Mutations in Exons 8 and 11 of c-kit Gene in Canine Subcutaneous Mast Cell Tumors and Their Association with Cell Proliferation

The prognostic significance of internal tandem duplication (ITD) mutations in exons 8 and 11 of c-kit has been well-described for canine cutaneous mast cell tumors (MCTs), but c-kit mutations have rarely been reported in subcutaneous MCTs. The objective of this study was to identify the prevalence of ITD mutations in exons 8 and 11 of c-kit in canine subcutaneous MCTs and to investigate its association with histologic grade, KIT pattern, and proliferation markers. ITD mutations in exons 8 and 11 of c-kit, mitotic count, Ki67 index, AgNOR number, Ki67xAgNOR score, KIT pattern, and histologic grade (two-tier system) were retrospectively recorded for 216 dogs with subcutaneous MCTs. ITD mutations in exons 8 and 11 of c-kit were detected in 23 (10.6%) and 12 (5.56%) subcutaneous MCTs, respectively. Exon 11 mutations were significantly associated with Kiupel high grade (p < 0.001) and increased mitotic count (p < 0.001) compared to subcutaneous MCTs with no mutations in exons 8 or 11 (p = 0.002) or subcutaneous MCTs with a mutation in exon 8 (p = 0.001). There was no significant association of either c-kit mutation with KIT patterns or proliferation activity. This study identified a higher prevalence of ITD mutations in exons 8 and 11 of c-kit in subcutaneous MCTs than previously reported. Like their cutaneous counterpart, subcutaneous MCTs with exon 11 mutations were more likely to be histologically high grade and have a higher mitotic count, whereas such associations were not observed in subcutaneous MCTs with exon 8 mutations

PID 2129 Recuperación del pastizal natural degradado en un monte nativo sometido a desarbustado mecánico

El objetivo general del proyecto fue evaluar la respuesta del pastizal natural al desarbustado mecánico, en un monte nativo en pastoreo con diferentes grados de enmalezamiento. En un establecimiento agropecuario mixto de Villaguay (Entre Ríos), se determinaron dos niveles de enmalezamiento con especies arbustivas (más del 30% y menos del 30% de cobertura) y en cada situación se estudió el efecto del desarbustado mecánico. Para monitorear la evolución del pastizal ,se midió la cobertura y biomasa del estrato herbáceo y arbustivo, en el período junio/08-agosto/10. Se realizó además toma de muestras de suelo en la situación inicial y final del ensayo (nov/10) para analizar el banco de semillas. Hacia noviembre/09, en las áreas desarbustadas se evidenció una tendencia favorable en la composición del pastizal, registrándose una importante reducción de especies arbustivas.  En áreas sin desarbustar (tanto en las de alta como en las de baja cobertura de arbustivas), si bien las especies forrajeras incrementaron su abundancia-cobertura, las no forrajeras (en especial Baccharis punctulata y Melica macra) mantuvieron valores similares a los iniciales. En el muestreo de marzo/10, se observó  una importante reinfestación con especies arbustivas en el lote en general, resultando mayor en los sectores con alto enmalezamiento inicial. El desarbustado mecánico evidenció una mayor eficiencia al aplicarse en áreas con bajo enmalezamiento inicial, donde B. punctulata representaba una mayor contribución porcentual  a la cobertura total de especies arbustivas. El impacto de este tipo de prácticas sobre el control de la chilca favoreció el desarrollo de M. macra, especie que incrementó significativamente su cobertura hacia finales del estudio, por lo que para el control de espartillo sería necesario recurrir a una práctica complementaria. De los resultados de este trabajo se deduce que un único desarbustado mecánico resulta insuficiente para el control de B. punctulata y M. macra, requiriéndose la aplicación de un ciclo de desarbustados cuya frecuencia dependerá de cada caso en particular.  Se observó una diferencia sustancial entre la composición de especies del banco de semillas y la vegetación establecida en el pastizal en estudio. A inicios del ensayo, en las áreas con baja cobertura de arbustivas, se determinó una densidad total media de 4093 semillas/m2 en el banco y una riqueza de 24 especies, siendo dominantes Salvia sp. (38,8%) y Polygonum convolvulus (27%). En el muestreo final, la densidad total fue de 6769 semillas/m2, con una riqueza específica de 9 especies, siendo las  dominantes una leguminosa (36%) y Stellaria media (32%).  En las áreas con alta cobertura inicial de arbustivas, la densidad total a inicios del ensayo fue de 2853 semillas/m2, mientras que la riqueza fue de 13 especies.  Una especie aún no identificada fue la que aportó la mayor densidad de semillas al banco (27,6%), seguida por Polygonum sp (15,4%) y Salvia sp. (10,4%). Al final del estudio se registró una densidad de 11076 semillas/m2. Paspalum sp. y Salvia sp. resultaron las especies de mayor aporte al banco (23% y 15%, respectivamente)

Case report: Sublingual mucinosis in a dog

Oral focal mucinosis (OFM) is a rare clinic-pathological condition histologically similar to focal skin mucinosis and thus, OFM is considered as the oral counterpart of cutaneous focal mucinosis (1, 2). Cutaneous mucinosis refers to an excessive deposition of mucinous substance in the dermis that clinically manifests as a thickening of the skin or as a vesicular appearance (3, 4). A generalized cutaneous mucinosis, of likely genetic origin, occurs primarily in Shar-pei dogs, giving them its characteristic appearance (5). In other breeds, severe mucinosis is associated with secondary diseases such as intertrigo, bacterial infections and entropion, all of which can lead to severe deterioration in the health of the animal (6). In human, OFM was first described and named by Tomich in 1974 (1). Its pathogenesis is still unclear, but an increased production of hyaluronic acid (HA) by fibroblasts in expense of collagen production and myxoid degeneration is suggested (7, 8). Clinically, oral lesions often present as a small (<1 cm) submucosal, single, pink, and slow-growing asymptomatic nodule containing gelatinous material (8, 9). The gingiva and palate are the most affected sites (9, 10). OFM has already been reported in literature in a dog as a nodular lesion on the buccal mucosa (11). This is the first case described with this type of presentation

A Retrospective Clinico-Pathologic Study of 35 Dogs with Urethral Transitional Cell Carcinoma Undergoing Treatment

: Chemotherapy and cyclooxygenase inhibitors (COXi) are primary treatments for canine urethral transitional cell carcinoma (uTCC), a tumor known for its aggressiveness and poor prognosis. This retrospective study aimed to evaluate the clinico-pathological characteristics, treatment modalities, and prognostic factors of 35 dogs with confirmed uTCC that received chemotherapy and COXi. Upon admission, urethral obstruction (UO) and urinary tract infection (UTI) were observed in seven (20%) dogs each. Gemcitabine (n = 20; 57.1%) and vinblastine (n = 10; 28.6%) were commonly used as first-line therapies, with four dogs also receiving radiation therapy. Based on RECIST, one (2.9%) dog achieved complete remission, nine (25.7%) partial remission, 20 (57.14%) showed stable disease, and five (14.3%) progressed. Among dogs with UO, six (85.7%) showed resolution or improvement after the first chemotherapy dose. The median time to local progression was 171 days (range: 107-235), and the median survival time was 333 days (range: 158-508). Dogs with UO upon admission had a higher risk of local progression, while both UO and UTI were associated with an increased risk of overall disease progression and tumor-related death. Additionally, gemcitabine significantly improved metastatic control. This study identified UO and UTI as negative prognostic factors, highlighting the importance of a multimodal approach in managing uTCC

Prevalence of p53 dysregulations in feline oral squamous cell carcinoma and non-neoplastic oral mucosa

Squamous cell carcinoma is the most common malignant oral tumor in cats. The late presentation is one of the factors contributing to the detrimental prognosis of this disease. The immunohistochemical expression of the p53 tumor suppressor protein has been reported in 24% to 65% of feline oral squamous cell carcinomas, but no study has systematically evaluated in this tumor the presence of p53 encoding gene (TP53) mutations. The aim of this retrospective study was to determine whether p53 immunohistochemistry accurately reflects the mutational status of the TP53 gene in feline oral squamous cell carcinoma. Additionally, the prevalence of p53 dysregulation in feline oral squamous cell carcinoma was compared with that of feline non-neoplastic oral mucosa, in order to investigate the relevance of these dysregulations in cancer development. The association between p53 dysregulations and exposure to environmental tobacco smoke and tumor characteristics was further assessed. Twenty-six incisional biopsies of oral squamous cell carcinomas and 10 cases each of lingual eosinophilic granuloma, chronic gingivostomatitis and normal oral mucosa were included in the study. Eighteen squamous cell carcinomas (69%) expressed p53 and 18 had mutations in exons 5\u20138 of TP53. The agreement between immunohistochemistry and mutation analysis was 77%. None of non-neoplastic oral mucosa samples had a positive immunohistochemical staining, while one case each of eosinophilic granuloma and chronic gingivostomatitis harbored TP53 mutations. Unlike previously hypothesized, p53 dysregulations were not associated with exposure to environmental tobacco smoke. These results suggest an important role of p53 in feline oral tumorigenesis. Additionally, the immunohistochemical detection of p53 expression appears to reflect the presence of TP53 mutations in the majority of cases. It remains to be determined if the screening for p53 dysregulations, alone or in association with other markers, can eventually contribute to the early detection of this devastating disease

Evaluation of Ki-67 expression in feline non-ocular melanocytic tumours

Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P  5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. Conclusions Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker

Clinical Features and Outcome of 79 Dogs With Digital Squamous Cell Carcinoma Undergoing Treatment: A SIONCOV Observational Study

In dogs, digit squamous cell carcinoma (SCC) is uncommon. Clinical signs are frequently underestimated, leading to a diagnostic delay. The purpose of this retrospective study was to report our experience regarding the clinical presentation, diagnostic work-up, treatment and outcome of 79 client-owned dogs with SCC of the digit. The greatest majority (84.8%) of dogs was dark-coated. Schnauzers represented approximately one third of the study population, and had a poorer outcome compared with other breeds. The majority of SCCs occurred in the front limbs (61%), and bone lysis was frequently observed (92.4%). Approximately 9% of dogs had involvement of multiple digits, and this was associated with a shorter time to progression (TTP; P = 0.047). Similarly, a duration of clinical signs >90 days was associated with a shorter TTP (P = 0.02). Regional lymph node metastases were documented in 17.7% of dogs at admission and were significantly associated with tumor-related death (P < 0.001). At presentation, none of the dogs had evidence of distant metastasis. Digit amputation achieved adequate local tumor control in the majority of cases. Adjuvant chemotherapy and radiation therapy were carried out in 21.5% of cases, with uncertain benefit. Due to the relatively non-aggressive clinical behavior of digit SCC, chemotherapy should only be offered in the case of metastatic disease. Approximately one fourth of dogs developed de novo SCCs during the follow-up. Careful examination of the digits should be encouraged in breeds considered at high risk and in dogs with a previous history of digital SCC

The effects of primary care monitoring strategies on COVID-19 related hospitalisation and mortality: a retrospective electronic medical records review in a northern Italian province, the MAGMA study

Background: Most symptomatic SARS-CoV-2 infections produce mild to moderate symptoms. Although most patients are managed in the outpatient setting, little is known about the effect of general practitioners' (GP) management strategies on the outcomes of COVID-19 outpatients in Italy. Objectives: Describe the management of Italian GPs of SARS-CoV-2 infected adult patients and explore whether GP active care and monitoring are associated with reducing hospitalisation and death. Methods: Retrospective observational study of SARS-CoV-2 infected adult outpatients managed by GPs in Modena (Italy) from March 2020 to April 2021. Information on management and monitoring strategies, patients' socio-demographic characteristics, comorbidities, and outcomes (hospitalisation and death due to COVID-19) were retrieved through an electronic medical record review and analysed descriptively and through multiple logistic regression. Results: Out of the 5340 patients from 46 GPs included in the study, 3014 (56%) received remote monitoring, and 840 (16%) had at least one home visit. More than 85% of severe or critical patients were actively monitored (73% daily) and 52% were visited at home. Changes over time in patients' therapeutic management were observed in concordance with the guidelines' release. Active daily remote monitoring and home visits were strongly associated with reduced hospitalisation rate (OR 0.52, 95% CI 0.33-0.80 and OR 0.50, 95% CI 0.33-0.78 respectively). Conclusion: GPs effectively managed an increasing number of outpatients during the first waves of the pandemic. Active monitoring and home visits were associated with reduced hospitalisation in COVID-19 outpatients