Color changing bioadhesive barrier for peripherally inserted central catheters.

Bacteria migration at catheter insertion sites presents a serious complication (bacteraemia) with high mortality rates. One strategy to mediate bacteraemia is a physical barrier at the skin-catheter interface. Herein a colorimetric biosensor adhesive (CathoGlu) is designed and evaluated for both colorimetric detection of bacterial infection and application as a bacteria barrier. The design intent combines viscous, hydrophobic bioadhesive with an organic pH indicator (bromothymol blue). Visual observation can then distinguish healthy skin at pH = ∼5 from an infected catheter insertion site at pH = ∼8. The liquid-to-biorubber transition of CathoGlu formulation occurs via a brief exposure to UVA penlight, providing an elastic barrier to the skin flora. Leachates from CathoGlu demonstrate no genotoxic and skin sensitization effect, assessed by OECD-recommended in vitro and in chemico assays. The CathoGlu formulation was found non-inferior against clinically approved 2-octyl-cyanoacrylate (Dermabond™), and adhesive tape (Micropore™) within an in vivo porcine model. CathoGlu skin adhesive provides new opportunities to prevent sepsis in challenging clinical situations.

Medical Specialty Interest Survey (MSIS): understanding career interest and specialty training in commencing Australian medical interns.

AIM: To assess specialisation interests in commencing interns and create a standardised survey to aid medical schools, supervisors and health services in quantifying, understanding and supporting medical career development to improve medical workforce planning. METHOD: The Medical Specialty Interest Survey (MSIS) cross-sectional study was used. Incoming interns at a multisite tertiary hospital network in Melbourne, Australia rated their desire to pursue each specialty as a career using a Likert scale (1-5). 47 Medical Board of Australia Medical Specialties were included in the survey. RESULTS: Completion rate was 123 of 124 (99.2%). The overall mean desirability was 2.62, suggesting on average more specialties were deemed less preferred. Critical care specialties were most popular, while surgical specialties had least interest. Gastroenterology and cardiology were most popular among internal medicine specialties. General practice had low correlation with other specialties (Pearson correlation mean R coefficient 0.106 compared with overall mean 0.208), suggesting interns interested in general practice exhibit less interest in other specialties, and interest in specialisation confers low interest in general practice. Psychiatry had the lowest mean R coefficient of 0.088. CONCLUSIONS: The MSIS quantifies relative interest in 47 medical specialties and specialty interest correlations among final-year medical students/incoming interns. The MSIS may be a tool for medical schools, healthcare services and government agencies to better understand the career interest among medical students and pre-vocational doctors and therefore improve doctor retention and well-being.

Protracted severe systemic cytomegalovirus disease in an immunosuppressed patient with ulcerative colitis.

A 33-year-old man with ulcerative colitis presented with 5-day history of fever, night sweats, abdominal pain and increased stool frequency. He was on mesalazine M/R 1 g once daily, 6-mercaptopurine (6-MP) 75 mg once daily and prednisolone 40 mg once daily. Examination revealed fever and tachycardia. Blood examinations identified a persistent leucopenia, C reactive protein of 23 mg/L and an initial alanine transaminase of 855 IU/L. Flexible sigmoidoscopy revealed well-demarcated, punched-out ulcers in the proximal rectum and distal sigmoid, with histology pathognomonic of cytomegalovirus (CMV). CMV DNA PCR was 51 140 copies/mL. Despite prompt withdrawal of 6-MP, steroids and initiation of intravenous ganciclovir on day 2 of admission, his systemic illness, diarrhoea and fever persisted until day 19 of antiviral therapy. Other copathogens and lymphoma were ruled out on serology and CT scan, respectively. After an unusually prolonged course of antiviral therapy, the patient made a full clinical recovery, bloods normalised and there were two consecutive undetectable CMV DNA PCRs.

Mercaptopurine versus placebo to prevent recurrence of Crohn's disease after surgical resection (TOPPIC): a multicentre, double-blind, randomised controlled trial.

BACKGROUND: Up to 60% of patients with Crohn's disease need intestinal resection within the first 10 years of diagnosis, and postoperative recurrence is common. We investigated whether mercaptopurine can prevent or delay postoperative clinical recurrence of Crohn's disease. METHODS: We did a randomised, placebo-controlled, double-blind trial at 29 UK secondary and tertiary hospitals of patients (aged >16 years in Scotland or >18 years in England and Wales) who had a confirmed diagnosis of Crohn's disease and had undergone intestinal resection. Patients were randomly assigned (1:1) by a computer-generated web-based randomisation system to oral daily mercaptopurine at a dose of 1 mg/kg bodyweight rounded to the nearest 25 mg or placebo; patients with low thiopurine methyltransferase activity received half the normal dose. Patients and their carers and physicians were masked to the treatment allocation. Patients were followed up for 3 years. The primary endpoint was clinical recurrence of Crohn's disease (Crohn's Disease Activity Index >150 plus 100-point increase in score) and the need for anti-inflammatory rescue treatment or primary surgical intervention. Primary and safety analyses were by intention to treat. Subgroup analyses by smoking status, previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis were also done. This trial is registered with the International Standard Randomised Controlled Trial Register (ISRCTN89489788) and the European Clinical Trials Database (EudraCT number 2006-005800-15). FINDINGS: Between June 6, 2008, and April 23, 2012, 240 patients with Crohn's disease were randomly assigned: 128 to mercaptopurine and 112 to placebo. All patients received at least one dose of study drug, and no randomly assigned patients were excluded from the analysis. 16 (13%) of patients in the mercaptopurine group versus 26 (23%) patients in the placebo group had a clinical recurrence of Crohn's disease and needed anti-inflammatory rescue treatment or primary surgical intervention (adjusted hazard ratio [HR] 0·54, 95% CI 0·27-1·06; p=0·07; unadjusted HR 0·53, 95% CI 0·28-0·99; p=0·046). In a subgroup analysis, three (10%) of 29 smokers in the mercaptopurine group and 12 (46%) of 26 in the placebo group had a clinical recurrence that needed treatment (HR 0·13, 95% CI 0·04-0·46), compared with 13 (13%) of 99 non-smokers in the mercaptopurine group and 14 (16%) of 86 in the placebo group (0·90, 0·42-1·94; pinteraction=0·018). The effect of mercaptopurine did not significantly differ from placebo for any of the other planned subgroup analyses (previous thiopurines, previous infliximab or methotrexate, previous surgery, duration of disease, or age at diagnosis). The incidence and types of adverse events were similar in the mercaptopurine and placebo groups. One patient on placebo died of ischaemic heart disease. Adverse events caused discontinuation of treatment in 39 (30%) of 128 patients in the mercaptopurine group versus 41 (37%) of 112 in the placebo group. INTERPRETATION: Mercaptopurine is effective in preventing postoperative clinical recurrence of Crohn's disease, but only in patients who are smokers. Thus, in smokers, thiopurine treatment seems to be justified in the postoperative period, although smoking cessation should be strongly encouraged given that smoking increases the risk of recurrence. FUNDING: Medical Research Council.

Meckel's diverticulum: new solutions for an old problem?

Meckel's diverticulum (MD) is the most commonly encountered true diverticulum in the small bowel. Although overall a rare cause of gastrointestinal bleeding, it remains an important differential in a child/young adult presenting with lower gastrointestinal bleeding. We present two MD cases, one associated with brisk bleeding resulting in haemodynamic instability and the other in insidious blood loss causing symptoms of chronic iron deficiency. These cases illustrate the heterogeneous nature of the clinical picture associated with Meckel's diverticulae, a condition most gastroenterological and surgical units will encounter. We subsequently discuss the diagnostic and management dilemma Meckel's diverticulae pose and appraise the latest evidence and management strategies in this regard.

Evolving strategies to reduce colectomy rates in primary sclerosing cholangitis-inflammatory bowel disease: clinical remission of corticosteroid refractory colitis post-liver transplant with vedolizumab.

Primary sclerosing cholangitis (PSC) is associated with inflammatory bowel disease (IBD) in approximately 70% of patients, with ulcerative colitis (UC) being the most common subtype of IBD identified. There is a paucity of data on the optimum management strategy for IBD flares in the post-liver transplant patient, particularly when refractory to conventional treatments. Vedolizumab is a novel gut-specific monoclonal antibody, which has recently been approved for use by National Institute for Health and Care Excellence for moderate-to-severe UC. We present an exemplar case of successful use of vedolizumab in the management of corticosteroid refractory PSC-IBD after liver transplantation.

Attitude to e-learning among newly qualified doctors.

BACKGROUND: e-Learning plays an increasingly important role in medical education. Much research has focused on the evaluation of individual modules among medical students or more senior trainee doctors. We studied the attitude of newly qualified foundation level-1 doctors (FY1s) towards a blended learning programme to gain insight into the perceived role of e-learning in relation to classroom and experiential learning. METHOD: The blended learning strategy consisted of weekly 3-hour sessions of lectures and flexible e-learning sessions. A questionnaire survey was conducted among 54 per cent (37/69) of FY1 doctors, towards the end of their first year post qualification. RESULTS: The majority of FY1s had to carry out additional e-learning outside of work. When asked where was best to carry out e-learning, 54 per cent preferred to e-learn both at work and at home, whereas 38 per cent preferred to e-learn outside of work exclusively. An equal preference for a classroom-only strategy and a blended programme was reported. Seventy-three per cent of the FY1s thought that e-learning should not be part of their compulsory weekly teaching programme. Fifty-four per cent of FY1s thought that e-learning had been useful for their education and training in their FY1 year. The e-learning package cited as being most useful was the safe prescribing e-programme, pioneered locally. CONCLUSION: Newly qualified doctors value e-learning as an adjunct to experiential and lecture-based teaching, and most prefer it as part of a blended learning programme at work or at home. Medical educators must place equal emphasis on the delivery and administration of e-learning as well as on the course design.

Accidental hijab pin ingestion in Muslim women: an emerging endoscopic emergency?

Ingested foreign body is an infrequent indication for emergency endoscopy in the adult gastroenterology practice. We describe the clinical features and endoscopic management of the first four cases of accidental ingestion of hijab pins by Muslim women in our unit, all presenting within a 12-month period. The pins were all successfully retrieved without any complications. In this report, we review published guidelines and the current literature, as well as discussing the approach (conservative vs proactive endoscopic retrieval) and timing of endoscopic treatment. The Muslim community may need to be alerted to the potential health hazard of hijab pins.

Investigational new drugs in the treatment of inflammatory bowel disease: a review.

The unraveling of the immuno-pathobiology of inflammatory bowel disease (IBD) in the past three decades has ushered in a new era of translational medicine. The biotechnology revolution has resulted in a paradigm shift in how clinicians view and treat IBD. Anti-tumor necrosis factor (TNF)-α strategies using infliximab and adalimumab currently dominate the therapeutic arena. Better understanding of how these biologicals work is driving the quest for loftier therapeutic goals of achieving mucosal healing, sustaining deep remission, and even modifying the natural history of IBD. However, not all patients respond to anti-TNF drugs. Immune-mediated adverse reactions and loss of efficacy with time also limit their use. There are many investigational drugs undergoing active clinical trials. Many have not fulfilled their early promises but some are potentially making the transition from bench to trial and to the bedside in the near future. Clinicians and investigators need to underpin our excitement with caution for the unknown long-term consequences of modulating cytokines and selective adhesion molecules in human. Here we provide an overview of investigational new drugs and other therapeutic strategies currently undergoing clinical trials in IBD.

Understanding of chemoprophylaxis and concordance in inflammatory bowel disease.

AIM: To assess patients' understanding for the reasons for taking 5-aminosalicylic acid or ursodeoxycholic acid as chemoprophylaxis against colorectal carcinoma associated with inflammatory bowel disease (IBD). METHODS: A questionnaire-based study using a 5-point opinion scale was performed. One hundred and ninety-two patients with colitis only and 74 patients with primary sclerosing cholangitis and IBD were invited to take part. RESULTS: Overall response rate was 58%. Sixty-four percent of patients claimed full concordance with chemoprophylaxis for maintenance of remission. Eighty-four percent of patients considered daily concordance during remission to be very important. Seventy-five percent stated they understood the reasons for taking the drugs. However, only 50% of the patients were aware of any link of their condition to bowel cancer. Seventy-nine percent of patients felt their concordance and understanding would be improved if they were informed of the chemoprophylactic potential of the medication. CONCLUSION: Despite good self-reported concordance, half of the patients were unaware of an association between colitis and bowel cancer. Explaining the potential chemoprophylactic benefits may enhance patients' overall concordance to 5-aminosalicylic acid and ursodeoxycholic acid and help maintain remission.

The class A macrophage scavenger receptor type I (SR-AI) recognizes complement iC3b and mediates NF-κB activation.

The macrophage scavenger receptor SR-AI binds to host tissue debris to perform clearance and it binds to bacteria for phagocytosis. In addition, SR-AI modulates macrophage activation through cell signaling. However, investigation of SR-AI signaling on macrophages is complicated due to its promiscuous ligand specificity that overlaps with other macrophage receptors. Therefore, we expressed SR-AI on HEK 293T cells to investigate its ligand binding and signaling. On 293Tcells, SR-AI could respond to E. coli DH5α, leading to NF-κB activation and IL-8 production. However, this requires E. coli DH5α to be sensitized by fresh serum that is treated with heat-inactivation or complement C3 depletion. Anti-C3 antibody inhibits the binding of SR-AI to serum-sensitized DH5α and blocks DH5α stimulation of SR-AI signaling. Further analysis showed that SR-AI can directly bind to purified iC3b but not C3 or C3b. By mutagenesis, The SRCR domain of SR-AI was found to be essential in SR-AI binding to serum-sensitized DH5α. These results revealed a novel property of SR-AI as a complement receptor for iC3b-opsonized bacteria that can elicit cell signaling.

Diffuse intestinal angiomatosis as a possible paraneoplastic manifestation of small cell lung cancer: a case of small bowel angiomatosis.

Vascular malformations are rare, incompletely understood and heterogeneous in presentation and clinical course. They are known to be associated with a number of benign syndromes, commonly presenting in childhood. Angiomatosis is a form of vascular malformation, hardly documented in the English literature, and has only rarely been described in the small bowel. We present a case of a middle-aged female who developed small bowel obstruction secondary to diffuse small bowel angiomatosis and subsequently developed aggressive multifocal small cell lung cancer 2 months later. Her condition rapidly deteriorated with multiple metastases and she passed away 4 months later secondary to brain metastases and diffuse disease. Small cell lung cancer is well known for its association with paraneoplastic syndromes and has been reported to cause a rise in vascular endothelial growth factor. We postulate that in this case angiomatosis presented as a paraneoplastic syndrome associated with small cell lung cancer.

Interleukin-8 induction by Burkholderia pseudomallei can occur without Toll-like receptor signaling but requires a functional type III secretion system.

Burkholderia pseudomallei is the causative agent of melioidosis, an infectious disease that can result in asymptomatic, chronic, or acute illness. In acute melioidosis, high levels of proinflammatory cytokines and chemokines are found in organs and blood, and neutrophils play a key role in controlling the infection. We showed that B. pseudomallei activates NF-kappaB via Toll-like receptor (TLR) 2, TLR4, and TLR5 but can also activate NF-kappaB and induce interleukin (IL)-8 without involving TLRs. TLR-independent activation depends on a functional Bsa type III secretion system (T3SS) and requires internalization. The mitogen-activated protein kinase (MAPK) inhibitors for p38 and c-Jun N-terminal kinase (JNK) severely impaired IL-8 induction by B. pseudomallei and reduced bacterial internalization. Furthermore, the T3SS mutant induced less JNK phosphorylation than did wild-type bacteria. Thus, in cells with no or low expression of TLRs, such as mucosal epithelial cells, B. pseudomallei can induce IL-8 via NF-kappaB and MAPK pathways, aided by Bsa T3SS.

Lipoxins: pro-resolution lipid mediators in intestinal inflammation.

Many inflammatory processes are self-limiting, suggesting the existence of endogenous anti-inflammatory mechanisms. Among the lipid mediators generated during cell-cell interactions are the lipoxins (LX, including LXA(4) and B(4)), a distinct class of lipoxygenase-derived eicosanoids. Aspirin acetylation of cyclooxygenase 2 also promotes the generation of a series of 15-epimers of LXA(4), known as aspirin-triggered lipoxins (ATL), that may account for some of the bioactivity profile of aspirin and possibly of nonsteroidal anti-inflammatory drugs. Native LX are rapidly inactivated in vivo, and stable analogs of LXA(4), LXB(4), and ATL have been synthesized that possess enhanced bioavailability and potency as anti-inflammatory eicosanoids. Here, we review current in vitro, ex vivo, and in vivo evidence supporting cytoprotective and proresolution roles for LX in intestinal inflammation. LXA(4), LXA(4) analogs, and ATL analogs inhibit neutrophil chemotaxis, adhesion to epithelium, and epithelial cell chemokine release. In addition, LX blunt TNF-alpha-stimulated inflammatory responses, cyclooxygenase product generation, and epithelial cell apoptosis and are cytoprotective for cytokine-activated colonic mucosa ex vivo. LX, ATL, and synthetic LX analogs have already been demonstrated to possess impressive antiinflammatory and proresolution efficacy in a range of experimental models of inflammation in vivo. Further elucidation of the role of LX in intestinal epithelial cell biology and immune function may yield novel therapeutic approaches in inflammatory bowel disease and possibly gastrointestinal cancer.