Are leukocyte and platelet abnormalities and complete blood count ratios potential prognostic markers in canine sepsis?

Background: Sepsis is a common disease in which early diagnosis and prognosis assessment are the main aims in order to arrange a prompt and effective treatment. Objectives: (1) To compare leukogram parameters (WBC, segmented and band neutrophils,lymphocytes,monocytes),plateletcount(PLT),meanplateletvolume(MPV), and some leukocyte/platelet ratio such as NLR, NBNLR, PLR, and MLR between dogs with systemic inflammatory response syndrome (SIRS) and sepsis. (2) To investigate any difference in the trend of these latter parameters between survivors and non-survivors septic dogs. Animals: 57 dogs with confirmed sepsis and 57 dogs with non-septic SIRS. Methods: A review of the medical records was conducted in order to find dogs with sepsis. Sepsis was defined as the presence of an infectious focus with fulfillment of systemic inflammatory response syndrome criteria (SIRS). Septic dogs had to have a CBC at admission and another CBC within 48h from the previous timepoint. Purebreds with CBC breed-related abnormalities were excluded, together with dogs without confirmed sepsis and dogs with only a single CBC. NLR, NBNLR, PLR, and MLR were calculated. Univariate analysis of all blood parameters studied was assessed between SIRS and septicdogs. Generalized Estimating Equations models for repeated measures were used to test if the blood parameters studied were modified between survivors and non-survivors in the septic group. Results: Septic dogs had lower median segmented neutrophils count and NLR compared to SIRSdogs (p=0.02andp=0.04, respectively).Lastly,septicdogs hada higherprevalenceoftoxicneutrophilthanSIRSdogs(p=0.01).Wefoundthatfora1-unit increase of PLR and MLR, the risk of death increased by 50.5 and 60%, respectively. Conclusion and Clinical Importance: Evaluation of NLR at hospital admission may be a useful marker of inflammation, although it showed low sensitivity in differentiating SIRS and septic dogs. The monitoring of some CBC parameters, especially PLR and MLR may be useful in the establishment of prognosis in septic dogs

Comparison of dogs treated for primary immune-mediated hemolytic anemia in Tuscany, Italy and Texas, USA

This retrospective study compared clinical characteristics between dogs treated for IMHA by veterinary teaching hospitals in Tuscany, Italy and Texas, USA between 2010 and 2018

Conformity and controversies in the diagnosis, staging and follow-up evaluation of canine nodal lymphoma: a systematic review of the last 15 years of published literature

Diagnostic methods used in the initial and post-treatment evaluation of canine lymphoma are heterogeneous and can vary within countries and institutions. Accurate reporting of clinical stage and response assessment is crucial in determining the treatment efficacy and predicting prognosis. This study comprises a systematic review of all available canine multicentric lymphoma studies published over 15 years. Data concerning diagnosis, clinical stage evaluation and response assessment procedures were extracted and compared. Sixty-three studies met the eligibility criteria. Fifty-five (87.3%) studies were non-randomized prospective or retrospective studies. The survey results also expose variations in diagnostic criteria and treatment response assessment in canine multicentric lymphoma. Variations in staging procedures performed and recorded led to an unquantifiable heterogeneity among patients in and between studies, making it difficult to compare treatment efficacies. Awareness of this inconsistency of procedure and reporting may help in the design of future clinical trials

Erythrogram patterns in dogs with chronic kidney disease

Anemia is considered a common finding in dogs with chronic kidney disease (CKD), typically as normochromic, normocytic, and non-regenerative. Although anemia can occur at any CKD IRIS (International Renal Interest Society) stage, its severity is related with the loss of kidney function. The aim of the present study was to retrospectively evaluate quantitative and morphological abnormalities of the erythrogram in dogs at different CKD IRIS stages. A total of 482 CBCs from 3648 initially screened were included in the study. Anemia was present in 302/482 (63%) dogs, in the majority of which it was normochromic, normocytic, and non-regenerative (295/302; 98%). The number of reticulocytes was <60,000/mu L in the majority of dogs (248/295; 84%), with a correlation between poor regeneration rate and progression of CKD (p = 0.0001). The frequency of anemia significantly differed (p = 0.0001) among the IRIS stages: 108/231 (47%) in IRIS 2, 77/109 (71%) in IRIS 3, and 117/142 (82%) in IRIS 4. Dogs at IRIS stages 3 and 4 were more likely to have moderate to severe anemia, compared to dogs at IRIS stage 2 (p = 0.0001). Anisocytosis was the most frequent morphological abnormality (291/482; 60%), whereas the presence of poikilocytosis showed an association with progression of IRIS stages (p = 0.009). Among different morphological abnormalities, the frequency of fragmented red blood cells and Howell-Jolly bodies showed a significant association with the progression of CKD. Anemia was a frequent finding in CKD dogs, mostly associated with none to poor regeneration rate. Similar to human medicine, advanced CKD stages are more frequently characterized by morphological alterations, such as fragmented red blood cells and Howell-Jolly bodies, which may suggest a more severe condition of reduced bone marrow activity and microangiopathy

Neutrophil-to-lymphocyte ratio (NLR) in canine inflammatory bowel disease (IBD)

Inflammatory bowel disease (IBD) is a multifactorial chronic inflammatory disorder leading to structural changes in the intestinal wall. In humans, the neutrophil-to-lymphocyte ratio (NLR) has been proposed as a promising marker of IBD. This study evaluated the possible clinical and prognostic significance of the NLR in dogs with IBD. This retrospective study enrolled 41 dogs diagnosed with IBD presented to University of Pisa from January 2017 to January 2018. For each dog, age, sex, canine chronic enteropathy clinical activity index (CCECAI), endoscopic and histopathological grading were recorded. Complete blood count, serum total protein, albumin, cholesterol, and C-reactive protein at the time of endoscopy were recorded. A control group (CG) of healthy dogs from a blood donor database was built. NLR was calculated for both IBD and CG as the ratio between absolute neutrophils and lymphocytes. Presence of crypt distension, lacteal dilation (LD), mucosal fibrosis, intraepithelial lymphocytes was recorded. Follow-up information was obtained from electronic medical records and dogs were classified as responders and non-responders based on CCECAI variation between admission and the first recheck. IRE dogs showed higher NLR compared to healthy dogs. NLR correlated negatively with total protein, albumin, and cholesterol and correlated positively with CCECAI. Dogs with LD showed higher NLR than dogs without LD. Non-responders showed higher NLR compared to responders. In conclusion, as in IBD human patients, the NLR acts as an inflammatory marker providing further information on severity of the disease and could be useful in predicting treatment response

Concurrent gastrointestinal signs in hypothyroid dogs

Few observations about prevalence and features of gastrointestinal (GI) signs in hypothyroid dogs (hypoT-dogs) are available.The study aimed (1) to evaluate concurrent GI signs in hypoT-dogs; (2) to analyze clinico-pathological and ultrasound features ofhypoT-dogs with and w/out GI signs, and (3) to analyzed GI signs follow-up after thyroid hormone replacement therapy (THRT).Medical records of hypoT-dogs from two Veterinary Teaching Hospitals were retrospectively reviewed. Dogs were classified ashypothyroid if TT4 or fT4 were low/normal with normal/high TSH or inadequate TSH-stimulation test response. Clinical history, GIsigns (vomiting, diarrhea, constipation), hematobiochemical parameters and abdominal ultrasound were collected. HypoT-dogs were divided based on the presence of at least one GI signs (GI group and not-GI group). Twenty-seven GI dogs had 3-4 weeks recheck from the beginning of THRT and information on GI signs were recorded. A total of 166 dogs were included (GI group, n=45, 27%; not-GI group, n=121, 73%). GI dogs showed nausea (42%), vomiting(40%), constipation (22%), large bowel diarrhea (40%), small bowel diarrhea (4%) and aspecific diarrhea (40%). No significant difference between GI and not-GI groups on hematobiochemical parameters was found. GI group had significantly higherfrequency (20%) of large intestine involvement than not-GI group at the ultrasound (P = 0.03; Chi-square test). Twenty-one out of27 GI dogs had a resolution of GI signs at recheck (P = 0.0001; McNemar test). Most of hypoT-dogs had concurrent GI signs mainly due to large bowel involvement. After THRT beginning the concurrent GI signs in hypoT-dogs seem to be reduce

Faecal microbiota in dogs with multicentric lymphoma

Malignant lymphoma B-cell type is the most common canine haematopoietic malignancy. Changes in intestinal microbiota have been implicated in few types of cancer in humans. The aim of this prospective and case-control study was to determine differences in faecal microbiota between healthy control dogs and dogs with multicentric lymphoma. Twelve dogs affected by multicentric, B-cell, stage III-IV lymphoma, and 21 healthy dogs were enrolled in the study. For each dog, faecal samples were analysed by Illumina sequencing of 16S rRNA genes and quantitative PCR (qPCR) for selected bacterial groups. Alpha diversity was significant lower in lymphoma dogs. Principal coordinate analysis plots showed different microbial clustering (P=.001) and linear discriminant analysis effect size revealed 28 differentially abundant bacterial groups in lymphoma and control dogs. The qPCR analysis showed significant lower abundance of Faecalibacterium spp. (q<.001), Fusobacterium spp. (q=.032), and Turicibacter spp. (q=.043) in dogs with lymphoma compared with control dogs. On the contrary, Streptococcus spp. was significantly higher in dogs with lymphoma (q=.041). The dysbiosis index was significantly higher (P<.0001) in dogs with lymphoma. In conclusion, both sequencing and qPCR analyses provided a global overview of faecal microbial communities and showed significant differences in the microbial communities of dogs presenting with multicentric lymphoma compared with healthy control dogs

Evaluation of Clinico-Pathological Alterations Including Some Leukocyte Ratios and Survival Rate in Dogs with IMHA Transfused and Not Transfused: A Retrospective Study

Immune-mediated hemolytic anaemia (IMHA) is a common hematological disorder in dogs. It can be primary or secondary and it is characterized by anti-RBC antibodies production. IMHA requires a detailed diagnostic pathway as well as a complex therapeutic approach that can include blood transfusion. Unfortunately, IMHA presents a high mortality rate, especially within 15 days after onset. This retrospective study evaluated: a) the clinical and clinico-pathological alterations that influenced the choice to perform a blood transfusion in an IMHA patient; b) if blood transfusion could be an additional therapeutic approach; c) application of leukocyte ratios in the prognosis. Sixty-seven cases of IMHA, both primary and secondary, admitted to the Veterinary Teaching Hospital between May 2010 and July 2018, were included. Signalment, history, clinical signs, clinico-pathological parameters and survival rate were collected. Patients were divided in two groups: 44 patients (IMHAnt) treated with immunosuppressive therapy alone (primary n=36, secondary n=8) and 23 patients (IMHAt), which received also a blood transfusion (primarily packed RBC) (primary n=16, secondary n=6). For all collected parameters, both groups were statistically compared. The IMHAt patients compared to IMHAnt patients (un-regarding to primary or secondary cause) presented: worse marks according to Tokyo Score System (TSS) (Chi Squared, p=0.003); a lower erythrocyte count (T-test, p=0.039), hemoglobin concentration (T-test, p=0.029) and platelet count (Mann-Withney, M-W, p=0.008); a higher value of band neutrophils (M-W, p=0.022), band neutrophil to lymphocyte ratio (M-W, p=0.005), (band neutrophil/neutrophil) to lymphocyte ratio (M-W, p=0.006) and a lower value of lymphocyte to monocyte ratio (M-W, p=0.013); a higher value of C-reactive protein (M-W, p=0.011) and activated partial thromboplastin time (M-W, p=0.014); and a lower survival rate at day 120 (Kaplan-Meyer, logrank, p=0.004) and not at 7, 15 and 30 days. Blood transfusions were performed based on the severity of clinical and clinico-pathological signs. IMHAt patients showed a more severe disease (according to TSS), a greater acute inflammatory condition and more coagulative defects. The high death rate among IMHAt patients at 120 days was related to their critical condition, which is probably why the desired benefit of blood transfusion wasn’t reached. However, a link between blood transfusions and the related worse clinical signs in IMHAt patients could not be ruled-out. Finally, the leukocyte ratios in dogs affected by IMHA were assessed for the first time so far and they were proven to be useful markers of acute inflammation and could have a prognostic value

Faecal microbiota in dogs with multicentric lymphoma

Malignant lymphoma B-cell type is the most common canine haematopoietic malignancy. Changes in intestinal microbiota have been implicated in few types of cancer in humans. The aim of this prospective and case-control study was to determine differences in faecal microbiota between healthy control dogs and dogs with multicentric lymphoma. Twelve dogs affected by multicentric, B-cell, stage III-IV lymphoma, and 21 healthy dogs were enrolled in the study. For each dog, faecal samples were analysed by Illumina sequencing of 16S rRNA genes and quantitative PCR (qPCR) for selected bacterial groups. Alpha diversity was significant lower in lymphoma dogs. Principal coordinate analysis plots showed different microbial clustering (P = .001) and linear discriminant analysis effect size revealed 28 differentially abundant bacterial groups in lymphoma and control dogs. The qPCR analysis showed significant lower abundance of Faecalibacterium spp. (q < .001), Fusobacterium spp. (q = .032), and Turicibacter spp. (q = .043) in dogs with lymphoma compared with control dogs. On the contrary, Streptococcus spp. was significantly higher in dogs with lymphoma (q = .041). The dysbiosis index was significantly higher (P < .0001) in dogs with lymphoma. In conclusion, both sequencing and qPCR analyses provided a global overview of faecal microbial communities and showed significant differences in the microbial communities of dogs presenting with multicentric lymphoma compared with healthy control dogs.dog

Tel-eVax: a genetic vaccine targeting telomerase for treatment of canine lymphoma

Background: we have recently shown that Tel-eVax, a genetic vaccine targeting dog telomerase (dTERT) and based on Adenovirus (Ad)/DNA Electro-Gene-Transfer (DNA–EGT) technology can induce strong immune response and increase overall survival (OS) of dogs affected by multicentric Diffuse Large B cell Lymphoma (DLBCL) when combined to COP therapy in a double-arm study. Here, we have utilized a clinically validated device for veterinary electroporation called Vet-ePorator , based on Cliniporator technology currently utilized and approved in Europe for electro- chemotherapy applications and adapted to electrogenetransfer (EGT). Methods: 17 dogs affected by DLBCL were vaccinated using two Ad vector injections (Prime phase) followed by TM DNA–EGT (Boost phase) by means of a Vet-ePorator device and treated in the same time with a 27-week Madison Wisconsin CHOP protocol. The immune response was measured by ELISA assays using pool of peptides. Results: No significant adverse effects were observed. The OS of vaccine/CHOP animals was 64.5 weeks, in line with the previous study. Dogs developed antibodies against the immunizing antigen. Conclusions: Tel-eVax in combination with CHOP is safe and immunogenic in lymphoma canine patients. These data confirm the therapeutic efficacy of dTERT vaccine and hold promise for the treatment of dogs affected by other cancer types. More importantly, our findings may translate to human clinical trials and represent new strategies for cancer treatment