Canine mammary gland disease in New Zealand: a review of samples from 797 dogs.

AIMS: To evaluate the proportions of canine mammary gland lesions submitted to a New Zealand diagnostic laboratory, that were neoplastic vs. non-neoplastic and, among neoplasms, malignant vs. benign, and to determine whether age, reproductive status or breed of dog, or size of the mammary mass were associated with the histological diagnosis. METHODS: Canine mammary gland biopsies submitted between the start of 2012 and the end of 2016 were selected from the surgical biopsy database of IDEXX Laboratories, NZ. For each case, details on age, breed, and reproductive status of the patient were registered as reported by the submitting veterinarians, along with the size (classified as small, medium or large) of the lesion and the histological diagnosis reported by the pathologists. χ2 tests and independent sample t-tests were performed to evaluate associations. RESULTS: Samples (n = 895) were submitted from 797 dogs, of which 673 had mammary neoplasms while 124 had non-neoplastic lesions. Neoplasms composed of a single nodule were found in 591/673 (87.8%) dogs, while 82/673 (12.2%) dogs had multiple nodules. Of the total 771 neoplasms, 432 (56.0%) were histologically malignant, while 339 (44.0%) were benign. Among malignancies, the most common histological sub-types were simple carcinoma (160/771; 20.8%), complex carcinoma (54/771; 7%), and ductal carcinoma (32/771; 4.2%), while benign mixed mammary tumour (128/771, 16.6%) and complex adenoma (105/771; 13.6%) were the most frequently reported benign mammary neoplasms. There was no evidence of a difference in age (p = 0.09) or reproductive status (p = 0.79) of the dog or the size of the mass (p = 0.21) between neoplastic and non-neoplastic lesions. However, neoplastic mammary gland lesions were more frequent in purebred dogs (612/671; 91.2%) than crossbred dogs (61/126; 48.4%; p < 0.001). There was no evidence of a difference in age (p = 0.15) reproductive status (p = 0.36) or breed (p = 0.45) of dog between malignant and benign neoplasms. There was an association between size and histological benign or malignant status of a neoplasm (φ = 0.65, p < 0.001). CONCLUSIONS: Most canine mammary gland samples submitted for examination were neoplastic with slightly more malignant than benign lesions. Masses submitted from purebred dogs were more likely to be neoplastic, while large neoplasms were more likely to be malignant. CLINICAL RELEVANCE: The present findings provide the first description of the distribution of mammary gland lesions in a relatively large number of dogs in New Zealand, representing a preliminary investigation of canine mammary gland diseases in this country.

Isolates, antimicrobial susceptibility profiles and multidrug resistance of bacteria cultured from samples collected from sheep in New Zealand (2003-2016).

Aim: To describe the common species, antimicrobial susceptibility and multidrug resistance (MDR) of bacteria cultured from samples submitted to veterinary diagnostic laboratories from sheep in New Zealand between 2003 and 2016. Methods: Bacterial culture and antimicrobial susceptibility test data from June 2003 to March 2016 for animals identified as sheep were obtained from two commercial veterinary diagnostic laboratories in New Zealand. Submission information included animal signalment, geographic origin, specimen description, the organisms cultured, and where available, antimicrobial susceptibilities of the isolates. MDR was defined as any isolate with resistance to ≥3 antimicrobial classes. Results: There were 1,971 unique laboratory submissions, yielding 2,188 isolates. Of the 1,971 submissions, the most commonly represented breeds were Romney (933; 47.3%), Romney cross (264; 13.4%), and Coopworth (197; 10.0%), and there were more submissions from females (1,006; 51.0%) than males (184; 9.3%). Most submissions were from Canterbury (549; 27.9%), Southland (471; 23.9%), and Manawatu-Wanganui (272; 13.8%) regions. Other signalment data were inconsistently described. Submitted samples most commonly originated from the gastrointestinal tract (852; 43.2%), faeces (378; 12.1%), or liver (146; 7.4%). Of the 2,188 isolates, 1,771 (80.9%) were identified by species and 247 (11.4%) by genus, with the most common isolates being Salmonella spp. (880; 40.2%), Campylobacter spp. (408; 18.6%), Listeria spp. (140; 6.4%) and Yersinia spp. (113; 5.2%). Susceptibility results were available for 117/2,188 (5.3%) isolates from 51/1,971 (2.6%) submissions. No antimicrobial susceptibility data were available for Salmonella spp., Campylobacter spp., Listeria spp. or Yersinia spp. Overall for the isolates tested, susceptibility to the fluoroquinolones and tetracyclines was greatest, and MDR was found in 24/117 (20.5%) isolates. MDR was a more frequent finding for Enterococcus spp., Bacillus spp., and Proteus mirabilis, but was infrequent in isolates of Staphylococcus aureus, alpha-haemolytic streptococci, Escherichia coli or Enterobacter spp. Conclusions and clinical relevance: This is the first report on antimicrobial susceptibility and MDR for isolates from laboratory submissions from sheep in New Zealand. The low numbers of isolates submitted for antimicrobial susceptibility testing during the period studied mean that these findings provide limited insights into antimicrobial resistance in this population, and highlight the need to address significant gaps in our understanding of why veterinarians do not more frequently submit samples from sheep for bacterial culture and susceptibility testing. Abbreviation: AMR: Antimicrobial resistance; MDR: Multidrug resistance.

Bacterial isolates, antimicrobial susceptibility and multidrug resistance in cultures from samples collected from beef and pre-production dairy cattle in New Zealand (2003-2016).

Aims: To describe the common species and the antimicrobial susceptibility of bacteria cultured from samples submitted to commercial veterinary diagnostic laboratories from beef and pre-production dairy cattle between 2003-2016, and to describe the proportion of isolates with multidrug resistance (MDR). Methods: Bacterial culture and antimicrobial susceptibility data from July 2003 to March 2016 were obtained from commercial veterinary diagnostic laboratories in New Zealand. Results were included from samples from beef cattle, irrespective of age or sex, dairy-breed females aged <2 years and dairy-breed males of any age. Submission information provided included the specimen description, the organisms cultured, and the antimicrobial susceptibilities of isolates, if tested. Antimicrobial resistance (AMR) was defined as any isolate not showing susceptibility to an antimicrobial compound and MDR as any isolate showing AMR to ≥3 antimicrobial classes. Results: There were 1,858 unique laboratory submissions, yielding 2,739 isolates. Of these submissions, most were from the Canterbury (389; 21.9%), Manawatu (388; 21.9%) Waikato (231; 12.4%) and Hawke's Bay (136; 7.3%) regions. There were 163 unique species identifications for the 2,739 isolates; the most common were Yersinia pseudotuberculosis (452; 16.5%), Campylobacter jejuni (249; 9.1%), Escherichia coli (230; 8.4%) and Salmonella enterica serovar Typhimurium (143; 5.2%). Only 251/2,739 (9.2%) isolates from 122/1,858 (6.6%) submissions had antimicrobial susceptibility results. There were no sensitivity results for Yersinia spp., and only one each for Salmonella spp., and Campylobacter spp. Amongst the isolates tested, susceptibility to ampicillin was lowest (33/56; 58.9%). Overall, 57/251 (20.7%) isolates tested for antimicrobial susceptibility had MDR, and MDR was most common for Enterococcus spp. (12/17; 71%) and E. coli (13/30; 43%). Conclusions and Clinical Relevance: This is the first report on antimicrobial susceptibility and MDR in New Zealand beef and pre-production dairy cattle. Findings highlight the limited use of bacterial culture and sensitivity testing by veterinarians and deficits in the information accompanying submissions. A national antimicrobial resistance surveillance strategy that specifically includes this population is recommended.

The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials.

The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i-IFTA) and its relationship to T cell-mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody-mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i-IFTA is associated with reduced graft survival. Furthermore, these groups presented that i-IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i-IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor-specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next-generation clinical trials.

Evaluation of C1q Status and Titer of De Novo Donor-Specific Antibodies as Predictors of Allograft Survival.

De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0.01) and was more common in class II versus class I dnDSAs (p < 0.01). C1q status correlated with tubulitis (p = 0.02) and C4d status (p = 0.03) in biopsies at the time of dnDSA development, but not T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR). De novo DSA titer correlated with Banff g, i, t, ptc, C4d scores, TCMR (p < 0.01) and ABMR (p < 0.01). Post-dnDSA graft loss was observed more frequently in recipients with C1q-positve dnDSA (p < 0.01) or dnDSA titer ≥ 1:1024 (p ≤ 0.01). However, after adjustment for clinical phenotype and nonadherence in multivariate models, neither C1q status nor dnDSA titer were independently associated with allograft loss, questioning the utility of these assays at the time of dnDSA development.

The Banff 2015 Kidney Meeting Report: Current Challenges in Rejection Classification and Prospects for Adopting Molecular Pathology.

The XIII Banff meeting, held in conjunction the Canadian Society of Transplantation in Vancouver, Canada, reviewed the clinical impact of updates of C4d-negative antibody-mediated rejection (ABMR) from the 2013 meeting, reports from active Banff Working Groups, the relationships of donor-specific antibody tests (anti-HLA and non-HLA) with transplant histopathology, and questions of molecular transplant diagnostics. The use of transcriptome gene sets, their resultant diagnostic classifiers, or common key genes to supplement the diagnosis and classification of rejection requires further consensus agreement and validation in biopsies. Newly introduced concepts include the i-IFTA score, comprising inflammation within areas of fibrosis and atrophy and acceptance of transplant arteriolopathy within the descriptions of chronic active T cell-mediated rejection (TCMR) or chronic ABMR. The pattern of mixed TCMR and ABMR was increasingly recognized. This report also includes improved definitions of TCMR and ABMR in pancreas transplants with specification of vascular lesions and prospects for defining a vascularized composite allograft rejection classification. The goal of the Banff process is ongoing integration of advances in histologic, serologic, and molecular diagnostic techniques to produce a consensus-based reporting system that offers precise composite scores, accurate routine diagnostics, and applicability to next-generation clinical trials.

Antimicrobial resistance patterns of bacteria isolated from canine urinary samples submitted to a New Zealand veterinary diagnostic laboratory between 2005-2012.

AIMS: To identify and describe culture and antimicrobial resistance (AMR) patterns in bacteria isolated from canine urinary samples submitted to a New Zealand veterinary diagnostic laboratory. METHODS: Records from a veterinary diagnostic laboratory were examined for bacterial isolates cultured from canine urine samples between January 2005 and December 2012. Culture and susceptibility results were compiled with information on the age, sex and breed of dog. Repeat submissions were removed. Susceptibility was assessed using results of the Kirby-Bauer disk diffusion method, for a standard panel including amoxicillin-clavulanic acid (AMC), cefovecin (from 2010-2012), cephalothin, clindamycin, enrofloxacin and trimethoprim-sulphonamide (TMS). RESULTS: A total of 5,786 urine samples were submitted for analysis, and 3,135 bacterial isolates were cultured from 2,184 samples. Of these 3,135 isolates, 1,104 (35.2%) were Escherichia coli, 442 (14.1%) were Staphylococcus spp., 357 (11.4%) Proteus mirabilis and 276 (8.8%) were Enterococcus spp. The frequency of culture-positive samples increased with increasing age in both female and male dogs (p<0.001). The percentage of E. coli isolates resistant to AMC and cephalothin increased between 2005 and 2012 (p<0.001), as did resistance to enrofloxacin (p=0.022), but there was no change in resistance to TMS (p=0.696). Enrofloxacin was the antimicrobial with the least resistance shown by the four most common bacteria isolated during the course of the study. CONCLUSIONS AND CLINICAL RELEVANCE: The results of this study provide important regional information regarding the prevalence of bacterial uropathogens and their susceptibility patterns. There was an increase in resistance to some commonly used antimicrobials in the treatment of urinary tract infections. Having access to regional antimicrobial susceptibility results is crucial when forming guidelines for the use of antimicrobials for the treatment of urinary tract infections. Given changes in practising habits and antimicrobial usage over time, ongoing monitoring and surveillance of resistance in pathogens is needed.

Interferon Gamma ELISPOT Testing as a Risk-Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT-01 Multicenter Study.

Previous studies suggest that quantifying donor-reactive memory T cells prior to kidney transplantation by interferon gamma enzyme-linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation-01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6- or 12-month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell-depleting, rabbit anti-thymocyte globulin (ATG). Within the no-ATG subset, IFNγELISPOT(neg) subjects had higher 6- and 12-month eGFRs than IFNγELISPOT(pos) subjects, independent of biopsy-proven AR, peak PRA, human leukocyte antigen mismatches, African-American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor-reactive memory T cells.

Rates and determinants of progression to graft failure in kidney allograft recipients with de novo donor-specific antibody.

Understanding rates and determinants of clinical pathologic progression for recipients with de novo donor-specific antibody (dnDSA), especially subclinical dnDSA, may identify surrogate endpoints and inform clinical trial design. A consecutive cohort of 508 renal transplant recipients (n = 64 with dnDSA) was studied. Recipients (n = 388) without dnDSA or dysfunction had an eGFR decline of -0.65 mL/min/1.73 m(2) /year. In recipients with dnDSA, the rate eGFR decline was significantly increased prior to dnDSA onset (-2.89 vs. -0.65 mL/min/1.73 m(2) /year, p < 0.0001) and accelerated post-dnDSA (-3.63 vs. -2.89 mL/min/1.73 m(2) /year, p < 0.0001), suggesting that dnDSA is both a marker and contributor to ongoing alloimmunity. Time to 50% post-dnDSA graft loss was longer in recipients with subclinical versus a clinical dnDSA phenotype (8.3 vs. 3.3 years, p < 0.0001). Analysis of 1091 allograft biopsies found that dnDSA and time independently predicted chronic glomerulopathy (cg), but not interstitial fibrosis and tubular atrophy (IFTA). Early T cell-mediated rejection, nonadherence, and time were multivariate predictors of IFTA. Independent risk factors for post-dnDSA graft survival available prior to, or at the time of, dnDSA detection were delayed graft function, nonadherence, dnDSA mean fluorescence intensity sum score, tubulitis, and cg. Ultimately, dnDSA is part of a continuum of mixed alloimmune-mediated injury, which requires solutions targeting T and B cells.

Urinary metabolomics for noninvasive detection of borderline and acute T cell-mediated rejection in children after kidney transplantation.

The goal of this study was to evaluate the utility of urinary metabolomics for noninvasive diagnosis of T cell-mediated rejection (TCMR) in pediatric kidney transplant recipients. Urine samples (n = 277) from 57 patients with surveillance or indication kidney biopsies were assayed for 134 unique metabolites by quantitative mass spectrometry. Samples without TCMR (n = 183) were compared to borderline tubulitis (n = 54) and TCMR (n = 30). Partial least squares discriminant analysis identified distinct classifiers for TCMR (area under receiver operating characteristic curve [AUC] = 0.892; 95% confidence interval [CI] 0.827-0.957) and borderline tubulitis (AUC = 0.836; 95% CI 0.781-0.892), respectively. Application of the TCMR classifier to borderline tubulitis samples yielded a discriminant score (-0.47 ± 0.33) mid-way between TCMR (-0.20 ± 0.34) and No TCMR (-0.80 ± 0.32) (p < 0.001 for all comparisons). Discriminant scoring for combined borderline/TCMR versus No TCMR (AUC = 0.900; 95% CI 0.859-0.940) applied to a validation cohort robustly distinguished between samples with (-0.08 ± 0.52) and without (-0.65 ± 0.54, p < 0.001) borderline/TCMR (p < 0.001). The TCMR discriminant score was driven by histological t-score, ct-score, donor-specific antibody and biopsy indication, and was unaffected by renal function, interstitial or microcirculatory inflammation, interstitial fibrosis or pyuria. These preliminary findings suggest that urinary metabolomics is a sensitive, specific and noninvasive tool for TCMR identification that is superior to serum creatinine, with minimal confounding by other allograft injury processes.

Banff 2013 meeting report: inclusion of c4d-negative antibody-mediated rejection and antibody-associated arterial lesions.

The 12th Banff Conference on Allograft Pathology was held in Comandatuba, Brazil, from August 19-23, 2013, and was preceded by a 2-day Latin American Symposium on Transplant Immunobiology and Immunopathology. The meeting was highlighted by the presentation of the findings of several working groups formed at the 2009 and 2011 Banff meetings to: (1) establish consensus criteria for diagnosing antibody-mediated rejection (ABMR) in the presence and absence of detectable C4d deposition; (2) develop consensus definitions and thresholds for glomerulitis (g score) and chronic glomerulopathy (cg score), associated with improved inter-observer agreement and correlation with clinical, molecular and serological data; (3) determine whether isolated lesions of intimal arteritis ("isolated v") represent acute rejection similar to intimal arteritis in the presence of tubulointerstitial inflammation; (4) compare different methodologies for evaluating interstitial fibrosis and for performing/evaluating implantation biopsies of renal allografts with regard to reproducibility and prediction of subsequent graft function; and (5) define clinically and prognostically significant morphologic criteria for subclassifying polyoma virus nephropathy. The key outcome of the 2013 conference is defining criteria for diagnosis of C4d-negative ABMR and respective modification of the Banff classification. In addition, three new Banff Working Groups were initiated.

Class II HLA epitope matching-A strategy to minimize de novo donor-specific antibody development and improve outcomes.

De novo donor-specific antibody (dnDSA) develops in 15-25% of renal transplant recipients within 5 years of transplantation and is associated with 40% lower graft survival at 10 years. HLA epitope matching is a novel strategy that may minimize dnDSA development. HLAMatchmaker software was used to characterize epitope mismatches at 395 potential HLA-DR/DQ/DP conformational epitopes for 286 donor-recipient pairs. Epitope specificities were assigned using single antigen HLA bead analysis and correlated with known monoclonal alloantibody epitope targets. Locus-specific epitope mismatches were more numerous in patients who developed HLA-DR dnDSA alone (21.4 vs. 13.2, p < 0.02) or HLA-DQ dnDSA alone (27.5 vs. 17.3, p < 0.001). An optimal threshold for epitope mismatches (10 for HLA-DR, 17 for HLA-DQ) was defined that was associated with minimal development of Class II dnDSA. Applying these thresholds, zero and 2.7% of patients developed dnDSA against HLA-DR and HLA-DQ, respectively, after a median of 6.9 years. Epitope specificity analysis revealed that 3 HLA-DR and 3 HLA-DQ epitopes were independent multivariate predictors of Class II dnDSA. HLA-DR and DQ epitope matching outperforms traditional low-resolution antigen-based matching and has the potential to minimize the risk of de novo Class II DSA development, thereby improving long-term graft outcome.

Multicenter validation of urinary CXCL9 as a risk-stratifying biomarker for kidney transplant injury.

Noninvasive biomarkers are needed to assess immune risk and ultimately guide therapeutic decision-making following kidney transplantation. A requisite step toward these goals is validation of markers that diagnose and/or predict relevant transplant endpoints. The Clinical Trials in Organ Transplantation-01 protocol is a multicenter observational study of biomarkers in 280 adult and pediatric first kidney transplant recipients. We compared and validated urinary mRNAs and proteins as biomarkers to diagnose biopsy-proven acute rejection (AR) and stratify patients into groups based on risk for developing AR or progressive renal dysfunction. Among markers tested for diagnosing AR, urinary CXCL9 mRNA (odds ratio [OR] 2.77, positive predictive value [PPV] 61.5%, negative predictive value [NPV] 83%) and CXCL9 protein (OR 3.40, PPV 67.6%, NPV 92%) were the most robust. Low urinary CXCL9 protein in 6-month posttransplant urines obtained from stable allograft recipients classified individuals least likely to develop future AR or a decrement in estimated glomerular filtration rate between 6 and 24 months (92.5-99.3% NPV). Our results support using urinary CXCL9 for clinical decision-making following kidney transplantation. In the context of acute dysfunction, low values can rule out infectious/immunological causes of injury. Absent urinary CXCL9 at 6 months posttransplant defines a subgroup at low risk for incipient immune injury.

The presence of p16 CDKN2A protein immunostaining within feline nasal planum squamous cell carcinomas is associated with an increased survival time and the presence of papillomaviral DNA.

In humans, oral SCCs are either caused by papillomavirus (PV) infection or by other carcinogens such as tobacco. As these 2 groups of SCCs have different causes they also have different clinical behaviors. Immunostaining using anti-p16(CDKN2A) protein (p16) antibodies is used to indicate a PV etiology in human oral SCCs and p16-positive SCCs have a more favorable prognosis. The present study investigated whether p16 immunostaining within feline nasal planum SCCs was similarly associated with the presence of PV DNA and with a longer survival time. Intense p16 immunostaining was visible in 32 of 51 (63%) SCCs. In 30 cats with nonexcised SCCs, cats with p16-positive neoplasms had a longer estimated mean survival time (643 days) than cats with p16-negative SCCs (217 days, P = .013). Papillomavirus DNA was amplified more frequently from p16-positive nasal planum SCCs (28 of 32) than p16-negative SCCs (5 of 19, P < .001). The different survival times in cats with p16-positive and p16-negative SCCs suggests that p16 could be a useful prognostic indicator in these common feline cancers. As the clinical behavior of the SCCs can be subdivided using p16 immunostaining, the 2 groups of SCCs may be caused by different factors, supporting a PV etiology in a proportion of feline nasal planum SCCs.

Evolution and clinical pathologic correlations of de novo donor-specific HLA antibody post kidney transplant.

The natural history for patients with de novo donor-specific antibodies (dnDSA) and the risk factors for its development have not been well defined. Furthermore, clinical and histologic correlation with serologic data is limited. We studied 315 consecutive renal transplants without pretransplant DSA, with a mean follow-up of 6.2 ± 2.9 years. Protocol (n = 215) and for cause (n = 163) biopsies were analyzed. Solid phase assays were used to screen for dnDSA posttransplant. A total of 47 out of 315 (15%) patients developed dnDSA at a mean of 4.6 ± 3.0 years posttransplant. Independent predictors of dnDSA were HLA-DRß1 MM > 0 (OR 5.66, p < 0.006); and nonadherence (OR 8.75, p < 0.001); with a strong trend toward clinical rejection episodes preceding dnDSA (OR 1.57 per rejection episode, p = 0.061). The median 10-year graft survival for those with dnDSA was lower than the No dnDSA group (57% vs. 96%, p < 0.0001). Pathology consistent with antibody-mediated injury can occur and progress in patients with dnDSA in the absence of graft dysfunction and furthermore, nonadherence and cellular rejection contribute to dnDSA development and progression to graft loss.

The effect of lifestyle and risk factor modification on occlusive peripheral arterial disease outcomes: standard healthcare vs structured programme-for a randomised controlled trial protocol.

BACKGROUND: Peripheral arterial disease (PAD) affects more than 200 million of the global population. PAD represents a marker for premature cardiovascular events. Patients with PAD, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as patients with a history of coronary or cerebrovascular disease. Despite the high prevalence of PAD and the strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive appropriate treatment for their atherosclerotic risk factors than those who are being treated for coronary artery disease. Atherosclerotic risk factor identification and modification play an important role in reducing the number of adverse outcomes among patients with atherosclerosis. Risk reduction therapy decreases the risk of cardiovascular mortality and morbidity in patients with PAD. In this study, we aim to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors. METHODS: This is a randomised, parallel group, active-control trial to compare the effectiveness of the risk factor modification intervention programme to standard healthcare in a tertiary vascular care centre, in the reduction of modified risk factors in PAD patients. The primary outcome of this study is to evaluate the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors at 3 and 12 months. The secondary outcomes are to compare the impact of the programme on clinical outcomes in PAD patients at 12 months. Secondary outcomes include amputation-free survival, clinical improvement, haemodynamic improvement, need for revascularisation procedures, outcomes of revascularisation procedures, changes in quality of life and the incidence of adverse events. DISCUSSION: This study will provide clear evidence on the effectiveness of a lifestyle and risk factor modification intervention programme in achieving treatment goals for PAD risk factors, through a high-quality, well-powered clinical trial. TRIAL REGISTRATION: This trial was registered (11/07/2017) on the European Clinical Trials Database (EudraCT number 2017-002964-41) and ClinicalTrials.gov ( NCT03935776 ) which was registered on 02 May 2019.

Peritubular capillaritis in renal allografts: prevalence, scoring system, reproducibility and clinicopathological correlates.

While glomerulitis is graded according to the Banff classification, no criteria for scoring peritubular capillaritis (PTC) have been established. We retrospectively applied PTC-scoring criteria to 688 renal allograft (46 preimplantation, 461 protocol, 181 indication) biopsies. A total of 26.3% of all analyzed biopsies had peritubular capillaritis (implant 0%, protocol 17.6%, indication 45.5%; p < 0.0001). The most common capillaritis pattern was of moderate severity (5-10 luminal cells), focal in extent (10-50% of PTC), with a minority of neutrophils. A total of 24% of C4d- compared with 75% of C4d+ biopsies showed capillaritis (p < 0.0001). More than 80% of biopsies with glomerulitis had peritubular capillaritis. A total of 50.4% of biopsies with borderline or T-cell mediated rejection (TCMR) and 14.1% of biopsies without TCMR or antibody-mediated rejection (ABMR) showed capillaritis (p < 0.0001). The inter-observer reproducibility of the PTC-scoring features was fair to moderate. Diffuse capillaritis detected in early protocol biopsies had significant negative prognostic impact in terms of glomerular filtration rate 2 years posttransplantation. Indication biopsies show a significantly higher prevalence of capillaritis than protocol biopsies (45.5% vs. 17.6%; p < 0.0001). Capillaritis is more frequent and pronounced in ABMR, but can be observed in TCMR cases. Thus, scoring of peritubular capillaritis is feasible and can provide prognostic and diagnostic information in renal allograft biopsies.

Banff 07 classification of renal allograft pathology: updates and future directions.

The 9th Banff Conference on Allograft Pathology was held in La Coruna, Spain on June 23-29, 2007. A total of 235 pathologists, clinicians and scientists met to address unsolved issues in transplantation and adapt the Banff schema for renal allograft rejection in response to emerging data and technologies. The outcome of the consensus discussions on renal pathology is provided in this article. Major updates from the 2007 Banff Conference were: inclusion of peritubular capillaritis grading, C4d scoring, interpretation of C4d deposition without morphological evidence of active rejection, application of the Banff criteria to zero-time and protocol biopsies and introduction of a new scoring for total interstitial inflammation (ti-score). In addition, emerging research data led to the establishment of collaborative working groups addressing issues like isolated 'v' lesion and incorporation of omics-technologies, paving the way for future combination of graft biopsy and molecular parameters within the Banff process.

Genetic diversity and zoonotic potential of Cryptosporidium parvum causing foal diarrhea.

Cryptosporidium isolates from diarrheic foals in New Zealand (n = 9) were identified as C. parvum, subtyped at two polymorphic loci, and compared with human (n = 45) and bovine (n = 8) isolates. Foal C. parvum isolates were genetically diverse, markedly similar to human and bovine isolates, and carried GP60 IIaA18G3R1 alleles, indicating a zoonotic potential.

Outcomes from a community-based hypertension educational programme: the West of Ireland Hypertension study.

BACKGROUND: Hypertension is a leading modifiable risk factor for premature cardiovascular disease. Research indicates a growing prevalence of hypertension among adults worldwide, with accompanying low levels of patient knowledge, and sub-optimal clinical management. AIMS: This study aims to explore the impact of a structured hypertension educational intervention on patient knowledge, lifestyle behaviours and blood pressure control. DESIGN: An observational, prospective cohort design was selected. METHODS: Participants were recruited through a public blood pressure screening event in a community-based setting. They were asked to complete a self-report questionnaire followed by an assessment of their blood pressure. Participants with high blood pressure were randomly assigned to either a control group or an intervention group. Those in the intervention group received an educational intervention on hypertension 4 weeks later. Both groups were recalled 4 months later for a repeat of the same initial assessment. RESULTS: Eighty-one participants with a mean age of 64 years were included in this study. There were no significant differences in the baseline measures between the two groups. Significant improvements were found in the intervention group compared with the control group in levels of hypertension knowledge and awareness (p = <0.001), exercise levels (p = 0.002) and weight (p = 0.003). Participants who underwent the intervention showed a greater reduction in both systolic (SBP) and diastolic (DBP) blood pressure (SBP 158.8 to 141.6 mmHg, p < 0.0001 and DBP 84.7 to 77.7 mmHg, p < 0.001). CONCLUSION: Providing a tailored educational intervention can positively impact on hypertension knowledge, self-care management and control within community-based settings.