Pharmacological NF-κB inhibition decreases cisplatin chemoresistance in muscle-invasive bladder cancer and reduces cisplatin-induced toxicities.

Most patients with muscle-invasive bladder cancer (MIBC) are not cured with platinum chemotherapy. Up-regulation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) is a major mechanism underlying chemoresistance, suggesting that its pharmacological inhibition may increase platinum efficacy. NF-κB signaling was investigated in two patient cohorts. The Cancer Genome Atlas (TCGA) was used to correlate NF-κB signaling and patient survival. The efficacy of cisplatin plus the NF-κB inhibitor dimethylaminoparthenolide (DMAPT) versus cisplatin or DMAPT alone was tested in vitro. Xenografted and immunocompetent MIBC mouse models were studied in vivo. Platinum-naive claudin-low MIBC showed constitutive NF-κB signaling and this was associated with reduced disease-specific survival in TCGA patients. Chemotherapy up-regulated NF-κB signaling and chemoresistance-associated genes, including SPHK1, PLAUR, and SERPINE1. In mice, DMAPT significantly improved the efficacy of cisplatin in both models. The combination preserved body weight, renal function, and morphology, reduced muscle fatigue and IL-6 serum levels, and did not aggravate immuno-hematological toxicity compared with cisplatin alone. These data provide a rationale for combining NF-κB inhibition with platinum-based chemotherapy and conducting a clinical trial in MIBC patients.

A Retrospective Analysis of Admission Trends and Outcomes in a Wildlife Rescue and Rehabilitation Center in Costa Rica.

The evaluation of data regarding rehabilitation practices provides reference values for comparison purposes among different rehabilitation centers to critically review protocols and efficiently improve each center. The aim of the present work was to present the main causes of admission to Rescate Wildlife Rescue Center for each taxonomic group, to determine the admission factors that influenced the release and mortality, and to determine the predictive factors of release and mortality of wildlife. To this end, a retrospective study was carried out based on 5785 admissions registered in the database of Rescate Wildlife Rescue Center in Costa Rica in 2020 and 2021. Statistical analysis consisted of sample characterization via the analysis of several categorical variables: species, order, class, age group, cause of admission, outcome, clinical classification and days in the hospital, and respective association with the mortality or release rate. Most of the rescue animals were birds (59.3%), then mammals (20.7%), reptiles (17.4%), and finally 'others' (2.6%). The main causes of admission were 'captivity' (34.9%), 'found' (23.3%), and 'trauma' (19.3%). Animals rescued due to 'captivity' and the classes 'birds' and 'reptiles' had the highest release rates. The causes of admission 'trauma' and 'orphanhood' and the class 'birds' had the highest mortality rates. In general, a greater number of days spent in the hospital and membership in the classes 'reptiles', 'juveniles', in need of 'basic care', or 'clinically healthy' were predictors of survival. In contrast, the age groups 'infant' and 'nestling' were predictors of mortality. These results demonstrate the value of maintaining, improving, and studying databases from wildlife rehabilitation centers, as they can provide useful information that can be used to enhance the allocation of economic resources, treatment methods, disease surveillance, public education, and regulatory decision-making, leading to a better understanding of threats to wildlife and subsequent implementation of conservation actions.

Carcinocythemia: First report in a cat and literature review.

A 6-year-old female neutered European Shorthair cat was presented with a 2-day history of lethargy and hyporexia. On physical examination, the cat was slightly depressed and had a 2.5 cm nodule in the left 3rd mammary gland. The hemogram revealed mild leukocytosis with mature neutrophilia and moderate thrombocytopenia. On blood smear evaluation, rare pleomorphic cells, possibly of epithelial origin, were observed mainly at the feathered edge. The animal died about 12 hours after presentation, and a necropsy was performed. On histopathology, the mammary nodule was diagnosed as a tubulopapillary adenocarcinoma with vascular invasion and widespread metastases. Immunocytochemical tests for cytokeratins (AE1/AE3) confirmed the epithelial phenotype of the neoplastic cells observed on the blood smear. The present report describes a feline mammary carcinoma with widespread metastases and the presence of malignant epithelial cells in the peripheral blood referred to as carcinocythemia. This condition has been previously described in people and dogs. To the author's knowledge, this is the first reported case of feline carcinocythemia. As in other species, the phenomenon was associated with a terminal phase of systemic malignancy.

Cytologic and immunocytochemical characterization of feline progressive histiocytosis.

BACKGROUND: Feline Progressive Histiocytosis (FPH) is a cutaneous dendritic cell neoplasm characterized by slow progression and spread to internal organs in the terminal stage. FPH is often misdiagnosed as an inflammatory reaction and has not been fully characterized from a cytologic diagnostic perspective. OBJECTIVES: The purpose of the study was to characterize the cytologic and immunocytochemical aspects useful for FPH diagnosis. METHODS: Fine-needle aspiration cytologic samples of 5 cases of FPH confirmed by skin biopsy and necropsy were evaluated. Immunocytochemistry with antibodies recognizing CD1a, CD1c, CD3, CD11b, CD18, CD21, and MHCII was performed on air-dried, acetone-fixed smears. E-cadherin expression was assessed on paraffin-embedded skin biopsies. Transmission electron microscopy (TEM) was performed in one case. RESULTS: Main cytologic findings on variably cellular samples were characterized by single to cohesive large, round to polygonal cells with intermediate to low N/C ratio, abundant clear homogeneous cytoplasm, and round to oval nuclei with rare bi- to multinucleated atypical cells, associated with low numbers of small lymphocytes and/or neutrophils. Neoplastic cells expressed CD1a, CD1c, CD11b, CD18, and MHCII. Anti-CD3 antibodies identified reactive T cells admixed with the neoplastic cells. E-cadherin expression was observed in all but one case. TEM failed to identify Birbeck granules in one case. CONCLUSIONS: FPH is a distinctive neoplastic lesion composed of nonphagocytizing histiocytes variably admixed with neutrophils and small mature lymphocytes. Immunocytochemical analysis with CD1 is mandatory to confirm a dendritic cell origin. Immunocytochemistry and cytomorphology allowed the specific and rapid diagnosis of FPH on cytologic samples.

Subcutaneous embryonal rhabdomyosarcoma in a dog: cytologic, immunocytochemical, histologic, and ultrastructural features.

A subcutaneous mass on the left antebrachium of an 11-year-old intact female English Pointer dog was evaluated presurgically by cytologic examination and immunocytochemical staining. The sample consisted of discrete, variably sized, markedly pleomorphic neoplastic cells that expressed vimentin with diffuse cytoplasmic staining, desmin with focal paranuclear staining, and myoglobin with diffuse cytoplasmic staining, consistent with a diagnosis of rhabdomyosarcoma. Lymphocytic and histiocytic markers were negative. Aspirates of the enlarged ipsilateral prescapular lymph node were positive for metastatic disease. Surgical excision of the tumor and lymph node were followed by histologic and electron microscopic examination. Histomorphologic appearance of neoplastic cells from the mass and the lymph node paralleled cytologic findings; the histologic diagnosis was round cell variant of embryonal rhabdomyosarcoma. By ultrastructural evaluation, cells contained numerous mitochondria and masses of cytoplasmic tangled myofilaments, features typical of rhabdomyoblasts. The dog received doxorubicin (30 mg/m(2) ) every 3 weeks for 5 treatments. Local recurrence developed 6 months after resection but was not treated. Despite a guarded prognosis and untreated local recurrence, the dog was still alive 18 months after surgery. Cytologic evaluation and immunocytochemical staining were pivotal for the presurgical diagnosis of rhabdomyosarcoma.

Analytical validation of the Sysmex XT-2000iV for cell counts in canine and feline effusions and concordance with cytologic diagnosis.

BACKGROUND: The Sysmex XT-2000iV is a hematology analyzer that combines laser and impedance technology. Its usefulness for determining cell counts in canine and feline intracavitary effusions has not yet been studied. OBJECTIVES: The objectives of this study were to evaluate the analytical performance of the Sysmex XT-2000iV for cell counts in effusions from dogs and cats, and to assess correlation with an impedance counter and concordance with diagnoses based on cytologic findings. METHODS: Effusions (43 pleural, 23 peritoneal, 6 pericardial) were analyzed from 32 dogs and 34 cats. Total nucleated cell count (TNCC), HCT, and RBC count were determined on the Sysmex and compared with those obtained on an impedance counter (Hemat 8, SEAC). Imprecision, linearity, and limit of detection were determined for the Sysmex. An algorithm was designed using quantitative and qualitative data from the Sysmex to classify the effusions and the results were compared with diagnoses based on cytologic findings. RESULTS: Intra-assay and interassay coefficients of variation on the Sysmex were variable. Linearity of TNCC was >or=0.993 for dogs and cats, with the exception of effusions from cats with feline infectious peritonitis, which had delta (Delta) TNC values >3.0. In comparison with the Hemat 8, a proportional error was found for TNCC on the Sysmex. Effusion classification based on the algorithm was concordant with that obtained by cytologic examination in 43/72 (60%) samples. Discordant results usually were due to the misclassification of cells with similar morphology (such as mesothelial and carcinoma cells) in Sysmex scattergrams. CONCLUSION: The Sysmex XT-2000iV provides a precise and accurate TNCC and has moderate concordance with cytologic findings for classifying canine and feline effusions. Although microscopic examination of effusions is necessary to achieve an accurate diagnosis, the Sysmex can provide preliminary information that may be helpful to cytopathologists.