Search

Central vestibular disease is one of the most common problems in pet rabbits. Encephalitozoon cuniculi infection appears to be the most frequent etiology, but other causes have been described. It is known that infective endocarditis can cause thromboembolic disease affecting multiple organ systems in dogs. Secondary embolism from bacterial endocarditis commonly occurs, mainly in the spleen and kidneys; but cerebral thromboembolism disease secondary to infective endocarditis has rarely been reported in dogs. In this case, an 8-year-old, neutered male rabbit (Oryctolagus cuniculus) presented with mild hyperthermia, left head tilt and rolling. Radiographic examination, complete blood count, serum biochemistry and abdominal ultrasound were unremarkable. Magnetic resonance imaging did not show any abnormalities in the central nervous system. An Encephalitozoon cuniculi serology was performed with elevated IgM and IgG titers (1:320; 1:1280 respectively), the patient was hospitalized and treated for encephalitozoonis but the rabbit died 8 days after presentation and the body was submitted for necropsy. Histopathological examination revealed multifocal necrotizing and suppurative myocarditis, with multiple emboli in kidneys, lungs and central nervous system. Polymerase chain reaction, immunohistochemistry, and Ziehl-Neelsen staining of samples from the central nervous system and kidneys yielded negative results for Encephalitozoon cuniculi. Due to the positive predictive value of 92% of indirect fluorescent antibody technique Encephalitozoon cuniculi serology, in this case a false positive was suspected. Based on the results, final diagnosis of cerebral thromboembolism secondary to infective endocarditis was emitted. This is the first report of this process naturally occurring in rabbits, and it should be included in the differential diagnosis of central vestibular syndrome in this species.

Background Miniature pigs have gained popularity as companion animals in the recent years in Spain. Due to the fact that their abandonment and crossing breeds with wild boars can cause severe problems, investigation about the health status is needed. Objectives The aim of this study was to determine their health status according to the clinical findings during physical examination and the results of antibody serology tests against selected infectious diseases. Methods Two‐hundred and eleven miniature pigs (Sus scrofa) were included in the study. Their origin, age, sex, housing conditions and diet were recorded. Results The housing of the animals ranged from wild animals to ones living in animal sanctuaries. The diet varied from a natural one in the wild to commercial and homemade food. Thirty animals out of two‐hundred and eleven were hybrids between miniature pigs and wild boars according to morphological characteristics. Antibody serology techniques of Influenza A virus, Hepatitis E virus, brucellosis, tuberculosis, African swine fever, Classical swine fever and Aujeszky's disease was performed. The prevalence for Influenza A was 5.30%, for Hepatitis E was 5.35% and the rest tested negative. It is important to control and monitor these zoonotic infections to prevent Public Health problems. Conclusions The results obtained from this investigation demonstrated that the animals' health status in this study is optimal and the diseases prevalence is similar or minor when compared to previous studies. This study confirms the hybridization of miniature pig and wild boar in Catalonia., This paper describes a research project about health status of free‐ranging pure and cross‐mixed miniature swine population from North East Spain based on analysis of diet, environment, clinical findings, physical examination, and antibody serology techniques.

We used magnetic resonance imaging (MRI) to evaluate the CNS, and confirmed CNS lesions histologically, in 3 psittacine birds with neurologic signs. One bird was recumbent as a result of non-ambulatory paraparesis, and 2 birds were ataxic with impaired proprioception. In all 3 cases, imaging was performed, and infectious diseases were excluded in cases 1 and 2. In case 1, a large mass arose from the left lung; in case 2, a multinodular coelomic mass encompassed the left caudal pulmonary area to the left cranial renal pole; and in case 3, a diffuse hyperintensity affected the lumbar spinal cord. In the first 2 cases, masses invaded the vertebral canal, causing spinal cord compression. All 3 birds were euthanized given the poor prognosis, and postmortem examinations were performed. The final diagnoses were pulmonary adenocarcinoma in cases 1 and 2, and granulomatous and lymphocytic leptomeningitis caused by Mycobacterium genavense in case 3. MRI enabled visualization of the lesions in the affected area of the CNS, and MRI findings were confirmed by histopathology. info:eu-repo/semantics/acceptedVersion

Altres ajuts: acords transformatius de la UAB Altres ajuts: BBVA Foundation; Grifols; National Agency for Research and Development of Chile, Grant/Award Number: 72180406; La Marató TV3, Grant/Award Number: 342/C/2021 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the coronavirus infectious disease 2019 (COVID-19) pandemic in humans, is able to infect several domestic, captive and wildlife animal species. Since reverse zoonotic transmission to pets has been demonstrated, it is crucial to determine their role in the epidemiology of the disease to prevent further spillover events and major spreads of SARS-CoV-2. In the present study, we determined the presence of virus and the seroprevalence to SARS-CoV-2, as well as the levels of neutralizing antibodies (nAbs) against several variants of concern (VOCs) in pets (cats, dogs and ferrets) and stray cats from North-Eastern of Spain. We confirmed that cats and dogs can be infected by different VOCs of SARS-CoV-2 and, together with ferrets, are able to develop nAbs against the ancestral (B.1), Alpha (B.1.1.7), Beta (B.1.315), Delta (B.1.617.2) and Omicron (BA.1) variants, with lower titres against the latest in dogs and cats, but not in ferrets. Although the prevalence of active SARS-CoV-2 infection measured as direct viral RNA detection was low (0.3%), presence of nAbs in pets living in COVID-19 positive households was relatively high (close to 25% in cats, 10% in dogs and 40% in ferrets). It is essential to continue monitoring SARS-CoV-2 infections in these animals due to their frequent contact with human populations, and we cannot discard the probability of a higher animal susceptibility to new potential SARS-CoV-2 VOCs.

Altres ajuts: acords transformatius de la UAB A 2-year-old male red fox (Vulpes vulpes) was presented for generalised tonic-clonic seizures, blindness, compulsive circling and behavioural changes that occurred since the animal was 2 months old. Neurological examination indicated a diffuse forebrain lesion. On magnetic resonance imaging of the brain, a severe dilation of both lateral ventricles was identified. Congenital hydrocephalus was suspected and the fox was treated with methylprednisolone, omeprazole and phenobarbital. Sixteen months later, the neurological signs had improved: the frequency of seizures had decreased to one seizure every 3 months and compulsive circling was less pronounced.

Living donor kidney transplantation (LDKT) is the best treatment for end-stage renal disease. In this setting, a significant percentage of transplants are not undertaken because of medical and nonmedical reasons of both donors and recipients. However, the impact of these discards in a transplant program has not been identified thoroughly so far. Our objective was to clarify key reasons for exclusion of LDKTs and the consequences for the discarded transplant candidates in the following 5 years.Analysis of donors' and recipients' characteristics of 781 couples evaluated in our hospital from January 2005 to December 2013. The consequences of discards in transplant candidates were analyzed in the cohort 2012 to 2013 (n = 106) and followed up until October 2018.In our study group, 402 (51.5%) LDKT couples were successfully donated, and 379 (48.5%) were excluded. Donor and transplant recipient candidates discarded were older at the evaluation (55.07 ± 12.14 years vs 51.73 ± 10.93 years, P .001; 48.81 ± 14.05 years vs 44.62 ± 13.91 years, P .001, respectively). The most frequent reason for kidney discard was medical contraindication found in the potential donor (47.5%; low eGFR, diabetes mellitus, impaired glucose tolerance, high blood pressure, cardiovascular pathology casually found during evaluation, and proteinuria). Of the discarded candidates from 2012 to 2013, 36.8% received a deceased donor kidney transplant, 17% a LDKT with another donor, 7.5% stayed on the waiting list, 18.9% died, 3.8% were excluded from the waiting list, and 14.2% were lost to follow-up.In most cases, transplantation was not undertaken because of donor pathology. Fifty-three percent of the discarded patients were eventually transplanted, with a 31.4% probability to receive an organ from another living donor.

An intact 1-year-old female rat (Rattus norvegicus) presented with a mass in the left axilla. Nodulectomy was subsequently performed, and biopsy results revealed a subcutaneous lymphangiosarcoma (LPS). Metronomic chemotherapy with toceranib and meloxicam was initiated. Three months later, a left axillary mass and an inguinal mass were observed. Histopathologic analysis confirmed the recurrence of a subcutaneous lymphangiosarcoma in the left axilla, and a mammary fibroadenoma in the inguinal area. The animal continued treatment with the same protocol of metronomic chemotherapy, and no tumor recurrence was observed. Lymphangiosarcoma is a rare, malignant neoplasm poorly described in animals. In the only previous report in rats, the LPS was located on the lumbosacral vertebrae. Lymphangiosarcoma should be included in the differential diagnosis of subcutaneous masses in rats.

Dilated cardiomyopathy is a relatively common disease in pet rats (Rattus norvegicus); however, there is a lack of radiographic references for the normal cardiac size in this species. The aim of this prospective, anatomical and reference interval study was to establish quantitative radiographic reference range measurements for the vertebral heart score (VHS) in rats. Right lateral (RL), ventrodorsal (VD), and dorsoventral (DV) radiographs of clinically healthy rats (n = 124) were evaluated. Measurements were performed by 2 expert readers who were unaware of signalment data. The mean values and references intervals of VHS were 7.7 and 7.0-8.5 for the RL, 7.5 and 6.6-8.6 for the VD, and 7.9 and 6.9-9.0 for the DV, with VHS values greater in males than in females. The measurements reported in this study can be used by the clinician as an objective tool to evaluate cardiac size in rats, in order to improve the diagnosis and treatment of cardiac diseases.

Donor/recipient molecular human leukocyte antigen (HLA) mismatch predicts primary B-cell alloimmune activation, yet the impact on de novo donor-specific T-cell alloimmunity (dnDST) remains undetermined. The hypothesis of our study is that donor/recipient HLA mismatches assessed at the molecular level may also influence a higher susceptibility to the development of posttransplant primary T-cell alloimmunity. In this prospective observational study, 169 consecutive kidney transplant recipients without preformed donor-specific antibodies (DSA) and with high resolution donor/recipient HLA typing were evaluated for HLA molecular mismatch scores using different informatic algorithms [amino acid mismatch, eplet MM, and Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II)]. Primary donor-specific alloimmune activation over the first 2 years posttransplantation was assessed by means of both dnDSA and dnDST using single antigen bead (SAB) and IFN-γ ELISPOT assays, respectively. Also, the predominant alloantigen presenting pathway priming DST alloimmunity and the contribution of main alloreactive T-cell subsets were further characterized in vitro. Pretransplantation, 78/169 (46%) were DST+ whereas 91/169 (54%) DST−. At 2 years, 54/169 (32%) patients showed detectable DST responses: 23/54 (42%) dnDST and 31/54 (57%) persistently positive (persistDST+). 24/169 (14%) patients developed dnDSA. A strong correlation was observed between the three distinct molecular mismatch scores and they all accurately predicted dnDSA formation, in particular at the DQ locus. Likewise, HLA molecular incompatibility predicted the advent of dnDST, especially when assessed by PIRCHE-II score (OR 1.014 95% CI 1.001–1.03, p=0.04). While pretransplant DST predicted the development of posttransplant BPAR (OR 5.18, 95% CI=1.64–16.34, p=0.005) and particularly T cell mediated rejection (OR 5.33, 95% CI=1.45–19.66, p=0.012), patients developing dnDST were at significantly higher risk of subsequent dnDSA formation (HR 2.64, 95% CI=1.08–6.45, p=0.03). In vitro experiments showed that unlike preformed DST that is predominantly primed by CD8+ direct pathway T cells, posttransplant DST may also be activated by the indirect pathway of alloantigen presentation, and predominantly driven by CD4+ alloreactive T cells in an important proportion of patients. De novo donor-specific cellular alloreactivity seems to precede subsequent humoral alloimmune activation and is influenced by a poor donor/recipient HLA molecular matching.

Background: Living-donor kidney transplant (LDKT) recipients undergoing desensitization for Human Leukocyte Antigen (HLA)-incompatibility have a high risk of developing antibody-mediated rejection (ABMR). The purpose of the study is to evaluate if residual B cell activity after desensitization could be estimated by the presence of circulating B cell-derived extracellular vesicles (BEVs).Methods: BEVs were isolated by Sepharose-based size exclusion chromatography and defined as CD19+ and HLA-II+ extracellular vesicles. We analyzed stored serum samples from positive crossmatch LDKT recipients before and after desensitization at first post-transplant biopsy and at 12-month protocol biopsy (n = 11). Control groups were formed by hypersensitized patients who were not submitted to desensitization (n = 10) and by low-risk recipients (n = 9). A prospective validation cohort of 11 patients also included the analysis of B cells subpopulations in recipients' blood and lymph nodes recovered upon graft implantation, along with BEVs analysis before and after desensitization.Results: We found out that CD19+ and HLA-II+BEVs dropped significantly after desensitization and relapse in patients who later developed ABMR was evident. We validated these findings in a proof-of-concept prospective cohort of 6 patients who received the same desensitization protocol and also in a control group of 5 LDKT recipients. In these patients, B cell subpopulations were also studied in recipients' blood and lymph nodes that were recovered before the graft implantation. We confirmed the significant drop in BEVs after desensitization and that this paralleled the reduction in CD19+cells in lymph nodes, while in peripheral blood B cells, this change was almost undetectable.Conclusions: BEVs reflected B cell residual activity after desensitization and this could be a valid surrogate of humoral alloreactivity in this setting.

Immunisation against Human Leucocyte Antigens (HLA) can be caused by pregnancy, blood transfusion, or organ transplants. The HLA antibody status of a given patient significantly influences their access and waiting time to transplant. For some highly sensitised patients (HSP) there is hardly any suitable donor available in the deceased donor pool of their allocation organisation and therefore they wait a very long time before being offered a kidney for transplant. Especially patients with rare HLA phenotypes in relation to the actual donor pool are waiting extremely long. As HLA phenotypes are different in the various European populations, we hypothesized that extension of the donor pool outside the respective allocation system will increase the chance of receiving a compatible transplant for this subgroup of highly sensitised patients. One of the objectives of the EUROSTAM project, (a Europe-wide Strategy to enhance Transplantation of highly sensitised patients on the basis of Acceptable HLA Mismatches) was to develop a tool to compare the chance of transplanting HSP in different European populations with donor organs from within and outside their own donor pool. Information on the HLA type and ABO blood group of the actual donor population, as well as the acceptable mismatches of long waiting HSP were obtained from the EUROSTAM partner organizations i.e. Eurotransplant (ET), UK National Health Service Blood and Transplant (NHSBT), Barcelona, Prague and Athens. Results from simulations using the newly developed tool shows that 195 (27%) of the 724 long waiting highly sensitised patients registered at each partner organisation have increased chances of transplant in a different European donor pool. This makes a strong case for sharing kidneys between European countries for selected difficult to transplant patients.

Background It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. Methods To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). Results Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). Conclusions This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.

The genus Malassezia is part of the normal skin mycobiota of a wide range of warm-blooded animals. In this genus, M. cuniculi is the only species described from rabbits. However, Malassezia species are rarely studied in lagomorphs. In the present study, the presence of Malassezia was assessed in samples from the external ear canal of healthy rabbits of different breeds. Cytological and culture techniques, Sanger sequencing, and Next-generation sequencing (NGS) were used to describe the ear mycobiota in the samples. Although no growth was observed in the cultured plates, cytological examination revealed the presence of round cells similar to those of Malassezia yeasts. For metagenomics analysis, the D1/D2 domain of the large subunit of the ribosomal DNA (LSU rDNA) was PCR amplified and the resulting reads were mapped against a custom-made cured database of 26S fungal sequences. NGS analysis revealed that Basidiomycota was the most abundant phylum in all the samples followed by Ascomycota. Malassezia was the most common genus presenting the highest abundance in the external ear canal. Malassezia phylotype 131 and M. cuniculi were the main sequences detected in the external auditory canal of rabbits. The study included both lop-eared and erect-eared rabbits and no differences were observed in the results when comparing both groups. This is the first attempt to study the external ear canal mycobiome of rabbits of different breeds using NGS. Lay Summary In the present study, the presence of Malassezia was assessed in samples from the external ear canal of healthy rabbits of different breeds. Cytological and culture techniques, Sanger sequencing, and Next-generation sequencing (NGS) were used to describe the ear mycobiota in the samples.

Introduction: Despite the different assays available for immune-risk stratification before living-donor kidney transplantation (LDKT), the precise type and number of tests to perform remain uncertain. Methods: In a cohort of 330 consecutive LDKT patients, all of which were complement-dependent cytotoxicity (CDC)−crossmatch negative, we retrospectively analyzed the impact on main clinical outcomes of most sensitive immunoassays (complement-dependent cytotoxicity−panel-reactive antibody [CDC-PRA], flow cytometry crossmatch [FC-XM], donor-specific antibodies [DSAs], and their complement-binding capacity DSA-C3d]), together with donor/recipient HLA eplet matching. Mean follow-up was 67 months (range 24−190 months). Results: Of 330 patients, 35 (11%) showed a CDC-PRA >20%; 17 (5%) FC-XM+; 30 (9%) DSA+, 18(5%) DSA-C3d+, with low overlapping results (10 patients positive in all donor-specific tests). Unlike HLA allele compatibility, the mean number of HLA class II eplet mismatches was higher in LDKT patients with positive baseline test results. DSA-C3d+ showed higher mean fluorescence intensity (MFI) DSA, with a cut-off MFI of 6192 accurately predicting complement fixation (area under the curve = 0.85, P = 0.008). Although all assays were associated with acute rejection (AR), only DSA-C3d+ (odds ratio [OR] = 6.64, P = 0.038) or high MFI-DSA (OR = 7.54, P = 0.038) independently predicted AR. Likewise, poorly HLA class II eplet−matched patients were at higher risk for AR, particularly patients with negative baseline test results (OR = 1.14, P = 0.019). Finally, previous AR and FC-XM+/DSA+, regardless of C3d positivity, independently predicted graft loss. Conclusion: Combining FC-XM and solid-phase assays with the evaluation of donor/recipient HLA eplet mismatches, are most accurate tools for immune-risk stratification prior LDKT. Keywords: acute rejection, crossmatch immunoassays, donor-specific antibodies, HLA matchmaker, immune risk stratification, living donor kidney transplantation

Cardiovascular disease, including congestive heart failure, pericardial disease, and atherosclerosis, is becoming increasingly better recognized in companion birds, small mammals, and reptiles. A wide range of medications is available to treat these conditions, including diuretics, vasodilators, positive and negative inotropes, antiarrhythmic agents, and pentoxifylline. This review systematically discusses each of these drug classes and their potential applications in exotic species. Although treatment approaches remain largely empirical and extrapolated from small animal and human medicine, the management strategies presented here have the potential to both maintain quality of life and extend survival time for the exotic cardiac patient.

Fifty-two guinea pigs ( Cavia porcellus ) with normal ophthalmic examinations were included in this study to determine whether there are differences in the intraocular pressure (IOP) according to age, while assessing the clinical usefulness of 2 different tonometry methods for this species. The animals were divided into 2 groups according to age: young (4 weeks old, 29 animals) and adult (3 to 36 months, 23 animals). Tonometry was performed oculus utro (OU) in the central cornea according to the manufacturer's recommendations. Only measurements with low standard deviation (SD 0.05) nor between sexes (p > 0.05). TonoVet readings were obtained faster than Tono-Pen VET readings (less than 1min vs 3.38 ± 1.27min, respectively [p

A Siberian hamster with multiple papillomatous lesions in the skin and gastrointestinal mucosa was evaluated using multiple diagnostic tests. Tissues collected from this hamster were examined through macroscopic, microscopic, immunohistochemical, and ultrastructural techniques. These multifocal papillomas were associated with a cutaneous basal cell carcinoma, sebaceous adenomas, sebaceus epitheliomas and demodicosis. Large amphophilic intranuclear inclusions were detected in keratinocytes and epithelial cells of both cutaneous and gastrointestinal papillomas. The intranuclear inclusions were strongly positive by immunohistochemistry for a papillomavirus (PV) structural antigen. Electronic-dense hexagonal viral particles 30 nm in diameter were observed within the nuclei of keratinocytes and gastrointestinal tract epithelial cells by transmission electron microscopy. No viral DNA was detected with polymerase chain reaction specific hamster or broad range PV primers. This report describes noninduced multicentric papillomatosis involving the gastric mucosa and gastroduodenal junction, which may have been the result of a new PV-type infection.

Two 2-year-old intact female rats ( Rattus norvegicus ) were presented with severe dyspnea and tachypnea. In rat 1, radiographic evaluation of the thorax revealed severe pleural effusion, and cardiomegaly was suspected, suggesting a severe congestive heart failure. Echocardiography and computed tomography (CT) revealed bilateral pleural effusion, severe dilated cardiomyopathy (DCM), hepatomegaly, and mild abdominal effusion. Thoracocentesis and cytological examination revealed a chylous effusion. The patient was treated with a low-fat diet, octreotide, and medication to treat heart disease (furosemide, benazepril, pimobendan, and digoxin). However, because of worsening clinical signs, the animal was euthanized 5 days following the initiation of treatment. At necropsy, the heart was enlarged and rounded, with evident dilation of both ventricles, and the final diagnosis determined to be a DCM and myocardial fibrosis. The cardiac disease appeared to cause a chronic passive liver and lung congestion that, finally, resulted in both pleural and abdominal effusions. In rat 2, radiographic analysis of the thorax revealed pleural effusion and (conceivably) cardiomegaly, suggesting a severe congestive heart failure. Echocardiography and CT revealed pleural effusion and severe DCM of 4 chambers without effective contractility. Thoracocentesis was performed on the patient with the subsequent cytological examination of aspirated fluid being assessed as a transudate rich in macrophages and cells compatible with mastocytes. Cardiac medications were initiated, and the patient was monitored on a weekly basis. The rat died 27 days after the initial diagnosis due to respiratory failure. During the necropsy examination, it was determined that the rat's heart was rounded, with enlargement of the left ventricle and thinning of the ventricular wall. The final disease diagnosis following the postmortem examination of rat 2 was a DCM and myocardial degeneration, which caused a chronic passive liver and lung congestion that resulted in a pleural effusion, hindering normal pulmonary activity. There is a paucity of published articles that describe DCM in rats. Recommended treatment of cardiovascular disease in this species is largely extrapolated from data obtained from cats, dogs, and ferrets. Further studies are warranted to detail the efficacy of therapeutic agents to treat cardiac disease in pet rats.

The anti-HLA antibody detection has been improved in sensitivity and specificity with solid-phase antigen bead (SAB) assays based on Luminex. However, false positive results due to denatured HLA (dHLA) may arise after single antigen test. The aim of this study was to compare the performance of the two Luminex technology-based anti-HLA detection kits available in the market in showing undesired anti-HLA antibody results. A prospective cohort was assessed for anti-HLA antibodies with single antigen A manufacturer (AM) kit and a comparison cohort with single antigen B manufacturer (BM) kit. A total of 11 out of 90 patients in a prospective cohort presented monospecific HLA-I antibodies with AM, and 5 out of 11 confirmed monospecific reaction with BM. Despite the confirmation of monospecific reaction with both manufacturers, 80% were assigned as dHLA reaction by specific crossmatch. Further comparative cohorts detected four out of six monospecific reactions with BM that were confirmed as possible dHLA reactions. A positive SAB test should rule out a reaction against a dHLA molecule, thus avoidance of prolonged waitlist periods or misattribution of anti-HLA reactions after transplantation.

Introduction Nonantigen-specific immunoadsorption (IA) has proven to be effective in acute antibody-mediated rejection (aAMR). However, there is a lack of solid studies evaluating the safety and efficacy of IA with antihuman Ig-columns in aAMR. For chronic-active AMR (cAMR), no studies have evaluated the efficacy of nonantingen-specific IA with antihuman Ig-columns. The purpose of this study was to evaluate the role of nonantigen-specific IA with antihuman Ig-columns in the treatment of both aAMR and cAMR in kidney transplantation. Material and methods In retrospective and observational study, kidney graft and recipient survival rates were assessed after treatment of aAMR and cAMR with nonantigen-specific IA with Ig-Flex columns (Therasorb) between January 2012 and May 2018. Protocols included nonantigen-specific IA, rituximab, intravenous immunoglobulin, and rescue plasma exchange, if necessary. Results The study included 14 patients with AMR (acute in 9, chronic active in 5). For aAMR, mean follow-up was 13 ± 6 months, and patient and graft survival were, respectively, of 100% and 83%, with a mean increase in estimated glomerular filtration rate (eGFR) of 7.98 ± 12.96, 10.18 ± 16.71, and 11.43 ± 13.85 mL/min/1.72 m2 (P > .05) at 3, 12 months after treatment, and at the end of follow-up, respectively. For cAMR, mean follow-up was 14 ± 8 months, and patient and graft survival were, respectively, of 100% and 60%, with an average increase in eGFR of 4.30 ± 7.86, 5.64 ± 10.47, and 14.5 ± 7.86 mL/min/m2 (P > .05) at 3, 12 months after IA treatment, and at the end of the follow-up, respectively, although 40% did not respond and required chronic hemodialysis. Conclusion Nonantigen-specific IA with Ig-Flex columns was safe and effective for aAMR treatment in kidney transplantation. In cAMR, IA with Ig-Flex columns was associated with a satisfactory kidney graft survival, suggesting that IA could potentially offer some benefits supporting its indication in cAMR.

The Eurotransplant (The Eurotransplant International Foundation) acceptable mismatch programme has been shown to be a successful tool to enhance transplantation of highly sensitized patients(HSPs). However, patients with rare HLA phenotypes in relation to the Eurotransplant donor population remain on the waiting list. EUROSTAM is an European Union funded project to explore the feasibility of a Europe-wide acceptable mismatch programme enabling transplantation of HSPs with rare HLA phenotypes within their own organ exchange organization. The present study, which forms part of the EUROSTAM project, assesses the differences in the practices of the laboratories in different countries with respect to their HLA antibody profiling and risk adverseness. In the serum exchange exercises of 18 samples, a high level of variability has been shown in both assays and interpretation of results. In the data exchange exercise when all participants were given the same Luminex raw data for analysis, a high degree of consensus was reached where the median fluorescent intensity values of beads were < 500 and >2000 for standard single antigen bead assays, or < 500 and >5000 for assignment of acceptable mismatches. The risk adverseness analysis has showed distinct pattems of attitudes towards the perceived risks based on HLA antibody assay results, most probably influenced by the local protocols of the clinical transplant programme of each laboratory. In order to ensure fairness and maintain consistencies of organ exchange among partner transplant centres, a centralized facility will be instrumental for a uniform definition of acceptable mismatches.

Veiled chameleons (Chamaeleo calyptratus) and panther chameleons (Furcifer pardalis) are the most popular chameleons over the world, and consequently, two of the most frequent species presenting to veterinary practices. However, published studies on normal ultrasonographic anatomy for these lizards are currently lacking. The objectives of this prospective anatomic study were to develop an ultrasound protocol for evaluation of the coelomic cavity in these species and describe the normal ultrasonographic anatomy of the coelomic organs. Seventeen healthy veiled chameleons and 15 healthy panther chameleons were included. A linear 18 MHz transducer was used. Chameleons were sedated and restrained in right lateral recumbency by an assistant. Longitudinal and transverse images were acquired, and authors recorded qualitative and quantitative ultrasonographic characteristics of the coelomic structures. The kidneys, liver, caudal vena cava, hepatic veins, portal vein, gallbladder, wall of the stomach and intestine, gonads and, when distended, urinary bladder could be visualized during ultrasonography of the coelomic cavity in both species. The spleen, pancreas, and adrenal glands could not be identified. Findings from the current study supported the use of ultrasonography for veiled chameleons (Chamaeleo calyptratus) and panther chameleons (Furcifer pardalis) with suspected intracoelomic diseases and provided normal reference information for future studies of these chameleon species.

Cutaneous mast cell tumours (cMCTs) are one of the most common cutaneous tumours in ferrets (Mustela putorius furo). However, limited information is available regarding cytological and histological features of these tumours and studies evaluating KIT expression are lacking in this species. The aims of this prospective study were to describe the most common clinical, cytological and histological features of cMCTs in ferrets and to compare the usefulness of different staining techniques in the diagnosis of these tumours in ferrets as well as evaluating KIT expression in neoplastic mast cells (MCs) by immunohistochemistry. Macroscopically, the tumours were small, round to plaque-like and frequently associated with surface crusting. The most common locations were the extremities and the trunk. MC granules were stained in all cases using toluidine blue (TB) and Wright-Giemsa stains in cytological specimens, but none stained with modified Wright's stain. Haematoxylin and eosin and TB on histological sections failed to stain MC granules in all the cases. Cytological and histological examination revealed low to moderate anisocytosis and anisokaryosis. An infiltrative rather than a delineated or encapsulated growth pattern was noted histologically in all cases. Eosinophilic infiltration was not uncommon and 'collagenolysis' was detected on cytological and histological examination. KIT expression was detected in all cases evaluated. In approximately one third of the cases the MCs exhibited KIT labelling pattern I and in the remaining ferrets, KIT pattern III. No correlation was found between KIT expression pattern and biological behaviour.

Background Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disease with limited response to currently available therapies. Alveolar type II (ATII) cells act as progenitor cells in the adult lung, contributing to alveolar repair during pulmonary injury. However, in IPF, ATII cells die and are replaced by fibroblasts and myofibroblasts. In previous preclinical studies, we demonstrated that ATII-cell intratracheal transplantation was able to reduce pulmonary fibrosis. The main objective of this study was to investigate the safety and tolerability of ATII-cell intratracheal transplantation in patients with IPF. Methods We enrolled 16 patients with moderate and progressive IPF who underwent ATII-cell intratracheal transplantation through fiberoptic bronchoscopy. We evaluated the safety and tolerability of ATII-cell transplantation by assessing the emergent adverse side effects that appeared within 12 months. Moreover, pulmonary function, respiratory symptoms, and disease extent during 12 months of follow-up were evaluated. Results No significant adverse events were associated with the ATII-cell intratracheal transplantation. After 12 months of follow-up, there was no deterioration in pulmonary function, respiratory symptoms, or disease extent. Conclusions Our results support the hypothesis that ATII-cell intratracheal transplantation is safe and well tolerated in patients with IPF. This study opens the door to designing a clinical trial to elucidate the potential beneficial effects of ATII-cell therapy in IPF.

Hedgehogs have increased in popularity as pets in Spain but there are no data of infection rates of this exotic animal with dermatophytes in our country. During the period of 2008-2011 a total of 20 pet hedgehogs (19 African pygmy hedgehogs and 1 Egyptian long-eared hedgehog) suspected of having dermatophytoses were studied. This is the first survey of the occurrence of T. erinacei in household hedgehogs in Spain. The T. erinacei infection rate was 50% (9 out of 19 African pygmy hedgehogs, and the one Egyptian long-eared hedgehog surveyed). Morphological identification of the isolates was confirmed by molecular analysis. All the strains had the same ITS sequence and showed 100% sequence similarity to T. erinacei type strain CBS 511.73 (AB 105793). The Spanish isolates were confirmed as T. erinacei urease positive. On the basis of ITS sequences, T. erinacei is a species close to but separate from the taxa included in the A. benhamiae complex. Review of the current literature on DNA-based methods for identification of species included in this complex has highlighted the urgent need to reach a consensus in species circumscription and classification system accepted by all mycologists.

Disorders of the kidneys and urinary tract are relatively common in rabbits. Survey radiographs and abdominal ultrasound have inherent limitations in the evaluation of the urinary tract in this species; because of that, contrast study modalities are a valuable diagnostic tool in rabbits with urinary disorders. The aims of this study were to describe digital fluoroscopic excretory urography (DFEU) and to determine the urogram phases in healthy New Zealand rabbits. The median time of beginning of the nephrographic and pyelographic phases was 10 seconds (IQR: 10-12 seconds) and 1.39 minutes (IQR: 1.27-1.60 minutes). The median time in which the contrast medium was visible in the urinary bladder was 1.58 minutes (IQR: 1.44-1.72 minutes). Results of this study indicate that DFEU provides a good degree of opacification of the kidneys as well as the ureters, and allows the evaluation of the urogram phases. Text not justifed in the proof version.

A 5-month-old, intact male ferret ( Mustela putorius furo ) was presented with apathy, tachypnea and exercise intolerance. On initial physical examination, tachypnea and cyanosis were the two primary clinical signs detected. The complete blood count also revealed a severe polycythemia, with lymphopenia, neutrophilia and eosinophilia. Further diagnostic imaging tests were performed. The thoracic radiographs revealed cardiomegaly and a diffuse alveolar pulmonary pattern. Consequently, an echocardiography was performed and showed an interventricular septal defect, pulmonic artery occlusion, overriding of the aorta and right ventricle hypertrophy. All abnormalities were compatible with a tetralogy of Fallot (TOF). As a treatment plan, a phlebotomy was performed and the ferret was posteriorly maintained with oxygen and fluid therapy. The following day, the hematocrit decreased 11% and the respiratory distress improved. Four days later, the ferret got clinically worse and was euthanized. A necropsy was performed and confirmed the presence of an extreme TOF with a diffused interstitial pneumonia secondary to Pneumocystis carinii . To the author's knowledge, this is the first report of an extreme tetralogy of Fallot with polycythemia in a ferret.

Cerebrospinal fluid analyses are important for diagnosis of neurologic problems in rabbits and for translational research projects using rabbits as models. Blind puncture of the cisterna magna is the current standard technique for sampling cerebrospinal fluid in this species. However, the complexity and small size of the cisterna magna and surrounding structures are limitations of this technique. Aims of this prospective, anatomic, pilot study were to (1) describe the normal anatomy of the atlanto-occipital region, (2) describe ultrasonographic anatomic landmarks, and (3) develop and evaluate a technique for ultrasound-guided puncture of the cisterna magna for cerebrospinal fluid sampling in rabbits. Thirty healthy rabbits were included and the study was conducted in three stages. Three rabbit cadavers were used for the first stage of the study. Then, the second stage was completed using 13 rabbit cadavers. Finally, the third stage was completed in 14 live rabbits. The ultrasound-guided puncture performed in 13 cadavers was successful at the first attempt in 10 cases, and at the second attempt in the remaining three cases. In the in vivo study, the ultrasound-guided puncture was successful in all 14 cases, without signs of complications. Findings supported the use of ultrasound-guided puncture of the cisterna magna as a safe technique that may be used routinely or when the sample of cerebrospinal fluid cannot be obtained with the blind technique in rabbits.

Reproduction diseases are common presentations in small rodents. Some can be presented to the clinician as an emergency where a fast and effective treatment is required. This article presents an overview of reproductive disorders in these species. Diseases affecting the ovary, uterus, testicles, and mammary gland are developed in rats, mice, hamsters, and gerbils: inflammatory, infectious, and neoplasia. Clinical signs, diagnosis, and treatment information are included. Some specific indications about the surgical reproduction procedures are described. Literature regarding reproductive disorders exists for squirrels and prairie dogs. Brief information about the normal anatomy of the reproductive system is given.

Background Stem cell therapy offers a promising approach to reduce the long-term mortality rate associated with heart failure after acute myocardial infarction (AMI). To date, in vivo translational studies have not yet fully studied the immune response to allogeneic adipose tissue-derived mesenchymal stem cells (ATMSCs). We analysed the immune response and the histological and functional effects of allogeneic ATMSCs in a porcine model of reperfused AMI and determine the effect of administration timing. Design Pigs that survived AMI (24/26) received intracoronary administration of culture medium after reperfusion (n = 6), ATMSCs after reperfusion (n = 6), culture medium 7 days after AMI (n = 6) or ATMSCs 7 days after AMI (n = 6). At 3-week follow-up, cardiac function, alloantibodies and histological analysis were evaluated. Results Administration of ATMSCs after reperfusion and 7 days after AMI resulted in similar rates of cell engraftment; some of those cells expressed endothelial, smooth muscle and cardiomyogenic cell lineage markers. Delivery of ATMSCs after reperfusion compared with that performed at 7 days was more effective in increasing: vascular density (249 ± 64 vs. 161 ± 37 vessels/mm2; P

The ferret has emerged as an excellent animal model to characterize several physiologic and pathologic conditions. The distribution and characterization of different types of immune system cells were studied in healthy ferret tissues. Eight primary antibodies were tested for immunohistochemistry in formalin-fixed tissues: anti-CD3, anti-CD79α, anti-CD20, anti-HLA-DR, anti-lysozyme, anti-CD163, anti-SWC3, and anti-Mac387. The anti-CD3 antibody labeled T cells mainly in interfollicular and paracortical areas of lymph nodes, cortex and thymic medulla, and periarteriolar lymphoid sheaths in the spleen. The anti-CD79α and anti-CD20 antibodies immunolabeled B cells located in lymphoid follicles at lymph nodes, spleen, and Peyer patches. The CD79α and CD20 antibodies also labeled cells with nonlymphoid morphology in atypical B-cell locations. The anti-HLA-DR antibody labeled macrophages, some populations of B and T lymphocytes, and different populations of dendritic cells in lymph nodes, Peyer patches, spleen, and thymus. The anti-lysozyme antibody immunolabeled macrophages in the liver, lymph nodes, spleen, and thymus. The Mac-387, CD163, and SWC3 antibodies did not show any positive reaction in formalin-fixed or frozen tissues. To elucidate the origin of the uncommon CD79α/CD20 positive cells, a double immunohistochemistry was carried out using the anti-HLA-DR + the anti-CD79α, the anti-HLA-DR + the anti-CD20, and the anti-lysozyme + the anti-CD79α antibodies. Double labeling was mainly observed when the anti-HLA-DR + the anti-CD79α antibodies were combined. The immunohistologic characterization and distribution of these immune system cells in healthy ferret tissues should be of value in future comparative studies of diseases in ferrets.

Noninvasive diagnosis of kidney allograft inflammation in transplant recipients with stable graft function (subclinical rejection) could permit more effective therapy and prevent later development of de novo anti-donor HLA antibodies and/or graft dysfunction. Here we tested whether quantifying posttransplant donor-specific alloreactive T-cells by IFN-γ ELISPOT assay noninvasively detects subclinical T–cell mediated rejection and/or predicts development of anti-donor HLA antibodies. Using an initial cross-sectional cohort of 60 kidney transplant patients with six-month surveillance biopsies, we found that negative donor-specific IFN-γ ELISPOT assays accurately ruled out the presence of subclinical T–cell mediated rejection. These results were validated using a distinct prospective cohort of 101 patients where donor-specific IFN-γ ELISPOT results at both three- and six-months posttransplant significantly differentiated patients with subclinical T–cell mediated rejection at six months, independent of other clinical variables (odds ratio 0.072, 95% confidence interval 0.008-0.653). The posttransplant donor-specific IFN-γ ELISPOT results independently associated with subsequent development of significant anti-donor HLA antibodies (0.085, 0.008-0.862) and with significantly worse two-year function (estimated glomerular filtration rate) compared to patients with a negative test. Thus, posttransplant immune monitoring by donor-specific IFN-γ ELISPOT can assess risk for developing subclinical T–cell mediated rejection and anti-donor HLA antibodies, potentially limiting the need for surveillance biopsies. Our study provides a guide for individualizing immunosuppression to improve posttransplant outcomes.

Access to kidney transplantation for patients with high levels of antibodies against HLA is a major challenge. This issue makes it difficult to detect compatible donors for those patients in a certain geographical area. Consequently, hypersensitized patients remain on the waiting list for long periods and their quality of life deteriorates. Our purpose was to increase access to transplantation for highly sensitized patients by developing a national priority allocation system based on virtual crossmatch. Between June 15, 2015, and May 15, 2016, 675 patients on the kidney transplant waiting list with calculated panel-reactive antibodies ≥98% and undergoing dialysis for at least 12 months were included in the study; 86.1% of the patients had previously received at least one transplant. Solid-phase immunoassays were used to identify class I and II HLA antibodies in all patients. Participating hospitals assigned to the program one of the kidneys of every identified brain-dead real donor between 18 and 70 years old. Survival data were collected for the recipients transplanted between June 15, 2015, and December 31, 2015. In all, 475 (290 male and 185 female) brain-dead donors were assigned to the program. Virtual crossmatch was negative for 191 (41%) donors, 149 offers were accepted, and 102 (21.8%) kidneys were transplanted. At the end of the study, patient and graft survival were both 93.4%. The implementation of a national prioritization system based on virtual crossmatch increased access to transplantation for highly sensitized patients, with excellent results in terms of patient and graft survival.