcome measure was the presence of peritonitis episodes.ResultsPeritoneal dialysis catheters were inserted in 243 patients, of which data were available for 233. Fifty-four patients experienced at least 1 episode of peritonitis. Overall, more patients in the most deprived group (vs least deprived) experienced peritonitis, although this was not statistically significant. When analyzing the severity of the peritonitis, within the ‘Education’ domain of the WIMD, significantly more patients from the most deprived group (compared with the least deprived group) experienced ‘2 or more peritonitis’ episodes ( p = 0.04) and were hospitalized for antibiotics ( p = 0.02).ConclusionThis study has shown that patients who live in more ‘educationally’ deprived areas are more likely to have multiple episodes of peritonitis requiring hospital admission following PD-catheter insertions.

The New York 1999 strain of West Nile virus (WNV) is nearly 100% fatal in the American crow (Corvus brachyrhynchos). We evaluated four WNV vaccine formulations in American crows, including intramuscular (i.m.) DNA vaccine, i.m. DNA vaccine with adjuvant, orally administered microencapsulated DNA vaccine, and i.m. killed vaccine. Neutralizing antibodies developed in approximately 80% of crows that received the DNA vaccine i.m. (with or without adjuvant), and in 44% that received the killed vaccine. However, no crows that received the oral microencapsulated DNA vaccine or the placebo developed WNV antibodies. All crows were challenged 10 wk after initial vaccination. No unvaccinated crows survived challenge, and survival rates were 44% (i.m. DNA vaccine), 60% (i.m. DNA vaccine with adjuvant), 0% (oral microencapsulated DNA vaccine), and 11% (killed vaccine). Peak viremia titers in the birds that survived were significantly lower as compared to titers in birds that died. Parenteral administration of a WNV DNA vaccine was associated with reduced mortality but did not provide sterile immunity.

To determine the influence of deprivation on outcomes for patients with oesophageal cancer.A total of 1196 consecutive patients with oesophageal carcinoma presenting to a regional multidisciplinary team between 1 January 1998 and 31 August 2005 were studied prospectively and deprivation scores calculated using the Indices of Multiple Deprivation (IMD) of the National Assembly for Wales. The patients were subdivided into quintiles for analysis.Inhabitants of the most deprived areas (quintile 5) were younger at presentation (median age 67 years versus 70 years, p = 0.01) and were more likely to have squamous cell carcinomas (SCCs) (p = 0.002) in comparison with patients from the least deprived areas (quintile 1). Stage of disease and morbidity did not correlate with deprivation quintile, but operative mortality was greater in quintile 1 versus 5 (1.9% versus 5.8%, p = 0.281). Overall 5-year survival for those patients undergoing oesophagectomy was unrelated to deprivation quintile (1 versus 5, 24% versus 33%, p = 0.8246), but was lower following definitive chemoradiotherapy (dCRT) for the least deprived quintiles (1, 23 versus 45, 35% versus 16%, p = 0.0272).Although deprivation was associated with younger age, SCC and a trend towards higher operative mortality, survival after diagnosis and oesophagectomy were unrelated to deprivation.

Gastric cancer can present with the endoscopic appearances of a benign gastric ulcer (GU). Opinion remains divided on the need for follow-up of patients diagnosed with GU, and the aim of this study was to examine the long-term outcomes of patients whose GU proved malignant on follow-up gastroscopy.Between October 1, 1995, and September 30, 2003, 25,579 gastroscopies were performed in one unit. These identified 544 patients with apparently benign GU, of whom 277 (51%) underwent 334 elective follow-up endoscopies. Twelve of these patients (4.3%) were shown to have a malignant ulcer; their outcomes were compared to those of the 296 other patients diagnosed with gastric cancers in this time frame.The patients in the GU cancer group had earlier stage disease (stage I, 33% vs 6.4%; chi2 = 11.2; DF1; P = 0.001), and were more likely to undergo R0 gastrectomy (50% vs 30%; chi2 = 2.064; DF1; P = 0.151) and to survive long term (46% vs 16%; log-rank chi2, 5.79; DF1; P = 0.0162) than patients in the comparison cohort.Gastroscopic follow-up of 50 patients with an apparently benign GU will identify 1 patient with a malignancy destined to survive for 5 years following R0 gastrectomy. This justifies the diagnostic effort of repeat gastroscopy to ensure complete healing of GU.

Background. Our goals were to measure the accuracy of specialist helical computed tomography (CT) in the preoperative staging of gastric cancer, to determine the relative benefit of progressive CT system technology, and to determine the magnitude of any learning curve in radiological interpretation. Methods. One hundred patients (median age, 70 years; range 27‐86 years; 68 male) underwent a preoperative CT (73 helical [hCT], 27 multislice [mCT]), performed by a single specialist radiologist, followed by surgery within 3 weeks. The strength of the agreement between the perceived CT stage and the histopathological stage was determined for each CT system and also for four serial cohorts of 25 patients, by the weighted Kappa statistic (Kw). Results. The Kw values for T, N, M1 liver, and M1 peritoneal stage were 0.40, 0.18, 0.36, and 0.09 for hCT, compared with 0.57, 0.67, 0.66 (all P < 0.001), and 0.24 (P 0.06) for mCT. Serial Kw for T and N stages improved from 0.26 and 0.14 in the first quartile of patients to 0.61 and 0.73 (P < 0.001) in the last quartile of patients. Conclusion. The role of CT in the preoperative staging of gastric cancer is becoming stronger as CT technology improves.

Socio-economic deprivation has an influence on the outcome for patients diagnosed with breast, colorectal and bronchial cancer, but there are few data on its association with gastric cancer. The aim of this study was to determine the influence of socio-economic deprivation on outcomes for patients with gastric cancer.Three hundred and thirty consecutive patients with gastric adenocarcinoma presenting to a single hospital between 1 October 1995 and 30 June 2004 were studied prospectively and deprivation scores calculated using the National Assembly for Wales Indices of Multiple Deprivation. The patients were subdivided into quintiles for analysis.Inhabitants of the most deprived areas (quintile 5) were younger at presentation (median 70 years versus 74 years, p=0.007), and experienced longer delays in diagnosis (18 weeks versus 9 weeks, p=0.02) when compared with patients from the least deprived areas (quintile 1). Operative mortality was 3-fold higher for patients from the most deprived areas when compared with patients from less deprived areas (15% versus 5%, p=0.03). There was no correlation between stage of disease and socio-economic deprivation. For patients undergoing potentially curative surgery, the 5-year survival for patients from the most deprived areas was 32%, compared with 66% for patients from the least deprived areas (p=0.03).Socio-economic deprivation was associated with younger age at diagnosis, longer diagnostic delay, greater operative mortality and a shorter duration of survival following R0 gastrectomy. These poorer outcomes were not explained by the stage of disease at diagnosis.

Juvenile alligators may help transmit West Nile virus in some areas., Recent evidence suggests that American alligators (Alligator mississippiensis) may be capable of transmitting West Nile virus (WNV) to other alligators. We experimentally exposed 24 juvenile alligators to WNV parenterally or orally. All became infected, and all but three sustained viremia titers >5.0 log10 PFU/mL (a threshold considered infectious for Culex quinquefasciatus mosquitoes) for 1 to 8 days. Noninoculated tankmates also became infected. The viremia profiles and multiple routes of infection suggest alligators may play an important role in WNV transmission in areas with high population densities of juvenile alligators.

In order to determine left ventricular global and regional myocardial functional reserve in endurance-trained and strength-trained athletes, and to identify predictors of exercise capacity, we studied 18 endurance-trained and 11 strength-trained athletes with left ventricular hypertrophy (172±27 and 188±39g/m2 respectively), and compared them with 14 sedentary controls. Global systolic (ejection fraction) and diastolic (transmitral flow) function, and regional longitudinal and transverse myocardial velocities [tissue Doppler echocardiography (TDE)], were measured at rest and immediately after exercise. In endurance-trained compared with strength-trained athletes, resting heart rate was lower (59±11 and 76±9beats/min respectively; P

INTRODUCTION: To expand the donor pool, kidney transplants are being performed using donors who were previously considered unacceptable. We applied the United Network for Organ Sharing criteria to define expanded criteria donors (ECD) within the donation after cardiac death (DCD) and donation after brain stem death (DBD) cohorts. We compared outcomes of DCD and DBD transplants with and without (standard criteria donor [SCD]) the ECD criteria. METHODS: This was a single-center retrospective study of all deceased donor transplants from 2004 to 2010 (n=359). Four groups were identified--DBD-SCD (n=154), DBD-ECD (n=93), DCD-SCD (n=78), and DCD-ECD (n=34). Kaplan-Meier analysis of graft and patient survival and multiple regression analysis of 1-year graft function were performed. RESULTS: One-year and two-year uncensored graft survivals were similar between DCD-ECD and DCD-SCD cohorts (1 year, 90% and 93%; 2 years, 81% and 93% respectively; log-rank test P=0.2). Median estimated glomerular filtration rate (eGFR) was lower in DCD-ECD recipients at 12 months (41 vs. 53 mL/min, P=0.003) and 24 months (33 vs. 54 mL/min, P

To identify new echocardiographic indexes of long-axis function that might differentiate between pathologic and physiologic left ventricular (LV) hypertrophy, we compared 60 subjects with different types of LV hypertrophy (group I: 15 patients with hypertrophic cardiomyopathy, group II: 15 patients with systemic hypertension, and group III: 30 athletes) with 20 normal subjects (group IV). The peak velocities of mitral annular motion at 4 sites were measured from the apex by tissue Doppler echocardiography. There were no differences in mean age and global ejection fraction between groups. Groups I and II had lower long-axis systolic and early diastolic velocities than the athletes (p

The concept of a subconsultant grade is not a new one and has existed within the NHS in various guises for a number of years (such as staff grades and senior registrars). In the main, changes in postgraduate education such as the Calman reforms and Modernising Medical Careers have aimed to reduce such roles as they are inevitably heavily weighted to service provision with limited prospects of career progression. However, the increasing discrepancy between the number of trainees completing their Certificate of Completion of Training (CCT) and the number of vacant consultant posts has pushed this contentious topic back to the fore.

To better understand the potential environmental health risk presented by West Nile virus (WNV)- contaminated feces, we quantified the amount of WNV present in the feces of experimentally infected American crows (Corvus brachyrhynchos) and fish crows (Corvus ossifragus). Peak fecal titers ranged from 10 3.5 to 10 8.8 plaque-forming units (PFU)/g for 10 American crows and from 10 2.3 to 10 6.4 PFU/g for 10 fish crows. The presence of infectious WNV in bird feces indicates a potential for direct transmission of WNV. Thus, handlers of sick or dead birds should take appropriate precautions to avoid exposure to fecal material.

BACKGROUND Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. METHODS We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. RESULTS Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P

The common house fly may be able to process certain features of images much faster than that of typical human vision. A computer model as well as a hardware model has been developed to simulate parts of the fly eye. One particular area of study in the software model has been motion detection. A new method is being developed that focuses on spot localization before motion detection. Models have been developed that can localize a spot in cylindrical coordinates with respect to the center receptor. Relative motion can be detected by analyzing the changes in the location of the spots. The advantage of this method is that it requires almost no memory. By reducing the memory required, faster frame rates can be achieved. Motion detection and spot localization will serve as the foundation for additional processing for segmentation and object recognition.

This study was designed to determine the number of cases and amount of operating room time required, for a population of 600,000, to provide definitive treatment in the form of cholecystectomy for all patients admitted as an emergency with cholecystitis. The total number of patients admitted to a single NHS trust in South East Wales with the diagnosis of cholecystitis during a 1-year period was assessed. The number of laparoscopic cholecystectomies performed and the time taken was investigated with the conversion rates. There were a total of 787 individual emergency admissions attributed to cholecystitis, and 224 patients (36%) underwent cholecystectomy on the same admission. The median operative time was 77 (range, 23–238) min, and the median operating room time was 108 (range, 37–278) min. To treat all patients definitively would necessitate 12 cholecystectomies per week, requiring 1,296 min or 5.4 sessions of operating room time. A population of 600,000 could be expected to generate enough emergency cholecystectomies to require more than one operating session per day. A significant increase in emergency operating room availability would be necessary to allow the provision of definitive treatment for all emergency admissions with cholelithiasis.

Socio-economic deprivation is an important determinant of poor health and is associated with a higher incidence of end-stage renal disease, higher mortality for dialysis patients and lower chance of being listed for transplantation. The influence of deprivation on outcomes following renal transplantation has not previously been reported in the United Kingdom. The Welsh Index of Multiple Deprivation was used to assess the influence of socio-economic deprivation on outcomes for 621 consecutive renal transplant recipients from a single centre in the United Kingdom transplanted between 1997 and 2005. Outcomes measured were rate of acute rejection and graft survival. Patients from the most deprived areas were significantly more likely to experience an episode of acute rejection requiring treatment (36% vs. 27%, p=0.01) and increasing overall deprivation correlated with increasing rates of rejection (p=0.03). Income deprivation was significantly and independently associated with graft survival (HR 1.484, p=0.046). Among patients who experienced acute rejection 5-year graft survival was 79% for those from the most deprived areas compared with 90% for patients from the least deprived areas (p = 0.018). Overall socio-economic deprivation is associated with higher rate of acute rejection following renal transplantation and income deprivation is a significant and independent predictor of graft survival.

Objective To evaluate audiotape-recorded consultations at which a new diagnosis of oesophageal or gastric cancer was given to patients with reference to information retention, psychological outcome and socio-economic deprivation. Methods Fifty-eight patients were randomised to receive audiotaped consultations or not. Thirty-one patients received tapes (12 oesophageal and 19 gastric cancers) and were compared with 27 control patients (12 oesophageal and 15 gastric cancers). All patients were re-interviewed and completed a hospital anxiety and depression (HAD) questionnaire. Socio-economic deprivation scores were calculated using National Indices of Multiple Deprivation. Results Patients randomised to receive tapes were more likely to retain information (31 patients) than control patients (18 patients, p = 0.001). Median (range) HAD scores were similar in both groups of patients [HAD A tape 6 (0–21) vs. no tape 5 (2–14), HAD D tape 3 (0–23) vs. 4 (0–10), respectively]. Deprivation correlated significantly with higher HAD A scores in control patients ( p = 0.039) but was not associated with information retention ( p = 0.667). Conclusion Taped consultations were associated with significantly better information retention without adverse psychological outcomes. Providing an audiotape may reduce the effect of socio-economic deprivation on patient anxiety. Practice implications Audiotaping, or its equivalent, would be a valuable tool in the multidisciplinary approach to cancers of the upper gastrointestinal tract.

Gastrointestinal (GI) hormones regulate several GI functions, including the proliferation and repair of normal mucosa, and hormone receptors may therefore be implicated in the growth, invasion, and metastasis of cancers of the GI tract. The aim of this study was to determine the cellular distribution of gastrin in intestinal-type gastric cancers, and to determine its relationship to outcomes after R0 gastrectomy.Eighty-six consecutive patients undergoing R0 gastrectomy for adenocarcinoma were studied. Normal gastric mucosa and tumor were stained for gastrin and their specific cellular distribution was determined.The duration of survival of patients whose tumors exhibited well-differentiated gastrin-positive tumor (GPT) cells (n = 12) was significantly poorer than that of patients whose tumors were GPT-negative (5-year survival, 30% vs 54%; P = 0.037). Patients with GPT-positive intestinal-type gastric cancer (5 of 47 patients) had the poorest survival of all (median, 14 months; 5-year survival, 0%; P = 0.006). In a multivariate analysis, only lymph node metastases (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.2 to 3.79; P = 0.01) and the presence of GPT cells (HR, 6.61; 95% CI, 1.74 to 25.09; P = 0.01) were independently and significantly associated with durations of survival in patients with intestinal-type gastric cancer.The presence of GPT cells in patients with gastric adenocarcinoma is a significant and independent prognostic indicator.

To better understand the potential environmental health risk presented by West Nile virus (WNV)-contaminated feces, we quantified the amount of WNV present in the feces of experimentally infected American crows (Corvus brachyrhynchos) and fish crows (Corvus ossifragus). Peak fecal titers ranged from 10(3.5) to 10(8.8) plaque-forming units (PFU)/g for 10 American crows and from 10(2.3) to 10(6.4) PFU/g for 10 fish crows. The presence of infectious WNV in bird feces indicates a potential for direct transmission of WNV. Thus, handlers of sick or dead birds should take appropriate precautions to avoid exposure to fecal material.

We aim to compare the outcomes of patients undergoing R0 esophagectomy by a multidisciplinary team (MDT) with outcomes after surgery alone performed by surgeons working independently in a UK cancer unit. An historical control group of 77 consecutive patients diagnosed with esophageal cancer and undergoing surgery with curative intent by six general surgeons between 1991 and 1997 (54 R0 esophagectomies) were compared with a group of 67 consecutive patients managed by the MDT between 1998 and 2003 (53 R0 esophagectomies, 26 patients received multimodal therapy). The proportion of patients undergoing open and closed laparotomy and thoracotomy decreased from 21% and 5%, respectively, in control patients, to 13% and 0% in MDT patients (chi2 = 11.90, DF = 1, P = 0.001; chi2 = 5.45, DF = 1, P = 0.02 respectively). MDT patients had lower operative mortality (5.7%vs. 26%; chi2 = 8.22, DF = 1, P = 0.004) than control patients, and were more likely to survive 5 years (52%vs. 10%, chi2 = 15.05, P = 0.0001). In a multivariate analysis, MDT management (HR = 0.337, 95% CI = 0.201-0.564, P < 0.001), lymph node metastases (HR = 1.728, 95% CI = 1.070-2.792, P = 0.025), and American Society of Anesthesiologists grade (HR = 2.207, 95% CI = 1.412-3.450, P = 0.001) were independently associated with duration of survival. Multidisciplinary team management and surgical subspecialization improved outcomes after surgery significantly for patients diagnosed with esophageal cancer.

Background: British Society of Gastroenterology guidelines recommend that gastrointestinal investigations should be considered in males and post-menopausal women presenting with iron-deficiency anaemia (IDA). Aim: To compare the diagnostic yields and clinical effectiveness of upper and lower gastrointestinal (GI) investigation in detecting malignancy among patients presenting with IDA. Design: Retrospective review of case notes, endoscopy records and radiology reports. Methods: We reviewed the results of 3798 investigations in 2600 patients presenting to our hospital with IDA from October 1995 to December 2003. The findings of the 2318 gastroscopies were compared with those of the 896 colonoscopies and the 584 barium enemas. Patients diagnosed with GI malignancy were identified and their outcomes determined. Results: Gastroscopy identified 44 patients with newly-diagnosed upper GI cancer (18 oesophageal, 26 gastric). Thus for patients being gastroscoped for IDA, the Numbers Needed to Investigate (NNI) to detect each cancer was 53. Five-year survival for these 44 patients was 10%, so the NNI to identify each curable upper GI malignancy was 527. Colonoscopy or barium enema identified 111 (7.5%) patients with newly diagnosed colorectal cancer, giving a NNI of 13. Their 5-year survival was 35%, giving a NNI to identify each curable colorectal cancer patient of 38. Discussion: Potentially curable gastrointestinal malignancy was diagnosed over 13 times more commonly using colonoscopy or barium enema vs. gastroscopy. For patients presenting with IDA, our findings favour investigating the lower GI tract first, or performing both gastroscopy and colonoscopy during the same endoscopy list.

Background The aim of this study was to determine the incidence and spectrum of alarm symptoms in patients with newly diagnosed gastric cancer, and to examine the relationship between symptoms and outcome. Methods Three hundred consecutive patients with gastric adenocarcinoma were studied prospectively. The outcomes of 40 patients (13·3 per cent) without alarm symptoms (21 men; median age 69 years) were compared with those of the 260 patients (86·7 per cent) with alarm symptoms (175 men; median age 72 years). Results It was possible to perform an R0 gastrectomy more often in patients without alarm symptoms (21 patients; 52 per cent) than in those with alarm symptoms (71 patients; 27·3 per cent) (χ2 = 10·35, 1 d.f., P = 0·001). The cumulative survival rate at 5 years was 38 per cent for patients without alarm symptoms versus 15·0 per cent for those with alarm symptoms (χ2 = 10·18, 1 d.f., P = 0·001). In a multivariate analysis, distant metastasis (hazard ratio (HR) 2·73 (95 per cent confidence interval (c.i.) 2·04 to 3·66); P < 0·001), overall stage of cancer (HR 1·83 (95 per cent c.i. 1·53 to 2·19); P < 0·001) and persistent vomiting at diagnosis (HR 1·66 (95 per cent c.i. 1·26 to 2·18); P < 0·001) were independently associated with length of survival. Conclusion Alarm symptoms are absent in a significant minority of patients with gastric cancer at diagnosis; these patients stand a better chance of curative surgery and long-term survival than those with alarm symptoms.

Although acute complications necessitating emergency hospital admission are well documented in patients with carcinoma of the colon, comparable data for patients with gastric carcinoma is thin. The aim of this study, therefore, was to examine the outcomes of patients presenting to hospital as acute admissions with emergency complications of previously undiagnosed gastric cancer.Three hundred consecutive patients with gastric adenocarcinoma were studied prospectively, and subdivided into two groups according to whether the patients were referred as acute emergencies ( n = 116) or as outpatients ( n = 184).The commonest emergency complications were: abdominal pain (57%), vomiting (41%), gastrointestinal bleeding (37%), dysphagia (26%), and a palpable mass (18%). Stages of disease were significantly more advanced in patients presenting acutely (I : II : III : IV = 7 : 11 : 27 : 71) compared with patients referred via outpatients (20 : 23 : 50 : 91, Chi(2) = 3.955; DF, 1; P = 0.047). R0 gastrectomy was significantly less likely after acute presentation (23 patients; 20%) compared with patients referred via outpatients (70 patients; 38%; Chi(2) = 11.037; DF, 1; P = 0.001). Cumulative 5-year survival for patients referred acutely was 9%, compared with 22% after outpatient referral (Chi(2) = 9.11; DF, 1; P = 0.0025). Multivariate analysis revealed two factors to be significantly and independently associated with durations of survival: stage of disease (hazard ratio [HR], 1.742; 95% confidence interval [CI], 1.493-2.034; P = 0.0001) and presentation with acute complications (HR, 1.561; 95% CI, 1.151-2.117; P = 0.004).Emergency complications of gastric cancer are a significant and independent prognostic marker of poor outcome.

Eosinophils are produced in the bone marrow from CD34+ eosinophil lineage-committed progenitors, whose levels in the bone marrow are elevated in a variety of human diseases. These findings suggest that increased eosinophil lineage-committed progenitor production is an important process in disease-associated eosinophilia. The pathways central to the biology of the eosinophil lineage-committed progenitor remain largely unknown. Thus, developing new methods to investigate the regulators of eosinophil lineage-committed progenitor differentiation is needed to identify potential therapeutic targets to specifically inhibit eosinophil production. We tested cytokine regimens to optimize liquid cultures for the study of eosinophil lineage-committed progenitor and eosinophil precursor differentiation into mature eosinophils. Stem cell factor (but not fms-related tyrosine kinase 3 ligand) was required for optimal yield of eosinophils. Furthermore, we evaluated the effects of cell preservation and scale on the culture, successfully culturing functional eosinophils from fresh and frozen murine bone marrow cells and in a standard-sized and 96-well culture format. In summary, we have developed an adaptable culture system that yields functionally competent eosinophils from murine low-density bone marrow cells and whose cytokine regime includes expansion of progenitors with stem cell factor alone with subsequent differentiation with interleukin 5.

Occult infection following renal transplantation is a common diagnostic problem facing nephrologists and transplant surgeons. Patients with adult polycystic kidney disease (APKD) are prone to recurrent infections in their native kidneys and this can present with little if any localizing signs. Conventional radiological imaging with computed tomography or ultrasonography has a low sensitivity and specificity in such patients due to anatomic distortion and poor native renal function, and therefore identifying the source of sepsis can be difficult. Two cases are presented where patients with APKD who had received kidney transplants were investigated unsuccessfully for occult sepsis. White cell-labeled scanning identified the location of the infection in the patients' native polycystic kidney in both cases, allowing targeted treatment in the form of native nephrectomy. White cell-labeled scanning has an important role in the investigation of occult infection in renal allograft recipients with APKD.

Eosinophils are bone marrow-derived granulocytes that normally comprise less than 5% of leukocytes in the blood, but can be found in higher numbers in tissues such as the bone marrow and gastrointestinal tract. Eosinophilia is associated with numerous clinical disorders including atopic diseases, parasitic infections, hypereosinophilic syndrome, and cancer. Expression of Spi-C was originally reported to be limited to B cell and macrophage lineages, but we have reported that upregulation of Spi-C expression within the lung was dependent on the presence of eosinophils in an experimental chronic asthma model. In this study we investigated the role of Spi-C during eosinophil differentiation. At baseline, we observed increased numbers of bone marrow and splenic eosinophils in Spi-C-deficient (Spi-CKO) mice. Stimulation of low-density bone marrow (LDBM) cells with the eosinophil-promoting cytokine IL-5 resulted in 100-fold increase in Spi-C mRNA expression. Cultured Spi-CKO LDBM cells had an accelerated rate of eosinophil progenitor (EoP) differentiation which yielded higher numbers of eosinophils with increased effector functions, including enhanced chemotaxis, granule protein production and release compared to wild-type mice. In addition, induction of asthma resulted in amplified airway eosinophilia in Spi-CKO mice compared to wild-type controls. Together our data indicate that Spi-C negatively regulates eosinophil differentiation during homeostasis and disease. Defining the molecular regulators of eosinophil differentiation and function will undoubtedly provide key information with clinical applications. Disclosures: Rothenberg: Teva Pharmaceutical: Consultancy, Ownership Interest receiving Other; Immune Pharmaceutical: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Ownership Interest receiving, Ownership Interest receiving Other.