Lit GIT, Hepatobiliary, Pancreatic Flashcards
(2 papers)
How useful was video capsule endoscopy (VES) in identifying GI bleeding (GIB) in dogs with microcytosis as compared to traditional endoscopy?
What were the complications & associated risk factors with use of VES to diagnose GIB in dogs?
Mabry JVIM 2019
Capsules were able to identify gastric mucosal lesions in 15/16 & SI lesions in 12/14 dogs, who had biochemical evidence of GI bleeding. However, most would have been identified by traditional endoscopy. Authors suggest use for cases post-negative endoscopy & inconclusive abdo imaging.
Stiller JVIM 2021
Most common complication - incomplete study.
Risk factors - PO admin (vs endoscopically admin capsules) - poor visualisation in stomach & colon, good in SI; simethicone or opioids, chronic enteropathy, capsule gastric transit time >6 hrs.
Overall VCE may be useful to ID bleeding GIT lesions in dogs with questionable GIB.
What was the utility of BUN/creatinine ratio (UCR) in differentiating GI bleeding (occult vs overt) from healthy dogs?
Stiller JVIM 2021
UCR overall not clinically useful marker of occult GIB - sig higher in overt GIB, but no sig diff between occult GIB & healthy dogs. Also no sig diff between upper vs lower GIB.
If normal [Hb] and Hct, much higher chance of being healthy vs occult GIB.
If encounter increased UCR in a dog w/o overt GIB, esp if Hct within middle-upper RI, GI protectants not indicated.
- What do the scoring systems MCAI and CAPCSI represent when used to assess hospitalised dogs with acute pancreatitis (AP)? What variables do these systems assess?
- Were these 2 scoring systems useful in differentiating survivors from non-survivors to discharge?
- Which 2 serum parameters were assessed as potential biomarkers for clinical progression in hosp dogs with AP, and were there any correlations identified with either of the above scoring systems?
Keany JVIM 2021
- MCAI = modified canine activity index (MCAI). Based on CIBDAI. Assesses 7 variables – activity, appetite, cranial abdo pain, V+, faecal consistency, dehydration, blood in faeces.
CAPCSI = canine acute pancreatitis clinical severity index. Assesses 4 variables: cardiac – any abnormal rate or rhythm), respiratory (presence of ARDs or pneumonia, dyspnea/tachypnea), intestinal integrity (GI signs, appetite, intestinal sounds on auscultation), vascular forces (SBP, alb < or >18g/dL). - MCAI - yes, CAPCSI - no (no sig diff)
- CRP & cPLI. Both were positively correlated with MCAI.
In cats that underwent choledochal stenting for the treatment of extrahepatic biliary obstruction (EHBO), EHBO recurrence was …. And occurred in …… cats, with …..being a major risk factor for recurrence. ……% cats survived to discharge, with …..positively associated with survival to discharge. Overall median survival time was…..days.
Griffin JVIM 2021
Common, 38.9% (40%), cholelithiasis, 78.3%, absence of peritoneal effusion, 931 days.
What is a normal CD: CBD ratio for cats? (CD = cystic duct)
What was the utility of measuring pancreatic enzyme activity in bile, in differentiating cats with normal vs abnormal (increased) CD/CBD ratios?
Fujimoto JVIM 2021
3.4
Cats with CD/CBD ratio >3.4 had significantly higher amylase activity in the bile vs cats with ratio <3.4.
*NB study population enrolled healthy cats, not sure if data applies to cats with cholangitis.
What does the G value represent on TEG?
What proportion of dogs with chronic enteropathy were hypercoagulable as measured by TEG?
G value of CE dogs negatively correlated with ……. (list 3 variables), and positively correlated with …. (list 1 variable).
G values were not significantly different between normo- & hypoalbuminemic dogs. (T/F)
Dixon JVIM 2021
G value = global measure of clot strength. Increased when hypercoagulable.
44.7%
Hct, serum albumin concentration & duration of CSx
Age
True
In dogs treated with meloxicam 0.2mg/kg PO SID x15d, what were the changes in hematologic, gastroscopic analysis results & serum gastrin concentrations at 3 timepoints (T5, T10, T15)?
How did gastroscopy and serum gastrin correlate with gastric ulceration (GU)?
Elfadadny JVIM 2021
- Decreased Hb, RBCC, PCV at T10 & T15.
- Increased serum gastrin, image analysis results (integrated density/ID, ulcer index/UI) over time
- Sig decrease in PI (pixel intensity) over time.
Gastroscopy = gold standard for early descriptive diagnosis of GU.
Serum gastrin = a good predictor of gastroscopic score of ulcers, increased concentration = good indicator for presence of GU.
What are the most common sonographic findings in cats with EPI? (List 4)
- Most common = minimal-no sonographic pancreatic changes (39% cats).
- Thin pancreatic parenchyma (27%)
- Pancreatic duct dilatation >2.5mm and/or tortuosity (27%)
- Diffuse SI dilatation with echogenic contents (36%)
Measurement of plasma lidocaine/ monoethylglycylxylidide concentration in dogs with liver shunts to assess shunt closure
a) Differences in [ ] between dogs with complete vs partial shunt closure
b) Sensitivity & specificity?
Devriendt JVIM 2021
a) Median [MEGX] was higher in dogs with closed EHPSS cf diagnosis, but not different in dogs with persistent shunting.
96.2% sens & 82.8% specificity.
Lidocaine is a commonly used analgesic drug in small animals, which is metabolized in the liver by cytochrome P450 to monoethylglycylxylidide (MEGX) and subsequently to glycylxylidide (GX).15 In human medicine, the hepatic metabolism of lidocaine is used as a dynamic liver function test.16-19 As MEGX accurately reflects the severity of hepatic dysfunction, it is not only a valuable test for quantitative evaluation of the liver dysfunction but it is also used as a prognostic predictor of liver diseases in adults.
1) Apart from ammonia, what other substances may contribute to the development of hepatic encephalopathy?
2) Changes in BCAA-to-AAA ratio in PSS dogs receiving medical tx, and correlation with neurological function?
Devriendt JVIM 2021
1) Increased [ ] of glutamine, glutamate, manganese; systemic inflammation. Decreased r branched-chain amino acids (BCAA): aromatic
amino acids (AAA) ratio can induce derangements in central NTR function –> trigger HE.
2) BCAA-to-AAA ratio remained low after starting medical tx, despite concurrent marked improvement in neuro score.
Ratio increased 3months post-sx, still indicates moderate-severe hepatic dysfunction.
What is the optimal cut-off CCECAI score for predicting diet responsiveness in PLE dogs?
Nagata JVIM 2020
CCECAI score sig lower in FR-PLE dogs.
Cut-off CCECAI of 8 had 88.9% Sp & 82.6% Sn.
Also longer survival, better prognosis in FR-PLE dogs.
Plasma renin activity (PRA) was significantly higher in ….. dogs, but was not significantly different in dogs with …… compared to congenital EHPSS & healthy dogs.
Plasma aldosterone was significantly ….. in the above 2 groups of dogs compared to cEHPSS & healthy dogs.
Study findings suggest that ……plays a role in the pathophysiology of portal hypertension in dogs.
Sakamoto JVIM 2020
Chronic hepatitis (CH)
Primary hypoplasia of the portal vein [PHPV]
Higher
RAAS activation
Describe:
1) Mechanisms by which Cu & Pb cause hepatic injury
2) Mechanisms for hepatic Cu accumulation (List 3)
Gori JVIM 2021
1)
- Defective hepatic metabolism
- Oxidative stress to hepatocytes (esp Pb)
- High intracellular Cu: oxidative damage –> hepatocellular necrosis & inflammation
2)
- Primary metabolic defects in hepatic Cu metabolism
- Cholestasis causing impaired biliary excretion of Cu
- Excess daily Cu intake
What were the correlations between a) hepatic [Cu] and hepatic [Pb], and b) hepatic [Cu] and/or [Pb] and bloodwork parameters in dogs with chronic hepatitis?
Gori JVIM 2021
Dogs with abnormal hepatic [Cu] may also have higher hepatic [Pb].
In dogs with high hepatic [Pb], microcytosis may be present.
What is the current recommended antibiotic class to treat dogs with E coli-associated GC?
What was the incidence of resistance to this antibiotic in GC dogs in a 2020 study? Which 3 regions of E coli was resistance mainly associated with?
What was the long-term outcome following treatment of GC dogs with MDR E coli isolates? Which alternative antibiotics were used in these cases?
Manchester JVIM 2020
Fluoroquinolones
62.5% (15/24 dogs) – common!
GyrA and parC mutations; plasmid-mediated resistance (less common)
Good long-term outcome (sustained complete clinical response for median of 59 months) in FQ-resistant dogs when treated with abx guided by susceptibility testing (carbapenems – meropenem or doxycycline).
When using spec FPL to diagnose pancreatitis in sick cats, the false positive rate was ……% as compared to a false negative rate of ……%.
(T/F) Selected biochemistry tests (ALT, ALKP, ALB, tCa, TBIL) were useful as adjunctive results to corroborate a diagnosis of pancreatitis.
Lee JVIM 2020
10%, 24%
False
What was the mortality rate in dogs with naturally occurring acute pancreatitis (AP)?
Select 2 parameters below which were associated with non-surviving dogs with AP, and if these were increased/decreased.
- Serum [α2AP]
- Serum [α1PI]
- Anti-thrombin activity
- Canine acute pancreatitis severity (CAPS) score
- Inflammatory cytokine [ ] (IL-6, TNF-a)
Kuzi JVIM 2020
19% mortality rate.
CAPS score - higher scores.
Anti-thrombin activity - decreased.
(Serum [α2AP] & [α1PI] not useful)
(IL-6 & TNF-a positively correlated with cPLI & CRP)
(3 papers)
a) What are the 4 different forms of B12?
b) What were the effects of IM hydroxocobalamin (OH-B12) administration in cats with B12 deficiency & GI disease? List 3.
c) What was the protocol used?
d) In comparison, what was the effect of 6 weeks of SQ cobalamin supplementation in cats with GI disease?
e) What about efficacy of PO cyanocobalamin in cats with CE?
Kook JVIM 2020
a) Naturally occurring forms - methyl-Cbl, adenosyl-Cbl, hydroxo-Cbl (OH-Cbl). Synthetic form - cyano-Cbl (CN-Cbl)
b)
- Decreased clinical disease activity score (appetite, V+, D+, BW, activity)
- Increased serum [B12]
- Decreased & eventually normalised MMA [ ] in 95% cats –> normalised cellular B12 deficiency
c) 300ug IM q2wks, B12 measured at wk 8 (before 4th injection) & wk 12 (1 month after 4th injection).
Kempf JVIM 2017
d) Overall, SQ protocol did not correct cellular B12 deficiency in this study.
- Normalised B12 levels & biochemical parameters transiently, but by 10 weeks post supp B12 had reduced again.
- Clinical disease activity score improved during treatment but increased after stopping.
- Serum/urine MMA concentrations did not normalise in 6-12/20 (30-60%) cats at week 6.
Toresson JFMS 2016
250mcg cyanocobalamin PO SID. 100% cats had supranormal B12 at 3-13wks.
Ki-67 is a marker of ……., while CD3 is a marker of …… activity. Dogs with chronic inflammatory enteropathies had ……. Ki-67/CD3 ratio in the ……region of intestinal biopsies, and this correlated with ……….as an indicator of clinical severity.
Karlovits JVIM 2020
Cellular proliferation
T-cell
Upregulated
Lamina propria crypt
CCECAI scores
T foetus causes chronic ……(small/large/mixed) intestinal diarrhoea.
Which of 2 faecal collection methods used to diagnose T foetus infection via PCR had a higher detection rate?
What is the recommended treatment for T foetus infection in cats? What were the 2 limitations to using this drug (wrt success rate)?
Hedgespeth JVIM 2020
Large intestinal D+
Loop technique had higher probability (OR 2.04) of positive T foetus PCR results vs colonic flush technique.
Ronidazole
Lack of association with PCR results
21% all-cause tx failure rate
Which serological markers & autoantibodies are potentially useful biomarkers to discriminate between dogs with IBD & acute GI disease/normal dogs?
Estruch JVIM 2020
IgA seropositivity against E. coli OmpC (outer membrane porin C)
- Spec 93-99%, sens 76-97%
Canine autoantibodies against polymorphonuclear leukocytes (APMNA)
- Spec 78-98%, sens 66-86%
How did IHC & clonality testing affect final diagnosis & clinical implications for cats with IBD vs LSA?
Biopsy samples from which GIT regions were the most useful? Upper SI, lower SI, upper + lower SI
Chow JVIM 2020
Integrating IHC and clonality testing with histo significantly increased no. of cases diagnosed with LSA (45.8% of defIBD cases & 100% of possLSA cases reclassified as LSA).
But clinical implications/consequence for patient outcome is unclear.
Upper SI. LSI samples rarely changed the diagnosis (only 2.3% LSA cases diagnosed based on LSI bx alone).
How did the spec CPL assay compare to 2 in-house assays (VetScan cPL, Vcheck cPL) in terms of:
- Result repeatability
- Pancreatic lipase concentration measurements?
Cridge JVIM 2020
- Spec cPL has the highest repeatability, while Vcheck cPL & VetScan cPL has significantly lower repeatability - both in-house assays may provide discrepant categorical results (“pancreatitis” vs “equivocal” vs “not pancreatitis”) for the same sample.
- Lower PLI concentrations on in-house cf spec CPL assay.
How did AUS correlate with spec CPL & clinical diagnosis in the diagnosis of pancreatitis in dogs?
What 3 AUS parameters were assessed?
Sensitivity & specificity of these parameters (in isolation & combination) to diagnose pancreatitis?
Cridge JVIM 2020
AUS weakly correlated with spec CPL, moderately correlated with clinical diagnosis. AUS changes did not correlate with spec CPL or CDx changes.
Pancreatic enlargement, pancreatic echogenicity, altered mesenteric echogenicity.
In isolation: 89% sensitivity & 43% specificity
Combo of 3 critieria: 43% sensitivity & 92% specificity
- What diagnostic test should be considered when surgically correcting peritoneopericardial and/or congenital central diaphragmatic hernias in dogs & cats?
- Reason for above test? (hint: association with type of organ disease)
- What 2 immunohistochemical stains are useful for diagnosis of the disease mentioned in 2?
Seibert JAVMA 2021
1. Liver biopsies of non-herniated liver tissues for histo
2. Ductal plate malformations (DPMs) are strongly associated with PPDH & CCDH in dogs & cats. (Types: congenital hepatic fibrosis, renal DPM).
3. Cytokeratin-19 (to stain ductal elements & illustrate malformative bile duct profile) & Ki-67 (assessment of cell proliferation). Allows differentiation from injuries provoking ductular reactions (e.g. traumatically herniated, torsed, or ischemic liver lobes).
- What was the survival & recurrence rate for cats with idiopathic megacolon that underwent subtotal colectomy?
- What factors were negatively correlated with survival?
- What additional procedure during surgery was associated with a less favourable outcome in these cats, and what are the reasons?
Grossman JAVMA 2021
1. 86% survival (14% died as a direct result of tx or complications of megacolon). 32% recurrent constipation (median 344d) - not associated with ICJ removal/retention.
2. Factors - BCS <4/9, pre-existing cardiac disease, major peri-op complications, long-term post-op liquid faeces.
3. Removal of the ICJ (associated with long-term liquid faeces & poorer owner-perceived outcome)
What surgical technique may be useful to reduce regurgitation in brachycephalic dogs poorly responsive to medical management?
Hosgood JAVMA 2021
Circumferential hiatal rim reconstruction combined with oesophagopexy.
Reconstruction of the diaphragmatic crural musculature around the oesophagus keeps the muscle contracted around the oesophagus to support GE tone during GES relaxation, thus preventing reflux. Oesophagopexy keeps the LES near the crural musculature sling.
What clinical and histologic findings were observed in dogs with ketoconazole-induced liver injury?
Long term prognosis for these dogs?
Macho JAVMA 2020
CSx - lethargy, anorexia, V+
Elevated serum liver enzymes.
Histo - variable lobular injury, mixed inflammatory infiltrates, conspicuous aggregates of ceroid-lipofuscin–engorged macrophages (Kupffer cells) that marked regions of parenchymal damage.
Long term px - 35% (5/14) developed chronic hepatitis (3 with pyogranulomatous inflammation). Survival after illness variable (3.5d to 41mths). 50% died due to liver-related causes.
Sequential bloodwork for LE monitoring advised pre & during tx.
- Which 3 methods are available for hepatic copper quantification in liver biopsies of dogs & cats?
- What was the level of agreement between quantitative results obtained by these methods?
Miller JAVMA 2021
1. Atomic absorption spectroscopy (AAS), inductively coupled plasma mass spectrometry (ICP-MS), digital image analysis of rhodanine-stained sections.
2. AAS & ICP-MS analysis often underestimated hepatic Cu concentrations vs digital image analysis. Coefficient of variation significantly increased for dogs with higher hepatic [Cu].
Dogs with gastrooesophageal intussusception (GEI):
1. Signalment
2. Survival rates (short & long term)
3. MST
4. Major post-operative (sx/endoscopic) complication & associated risk factors
Grimes JAVMA 2020
1. Young dogs (median 13mths), males (72%), GSD (33%)
2. 88% survived to discharge
3. MST 995d
4. Persistent regurgitation. Risk factors - dogs with acute (</=7d) signs or previous dx of megaO.
What clinical manifestations can be seen with protoporphyric hepatopathy in dogs?
Disease pathogenesis?
Treatment?
Kunz JAVMA 2020
Bloodwork findings consistent with liver dysfunction (microcytosis +/- anemia, hypochol, hyperBIL)
Poor growth, skin lesions (protoporphyric photosensitivity), pigmentary hepatopathy (dark brown-black liver).
Pathogenesis - porphyria syndromes reflect disrupted heme synthesis. Occurs due to defects in cytosolic and mitochondrial enzymes (predominantly in the BM & liver) responsible for heme synthesis. CSx associated with the accumulation of intermediates of the heme
synthetic pathway: porphyrins (heme, protoporphyrin, and oxidative products
of porphyrinogens) and porphyrin precursors.
Tx - avoiding conditions known to induce heme synthesis and catabolism, UDCA, SAME & vit E, avoiding sunlight exposure.
What patient, clinical, endoscopic & histologic features were observed in dogs with histologic diagnosis of chronic gastritis with lymphofollicular hyperplasia?
Faucher JAVMA 2020
Patient - younger, brachycephalics
CSx - less commonly reduced BCS or D+, more commonly inspiratory dyspnea & exercise intolerance (may occur as a consequence of increased negative intrathoracic pressure)
Endoscopic - gastric mucosal hyperaemia & discolouration
Histo - more severe gastritis
What novel interventional technique was used in a dog with EHBDO secondary to pancreatitis refractory to medical management? Other potential indications for procedure?
Chmelovski JAVMA 2020
US & fluoroscopic-guided placement of percutaneous transhepatic cholecystostomy drainage (PCD) catheter - to facilitate continual biliary drainage. Bile recycled by adminstering bile back to patient via NG tube - clinical improvement within 24hrs. Removed after 5 weeks when repeat cholangiography confirmed BD patency.
Other indications - transient causes of EHBO, patients too unstable to undergo more invasive biliary diversion techniques, biliary diseases that can be medically managed otherwise.
What was the risk of dehiscence & non-survival to discharge in cats undergoing large intestinal full thickness incisional biopsies?
List the risk factors associated with:
- Wound dehiscence only
- Non-survival to discharge only
- Both of the above
Lux JAVMA 2021
Dehiscence rate ~8%, non-survival 6%
Risk factors:
- Non-survival to discharge: low serum glob, repair of colonic trauma or dehiscence, post-op colonic dehiscence.
- Dehiscence: hypoalbuminemia, renal dysfunction, blood product admin, admin of >2 abx classes, intra-abdominal faecal contamination.
- Both: band Np, partial colectomy with colonic R&A, blood product admin, post-op CPA, incisional inflammation/ infection, blood product administration.
Dogs undergoing intestinal R&A had ….(higher/lower) dehiscence rates of ……% compared to …..% in dogs undergoing enterotomy. What 2 other factors were associated with increased risk of intestinal dehiscence for either surgical procedures?
Lopez JAVMA 2021
Higher (~6x), 18%, 3.8%
ASA class >3, older age
What was the main neurological sign observed in dogs undergoing PSS attenuation that developed PANS? What % of these dogs developed additional neuro signs?
What was the progression & recurrence rate of PANS both short & long term?
Escribano Carrera JAVMA 2021
Seizures. 40% additional neuro signs.
48% neuro signs resolved by discharge. Most neuro signs (apart from seizures) resolved within 1 month post-op.
Recurrent seizures in 50% dogs.
If survive at least 30 days, likely to survive >6mths & can live a good QOL.
Most common aetiology for sialoceles in dogs?
What medication may be a viable treatment option for dogs with sialoceles?
Ortillés JAVMA 2020
Idiopathic (88%) -* ddx sialadenitis, siadenolithiasis, FB, trauma, neoplasia, HWD, post-op complication, congenita maxillary malformation*
N-acetylcysteine 10% as an intracanalicular injection - mucolytic effects (also anti-inflammatory & anti-oxidant). Can be given at time of diagnostic imaging.
How many cases can you reuse endoscopic cup biopsy forceps for while maintaining procurement of good quality biopsies?
Cartwright JVIM 2016
10-15 cases
What is the preferred biopsy forcep size in cats to yield diagnostic quality endoscopic biopsies?
Bottero JVIM 2019
Large (2.4mm) forceps rather than small (1.8mm)
What modalities exist to measure gastric emptying in cats? How reliable are these tests?
Husnik JVIM 2017
- Radionuclide scintigraphy (99mTC) gold standard.
- AUS - in this study showed good correlation with scintigraphy; considered a suitable alternative.
- Liquid barium sulfate gastrogram - unreliable (insensitive).
- Breath testing with 13C isotope-labelled sodium acetate - fair correlation with scintigraphy.
Which 2 drugs have a prokinetic effect on the stomach of healthy cats as assessed sonographically? In contrast, which drug can cause delayed gastric emptying in these cats? Include the MOA of these drugs in your answer.
Husnik JVIM 2017
Metoclopramide & erythromycin - shorten GE times & increase the motility index of antral contractions.
- Erythromycin: motilin agonist, initiates interdigestive type III migrating motor complexes (MMCs)
Exenatide causes an initial delay in GE.
- MOA: glucagon-like peptide-1 (GLP-1) analogue. GLP-1 (incretins) are normally secreted by GIT in response to food intake, promote satiety, effect GE to reduce post-prandial glycemic excursions.
What was the incidence of GI bleeding (subclinical vs clinical) in dogs receiving chronic NSAID therapy? Did this vary across use of different NSAIDs?
Mabry JVIM 2021
Subclinical GI erosions common in NSAID-treated dogs (83%) cf control dogs (with chronic enteropathy). Erosions seen with all 3 NSAID types (carprofen > meloxicam > firocoxib).
(2 papers)
What is the utility of abdominal CT for identifying mechanical GI obstructions in dogs?
What about the utility of laparoscopy vs ex lap?
Winter JAVMA 2017
Complete agreement with exlap (both partial & complete obstruction). Feasible, rapid & accurate modality, faster than US.
Obstructed dogs had significantly larger intestinal diameter ratios.
Barry JAVMA 2017
Laparoscopy was feasible & clinically applicable in select cases of dogs with suspected GI obstruction. Smaller incision length (25% that of ex lap), duration 36min (vs 12min for ex lap). Still recommend keeping liberal criteria to convert to an open sx approach to address other identified lesions.
(2 papers)
What are unique but normal findings of the caecum identifiable on US & endoscopy in asymptomatic cats?
Is loss of caecal wall layering on US predictive of malignancy in cats?
Hahn JFMS 2016
AUS - lymphoid follicles in caecal mucosa & submucosa (forms a follicular layer). Endoscopy - dimpled appearance of caecal mucosa.
Hahn JFMS 2017
No. Loss of caecal wall layering on US identified in 7/18 (39%) cats; did not appear as a reliable predictor of the severity of histologic inflammation or malignancy. Neither did local steatitis or LN size.
What is the PPV for ultrasound to predict mucosal SI disease in cats (based on History) vs submucosal/muscularis lesions?
Guttin JVIM 2019
In a population with a high prevalence of GI disease, the PPV for ultrasound predicting mucosal disease on histology was HIGH (72-100%) but LOW for submucosal/muscularis lesions (18-57%).
Meaning SI submucosal & muscularis disease may still be apparent despite lack of US lesions, suggesting full-thickness biopsy
may not be essential in these cats.
What is a neutrophil-based biomarker for chronic enteropathy in dogs? What assays can be used to measure this & what is the Sn/Sp of this biomarker?
What 2 other antibodies may biomarker-positive dogs test positive to that were assessed in this study?
Florey JVIM 2017
Perinuclear antineutrophil cytoplasmic antibodies (pANCAs).
Serum marker for dogs with food responsive enteropathy - higher seropositivity vs SRE.
**Indirect immunofluorescence (IIF) **- timing consuming & low inter-observer agreement.
This study - used a human granulocyte IF assay. Assessed for pANCAs & cytoplasmic ANCAs (cANCAs). Quick & easy to perform; good agreement with previous assays.
Seropositivity (cANCA+ or pANCA+) Sn 61%, Sp 100% to predict FRE.
Myeloperoxidase (MPO), proteinase-3 (PR-3) protein antibodies - enzymes that may be involved in neutrophil degranulation and generation of ROS etc.
What differences in peripheral blood lymphocyte (PBL) subtypes were noted between dogs with IBD vs healthy controls, as assessed using flow cytometry?
Did this change after treatment & achievement of clinical remission in IBD dogs?
Galler JVIM 2017
IBD dogs had significantly decreased CD21+ B cells &
TCR-gamma-delta+ T lymphocytes
No changes pre & post-treatment/clinical remission.
(3 papers)
What transporter mediates intestinal absorption of bile acids, and which regions of the GIT is this expressed?
What changes in bile acid metabolism are expected in dogs with chronic enteropathy?
What are the effects of a 7-day course of tylosin on faecal bile acids & microbiota in healthy dogs?
What are the effects of corticosteroid treatment on faecal bile acids & microbiota in dogs with SRE?
Giaretta JVIM 2018
* Apical sodium-dependent bile acid transporter (ASBT). Expressed in ileum (highest), caecum & colon.
* CE dogs had increased % of primary bile acids (reduced hydroxylation to secondary BAs by depletion of C. hiranonis).
* Also downregulated ABST expression, which negatively correlated with histopathologic score.
Manchester JVIM 2018
* At D7 of tylosin - decreased faecal microbiota diversity (decreased anaerobes Fusobacteriaceae & Veillonellaceae)
* At D21 & D63 - increased primary unconjugated BAs. Changes in bacteria taxa did not uniformly resolve weeks after tylosin discontinuation.
Guard JVIM 2019
* Steroid tx did not change dysbiosis index, but significantly increased % of secondary faecal unconjugated BA at 2-3mths (28% to 94%) - suggesting steroids have regulatory effect on faecal BAs.
What RBC abnormalities are more common in dogs with GI lymphoma vs chronic enteropathy?
Parachini-Winter JAVMA 2019
Anaemia
3+ RBC anomalies, (Sn 71%, Sp 70%)
Particularly presence of eccentrocytes (29% LSA vs 4% CIE)
Eccentrocytes reflect oxidative injury.
What is calprotectin? What can it potentially differentiate in dogs?
Heilmann JVIM 2018
Calprotectin (CAL) = DAMP, a product of macrophages and neutrophils, ligand is TLR4.
* In this study, faecal CAL was able to differentiate IRE/SRE dogs from FRE & ARE dogs using a cut-off of 15.2+ug/g with Sn 80% & Sp 75%.
* Higher FCAL in dogs with no/partial response vs complete response.
* Also correlated with CCECAI score, faecal S100A12 but not CRP –> may be useful marker of disease severity (need larger studies).
Heilmann JVIM 2018 (review)?
Calprotectin was associated with CIBDAI score & significantly decreased after treatment.
Are faecal calprotectin & IgA useful for puppies in diagnosis of enteropathogens?
Grellet JVIM 2016
No.
Faecal CAL was influenced by age though (higher concentrations in younger pups).
Faecal IgA concentration was LOWER in pups shedding 1+ enteropathogen vs none, but not influenced by age.
What bacterial groups are assessed in the Dysbiosis index? What is its diagnostic performance?
Heilmann JVIM 2018 (Biomarker review)
Total 7 groups. Blautia, Clostridium hiranonis, E. coli, Faecalibacterium, Fusobacterium, Streptococcus & Turicibacter.
Sn 74%, Sp 95%
Mnemonic: Best Friends Take Care (of you) & Solve Everything Forever
What tests may screen soft coated wheaten terriers for PLE prior to clinical signs?
Heilmann JVIM 2018 (biomarker review)
Faecal alpha protease inhibitor (FPAI) & perinuclear anti-neutrophilic cytoplasmic antibodies (pANCAs) (latter also used to detect dogs with FRE)
What biomarker may be able to predict requirement for immunosuppressive treatment in CE dogs?
Heilmann JVIM 2018 (biomarker review)
CRP 9.1+; Sn 72%, Sp 100%
(3 papers)
In dogs with CIE:
What is a marker of eosinophil activation/degranulation? Is it useful to differentiate amongst CE dogs?
Did this marker correlate with peripheral eosinophilia or clinical severity scores?
What immunohistochemical stain can be used to highlight degranulated/activated Eos on GI biopsies? What is the limitation of routine H&E in identifying these Eos?
What is a marker of mast cell activation?
Heilmann JVIM 2018 (biomarker review)
* Serum 3-Bromotyrosine (3-BrY) for Eos
Sattasathuchana JVIM 2017
* Serum 3-BrY higher in SRE > FRE > Healthy dogs
* Serum 3-BrY not associated with peripheral Eos counts or CCECAI.
Bastan JVIM 2018
* Routine H&E can detect intact but not degranulated/activated Eos.
* Immunolabelling with monoclonal antibodies against eosinophil granule protein eosinophil peroxidase (Epx).
* Sig higher intact & degranulated Eos in duodenal LP of dogs with eosinophilic enteritis (EE) & mixed enteritis vs controls.
Heilmann JVIM 2018 (biomarker review)
* N-methylhistamine for mast cells
What factors in canine CIE are associated with lower Vitamin D?
Wennogle JVIM 2019
* Higher CCECAI scores, lower Vitamin E (alpha tocopherol), lower cholesterol & lower albumin, higher histopathologic scores (duodenum + ileum).
* Serum Vit D binding protein (VDBP) concentrations were not different.
* Hypothesis: fat malabsorption contributes
What cytokines are underexpressed in duodenal biopsies of GSDs with CE? What immunologic phenotype may this be associated with?
Kathrani JVIM 2019
Lower IL-13 & IL-33 mRNA expression in GSDs (vs non-GSDs with CE & healthy Beagles).
Th2 cytokines.
(2 papers)
Which plasma amino acid has been associated with a higher CCECAI score in dogs?
Which plasma amino acid is lower in dogs with PLE? Which biochemical parameter did this correlate with?
Yu JVIM 2019
Serine
(Methionine & tryptophan [ ]s also lower in IBD dogs vs controls)
Kathrani JVIM 2018
Tryptophan (unknown if role in pathogenesis or consequence of PLE). Correlated with serum albumin.
What organism is neutrophilic enteritis in cats associated with?
Maunder JVIM 2016
Campylobacter coli
Are serum & saliva assays to detect allergen-specific globulins useful for identifying adverse food reactions in dogs?
What is the gold standard diagnostic test?
Lam JAVMA 2019
No, high level of positive results in healthy dogs.
Elimination diet trials = gold standard.
What is the difference in GI biopsy samples between CE dogs with normal vs low albumin?
Jablonski Wennogle JVIM 2017
More likely to have villous stunting, crypt distension, lacteal dilation, intraepithelial lymphocytes & LP neutrophils. Also had higher histo scores for these parameters.
(2 papers)
What parameters do contrast enhanced ultrasonography assess and what can it potentially detect?
Did these parameters differ between CIE, lymphoma and healthy dogs; and following treatment in affected dogs?
Nisa JVIM 2019
* Duodenal inflammation (CEUS assessed intestinal perfusion parameters. Time intensity curves used to assess peak intensity (PI)).
* PI & AUC were higher in symptomatic CE dogs & correlated with clinical score - potentially useful parameters to exclude CIE. But perfusion parameters for lymphoma dogs did not differ cf CIE or healthy dogs.
Linta JVIM 2021
* Similarly found higher PI & AUC in duodenum of CIE vs healthy dogs. But parameters did not change with treatment.
What was the effect of feeding an animal protein-free diet for 60 days on the microbiome in dogs with FRE?
Bresciani JVIM 2018
Increased microbiota richness in FRE dogs (closer to healthy microbiota), no changes in healthy dogs.
What are short chain fatty acids & their roles?
What changes to SCFAs have been seen in dogs with CE?
Minamoto JVIM 2019
Major end products of bacterial carbohydrate fermentation in the intestinal tract.
Reduced total concentrations of SCFA, including acetate & propionate. Accompanied by higher dysbiosis index & reduced microbial diversity.
Barko JVIM 2018 Review
- Essential energy source for colonocytes
- Signaling molecules > act thru’ receptors (GPR41) in enteroendocrine cells to decrease gut transit time, increase SCFA recovery & promote adiposity.
- Maintain intestinal epithelial barrier - strengthen tight junctions, regulate intestinal motility, stimulate pdtn of anti-inflammatory compounds.
- Bind to G-protein receptor on neutrophils to decrease migration > downregulate inflammation.
(2 papers)
What is the diagnostic utility of the ePARR protocol in differentiating lymphoma from other cases in dogs? Did this differ with sample type (FFPE vs fresh frozen tissue vs FNA)?
Is clonality on PARR always associated with neoplasia?
Ehrhart JVIM 2018
For discrimination of LSA, ePARR had:
* 92% Sn & 92% Sp, 92% accuracy for FFPE tissues
* 85% Sn & 85% accuracy for flow cytometry
* 100% Sn & 100% Sp & 100% accuracyfor FNA
ePARR performed poorer for immunophenotyping (B vs T cell) rather than differentiating between LSA vs non-LSA>
Marsilio JVIM 2019
No. Clonality (consistent with SCL or emerging) was detected in healthy cats that did not develop GI signs on long term FU.
Possible reasons include benign clonality (can occur from antigenic stimulation), pseudoclonality due to insufficient target DNA, or primer binding issues.
What scintigraphy could be useful to diagnose PLE in dogs?
Engelmann JVIM 2017
99mTc labelled human serum albumin (HSA) given IV.
Abdo imaging obtained at 10, 60, 120, 240min post injection. Positive result for PLE = exudation of 99mTc into the intestinal tract.
Does gastrooesophageal and/or laryngopharyngeal reflux occur in healthy dogs as detected by nuclear scintigraphy? What about aspiration?
Grobman JVIM 2020
Reflux but not aspiration is common in healthy dogs (100% of dogs in this study). Frequency ~2 events/5mins, duration ~6sec.
By how much does a 1 point increase in CCECAI increase the hazard of death in PLE dogs?
Kathrani JVIM 2019
22.9%.
Dogs with CCECAI score </= 8 & urea </= 7mmol/L survived 256-279 days longer than dogs with CCECAI >8 and/or urea >7mmol/L.
Are there any diagnostic features which can predict clinical response or outcome in dogs with PLE?
What survival differences are there between PLE dogs receving steroid monotherapy vs steroid+2nd line immunosuppressant?
Salavati Schmit JVIM 2019
No diagnostic feature was predictive of clinical response or outcome.
Median time until serum albumin reached >20 g/L = 13 days. MST 85d for steroid only dogs (13-463d), 166d for pred+2nd IS dogs (8-390d). Looking at range of MST, steroid tx alone can be appropriate for dogs with PLE.
What cells predominate in the LN paracortex vs germinal centre? Where does lymph enter the LN?
Craven JVIM 2019 (PLE review)
Paracortex: T cell
Germinal centre: B cell
Lymph enters subcapsular sinus & cortex
What IHC markers can be used to differentiate lymphatics from capillary endothelium?
Craven JVIM 2019 (PLE review)
Prox-1 & CD31
What bacteria/toxin is associated with AHDS in dogs?
Sindern JVIM 2018
Clostridium perfringens which encodes pore-forming toxin genes NetE & NetF.
Prevalent in 48% AHDS dogs (0% CPV dogs & 12% healthy dogs).
What is intestinal leiomyositis?
Describe associated imaging findings.
What is an important consideration when obtaining intestinal biopsies for diagnosis?
Treatment options & prognosis?
Zacuto JVIM 2016
Suspect autoimmune condition affecting intestinal s.m. Causes dysmotility and pseudoobstruction.
Marked gastric distention & dilated SI.
Requires full thickness GI biopsies for diagnosis (disease in muscularis propria layer)
Histology - mononuclear inflammation, myofiber degeneration & fibrosis.
Various treatments trialled without significant clinical improvement. Prognosis guarded; MST 19d.
What % of dogs with acute haemorrhagic D+ subsequently develop chronic GI signs?
Skotnitzki JVIM 2021
28% of AHDS dogs, median 4 years for development of chronic GI signs.
Possible that AHDS induced severe intestinal mucosal damage & associated barrier dysfunction may trigge chronic GI disease later in life.
What % of dogs attending dog parks in N California had enteropathogens detected? The presence of which pathogen affected faecal consistency in these dogs, and what diagnostic tests for reliable for its detection?
Hascall JVIM 2016
38% dogs (of which 46% had D+).
Presence of Giardia associated with D+ (9% dogs infected)
**Giardia PCR not useful; **negative in 41% dogs that were faecal float positive or direct fluorescent antibody test. Identification of Giardia cysts also variably reliable depending on lab.
Which 2 enzymes is cobalamin a cofactor for?
What does an increase in methylmalonic acid (MMA) lead to?
What are methods of identifying cobalamin deficiency apart from a serum cobalamin level?
Kather JVIM 2019 (Cobalamin review)
Methionine synthase & Methylmalonyl CoA.
MMA increases if MMCoA not active. MMA inhibits carbamoyl phosphate synthetase (which converts ammonia to carbamoyl phosphate) –> hyperNH3 results
Increased serum homocysteine & MMA concentrations.
What is Imerslund-Gräsbeck syndrome?
What breeds does it affect?
What treatment options exist?
Kook JVIM 2018
Congenital cobalamin malabsorption.
Beagles. Also Aus Shepherds, Beagles, Border Collies, Giant
Schnauzers.
Maintenance dose of monthly or bimonthly 1mg SQ HYDROXOcobalamin (OH-Cl) was effective in this paper - both resulted in similar urinary MMA concentrations.
Kook JVIM 2019
1mg PO SID was also effective to maintain urinary [MMA] WRI.
What type of anemia can be observed in a hypocobalaminemic state? Was this observed in a population of anemic dogs?
Stanley JVIM 2019
Megaloblastic (macrocytic), non-regenerative.
Anemic dogs had high prevalence of vitamin B deficiencies (NR: 64% hypoB12, 18% hypofolatemic) but no association of low B12 with megaloblastic anemia.
What hematologic parameters are altered in pregnant bitches? Which stage of pregnancy were these observed (early or late)?
Did changes influence neonatal survival?
Nivy JVIM 2019
Anemia common in LATE pregnancy.
Also associated with increased serum iron & transferrin saturation (opposite of women), decreased serum B12 (severity increased with larger litter size & parity no.).
No association with neonatal survival.
Was PO cobalamin supplementation effective for treatment of hypocobalaminemic dogs with chronic enteropathies?
Toresson JVIM 2016
Yes, 100% dogs (51/51) became normocobalaminemic. Serum B12 rechecked at 20-200days. Used CYANOcobalamin of various brands.
(NB: Protexin cobalazorb = cyanocobalamin)
(2 papers)
What are the effects of metronidazole on:
- Dogs with acute diarrhoea
- Faecal microbiome & metabolome of healthy dogs?
Langlois JVIM 2020 (acute D+ dogs)
Metro reduced time to resolution of D+ (2.1 vs 3.6 days) and reduced % of dogs with C perfringens carriage post treatment (23% vcs 78%). Long term effects and overall utility not studied.
Pilla JVIM 2020
Metro x14d in combo with hydrolyzed protein diet vs metro only vs healthy dogs.
Metro significantly decreased microbiome richness (impt bacteria e.g. Fusobacteria) that did not fully resolve 4 weeks after stopping drug. Increased dysbiosis index, faecal total lactate; decreased 2’ bile acids (deoxycholic acid & lithocholic acid).
What is the effect of hospitalisation on gastric emptying time in dogs?
Warrit JAVMA 2017
Assessed using wireless motility capsule.
Hosp prolongs gastric emptying time. Median 71hrs vs 17hrs @ home.
Based on a systemic review, is probiotic administration effective in preventing or treating acute vs chronic GI disease in dogs?
Jensen JVIM 2019
Limited-negligible effect for prevention or treatment of acute GI disease.
For chronic GI disease, dietary intervention remains most impt. Probiotics didn’t seem to significantly improve clinical signs.
But overall noted that studies were often underpowered.
What was the effect of Synbiotic administration on diarrhoea in kennelled dogs?
Rose JVIM 2017
Pre-probiotic mixture. Decreased incidence (18.8% vs 27.2%), no. of days (2 vs 3.2), & occurrence of 2+ days of D+ (4.6% vs 8%).
