Clinical findings, treatment and outcome of trapped neutrophil syndrome in Border Collies: 12 cases (2011-2022).

OBJECTIVES: This study aimed to evaluate clinical signs, diagnostic findings, treatment administered and short- (survival to 28 days) and long-term prognosis (survival >6 months) in dogs diagnosed with trapped neutrophil syndrome. MATERIALS AND METHODS: Medical records of 12 dogs (10 Border Collies and two Border Collie Crossbreeds) homozygous for VPS13B gene mutation causing trapped neutrophil syndrome from seven veterinary institutions between January 2011 and June 2022 were evaluated retrospectively. RESULTS: The most common clinical signs at the time of diagnosis were pyrexia, abnormal gait and gastrointestinal signs. Concurrent metaphyseal osteopathy and immune-mediated polyarthritis were common. Seven dogs had a segmented neutrophil count below, four dogs within and one dog above the analyser reference interval at presentation. Two dogs had a septic source identified and both were additionally identified to be homozygous mutant positive on DNA testing by polymerase chain reaction (PCR) for canine cyclic neutropenia. All dogs received at least one antimicrobial agent and 10 dogs received treatment with prednisone or prednisolone (median starting dose 1 mg/kg/day; range 0.5 to 2.5 mg/kg/day). Nine dogs were alive at 28 days and six dogs were alive at 6 months post-diagnosis. CLINICAL SIGNIFICANCE: Trapped neutrophil syndrome should be suspected in young Border Collies with pyrexia, lameness and gastrointestinal signs. Neutropenia may not always be present and long-term survival is possible. A septic focus was not commonly identified in our population; however, our results suggest that if identified, testing for concurrent canine cyclic neutropenia should be considered.

Multi-pathogen serological survey of migratory caribou herds: A snapshot in time.

Pathogens can impact host survival, fecundity, and population dynamics even when no obvious disease is observed. Few baseline data on pathogen prevalence and diversity of caribou are available, which hampers our ability to track changes over time and evaluate impacts on caribou health. Archived blood samples collected from ten migratory caribou herds in Canada and two in Greenland were used to test for exposure to pathogens that have the potential to effect population productivity, are zoonotic or are emerging. Relationships between seroprevalence and individual, population, and other health parameters were also examined. For adult caribou, the highest overall seroprevalence was for alphaherpesvirus (49%, n = 722), pestivirus (49%, n = 572) and Neospora caninum (27%, n = 452). Lower seroprevalence was found for parainfluenza virus type 3 (9%, n = 708), Brucella suis (2%, n = 758), and Toxoplasma gondii (2%, n = 706). No animal tested positive for antibodies against West Nile virus (n = 418) or bovine respiratory syncytial virus (n = 417). This extensive multi-pathogen survey of migratory caribou herds provides evidence that caribou are exposed to pathogens that may have impacts on herd health and revealed potential interactions between pathogens as well as geographical differences in pathogen exposure that could be linked to the bio-geographical history of caribou. Caribou are a keystone species and the socio-economic cornerstone of many indigenous cultures across the North. The results from this study highlight the urgent need for a better understanding of pathogen diversity and the impact of pathogens on caribou health.

Colonoscopy conversion after flexible sigmoidoscopy screening: results from the UK Bowel Scope Screening Programme.

AIM: In the UK Bowel Scope Screening Programme (BSSP), patients progress to colonoscopy based on high-risk features on flexible sigmoidoscopy (FS). We aim to assess the practice of colonoscopy conversion and predictors of detection of additional adenomas on colonoscopy. METHOD: The Bowel Cancer Screening database was interrogated and collated with endoscopic and histological findings from patients undergoing colonoscopy following FS between August 2013 and August 2016. Multivariate analysis was performed to identify predictors of new adenomas. RESULTS: FS was performed on 11 711 patients, with an adenoma detection rate (ADR) of 8.5% and conversion to colonoscopy in 421 (3.6%). The additional ADR at colonoscopy was 35.2%, with one additional malignant diagnosis (0.26%). The adenoma miss rate was 3.6%. On multivariate analysis, a polyp ≥ 10 mm was the only high-risk indication associated with additional ADR at colonoscopy (OR 3.68, 95% CI 1.51-3.65, P < 0.001), in addition to male gender (OR 2.36, 95% CI 1.46-3.83, P < 0.001). Predictors of detection of a new adenoma ≥ 10 mm included: villous adenoma (P = 0.002), polyp ≥ 10 mm (P = 0.007) and male gender (P = 0.039). The presence of any conversion criterion was associated with the detection of any proximal adenoma (P < 0.001) and adenoma ≥ 10 mm (P = 0.031). CONCLUSION: Male gender, polyps ≥ 10 mm and villous-preponderant histology at FS were predictors of adenomas < 10 mm and ≥ 10 mm at colonoscopy. Further data are required to assess the role for gender-based stratification of conversion criteria.

Report of the Association of Coloproctology of Great Britain and Ireland/British Society of Gastroenterology Colorectal Polyp Working Group: the development of a complex colorectal polyp minimum dataset.

AIM: The management of large non-pedunculated colorectal polyps (LNPCPs) is complex, with widespread variation in management and outcome, even amongst experienced clinicians. Variations in the assessment and decision-making processes are likely to be a major factor in this variability. The creation of a standardized minimum dataset to aid decision-making may therefore result in improved clinical management. METHOD: An official working group of 13 multidisciplinary specialists was appointed by the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and the British Society of Gastroenterology (BSG) to develop a minimum dataset on LNPCPs. The literature review used to structure the ACPGBI/BSG guidelines for the management of LNPCPs was used by a steering subcommittee to identify various parameters pertaining to the decision-making processes in the assessment and management of LNPCPs. A modified Delphi consensus process was then used for voting on proposed parameters over multiple voting rounds with at least 80% agreement defined as consensus. The minimum dataset was used in a pilot process to ensure rigidity and usability. RESULTS: A 23-parameter minimum dataset with parameters relating to patient and lesion factors, including six parameters relating to image retrieval, was formulated over four rounds of voting with two pilot processes to test rigidity and usability. CONCLUSION: This paper describes the development of the first reported evidence-based and expert consensus minimum dataset for the management of LNPCPs. It is anticipated that this dataset will allow comprehensive and standardized lesion assessment to improve decision-making in the assessment and management of LNPCPs.

British Society of Gastroenterology/Association of Coloproctologists of Great Britain and Ireland guidelines for the management of large non-pedunculated colorectal polyps

These guidelines provide an evidence-based framework for the management of patients with large non-pedunculated colorectal polyps (LNPCPs), in addition to identifying key performance indicators (KPIs) that permit the audit of quality outcomes. These are areas not previously covered by British Society of Gastroenterology (BSG) Guidelines.A National Institute of Health and Care Excellence (NICE) compliant BSG guideline development process was used throughout and the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool was used to structure the guideline development process. A systematic review of literature was conducted for English language articles up to May 2014 concerning the assessment and management of LNPCPs. Quality of evaluated studies was assessed using the Scottish Intercollegiate Guidelines Network (SIGN) Methodology Checklist System. Proposed recommendation statements were evaluated by each member of the Guideline Development Group (GDG) on a scale from 1 (strongly agree) to 5 (strongly disagree) with >80% agreement required for consensus to be reached. Where consensus was not reached a modified Delphi process was used to re-evaluate and modify proposed statements until consensus was reached or the statement discarded. A round table meeting was subsequently held to finalise recommendations and to evaluate the strength of evidence discussed. The GRADE tool was used to assess the strength of evidence and strength of recommendation for finalised statements.KPIs, a training framework and potential research questions for the management of LNPCPs were also developed. It is hoped that these guidelines will improve the assessment and management of LNPCPs.

Improvement over time in outcomes for patients undergoing endoscopic therapy for Barrett's oesophagus-related neoplasia: 6-year experience from the first 500 patients treated in the UK patient registry.

BACKGROUND: Barrett's oesophagus (BE) is a pre-malignant condition leading to oesophageal adenocarcinoma (OAC). Treatment of neoplasia at an early stage is desirable. Combined endoscopic mucosal resection (EMR) followed by radiofrequency ablation (RFA) is an alternative to surgery for patients with BE-related neoplasia. METHODS: We examined prospective data from the UK registry of patients undergoing RFA/EMR for BE-related neoplasia from 2008 to 2013. Before RFA, visible lesions were removed by EMR. Thereafter, patients had RFA 3-monthly until all BE was ablated or cancer developed (endpoints). End of treatment biopsies were recommended at around 12 months from first RFA treatment or when endpoints were reached. Outcomes for clearance of dysplasia (CR-D) and BE (CR-IM) at end of treatment were assessed over two time periods (2008-2010 and 2011-2013). Durability of successful treatment and progression to OAC were also evaluated. RESULTS: 508 patients have completed treatment. CR-D and CR-IM improved significantly between the former and later time periods, from 77% and 56% to 92% and 83%, respectively (p<0.0001). EMR for visible lesions prior to RFA increased from 48% to 60% (p=0.013). Rescue EMR after RFA decreased from 13% to 2% (p<0.0001). Progression to OAC at 12 months is not significantly different (3.6% vs 2.1%, p=0.51). CONCLUSIONS: Clinical outcomes for BE neoplasia have improved significantly over the past 6 years with improved lesion recognition and aggressive resection of visible lesions before RFA. Despite advances in technique, the rate of cancer progression remains 2-4% at 1 year in these high-risk patients. TRIAL REGISTRATION NUMBER: ISRCTN93069556.

Colorectal cancer incidence and trend in UK South Asians: a 20-year study.

AIMS: South Asians comprise 13.6% of the Wolverhampton population. We aimed to compare the incidence and trend of colorectal cancer in this subgroup with the non South Asian population over a 20-year period. METHOD: Patients of South Asian origin diagnosed with colorectal cancer from 1989 to 2008 were identified from the hospital histopathology database and compared with those of non South Asian origin. 1991 and 2001 census data were used to standardize for differing age and sex distributions in the two study populations. RESULTS: The median unadjusted incidence of colorectal cancer from 1989 to 2008 was 6.17 per 100,000 per year in South Asians compared with 71.70 per 100,000 per year in non South Asians (77.79% white British). The age and sex adjusted odds ratio for colorectal cancer in South Asians was 0.2 (P < 0.001). There was an equal increased trend in the incidence in both the South Asians and non South Asians over the study period (0.8% per year). In patients < 50 years, the gender difference in the incidence of cancer was not significant, but as age increased this rose significantly (males > females). CONCLUSION: There was a markedly lower incidence of colorectal cancer in South Asians compared with non South Asians, maintained over 20 years. Colorectal cancer incidence increased by a small and similar amount over the period in both groups. There was a male preponderance of colorectal cancer in both populations over 50 years.

Endoscopy and antiplatelet agents. European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

With the increasing use of antiplatelet agents (APA), their management during the periendoscopic period has become a more common and more difficult problem. The increase in use is due to the availability of new drugs and the widespread use of drug-eluting coronary stents. Acute coronary syndromes can occur when APA therapy is withheld for noncardiovascular interventions. Guidelines about APA management during the periendoscopic period are traditionally based on assessments of the procedure-related risk of bleeding and the risk of thrombosis if APA are stopped. New data allow better assessment of these risks, of the necessary duration of APA discontinuation before endoscopy, of the use of alternative procedures (mostly for endoscopic retrograde cholangiopancreatography [ERCP]), and of endoscopic methods that can be used to prevent bleeding (following colonic polypectomy). This guideline makes graded, evidence-based, recommendations for the management of APA for all currently performed endoscopic procedures. A short summary and two tables are included for quick reference.

A role for human endogenous retrovirus-K (HML-2) in rheumatoid arthritis: investigating mechanisms of pathogenesis.

Human endogenous retroviruses (HERVs) are remnants of ancient retroviral infections within the human genome. These molecular fossils draw parallels with present-day exogenous retroviruses and have been linked previously with immunopathology within rheumatoid arthritis (RA). Mechanisms of pathogenesis for HERV-K in RA such as molecular mimicry were investigated. To clarify a role for HERVs in RA, potential autoantigens implicated in autoimmunity were scanned for sequence identity with retroviral epitopes. Short retroviral peptides modelling shared epitopes were synthesized, to survey anti-serum of RA patients and disease controls. A novel real-time polymerase chain reaction (PCR) assay was also developed to quantify accurately levels of HERV-K (HML-2) gag expression, relative to normalized housekeeping gene expression. Both serological and molecular assays showed significant increases in HERV-K (HML-2) gag activity in RA patients, compared to disease controls. The real-time PCR assay identified significant up-regulation in HERV-K mRNA levels in RA patients compared to inflammatory and healthy controls. Exogenous viral protein expression and proinflammatory cytokines were also shown to exert modulatory effects over HERV-K (HML-2) transcription. From our data, it can be concluded that RA patients exhibited significantly elevated levels of HERV-K (HML-2) gag activity compared to controls. Additional factors influencing HERV activity within the synovium were also identified. The significant variation in RA patients, both serologically and transcriptionally, may be an indication that RA is an umbrella term for a number of separate disease entities, of which particular HERV polymorphisms may play a role in development.

Downstaging of colorectal cancer by the National Bowel Cancer Screening programme in England: first round data from the first centre.

OBJECTIVE: Data from randomized controlled trials of Colorectal Cancer (CRC) screening in Nottingham, UK and Funen, Denmark and pilot data from the English and Scottish arms of the National Bowel Cancer Screening Programme (NBCSP) have demonstrated predominantly early-stage disease amongst the screened population. The aim of this study was to investigate whether downstaging of cancers occurred in the NBCSP in Wolverhampton. METHOD: A case-control study was performed to compare the staging of CRC diagnosed in the NBCSP-screened population during the prevalent round (2 years) of screening, with cancers diagnosed prior to the introduction of the NBCSP. RESULTS: The total population in the screening area is 899 000. A total of 108 346 FOB kits were sent out of which 55 931 were returned (51.6% uptake), A total of 1039 colonoscopies were performed with a 94.75% unadjusted caecal intubation rate. There were three complications (haemorrhages 3) and no perforations. The NBCSP in Wolverhampton identified 106 (75% male) CRC in the first 2 years with 45.3% Dukes A, 21.7% B, 29.2% C and 3.8% D. Two hundred and fifty-six (61% male) CRC were identified in the control group, 10.1% Dukes A, 50.0% B, 36.3% C and 3.5% D. There was a highly significant shift towards earlier stage disease in the screened group (P < 0.0001). CONCLUSION: The 2-year data from the first English centre to start bowel cancer screening demonstrates significant downstaging of cancer, consistent with both the RCT and pilot data.

Prognostic and accuracy data of multidetector CT coronary angiography in an established clinical service.

AIM: To assess the accuracy of clinical coronary computed tomography angiography (CTA) data compared to invasive coronary angiography, and to determine the prognostic value of a negative coronary CTA examination in symptomatic, intermediate-risk patients. METHODS: Thirty-seven months of coronary CTA data were audited. Seventy-eight patients were identified who had undergone coronary CTA followed by invasive coronary angiography (ICA) to determine the accuracy of CTA versus ICA. One hundred and seventy-eight patients were identified who had a "negative" coronary CTA to enable evaluation of the prognostic value of a negative CTA examination. RESULTS: Of the 78 patients in the accuracy analysis group there were 43 true-negative, two false-negative, 26 true-positive, and seven false-positive results producing a sensitivity of 92.9%, specificity of 86%, negative predictive value of 95.6%, and positive predictive value of 78.8%. The 178 patients who had a negative coronary CTA examination were followed up for a mean of 366 days and were all alive (0% mortality) with no episodes of myocardial infarction or unstable angina; two patients underwent elective revascularization procedures (1.1%). CONCLUSION: According to medium-term analysis, the accuracy of the clinical coronary CTA programme is in line with published trial data, producing excellent sensitivity and negative predictive values. The finding of a negative coronary CTA in symptomatic, intermediate-risk patients appears to confer a good prognosis, at mean follow-up of 1 year, with no deaths or episodes of myocardial infarction or unstable angina. This suggests that the prognostic value of a negative coronary CTA may be similar to that conferred by negative myocardial perfusion scintigraphy or stress echocardiography.

Imaging the heart valves using ECG-gated 64-detector row cardiac CT.

Multi-detector row cardiac CT imaging demonstrates clinical usefulness in valvular heart disease, for which CT has not been traditionally used. Electrocardiographic (ECG)-gated CT coronary angiography also has an established clinical role with an increasingly solid evidence base, and the same data set in these patients also provides valuable information about chamber and valvular structure and function; this information should also be considered when interpreting cardiac CT and non-ECG gated thoracic imaging. Although true flow data cannot be achieved using CT, as with echocardiography and MRI, there are a number of imaging features that may be used when interpreting and inferring valve pathology. This article discusses the role of currently available imaging modalities and the rationale for cardiac CT, while focusing on the CT interpretation of valvular heart disease with respect to the relevant pathophysiology and management options that have importance to the radiologist. A suggested method of post-processing image review is provided with reference to a variety of normal and pathological pictorial illustrations.

Historical and ecological determinants of genetic structure in arctic canids.

Wolves (Canis lupus) and arctic foxes (Alopex lagopus) are the only canid species found throughout the mainland tundra and arctic islands of North America. Contrasting evolutionary histories, and the contemporary ecology of each species, have combined to produce their divergent population genetic characteristics. Arctic foxes are more variable than wolves, and both island and mainland fox populations possess similarly high microsatellite variation. These differences result from larger effective population sizes in arctic foxes, and the fact that, unlike wolves, foxes were not isolated in discrete refugia during the Pleistocene. Despite the large physical distances and distinct ecotypes represented, a single, panmictic population of arctic foxes was found which spans the Svalbard Archipelago and the North American range of the species. This pattern likely reflects both the absence of historical population bottlenecks and current, high levels of gene flow following frequent long-distance foraging movements. In contrast, genetic structure in wolves correlates strongly to transitions in habitat type, and is probably determined by natal habitat-biased dispersal. Nonrandom dispersal may be cued by relative levels of vegetation cover between tundra and forest habitats, but especially by wolf prey specialization on ungulate species of familiar type and behaviour (sedentary or migratory). Results presented here suggest that, through its influence on sea ice, vegetation, prey dynamics and distribution, continued arctic climate change may have effects as dramatic as those of the Pleistocene on the genetic structure of arctic canid species.

Protostrongylid parasites and pneumonia in captive and wild thinhorn sheep (Ovis dalli).

We describe health significance of protostrongylid parasites (Parelaphostrongylus odocoilei and Protostrongylus stilesi) and other respiratory pathogens in more than 50 naturally infected Dall's sheep (Ovis dalli dalli) from the Mackenzie Mountains, Northwest Territories (1998-2002) as well as in three Stone's sheep (O. d. stonei) experimentally infected with P. odocoilei (2000-2002). Histological lesions in the brain and distribution of P. odocoilei in the muscles of experimentally and naturally infected sheep were consistent with a previously hypothesized "central nervous system to muscle" pattern of migration for P. odocoilei. Dimensions of granulomas associated with eggs of P. odocoilei and density of protostrongylid eggs and larvae in the cranial lung correlated with intensity of larvae in feces, and all varied with season of collection. Prevalence of P. stilesi based on the presence of larvae in feces underestimated true prevalence (based on examination of lungs) in wild Dall's sheep collected in summer and fall. Similarly, counts of both types of protostrongylid larvae in feces were unreliable indicators of parasitic infection in wild Dall's sheep with concomitant bacterial pneumonia associated with Arcanobacterium pyogenes, Pasteurella sp., and Mannheimia sp. Diffuse, interstitial pneumonia due to P. odocoilei led to fatal pulmonary hemorrhage and edema after exertion in one experimentally infected Stone's sheep and one naturally infected Dall's sheep. Bacterial and verminous pneumonia associated with pathogens endemic in wild Dall's sheep in the Mackenzie Mountains caused sporadic mortalities. There was no evidence of respiratory viruses or bacterial strains associated with domestic ruminants, from which this population of wild sheep has been historically isolated.

The dynamics of size-at-age variability.

In this paper, we propose a theoretical framework within which a unified treatment of the key sources of size-at-age variability-size dependence of growth rate, stochastic growth rate variations and individual-to-individual variability in growth performance-is possible. We use this framework to develop a general criterion for growth depensation in cohorts, which we define as the increase of the coefficient of variation of size-at-age, with increasing age. We use this criterion to show that size dependence of growth rate, acting alone, is depensatory only if the growth rate increases faster than linearly with size (that is, if growth is faster than exponential), while stochastic growth rate variation is invariably depensatory. Many species exhibit growth rates that scale less than linearly with size; indeed the commonly used von Bertalanffy model shows growth rates which actually decrease with size. In such a species, the size dependence of growth rate acts compensatorily, while stochastic growth rate variability is depensatory. We show that the tension between these two mechanisms leads to quasi-stationary size-at-age variability, which we can calculate analytically in some special cases and obtain by a simple numerical procedure where analysis is impractical.

Evidence for cryptic glacial refugia from North American mountain sheep mitochondrial DNA.

The separation of populations by ice sheets into large refugia can account for much of the genetic diversity found in present day populations. The evolutionary implications of small glacial refugia have not been as thoroughly explored. To examine refugial origins of North American mountain sheep Ovis spp., we analyzed a 604 bp portion of the mitochondrial DNA (mtDNA) control region from 223 O. dalli and O. canadensis. Major refugia were identified in eastern Beringia and southern North America, and we found evidence for two smaller refugia situated between the Laurentide and Cordilleran glaciers. Our results are the first to demonstrate support for survival of any organism in the latter two refugia. These refugia also appear to have conserved a genetic signal that confirms past hybridization of O. dalli and O. canadensis.

Management and outcomes of acute coronary syndrome with minimal myocardial necrosis: analysis of a large prospective registry from a non-interventional centre.

The aim of this study was to assess the clinical risk of minimal myonecrosis below the cut-off for acute myocardial infarction (MI) in comparison with other grades of acute coronary syndrome (ACS). One-thousand four hundred and sixty seven consecutive patients with ACS admitted between May 2001 and April 2002 were studied in a non-interventional centre. Patients were divided into unstable angina (UA) (cTnT < 0.01 microg/l), non-ST elevation ACS with minimal myonecrosis (0.01 or= 0.1 microg/L) and ST elevation myocardial infarction (STEMI). UA (n = 638) was associated with the fewest events at 6 months (2% cardiac death or MI). Patients with any myonecrosis (n = 829) had worse outcomes (6-month cardiac death or MI 18.3-23.3%). Compared with ACS patients with minimal myonecrosis, UA patients were at significantly lower risk (OR 0.21, 95% CI 0.12-0.45, p < 0.001), NSTEMI patients were at similar risk (OR 1.45, 95% CI 0.89-2.35, p = 0.13), and STEMI patients were at higher risk (OR 2.12 95% CI 1.26-3.85, p = 0.008) in adjusted analyses. Nearly 85% of cardiac deaths occurred within 6 months. The risk of adverse events was higher among patients managed by non-cardiologists (OR 1.66, 95% CI 1-2.75, p = 0.049). Patients with non-ST elevation ACS and minimal myonecrosis are a high-risk group more comparable with NSTEMI and clearly distinguishable from patients with UA.