Mast cells are upregulated in hidradenitis suppurativa tissue, associated with epithelialized tunnels and normalized by spleen tyrosine kinase antagonism.

Mast cells have traditionally been associated with allergic inflammatory responses; however, they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing-associated pathways; however, the role of mast cells in the disease is unexplored. We demonstrate that mast cell-associated gene expression (using whole tissue RNAseq) is upregulated, and in-silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive mast cells (identified using IHC) localize adjacent to epithelialized tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF-alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell-associated gene transcripts, associated biochemical pathways and the number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is paralleled with B cell/plasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.

Habitat and climate influence hybridization among three genetically distinct Canada jay (Perisoreus canadensis) morphotypes in an avian hybrid zone complex.

Examining the frequency and distribution of hybrids across contact zones provide insights into the factors mediating hybridization. In this study, we examined the effect of habitat and climate on hybridization patterns for three phenotypically, genetically, and ecologically distinct groups of the Canada jay (Perisoreus canadensis) in a secondary contact zone in western North America. Additionally, we tested whether the frequency of hybridization involving the three groups (referred to as Boreal, Pacific and Rocky Mountain morphotypes) is similar across the hybrid zones or whether some pairs have hybridized more frequently than others. We reanalyzed microsatellite, mtDNA and plumage data, and new microsatellite and plumage data for 526 individuals to identify putative genetic and phenotypic hybrids. The genetically and phenotypically distinct groups are associated with different habitats and occupy distinct climate niches across the contact zone. Most putative genetic hybrids (86%) had Rocky Mountain ancestry. Hybrids were observed most commonly in intermediate climate niches and in habitats where Engelmann spruce (Picea engelmannii) overlaps broadly with boreal and subalpine tree species. Our finding that hybrids occupy intermediate climate niches relative to parental morphotypes matches patterns for other plant and animal species found in this region. This study demonstrates how habitat and climate influence hybridization patterns in areas of secondary contact and adds to the growing body of research on tri-species hybrid zones.

Whole-genome sequencing links cases dispersed in time, place, and person while supporting healthcare worker management in an outbreak of Panton-Valentine leucocidin meticillin-resistant Staphylococcus aureus; and a review of literature.

This is a report on an outbreak of Panton-Valentine leucocidin-producing meticillin-resistant Staphylococcus aureus (PVL-MRSA) in an intensive care unit (ICU) during the COVID-19 pandemic that affected seven patients and a member of staff. Six patients were infected over a period of ten months on ICU by the same strain of PVL-MRSA, and a historic case identified outside of the ICU. All cases were linked to a healthcare worker (HCW) who was colonized with the organism. Failed topical decolonization therapy, without systemic antibiotic therapy, resulted in ongoing transmission and one preventable acquisition of PVL-MRSA. The outbreak identifies the support that may be needed for HCWs implicated in outbreaks. It also demonstrates the role of whole-genome sequencing in identifying dispersed and historic cases related to the outbreak, which in turn aids decision-making in outbreak management and HCW support. This report also includes a review of literature of PVL-MRSA-associated outbreaks in healthcare and highlights the need for review of current national guidance in the management of HCWs' decolonization regimen and return-to-work recommendations in such outbreaks.

Choice between food and cocaine or fentanyl reinforcers under fixed and variable schedules in female and male rhesus monkeys.

RATIONALE: Illicit drugs may be unpredictable in terms of the time and effort required to obtain them, and this can be modeled with variable- (VR) vs. fixed-ratio (FR) schedules. In a recent experiment (Zamarripa et al. 2023), the potency of cocaine to maintain choice was greatest under a VR (compared with a FR) when food was available under a FR schedule. OBJECTIVES: The goal of the current study was to extend prior choice results with VR vs. FR schedules to a more efficient procedure with cocaine or fentanyl vs. food. Furthermore, the FR schedule of food delivery was manipulated to determine whether increased drug choice under a VR (compared with a FR) schedule depends on the size of the schedule of nondrug reinforcement. METHODS: Adult female (n = 2) and male (n = 4) monkeys chose between cocaine (0-30 µg/kg/injection) or fentanyl (0-1.0 µg/kg/injection) and food (2 pellets/delivery) under a 5-component procedure. In different conditions, food was available under a FR 25, 50, or 100 and cocaine or fentanyl were available under FR or VR 100 schedules. RESULTS: Cocaine's potency to maintain choice was greatest under a VR 100 (compared with FR 100) when food was available under a FR 50 or 100, and fentanyl's potency to maintain choice was generally greatest under a VR 100 (compared with FR 100) when food was available under a FR 25 or 100. However, outcomes between FR and VR schedules with fentanyl were less robust compared with cocaine. CONCLUSION: Variability in the time and effort required to obtain illicit drugs could contribute to excessive allocation of behavior toward drug use at the expense of more predictable nondrug alternatives, supporting treatment or policies aimed at making drug access more predictable through agonist medications or a safe supply. The impact of variable requirements on drug choice may be reduced if nondrug reinforcers are relatively less costly, supporting the use of low-cost reinforcers in behavioral therapies like contingency management.

Cancer detection in clinical practice and using blood-based liquid biopsy: A retrospective audit of over 350 dogs.

BACKGROUND: Guidelines-driven screening protocols for early cancer detection in dogs are lacking, and cancer often is detected at advanced stages. HYPOTHESIS/OBJECTIVES: To examine how cancer typically is detected in dogs and whether the addition of a next-generation sequencing-based "liquid biopsy" test to a wellness visit has the potential to enhance cancer detection. ANIMALS: Client-owned dogs with definitive cancer diagnoses enrolled in a clinical validation study for a novel blood-based multicancer early detection test. METHODS: Retrospective medical record review was performed to establish the history and presenting complaint that ultimately led to a definitive cancer diagnosis. Blood samples were subjected to DNA extraction, library preparation, and next-generation sequencing. Sequencing data were analyzed using an internally developed bioinformatics pipeline to detect genomic alterations associated with the presence of cancer. RESULTS: In an unselected cohort of 359 cancer-diagnosed dogs, 4% of cases were detected during a wellness visit, 8% were detected incidentally, and 88% were detected after the owner reported clinical signs suggestive of cancer. Liquid biopsy detected disease in 54.7% (95% confidence interval [CI], 49.5%-59.8%) of patients, including 32% of dogs with early-stage cancer, 48% of preclinical dogs, and 84% of dogs with advanced-stage disease. CONCLUSIONS/CLINICAL IMPORTANCE: Most cases of cancer were diagnosed after the onset of clinical signs; only 4% of dogs had cancer detected using the current standard of care (i.e., wellness visit). Liquid biopsy has the potential to increase detection of cancer when added to a dog's wellness visit.

Optimising the use of physiotherapy resources after manipulation under anaesthetic for frozen shoulder.

INTRODUCTION: Manipulation under anaesthetic (MUA) is a successful treatment for frozen shoulder (FS), and the recovery period and recurrence rates may be reduced by postoperative physiotherapy. This study evaluates two physiotherapy pathways for patients undergoing MUA for FS. METHODS: Between 2016 and 2018, 248 age- and sex-matched patients presented to either a NHS secondary care upper limb service or the lead author's independent practice with a diagnosis of FS. The patients had differential access to postprocedure physiotherapy based on which service they presented to. In Group 1, physiotherapy advice only was given to the patient. In Group 2, supervised hydrotherapy and physiotherapy occurred postoperatively. Pre- and postprocedure Oxford Shoulder Scores (OSS) were collected for each group. Analysis of covariance (ANCOVA) was used to measure the effect of physiotherapy on postoperative OSS. RESULTS: Group 2 showed a significantly greater improvement in postprocedure OSS when compared with Group 1 (18.2 vs 16.7) p<0.001). The estimated maximum effect of physiotherapy on postoperative OSS was an increase of 3.2. CONCLUSION: Following MUA for FS, a statistically significant increase in OSS was detected in patients receiving postprocedure physiotherapy compared with advice alone. There was no difference in recurrence rates. The increase in OSS (3.2) is below the minimal clinically important difference, raising questions regarding the relative importance of postprocedure physiotherapy in a resource-limited environment.

Synthesis and Stability Studies of a Simplified, Thiazole-Containing Macrocycle of the Anticancer Agent Salarin C.

While salarin C (SalaC) is a potent marine cytotoxin, Kashman demonstrated that congeners which had undergone Wasserman rearrangement exhibit little to no cytotoxicity. Given that thiazoles are known to undergo Wasserman rearrangement at a significantly reduced rate, we hypothesized that a thiazole-containing SalaC would exhibit greater stability without significantly altering the macrocyclic conformation. Herein, we describe the synthesis of a simplified, thiazole-containing macrocycle which demonstrates significantly improved stability under identical aerobic conditions.

The COVANOS trial - insight into post-COVID olfactory dysfunction and the role of smell training.

BACKGROUND: Olfactory dysfunction is a cardinal symptom of COVID-19 infection, however, studies assessing long-term olfactory dysfunction are limited and no randomised-controlled trials (RCTs) of early olfactory training have been conducted. METHODOLOGY: We conducted a prospective, multi-centre study consisting of baseline psychophysical measurements of smell and taste function. Eligible participants were further recruited into a 12-week RCT of olfactory training versus control (safety information). Patient-reported outcomes were measured using an electronic survey and BSIT at baseline and 12 weeks. An additional 1-year follow-up was open to all participants. RESULTS: 218 individuals with a sudden loss of sense of smell of at least 4-weeks were recruited. Psychophysical smell loss was observed in only 32.1%; 63 participants were recruited into the RCT. The absolute difference in BSIT improvement after 12 weeks was 0.45 higher in the intervention arm. 76 participants completed 1-year follow-up; 10/19 (52.6%) of participants with an abnormal baseline BSIT test scored below the normal threshold at 1-year, and 24/29 (82.8%) had persistent parosmia. CONCLUSIONS: Early olfactory training may be helpful, although our findings are inconclusive. Notably, a number of individuals who completed the 1-year assessment had persistent smell loss and parosmia at 1-year. As such, both should be considered important entities of long-Covid and further studies to improve management are highly warranted.

Diagnosis and histopathologic prognostication of canine melanocytic neoplasms: A consensus of the Oncology-Pathology Working Group.

One of the primary objectives of the Oncology Pathology Working Group (OPWG) is for oncologists and pathologists to collaboratively generate consensus documents to standardize aspects of and provide guidelines for veterinary oncologic pathology. Consensus is established through review of relevant peer-reviewed literature relative to a subgroup's particular focus. In this article, the authors provide a critical review of the current literature for the diagnosis of, and histopathologic prognostication for, canine cutaneous and oral/lip melanocytic neoplasms, suggest guidelines for reporting, provide recommendations for clinical interpretation, and discuss future directions. This document represents the opinions of the working group and the authors and does not constitute a formal endorsement by the American College of Veterinary Pathologists, American College of Veterinary Internal Medicine or the Veterinary Cancer Society.

Clinical validation of a next-generation sequencing-based multi-cancer early detection "liquid biopsy" blood test in over 1,000 dogs using an independent testing set: The CANcer Detection in Dogs (CANDiD) study.

Cancer is the leading cause of death in dogs, yet there are no established screening paradigms for early detection. Liquid biopsy methods that interrogate cancer-derived genomic alterations in cell-free DNA in blood are being adopted for multi-cancer early detection in human medicine and are now available for veterinary use. The CANcer Detection in Dogs (CANDiD) study is an international, multi-center clinical study designed to validate the performance of a novel multi-cancer early detection "liquid biopsy" test developed for noninvasive detection and characterization of cancer in dogs using next-generation sequencing (NGS) of blood-derived DNA; study results are reported here. In total, 1,358 cancer-diagnosed and presumably cancer-free dogs were enrolled in the study, representing the range of breeds, weights, ages, and cancer types seen in routine clinical practice; 1,100 subjects met inclusion criteria for analysis and were used in the validation of the test. Overall, the liquid biopsy test demonstrated a 54.7% (95% CI: 49.3-60.0%) sensitivity and a 98.5% (95% CI: 97.0-99.3%) specificity. For three of the most aggressive canine cancers (lymphoma, hemangiosarcoma, osteosarcoma), the detection rate was 85.4% (95% CI: 78.4-90.9%); and for eight of the most common canine cancers (lymphoma, hemangiosarcoma, osteosarcoma, soft tissue sarcoma, mast cell tumor, mammary gland carcinoma, anal sac adenocarcinoma, malignant melanoma), the detection rate was 61.9% (95% CI: 55.3-68.1%). The test detected cancer signal in patients representing 30 distinct cancer types and provided a Cancer Signal Origin prediction for a subset of patients with hematological malignancies. Furthermore, the test accurately detected cancer signal in four presumably cancer-free subjects before the onset of clinical signs, further supporting the utility of liquid biopsy as an early detection test. Taken together, these findings demonstrate that NGS-based liquid biopsy can offer a novel option for noninvasive multi-cancer detection in dogs.

Circulating Endocannabinoids in Canine Multicentric Lymphoma Patients.

The endocannabinoid system is increasingly being implicated in the pathogenesis and progression of various human cancers. Specifically, increased levels of 2-arachidonoylglycerol (2-AG) and oleoythanolamide (OEA) have been demonstrated in human diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL) patients, respectively. The objectives of this paper were to compare 2-AG, OEA, N-arachidonoylethanolamine (AEA), and palmitoylethanolamide (PEA) levels between dogs with multicentric lymphoma and healthy control dogs. In addition, evaluate 2-AG, OEA, AEA, and PEA levels as biomarkers for progression free interval (PFI) and overall survival time (OST) in the dogs with lymphoma. The study consisted of 26 dogs with multicentric B cell lymphoma, 14 dogs with multicentric T cell lymphoma, and 12 healthy control dogs. Serum 2-AG, OEA, AEA, and PEA levels were measured using liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) in dogs with lymphoma and in healthy dogs. OEA, AEA, and PEA levels were significantly elevated in dogs with lymphoma compared to healthy controls (p < 0.05). Total AG was significantly higher in healthy control dogs (p = 0.049). There was no significant difference between dogs with B cell and T cell lymphoma for any of the measured endocannabinoids. Elevated PEA was significantly associated with decreased PFI (p = 0.04) in dogs with lymphoma with a hazards ratio of 1.816 [95% Confidence Interval (CI): 1.020-3.232]. Overall, dogs with lymphoma have elevated levels of OEA, AEA, and PEA. PEA levels have the potential to be a prognostic biomarker.

RNA-Seq analysis of gene expression in 25 cases of canine lymphoma undergoing CHOP chemotherapy.

OBJECTIVES: Canine lymphoma, the most common hematological cancer in dogs, shares many molecular and clinical characteristics with human Non-Hodgkin lymphoma (NHL). The standard treatment for canine lymphoma is "CHOP" multiagent chemotherapy protocol consisting of Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Vincristine (Oncovin™), and Prednisone. Approximately 70-85% of patients treated with CHOP achieve clinical remission. However, duration of remission varies and the majority of dogs eventually relapse. To identify possible biomarkers for patients failing to achieve remission, we performed RNA-Seq analysis on 25 cases of canine lymphoma obtained prior the start of their CHOP therapy regime and assessed gene expression associated with patient progression free survival (PFS). DATA DESCRIPTION: The data consists of (1) raw RNA-Seq reads in 75 bp fastq format from fine needle aspirate samples of enlarged lymph nodes from canine patients with naturally occurring lymphoma; (2) Fragments Per Kilobase Million (FPKM) values for each sample; (3) raw transcript counts for each sample; (4) anonymized patient details including PFS; (5) heat map of gene expression and (6) Cox proportional hazard analysis showing significantly expressed genes. These data may be useful for comparative analysis of gene expression in human NHL and analysis of gene expression associated with disease outcome in canine lymphoma.

Imaging in neonatal respiratory disease.

The purpose of this review is to describe the current state of the art in clinical imaging for NICU patients, divided into major areas that correspond to likely phenotypes of neonatal respiratory disease: airway abnormalities, parenchymal disease, and pulmonary vascular disease. All common imaging modalities (ultrasound, X-ray, CT, and MRI) are discussed, with an emphasis on modalities that are most relevant to the individual underlying aspects of disease. Some promising aspects of dynamic and functional imaging are included, where there may be future clinical applicability.

Statin Associated Autoimmune Myonecrosis: Case Report With Delayed Onset and Treatment Challenges.

PURPOSE: A case of delayed statin associated autoimmune myopathy (SAAM) is presented along with review of clinical findings and treatment strategies. SUMMARY: A 54 year old male presented with proximal extremity weakness, difficulty ambulating, and dysphagia. Symptoms began when restarting atorvastatin 40 mg daily for a recent NSTEMI, following 10 years of statin use, interrupted after diagnosis of NASH. Relevant labs included CK of 13,618 IU/L, ALT/ AST of 568/407 IU/L, while additional liver, renal, and toxicology tests were normal. Following treatment response to prednisone 40 mg daily for 3 days, outpatient testing for anti-HMGCR antibodies was ordered.Twelve days from discharge, the patient was readmitted for myalgia and dysphagia, CK = 6042 IU/L, ALT/AST = 360/112 IU/L, and positive anti-HMGCR antibodies. Newly diagnosed with SAAM, symptoms improved with methylprednisolone and intravenous immunoglobulin (IVIG), continuing outpatient as daily prednisone and monthly IVIG. Four days later, the patient relapsed with worsened weakness and dysphagia, CK = 5812 IU/L, and ALT/AST = 647/337 IU/L. After response to methylprednisolone and rituximab, the patient was discharged on a corticosteroid taper, biweekly rituximab, and monthly IVIG. Two weeks later, a final admission involved a syncopal episode and fall, with a CK = 1461 IU/L. Treatment included IVIG, rituximab, and corticosteroid taper, which lead to remission for greater than 6 months. CONCLUSION: Statin associated autoimmune myopathy occurred when restarting atorvastatin, following 10 years of statin use. Clinical findings and positive anti-HMGCR antibodies confirmed the diagnosis. Recurrent relapses required triple combination therapy including addition of rituximab to achieve remission.

Echocardiography-derived septal curvature correlated with invasive hemodynamics in pediatric pulmonary hypertension.

BACKGROUND: Right ventricular function and afterload are associated with clinical outcomes in pulmonary hypertension (PH). MRI-derived interventricular septal curvature has been associated with invasive hemodynamics in PH patients. This study sought to determine the relationship of echocardiography derived septal curvature with invasive hemodynamics in pediatric PH patients. METHODS: A single center chart review identified 56 pediatric patients with PH and 50 control patients with adequate echocardiography to assess septal curvature within one month of initial cardiac catheterization. Echocardiographic indices of septal flattening including end-systolic eccentricity index (EIs), maximum EI (EImax), minimum septal curvature (SCmin), and average SC (SCavg) were determined. RESULTS: PH patients had a median right ventricular systolic pressure of 64 mmHg (interquartile range (IQR) 48-81), mean pulmonary artery pressure of 44 mmHg (IQR 32-57), pulmonary vascular resistance of 7.9 iWU (IQR 4.8-12.9), and pulmonary capillary wedge pressure of 10 mmHg (IQR 8-12). Patients with PH had higher EIs and EImax and lower SCmin and SCavg compared to control patients. SCavg demonstrated the strongest association with right ventricular systolic pressure (R2 0.73, p < 0.0001), mean pulmonary artery pressure (R2 0.63, p < 0.0001), and pulmonary vascular resistance (R2 0.47, p < 0.0001). All septal curvature indices were associated with the composite adverse outcome, including Potts shunt, lung transplantation, and death. SCmin (HR 0.29; 95%CI 0.07-0.97) and SCavg (HR 0.15; 95%CI 0.03-0.72) were the only septal flattening indices associated with death. CONCLUSIONS: Echocardiography derived septal curvature is a non-invasive marker of ventricular afterload and adverse outcomes.

Evaluation of lymphocyte-specific programmed cell death protein 1 receptor expression and cytokines in blood and urine in canine urothelial carcinoma patients.

Urothelial carcinoma (UC) is the most common urinary tumour in dogs. Despite a range of treatment options, prognosis remains poor in dogs. In people, breakthroughs with checkpoint inhibitors have established new standards of care for muscle-invasive bladder cancer patients and elevated levels of programmed cell death protein 1 (PD-1) suggest immune checkpoint blockade may be a novel target for therapy. The goal of this study was to determine if canine UC patients express elevated levels of lymphocyte-specific PD-1 and/or urinary cytokine biomarkers compared to healthy dogs. Paired blood and urine were evaluated in 10 canine UC patients, five cystitis patients and 10 control dogs for lymphocyte-specific PD-1 expression via flow cytometry and relative cytokine expression. In UC patients, PD-1 expression was significantly elevated on CD8+ lymphocytes in urine samples. UC patients had a higher CD4:CD8 ratio in their urine compared to healthy dogs, however, there was no significant variation in the CD8:Treg ratio between any group. Cystitis patients had significantly elevated levels of CD4+ T cells, CD8+ T cells and Tregs in their blood samples compared to UC patients and healthy dogs. Cytokine analysis demonstrated significant elevations in urinary cytokines (granulocyte-macrophage colony-stimulating factor, interferon-gamma [IFN-γ], interleukin (IL)-2, IL-6 IL-7, IL-8 and IL-15, IP-10, KC-like, IL-18, monocyte chemoattractant protein-1 and tumour necrosis factor-alpha). Several of these cytokines have been previously correlated with both lymphocyte-specific PD-1 expression (IFN-γ, IL-2, IL-7 and IL-15) in muscle-invasive urothelial carcinoma in humans. Our results provide evidence of urinary lymphocyte PD-1 expression and future studies could elucidate whether veterinary UC patients will respond favourably to anti-PD-1 immune checkpoint inhibitor therapy.

Managing hospitalized patients with a COPD exacerbation: the role of hospitalists and the multidisciplinary team.

Exacerbations of chronic obstructive pulmonary disease (COPD) are associated with high rates of hospitalizations, costs, and morbidity. Therefore, hospitalists and the multidisciplinary team (hospital team) need to take a proactive approach to ensure patients are effectively managed from hospital admission to postdischarge. Comprehensive screening and diagnostic testing of patients at admission will enable an accurate diagnosis of COPD exacerbations, and severity, as well as other factors that may impact the length of hospital stay. Depending on the exacerbation severity and cause, pharmacotherapies may include short-acting bronchodilators, systemic corticosteroids, and antibiotics. Oxygen and/or ventilatory support may benefit patients with demonstrable hypoxemia. In preparation for discharge, the hospital team should ensure that patients receive the appropriate maintenance therapy, are counseled on their medications including inhalation devices, and proactively discuss smoking cessation and vaccinations. For follow-up, effective communication can be achieved by transferring discharge summaries to the primary care physician via an inpatient case manager. An inpatient case manager can support both the hospitalist and the patient in scheduling follow-up appointments, sending patient reminders, and confirming that a first outpatient visit has occurred. A PubMed search (prior to 26 January 2021) was conducted using terms such as: COPD, exacerbation, hospitalization. This narrative review focuses on the challenges the hospital team encounters in achieving optimal outcomes in the management of patients with COPD exacerbations. Additionally, we propose a novel simplified algorithm that may help the hospital team to be more proactive in the diagnosis and management of patients with COPD exacerbations.

Evaluation of PD-1 and PD-L1 expression in canine urothelial carcinoma cell lines.

Urothelial carcinoma (UC) is the most common urinary tumor in dogs and despite combinational therapies, only modest improvements in survival have been achieved in recent years. Given the utility of monoclonal antibodies against PD-1 and PD-L1 in human UC, we evaluated the protein and mRNA expression in three established canine urothelial carcinoma cell lines. Flow cytometry and western blot analysis confirmed cell line expression of both molecules in varying degrees. Reverse transcription PCR (RT-PCR) documented mRNA expression in all three cell lines for both PD-1 and PD-L1. Fluorescence microscopy was consistent with strong PD-1 and PD-L1 expression in the canine cell lines and was in line with previous human literature. Importantly, the flow cytometry work described in this study revealed higher cell intrinsic PD-1 expression in these cell lines which may have implications for tumor behavior and potential treatment opportunities in the future. Further work is necessary to determine the expression patterns in canine UC and potential for benefit with immunotherapy directed against PD-1 and PD-L1.

Unilateral primary carcinoma of the kidney with central nervous system invasion and vertebral lysis in a cat.

Case summary: A young adult female spayed domestic shorthair cat presented for acute hindlimb weakness and anorexia with a 1-month history of lethargy, hyporexia and weight loss. A mass was palpable in the caudolateral abdomen and the left hindlimb was diffusely edematous. Abdominal ultrasound showed hydronephrosis of the left kidney with suspected hydroureter and heterogeneous tissue in the dorsal abdomen. CT evaluation confirmed a mass extending from the left kidney through the lumbar musculature with hydronephrosis, aortic attenuation, caudal vena caval thrombosis and lysis of vertebrae 4 and 5. Fine-needle aspiration of the mass suggested squamous cell carcinoma. Owing to clinical deterioration, euthanasia was elected. At necropsy, the left kidney was firmly adhered to the lumbar region with tissue that obliterated the musculature and surrounded the aorta and vena cava. There was hydronephrosis of the left kidney. Histopathologic evaluation of the mass revealed islands of neoplastic epithelial cells separated by fibrous connective tissue and areas of gradual keratinization with rare squamous metaplasia. The histologic diagnosis was invasive carcinoma with desmoplasia and vascular invasion. Relevance and novel information: Primary carcinomas of the kidney in cats are rare and this report documents a progression of disease not previously reported in cats. This is the second reported case of a primary carcinoma of renal origin with features of squamous cell carcinoma in a cat, and the first with lumbar and vascular invasion. This is also the first use of kidney injury molecule-1 to help investigate tumor differentiation in cats.