Each study was graded; all were case series, which scored 3 on the Scottish Intercollegiate Guidelines Network (SIGN) grading [ 21] and 'very low' on the Grading of Recommendations Assessment, Development and Evaluation (GRADE) [ 22], thus any estimate of the effect is very uncertain.
We graded the quality of each study reviewed on a scale of 1 to 4 according to the Scottish Intercollegiate Guidelines Network (SIGN) grading system [ 54].
The cumulative strength of the body of evidence for each intervention was then graded as A, B, C, or D using the SIGN grading system; impact estimates for each intervention were further cumulatively assessed as having no/negative, uncertain, some or clear evidence of benefit.
A grading scale of 1 to 3 was used to identify the severity of these signs in which grade 1 was "absence of signs"; grade 2 was "slight"; and grade 3 was "severe".
All dogs had some kind of respiratory signs (Table 1): only one dog had a mild grade of respiratory signs (grade 1), 13 (26%) suffered from a moderate grade (grade 2) and 36 (72%) from a severe grade (grade 3).
Just one horse with grade 4 neurological signs was 4 years old and the 3 other horses suffering from neurological signs grade 4 were over 9 years of age.
Enteritis: CTC AE grade 1 = asymptomatic; grade 2 = abdominal pain, mucus or blood in stool; grade 3 = severe or persistent abdominal pain, fever, ileus, peritoneal signs; grade 4 = life-threatening consequences, urgent intervention indicated.
Responses were scored according to the following clinical assessment scale [ 31]: grade 0, absence of clinical signs; grade 1, hanging tail or impaired righting; grade 2, mild paresis of one hind limb; grade 3, paresis of two hind limbs; and grade 4, full paralysis of one or two hind limbs/moribund.
In the same study, severe, life-threatening, or fatal (diarrhea of 7 or more stools above baseline, fever, peritoneal signs; Grade 3 5) immune-mediated enterocolitis occurred in 34 (7%) patients and moderate (diarrhea with up to 6 stools above baseline, abdominal pain, mucus or blood in stool) Grade 2 both ileitis and colitis occurred in 28 (5%) Ipilimumab-treated patients.
Of these, 605 had gradable retinal photographs of sufficient quality for retinopathy grading, 486 for retinal arteriolar wall signs grading, and 541 for quantitative assessment.
Clinical data included the rectal temperature, an assessment of the severity of systemic signs (graded as none, weak, moderate or severe) and local clinical signs of the affected gland, including whether or not gangrene was present (i.e., cold and blue udder and teat skin).
