Consensus-based training and assessment model for general surgery.

BACKGROUND: Surgical education is becoming competency-based with the implementation of in-training milestones. Training guidelines should reflect these changes and determine the specific procedures for such milestone assessments. This study aimed to develop a consensus view regarding operative procedures and tasks considered appropriate for junior and senior trainees, and the procedures that can be used as technical milestone assessments for trainee progression in general surgery. METHODS: A Delphi process was followed where questionnaires were distributed to all 17 Canadian general surgery programme directors. Items were ranked on a 5-point Likert scale, with consensus defined as Cronbach's α of at least 0·70. Items rated 4 or above on the 5-point Likert scale by 80 per cent of the programme directors were included in the models. RESULTS: Two Delphi rounds were completed, with 14 programme directors taking part in round one and 11 in round two. The overall consensus was high (Cronbach's α = 0·98). The training model included 101 unique procedures and tasks, 24 specific to junior trainees, 68 specific to senior trainees, and nine appropriate to all. The assessment model included four procedures. CONCLUSION: A system of operative procedures and tasks for junior- and senior-level trainees has been developed along with an assessment model for trainee progression. These can be used as milestones in competency-based assessments.

Influenza surveillance in animals: what is our capacity to detect emerging influenza viruses with zoonotic potential?

A survey of national animal influenza surveillance programmes was conducted to assess the current capacity to detect influenza viruses with zoonotic potential in animals (i.e. those influenza viruses that can be naturally transmitted between animals and humans) at regional and global levels. Information on 587 animal influenza surveillance system components was collected for 99 countries from Chief Veterinary Officers (CVOs) (n = 94) and published literature. Less than 1% (n = 4) of these components were specifically aimed at detecting influenza viruses with pandemic potential in animals (i.e. those influenza viruses that are capable of causing epidemic spread in human populations over large geographical regions or worldwide), which would have zoonotic potential as a prerequisite. Those countries that sought to detect influenza viruses with pandemic potential searched for such viruses exclusively in domestic pigs. This work shows the global need for increasing surveillance that targets potentially zoonotic influenza viruses in relevant animal species.

Service evaluation to establish the sensitivity, specificity and additional value of broad-range 16S rDNA PCR for the diagnosis of infective endocarditis from resected endocardial material in patients from eight UK and Ireland hospitals.

Infective endocarditis (IE) can be diagnosed in the clinical microbiology laboratory by culturing explanted heart valve material. We present a service evaluation that examines the sensitivity and specificity of a broad-range 16S rDNA polymerase chain reaction (PCR) assay for the detection of the causative microbe in culture-proven and culture-negative cases of IE. A clinical case-note review was performed for 151 patients, from eight UK and Ireland hospitals, whose endocardial specimens were referred to the Microbiology Laboratory at Great Ormond Street Hospital (GOSH) for broad-range 16S rDNA PCR over a 12-year period. PCR detects the causative microbe in 35/47 cases of culture-proven IE and provides an aetiological agent in 43/69 cases of culture-negative IE. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the 16S rDNA PCR assay were calculated for this series of selected samples using the clinical diagnosis of IE as the reference standard. The values obtained are as follows: sensitivity = 67 %, specificity = 91 %, PPV = 96 % and NPV = 46 %. A wide range of organisms are detected by PCR, with Streptococcus spp. detected most frequently and a relatively large number of cases of Bartonella spp. and Tropheryma whipplei IE. PCR testing of explanted heart valves is recommended in addition to culture techniques to increase diagnostic yield. The data describing the aetiological agents in a large UK and Ireland series of culture-negative IE will allow future development of the diagnostic algorithm to include real-time PCR assays targeted at specific organisms.

The use of a two-gene sequencing approach to accurately distinguish between the species within the Mycobacterium abscessus complex and Mycobacterium chelonae.

Mycobacterium abscessus [M. abscessus (sensu lato) or M. abscessus complex] comprises three closely related species: M. abscessus (sensu stricto), hereafter referred to as M. abscessus, M. bolletii and M. massiliense. We describe here an accurate and robust method for distinguishing M. chelonae from M. abscessus, M. bolletii and M. massiliense, using polymerase chain reaction (PCR) and the sequencing of house-keeping gene targets (hsp65 and rpoB). Sequencing of the sodA gene is of little additional value in discriminating between species, but M. massiliense can be rapidly identified by amplification of the truncated erm(41) gene without the need for amplicon sequencing. We have applied the method to 81 isolates from 40 patients from two hospitals, the majority of whom were cystic fibrosis (CF) patients. Of these patients, 21 had previously been identified as M. chelonae and 59 as M. abscessus complex using commercial line probe assays. We identified these as 46 M. abscessus isolates, 20 M. massiliense isolates, five M. bolletii isolates and nine M. chelonae isolates and confirmed the one M. fortuitum isolate. This is the first study that has identified the individual members of the M. abscessus complex in a UK cohort of mainly CF patients.

Laryngeal constriction during hypoxic gasping and its role in improving autoresuscitation in two mouse strains.

Laryngeal closure following hypoxic gasps has been documented, but its efficacy in improving autoresuscitation capacity is unknown. We studied SWR/J mice who normally cannot autoresuscitate and the C57/BLJ strain who can. We evaluated the effects of elevated end-inspiratory lung volume immediately following a gasp. We compared upper airway-intact mice with tracheostomized mice in which the vocal cords are bypassed. We used the techniques of repeated autoresuscitate trials to test autoresuscitation capability. Both SWR/J and C57/BLJ mice could maintain elevated lung volume immediately after a gasp (breath holding). Such breath holding increased autoresuscitation ability in C57/BLJ mice but did not in SWR/J mice. In SWR/J mice, the duration of the breath holds was less than that in the C57/BLJ mice. These findings indicate that gasp-associated breath holding improves autoresuscitation capability during repeated autoresuscitation trials. Also, they show that SWR/J mice have a deficiency in central nervous system mechanisms regulating glottic closure during hypoxic gasping.

Sex-specific quantitative trait loci linked to autoresuscitation failure in SWR/J mice.

Autoresuscitation (AR) is a highly conserved response among mammals, which allows survival from transient extreme hypoxia. During hypoxia, bradycardia, and hypoxic gasping develop after a brief period of hyperactivity. Normally, AR occurs if oxygen is restored during the gasping period where an initial heart rate increase is rapidly followed resumption or eupneic breathing. Humans and other mammals can survive multiple immediately repeated AR. A defective AR capacity has been implicated in Sudden Infant Death Syndrome. We had reported earlier that inbred strains of mice such as BALB/cJ could survive a characteristic number of immediately repeated AR trials, but that SWR/J mice failed to AR from a single hypoxic episode. We now report that strains closely related to SWR/J, FVB/N and SJL/J exhibit partial resuscitation defects relative to BALB/cJ or other mouse strains, establishing a genetic basis for variation in AR failure. The AR trial phenotype of BALB/cJ x SWR/J intercross F(1) and F(2) mice was consistent with BALB/cJ dominance and a discrete number of loci. Genome-wide mapping conducted with 60 intercross F(2) animals linked two loci to the number of AR trials survived, including one sex-specific locus with male expression, consistent with the observed 50% male bias for Sudden Infant Death Syndrome in humans. A locus carried on SWR/J chromosome 10 seems to be particularly important in AR failure and was confirmed in a partial consomic line. These results establish a genetic basis for AR failure phenotype in mice, with relevance to Sudden Infant Death Syndrome.

Bovine TB infection status in cattle in Great Britain in 2015.

This report, provided by the APHA, presents the key descriptive epidemiological parameters of bovine TB in cattle in Great Britain from January 1 to December 31, 2015, providing summary information on the epidemic, including key statistics and epidemiological parameters as presented in the annual surveillance report for Great Britain, with supporting detail from specific reports for England and Wales. It updates the previous annual summaries for 2012 to 2014, also published in Veterinary Record.

Aeromonas veronii biovar sobria bacteraemia with septic arthritis confirmed by 16S rDNA PCR in an immunocompetent adult.

An 81-year-old man developed septic arthritis and bacteraemia with Aeromonas veronii biovar sobria. Cultures of the joint wash-out fluid were negative; however, DNA matching that of Aeromonas veronii was identified by 16S rDNA PCR. The patient was successfully treated with a 4 week course of ciprofloxacin. No recognized risk factors were found.

Bovine TB surveillance in Great Britain in 2014.

This report, provided by the APHA, summarises the key descriptive epidemiological parameters of bovine TB in cattle in Great Britain from January 1 to December 31, 2014. It summarises some of the temporal trends observed over a longer period and highlights some differences and similarities between Scotland, Wales and the three bovine TB risk areas of England. It updates the previous annual summaries for 2012 and 2013, also published inVeterinary Record(VR, June 14, 2014, vol 174, pp 600-604; March 28, 2015, vol 176, pp 326-330).

Bovine TB infection status in cattle in Great Britain in 2013.

This report, provided by the APHA, summarises the infection status of bovine TB in cattle in Great Britain from January 1 to December 31, 2013 and describes some of the temporal trends observed over a longer period. It updates the previous annual summary for 2012, also published in Veterinary Record (VR, June 14, 2014, vol 174, pp 600-604).

Spatial proximity and sequence localization of the reactive sulfhydryls of porphobilinogen synthase.

The zinc metalloenzyme porphobilinogen synthase (PBGS) contains several functionally important, but previously unidentified, reactive sulfhydryl groups. The enzyme has been modified with the reversible sulfhydryl-specific nitroxide spin label derivative of methyl methanethiosulfonate (MMTS), (1-oxyl-2,2,5,5-tetramethyl-delta 3-pyrroline-3-methyl)methanethiosulfonate (SL-MMTS) (Berliner, L. J., Grunwald, J., Hankovszky, H. O., & Hideg, K., 1982, Anal. Biochem. 119, 450-455). EPR spectra show that SL-MMTS labels three groups per PBGS subunit (24 per octamer), as does MMTS. EPR signals reflecting nitroxides of different mobilities are observed. Two of the three modified cysteines have been identified as Cys-119 and Cys-223 by sequencing peptides produced by an Asp-N protease digest of the modified protein. Because MMTS-reactive thiols have been implicated as ligands to the required Zn(II), EPR spectroscopy has been used to determine the spatial proximity of the modified cysteine residues. A forbidden (delta m = 2) EPR transition is observed indicating a through-space dipolar interaction between at least two of the nitroxides. The relative intensity of the forbidden and allowed transitions show that at least two of the unpaired electrons are within at most 7.6 A of each other. SL-MMTS-modified PBGS loses all Zn(II) and cannot catalyze product formation. The modified enzyme retains the ability to bind one of the two substrates at each active site. Binding of this substrate has no influence on the EPR spectral properties of the spin-labeled enzyme, or on the rate of release of the nitroxides when 2-mercaptoethanol is added.(ABSTRACT TRUNCATED AT 250 WORDS)

Coarctation index: identification of recurrent coarctation in infants with hypoplastic left heart syndrome after the Norwood procedure.

Assessment of recurrent coarctation after the Norwood procedure by routine measures is complicated by the unusual physiology caused by the presence of a modified Blalock-Tausig shunt with distal aortic arch obstruction. We present a new index that uses 2-dimensional measurement of the reconstructed aortic arch, which is highly sensitive and specific in identifying recurrent coarctation after the Norwood procedure in children with hypoplastic left heart syndrome.

Treatment options in hormone-refractory prostate cancer: current and future approaches.

Prostate cancer is the second leading cause of cancer mortality among men in Western countries. The initial treatment of advanced prostate cancer is suppression of testicular androgen production by medical or surgical castration, but nearly all men with metastases will develop disease progression. Patients with hormone refractory prostate cancer (HRPC) have a median survival of approximately 18 months and no therapy has yet demonstrated a definitive survival advantage. However, in the past several years, a number of promising new treatment strategies have emerged. One of the most important new treatment strategies involves secondary hormonal manipulation after the failure of primary androgen deprivation. This approach is predicated on the recognition that HRPC is a heterogeneous disease and some patients may respond to alternative hormonal interventions despite the presence of castrate levels of testosterone. Until recently, cytotoxic chemotherapy was felt to be relatively ineffective in the treatment of HRPC. Combination regimens incorporating new active agents have demonstrated significant activity in this setting, renewing interest in the use of chemotherapy to treat HRPC. Recent advances in the understanding of prostate cancer biology have led to the development of drugs directed against precise molecular alterations in the prostate tumour cell. Biologic agents now in development include those capable of altering signal transduction, blocking angiogenesis, inhibiting cell cycle progression, and stimulating apoptosis. In addition, many types of immune therapies are showing promise. Evaluating these agents, and incorporating them into existing regimens, are major goals of ongoing clinical research in advanced prostate cancer.

Hormonal treatment for prostate cancer.

For nearly six decades the preferred primary treatment for advanced prostate cancer has been continuous suppression of testicular androgen production by medical or surgical castration. While androgen deprivation is effective in inducing tumour regression in the large majority of cases, essentially all patients will develop progressive disease. In addition androgen deprivation may be associated with a variety of side effects. Thus, strategies that minimise the use of these agents could potentially lower the morbidity and cost associated with the treatment of advanced prostate cancer. In the era of prostate-specific antigen (PSA) testing, hormonal therapy is being used earlier in the course of the disease when the only evidence of recurrent disease is an elevated PSA. These men may survive for many years and thus have the potential for long periods of exposure to hormonal therapy and its side effects. It has been hoped that the development of alternative hormonal interventions might lead to both enhanced antitumour efficacy as well as improvements in side effect profile.

Intestinal mucosal permeability to 51Cr-ethylenediaminetetraacetic acid is increased after bilateral lower extremity ischemia-reperfusion in the rat.

BACKGROUND: Despite successful revascularization of ischemic extremities, multiorgan dysfunction syndrome develops in some patients. Mechanisms responsible for this are not known; however, the gastrointestinal tract has been implicated as a possible mediator. Our objective was to demonstrate increased intestinal mucosal permeability after bilateral hindlimb ischemia-reperfusion (I-R) in a rodent model. METHODS: Sixteen male Wistar rats were randomized either to 4 hours of bilateral hindlimb tourniquet ischemia and 24 hours of reperfusion (n = 8) or control groups (n = 8). The animals received 10 MuCi 51Cr-ethylenediaminetetraacetic acid (EDTA) by gavage, and excretion was measured in urine collected every 8 hours in 16 animals and every 4 hours in 8 animals. Arterial blood pressure was monitored continuously. Intravenous normal saline solution (3 ml/hr) with fentanyl (2 microgram/100 gm/hr) was continuously administered. Immediately before death complete blood count and levels of arterial lactate, creatinine, and urea were obtained. Mesenteric lymph nodes were harvested from the ileocecal region and cultured. Distal small bowel and proximal colon were preserved for histologic analysis. An additional 11 rats, six experimental and five control, were evaluated for mesenteric lymph node cultures only. RESULTS: Urinary excretion of 51Cr-EDTA was significantly greater in the I-R group between 0 and 8 hours (p < 0.02) and 8 to 16 hours (p < 0.0002) of reperfusion. This increase occurred as early as 4 to 8 hours of reperfusion (p < 0.0001). Urine volume in the I-R group was significantly reduced during 0 to 4 hours of reperfusion (p < 0.002). Hemoglobin and lactate level were significantly different in the I-R group. Leukocyte and platelet counts, levels of creatinine and urea, and colony counts from mesenteric lymph nodes were similar in I-R and control groups. Blinded histologic analysis of bowel segments did not reveal morphologic differences. CONCLUSIONS: Bilateral hindlimb I-R produces remote intestinal mucosal injury shown by significantly increased permeability to 51Cr-EDTA. Such increased mucosal permeability may be important in the development of multiorgan dysfunction syndrome in patients who sustain lower extremity I-R injury.