Paolo Pazzi

Background: Hypoalbuminemia (HA) is associated with a higher case fatality rate in people. Hypothesis/Objectives: To describe the affected organ systems and pathoetiologies in cats with mild (2.5-2.9 g/dL), moderate (2-2.4 g/dL), or severe (< 2 g/dL) HA, and compare hospitalization and survival times to cats without HA (wHA; ≥ 3 g/dL). Animals: Eight hundred thirty-two HA and 832 wHA cats. Methods: Retrospective case-control study of cats with plasma albumin concentrations measured between 2017 and 2023. Diagnoses were categorized by organ system and pathoetiology and subsequently compared among HA and wHA groups. Hospitalization and survival times were compared. Results: HA prevalence was 32% (948/2927); 116 cats were excluded. Cats with HA were more often diagnosed with infectious (211/832, 25%) or neoplastic (198/832, 24%) pathoetiologies, and diseases affecting the hematopoietic (140/832, 17%) or multisystemic (71/832, 9%) organ systems compared to cats wHA (P < .001 for all). Cats with severe HA were more likely to have infectious diseases than all other severities (P < .001). Cats with HA had longer hospitalizations and shorter survival than wHA cats (P < .001). Cats with severe HA had significantly shorter restricted mean survival times from admission to 6 months (71 days, 95% CI 51-92 days) than wHA (144 days, 95% CI 138-149 days, P < .001), mild HA (119 days, 95% CI 111-127, P < .001), and moderate HA (108 days, 95% CI 95-122 days, P = .02) cats. Conclusions and clinical importance: In cats with severe HA, investigation of infectious diseases should be prioritized.

Hemostatic dysfunction is a prevalent and significant complication in tumor-bearing dogs, driven by complex interactions between the tumor microenvironment and the host's coagulation system. This narrative review examines primary and secondary hemostatic alterations, fibrinolytic abnormalities, and prognostic indicators associated with hemostatic variables in canine lymphoma, carcinoma, and sarcoma. In lymphoma, the true prevalence of thromboembolic disease (TED) is unknown; clinically significant hemostatic alterations are typically associated with advanced stages, characterized by persistent hypercoagulability, or elevated D-dimer concentrations, and may be associated with a poor prognosis. Carcinomas are associated with TED, and hemostatic alterations are common, typically characterized by reactive thrombocytosis, hyperfibrinogenemia, and viscoelastic evidence of hypercoagulability. Sarcomas appear to be most associated with TED. Soft tissue sarcoma and osteosarcoma exhibit different hemostatic alterations and prognostic variables compared with hemangiosarcoma, and these differences are typically related to the stage of the disease. By synthesizing current evidence, recent advances, and key knowledge gaps, this review identifies the need to define tumor-specific hemostatic diagnostic profiles in tumor-bearing dogs and subsequently develop tailored thromboprophylaxis strategies. This may ultimately improve survival by enabling targeted management of hemostatic alterations and, potentially, by mitigating metastatic progression.

Cancer is a leading cause of death in humans and dogs. Several erythrocyte and platelet characteristics (indices and morphology) have shown promise as indicators of metastasis in humans. Similar studies have not been performed in dogs. This study evaluated erythrocyte and platelet characteristics measured on the Advia 2120i in 59 tumor-bearing dogs with carcinoma or sarcoma. Tumor-bearing dogs with and without intracavitary hemorrhage that underwent complete post-mortem and histopathology examinations were compared to healthy age-controlled dogs. Carcinoma- and sarcoma-bearing dogs without hemorrhage were compared. All tumor-bearing dogs without hemorrhage or metastasis were compared to those with metastasis, and characteristics were evaluated as indicators of metastasis. Tumor-bearing dogs without intracavitary hemorrhage (n = 49) had decreased hematocrit (p = 0.002) and reticulocyte hemoglobin content (p = 0.022), and increase in anisocytosis (p = 0.002), polychromasia (p = 0.002), macrocytosis (p = 0.032), codocytes (p = 0.022), absolute reticulocyte count (p = 0.035), platelet concentration (p = 0.002), plateletcrit (p = 0.022), and platelet volume distribution width (p = 0.022) compared to healthy dogs (n = 20). In tumor-bearing dogs with intracavitary hemorrhage (n = 10), additional significant differences were reflective of acute hemorrhage. No difference in characteristics between carcinoma- and sarcoma-bearing dogs without hemorrhage was identified. After correction for multiple comparisons, no differences in erythrocyte or platelet characteristics were identified between tumor-bearing dogs without intracavitary hemorrhage and metastasis and those without metastasis. Significant differences in characteristics exist between tumor-bearing dogs and healthy dogs. Based on the limited number of dogs in this preliminary study, no red blood cell or platelet characteristics were associated with metastatic disease in tumor-bearing dogs without hemorrhage.

Objectives: Identify alterations in biochemical and haemostatic variables between tumour‐bearing dogs with and without metastasis that can be used to predict the presence of metastasis. Materials and Methods: Thirty dogs with sarcoma and 29 with carcinoma were included in the analysis. Serum biochemistry profiles and haemostatic variables (haematocrit value, platelet count, thromboelastography (TEG), fibrinogen, Factor X, VII, antithrombin activity and D‐dimer concentration) were measured for all dogs. All dogs underwent complete post‐mortem and histopathological evaluations. For tumour‐bearing dogs without intracavitary haemorrhage, measured variables were compared between dogs with and without metastasis, and univariate and multivariable analysis were performed to identify predictors of metastasis. Results: Metastasis was identified in 31 of 59 (53%) dogs, of which 5 of 31 (16%) had metastasis to the regional lymph node only and 26 of 31 (84%) had distant metastasis. Sodium, ionised calcium, TEG lysis % at 30 and 60 minutes (Ly60) were significantly lower in tumour‐bearing dogs without intracavitary haemorrhage with metastasis compared to dogs without metastasis. Multivariable analysis identified sodium 95% :45% to 82%) and 63% specific (CI _95% :44% to 81%); and Ly60 < 1.0% as 68% sensitive (CI _95% : 49% to 88%) and 78% specific (CI _95% :61% to 95%) for prediction of the presence of metastasis. Parallel interpretation of lower sodium and decreased Ly60 resulted in high sensitivity (96%) for the presence of metastasis. Clinical Significance: Sodium and TEG‐based decreased fibrinolysis were associated with metastasis in tumour‐bearing dogs without haemorrhage; when identified, they should prompt further diagnostics to detect possible metastasis of a primary carcinoma or sarcoma.

Background: It is unknown if tumors or concomitant renal disease influence neutrophil gelatinase–associated lipocalin (NGAL) and symmetric dimethylarginine (SDMA) concentrations in tumor-bearing dogs. Objectives: Determine the effect of tumor presence, tumor type, and metastasis on concentrations of serum NGAL (sNGAL), SDMA, urinary NGAL (uNGAL), and uNGAL-to-creatinine ratio (uNGAL/Cr) in dogs with carcinoma or sarcoma without clinically relevant renal disease. Animals: Twenty-one dogs with carcinoma, 18 with sarcoma, and 20 healthy age-controlled dogs. Methods: Concentrations of sNGAL, SDMA, and uNGAL, and uNGAL/Cr ratio were measured from banked samples collected during a previous prospective study. Patient clinicopathological and histopathology records were reviewed, and those with renal azotemia or moderate to severe histopathological renal abnormalities were classified as having clinically relevant renal disease. Biomarker concentrations were compared between tumor-bearing dogs without clinically relevant renal disease and healthy age-controlled dogs. Additionally, comparisons were made between dogs with carcinoma and sarcoma, as well as between dogs with and without metastasis. Correlations between uNGAL and sNGAL concentrations, along with acute phase protein (APP) concentrations, were also analyzed. Results: Tumor-bearing dogs without clinically relevant renal disease had increased uNGAL/Cr (p < 0.001), but not sNGAL, compared with healthy controls. Although median SDMA concentrations did not significantly differ between groups, increased concentrations were found in 32% of dogs with carcinoma and 20% of dogs with sarcoma. No differences were found between dogs with carcinoma and those with sarcoma, or between dogs with metastasis and those without. Urinary and serum NGAL concentrations were moderately correlated, while weak to no correlations were observed with APPs. Conclusion: Carcinomas and sarcomas, but not metastasis, influence uNGAL/Cr and SDMA concentrations in dogs.

Background: Knowledge of the prevalence of thromboemboli and the associated hemostatic status in dogs with carcinoma or sarcoma is unknown and might allow earlier intervention. Objectives: Estimate prevalence of thromboemboli and their association with hemostatic changes in dogs with carcinomas or sarcomas; estimate predictive values of hemostatic variables for thromboembolic disease in tumor-bearing dogs. Animals: Thirty-two dogs with sarcoma, 30 with carcinoma, 20 healthy age-controlled dogs. Methods: Prospective cross-sectional study. A hemostasis panel (platelet concentration, thromboelastography, fibrinogen and D-dimer concentration, factor X, VII and antithrombin activity) was performed in all dogs. Tumor-bearing dogs underwent complete post mortem and histopathological evaluation. Comparisons between healthy dogs and tumor-bearing dogs with and without intracavitary hemorrhage; and tumor-bearing dogs with and without microthrombi were analyzed. Results: Thromboembolic disease was identified in 32/62 (52%, 95% CI: 39%-65%) tumor-bearing dogs. Microthrombi were identified in 31/62 (50%, 95% CI: 37%-63%) dogs, 21/31 (68%, 95% CI: 49%-83%) had exclusively intra-tumoral microthrombi, 10/31 (32%, 95% CI: 17%-51%) had distant microthrombi. Macrothrombi were identified in 3 tumor-bearing dogs. Hemostatic changes potentially consistent with overt and non-overt disseminated intravascular coagulation were identified in some tumor-bearing dogs. D-dimer concentrations were significantly higher (P = .02) and platelet concentration significantly lower (P = .03) in tumor-bearing dogs with microthrombi compared to tumor-bearing dogs without microthrombi. D-dimer concentration above 500 ng/mL was 80% sensitive and 41% specific for the prediction of microthrombi presence. Conclusion: The high microthrombi prevalence and concomitant hemostatic dysfunction in dogs with carcinomas or sarcomas has not previously been reported, though the clinical importance is unknown. Increased D-dimer concentration might increase suspicion of microthrombi.

Canine parvovirus (CPV) is a common cause of enteritis, immune suppression and systemic inflammation in young dogs. Endothelial markers, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and molecules that upregulate their expression, such as high mobility group box 1 protein (HMGB-1), provide insight into the state of the endothelium during inflammation. This study aimed to determine if circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 were altered in CPV enteritis compared to healthy controls, and whether a correlation existed between these molecules and the degree of inflammation. Thirty dogs with naturally occurring CPV enteritis and ten control dogs were included. Physical examinations, complete blood count and C-reactive protein (CRP) measurements were performed on all dogs at presentation. The concentrations of ICAM-1, VCAM-1 and HMGB-1 were measured using commercially available canine-specific enzyme-linked immunosorbent assay (ELISA) kits. In dogs with CPV enteritis, ICAM-1 concentrations were significantly lower (median: 5.9 [IQR: 4.3-8.3]) and CRP higher (134 [IQR: 85-195]) compared to controls (8.0 [IQR: 6.9-10.3], p = 0.008; 1 [IQR: 0-7], p < 0.001). No significant difference was found for VCAM- 1 and HMGB-1. A strong correlation was identified between VCAM-1 and segmented neutrophil count (r = 0.612, p < 0.001). Despite the presence of systemic inflammation in CPV enteritis, evidenced by high CRP concentrations, our results suggest circulating concentrations of ICAM-1, VCAM-1 and HMGB-1 failed to show an increase. Endothelial activation with subsequent leukocyte adhesion and transmigration through the endothelium may be affected in CPV enteritis and these findings require further investigation.

Critical appraisal of the available literature for the treatment of canine oral malignant melanoma (OMM) is lacking. This critical review aimed to evaluate the current literature and provide treatment recommendations and possible suggestions for future canine OMM research. PubMed, Web of Science and Google Scholar were searched in June 2021, for terms relevant to treatment of OMM. Inclusion and exclusion criteria were applied and information on clinical response and outcome extracted. Eighty-one studies were included. The overall level of evidence supporting the various canine OMM treatment options was low. The majority of studies included confounding treatment modalities and lacked randomization, control groups and consistency in reporting clinical response and outcomes. Within these limitations, surgery remains the mainstay of therapy. Adjunctive radiotherapy provided good local control and improved median survival times (MST), chemotherapy did not offer survival benefit beyond that of surgery, while electrochemotherapy may offer a potential alternative to radiotherapy. Immunotherapy holds the most promise in extending MST in the surgical adjunctive setting, in particular the combination of gene therapy and autologous vaccination. Prospective, randomized, double-blinded clinical trials, with a lack of confounding factors and reporting based on established guidelines would allow comparison and recommendations for the treatment of canine OMM.

Macroscopic thromboembolic disease has been associated with canine neoplasia, whereas prevalence studies of concurrent microthrombi and tumour‐cell emboli are lacking. This retrospective study investigated microthrombi and tumour cell emboli by reviewing pathology records of dogs diagnosed with lymphoma, sarcoma, carcinoma and mast cell tumours with a concurrent description of thrombi or emboli. Pathology reports and medical records of cases with either tumour biopsies and/or post mortems with a diagnosis of neoplasia were reviewed for the presence of microthrombi, macrothrombi and/or tumour‐cell emboli and the association with tumour type. Of the 28 895 canine cases in the database, 21 252 (73.5%) were antemortem biopsy specimens and 7643 were post mortems (26.5%); 2274 solid tumours were identified, 2107 (92.7%) were antemortem biopsy diagnoses and 167 (7.3%) were post mortem diagnoses. The prevalence of solid tumour types in the database (28 895 cases) was 872 (3.0%) lymphoma, 722 (2.5%) sarcoma, 455 (1.6%) carcinoma and 225 (0.8%) mast cell tumour. The prevalence of microthrombi associated with these tumours was 58/2274 (2.6%). Intra‐tumoral microthrombi were reported in 53/2274 (2.3%) cases, the majority in sarcomas (37/53, 69.8%). No macrothrombi were reported. Tumour‐cell emboli were identified in 39/2274 (1.7%) cases, 31/39 (79.5%) were extra‐tumoral or distant emboli, and carcinoma the most commonly associated tumour (29/39; 74.4%). Microthrombi were reported in 2.6% of cases, the majority in sarcomas and tumour‐cell emboli were identified in 1.7% of cases, the majority carcinomas. Prospective investigations are necessary to explore the potential clinical and prognostic implications of microthrombi and tumour‐cell emboli in canine neoplasia.