A growth hormone receptor SNP promotes lung cancer by impairment of SOCS2-mediated degradation.

Both humans and mice lacking functional growth hormone (GH) receptors are known to be resistant to cancer. Further, autocrine GH has been reported to act as a cancer promoter. Here we present the first example of a variant of the GH receptor (GHR) associated with cancer promotion, in this case lung cancer. We show that the GHRP495T variant located in the receptor intracellular domain is able to prolong the GH signal in vitro using stably expressing mouse pro-B-cell and human lung cell lines. This is relevant because GH secretion is pulsatile, and extending the signal duration makes it resemble autocrine GH action. Signal duration for the activated GHR is primarily controlled by suppressor of cytokine signalling 2 (SOCS2), the substrate recognition component of the E3 protein ligase responsible for ubiquitinylation and degradation of the GHR. SOCS2 is induced by a GH pulse and we show that SOCS2 binding to the GHR is impaired by a threonine substitution at Pro 495. This results in decreased internalisation and degradation of the receptor evident in TIRF microscopy and by measurement of mature (surface) receptor expression. Mutational analysis showed that the residue at position 495 impairs SOCS2 binding only when a threonine is present, consistent with interference with the adjacent Thr494. The latter is key for SOCS2 binding, together with nearby Tyr487, which must be phosphorylated for SOCS2 binding. We also undertook nuclear magnetic resonance spectroscopy approach for structural comparison of the SOCS2 binding scaffold Ile455-Ser588, and concluded that this single substitution has altered the structure of the SOCS2 binding site. Importantly, we find that lung BEAS-2B cells expressing GHRP495T display increased expression of transcripts associated with tumour proliferation, epithelial-mesenchymal transition and metastases (TWIST1, SNAI2, EGFR, MYC and CCND1) at 2 h after a GH pulse. This is consistent with prolonged GH signalling acting to promote cancer progression in lung cancer.

UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included.These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings;1. Patient populations involved in AYP transition. 2. Risks of failing transition or poor transition. 3. Models of AYP transition. 4. Patient and carer/parent perspective in AYP transition. 5. Surgical perspective.(AU)

Outcome of elective withdrawal of anti-tumour necrosis factor-α therapy in patients with Crohn's disease in established remission.

BACKGROUND AND AIMS: Outcomes of cessation of anti-TNF therapy for Crohn's disease (CD) in clinical and/or endoscopic remission in routine clinical practice is uncertain. This study aimed to evaluate clinical outcomes and factors associated with relapse in CD patients following formal disease assessment and elective anti-TNF withdrawal. METHODS: Prospective observational study of CD patients in whom anti-TNF therapy was stopped electively after ≥12months and follow-up of ≥6months. Investigations at assessment prior to cessation included ≥1 of clinical assessment, endoscopic and/or imaging. Relapse was defined as recurrent symptoms of CD requiring medical or surgical therapy. RESULTS: Eighty-six patients received anti-TNF for a median duration of 23 (12-80) months for severe active luminal (70%), fistulating perianal (25.5%) and other fistulating disease (4.5%). Relapse rates at 90,180 and 365days were 4.7%, 18.6% and 36%, respectively. If anti-TNF dose escalation occurred 6months prior to withdrawal, 88% (7/8) relapsed. Based on multivariate analysis, risk factors for relapse include ileocolonic disease at diagnosis and previous anti-TNF therapy. An elevated faecal calprotectin (FC) is likely to predict relapse (p=0.02), with a PPV of 66.7% at >50µg/g. Of 36 patients who relapsed, 31 were retreated with anti-TNF, with an overall recapture rate of 93%. CONCLUSION: Relapse rates at 1year following elective withdrawal of anti-TNF are 36%, with high retreatment response rate. Predictors of relapse include ileocolonic involvement, previous anti-TNF therapy and raised FC. Endoscopic/radiologic assessment prior to cessation of therapy does not appear to predict those at lower risk of relapse.

Systematic review: psychological morbidity in young people with inflammatory bowel disease - risk factors and impacts.

BACKGROUND: Psychological morbidity in young people aged 10-24 years, with inflammatory bowel disease (IBD) is increased, but risk factors for and impacts of this are unclear. AIM: To undertake a systematic literature review of the risk factors for and impact of psychological morbidity in young people with IBD. METHODS: Electronic searches for English-language articles were performed with keywords relating to psychological morbidity according to DSM-IV and subsequent criteria; young people; and IBD in the MEDLINE, PsychInfo, Web of Science and CINAHL databases for studies published from 1994 to September 2014. RESULTS: One thousand four hundred and forty-four studies were identified, of which 30 met the inclusion criteria. The majority measured depression and anxiety symptoms, with a small proportion examining externalising behaviours. Identifiable risk factors for psychological morbidity included: increased disease severity (r(2) = 0.152, P < 0.001), lower socioeconomic status (r(2) = 0.046, P < 0.001), corticosteroids (P ≤ 0.001), parental stress (r = 0.35, P < 0.001) and older age at diagnosis (r = 0.28, P = 0.0006). Impacts of psychological morbidity in young people with IBD were wide-ranging and included abdominal pain (r = 0.33; P < 0.001), sleep dysfunction (P < 0.05), psychotropic drug use (HR 4.16, 95% CI 2.76-6.27), non-adherence to medication (12.6% reduction) and negative illness perceptions (r = -0.43). CONCLUSIONS: Psychological morbidity affects young people with IBD in a range of ways, highlighting the need for psychological interventions to improve outcomes. Identified risk factors provide an opportunity to develop targeted therapies for a vulnerable group. Further research is required to examine groups under-represented in this review, such as those with severe IBD and those from ethnic minorities.

Problems and solutions in delivering global surgery in the 21st century.

BACKGROUND: Surgery has had low priority in global health planning, so the delivery of surgical care in low- and middle-income countries is often poorly resourced. A recent Lancet Commission on Global Surgery has highlighted the need for change. METHODS: A consensus view of the problems and solutions was identified by individual surgeons from high-income countries, familiar with surgical care in remote and poorer environments, based on recent publications related to global surgery. RESULTS: The major issues identified were: the perceived unimportance of surgery, shortage of personnel, lack of appropriate training and failure to establish surgical standards, failure to appreciate local needs and poor coordination of service delivery. CONCLUSION: Surgery deserves a higher priority in global health resource allocation. Lessons learned from participation in humanitarian crises should be considered in surgical developments.

Selective non-operative management of penetrating liver injuries at a UK tertiary referral centre.

INTRODUCTION: Selective non-operative management (SNOM) of penetrating abdominal injuries has increasingly been applied in North America in the last decade. However, there is less acceptance of SNOM among UK surgeons and there are limited data on UK practice. We aimed to review our management of penetrating liver injuries and, specifically, the application of SNOM. METHODS: A retrospective review was performed of patients presenting with penetrating liver injuries between June 2005 and November 2013. RESULTS: Thirty-one patients sustained liver injuries due to penetrating trauma. The vast majority (97%) were due to stab wounds. The median injury severity score was 14 and a quarter of patients had concomitant thoracic injuries. Twelve patients (39%) underwent immediate surgery owing to haemodynamic instability, evisceration, retained weapon or diffuse peritonism. Nineteen patients were stable to undergo computed tomography (CT), ten of whom were selected subsequently for SNOM. SNOM was successful in eight cases. Both patients who failed SNOM had arterial phase contrast extravasation evident on their initial CT. Angioembolisation was not employed in either case. All major complications and the only death occurred in the operatively managed group. No significant complications of SNOM were identified and there were no transfusions in the non-operated group. Those undergoing operative management had longer lengths of stay than those undergoing SNOM (median stay 6.5 vs 3.0 days, p<0.05). CONCLUSIONS: SNOM is a safe strategy for patients with penetrating liver injuries in a UK setting. Patient selection is critical and CT is a vital triage tool. Arterial phase contrast extravasation may predict failure of SNOM and adjunctive angioembolisation should be considered for this group.

Damage control surgery in the era of damage control resuscitation.

Damage control surgery (DCS) is a concept of abbreviated laparotomy, designed to prioritize short-term physiological recovery over anatomical reconstruction in the seriously injured and compromised patient. Over the last 10 yr, a new addition to the damage control paradigm has emerged, referred to as damage control resuscitation (DCR). This focuses on initial hypotensive resuscitation and early use of blood products to prevent the lethal triad of acidosis, coagulopathy, and hypothermia. This review aims to present the evidence behind DCR and its current application, and also to present a strategy of overall damage control to include DCR and DCS in conjunction. The use of DCR and DCS have been associated with improved outcomes for the severely injured and wider adoption of these principles where appropriate may allow this trend of improved survival to continue. In particular, DCR may allow borderline patients, who would previously have required DCS, to undergo early definitive surgery as their physiological derangement is corrected earlier.

Adsorption uptake of synthetic organic chemicals by carbon nanotubes and activated carbons.

Carbon nanotubes (CNTs) have shown great promise as high performance materials for adsorbing priority pollutants from water and wastewater. This study compared uptake of two contaminants of interest in drinking water treatment (atrazine and trichloroethylene) by nine different types of carbonaceous adsorbents: three different types of single walled carbon nanotubes (SWNTs), three different sized multi-walled nanotubes (MWNTs), two granular activated carbons (GACs) and a powdered activated carbon (PAC). On a mass basis, the activated carbons exhibited the highest uptake, followed by SWNTs and MWNTs. However, metallic impurities in SWNTs and multiple walls in MWNTs contribute to adsorbent mass but do not contribute commensurate adsorption sites. Therefore, when uptake was normalized by purity (carbon content) and surface area (instead of mass), the isotherms collapsed and much of the CNT data was comparable to the activated carbons, indicating that these two characteristics drive much of the observed differences between activated carbons and CNT materials. For the limited data set here, the Raman D:G ratio as a measure of disordered non-nanotube graphitic components was not a good predictor of adsorption from solution. Uptake of atrazine by MWNTs having a range of lengths and diameters was comparable and their Freundlich isotherms were statistically similar, and we found no impact of solution pH on the adsorption of either atrazine or trichloroethylene in the range of naturally occurring surface water (pH = 5.7-8.3). Experiments were performed using a suite of model aromatic compounds having a range of π-electron energy to investigate the role of π-π electron donor-acceptor interactions on organic compound uptake by SWNTs. For the compounds studied, hydrophobic interactions were the dominant mechanism in the uptake by both SWNTs and activated carbon. However, comparing the uptake of naphthalene and phenanthrene by activated carbon and SWNTs, size exclusion effects appear to be more pronounced with activated carbon materials, perhaps due to smaller pore sizes or larger adsorption surface areas in small pores.

The use of improvised bullet markers with 3D CT reconstruction in the evaluation of penetrating trauma.

Radio-opaque markers placed over entry and exit wounds, have been used to help evaluate penetrating injuries and provide a permanent record of wound location on plain radiographs. To date there are no published reports of the application of improvised bullet markers in the evaluation of penetrating injuries using computed tomography (CT). We report a series of 4 cases where bullet markers were used in combination with three-dimensional (3D) computerised tomography (CT) to ascertain the path of the bullets and to assess damage to vital structures. We believe that the use of bullet markers in penetrating trauma casualties undergoing CT is valuable in the surgical decision making process and allows planning of surgical approaches.

Training for overseas operational deployments and the DMCC.

Through the DMCC and similar comprehensive training, Military and NGO personnel can prepare for deployment with a greater understanding of the issues that will confront them whilst there. Progression through the modules will provide them with a greater skill set to meet the challenges that await them and allow them to be an effective and valuable member of the team.

Information required to provide informed consent for endoscopy: an observational study of patients' expectations.

BACKGROUND AND STUDY AIMS: The aim of this study was to determine how much information patients require about the risk of complications in order to provide informed consent to undergo endoscopy. PATIENTS AND METHODS: Endoscopic complications and their consequences were discussed with consecutive patients who had undergone endoscopy. The patients were asked how common each complication would have to be for them to require information about the complication before providing adequately informed consent. RESULTS: Data were obtained from 150 gastroscopy patients (51% male, median age 55.5 years) and 150 colonoscopy patients (60% male, median age 54.4 years). Patients in both groups were more likely to want to know about major rather than minor complications at a lower level of risk (P < 0.001 at a risk greater than one in 1000). Similar proportions of gastroscopy patients (n = 29, 19%) and colonoscopy patients (n = 21, 14 %) wanted to know about all possible complications, no matter how inconsequential or rare. Colonoscopy patients were less likely to want no information about any complications than gastroscopy patients (n = 1, 0.7% and n = 15, 10%, respectively; P < 0.001). CONCLUSIONS: The information patients require in order to provide informed consent is very variable. Many appear to make a judgement about the need for information depending on the perceived severity of the complication, but some want information about all complications, irrespective of risk and severity. The level of risk at which they require this information is likely to be higher than the level used by doctors who are obtaining consent from patients. The process may be improved by providing procedure-specific information leaflets that offer information regarding common and serious complications.

Synchronous liver resection and cryotherapy for colorectal metastases: survival analysis.

INTRODUCTION: The value of synchronous liver resection and cryotherapy ablation remains controversial for colorectal metastases where complete resection is not possible by conventional liver surgery alone. OBJECTIVE: To review the long-term survival of patients treated using this approach at our institution. METHODS: A review was undertaken of data held in the prospectively collected liver surgery database of all patients who underwent synchronous liver resection and cryotherapy. Survival analysis was performed and data recorded on the total number of metastases at initial surgery and the number of lesions treated by cryoablation. RESULTS: Ninety-three patients with colorectal metastases underwent synchronous liver resection and cryotherapy. Data were available on 86 patients with a median follow-up of 18 months (range 1-83). The median number of metastases at initial surgery was four (range 2-11) and the number of lesions treated by cryotherapy ablation was two (range 1-8). Eighty-four per cent had a hepatic artery catheter inserted at surgery and at least one cycle of post-operative hepatic artery chemotherapy. One-, three- and five-year survival was 85%, 43% and 19% respectively, with a median survival of 33 months (95% confidence interval 19.9-42.1). Site of recurrence was recorded and presented. CONCLUSIONS: Patients with liver metastases that are not amenable to resection alone can achieve worthwhile median survival with synchronous liver resection and cryotherapy ablation.

Validation of direct intraabdominal pressure measurement using a continuous indwelling compartment pressure monitor.

BACKGROUND: According to recommendations, intraabdominal pressure should be monitored every 8 hours for patients at high risk of abdominal compartment syndrome. Continuous intraabdominal pressure monitoring may be valuable for these patients. METHODS: For 15 patients undergoing laparoscopic surgery, a pressure monitor was introduced after formation of pneumoperitoneum. During the procedure, the laparoscopic insufflator pressure was varied. The pressure monitor values and the time to equilibrium were recorded. RESULTS: Altogether, 152 pressure recordings were taken for the patients studied. The measurements from the insufflator and pressure monitor were compared using a Bland-Altman plot. The mean difference between the techniques was 0.04 +/- 3.8, and 95% of the points from the pressure monitor were within two standard deviations of the mean difference. Pressure changes were essentially "real time." CONCLUSIONS: The intracompartmental pressure monitor provides accurate, rapid, and direct measurement of intraabdominal pressure, and may be a useful tool for continuous intraabdominal pressure measurement among patients at risk of abdominal compartment syndrome.

FAST on operational military deployment.

BACKGROUND AND OBJECTIVE: Handheld ultrasound, because of its light weight, size, rugged design, and relative simplicity of use is ideal for use on operational military deployment. These machines have been used in the diagnosis of a range of traumatic conditions including abdominal, thoracic, and extremity trauma in the hospital environment, yet few data exist on their use during military operations. This paper presents experience of handheld focused assessment with sonography for trauma (FAST) on operational military deployment. METHOD: Over a two month period, handheld FAST was performed by a single surgeon during the circulation phase of the primary survey in trauma patients presenting to the British Military Hospital in Iraq. RESULTS: Fifteen from casualties underwent a FAST examination. Ten were victims of blunt trauma, two had received injuries anti-personnel mines, and three had penetrating injuries from ballistic trauma. There was one positive FAST, confirmed at laparotomy as bleeding from a liver injury. Thirteen scans were negative and remained negative on repeat FAST at 6 hours. One further patient with a negative FAST underwent laparotomy because of transectory, there was no intra-abdominal blood or fluid at surgery. CONCLUSION: Handheld FAST is a valuable technique for investigating abdominal or thoracic bleeding in single or multiple casualty events on operational military deployment.

Ultrasound-guided insertion of subclavian venous access ports.

INTRODUCTION: Central venous cannulation is an integral part of venous access port (portacath) placement for intravenous chemotherapy. NICE guidelines have suggested that CVC should be performed under ultrasound guidance. The technique of ultrasound-guided subclavian cannulation is reviewed and our experience presented. PATIENTS AND METHODS: Retrospective analysis of data on patients undergoing ultrasound-guided portacath placement for the failure rate and the incidence of complications. RESULTS: We were successful in cannulating the subclavian vein in 44 of 55 patients. There was one arterial puncture and no haemothorax or pneumothorax with the technique (complication rate 1.8%). CONCLUSION: An ultrasound-guided approach should be the standard technique for central venous cannulation in portacath placement.