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Obesity-associated chronic conditions (OCC) are prevalent in medically underserved areas of the Southern US. Continuity of care with a primary care provider is associated with reduced preventable healthcare utilization, yet little is known regarding the impact of continuity of care among populations with OCC. This study aimed to examine whether continuity of care protects patients living with OCC and the subgroup with type 2 diabetes (OCC+T2D) from emergency department (ED) and hospitalizations, and whether these effects are modified by race and patient residence in health professional shortage areas (HPSA) METHODS: We conducted a retrospective federated cohort meta-analysis of 2015-2018 data from four large practice-based research networks in the Southern U.S. among adult patients with obesity and one more more additional diagnosed OCC. The outcomes included overall and preventable ED visits and hospitalizations. Continuity of care was assessed at the clinic-level using the Bice-Boxerman Continuity of Care Index RESULTS: A total of 111,437 patients with OCC and 47,071 patients with OCC+T2D from the four large practice-based research networks in the South were included in the meta-analysis. Continuity of Care index varied among sites from a mean (SD) of 0.6 (0.4) to 0.9 (0.2). Meta-analysis demonstrated that, regardless of race or residence in HPSA, continuity of care significantly protected OCC patients from preventable ED visits (IRR:0.95; CI:0.92-0.98) and protected OCC+T2D patients from overall ED visits (IRR:0.92; CI:0.85-0.99), preventable ED visits (IRR:0.95; CI:0.91-0.99), and overall hospitalizations (IRR:0.96; CI:0.93-0.98) CONCLUSION: Improving continuity of care may reduce ED and hospital use for patients with OCC and particularly those with OCC+T2D.

Magnetic resonance imaging (MRI) has been used to evaluate dogs with suspected prostatic neoplasia, however, published studies describing MRI characteristics of canine prostatic neoplasia are currently lacking. The aims of the current retrospective case series study were to describe MRI findings of the pelvic region in dogs with a histopathologic or cytologic diagnosis of prostatic neoplasia. Retrospective analysis of these images was then performed by a board-certified veterinary radiologist for shared imaging characteristics. The most consistent characteristics were heterogeneous hyperintensity of the tumor on T2-weighted images (10/10) and short tau inversion recovery images (10/10), prostatic capsular margin distortion by the tumor (10/10), cavitations (10/10), complete effacement of the prostatic architecture (9/10), neurovascular bundle (NVB) compression or invasion (9/10), heterogeneous isointensity of the tumor on T1-weighted images (9/10), and strong contrast enhancement of the tumor (8/10). Additional features included an overlying pattern of distorted radiating striations (7/10), regional lymphadenomegaly (5/10), mineralization within the mass (5/10), urinary bladder trigone involvement (6/10), and post-prostatic urethral involvement (7/10). These findings supported the use of MRI as an adjunct imaging modality for diagnosis and therapeutic planning of prostatic neoplasia and including prostatic neoplasia as a likely differential diagnosis for dogs with these MRI characteristics.

Supplementary Table 3 contains a summary of the outcomes, with statistical comparisons, of the dogs enrolled in the SOC clinical trial arm. This includes the DFI and outcomes of the groups of dogs stratified by tumor location and ALP status.

Supplementary Fig. 1 depicts the chronology of clinical trial visits and associated procedures for dogs enrolled in this clinical trial.

Background: Germline genetic variants in PLCE1 (10q23) have demonstrated consistent associations with risk of esophageal squamous cell carcinoma (ESCC) and gastric cancer among Chinese. We evaluated PLCE1 mRNA and protein expression in paired tumor-normal tissues, and their relationship with survival.Methods:PLCE1 mRNA was profiled using three probes in the Affymetrix GeneChip U133 for paired tumor-normal tissues of ESCC (n = 132), gastric cardia adenocarcinoma (GCA, n = 62), and gastric noncardia adenocarcinoma (GNCA, n = 72). We used immunohistochemistry to detect PLCE1 protein on slides from tissue microarrays in paired tumor-normal tissues of ESCC (n = 303), and tumors of GCA (n = 298) and GNCA (n = 124).Results: Compared with normal tissues, PLCE1 mRNA expression was significantly reduced in ESCC tumors (P = 0.03, probe_205112_at), as well as in GCA and GNCA tumors (P < 0.0001, each probe). Protein expression was nonsignificantly reduced in ESCC tumors (P = 0.51). Increased tumor-normal mRNA fold change (probe_205112_at) was associated with longer survival in ESCC (9.6 months for highest vs. lowest quartile; Ptrend = 0.02). Increased mRNA tumor-normal fold change (probe_205111_at) was associated with longer survival for GCA (10.7 months for highest quartile; Ptrend = 0.04), but not for GNCA cases (P = 0.72). Similar to mRNA, elevated tumor-normal fold change for protein in ESCC was also associated with improved survival (8.1 months for highest quartile; Ptrend = 0.04).Conclusions: Dysregulated PLCE1 mRNA expression was observed for both ESCC (one probe only) and GCA tumors, and the altered PLCE1 expression seems to be associated with cancer prognosis.Impact: A potential role for PLCE1 in the early detection and/or therapy of ESCC and GCA warrants further investigation. Cancer Epidemiol Biomarkers Prev; 23(8); 1579–88. ©2014 AACR.

Supplementary Table 2 contains the summary comparison of both the Intent-to-treat and Per-protocol analyses of clinical outcomes for dogs enrolled in Standard of Care (SOC) and Standard of Care + sirolimus

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Purpose:The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression.Patients and Methods:A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes.Results:There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively.Conclusions:In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

PDF - 194K, Supplementary Figure S1. Immunohistochemistry for PLCE1 protein expression with areas of annotation selected for image quantification (20x.)Supplementary Table S1. PLCE1 mRNA expression in GCA, GNCA and ESCC tumor tissues and tumor-normal expression fold change by characteristics of the subjects. Supplementary Table S2. PLCE1 protein expression in GCA, GNCA and ESCC tumor tissues and tumor-normal expression fold change in ESCC by characteristics of the participants. Supplementary Table S3. The probe-specific association between PLCE1 mRNA expression in tumors and tumor-normal fold change and mortality of ESCC, GCA, and GNCAs. Supplementary Table S4. Spearman correlation coefficients (P values) between PLCE1 mRNA expression in normal tissues of ESCC, GCA, and GNCA and selected PLCE1 SNPs.

Supplementary Table 4 contains a summary of the outcomes, with statistical comparisons, of the dogs enrolled in the SOC + sirolimus clinical trial arm. This includes the DFI and outcomes of the groups of dogs stratified by tumor location and ALP status.

Supplementary Table 1 contains the inclusion and exclusion criteria for pet dogs considered for enrollment into the SOC and SOC + S clinical trial arms.

Supplementary Fig. 2 shows the walk-in pharmacokinetics, both measured results and simulated values, for dogs treated with oral sirolimus in preparation for the definitive adjuvant trial.

Purpose:Only one chemical class of topoisomerase I (TOP1) inhibitors is FDA approved, the camptothecins with irinotecan and topotecan widely used. Because of their limitations (chemical instability, drug efflux-mediated resistance, and diarrhea), novel TOP1 inhibitors are warranted. Indenoisoquinoline non-camptothecin topoisomerase I (TOP1) inhibitors overcome chemical instability and drug resistance that limit camptothecin use. Three indenoisoquinolines, LMP400 (indotecan), LMP776 (indimitecan), and LMP744, were examined in a phase I study for lymphoma-bearing dogs to evaluate differential efficacy, pharmacodynamics, toxicology, and pharmacokinetics.Experimental Design:Eighty-four client-owned dogs with lymphomas were enrolled in dose-escalation cohorts for each indenoisoquinoline, with an expansion phase for LMP744. Efficacy, tolerability, pharmacokinetics, and target engagement were determined.Results:The MTDs were 17.5 mg/m2 for LMP 776 and 100 mg/m2 for LMP744; bone marrow toxicity was dose-limiting; up to 65 mg/m2 LMP400 was well-tolerated and MTD was not reached. None of the drugs induced notable diarrhea. Sustained tumor accumulation was observed for LMP744; γH2AX induction was demonstrated in tumors 2 and 6 hours after treatment; a decrease in TOP1 protein was observed in most lymphoma samples across all compounds and dose levels, which is consistent with the fact that tumor response was also observed at low doses LMP744. Objective responses were documented for all indenoisoquinolines; efficacy (13/19 dogs) was greatest for LMP744.Conclusions:These results demonstrate proof-of-mechanism for indenoisoquinoline TOP1 inhibitors supporting their further clinical development. They also highlight the value of the NCI Comparative Oncology Program (https://ccr.cancer.gov/Comparative-Oncology-Program) for evaluating novel therapies in immunocompetent pets with cancers.

Problem: West Virginia perennially leads the US in child obesity and adult heart disease. We had screened over 100,000 school children for cardiometabolic risk factors (CMRF) in the Coronary Artery Risk Detection in Appalachian Communities (CARDIAC) program over 20 years until the 2017 economic downturn. 60,000 had lipid panels. WVU Health System includes encounters with over 200,000 WV children. We hypothesize that CMRF screening has decreased without the statewide CARDIAC Program. Methods: We queried our instance of Epic Electronic Health Record that includes much of northern WV to ascertain BMI, Total Cholesterol (TC) , Low Density Lipoprotein Cholesterol (LDL), triglyceride level (TG) and hemoglobin A1C. We also searched for use of cholesterol-lowering medicines. Results: 137,566 children under 18 years had a BMI measure and we have reported a 5%ile increase in the COVID era. Only 8498 have had a total cholesterol check (avg ± SD 159+34 mg/dl), 9964 had triglyceride (109 ± 74 mg/dl) and 4874 had LDL (92.04 ± 29.8 mg/dl). 2609 children had average HA1C 6.03 ± 1.7%. 607 children had LDL ≥ 130 mg/dl including 174 with LDL ≥ 160 mg/dl. 33 were given lipid-lowering medication and had LDL change from 248 ± 86 mg/dl to 181 ± 42 mg/dl at follow-up. Average decrease was 67 ± 79 mg/dl (p < 0.0001). Conclusion: Few children are being screened for TC, LDL and TG absent the statewide CARDIAC lipid screening program in WV. Lipid-lowering medicines are sparsely used in children with significant risk of Familial Hypercholesterolemia (FH). Family history is not available for the cohort. None in FH range were below the 130 mg/dl LDL target value after treatment. In this pediatric population with usual incidence of FH and high prevalence of dyslipidemia of obesity with high BMI and TG levels, little lipid screening is occurring without the statewide school-based program. Child health care providers need to intervene to prevent even greater WV coronary disease in the future. Policy-makers can impact the future health of WV school children by promoting and funding screening for cardiometabolic risk factors now.

Iron has been emerging as a key contributor to aging-associated, chronic disorders due to the propensity for generating reactive oxygen species. To date, there are a limited number of publications exploring the role of iron in the pathogenesis of primary/age-related osteoarthritis (OA). The objective of this study was to determine whether reduced iron via pharmacologic iron chelation with deferoxamine (DFO) affected the development and/or severity of cartilage lesions in a primary OA model. At 12-weeks-of-age, 15 male Dunkin-Hartley guinea pigs received either 46 mg/kg DFO (n = 8) or vehicle control (n = 7) injected subcutaneously twice daily for five days each week. Movement changes, captured via overhead enclosure monitoring, were also determined. Termination occurred at 30-weeks-of-age. Iron was quantified in serum, urine, liver, and femoral head articular cartilage. Left knees were evaluated for: structural changes using histopathology guidelines; and immunohistochemistry. Gene expression analysis was conducted on right knee articular cartilage. DFO reduced iron levels in femoral head articular cartilage (p = 0.0006) and liver (p = 0.02), and increased iron within urine (p = 0.04) and serum (p = 0.0009). Mobility of control animals declined, while the DFO group maintained activity levels similar to the first month of treatment (p = 0.05). OA-associated cartilage lesions were reduced in knees of DFO animals (p = 0.0001), with chondrocyte hypocellularity a key histologic difference between groups (p 0.0001). DFO-receiving animals had increased immunostaining for phosphorylated adenosine monophosphate activated protein kinase alpha within knee articular cartilage; lower transcript counts of several proapoptotic genes (p = 0.04-0.0004) and matrix-degrading enzymes (p = 0.02-0.0001), and increased expression of the anti-apoptotic gene Bcl-2 (p 0.0001) and a tissue inhibitor of matrix-metalloproteinases (p = 0.03) were also observed. These results suggest that iron chelation delayed the progression of primary OA in an animal model and could hold potential as a translational intervention. These findings provide expanded insight into factors that may contribute to the pathogenesis of primary OA.

The purpose of this study was to determine whether prostatic aspirate culture is a superior method to detect infection compared to culture of urine collected by cystocentesis in dogs with prostatic neoplasia.A prospective study was conducted and dogs with suspected or confirmed prostatic neoplasia were enrolled. Urinalysis was done and culture and antimicrobial susceptibility testing was performed on paired urine and prostatic aspirate samples collected at a single timepoint.Ten dogs with prostatic neoplasia were enrolled. All dogs had one or more clinical sign consistent with lower urinary tract disease. One dog (10%) had a positive urine culture, but negative prostatic aspirate culture, one dog (10%) had a positive prostatic aspirate culture, but negative urine culture, and one dog (10%) had both positive urine and prostatic aspirate cultures. Using prostatic aspirate culture as the reference standard, urine culture had a sensitivity for detecting infection of 87.5% (95% confidence interval 52.9 to 99.4) and specificity of 50% (92.6 to 97.4) in this population of dogs.Positive cultures were uncommon with both culture collection methods. Study results did not identify prostatic aspirate culture to be a more sensitive method of detecting prostatic infection than urine culture collected by cystocentesis in these dogs with prostatic neoplasia.

A diverting loop ileostomy (DLI) is used to protect a distal gastrointestinal anastomosis at risk of leakage. While patients typically prefer early DLI closure, surgeons vary in opinion regarding optimal timing. This study evaluated whether the timing of DLI closure impacts outcomes. A retrospective review was performed on patients who underwent DLI creation within one health care system between 2012 and 2020. Patient characteristics and postoperative outcomes were compared across ileostomies closed in ≤2 months, 2-4 months, and >4 months. Outcomes examined included anastomotic leak, other complications, reintervention, and death within 30 days. A total of 500 DLIs were analyzed for the study, 455 of which were closed. The three closure groups were similar in patient characteristics and comorbidities. None of the outcome variables analyzed in this study demonstrated a statistically significant difference between groups, suggesting that in patients otherwise fit for surgery, DLI closure can be safely performed within 2 months of creation.

Biliary dyskinesia (BD) is a well-established gallbladder pathology in adult patients and rates of cholecystectomy for BD continue to rise in the United States. Many pediatric patients with vague abdominal pain of variable duration are evaluated for biliary dyskinesia. It remains unknown which cohort of pediatric patients diagnosed with BD are most likely to have sustained improvement in symptoms following laparoscopic cholecystectomy. We aimed to determine whether cholecystectomy resulted in symptom relief and led to a reduction in the number of medical visits related to gastrointestinal (GI) symptoms after surgery. We performed a multi-institution retrospective review of all children

PurposeAlthough recombinant human interleukin-15 (rhIL-15) has generated much excitement as an immunotherapeutic agent for cancer, activity in human clinical trials has been modest to date, in part due to the risks of toxicity with significant dose escalation. Since pulmonary metastases are a major site of distant failure in human and dog cancers, we sought to investigate inhaled rhIL-15 in dogs with naturally occurring lung metastases from osteosarcoma (OSA) or melanoma. We hypothesized a favorable benefit/risk profile given the concentrated delivery to the lungs with decreased systemic exposure.Experimental designWe performed a phase I trial of inhaled rhIL-15 in dogs with gross pulmonary metastases using a traditional 3+3 cohort design. A starting dose of 10 µg twice daily × 14 days was used based on human, non-human primate, and murine studies. Safety, dose-limiting toxicities (DLT), and maximum tolerated dose (MTD) were the primary objectives, while response rates, progression-free and overall survival (OS), and pharmacokinetic and immune correlative analyses were secondary.ResultsFrom October 2018 to December 2020, we enrolled 21 dogs with 18 dogs reaching the 28-day response assessment to be evaluable. At dose level 5 (70 μg), we observed two DLTs, thereby establishing 50 µg twice daily × 14 days as the MTD and recommended phase 2 dose. Among 18 evaluable dogs, we observed one complete response >1 year, one partial response with resolution of multiple target lesions, and five stable disease for an overall clinical benefit rate of 39%. Plasma rhIL-15 quantitation revealed detectable and sustained rhIL-15 concentrations between 1-hour and 6 hour postnebulization. Decreased pretreatment lymphocyte counts were significantly associated with clinical benefit. Cytotoxicity assays of banked peripheral blood mononuclear cells revealed significant increases in peak cytotoxicity against canine melanoma and OSA targets that correlated with OS.ConclusionsIn this first-in-dog clinical trial of inhaled rhIL-15 in dogs with advanced metastatic disease, we observed promising clinical activity when administered as a monotherapy for only 14 days. These data have significant clinical and biological implications for both dogs and humans with refractory lung metastases and support exploration of combinatorial therapies using inhaled rhIL-15.

Background: Several reports have observed that cancer patients who recently underwent chemotherapy or surgery had a higher risk of severe events compared with patients without cancer. Limited data is available on outcomes in specific cancer types, as well as the impact of non-cytotoxic systemic treatment, such as targeted therapy and hormonal therapy on severe outcomes. We aim to identify whether active treatment impacts severe outcomes (rate of hospitalization, ICU admission, intubation, and death) in breast cancer patients. Methods: We conducted a multicenter study in the state of Louisiana, throughout the Ochsner Health System, in both tertiary and non-tertiary centers. Patients must carry a diagnosis of breast cancer, and have a completed SARS-CoV-2 test between March 1st and April 30th, 2020. Chi-squared and Fisher’s exact tests were performed to compare the proportion of patients experiencing severe outcomes between treatment groups. Results: As of April 30, 2020, a total of 70 patients with breast cancer who had a positive SARS-COV-2 test were identified. Median age 64.5, median BMI 30.8, 62.9% (n=44) black, 27.1% (n=19) current/former smokers, HTN (n=52) and DM2 (n=22) were the most common comorbidities, and 12.9% (n=9) of patients had stage IV disease. Of these patients, 58.6% (n=41) were on hormonal treatment, and another 12.9% (n=9) were receiving other forms of systemic therapy (cytotoxic chemotherapy or targeted therapy). In terms of severe outcomes, 32.9% (n=23) of patients required hospitalization, 8.6% (n=6) required ICU admission with 7.1% (n=5) patients requiring intubation, 11.4% (n=8) of patients died. There was not a statistical difference in rate of severe outcomes (rate of hospitalization, ICU admission, intubation, and death) among breast cancer patients receiving active treatment (chemotherapy, targeted therapy, or hormonal therapy) vs those receiving no active treatment. There was also no difference in terms of severe outcomes by race. Conclusion: With an ongoing global COVID-19 pandemic, it is important to identify how the treatment and management of cancer impacts COVID-19 outcomes. This small cohort does not identify active treatment as a risk factor for increased rate of severe outcomes in patients with breast cancer. Further analyses describing impact of specific hormonal and chemotherapy regimens on risk of hospitalization and death will be completed by time of presentation. Citation Format: Karine Tawagi, Jeff Burton, Michael Lunski, Diana Maslov, John Cole. Breast cancer and COVID-19: Impact of active treatment on severe outcomes [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-47.

The updated VCOG‐CTCAE v2 guidelines contain several important updates and additions since the last update (v1.1) was released in 2011 and published within Veterinary and Comparative Oncology in 2016. As the Veterinary Cooperative Oncology Group (VCOG) is no longer an active entity, the original authors and contributors to the VCOG‐CTCAE v1.0 and v1.1 were consulted for input, and additional co‐authors sought for expansion and refinement of the adverse event (AE) categories. VCOG‐CTCAE v2 includes expanded neurology, cardiac and immunologic AE sections, and the addition of procedural‐specific AEs. It is our intent that, through inclusion of additional authors from ACVIM subspecialties and the American College of Veterinary Surgery, that we can more comprehensively capture AEs that are observed during clinical studies conducted across a variety of disease states, clinical scenarios, and body systems. It is also our intent that these updated veterinary CTCAE guidelines will offer improved application and ease of use within veterinary practice in general, as well as within clinical trials that assess new therapeutic strategies for animals with a variety of diseases. Throughout the revision process, we strived to ensure the grading structure for each AE category was reflective of the decision‐making process applied to determination of dose‐limiting events. As phase I trial decisions are based on these criteria and ultimately determine the maximally tolerated dose, there is impact on standard dosing recommendations for any new drug registration or application. This document should be updated regularly to reflect ongoing application to clinical studies carried out in veterinary patients.

Mercury (Hg) pollution is an environmental problem that adversely affects human and ecosystem health at local, regional, and global scales—including within New York State. More than two-thirds of the Hg currently released to the environment originates, either directly or indirectly, from human activities. Since the early 1800s, global atmospheric Hg concentrations have increased by three- to eight-fold over natural levels. In the U.S., atmospheric emissions and point-source releases to waterways increased following industrialization into the mid-1980s. Since then, water discharges have largely been curtailed. As a result, Hg emissions, atmospheric concentrations, and deposition over the past few decades have declined across the eastern U.S. Despite these decreases, Hg pollution persists. To inform policy efforts and to advance public understanding, the New York State Energy Research and Development Authority (NYSERDA) sponsored a scientific synthesis of information on Hg in New York State. This effort includes 23 papers focused on Hg in atmospheric deposition, water, fish, and wildlife published in Ecotoxicology. New York State experiences Hg contamination largely due to atmospheric deposition. Some landscapes are inherently sensitive to Hg inputs driven by the transport of inorganic Hg to zones of methylation, the conversion of inorganic Hg to methylmercury, and the bioaccumulation and biomagnification along food webs. Mercury concentrations exceed human and ecological risk thresholds in many areas of New York State, particularly the Adirondacks, Catskills, and parts of Long Island. Mercury concentrations in some biota have declined in the Eastern Great Lakes Lowlands and the Northeastern Highlands over the last four decades, concurrent with decreases in water releases and air emissions from regional and U.S. sources. However, widespread changes have not occurred in other ecoregions of New York State. While the timing and magnitude of the response of Hg levels in biota varies, policies expected to further diminish Hg emissions should continue to decrease Hg concentrations in food webs, yielding benefits to the fish, wildlife, and people of New York State. Anticipated improvements in the Hg status of aquatic ecosystems are likely to be greatest for inland surface waters and should be roughly proportional to declines in atmospheric Hg deposition. Efforts that advance recovery from Hg pollution in recent years have yielded significant progress, but Hg remains a pollutant of concern. Indeed, due to this extensive compilation of Hg observations in biota, it appears that the extent and intensity of the contamination on the New York landscape and waterscape is greater than previously recognized. Understanding the extent of Hg contamination and recovery following decreases in atmospheric Hg deposition will require further study, underscoring the need to continue existing monitoring efforts.

Visceral leiomyosarcoma is well described in dogs, but information about non-visceral locations and prevalence is lacking. The diagnosis of leiomyosarcoma is challenging without a gold standard, and often includes the use of immunohistochemical (IHC) stains. We used defined histopathologic patterns, histochemical staining, and IHC staining for smooth muscle actin (SMA), desmin, and laminin to characterize suspected non-visceral leiomyosarcoma in dogs at a single academic institution. In a retrospective search, we identified 24 dogs with a definitive or suspected histologic diagnosis of leiomyosarcoma in a non-visceral location. Histopathology results and clinical details were obtained. Biopsy sections were reviewed by a single pathologist using standardized histologic criteria, including light microscopic appearance, immunohistochemistry (more than two-thirds of neoplastic cells labeled with SMA and desmin or laminin), and histochemical staining (minimal-to-mild matrix deposition by Masson trichrome). Of the 24 cases of possible non-visceral leiomyosarcomas, 4 were consistent with a definitive diagnosis of non-visceral leiomyosarcoma (3) or leiomyoma (1) based on the established criteria. Only the leiomyoma had more than two-thirds of neoplastic cells label with all 3 markers; all 3 leiomyosarcomas had more than two-thirds of neoplastic cells label with SMA and laminin. Our data highlight the uncommon nature of non-visceral leiomyosarcoma and the importance of IHC for their diagnosis. A definitive diagnosis could not be made based on SMA alone, and desmin was not useful in this cohort. Further studies are needed to clarify the histopathologic, IHC, and clinical features of canine non-visceral SMA-positive mesenchymal tumors.

Nodal small cell B-cell lymphoma subtypes in dogs cannot be distinguished by flow cytometry and information regarding treatment, prognosis, and outcome are limited.Objectives were to describe outcome in dogs with nodal small cell B-cell lymphoma diagnosed by flow cytometry and correlate clinical and laboratory data with survival. We hypothesized that B-cell Ki67 expression measured by flow cytometry is associated with shorter progression free survival (PFS) and overall survival (OS).Forty-nine dogs with nodal small cell B-cell lymphoma, defined by80% CD21+ B-cells by flow cytometry and small-sized B-cells by forward scatter.Retrospective study reviewing treatment and outcome data extracted from medical records. Percentage of Ki67-expressing B-cells was measured by flow cytometry. Clinical, laboratory, and flow cytometry data were assessed for association with outcome.Median percentage of B-cell Ki67 was 41% (range, 3%-97%). Median PFS was 119 days and median OS was 222 days (n = 49). Among cases treated with CHOP-based chemotherapy (n = 32), median PFS was 70 days, median OS was 267 days, and 50% of cases achieved complete response. Low percentage of B-cell Ki67 (≤11%) was associated with prolonged OS by univariable analysis. Greater age, substage B, high B-cell CD25 expression and low B-cell CD21 and class II major histocompatibility complex expression by flow cytometry were independently associated with shorter OS.Most nodal small cell B-cell lymphoma cases had aggressive disease. Low Ki67 expression can help identify cases with better prognosis. Age, substage, and flow cytometry variables are useful prognostic factors.

Aim Improve clerking of vascular patients at Royal Devon and Exeter (RDE) hospital presenting with acute limb ischaemia (ALI) using standardized electronic proforma. Method Results A total of 65 patients presented to vascular surgery during the 3-month period. Of these 20 patients presented with ‘acute limb ischaemia’. Documentation of rest pain (75%), pulses (Dorsalis paedis in 90%) and exam finding of cold feet (95%) was adequate. However, poor documentation of vascular risk factors such as previous stroke (20%) and atrial fibrillation (15%) was identified. ECG was performed on admission in only 35% patients. Examination like ABPI (10%) and Buerger's test (15%) were also inadequately documented. Conclusions This audit shows inadequate clerking of vascular patients presenting with ALI. The second cycle will include further data collection post-implementation of the electronic proforma to analyse improvements in documentation of the above-mentioned factors at initial clerking.