Renal alterations in cats (Felis catus) housed in shelters and affected by systemic AA-amyloidosis: Clinicopathological data, histopathology, and ultrastructural features.

AA-amyloidosis is frequent in shelter cats, and chronic kidney disease is the foremost cause of death. The aims were to describe kidney laboratory and microscopic findings in shelter cats with AA-amyloidosis. Cats were included if kidney specimens were collected post-mortem and laboratory data were available within 6 months before death. Renal lesions were evaluated with optical and electron microscopy. Mass spectrometry was used to characterize amyloid. Nine domestic short-hair cats were included; 4 females and 5 males with a median age of 8 years (range = 2-13). All cats had blood analyses and urinalyses available. Serum creatinine concentrations were increased in 6 cats and symmetric dimethylarginine was increased in all of the cats. All of the cats had proteinuria. Eight of 9 cats had amyloid in the medulla, and 9 had amyloid in the cortex (glomeruli). All cats had amyloid in the interstitium. Six cats had concurrent interstitial nephritis and 1 had membranoproliferative glomerulonephritis. All cats had extrarenal amyloid deposits. Amyloid was AA in each case. In conclusion, renal deposition of amyloid occurs in both cortex and medulla in shelter cats and is associated with azotemia and proteinuria. Renal involvement of systemic AA-amyloidosis should be considered in shelter cats with chronic kidney disease. The cat represents a natural model of renal AA-amyloidosis.

Gastrointestinal ultrasonographic findings in cats with Feline panleukopenia: a case series.

BACKGROUND: Feline panleukopenia virus (FPV) is very resistant and highly contagious and infects domestic cats and other felids. FPV is particularly widespread among sheltered cats, and is associated with high morbidity and mortality, causing severe gastroenteritis characterized by anorexia, lethargy, fever, dehydration, hemorrhagic diarrhea, and vomiting. There is currently no data on the ultrasonographic features of cats affected with FPV. This case series describes abdominal ultrasonographic findings in shelter cats with naturally-occurring FPV, and assesses whether are associated with clinical and laboratory findings. Cats affected by FPV were enrolled in the study if an abdominal ultrasound was performed within 12 hours of diagnosis. Clinical, laboratory and survival data were collected from medical records. Ultrasonographic examinations were reviewed for gastrointestinal abnormalities and their associations with the above data were explored. RESULTS: Twenty-one cats were included. Nine cats (42.9%) died and 12 (57.1%) recovered. Based on ultrasonography, the duodenum and jejunum showed thinning of the mucosal layer in 70.6% and 66.6% of cats, thickening of the muscular layer in 52.9% and 57.1% of cats, and hyperechogenicity of the mucosa in 41.2% and 33.3%. Jejunal hyperechoic mucosal band paralleling the submucosa and irregular luminal surface were both observed in 33.3% of the cats. Survival was positively associated with increased jejunal mucosal echogenicity (P = 0.003) and hyperechoic mucosal band (P = 0.003). Peritoneal free fluid was positively associated with vomiting (P = 0.002). CONCLUSIONS: This study provides ultrasonographic features of naturally-occurring FPV in cats, which, as expected, are compatible with gastroenteropathy. The most frequent findings were diffuse small intestine mucosal layer thinning, muscular layer thickening and mucosal hyperechogenicity, jejunal hyperechoic mucosal band and irregular luminal surface. Ultrasonographic features may be useful to complete the clinical picture and assess the severity of the gastroenteropathy in FPV cats. Prospective studies are needed to confirm ultrasonographic prognostic factors.

Diabetic remission in a cat treated with an implantable pump to deliver insulin.

A diabetic cat was referred because of poor metabolic control and difficulties the owner experienced injecting insulin. A pump, telemetrically controlled with a smartphone, was implanted subcutaneously to deliver insulin. Before implantation, the pump reservoir was filled with a rapid-acting human recombinant insulin. The insulin was administered through continuous infusion or periodic boluses over 2 weeks while the cat was hospitalized and over another 2 weeks after discharge from the hospital. Adjustments of insulin dosage were performed based on blood glucose concentrations measured with a continuous blood monitoring system (CGMS). The cat achieved diabetic remission that is still lasting after 1 year. The treatment protocol adopted in this cat contributed to achieving remission. The owner's unwillingness to inject insulin into an uncooperative cat was circumvented with the implantable pump. Key clinical message: The implantable subcutaneous pump, telemetrically controlled by a smartphone, easily allowed the clinician to modify the type of administration and the amount of insulin delivered; the concurrent use of a CGMS allowed detection of sudden changes in blood glucose while limiting stress to the cat.

Rémission du diabète chez un chat traité avec une pompe implantable pour administrer l'insuline.Un chat diabétique fut référé pour cause de pauvre contrôle métabolique et des difficultés rencontrées par le propriétaire pour injecter l'insuline. Une pompe, contrôlée par télémétrie avec un téléphone intelligent, fut implantée sous-cutané afin d'injecter l'insuline. Avant l'implantation, le réservoir de la pompe fut rempli avec une insuline humaine recombinante à action rapide. L'insuline était administrée par infusion continue ou des bolus périodiques pendant une période de 2 semaines alors que le chat était hospitalisé et pendant un 2 semaines supplémentaires après avoir obtenu son congé de l'hôpital. Des ajustements du dosage de l'insuline furent effectués sur la base des concentrations de glucose sanguin mesurées par un système continu de surveillance du sang (CGMS). Une rémission du diabète fut possible pour ce chat et persiste toujours après 1 an. Le protocole de traitement adopté chez ce chat a contribué à atteindre cette rémission. La réticence du propriétaire à injecter l'insuline chez un chat non-collaborateur fut contournée par une pompe implantable.Message clinique important :La pompe implantable sous-cutanée, contrôlée par télémétrie avec un téléphone intelligent, a facilement permis au clinicien de modifier le type d'administration et la quantité d'insuline donnée; l'utilisation concomitante d'un CGMS a permis la détection de changements soudains dans la glycémie tout en limitant le stress au chat.(Traduit par Dr Serge Messier).

Immune-complex glomerulonephritis in cats: a retrospective study based on clinico-pathological data, histopathology and ultrastructural features.

BACKGROUND: Chronic kidney disease (CKD) has typically a non-immune mediated origin in cats and immune-complex glomerulonephritis (ICGN) is scarcely described. Aims of this study were to characterize ICGN by light and electron microscopy and identify associations with clinico-pathological findings. In addition, comparisons between cats with ICGN and non immune-complex glomerulonephritis (non-ICGN) were performed. Renal samples examined between 2010 and 2019 were considered if both light and electron microscopy were performed. Signalment, feline immunodeficiency virus (FIV) and leukemia virus (FeLV) status, serum creatinine concentration, urine protein-to-creatinine (UPC) ratio, systolic blood pressure (SBP) and International Renal Interest Society (IRIS) stage were retrieved and used for comparisons. RESULTS: Sixty-eight client-owned cats were included. Thirty-seven cats (54.4%) had ICGN and 31 (45.6%) non-ICGN. Eighteen (48.6%) with ICGN had membranous glomerulonephropathy (MGN), 14 (37.8%) membranoproliferative glomerulonephritis (MPGN), and 5 (13.5%) mesangioproliferative glomerulonephritis (MeGN). Clinico-pathological data were not associated with any type of ICGN. Among cats with non-ICGN, 11 (35.5%) had end-stage CKD, 9 (29%) focal segmental glomerulosclerosis, 6 (19.4%) global and multifocal mesangiosclerosis, 2 (6.5%) glomerular atrophy, 2 (6.5%) renal dysplasia and 1 (3.1%) amyloidosis. Eight (25.8%) cats with non-ICGN had chronic interstitial nephritis (CIN) grade 1, 13 (41.9%) grade 2 and 10 (32.3%) grade 3; creatinine and UPC ratio increased with CIN grades (p = 0.001, p < 0.001). Cats with ICGN were more frequently FIV or FeLV-infected (OR:11.4; 95%CI:1.4-94.4; p = 0.024), had higher UPC ratio (OR:6.8; 95%CI:2.5-18.2; p < 0.001) and were younger (OR:0.9; 95%CI:0.7-1.0; p = 0.042) than cats with non-ICGN. CONCLUSIONS: MGN and MPGN were the most common morphological diagnoses of ICGN in cats. Unfortunately, none of the investigated findings differentiated ICGN morphological diagnoses. Serum creatinine concentration and UPC ratio were directly associated with grades of CIN (p = 0.001 and p < 0.001, respectively), confirming previous literature. More ICGN than non-ICGN was observed in cats with retroviral infections, younger cats and higher UPC ratio.

Pheochromocytoma in Dogs Undergoing Adrenalectomy.

Pheochromocytoma is frequent in dogs and carries a guarded prognosis. Current histological criteria may not predict malignant behavior in dogs, similar to humans. In humans, characterization of tumors has been refined using the pheochromocytoma of the adrenal gland scaled score (PASS) and by immunohistochemistry. The study aim was to investigate PASS and immunohistochemical markers used in humans in 24 dogs with pheochromocytoma that underwent adrenalectomy. Dogs with pheochromocytomas were reviewed and tumors collected. Histological sections were evaluated to apply the PASS and were single-labeled for chromogranin A, Ki-67, COX-2, p53, BCL-2, c-erbB-2, vascular endothelial growth factor, and S100. Survival, age, and vascular and capsular invasion were compared for PASS and immunohistochemical markers; results of PASS were also compared for each marker. Associations between markers were tested. PASS and immunohistochemical markers did not differ for survival, age, and vascular and capsular invasion. Tumors showing BCL-2 expression in >50% cells had lower PASS than those with lower expression (PASS: 7 ± 2 vs 9 ± 2; P = .011). Tumors positive for S100 had higher PASS than those that were negative (PASS: 10 ± 2 vs 7 ± 2; P = .001). Results of the different markers were not associated. In conclusion, in the context of canine pheochromocytoma, PASS and the selected immunohistochemical markers are not associated with survival, age, or vascular or capsular invasion. The higher PASS in S100-positive tumors may indicate that pheochromocytomas developing morphologic changes acquire S100 expression. The significance of lower PASS in tumors with elevated BCL-2 expression is uncertain. Overall, the use of PASS and the present immunohistochemical markers may not be useful in dogs with pheochromocytoma.

EVALUATION OF THE COMPUTED TOMOGRAPHIC "SENTINEL CLOT SIGN" TO IDENTIFY BLEEDING ABDOMINAL ORGANS IN DOGS WITH HEMOABDOMEN.

The CT "sentinel clot sign" has been defined as the highest attenuation hematoma adjacent to a bleeding organ in humans with hemoabdomen. The aims of this retrospective descriptive multicenter study were to describe CT findings in a sample of dogs with surgically or necropsy confirmed intra-abdominal bleeding and determine prevalence of the "sentinel clot sign" adjacent to the location of bleeding. Medical records between 2012 and 2014 were searched for dogs with hemoabdomen and in which the origin of the bleeding was confirmed either with surgery or necropsy. Retrieved CT images were reviewed for the presence and localization of the "sentinel clot sign," HU measurements of the "sentinel clot sign" and hemoabdomen, and presence of extravasation of contrast media within the abdominal cavity. Nineteen dogs were included. Three dogs were excluded due to the low amount of blood that did not allow the identification of a "sentinel clot sign." A "sentinel clot sign" was detected in the proximity of the confirmed bleeding organ in 14/16 (88%) of the patients. The mean HU of the "sentinel clot sign" was 56 (range: 43-70) while that of the hemoabdomen was 34 (range: 20-45). Active hemorrhage was identified as extravasation of contrast medium within the peritoneal cavity from the bleeding organ in three dogs. In conclusion, the CT "sentinel clot sign" may be helpful for identifying the source of bleeding in dogs with hemoabdomen.

Emergence of cutaneous neosporosis in a dog receiving immunosuppressive therapy: molecular identification and management.

BACKGROUND: Neosporosis is a multisystemic disease caused by the intracellular protozoan Neospora caninum. In dogs the disease primarily affects the central nervous system. Canine cutaneous neosporosis is a rare condition often associated with old age or concurrent immunosuppressive treatments for different underlying conditions. ANIMALS: A 10-year-old female spayed golden retriever dog affected by primary immune-mediated myelofibrosis and treated with immunosuppressive therapies for 6 weeks that developed severe cutaneous lesions. METHODS: Definitive diagnosis was based on several investigation techniques including serology (immunoblotting), immunohistochemistry (IHC), species-specific conventional and real-time PCR, and DNA sequencing. RESULTS: Remission of cutaneous neosporosis was obtained with the administration of clindamycin while the concurrent immunosuppressive therapy was maintained to manage the underlying primary condition. CONCLUSIONS AND CLINICAL IMPORTANCE: To the best of the authors' knowledge this is the first report of species-specific PCR and DNA sequencing used as diagnostic methods for canine cutaneous neosporosis emerging in a dog receiving immunosuppressive therapy.

AA-amyloidosis in cats (Felis catus) housed in shelters.

Systemic AA-amyloidosis is a protein-misfolding disease characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. A high prevalence of AA-amyloidosis has been reported in captive cheetahs and a horizontal transmission has been proposed. In domestic cats, AA-amyloidosis has been mainly described in predisposed breeds but only rarely reported in domestic short-hair cats. Aims of the study were to determine AA-amyloidosis prevalence in dead shelter cats. Liver, kidney, spleen and bile were collected at death in cats from 3 shelters. AA-amyloidosis was scored. Shedding of amyloid fibrils was investigated with western blot in bile and scored. Descriptive statistics were calculated. In the three shelters investigated, prevalence of AA-amyloidosis was 57.1% (16/28 cats), 73.0% (19/26) and 52.0% (13/25), respectively. In 72.9% of cats (35 in total) three organs were affected concurrently. Histopathology and immunofluorescence of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B = 0.026, CI95% = 0.007-0.046; p = 0.010). AA-amyloidosis was very frequent in shelter cats. Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease. In conclusion, AA-amyloidosis was very frequent in shelter cats and those staying longer had more deposits. The cat may represent a natural model of AA-amyloidosis.

Cryo-EM structure of ex vivo fibrils associated with extreme AA amyloidosis prevalence in a cat shelter.

AA amyloidosis is a systemic disease characterized by deposition of misfolded serum amyloid A protein (SAA) into cross-ß amyloid in multiple organs in humans and animals. AA amyloidosis occurs at high SAA serum levels during chronic inflammation. Prion-like transmission was reported as possible cause of extreme AA amyloidosis prevalence in captive animals, e.g. 70% in cheetah and 57-73% in domestic short hair (DSH) cats kept in zoos and shelters, respectively. Herein, we present the 3.3 Å cryo-EM structure of AA amyloid extracted post-mortem from the kidney of a DSH cat with renal failure, deceased in a shelter with extreme disease prevalence. The structure reveals a cross-ß architecture assembled from two 76-residue long proto-filaments. Despite >70% sequence homology to mouse and human SAA, the cat SAA variant adopts a distinct amyloid fold. Inclusion of an eight-residue insert unique to feline SAA contributes to increased amyloid stability. The presented feline AA amyloid structure is fully compatible with the 99% identical amino acid sequence of amyloid fragments of captive cheetah.

Treatment with Class A CpG Oligodeoxynucleotides in Cats with Naturally Occurring Feline Parvovirus Infection: A Prospective Study.

Feline parvovirus (FPV) causes severe gastroenteritis and leukopenia in cats; the outcome is poor. Information regarding specific treatments is lacking. Class A CpG oligodeoxynucleotides (CpG-A) are short single-stranded DNAs, stimulating type I interferon production. In cats, CpG-A induced an antiviral response in vivo and inhibited FPV replication in vitro. The aim was to prospectively investigate the effects of CpG-A on survival, clinical score, hematological findings, antiviral response (cytokines), viremia, and fecal shedding (real-time qPCR) in cats naturally infected with FPV. Forty-two FPV-infected cats were randomized to receive 100 µg/kg of CpG-A (n = 22) or placebo (n = 20) subcutaneously, on admission and after 48 h. Blood and fecal samples were collected on admission, after 1, 3, and 7 days. All 22 cats showed short duration pain during CpG-A injections. The survival rate, clinical score, leukocyte and erythrocyte counts, viremia, and fecal shedding at any time-point did not differ between cats treated with CpG-A (50%) and placebo (40%). Antiviral myxovirus resistance (Mx) gene transcription increased in both groups from day 1 to 3 (p = 0.005). Antibodies against FPV on admission were associated with survival in cats (p = 0.002). In conclusion, CpG-A treatment did not improve the outcome in cats with FPV infection. FPV infection produced an antiviral response.

Survival estimates and outcome predictors for shelter cats with feline panleukopenia virus infection.

OBJECTIVE To determine survival estimates and outcome predictors for shelter cats with feline panleukopenia virus (FPV) infection. DESIGN Retrospective cohort study. ANIMALS 177 shelter cats with FPV infection. PROCEDURES Medical records of cats treated for FPV infection from 2011 through 2013 were reviewed to collect information pertaining to signalment; history; results of physical examination, CBC, serum biochemical analysis, and blood gas analysis; and treatments (antimicrobials, antiparasitics, antivirals, antiemetics, analgesics, crystalloid or colloid solutions, and blood products). Survival time and outcome predictors were determined by means of Kaplan-Meier estimation, logistic regression, and mixed-model ANOVA. RESULTS Median survival time after hospital admission was 3 days; 20.3% (36/177) of cats survived to discharge from the hospital. Risk of nonsurvival was greater in cats with (vs without) signs of lethargy, rectal temperature < 37.9°C (I00.2°F), or low body weight at hospital admission. Lower (vs higher) leukocyte count on days 3,4, and 7 of hospitalization, but not at admission, was associated with nonsurvival. Amoxicillin-clavulanic acid, antiparasitics, and maropitant but not interferon-ω were associated with survival, whereas glucose infusion was associated with nonsurvival. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that FPV infection carried a poor prognosis for shelter cats. Several variables measured at admission or during hospitalization were associated with outcome. Remarkably and contrary to the existing literature, leukopenia at admission had no association with outcome, possibly owing to early prevention of complications.

Radiological investigation of an over 2000-year-old Egyptian mummy of a cat.

A radiographical study of a cat mummy from the Egyptian collection of the National Archeological Museum in Parma, Italy was carried out in order to evaluate the content and to describe how cats were wrapped and mummified. The mummy contained the complete skeleton of a 4-5-month-old cat. Radiology revealed the position of the cat's body; it was wrapped to occupy the smallest space possible. In order to better position the cat, the ribs of the thorax were compressed cranio-caudally and the fore limbs were then positioned very close to the thorax. The hind limbs were flexed close to the lumbar spine and the tibio-tarsal joints were subluxated to allow the repositioning of the tarsal, metatarsal and phalanx bones cranio-caudally near the tibiae. A coccygeal vertebra was fractured in order to reposition the tail as close as possible to the body. Atlanto-occipital subluxation and a fracture/hole was present in the occipital region of the skull: whether this was made for draining skull contents as a mummification process and/or to euthanase the cat remains open for discussion.