Prospective cohort study of surgical trainee experience of access to gastrointestinal endoscopy training in the UK and Ireland.

INTRODUCTION: Surgical trainees are reporting barriers to training in gastrointestinal (GI) endoscopy. This snapshot survey aimed to gather data on variation in access to quality GI endoscopy training for Colorectal and Upper Gastrointestinal (GI) surgical trainees across the UK and Ireland. MATERIALS AND METHODS: An online 20-point survey was designed and distributed nationally to surgical trainee members of the Association of Surgeons in Training (ASiT), Dukes and The Roux Group (formerly Association of Upper Gastrointestinal Surgeons of Great Britain and Ireland Trainees). The survey was designed in collaboration with The Roux Group for Upper GI trainees and the Dukes' Club for Colorectal trainees. RESULTS: 218 responses were received, most with a Colorectal or Upper GI sub-specialty interest (colorectal 56.0%; upper GI surgery 25.7%). Only 28.6% of trainees attended a dedicated training endoscopy list at least once a week with 28.1% not attending any at all. Less than half of trainees reported having endoscopy formally timetabled on rotas (36.9%). Most trainees (88.0%) encountered difficulties in gaining endoscopy training including lack of available lists (77.2%), conflicting operative commitments (59.4%), preferential allocation of lists to gastroenterology trainees (57.9%) and resistance from endoscopy departmental leads (38.6%). Regarding JAG accreditation, 77.1% respondents felt it should be mandatory prior to CCT with 80.3% believing this would lead to better access to dedicated endoscopy training equivalent to gastroenterology trainees. 93.1% trainees felt that attaining JAG accreditation by surgical trainees was important to patient care. DISCUSSION: This study demonstrates significant barriers in accessing GI endoscopy training for general surgical trainees which urgently needs to be improved. In order to meet JAG training requirements for surgical trainees, a multifaceted collaborative approach from surgical and gastroenterology training bodies, local JAG trainers and the General Surgery SAC and JCST is required. This is to ensure that endoscopy is promoted and a robust model of training is successfully designed and delivered to general surgery trainees.

Outcomes of surgery in patients aged ≥90 years in the general surgical setting.

Introduction An increasing proportion of the population is living into their nineties and beyond. These high risk patients are now presenting more frequently to both elective and emergency surgical services. There is limited research looking at outcomes of general surgical procedures in nonagenarians and centenarians to guide surgeons assessing these cases. Methods A retrospective analysis was conducted of all patients aged ≥90 years undergoing elective and emergency general surgical procedures at a tertiary care facility between 2009 and 2015. Vascular, breast and endocrine procedures were excluded. Patient demographics and characteristics were collated. Primary outcomes were 30-day and 90-day mortality rates. The impact of ASA (American Society of Anesthesiologists) grade, operation severity and emergency presentation was assessed using multivariate analysis. Results Overall, 161 patients (58 elective, 103 emergency) were identified for inclusion in the study. The mean patient age was 92.8 years (range: 90-106 years). The 90-day mortality rates were 5.2% and 19.4% for elective and emergency procedures respectively (p=0.013). The median survival was 29 and 19 months respectively (p=0.001). Emergency and major gastrointestinal operations were associated with a significant increase in mortality. Patients undergoing emergency major colonic or upper gastrointestinal surgery had a 90-day mortality rate of 53.8%. Conclusions The risk for patients aged over 90 years having an elective procedure differs significantly in the short term from those having emergency surgery. In selected cases, elective surgery carries an acceptable mortality risk. Emergency surgery is associated with a significantly increased risk of death, particularly after major gastrointestinal resections.

Orthopaedic surgical site infection surveillance in NHS England: national audit of current practice.

AIMS: The importance of accurate identification and reporting of surgical site infection (SSI) is well recognised but poorly defined. Public Health England (PHE) mandated collection of orthopaedic SSI data in 2004. Data submission is required in one of four categories (hip prosthesis, knee prosthesis, repair of neck of femur, reduction of long bone fracture) for one quarter per year. Trusts are encouraged to carry out post-discharge surveillance but this is not mandatory. Recent papers in the orthopaedic literature have highlighted the importance of SSI surveillance and the heterogeneity of surveillance methods. However, details of current orthopaedic SSI surveillance practice has not been described or quantified. PATIENTS AND METHODS: All 147 NHS trusts in England were audited using a structured questionnaire. Data was collected in the following categories: data collection; data submission to PHE; definitions used; resource constraints; post-discharge surveillance and SSI rates in the four PHE categories. The response rate was 87.7%. RESULTS: Variation in practice was clear in all categories in terms of methods and timings of data collection and data submission. There was little agreement on SSI definitions. At least six different definitions were used, some trusts using more than one definition. Post-discharge surveillance was carried out by 62% of respondents but there was again variation in both the methods and staff used. More than half of the respondents felt that SSI surveillance in their unit was limited by resource constraints. SSI rates ranged from 0% to 10%. CONCLUSION: This paper quantifies the heterogeneity of SSI surveillance in England. It highlights the importance of adequate resourcing and the unreliability of relying on voluntary data collection and submission. Conformity of definitions and methods are recommended to enable meaningful SSI data to be collated. Cite this article: Bone Joint J 2017;99-B:171-4.

Inorganic and organozinc fluorocarboxylates: synthesis, structure and materials chemistry.

The organozinc fluorocarboxylates RZnO2CRf and RZnO2CRf·TMEDA, along with Zn(O2CRf)2·TMEDA (R = Me, Et; Rf = C2F5, C3F7) have been synthesized. The structures of EtZnO2C2F5 (5), EtZnO2C3F7 (7), EtZnO2C2F5·TMEDA (11), Zn(O2C2F5)2·TMEDA (13), along with products from the adventitious reaction with either O2 or H2O, Zn10Me4(OMe)4(O2CC2F5)12 (2), Zn9Et2(O2CC2F5)12(O)2 (6), Zn8Et4(OEt)4(O2CC3F7)6(O) (8), [Zn(O2CC3F7)2·TMEDA]2·H2O (15) have been determined. Thin films of oriented ZnO have been deposited on glass substrates by low-pressure chemical vapor deposition (LPCVD) using 3 and 10 as precursors, though no fluorine incorporation in the films was noted. LPCVD using 13 as precursor also yielded fluorine-free ZnO, but lacking the oriented growth observed using 3, 10. However, 5, which exhibits short intermolecular Zn···F contacts in the solid state, thermally decomposes to bulk ZnF2.

Formation of PbS materials from lead xanthate precursors.

Six lead xanthate adducts Pb(S(2)COR)(2).L [R = Et, (n)Bu, L = bipy, TMEDA (tetramethylethylenediamine), PMDETA (pentamethyldiethylenetriamine)] have been synthesised and the structures of all, save Pb(S(2)COBu(n))(2).TMEDA (4) which is an oil, determined. Pb(S(2)COEt)(2).TMEDA (3) is seven-coordinate at lead through three chelating ligands and one weak intermolecular Pb‥S interaction. Both Pb(S(2)COR)(2).bipy [R = Et (1), (n)Bu (2)] are dimers in which one xanthate is terminal and the other µ(2) bridging at each sulphur, generating an eight-coordinate lead when the bipy donor is included. Both Pb(S(2)COR)(2).PMDETA [R = Et (5), (n)Bu (6)] are seven-coordinate at lead by virtue of two bidentate chelating xanthate ligands and a tridentate PMDETA; there are no intermolecular interactions. Trends in the (207)Pb NMR chemical shifts mirror the changes in the intramolecular coordination number across the series. Pb(S(2)COEt)(2).TMEDA (3) has been used to deposit PbS films on glass, Mo-coated glass and Si by AACVD. Pb(S(2)COEt)(2) also generated PbS nanocubes when decomposed under an autogenerated pressure.

Role of calcium in the pathway for milk protein secretion and possible relevance for mammary gland physiology.

In an attempt to define control points within the secretory pathway for casein synthesis and secretion, we have examined the role of both cytosolic and intra-organelle Ca2+ in the control of casein synthesis, phosphorylation and secretion. In addition, the possible role of cell volume changes in stretch-activation of Ca2+ signals was examined. Examination of the kinetics of casein secretion from freshly isolated lactating mouse mammary acini showed that a portion of the newly synthesized casein was secreted in a constitutive manner. A further portion remained within the cells, and this was released following elevation of the intracellular free calcium concentration ([Ca2+]i) using ionomycin, indicating the presence of a Ca(2+)-regulated pathway for casein release. An increase in [Ca2+]i occurred in response to hypotonic challenge to induce cell swelling, and this involved both Ca2+ entry and Ca2+ mobilization from intracellular stores. Experiments examining the effects of depletion of intra-organelle Ca2+ indicated that intra-organelle Ca2+ was required for maintained casein phosphorylation, but not its secretion. Depletion of Ca2+ from the endoplasmic reticulum led to a marked inhibition of casein synthesis. The possible significance of these control mechanisms for the physiology of the mammary gland is discussed.

Evidence against an acute inhibitory role of nSec-1 (munc-18) in late steps of regulated exocytosis in chromaffin and PC12 cells.

nSec-1 (munc-18) is a mammalian homologue of proteins implicated in constitutive exocytosis in yeast and neurotransmission in Caenorhabditis elegans and Drosophila. Mutant phenotypes in these species suggest that nSec-1 is likely to be required for neurotransmission. Various other data have been interpreted as suggesting that nSec-1 could also be a negative regulator of Ca2+-dependent exocytosis. We have tested this possibility by introducing exogenous nSec-1 into permeabilised chromaffin or PC12 cells and examining its effects on Ca2+-induced and alpha-soluble N-ethylmaleimide-sensitive fusion protein attachment protein-stimulated exocytosis. No effects of exogenous nSec-1 were observed in these assays. In addition, the effect of nSec-1 overexpression in transiently transfected PC12 cells on reporter growth hormone (GH) secretion was examined. Overexpression of nSec-1 resulted in a marked increase in GH production, reflected in an increase in both cell-associated and medium GH levels. The relative amounts retained in the cells were unaffected by nSec-1 overexpression, indicating that GH storage was unaffected and that the major effect was on its synthesis. In contrast, nSec-1 overexpression did not affect the proportion of GH that was released following stimulation in intact or permeabilised cells. These results suggest either that nSec-1 is already expressed at sufficient levels and remains so following permeabilisation or that nSec-1 may not be an acute inhibitory regulator of Ca2+-dependent exocytosis in chromaffin or PC12 cells.

A hypo-osmotically induced increase in intracellular Ca2+ in lactating mouse mammary epithelial cells involving Ca2+ influx.

Using a fluorescent Ca2+-sensitive dye, we studied the effect of hypo-osmotic stress on the intracellular free Ca2+ concentration ([Ca2+]i) in acini freshly isolated from lactating mouse mammary gland. The basal [Ca2+]i of mammary acini was unaffected by a 50% (v/v) dilution of suspensions with isotonic or hypertonic buffer, or after ionic (iso-osmotic) dilution (external Ca2+ was 3 mM). Hypo-osmotic dilution (50%) elicited a rapid increase in [Ca2+]i comprising a large, transient elevation, followed by a maintained plateau phase. No hypo-osmotically induced rise in [Ca2+]i was observed in the absence of extracellular Ca2+. Neither microtubule disassembly using nocodazole nor actin disruption with cytochalasin D prevented hypo-osmotically evoked stimulation of [Ca2+]i. Pre-incubation of acini with nifedipine did not prevent hypo-osmotically induced stimulation of [Ca2+]i, whereas a non-specific cation channel blocker, gadolinium, partially inhibited the increases in [Ca2+]i induced by hypo-osmotic stress. Furthermore, the transient component was still apparent, and not diminished in magnitude, after [Ca2+]i had been elevated by mobilisation of Ca2+ from intracellular stores using thapsigargin. The results demonstrate that hypo-osmotic stress generates an increase in [Ca2+]i in lactating mammary epithelial cells, the major, transient component of which appears to be due to influx of extracellular Ca2+.

Similar effects of alpha- and beta-SNAP on Ca(2+)-regulated exocytosis.

Soluble N-ethylmaleimide-sensitive fusion protein attachment proteins (SNAP) proteins function in Ca(2+)-regulated exocytosis. Recent work (Schiavo et al. (1996) Nature 378, 733-736) based on in vitro protein interactions has raised the possibility that alpha- and beta-SNAPs have distinct roles in exocytosis. We have examined this possibility by comparing the activities of recombinant alpha- and beta-SNAPs. Both of these proteins were able to similarly bind NSF and activate its ATPase activity but to a lesser extent than gamma-SNAP. When introduced into digitoninpermeabilised chromaffin cells, both alpha- and beta-SNAP stimulated Ca(2+)-regulated exocytosis in a MgATP-dependent manner. The dose-response relationships for these proteins were essentially the same and addition of both proteins did not lead to any further increase in exocytosis above that due to each protein alone. We conclude that alpha- and beta-SNAPs are interchangeable isoforms with similar functions in regulated exocytosis.

The role of lipocortin-1 in dexamethasone-induced suppression of PGE2 and TNF alpha release from human peripheral blood mononuclear cells.

1.Lipocortin-1 and its N-terminal derivatives exert potent inhibitory actions in various models of acute inflammation. The present study examined the ability of lipocortin (LC)-1 to suppress the release of the acute pro-inflammatory mediators, tumour necrosis factor (TNF alpha) and prostaglandin E2 (PGE2) from human peripheral blood mononuclear cells (PBMC) stimulated with lipopolysaccharide (LPS) or recombinant human interleukin-1 beta (rhIL-1 beta). 2. LPS (10 micrograms ml-1) stimulated release of TNF alpha and PGE2 from PBMC was significantly inhibited by (4 h) co-incubation of the cells with 10(-6) M dexamethasone (Dex), but not with 10(-9) M to 10(-7) M of a N-terminal fragment (amino acids 1-188) of recombinant human LC-1 (LC-1 fragment). However, Dex suppression of LPS-stimulated TNF alpha and PGE2 secretion from PBMC was reversed when polyclonal antibody to LC-1 fragment (1:10,000 dilution) was included in the medium. rhIL-1 beta (5 x 10(-8) M)-stimulated release of TNF alpha and PGE2 from PBMC (after 18 h) was abolished by co-incubation of the cells with 10(-7) M LC-1 fragment. 3. After incubation with Dex (4 h), cellular proteins from PBMC were immunoblotted using anti-LC-1 fragment antibody (which showed to cross-reactivity with human annexins 2 to 6). Dex caused no increase in immunoreactive (ir)LC-1 content of PBMC, although there was a three fold increase in the amount of a lower mass species with LC-1-like immunoreactivity. This was accompanied by the appearance of irLC-1 in the extracellular medium. 4. The results of the present study implicate endogenous LC-1 in glucocorticoid suppression of TNF alpha and PGE2 release from human PBMC and suggest an extracellular site of action for LC-1. LC-1 may also inhibit rhIL-1 beta-stimulated TNF alpha and PGE2 secretion from PBMC.

Lipocortin-1 inhibits CRH stimulation of plasma ACTH and IL-1 beta-stimulated hypothalamic CRH release in rats.

A 188-amino acid NH2-terminal fragment of recombinant human lipocortin-1 (rhLC-1) (LC-1 fragment) mimics glucocorticoid (and rhLC-1) inhibition of corticotrophin-releasing hormone (CRH)-stimulated release of adrenocorticotrophin (ACTH) from rat anterior pituitary and cytokine-stimulated CRH release from rat hypothalamus in vitro. The present in vivo study examined the effect of LC-1 fragment on CRH stimulation of rat plasma ACTH and release of rat hypothalamic CRH. Coinjection of LC-1 fragment inhibited the increase in plasma ACTH concentration stimulated by either central (76% inhibition) or peripheral (72% inhibition) injection of CRH and abolished the (62%) depletion of hypothalamic immunoreactive (ir)CRH stimulated by central injection of interleukin-1 beta. Central injection of the CRH functional analogue sauvagine led to a 46% reduction (P > 0.05, 2-way analysis of variance) in rat hypothalamic irCRH content, which was reversed by coinjection of LC-1 fragment. These results indicate that LC-1 can suppress the activity of the hypothalamic-pituitary axis in the rat, possibly by inhibiting a positive feedback mechanism controlling release of hypothalamic CRH.

Transforming growth factor-beta 1 inhibits casein secretion from differentiating mammary-gland explants but not from lactating mammary cells.

Transforming growth factor-beta (TGF beta) is important in the maturation and function of the mammary gland and is present in milk. We have examined whether, in addition to inhibiting lactogenesis, TGF beta exerts acute regulatory effects on lactating mammary cells. The isoform TGF beta 1 at 5 and 50 ng/ml suppressed the onset of lactation and the subsequent production of beta-casein by differentiating mouse mammary explants from pregnant mice. By contrast, it did not inhibit protein synthesis or secretion from acini isolated from lactating-mouse mammary gland or protein secretion from explants from lactating mice. These data indicate that TGF beta inhibits the onset of casein secretion, but is not an acute regulator of casein synthesis or secretion from differentiated lactating mammary cells.