GI And Hepatic All Literature Flashcards
Objective - to prospectively evaluate kaolin activated TEG in dogs with acute liver disease (ALD) and compare with plasma based coagulation assays
21 dogs with acute liver disease diagnosed based on clinical presentation, minimum database, PT/PTT, and TEG. A subset also had fibrinogen, antithrombin, protein C, D diners, VWF measured. a PT >1.5 x prolonged defined acute liver failure.
Dogs with acute liver disease had increases in R, K, LY30, PT, PTT and vWF with DECREASES in alpha angle, MA, G, AT activity, and protein C activity.
**Overall - ~50% of dogs were hypocoagulable, 38% of dogs were normocoagulable, and 9% were hypercoagulable based on TEG
**38% of dogs had increases in LY30, indicating hyper fibrinolysis, and a majority of these dogs were also hypocoagulable
hypocoagulable and hyperfibrinolytic dogs had lower fibrinogen and protein C activities than dogs without these abnormalities
Acute liver failure dogs had greater increases in K (time to 20 mm clot formation) and LY30 (% of clot degraded 30 min after reacting MA or maximal clot strength), and decreases in MA, G (measure of clot strength/ firmness) and protein C activity than dogs with less severe hepatic impairment.
dogs with acute liver failure typically become hypocoagulable and hypofibrinolytic with progressive functional impairement.
**TEG was discordant from traditional coagulation testing 25% of the time
Objective - to characterize the observed incidence, timing and risk factors for azathioprine hepatotoxicosis in dogs treated clinically, and to determine the relationship between the development of hepatotoxicosis and cytopenias
**Hepatotoxicity (as defined by a >2 fold increase in serum ALT) was observed in 15% (5/34) dogs with a median onset of 14 days. Dogs had a median 9 fold ALT increase and 8 fold ALP increase, which stabilized or resolved after the drug was stopped or the dose was reduced. GSD were overrepresented
**Thrombocytopenia or neutropenia were seen in 8% of dogs, but occurred later in treatment (median onset 53 days into treatment)
What is the mechanism of action of azathioprine?
Purine analog, immunosuppressive
Is hepatotoxicity secondary to azathioprine idiosyncratic or dose dependent?
It’s BOTH - WOW!
Objective - to describe the distribution of histopathologic abnormalities between liver lobes.
Population - prospective study evaluating 70 dogs undergoing necropsy - liver samples were obtained from all lobes
***In the study population, biopsy of at least 2 liver lobes identified the predominant histologic abnormality in 99% of cases **
14% of dogs had = 3 lobes in agreement and could not be assigned a predominant diagnosis
The same diagnosis was present in 6/6 lobes in 57% of dogs , 5/6 lobes in 15% dogs, 4/6 loves in 15% of dogs, 3/6 lobes in 10% of dogs, and 2/6 lobes in 4% of dogs
****Biopsy of more than one lobe is important in obtaining representative samples
Objective - To investigate the effect of a low copper, high zinc diet on hepatic copper concentration in labs with increased hepatic copper concentrations
Populations - 28 clinically healthy labs with a mean hepatic copper concentration of 919 mg/kg dw that were related to dogs previously diagnosed with clinical copper associated hepatitis
Dogs were fed a low copper, high zinc diet, and hepatic copper concentrations were determined in liver biopsy samples approximately every 6 months
**54% of dogs responded - hepatic copper concentrations decreased a mean of 710 mg/kg dw copper to 343 mg/kg dw after a median of 7.1 months. Dogs that were more severely affected or that were from a severely affected pedigree were less likely to respond to copper restricted diet and zinc
**21% of dogs continued to accumulate copper despite diet
Objective - to compare histopathologic results of liver samples obtained by punch, cup, and 14 gauge needle to large wedge samples collected at necropsy.
Population - prospective study 70 dogs undergoing necropsy
***Mean number of portal triads observed by each sampling method were: 2.9 in needle samples, 3.4 in cup samples, 12 in punch samples, and 31 in necropsy samples (control).
**66% of needle samples, 60% of cup samples, and 69% of cup samples were in agreement with necropsy control samples. Indicates that histopathologic interpretation of a liver sample in dogs is unlikely to vary if biopsy specimens contains 3-12 portal triads. The accuracy of test methods was low compared to control. Getting multiple lobes is more important than sampling technique.
Objective - to examine the effects of PO administered ranitidine and omeprazole on intragastric pH in cats and to compare the efficacy of once daily vs twice daily dosage regimens for omeprazole
Randomized 4 way cross over design - cats were given enteric coated omeprazole granules q 24 or q 12, ranitidine (1.5-2.3 mg/kg q 12h) and placebo. Intragastric pH was monitored for 96 hours continuously.
**BID omeprazole administration raised intragastric pH >/= 3 and >/= 4 67% and 55% of the time respectively. All other treatments (ranitidine, SID omeprazole, placebo) did not raise intragastric pH for as long, but SID omeprazole raised pH ~15-20% of the time.
**BID omeprazole = best
Background - Serum N terminal pro-C-natriuretic peptide (NT-proCNP) - thought to be a potential diagnostic biomarker for sepsis
Objective - to evaluate the use of an ELISA for the measurement of NT-pro-CNP in canine abdominal fluid and to describe the peri operative pattern of abdominal fluid and serum NT-proCNP in dogs with septic peritonitis
Prospective pilot study of 5 dogs with non septic peritoneal effusion, 12 dogs with septic peritoneal effusion
**dogs with septic peritonitis had lower abdominal fluid NT-proCNP than concurrent serum concentrations, and lower than control canine abdominal fluid concentrations. Post-operatively, abdominal fluid NT-proCNP concentrations remained lower than serum, except on day 4. Low serum NT-proCNP cannot be explained by abdominal compartmentalization. Unknown diagnostic utility for sepsis
Objective - to determine feasibility of using contrast enhanced ultrasound to detect pancreatic and duodenal perfusion changes in naturally occurring canine pancreatitis
**Dogs with pancreatitis tended to have delayed time to peak hyperechoic enhancement with prolonged hyperechoic enhancement of the pancreas. Duodenal peak intensity was also increased.
Objective - to compare the effect of PO administered famotidine, fractionated omeprazole tablet, and omeprazole reformulated paste on intragastric pH in cats in a four way crossover design
**both omeprazole formulations administered BID were superior to famotidine in gastric acid suppression
**In healthy cats, gastric acid suppression (gastric pH >/= 3) was superior in fractionated enteric coated omeprazole (68%) and reformulated omeprazole paste (74%) compared to famotidine (43%) and placebo (16%)
- *Reformulated omeprazole paste was still effective in gastric acid suppression despite the disruption in enteric coating
- *Omeprazole levels by HPLC were similar between the two formulations
Objective - to compare the effect of IV coadministration of famotidine and pantoprazole to mono therapy with pantoprazole on intragastric pH in dogs.
Randomized 2 way crossover placebo controlled design
Dogs initially received saline for 24 hours, then 1 mg/kg pantoprazole q 12h for 3 days, then famotidine + pantoprazole for 3 days
**Results were comparable for combination treatment and stand alone treatment. Pantoprazole alone (MPT pH >3 79% MPT pH >4 68%) compared to dual therapy (MPT pH >3, 74%, MPT >4 64%)
**Note - human targets to treat gastroduodenal ulceration = Mean percentage time (MPT) pH > 3, 75% and MPT > 4, 67%
What is the mechanism of action of pantoprazole?
It is a proton pump inhibitor
PPIs become protonated and trapped in their active form in the acidic environment of parietal cells. After activation, PPIs form disulfide bonds with available active parietal cell H/K ATPase enzymes
After 24 hours of PPI treatment, how much gastric acid suppression typically occurs?
30% of maximum
When is the maximal inhibitor effect of PPIs though to plateau?
4 days
Prospective pilot case series of 10 dogs with pancreatitis
3 phase angiographic CT scan was performed under sedation, then dogs had US guided aspiration of the pnacreas performed and blood drawn for cPLI
**an enlarged homogeneously to heterogeneously attenuating and contrast enhancing pancreas with ill defined borders was seen on CT in all dogs. CT found more features characterizing pancreatic abnormalities compared to ultrasound (thrombi were found in 30% of dogs). The dogs with heterogeneous contrast (potentially indicative of necrosis) enhancement had an overall poorer outcome than those with homogeneous contrast enhancement.
Objective - to examine the relationship between serum 25 hydroxyvitamin D concentrations at diagnosis and clinical outcome in dogs with chronic enteropathy
**retrospective review
**serum concentrations of 25 hydroxyvitamin D at the time of chronic enteropathy diagnosis were significantly lower in non survivors (4.4 Ng/ml) compared to those that survived (25 Ng/ml)
36% of dogs did not survive
**Serum 25 hydroxyvitamin D concentration was a significant predictor of death in dogs with chronic enteropathy (OR 1.1).
Objective - to determine if there is an association between the histologic diagnosis of gall bladder mucocele in dogs and administration of selected drugs
Retrospective study app 81 dogs with a histologic diagnosis of GBM and 162 age, breed and admission date matched controls
- *Dogs with GBM were 2.2 x more likely to have been treated with levothyroxine (have hypothyroidism)
- *GBM dogs were 3.6 more likely to have reported treatment for Cushings disease
- *2.3 x more likely to have reported use of products containing imidocloprid
- *Analysis of Shetland sheepdogs only — Shetland sheep dogs with GBM were 9.3 x more likely to have used imidocloprid than control Shetland sheepdogs (28% of GBM cases of Shetland sheepdogs were associated with this drug
What breeds are potentially predisposed to gallbladder mucoceles?
Shetland sheepdog Cocker spaniel Pomeranians Miniature schnauzers Chihuahua
Background - administration of probiotics alleviate colitis in people. In vitro effects of the probiotic Enterococcus faecium NCIMB 10415 E1707 (EF) previously have been evaluated using canine cells
Hypothesis - Administration of EF to dogs with food responsive chronic enteropathy will improve clinical outcome and decrease the intestinal inflammatory profile
Dogs received a hydrolyzed elimination diet trial plus either a synbotic product containing EF or a placebo
**there was no difference between the EF group and the placebo group regarding clinical efficacy (CCECAI), histology scores or expression of any of the investigated genes (various inflammatory cytokines). Standard dietary treatment induced rapid clinical response in all cases. Underpowered study.
Objective - to evaluate the safety and diagnostic utility of percutaneous ultrasound guided cholecystocentesis in cats with suspected hepatobiliary disease
Retrospective study of 83 cats that underwent cholecystocentesis
- *Complications were in 17% of cases, mostly minor but included increased abdominal fluid (most common), then needle tip occlusion, failure to penetrate GB, pneumoperitoneum — most complications were associated with other procedures
- *NO reports of GB rupture, bile peritonitis, or hypotension necessitating emergent treatment
- *87% of cats survived to discharge, and those that died - there was no definitive association with cholcytocentesis
- *Bacteria was seen cytologically in 14% of samples and cultures were positive in 14% of samples, and cytology agreed to culture results < 50% of the time. The most common cytologic diagnosis was hepatic lipidosis, while the most common histopathologic diagnosis was cholangitis
- **useful diagnostic information was found in ~30% of cats
Objectives - to report the hematological parameters and coagulation times for cats with congenital PSS, and the influence of surgical shunt attenuation on these parameters; and second, to identify any association between prolongation in coagulation profiles and incidence of peri operative hemorrhage
Retrospective study of 42 cats that underwent surgical shunt attenuation
- *86% of cats had extrahepatic CPSS
- *14% of cats had intrahepatic CPSS
- **~75% cats were micro cystic pre operatively
- *postoperatively there was a significant increased in HCT, MCV, and MCH, but most patients were still microcytic postoperatively despite this increase.
- *Preoperative PT was high in 88% of cats and PTT was high in 69% of cats - no peri operative clinical bleeding was seen
Microcytosis was not associated with shunt type or ability to completely attenuate the shunt
Objective - to describe the extent of bleeding and the occurrence of complications after percutaneous ultrasound guided liver biopsy in cats
Bleeding post biopsy was classified as minor or major dependent on whether there was a less than 6% drop or greater than 6% drop in PCV
- **18G needle was used for biopsy
- *All cats had a drop in PCV after biopsy. The mean change in PCV was - 6.9% (to up to an 11% drop in PCV)
- *minor bleeding occurred in 43%, major bleeding occurred in 57% of cats, non lethal bleeding complications occurred in 17%. Neither the complication rate nor the presence of major bleeding were significantly associated with high morbidity/ mortality
- cats with complications had a lower pre biopsy PCV, and major bleeding was more likely when there was a diagnosis of hepatic lipidosis.
- *There was no correlation between change in PCV or complications and signalment, coagulation parameters, serum parameters, number of biopsies, ultrasound findings, radiologist experience, concurrent procedures and vitamin K administration
- *conventional coagulation tests did not predict complications or the magnitude of change in PCV
Objective - to assess serum lipoprotein profiles using rapid single spin continuous lipoprotein density profiling in healthy control cats and cats with hepatic lipidosis
23 hepatic lipidosis, 20 healthy controls
- *LDL content was significantly higher in cats with hepatic lipidosis than in healthy controls
- *HDL was LOWER in cats with hepatic lipidosis than healthy controls
- *there was no difference in triglyceride and cholesterol levels between groups
***The specific fraction (1.037-1.043 g/ml) within nominal LDL in serum distinguished healthy controls From cats with hepatic lipidosis with a sensitivity of 87% and 90% — in other words - amounts of lipid within the density = 1.037-1.043 g/ml fraction of serum distinguished healthy cats from cats with hepatic lipidosis at a cut off of 7.6%
Objective - to describe the ultrasonographic, endoscopic and histological characteristics of the cecum and ileocecocolic junction in cats suffering from chronic c/s compatible with cecocolic disease
61% of cats had ultrasound abnormalities adjacent to the ICJ (lymphadenopathy, steatitis)
72% of cats had abnormalities on ultrasound directly related to the junction (wall thickening, loss of wall layering)
**94% of cats had at least one abnormality
**Endoscopically, hypermedia, edema, discoloration, and/or erosions were found in all cats. Accentuation of the dimpled pattern (more accentuated) indicated less severe endoscopic lesions scoring
81% of cats had typhlitis, one had lymphoma, two were normal. All cats with typhlitis also had colitis.
There was only slight agreement between endoscopic and histologic cecal results regarding severity of lesions.
**loss of cecal wall layering (found in 38%) of cats - was not a reliable predictor of severity of inflammation or of malignancy. Neither did local steatitis or lymph node size
- **overall, ultrasonographic findings did not correlate with disease severity, nor did endoscopic findings. Chronicity of clinical signs appeared to correlate with disease severity, as well as the loss of the dimpled pattern in the cecum on endoscopic evaluation (potentially correlated with neoplasia).
- *most common histologic diagnosis was typhlitis
Objective - to report the ultrasonographic and clinicopathologic findings in cats with confirmed pyloroduodenal adenomatous polyps
**pyloroduodenal polyps appeared as small, moderately echogenic and homogeneous nodules filling most of the proximal duodenal lumen. Can be mistaken for ingesta
**most common presenting signs: vomiting and anorexia (67%), and lethargy (50%). 33% presented with anemia suggestive of active bleeding. One cat presented with EHBDO. 83% survived surgical resection
**prognosis - excellent with prolonged survival
Objective - to describe the clinical characteristics and frequency of malignant vs non-malignant causes of spontaneous GI perforation in cats
13 cats retrospectively reviewed - all had NON-surgical trauma, and no evidence of foreign body perforation
- *40% of cats had concurrent disease
- *gastric (46%) and duodenal perforations were most common. Histopathologic examination revealed ~50% had alimentary lymphoma (55%). The other half had LP IBD (45%), necrotic suppuration enteritis.
- *15% of cats had previously received NSAIDS
Objective - to assess the possible effects of sex, age, and breed on evolution of pancreatitis, and to understand if low values of serum iCa can be considered as a prognostic risk factor for determining clinical course of disease
- *On the day of diagnosis of pancreatitis, 58% were hypocalcemic, 33% were normocalcemic and 8% were hypercalcemic
- *at presentation, iCA was higher in non survivors than survivors
- on day of recovery or death, 75% were normocalcemic and 25% were hypocalcemic. The mean iCa in the fatal (died) group was 0.88, while for the non fatal group it was 1.1. There was no sex or age predisposition for disease development, but DSH were more prone to develop panc.
**hypocalcemia is common in patients with pancreatitis, and may be a poor prognostic indicator (if <1)
What are the potential mechanisms for hypocalcemia in acute pancreatitis?
- Hypoalbuminemia (negative acute phase)
- Acid base changes (acidosis may increase iCa by decreasing amount bound to albumin)
- Hijack of calcium salts in peripancreatic fat or local soft tissue
- Increase of FFA and calcitonin concentration
- Resistance to parathyroid hormone effects (which also can be related to secondary hypomagnesemia)
Objective - to assess the analytical sensitivity of fecal occult blood testing in cats
All cats were fed an animal protein free diet prior to study entry. Then cats were fed a bunch of blood of varying amounts.
- *melena was noted at 30 and 45 mg HGB/kg of blood administered
- *fecal occult blood was only detected a 1.5 mg/kg in one cat, 3 cats had 3 mg/kg detected. IT was detected in all cats with higher volumes of blood administered.
**administration of 15 mg/kg HGB (1.5 ml blood) was sufficient for positive results in call cats. Animals must be on an animal protein free diet and does not have a medication history that could result in false positive results before using this test.
What diets may result in false positive or false negative fecal occult blood testing?
Diets with animal protein
Diets with high peroxidase activity
Diets high in vitamin C
Objective - to evaluate ultrasonographic changes in the small intestine of cats with clinical signs of GI disease and low or low normal serum cobalamin concentrations
Small intestinal ultrasound changes were detected in 65% of cats. — abnormalities included thickening, loss of wall layer definition, echogenicity alterations and discrete masses. Serum cobalamin concentrations were low in a variety of cases included normal GI biopsies. Cobalamin was significantly lower in cases of lymphoma or IBD compared to other causes. No difference was found between cobalamin and presence of ultrasound abnormalities, specific ultrasound changes or albumin concentration
**35% of symptomatic cats with hypocobalaminemia or low normal cobalamin may have ultrasonographically normal SI. For the majority of cats (91%), histopathologic abnormalities were seen in the SI, regardless of ultrasound changes. GI disease should not be excluded on the basis of low normal cobalamin and a normal ultrasound
**The complication rate within 48 hours of ultrasound and/or aspirate procedure did not differ among pancreatic aspirate cats (11%) and control FNA (14% - something other than the pancreas was FNAd) and no FNA cats (8%).
- *There was no difference in rate of survival to discharge (82%, 84%, 83%) or length of hospital stay in all three groups
- *the cytologic recovery rate for pancreatic samples was 67%, and correlation with histopathology available in 7 cases was 86%
important
Objective - to retrospectively evaluate the effects of acid suppressant therapy in a population of cats with CKD. I.e. to evaluate the effects of acid suppressant therapy on clinicopathologic variables and progression of CKD over time.
**retrospective study evaluating cats that received 1) PPI, 2) histamine 2 RB, 3) combined acid suppressant therapy (PPI + H2RA), or 4 ) no acid suppressant therapy
** Both classes of acid suppressants are relatively well tolerated in cats with CKD and are not significantly associated with CKD progression. ** Significant increase in sodium was noted independent of stage of CKD in cats receiving PPI therapy. Decreased Mg was noted in two early stage CKD cats
Objective - to determine whether feline chronic gingivostomatitis is more prevalent in shared vs single cat households, whether the number of cohabitating cats or outdoor access represent risk factors for stomatitis, and whether the number of cohabitating cats is a useful prognostic indicator for standard surgical treatment
** cats with chronic gingivostomatitis were significantly more likely to come from shared households, and had significantly more total cats per house compared with controls.
** cats in shared households had significantly higher odds of chronic gingivostomatitis compared with those from single cat households. - suggests potential infectious etiology
**historical signs of URI and outdoor access were not associated with chronic gingivostomatitis. Number of cohabitating cats was not associated with surgical outcome.
Objective - to present clinical and laboratory data of 13 cats with Feline eosinophilic sclerosing fibroplasia
**disease most often seen in middle aged to older cats, male rag dolls being the most common. Cats had a prolonged history of vomiting and/or diarrhea. Lesions were typically large, hard, non painful, easily palpable (85%) and most commonly situated near the pylorus or ICJ. Lesions were heterogeneous ultrasonographically and on sectioning during abdominal explore or necropsy. Masses were hard and gritty on FNA. Bacteria were commonly detected within masses using either culture or conventional microscopy or FISH (62%). Consistent bacterial morphology was not seen among different cases.
** can be confused with lymphoma, granulomatous, or adenocarcinoma. Not all cats in this case series had a peripheral eosinophilia
**treatment - debunking, immunosuppressive therapy, anti-microbial agents. Outcome was poor due to delay in diagnosis and appropriate treatment. (62% mortality)
Background - multiple feline diseases involving the GI, pancreas, liver, and biliary tree can cause abnormal serum cobalamin and folate. Factors other than disease (e.g. age in particular) has also been suggested to have an effect on serum cobalamin and folate concentration.
Objective - To evaluate the effect of age, sex and body weight on the serum concentration of folate and cobalamin in cats fed the same diet.
**Serum cobalamin was associated with age (higher in younger cats), and males had higher concentrations than females. Serum folate increased with age. All cats were in a research colony and fed a consistent diet, indicating that there are underlying comorbidities placing older cats at risk for cobalamin deficiency.
Objective - to compare the rapid in house SNAP fPL with the standard test spec fPL and to evaluate the use of SNAP fPL to diagnose pancreatitis in an emergency setting
70% of cats tested below the cut off level for pancreatitis with SNAP and Spec cPL
19% tested above the cutoff level with both tests
10% of cats had discordant results
Comparison of both SNAP and spec fPL yielded 98% agreement when spec fPL was = 3.5 and 90% agreement when spec fPL was >/= 5.4
The SNAP fPL is a good rule out test for pancreatitis.
Objective - to assess the performance of preliminary clinical information (e.g. ultrasound) in predicting the histopathological reserve of abnormalities in alimentary tract organs in cats
Clinical signs were generally poor markers for the presence of lesions in the alimentary tract.
Liver enzyme elevation was specific for detecting histopathologic abnormalities of the liver (88-100%) but not sensitive (11-50%).
Pancreatic histopath abnormalities were present in 33% of cats with an abnormal fPLI, and 75% of cats with negative fPLI.
Ultrasonographic abnormalities were relatively specific for intestinal (57-100%) and liver (71-80%) histopath abnormalities, but ultrasound lacked sensitivity for both organs. Ultrasound was sensitive (50-80%) but not specific ( 17-22%) for detecting pancreatic lesions
**ultrasound and clinical signs are precise indicators of diseased organ. Normal ultrasound does not rule out histopathologic evidence of disease.
Background - microRNAs are potential biomarkers for hepatobiliary disease in humans and dogs
Objective - to measure serum concentrations of an established group of microRNAs in dogs and to investigate their concentrations in various types of hepatobiliary diseases.
**no different microRNA concentrations were found in the adenocarcinoma and congenital PSS groups. In other diseases:
**MiR-122 was highest in the mucocele group.
dogs with biliary diseases, miR-21 and miR-222 were only increased in dogs with mucoceles.
** uniquely increased micro-RNAs were found in hepatocellular carcinoma group (mi-R-200c) and the chronic hepatitis group (miR-126)
What are mature micro-RNAs? How might they make good biomarkers of disease?
Class of small noncoding RNAs that are important regulators of post-transcriptional gene expression. They play critical roles in the regulation of multiple aspects of liver development.
They are potential stable candidate biomarkers for various hepatobiliary diseases in people
There are both hepatocyte derived and cholangitis yet derived micro-RNAs
Objective - to investigate the frequency of enteritis, cholangitis, pancreatitis, or some combination of these in symptomatic and asymptomatic cats, compare clinicopathological features, and correlate histopathological with lab findings
**Inflammatory lesions were detected in all symptomatic and asymptomatic cats, but not in normal cats. Triaditis was identified in only symptomatic cats (30% of symptomatic cats).
- in symptomatic and asymptomatic cats, inflammation of >1 organ was seen in 57% of cats and always involved IBD.
- *There was no statistically significant difference in the severity of histopath lesions of either a single organ or a combination of several organs between symptomatic and asymptomatic cats.
- *histopathologic lesions of IBD were more severe in cats with triaditis than cats with IBD present alone, suggesting IBD may play a role in the development of pancreatitis
Objective - to characterize the clinical features of bacterial cholangitis/ cholecystitis in dogs
**typical b/w findings were LE elevation, hyperbilirubinemia and inflammatory leukogram — nonspecific
Ultrasound findings aided in decision making in the majority of cases
**The most frequent isolates on GB FNA were E. Coli (65%), Enterococcus (23%), and Clostridium (19%)
**antibiotic resistance was an important feature of aerobic isolates - 62% of E. Coli isolates were MDR
Biliary tract rupture complicated ~1/3rd of cases, associated with 50% mortality in those cases
Discharged dogs had a guarded prognosis
**bile culture yielded more positives than liver culture
Objective - to determine the course of biliary sludge in dogs
Prospective observational study of dogs with biliary sludge - dogs had serial ultrasound over the course of one year to monitor the degree of biliary sludge based on proportion of GB filled and gravity dependency of sludge
After one year of follow up, the degree of sludge was mild (34%), moderate (47%), moderate to severe (13%), and severe (3%) or absent (3%)
**In healthy asymptomatic dogs > 4 YO, there was a high prevalence (57%) of biliary sludge. There was no significant difference in the median degree of sludge over 1 year, and no significant changes in the gravity dependency of sludge over one year. A subset of dogs (24%) with initial gravity dependent sludge developed a combination of non dependent and dependent sludge. Most dogs had static sludge at the end of the study. All dogs were asymptomatic.
What factors promote the formation of biliary sludge?
Biliary status and modifications to bile within the GB, mucous hypersecretion
Hydrophobic BAS stimulate mucus secretion from the GB epithelium.
Objective - to investigate the use of ultrasound guided cholecystocentesis to collect bile samples from cats with known platynosomosis and to determine if bile analysis could be a diagnostic test.
Fecal and bile egg counts were performed, then euthanasia and necropsy exam as done in all cats (27 free roaming cats)
**All cats had ultrasound evidence of cholangitis/ cholecystitis. Postmortem exam showed no overt GB damage or leakage. **Median platynosomum spp egg counts were higher in bile (1450 eggs/ml) as compared to feces (46 eggs/ ml) - cholecystocentesis may have higher diagnostic yield than fecal
What is “lizard poisoning”?
Platynosomum spp infection - liver fluke acquired by eating lizards - disease causes chronic cholangitis in cats .
Fluke resides in the gallbladder and biliary ducts of the infected cat creating inflammation within bile ducts and portal areas.
Disease prevalence is high in tropical regions (e.g. Carribbean)
C/s - nonspecific - chronic mucoid diarrhea and icterus in chronic disease, acutely may see inappetence and lethargy
Typically abdominal pain, icterus, and hepatomegaly occur between the 7th-16th week post infection but these signs may be transient. Non specific clinical signs can recur once disease becomes chronic as the adult flukes persist for extended period of time
Objective - to retrospectively evaluate whether oral cobalamin supplementation can restore normocobalaminemia in dogs with chronic enteropathy and hypocobalaminemia.
**all 51 dogs with various signs of chronic enteropathy and hypocoablaminemia became normocobalaminemic with oral cobalamin supplementation. The mean increase in serum cobalamin after treatment was 794 Ng/ml. Oral cobalamin raised from mean of 223 to 1017 post oral supplementation.
**unknown if oral supplementation results in normalized cellular cobalamin status
Background - intestinal leiomyositis is a suspected autoimmune disorder affecting the muscularis propria layer of the GI tract and is a cause of chronic intestinal pseudo-obstruction in humans and animals
Objective - to characterize the clinical presentation, histopathologic features, and outcome of dogs with leiomyositis in an effort to optimize treatment and prognosis.
- *In a retrospective case series of dogs with intestinal leiomyositis, the median age of disease onset was 5.4 YO. Clinical signs included vomiting, regurgitation, and small bowel diarrhea. The median duration of c/s prior to presentation was 13 days (wide range). Diagnostic imaging showed marked gastric distension with dilated SI in 66% of dogs
- histopath (full thickness biopsies) - mononuclear inflammation, myofiber degeneration, and necrosis and fibrosis centered within the region of myofiber loss in the intestinal muscularis.
**all dogs received various combinations of immunomodulatory and prokinetic treatment, antimicrobial agents, antiemetics, and IV fluids - NO dogs showed clinically relevant improvement with treatment. MST - 19 days post diagnosis. Grave prognosis (risk of aspiration pneumonia, progressive weight loss)
How is chronic intestinal pseudo-obstruction histologically classified?
Refers to intestinal leiomyositis in veterinary medicine
Histo classifications: myopathies, mesenchymopathic, and neuropathic
BAckground - fecal calprotectin and IgA are markers of intestinal inflammation and immunity in adult dogs
Objective - to evaluate whether fecal calprotectin and IgA concentrations in puppies are influenced by fecal moisture or enteropathogen shedding.
Prospective study of 324 puppies
- *higher concentrations of IgA and calprotectin were found in dried feces
- *calprotectin concentration was influenced by age (higher concentrations in younger puppies), but not by viral or parasitic infection.
- *Fecal IgA concentration was influenced by enteropathogen shedding, with lower fecal IgA in puppies shedding >/= 1 enteropathogen compared to puppies without any enteropathogen shedding. It was not influenced by age. It was not useful in diagnosing infection
**Fecal calprotectin and IgA were of no diagnostic value in detecting presence of enteropathogen
In a prospective pathologist blinded study comparing single use and reusable alligator standard cup biopsy forceps with 5 randomized reusable forceps, sample quality of GI biopsies was assessed by a single pathologist.
**There was no difference in adequacy, depth, villi number, or crush artifact in the 4 intestinal areas between forceps type with 10-15 uses of reusable forceps. Re-usable forceps obtain equivalent quality biopsies with 10-15 repeat uses, making them an economically viable option.
Objective - to determine whether a drug interaction exists when sucralfate is administered to fed dogs concurrently with ciprofloxacin or enrofloxacin, and whether a 2 hour delay between fluoroquinolone and sucralfate affects fluoroquinolone absorption.
Prospective randomized crossover study of 50 healthy greyhounds.
- *the mean relative oral bioavailability for ciprofloxacin and concurrent sucralfate was 48% compared to ciprofloxacin alone. Bioavailability was improved to 87% when there was a 2 hour delay prior to sucralfate administration.
- *Relative bioavailability for enrofloxacin and concurrent sucralfate was 104% (no significant difference between enro + sucralfate and enro alone)
Objective - to determine the diagnostic utility of cytological assessments of bile aspirates
Retrospective study of 56 dogs and 78 cats with bile collected by cholecystocentesis
- *infectious agents were found in 30% of dog bile aspirates and 22% of cat bile aspirates. Inflammation was found in 5% of dog bile and 19% of cat bile.
- *presence of microorganisms was more commonly seen on cytology (24%) than by culture (21%).
- most common bacterial isolates were E. Coli and Enterococcus isolated from 15% and 7% of all cultures
Objective - to evaluate complications associated with PEG tube use in dogs and cats on steroids
Retrospective study of 42 animals - some on steroids, some not
**The prevalence of complications was similar between groups. In the steroid group, 43% developed complications classified as severe (purulent discharge around stoma, tube dislodgement, tube chewed at stoma) in comparison to the no steroid group (18%)
Objective - to compare the results of the spec fPL and the DGGR assays with standardized histologic assessment of the pancreas in 60 cats that presented for necropsy
- *sensitivity and specific of fPL with a cutoff of >/= 5.4 was 42% and 100%
- *sensitivity of DGGR assay (cutoff >26 U/L) was 36.8% and 100%.
- When up to 10% lymphocytic inflammation was considered normal, PLI sensitivity was 61%, specificity 69% with the same cutoff
- DGGR sensitivity was 67% and specificity was 79%
- *both assays performed similarly, but had poor sensitivity, and did not correlate well with histopathology
- *histopathology of the pancreas at necropsy showed high rates of nodular fibrosis (95%) and lymphocytic inflammation (93%)
Objective - prospective study evaluating 23 dogs and cats presenting with GI signs, and comparing 3 methods of handling endoscopically obtained GI biopsies specimens from collection to lab processing, and to determine if any technique produced superior results.
Techniques: 1) mounted on cucumber slice, 2) mounted on a moisturized synthetic foam sponge, 3) floating free in formalin
**specimens mounted on a cucumber slice and on sponge were significantly wider. Specimens on a sponge had significantly fewer artifacts compared to those on cucumber slice and those floating free in formalin. Confidence in the diagnosis was also superior with sponge technique of free floating specimens.
Objectives - to retrospectively evaluate the clinical utility of diagnostic laboratory tests in dogs with acute pancreatitis in a primary care hospital
—Retrospective case control study of 64 dogs with c/s suggesting acute pancreatitis diagnosed with non pancreatic disease or acute pancreatitis
- *Activities of amylase and FUJI Dri CHEM lipase and cPLI were higher in the acute pancreatitis group than in the nonpancreatic disease group.
- *Sensitivity of FDP lip for diagnosing acute pancreatitis was 100% and specificity was ~90%.
- *higher ALT was associated with extended duration of hospitalization
- *significant difference in CRP concentration before and 5 days after hospitalization was found - might be useful in monitoring clinical recovery from panc. FUJI DRI CHEM did not decrease significantly 5 days post hospitalization
Retrospective evaluation of 7 cats with Neutrophilic IBD and 8 cats with Lymphoplasmacytic IBD (control)
Duodenal biopsy specimens were reviewed, and FISH targeting either all eubacteria or individual Campylobacter spp. was performed on archived samples. Neutrophils were detected on the same samples using a FISH probe for neutrophil elastase
**Campylobacter coli was present in 6/7 (85%) of cats with Neutrophilic IBD and 12% of cats with LP IBD. Cats with Neutrophilic IBD had significantly higher counts of C. Coli in mucosa than cats with LP IBD. Colocalization of neutrophils and C. Coli was demonstrated, with C. Coli closer to the neutrophils than any other bacteria.
**C. Coli may be a stimulus for feline Neutrophilic IBD
Objective - to investigate BHOB concentrations in dogs with acute pancreatitis
prospective clinical study of 154 client owned dogs without DM enrolled in 1) acute pancreatitis group, 2) sick without acute pancreatitis diagnosis, 3) fasted group
**Median BOHB concentrations were significantly higher in dogs with acute pancreatitis (diagnosed based on vomiting, anorexia, and either ultrasound or cPLI [SNAP or quant]) - (0.3 mmol/L in panc dogs, 0.2 in sick dogs, 0.1 fasted dogs)
Median BOHB was significantly higher in sick dogs w/o acute panc compared to fasted dogs
** the magnitude of increase is not clinically significant and would not confound a diagnosis of DKA
IMPORTANT
Background - chronic PPI administration has been associated with electrolyte and cobalamin deficiency, disrupted bone homeostasis, hyper gastrin Emma, and rebound acid hypersecretion in people.
Objectives - prolonged oral omeprazole results in altered bone mineral density or content, serum calcium, magnesium, cobalamin and gastrin concentrations in healthy cats.
6 healthy cats received placebo followed by omeprazole for 60 days.
** No significant difference in serum Ca, Mg, cobalamin, and bone density was found between placebo and omeprazole admin. Serum gastrin was significantly higher during omeprazole treatment compared to placebo. Gastric hyperacidity (rebound acid hypersecretion) was seen with intragastric pH monitoring after stopping omeprazole. Otherwise omeprazole was safe in these patients and relatively well tolerated
BAckground - Purflubutane micro bubbles - ultrasound contrast agent that is phagocytized by Kupffer cells
Objective - to determine whether the washout ratio in the hepatic vein (HV) measured by contrast enhanced ultrasound can distinguish between inflammatory and noninflammatory liver disease in dogs
**PRospective study of 41 dogs with hepatic disease (various underlying etiologies). 6 dogs enrolled as healthy controls
Washout ratio = attenuation rate from peak intensity to the intensity at the end of the contrast ultrasound study (2 minutes). If Kupffer cell function is normal, the wash out ratio will be high (closer to 100%)
Washout ratio in the hepatitis group was lower (18%) than the portal vein hypoplasia group (52%), CPSS group (60%), other hepatopathy group(70%), and normal dogs (78%).
****Washout ratio of = 37% resulted in a 100% sensitivity and 85% specificity for prediction of hepatitis. A low washout ratio could potentially distinguish hepatitis from other non-inflammatory disorders. Result might reflect impaired Kupffer cell phagocytosis in dogs with hepatitis.
Objective - to evaluate TEG results and associations with conentional coagulation results and indicators of disease severity and prognosis in dogs with chronic hepatopathies
**Dogs with chronic hepatopathy had significant increases in R (time to initiation of fibrin clot), K (time to achieve 20 mm clot), and LY30 (% of clot degraded 30 min after strongest clot has formed), and decreased angles.
42% were normocoagulable
33% were hypercoagulable
23% were hypocoagulable
Clinical score (more severe disease= higher PT) correlated with PT, MA, and R.
** 24% had hyper fibrinolysis
***Dogs with portal hypertension/ end stage disease were hypocoagulable. - decreased fibrinogen, PT/PTT prolonged
High fibrinogen correlated with higher G value (hypercoagulable).
Objective - to determine the sensitivity and specificity of ALT, ALP and BA for detecting primary hepatitis in clinically healthy labs and investigate whether ALT and ALP can discriminate between dogs with primary hepatitis and dogs with nonspecific reactive hepatitis
Retrospective study of 191 clinically healthy and 51 clinically ill labs with hepatic histopathology
64% of clinically healthy labs had inflammatory infiltrates on hepatic histopathology
Sensitivity of ALT, ALP, and BA in clinically healthy population for detecting acute hepatitis was 45, 15, 15% respectively. Specificity was >90% for acute hepatitis for all. For chronic hepatitis, sensitivity was 71,35,13% respectively, and specificity was >90%. For reactive hepatitis, specificity was > 90%
***Median ALT elevation was higher in primary hepatitis cases compared to reactive hepatitis cases. There was no difference between ALP in dogs with primary hepatitis over dogs with reactive hepatitis. ALT, ALP and BA had poor sensitivity (best for chronic hepatitis) and relatively good specificity in identification of acute hepatitis, chronic hepatitis, or reactive hepatitis. ALT had the best sensitivity (71%) in identification of chronic hepatitis and acute hepatopathy (45%). Copper levels were not associated with ALT, ALP, bile acids
Background - grading schemes for the assessment of hepatic fibrosis and necroinflammatory activity in humans previously have been applied to dogs with chronic hepatitis.
Objective - To assess interobserver agreement associated with pathologists using a previously published histological scoring scheme to assess hepatic fibrosis and necroinflmmatory activity in dogs and to compare fibrosis scores assigned to serial sections stained with H+ E and picrosirius red.
Prospective study of histological sections of liver from 50 dogs.
**There was fair interobserver agreement when 6 different pathologists assessed fibrosis (kappa = 0.36) and poor agreement when they assessed necroinflammatory activity (kappa = 0.16) using the scoring scheme in this study.
What is kappa statistic?
Used to estimate interobserver agreement for data
K of 0 represents no agreement
K of 1 represents complete agreement
Background - the portal vein diameter increases in humans with portal hypertension. There is no evidence of portal vein enlargement in dogs with portal hypertension
Objective - to measure portal vein to aorta ratio in dogs with portal hypertension (secondary to chronic hepatitis or portal vein hypoplasia), dogs with extrahepatic PSS, and in healthy dogs and to evaluate relationship between portal vein to aorta ratio and splenic pulp pressure.
Retrospective study - portal vein/ aorta ratio was calculated with CT images, and splenic pulp pressure was measured at the time of liver biopsy (25 dogs with acquired portosystemic collaterals, 32 dogs with extrahepatic PSS, and 20 healthy dogs
** In dogs with acquired PSS collaterals, portal vein to aorta ratio determined by CT was lowest in dogs with primary hypoplasia of the portal vein (0.4), and extrahepatic PSS (0.3), compared to healthy dogs (1) and dogs with chronic hepatitis (1.4). When all dogs were considered, portal vein to aorta ratio positively correlated with splenic pulp pressure
Background - endothelin 1 is an amino acid with potent vasoactive properties, which increases intrahepatic resistance in patients with chronic hepatitis or cirrhosis.
Objectives - to compare hepatic and plasma endothelin 1 levels in healthy dogs and dogs with chronic hepatitis. To examine the relationship between plasma endothelin 1 level and portal vein pressure in dogs with chronic hepatitis
Prospective case control study of 14 healthy dogs and 20 dogs with chronic hepatitis
**Hepatic endothelin 1 mRNA levels were 3.7 x higher in dogs with chronic hepatitis than in healthy dogs. The median hepatic (hepatic mRNA expression, hepatic endothelin 1 measured by ELISA) and plasma endothelin 1 levels were significantly higher in dogs with chronic hepatitis (13.2 pg/mg liver, 0.99 mg/dL plasma) vs healthy dogs (3.42 liver, 0.71 plasma). There was a weak correlation between plasma endothelin 1 and splenic pulp pressure (marker of PH) in dogs with chronic hepatitis. Endothelin 1 may play a role in the pathogenesis of portal hypertension secondary to chronic hepatitis.
What is the physiological function of endothelin 1?
Functions mediated by two endothelin receptors: ETA and ETB
Endothelin 1 is produced and released from sinusoidal endothelial cells and exerts paracrine effects on ETA receptors in vascular smooth muscle and hepatic Stellate cells, thus inducing vasoconstriction.
ET1 also exerts autocrine, intracrine, or both effects on sinusoidal endothelial cells via induction of ETB receptor mediated release of vascular relaxing factors such as NO and prostacyclin
These receptors regulate vascular tone
ET1 is increased in plasma and liver tissue in patients with Chronic hepatitis or cirrhosis, and this increase is proportional to disease severity in people
Background - serum IL6, chemokine ligand 2 (CCL2), CRP and the ratio of AST to ALT have been correlated with fibrosis and necroinflammatory activity in people with various hepatopathies
Objective - to determine whether increases in serum IL6, CCL2, CRP or AST:ALT were associated with moderate to severe fibrosis or necroinflammatory activity in dogs with various hepatopathies.
Prospective study of 44 client owned dogs with liver disease and 10 healthy dogs, all undergoing liver biopsy
- *Median IL6 was 2x as high in dogs with high fibrosis scores (15.5) compared to dogs with low fibrosis scores (7.6) with marginal significance.
- *Median CCL2 was significantly higher in dog with active necroinflammation (444 pg/ml) compared to dogs without detectable necroinflammation (326), but with considerable overlap between groups.
- *Neither serum CRP or AST:ALT ratios were different based on fibrosis or necroinflammatory score.
- **None of the markers used had significant diagnostic utility based on significant overlap between groups. May be useful in monitoring disease progression.
Objective - to determine the value of gallbladder ultrasound in predicting bile bacterial culture results, identify most common bacterial isolates from bile, and describe complications after cholecystocentesis in dogs and cats with suspected hepatobiliary disease
**Abnormal GB ultrasound had a high sensitivity (96%) and low specificity (49%) in cats with positive and negative bile bacterial culture results (negative predictive value 96%).
**a normal ultrasound in cats had high NPV (96%)
**thickened GB wall or GB sludge was statistically associated with higher odds of positive bile culture in cats, but there was a high false negative rate (still had negative cultures with abnormal ultrasound)
**GB ultrasound had a lower sensitivity (81%) , specificity (31%), positive predictive value (20%) and NPV (88%) in dogs.
The most common isolates were of enteric origin, and prevalence of infection was higher in cats. Complication rate was low (3.4%)
Background - immune system involvement is suggested as an underlying cause for Doberman hepatitis based on female predisposition, lymphocyte infiltration, abnormal hepatocyte expression of MHC II antigens, and homozygosity for DLA DRB1*00601
Objective - to measure serum ANA and serum anti-histone antibodies in Dobermans with hepatitis. To determine whether increased serum ANA or serum anti histone antibodies could be used to support diagnosis of Doberman hepatitis.
***In ELISA (IgG ELISA), increased concentrations of AHA were found in 92% of dogs in the sub clinical stage of hepatitis and 85% of dogs in the clinical stage compared with none of the control dogs.
Anti-histone antibodies indicate autoimmune activity, so this could be a novel screening tool for Dobermans for increased ALT
Background - increased delivery of taurine conjugated bile acids to the distal bowel can lead to dysbiosis resulting in colitis in mouse models of IBD. Cats conjugate bile acids solely with taurine and these conjugated bile acids are absorbed from the terminal ileum. Clinically relevant ideal disease may impair the absorption of taurine conjugated bile acids resulting in decreased whole body taurine concentrations.
Objective - to determine whether whole blood taurine concentrations are decreased at the time of diagnosis in cats with IBD and to correlate concentrations with clinical and lab variables
**Whole blood taurine remained within RI. Cats with predominant large bowel signs had significantly lower concentrations than did cats with small bowel and mixed bowel clinical signs. This difference remained significant when assessed only in cats with chronic inflammatory enteropathy.
Why is taurine an essential amino acid in cats?
They lack the metabolic pathways to synthesize it from the precursors methionine and cysteine
Which amino acid is the sole amino acid in cats used to conjugate bile acids? Where are they absorbed?
Taurine, absorbed in the terminal ileum
Objective - to assess correlation between scintigraphic and ultrasonographic measurements of gastric emptying time in healthy cats. Variability of ultrasonographic gastric emptying time and correlation between scintigraphy and ultrasonographic parameters and gastric motility were evaluated.
Prospective study - scintigraphic gastric emptying time was determined, and each cat had 3 separate ultrasonographic assessments of gastric emptying after test meal consumption. The motility index of natural contractions was plotted against time and time for each fraction of the area under the motility index curve was determined. Ultrasonographic gastric emptying time and motility index were correlated to scintigraphic gastric emptying time.
**There was good correlation between scintigraphic and ultrasonographic gastric emptying time. There was moderate inter-individual variability.
What is the historic gold standard technique for assessment of gastric emptying time?
Scintigraphy
BAckground - perinuclear anti-neutrophil cytoplasmic antibodies (pANCA) previously have been shown to be serum markers in dogs with chronic enteropathies, with dogs with food responsive disease having higher frequencies of seropositivity than dogs with steroid responsive disease. The indirect immunmofluorescence assay previously used is time consuming with low interobserver agreement
**anti-neutrophil cytoplasmic antibodies (ANCA) are antibodies directed against neutrophil granule components.
Objective - To determine whether a commercially available granulomatous IIF assay for humans could be used to detect perinuclear anti Neutrophilic cytoplasmic antibodies in dogs.
Prospective study of 44 dogs with food responsive disease and 20 dogs with steroid responsive disease, 20 control dogs, 38 wheaten or cross bred wheaten
- *The sensitivity of granulocyte indirect immunofluescence assay (commercially available human assay) to predict food responsive disease in dogs was 61% and specificity was 100%.
- *There was substantial agreement (k= 0.77) between the two assays (commercial assay and previously published method) to detect ANCA in the same serum samples from wheaten with PLE/PLN
OBjective - to develop a protocol with custom kennels designed to allow free feeding of 3 optimized formulations of contrast media and diets that address limitations of current video fluoroscopic swallow study protocols.
Prospective study of healthy juvenile, adult and geriatric dogs. Custom kennels were developed to maintain natural feeding behaviors and three food consistencies (thin, puréed food, and dry kibble) were formulated with either iohexol or barium.
**The development of the standardized protocol resulted in successful collection of swallow data in healthy dogs. There were no significant differences in small metrics among age groups. Swallow metrics were affected by food consistency. There was significant variability in healthy dogs when evaluated under physiologic conditions. Features typically attributed to pathological states (such as GERD), were seen in healthy dogs.
Objective - to evaluate the short and long term outcomes and analyze risk factors for death in dogs with esophageal foreign body obstruction.
Retrospective study of 222 dogs with esophageal foreign bodies
- *Foreign material was most commonly Osseous (81%) and the most common site of obstruction was the distal esophagus (49%)
- *Duration of c/s was not associated with risk of death. 92% of dogs had successful scope retrieval, but 6% required surgery
- *there was a 5% in hospital fatality rate, and risk of death was significantly higher with surgery (odds ratio 20.1), esophageal perforation (odds ratio 66), and postprocedure esophageal hemorrhage (odds 12) increased in hospital death risk.
- *Esophageal strictures were reported in 2% of survivors.
IMPORTANT
Background - prolonged famotidine use in people results in decreased efficacy
Objective - to compare the effect of repeated oral administration of famotidine or placebo on intragastric pH and serum gastrin in 6 healthy adult colony beagle dogs.
Design - randomized 2 factor repeated measures crossover design. Intragastric pH monitoring was done at the beginning and the end of the treatment period (day 12-13). Mean pH and mean percentage time (MPT) that intragastric pH was >/= 3 or >/= 4 were compared between and within groups. Serum gastrin was measured at the beginning and end of the treatment period.
- **Continued administration of famotidine resulted in a significant decrease in mean pH, MPT>3, and MPT >4 on day 12 and day 13. Mean decrease in pH was 1.6 on days 12 and 13. A mean decrease of MPT >3 and MPT >4 by 33 and 45% were seen for the same time period.
- *In healthy dogs given famotidine, gastrin levels increased compared to baseline on day 3
Background - elevated homocysteine (possibly due to reduced GFR or abnormal homocysteine metabolism in the liver) and decreased folate concentrations are seen in humans with hypothyroidism and can influence the development of numerous secondary disorders
Objective - to assess total homocysteine concentrations in serum and to examine its relationship with the concentration of folate and thyroid hormones (TT4 and fT4)
Prospective study of 10 healthy and 19 hypothyroid dogs
**Hypothyroid dogs had increased homocysteine two fold (22) and decreased folate (21) compared to healthy dogs (11.5 homocysteine and 31 folate). In sick dogs, total homocysteine was inversely correlated with folic acid, TT4, and fT4
What is homocysteine?
Endogenous amino acid containing sulfur that is created as a result of systemic conversion of methionine
Most homocysteine is remethylated to methionine or transsulfurated to cysteine. Folate lowers toxic homocysteine levels
Elevated homocysteine is a sensitive marker in people as a risk factor for clotting, cardiovascular and neurodegenerative disorders as well as folic acid deficiency.
Objective - to determine whether synbiotic co-administration mitigates antibiotic associated GI signs in healthy research cats treated with clindamycin.
**Cats that received the synbiotic one hour after clinddamycin were more likely to complete the treatment period, and cats vomited less frequently while receiving the synbiotic but this was not significant. Cats had higher food intake while receiving the synbiotic. There was no significant effect of treatment on fecal scores, which significantly increased over time (i.e. it did not reduce the risk of antibiotic associated diarrhea). The clinical benefits of the synbiotic may persistent for at least 6 weeks after discontinuation
What is a synbiotic?
Mixture of prebiotic and probiotic (e.g. Proviable)
Objective - to determine whether pre-anesthetic orally administered omeprazole increases gastric and esophageal pH and increases serum gastrin concentration in anesthetized cats, and to determine the prevalence of gastro-esophageal reflux.
**Mean gastric pH in cats that received ompeprazole was higher than placebo (7.2 vs 2.8). Omeprazole administration was not significantly associated with a significant increase in serum gastrin concentration. 33% of cats had >/= 1 episode of reflux during anesthesia (similar prevalence to dogs). Odds of placebo group having at least 1 reflux event was 2.75 x higher than odds of reflux in the omeprazole group - this finding was not statistically significant. Omeprazole was administered 24 hours and 4 hours prior to induction.
BAckground - esomeprazole is an s-enantiomer of omeprazole that has favorable pharmacokinetics and efficacious acid suppressant properties in people.
Objective - to determine the pharmacokinetics of esomeprazole administered via various routes (pK study) and to investigate the effect of esomeprazole on intragastric pH (PD study)
In the PK study, dogs received IV, SQ, or oral doses of esomeprazole at a dose of 1 mg/kg and esomeprazole plasma concentrations were measured. Intragastric pH was recorded without medication (baseline) and following IV, SQ or PO dosing.
- *bioavailability of oral enteric coated esomeprazole was 71%, bioavailability of SQ injection was 106%. Half life was one hour.
- *MPT pH >3 was 59 %, and MPT pH >4 was 41% in the IV injection group.
- *MPT pH > 3 76%, MPT >4 63% in the SQ group, and MPT >3 88% MPT >4 83% in the PO group.
- *all MPTs were significantly increased compared to baseline regardless of route of administration. No adverse effects were seen.
Objective - to evaluate the differences in the expression of leptin and leptin receptor between dogs with and without gall bladder mucocele
**Serum leptin concentrations were higher in dogs with gall bladder mucocele than healthy dogs. Patients with mucoceles that had surgery had higher leptin than those that did not. There was no difference in leptin in the GBM group in dogs that did or did not have endocrinopathies. **The mRNA expression levels of leptin and its receptor were increased in the gall bladder tissues of dogs with gallbladder mucoceles, suggesting that dysregulation of leptin might be involved in the pathophysiologic of GBM.
What role does leptin play in regards to the gallbladder?
Either directly or indirectly regulates physiological mechanisms of the GB, including modulation of GB motility through effects on neurotransmitters, secretion and resorption of water and electrolytes by upregulation or down regulation of gall bladder genes related to water, chloride, sodium and bicarbonate transport.
Leptin dysreguation can result in a change in bile components within the gallbladder and causes diseases of the GB such as cholelithiasis.
Objectives: 1) to compare the peripheral blood lymphocytes by flow cytomertry in IBD dogs and healthy controls and 2) to compare the peripheral blood lymphocytes in IBD dogs at the time of diagnosis and in dogs in clinical remission.
**IBD patients peripheral blood lymphocytes had decreased percentages of TCRgammadelta + T lymphocytes and CD21+ B cells compared to healthy controls. There were no significant differences in peripheral blood lymphocytes in pretreatment and follow up samples.
In a previous study using FLOW cytometry to characterize canine intestinal intraepithelial lymphocytes, which intraepithelial lymphocytes were reported to be increased in number?
TCR gamma delta + T cells
Increased CD3+ T cells, plasma cells, B cells have also been documented
Objective - to compare histopathologic findings in dogs with biopsy diagnosed inflammatory chronic enteropathy with and without hypoalbuminemia.
- *Dogs in the chronic enteropathy with hypoalbuminemia group were more likely to have villous stunting, epithelial injury, crypt distension, and lacteal dilatATION and were more likely to have intraepithelial lymphocytes and lamina propria neutrophils than dogs that were not hypoalbuminemic. Dogs with hypoalbuminemia had more severe histopathologic changes overall based on WSAVA scoring.
- *There was no difference in Lymphoplasmacytic inflammation
BAckground: 3-Br-Y is a by product of hypobromous acid, and is generated during a reaction catalyzed by eosinophil peroxidase that occurs after activation of Eosinophils in the tissues. This has been studied as a biomarker in humans and dogs with eosinophilic related disease. There are increased 3-Br-Y concentrations in dogs with Lymphoplasmacytic enteritis and eosinophilic gastroenteritis
Objectives: 1. To evaluate a possible association of peripheral eosinophilia in dogs with food responsive disease, steroid responsive disease, and controls. 2. To determine the correlation between serum 3-Br-Y concentrations and peripheral eosinophil counts. 3) to compare serum 3-BrY concentrations between dogs with food responsive, steroid responsive diseases and healthy controls. 4) to determine the relationship between canine chronic enteropathy clinical activity index and serum 3-BrY concentrations
** There was no association of peripheral eosinophilia in dogs with food responsive or steroid responsive disease and healthy controls. There was no correlation between peripheral eosinophil counts and serum 3-BrY concentrations. **Serum 3-BrY concentrations in dogs with steroid responsive disease were significantly higher than in dogs with food responsive disease or in healthy dogs. ***Serum 3-BrY concentrations in dogs with food responsive disease were higher than in healthy dogs (SRD—> FRD—> healthy). There was no significant correlation between CCECAI and serum 3-BrY concentrations.
What is CCECAI?
Canine chronic enteropathy activity index - used to investigate prognostic outcome in dogs with chronic enteropathy. It is a combination of 9 variables including the dog’s attitude, appetite, vomiting, fecal consistency, fecal frequency, weight loss, albumin, ascites, and peripheral edema and priorities.
A high CCECAI is a negative prognostic indicator.
**CCECAI scores were not correlated with histopathologic score in one study
IMPORTANT
Objective - to determine if cats with CKD have decreased gastric pH compared to age matched healthy cats.
Prospective study of 10 CKD cats and 9 healthy controls
** no significant differences in serum gastrin concentrations were seen between groups OR any pH parameters including mean gastric pH. — cats with CKD may not have gastric hyperacidity compared to healthy cats and therefore may not need acid suppression. The majority of the cats were IRIS STage II CKD - no differences in mean gastric pH was found between IRIS stages (number of late stage CKD patients was lower - 50% IRIS STage II, 40% stage III, 10% stage IV)
What gastric changes are most commonly observed in cats with CKD? What does this mean for the potential need for gastric acid suppression?
Gastric mineralization, gastric gland atrophy, and hypergastrinemia. NOT ulcerative or erosive gastropathy
Potentially indicates that gastric acid suppression may not be needed.
OBJECTIVE - to determine whether supplementing dogs entering an animal shelter with a synbiotic would decrease the incidence of diarrhea.
773 dogs entering an animal shelter in the uK - prospective double blind randomized placebo controlled trial
Dogs given the synbiotic had a lower mean percentage of days of diarrhea, lower incidence of diarrhea within the first 14 days of their stay, and decreased the occurrence of two or more consecutive days of diarrhea compared to placebo.
Objective - to evaluate the effect of cobalamin supplementation on clinical signs, serum and urine methylmalonic acid concentrations over 16 weeks.
Prospective study of 21 hypocobalaminemic cats with chronic enteropathy receiving injectable cobalamin
FCEAI was graded at each time point
**clinical disease activity sore decreased during supplementation and increased after treatment discontinuation
Median serum cobalamin increased significantly from pre to post supplementation. They decreased after supplementation was discontinued with time (worsening was documented 4 and 10 weeks post last injection). Serum MMA decreased then increased after supplementation was discontinued. The same pattern was seen for urine MMA concentration. By the end of the 6 week treatment course, serum cobalamin was normal 95% of cats, serum MMA was normal in 40%, and urine MMA was normal in 70%
Why is cobalamin an important cofactor in cellular metabolism?
It is needed as a cofactor for the conversion of methylmalonyl CoA to succinylcholine CoA via methylamlonylCoA mutate and for re-methylation of homocysteine via methionine synthase
In humans, cobalamin deficiency causes increases in MMA and total homocysteine concentrations
MMA is a preferred marker when monitoring responses to cobalamin supplementation
In a study of 10 dogs of various breeds at risk for GDV that underwent lap gastropexy and had post operative gastric motility assessed, no complications associated with surgery of the motility capsule administration were noted.
There were no significant differences in gastric emptying time, small/large bowel transit time, and whole gut transit time before and after laparoscopic assessed gastropexy.
Objectives. - 1) to predict iCa concentrations from biochemical results and compare the diagnostic performance of predicted iCa to those of total calcium concentration and 2 corrected formulas. 2) to study the relationship between biochemical results and variation of measured iCa concentration.
**total calcium, albumin, and chloride had the highest impact on measured iCa variation. Measured iCa concentration was better correlated with predicted iCa than with total calcium and corrected total calcium, and had higher overall diagnostic accuracy to diagnose hypercalcemia and hypocalcemia (but not significantly for hypercalcemia).
- *For hypercalcemia, piCa sensitivity was 64% and specificity was 99.6% (more sensitive and specific than TCA or corrected TCA) (PPV 90%, NPV 98%)
- *For hypocalcemia, piCa sensitivity was 22% and specificity was 98.4% (PPV 71%, NPV 89%)
- *predicted iCa was more useful than total calcium. Nothing is better than measured iCa
Objective - to investigate whether gingivostomatitis occurs concurrently with esophagitis, if chronic gingivostomatitis treatment contributes to esophagitis, and if esophagitis exacerbates signs of chronic gingivostomatitis.
Prospective study of 58 cats with chronic gingivostomatitis and 12 healthy controls with no signs of oral disease
**the majority of cats (98%) with c/s of gingivostomatitis also had some degree of esophagitis, especially in the proximal and distal parts, (distal more common) compared to healthy controls. No cats had GI signs or signs of esophageal disease, and the salivary and esophageal lumen pH was not different between stomatitis cats and controls.
Objective - to evaluate the underlying causes and predictors of outcome in dogs with chronic diarrhea
Retrospective study of 136 dogs with chronic diarrhea >/= 3 weeks duration
**90% of dogs were diagnosed with a primary enteropathy: IBD (71% - with the majority being diet responsive), infectious (13%), neoplasticism (4%), mechanical disease or vasculitis (rare causes)
**The other 10% of dogs had secondary causes - EPI (6%), endocrine (2%), one dog each had hepatic, renal, cardiac disease.
**87% of dogs had clinical remission, 13% died or did not respond to treatment.
Lack of recovery was correlated with dogs with primary inflammatory/idiopathic or neoplastic diseases and was associated with increased disease severity score (weight loss, poor appetite), anemia, severe hypoalbuminemia, and severe hypocobalaminemia.
**moderate to severe vomiting was associated with extragastrointestinal disease
BAckground - scintigraphy is a sensitive tool in people to confirm PLE and allows for localization of protein loss
In dogs with PLE, focal small intestinal and diffuse SI radiopharmaceutical exudation into the bowel was noted in 2 AND 3 dogs. In 2 dogs, there was disagreement about whether radiopharmaceutical exudation was focal or diffuse. Only 1 control dog had exudation of radiopharmaceutical into the GI tract.
**99mTc labeled human serum albumin scintigraphy is feasible
Objective - to evaluate the relationship between disease severity and serum and fecal biomarkers in dogs with idiopathic IBD before and after treatment.
Prospective case control study of 16 dogs with idiopathic IBD and 13 healthy dogs
Canine IBD activity index clinical score (CIBDAI), serum concentrations of CRP, perinuclear cytoplasmic antibodies (pANCA), and serum, and fecal canine calprotectin were measured before and after 21 days of treatment
Serum CRP, fecal canine calprotectin and CIBDAI scores were significantly increased in dogs with IBD before treatment compared with serum CRP, fecal canine calprotectin, and CIBDAI after treatment.
***There were no significant associations between CIBDAI scores and before or after treatment serum biomarkers. There was a significant association between fecal cCP and CIBDAI scores before treatment. CRP and fecal cCP significantly decreased after treatment.
***In dogs with idiopathic IBD receiving non-standardize treatment for 3 weeks, CIBDAI, CRP and fecal canine calprotectin (but no serum calprotectin or pANCA) improved. Fecal calprotectin was associated with CIBDAI scores before treatment- biomarker for severe disease.
Objective - to evaluate standardized cobalamin supplementation scheme in beagles with selected intestinal cobalamin malabsorption (Imerslund-grasbeck syndrome). To determine if a single parenteral dose of 1 mg of hydroxycobalamin would maintain clinical and metabolic remission for up to 2 months.
**median urinary MMA concentrations did not differ between dogs with selective cobalamin malabsorption receiving monthly or bimonthly injections. A maintenance dose of 1 mg IM monthly or bimonthly is adequate.
**selective cobalamin malabsorption = CUBN mutation - abnormal cubulin protein resulting in cobalamin malbsorption)
OBJECTIVE - to investigate the use of an in dwelling balloon dilatATION esophagostomy tube (BE-Tube) for treatment of benign esophageal strictures in dogs and cats.
Initial balloon dilation was performed followed by B tube placement. Owners performed twice daily at home inflations for approximately 6 weeks. Repeat endoscopy was performed before B tube removal.
- *Btube management was relatively well tolerated and effective in maintaining dilation of the esophageal stricture while in place. The majority of animals (92%) had a significantly improved modified dysphagia score by the end of treatment.
- *Major complication rate (requiring tube replacement) was 17%
- *Minor complications (regurgitation, site infection ) was 58%
- *A majority (66%) of tubes needed to cross the LES, however this did not increase the frequency of regurgitation or vomiting.
What is the current standard of care for management of esophageal strictures? On average, how many treatments do patients require and what is to percentage of positive outcomes?
Esophageal balloon dilation
Average 2.5-4.5 treatments
Positive outcome in 70-88%
Objective - to determine the level of agreement among each of the 4 assays and a clinical suspicion score, level of agreement among the assays, and sensitivity/specificity of each assay in a clinically relevant patient group.
Prospective study of 50 client owned dogs with clinical signs of GI disease
**The sensitivities of the assays ranged from 74% - 100% The specificities: SNAP cPL 72-78% Spec cPL 74-81% Vets can cPL rapid 77-84% Precision pSL 64-74%
- good to excellent agreement was seen among the four assays (0.6-0.68). Sensitivity of Vetscan was 74-83% and specificity of Vetscan was 77-84%.
- *level of agreement between individual diagnostic tests for pancreatitis and the clinical suspicion score was good. No single test had high enough diagnostic specific to conclusively diagnose pancreatitis based on single test.
Background - sialocele is a collection of saliva that has leaked from a damaged salivary gland or duct and is surrounded by granulation tissue. Surgery is the first line treatment. Recurrence rate after surgery is 5-14%. Salivary gland tissue is sensitive to RT.
Objective - to characterize response rate and clinical course of dogs with sialocele treated with RT and to determine a starting dose for clinical use.
In a retrospective study of 11 dogs with sialocele that underwent RT, all dogs had a cervical sialocele. All dogs received varying fractions of 4 Gy (from 12 up to 20 Gy).
54% achieved a complete response.
45% achieved a partial response.
27% had progression of their sialocele 2, 3, 9 months after RT (all three had received 12 Gy initially) and 2 received 2 additional fractions of 4 Gy (cumulative 20 Gy dose), and subsequently achieved remission for >2 years.
**RT doses in fractions of 4Gy with a cumulative doses of 16 - 20 Gy appear effective
Objective - to develop a canine ex vivo model of stress related mucosal disease and to determine the effect of sucralfate on mucosal barrier function in this model
Sucralfate was applied to ex vivo canine gastric mucosa (harvested from healthy euthanized dogs) before and after acid injury. Barrier function was assessed by measurement of trans epithelial electrical resistance and radio labeled mannitol flux.
Sucralfate application to acid injury gastric mucosa at the time of injury or after injury significantly hastened recovery of barrier function.
Background - mucosal imbalance of IL1 beta and IL1 receptor antagonist (Ra) has been reported in the duodenal mucosa of dogs with IBD. The ratio of IL1 beta and IL 1 receptor antagonist may affect the expression of occludin (tight junction component)
Objective - to measure the expression of IL1 beta and IL1 receptor antagonist proteins in the colonic mucosal of dogs with IBD, and to determine the effect of IL1 beta on the expression of occludin (ocln) mRNA, a tight junction component, in the duodenal and colonic mucosa of dogs with IBD
*** The ratio of IL1 beta to IL1 receptor antagonist in the colonic mucosa was higher in dogs with IBD than healthy dogs.
IL 1 beta suppressed expression of ocln mRNA in the colonic mucosa, but not the duodenal mucosa of healthy dogs. **Expression of the ocln mRNA in the colonic mucosa, but not in the duodenal mucosa was significantly lower in dog with IBD than healthy dogs.
What role does IL1 beta play in inflammatory bowel disease?
It is a pro inflammatory cytokine that plays an important role in initiation and amplification of inflammation in various tissues including the intestine.
The IL1 receptor antagonist (Ra) is an endogenous antagonist of IL1a and IL1beta and binds to the IL1 receptor 1 - it inhibits biologically activity of IL1 alpha and Berta.
Significant increases in the IL1beta: IL1 receptor antagonist ratio have been reported in intestinal mucosa of the smal and large bowel in human patients with Crohn’s disease, and in the duodenal mucosa of dogs with IBD.
An increased IL1 beta to IL1 Ra ratio may be involved in the pathogenesis of IBD in people and dogs.
Objective - to evaluate changes in the fecal micro iota in dogs with food responsive chronic enteropathy and in healthy control dogs before and after an elimination diet trial with an animal protein free diet.
Dogs with food responsive IBD and healthy controls were fed an animal protein free diet for 60 days. Fecal microbiota was analyzed by 16s rRNA sequencing and quantitative PCR.
**A lower bacterial alpha diversity was seen in FR enteropathy dogs at baseline compared to healthy controls. Alpha diversity increased in FRE dogs after diet trial. Microbial communities were still different in food responsive enteropathy dogs after the trial compared with control dogs at baseline. In healthy control dogs, the fecal microbiota did not show a significant modification after administration of animal protein free diet.
**feeding an animal protein free diet to dogs with food responsive enteropathy led to partial recovery of the fecal microbiota by significantly increasing microbiota richness, which was significantly closer to healthy microbiota after treatment. No changes were noted in healthy controls.
Background - serum citrulline is a useful biomarker in human intestinal disease and indicates globally reduced enterocytes mass and absorptive function in various disease states.
Objective - to determine whether serum citrulline concentration is a biomarker in chronic enteropathy in healthy dogs. To provide useful information regarding optimal treatment or to predict outcome.
Retrospective study of dogs with chronic enteropathy and age matched controls with no GI disease
**serum citrulline concentration did not differ between dogs with chronic enteropathy and controls. Serum citrulline concentration was also similar between dogs with FRE and antibiotic responsive diarrhea. It did not correlate to CIBDAI or to serum albumin concentrations. Citrulline is not helpful in diagnostic investigation and management of dogs with chronic enteropathy.
Background - intestinal absorption of bile acids is mediated by the apical sodium dependent bile acid transporter. Fecal bile acid dysmetabolism has been reported in dogs with chronic enteropathy and is suspected to be due to decrease in this transporter protein.
Objective - characterization of apical sodium dependent bile acid transporter distribution along the intestinal tract of control dogs and comparison to dogs with chronic enteropathy
Study of 24 IBD dogs and 11 control dogs
- ASBT expression was higher in ileum, colon, and cecum in control dogs
- *Dogs with chronic inflammatory enteropathy had decreased expression of apical sodium dependent bile acid transporter protein in the ileum, and this was negatively correlated with histopathological score. Dogs with chronic enteropathy had a significantly increased percentage of primary bile acids in feces compared to controls. The fecal dysbiosis index was significantly higher in chronic enteropathy dogs than control dogs.
Background - calprotectin is a marker of inflammation.
PRospective case control study evaluating fecal calprotectin in dogs with chronic enteropathy confirmed by biopsy.
**fecal calprotectin correlated with CCECAI and fecal S100A12, some inflammatory criteria, and some inflammation scores but not CRP. Dogs with steroid responsive enteropathy had higher fecal calprotectin concentrations than dogs with food/antibiotic responsive disease, and dogs in the steroid responsive group with more severe disease (partial or non-responders) had higher fecal calprotectin than dogs with complete response. Nothing reached statistical significance.
- *A fecal calprotectin >/= 15.2 mcg/g separated responders from non-responders with 80% sensitivity and 75% specificity
- *CCECAI and CRP as a single variable out-performed calprotectin. Using CRP, CCECAI and calprotectin together increased ability to differentiate steroid responsive from food/ antibiotic responsive disease.
What do canine calprotectin, S100A8/A9 protein complex, and S100A12 have in common?
They are calcium binding proteins of the S100/calgranulin family that have been shown to be associated with acute and chronic inflammation and with malignant transformation. These proteins. Are involved in the regulation of cell proliferation and metastasis, and after their extracellular release function as endogenous danger signaling molecules (alarming)
In Canine chronic inflammatory enteropathy, the expression of mucosal S100 mRNA was shown to be increased 11 fold. Fecal calprotectin an S100A12 have been shown to be correlated with clinical disease activity. S100A12 has been shown to be correlated with severity of endoscopic lesions and response to treatment
Objective - to develop a more sensitive method for identifying and quantifying both intact and degranulated eosinophils to diagnose eosinophilic GI disease more accurately. These changes do not show up as easily on H and E staining.
**IHC with eosinophil peroxidase monoclonal antibody labeled duodenal sections resulted in better detection of intact eosinophils than with H and E sections. Similar findings were noted in the stomach and colon. Eosinophil peroxidase monoclonal antibody labeled tissues allowed for assessment of eosinophil degranulation. There were more intact and degranulated eosinophils in the eosinophilic and LP/ mixed GI disease than in the control group.
Background - certain amino acids are decreased in people with IBD and supplementation with the same AA has shown beneficial effects in animal models of IBD
Objective - to determine if serum AA concentrations are abnormal in dogs with PLE and correlated with clinical and lab variables and outcome.
Retrospective study of dogs with PLE and 12 apparently healthy dogs
**serum tryptophan was significantly decreased in PLE dogs compared to healthy controls. There were no significant differences in the other 29 serum amino acids measured between PLE dogs and apparently healthy dogs.
Retrospective study with the objective of describing a large cohort of cats with pancreatitis requiring hospitalization
- *78% of cats survived to discharge. Median time from onset to presentation was longer in non survivors. Causes of pancreatitis included: recent GA, trauma, hemodynamic compromise and organophosphate intoxication. 87% of cases were idiopathic.
- *ultrasonographic findings consistent with pancreatitis were noted in 87% of cats, including an enlarged pancreas (81%), hyper or hypoechoic pancreas, EHBDO, and increased peripancreatic echogenicity.
- *lethargy, pleural effusion, hypoglycemia, ionized hypocalcemia, azotemia, parenteral nutrition administration, and persistent anorexia during hospitalization were more common in non survivors.
- *antibiotics were more frequently given to survivors.
- *none of the variables were statistically significant.
Background - hepatic circulatory disturbances have been associated with obesity and fatty liver in humans.
Objective - to investigate the influence of BCS on liver hemodynamic indices
Prospective observational study of dogs of varying breeds and BCS. Mean portal velocity, portal blood flow volume, portal congestion index, hepatic artery resistivity index, and hepatic vein spectral wave were obtained
**Obese dogs had a lower mean portal velocity, higher percentage of abnormal hepatic vein spectral wave and higher median ALP than did ideal dogs. Overweight and obese dogs had lower portal blood flow volume than ideal dogs. Overweight dogs had higher median GGT. There was no difference in pulsed congestion index, hepatic arterial resistivity index, and median ALT among groups.
**obese dogs had altered portal vein indices (lower mean portal flow velocity) and hepatic vein spectral wave (abnormal), and these were associated with LE elevation (increased ALP and GGT, not ALT)
MicroRNA-122 (miR-122) is a sensitive and specific biomarker of liver injury in humans and rodents.
Objective - to establish the reference interval for miR-122 in healthy dogs and determine performance in a range of dog breeds with liver disease and control animals with non-liver disease
Retrospective study of dogs with non-liver disease, healthy dogs, and dogs with histologically confirmed liver disease.
**There were no difference in miR-122 concentrations between healthy dogs and dogs with non-liver disease. MiR-122 was higher in dogs with liver disease. It identified dogs with liver disease with high accuracy (ROC AUC 0.93). The upper limit of normal for healthy dogs (3312 copies/microL) had a sensitivity of 77% and a specificity of 97% for identifying liver disease
Background - liver disease prolongs Mirtazapine half life in humans
Objective - to determine pharmacokinetics of orally administered mirtazapine in vivo and in vitro in cats with liver disease and healthy cats
**Time to reach maximum serum concentration was longer in liver disease cats than control cats. The calculated half life of liver disease cats was longer compared to controls. Mirtazapine half life was correlated with ALT and T. Bile. Delayed metabolism of Mirtazapine by hepatic microsomes in liver disease cats was also documented.
Background - p21, a cell cycle inhibitor and marker of cellular senescence, is upregulated in human liver disease and is a better prognostic marker than histological or clinical scoring systems.
Objective - to quantify hepatocyte p21 immunopositivity in histopathology samples from dogs with chronic hepatitis and determine its association with outcome.
**hepatocyte P21 immunopositivity in dogs with chronic hepatitis was high and exceeded 70% in 88% of cases with no association with age. p21 immunopositivity was low in control dogs and was positively correlated with age. Dogs with p21 immunopositivity > 92% had shorter survival compared to dogs with <89 % immunopositivity. Increasing hepatocyte p21 immunopositivity was negatively associated with survival time.
Objective - to investigate hepatic copper concentrations in dogs and explore temporal, demographic and histologic associations spanning 34 years.
**Median copper concentration was higher over time in both predisposed and nonpredisposed breeds. The proportion of hepatic copper concentration > 300 mcg/g increased in both of these groups during these time periods — 49% in non-predisposed breeds and 71% in predisposed breeds. Median hepatic copper concentration in dogs with hepatitis increased 3 fold over time in both predisposed and non-predisposed breeds.
Objective - to build a model with plasma albumin concentration and mRNA expression levels of hepatic gene products as predictors of recovery from PSS after surgery
prediction model was constructed using 2 case control studies of recovered and non recovered dogs after shunt attenuation
Study 1 - 43 genes were differently expressed in recovered and nonrecovered dogs. Mean pre-op albumin in recovered dogs was higher compared to non-recovered dogs. **the best fitting prediction model in the 2nd study included pre-operative plasma albumin concentration and intraoperative DHDH, ERLEC1, LYSMD1 gene expression (hepatic mRNA expression selected from genome) levels.
**Model operated at 77% sensitivity and 90% specificity
Objective - to investigate cases of gall bladder mucocele and identify variables associated with survival and the sensitivity and specificity of ultrasound to identify GB rupture
- *dogs with GBM and GB rupture with bile peritonitis at the time of surgery were 2.7 x more likely to die than dogs without GB rupture and bile peritonitis.
- *No significant associations were found between survival and positive bile culture, antibiotics, or time (days) from ultrasonographic ID of GBM to time of surgery.
- *minority of cases (14%) were culture positive, but many received abx prior to sx
- *For ultrasound ID of GB rupture: sensitivity 56%, specificity 92%, positive likelihood ratio 6.74, negative likelihood ratio 0.44 (I.e. poor sensitivity for ID of GB rupture)
Objective - to describe the history, c/s, diagnosis, treatment, and outcomes of dogs with gall bladder agenesis.
- *Chihuahuas were most common
- *Median age at presentation was 1.9 YO.
- *common c/s included vomiting (36%), anorexia (12%), ascites (12%), diarrhea (5%), lethargy (5%), and seizures (5%). CBD dilation without obstruction was seen in 70% of dogs identified via CT cholangiography (GB agenesis seen in 73% of cases and vestigial GB seen in 23% of cases). 82% had malformed liver lobes grossly. 36% had acquired portosystemic collaterals. Ductal plate malformation was confirmed histologically in 94% of dogs.
Objective - to determine risk factors, clinical features, and response to treatment of GBM in Border Terriers.
- *odds of identification of GBM in a border terrier was 85 X that of other breeds in the study population. Border terriers had similar clinical signs and clinical path changes to other breeds with GBM. There was no evidence that endocrinopathies were associated with GBM in border terriers.
- *Other potentially predisposed breed - Affenpinscher
- *there were significantly more portal triads (21 vs 14) and a higher surface area (20 mm2 vs 11.5) in the 5 mm cup samples compared to the 3 mm cup samples.
- *Kappa coefficients and percentage agreement for histologic diagnosis as compared to wedge biopsy were not different between the two instrument sizes.
**3mm and 5mm cup biopsy forceps yield similar diagnostic accuracy in collection of liver biopsies.
Most common clinical signs of dogs with cholangitis/ cholangiohepatitis: vomiting (72%), lethargy (70%), and inappetence (65%).
Most dogs had (98%) had LE elevation, hyperbilirubinemia (64%), and hypercholesterolemia (56%)
Ultrasonographic abnormalities were seen in 84% of cases
On histopathology, 98% had Neutrophilic cholangitis or cholangiohepatitis, while 1 dog had lymphocytic cholangitis. Most cases (77%) were chronic. Evidence of concurrent biliary disease and biliary obstruction were common (~45%).
47% of bile cultures and 44% of liver tissue culture were positive, with E. Coli and enterococcus being most common.
Median survival was 671 days (1.8 years). Dogs that did not have a cholecystectomy performed had a 2.1 x greater hazard for death compared to dogs that did. Older dogs had a 5 x greater hazard for death than younger dogs.
