Congenital Left Ventricular Aneurysm.

This paper presents the case of a 30-year-old man who was diagnosed with an apical-lateral wall left ventricular aneurysm with scarring, prominent left ventricular trabeculations, and mildly diminished systolic function. Working diagnosis was a congenital left ventricular aneurysm in the setting of left ventricular noncompaction, yet with a questionable defect of the pericardium.

PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer.

PURPOSE: To assess safety and immune biomarkers after preoperative radiation therapy (RT) and anti-PD1 therapy in breast cancer. MATERIALS AND METHODS: A phase I/IIb trial of pembrolizumab with RT was conducted in patients with triple-negative breast cancer (TNBC) and hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. All received pembrolizumab followed by a second cycle + RT (anti-PD1/RT) of 24 Gy/three daily fractions delivered to the breast tumor and then neoadjuvant chemotherapy (NAC). Blood and tumor biopsies were obtained at baseline, after anti-PD1, and after anti-PD-RT. Coprimary end points were safety and change in tumor-infiltrating lymphocytes (TILs). Secondary end points were pathologic complete response (pCR), residual cancer burden (RCB) rates, and event-free survival (EFS). RESULTS: Sixty-six patients with stage I-III breast cancer (54 TNBC, 12 HR+/HER2-) were enrolled. The median follow-up was 32 months. Safety end point was met. Incidence of grade ≥3 toxicities was 41%. The pCR rate was 59.2%, 33.3%, and 54.5% for the TNBC, HR+/HER2-, and entire cohort, respectively. A total of 77.8% of TNBC and 41.6% of HR+/HER2- had a near pCR (RCB 0-1). The 3-year EFS was 80%. In the entire cohort, PD-L1 expression increased after anti-PD1 (median Combined Positive Score [CPS], 7.49-23.20; 95% CI, -41.88 to -6.30; P = .044) and anti-PD1/RT (median CPS, 7.49-23.41; 95% CI, -41.88 to -6.30; P = .009), compared with baseline. In TNBC, adding RT to anti-PD1 significantly decreased TILs (28.9%-17.1%; 95% CI, 2.46 to 21.09; P = .014). Baseline TILs correlated with PD-L1 expression and TNF-a. CONCLUSION: Preoperative RT with pembrolizumab is safe and results in high pCR rates and 3-year EFS, despite the lack of pembrolizumab during NAC. PD-L1 and TILs may be predictive biomarkers for preoperative anti-PD1/RT response. Reduction in TILs after adding RT to anti-PD1 highlights the importance of treatment sequencing.

Circulating tumor DNA (ctDNA) as a biomarker of response to therapy in advanced Hepatocellular carcinoma treated with Nivolumab.

BACKGROUND: Circulating tumor DNA (ctDNA) is a promising non-invasive marker for detection, diagnosis, treatment selection, and prognosis of hepatocellular carcinoma (HCC). OBJECTIVE: This study aimed to examine the utility of ctDNA as a prognostic and predictive tool in HCC patients treated with nivolumab. METHODS: We analyzed pre-treatment ctDNA from 44 HCC patients using comprehensive genomic testing on a commercially available platform. We utilized log rank test and univariate Cox models to correlate overall survival (OS) and progression-free survival (PFS) with ctDNA expressions. RESULTS: Of 44 patients, 77.3% were men with median age of 67 years. All but 3 patients had at least one alteration identified, and TP53 was the most commonly altered gene (52.3%). Median OS was 17.5 months (95% CI: 12.7, NA). Mutations involving PIK3CA, BRCA1, and CCND1 amplification were associated with shorter OS (P 0.0001, 0.0001 and 0.01, respectively). Median PFS time was 4.01 months (95% CI: 3.06, 9.33). Mutations involving KIT and PIK3CA were associated with shorter PFS (P 0.0001 and 0.0004, respectively), while mutation involving CTNNB1 were associated with longer PFS (p= 0.04). CONCLUSIONS: ctDNA profiling may provide a benefit for prediction of survival and progression of HCC patients treated with nivolumab. Future studies are needed for confirmation.

Updates in Arrhythmia Management in Adult Congenital Heart Disease.

Arrhythmias are highly prevalent in adults with congenital heart disease. For the clinician caring for this population, an understanding of pathophysiology, diagnosis, and management of arrhythmia is essential. Herein we review the latest updates in diagnostics and treatment of tachyarrhythmias and bradyarrhythmias, all in the context of congenital anatomy, hemodynamics, and standard invasive palliations for congenital heart disease.

The doodle dilemma: How the physical health of 'Designer-crossbreed' Cockapoo, Labradoodle and Cavapoo dogs' compares to their purebred progenitor breeds.

Booming UK ownership of designer-crossbreed dogs resulting from intentional crossing of distinct purebred breeds is often motivated by perceived enhanced health, despite limited evidence supporting a strong 'hybrid vigour' effect in dogs. Improved evidence on the relative health of designer-crossbreed dogs could support prospective owners to make better acquisition decisions when choosing their new dog. This study used a cross-sectional survey of UK owners of three common designer-crossbreeds (Cavapoo, Cockapoo, and Labradoodle) and their progenitor breeds (Cavalier King Charles Spaniel, Cocker Spaniel, Labrador Retriever, and Poodle) to collect owner-reported health disorder information. The authors hypothesised that designer-crossbred breeds have lower odds of common disorders compared to their progenitor breeds. Multivariable analysis accounted for confounding between breeds: dog age, sex, neuter status, and owner age and gender. The odds for the 57 most common disorders were compared across the three designer-crossbreeds with each of their two progenitor breeds (342 comparisons). Valid responses were received for 9,402 dogs. The odds did not differ statistically significantly between the designer-crossbreeds and their relevant progenitor breeds in 86.6% (n = 296) of health comparisons. Designer-crossbreeds had higher odds for 7.0% (n = 24) of disorders studied, and lower odds for 6.4% (n = 22). These findings suggest limited differences in overall health status between the three designer-crossbreeds and their purebred progenitors, challenging widespread beliefs in positive hybrid vigour effects for health in this emerging designer-crossbreed demographic. Equally, the current study did not suggest that designer-crossbreeds have poorer health as has also been purported. Therefore, owners could more appropriately base acquisition decisions between designer-crossbreeds and their purebred progenitors on other factors important to canine welfare such as breeding conditions, temperament, conformation and health of parents.

Cancer tissue of origin constrains the growth and metabolism of metastases.

Metastases arise from subsets of cancer cells that disseminate from the primary tumour1,2. The ability of cancer cells to thrive in a new tissue site is influenced by genetic and epigenetic changes that are important for disease initiation and progression, but these factors alone do not predict if and where cancers metastasize3,4. Specific cancer types metastasize to consistent subsets of tissues, suggesting that primary tumour-associated factors influence where cancers can grow. We find primary and metastatic pancreatic tumours have metabolic similarities and that the tumour-initiating capacity and proliferation of both primary-derived and metastasis-derived cells is favoured in the primary site relative to the metastatic site. Moreover, propagating cells as tumours in the lung or the liver does not enhance their relative ability to form large tumours in those sites, change their preference to grow in the primary site, nor stably alter aspects of their metabolism relative to primary tumours. Primary liver and lung cancer cells also exhibit a preference to grow in their primary site relative to metastatic sites. These data suggest cancer tissue of origin influences both primary and metastatic tumour metabolism and may impact where cancer cells can metastasize.

Translational modeling-based evidence for enhanced efficacy of standard-of-care drugs in combination with anti-microRNA-155 in non-small-cell lung cancer.

BACKGROUND: Elevated microRNA-155 (miR-155) expression in non-small-cell lung cancer (NSCLC) promotes cisplatin resistance and negatively impacts treatment outcomes. However, miR-155 can also boost anti-tumor immunity by suppressing PD-L1 expression. Therapeutic targeting of miR-155 through its antagonist, anti-miR-155, has proven challenging due to its dual molecular effects. METHODS: We developed a multiscale mechanistic model, calibrated with in vivo data and then extrapolated to humans, to investigate the therapeutic effects of nanoparticle-delivered anti-miR-155 in NSCLC, alone or in combination with standard-of-care drugs. RESULTS: Model simulations and analyses of the clinical scenario revealed that monotherapy with anti-miR-155 at a dose of 2.5 mg/kg administered once every three weeks has substantial anti-cancer activity. It led to a median progression-free survival (PFS) of 6.7 months, which compared favorably to cisplatin and immune checkpoint inhibitors. Further, we explored the combinations of anti-miR-155 with standard-of-care drugs, and found strongly synergistic two- and three-drug combinations. A three-drug combination of anti-miR-155, cisplatin, and pembrolizumab resulted in a median PFS of 13.1 months, while a two-drug combination of anti-miR-155 and cisplatin resulted in a median PFS of 11.3 months, which emerged as a more practical option due to its simple design and cost-effectiveness. Our analyses also provided valuable insights into unfavorable dose ratios for drug combinations, highlighting the need for optimizing dose regimens to prevent antagonistic effects. CONCLUSIONS: This work bridges the gap between preclinical development and clinical translation of anti-miR-155 and unravels the potential of anti-miR-155 combination therapies in NSCLC.

Evolution of Initial Treatment for Desmoid Tumors.

INTRODUCTION: Desmoid tumors (DTs) are rare, fibroblastic cell proliferations that can exhibit locally aggressive behavior but lack metastatic potential. Initial management has traditionally involved upfront resection; however, contemporary guidelines and expert panels have increasingly advocated for prioritizing active surveillance strategies. METHODS: A single-institution, retrospective chart review identified all patients diagnosed with a primary DT at any site from 2007 to 2020. The primary outcome was the initial management strategy over time. Secondary outcomes included treatment-free survival (TFS) and time to treatment (TTT) for those undergoing active surveillance, as well as recurrence-free survival (RFS) and time to recurrence for those undergoing resection. RESULTS: Overall, 103 patients were included, with 68% female and a median follow-up of 44 months [24-74]. The most common tumor locations included the abdominal wall (27%), intra-abdominal/mesenteric (25%), chest wall (19%), and extremity (10%). Initial management included resection (60%), systemic therapy (20%), active surveillance (18%), and cryoablation (2%). Rates of surgical resection significantly decreased (p < 0.001) over time, from 69.6% prior to 2018 to 29.2% after 2018. For those treated with upfront resection, 5-year RFS was 41.2%, and for patients undergoing initial active surveillance, TFS was 66.7% at 2 years, with a median TTT of 4 months [4-10]. CONCLUSIONS: This single-institution cohort at a tertiary medical center spanning over a decade demonstrates the transition to active surveillance for initial management of DTs, and highlights salient metrics in the era of surveillance. This trend mirrors recommended treatment strategies by expert panels and consensus guidelines.

Conformation-associated health in pet rabbits in the UK: A VetCompass cohort study.

BACKGROUND: Domestic rabbit breeds vary substantially from the wild rabbit body type. However, little is known about how the conformation of pet rabbits influences their health. METHODS: Data were extracted from VetCompass anonymised clinical records of rabbits under UK primary veterinary care during 2019. RESULTS: The study included 162,107 rabbits. Based on 88,693 rabbits with relevant breed information recorded, skull shape was classified as brachycephalic (79.69%), mesaticephalic (16.80%) and dolichocephalic (3.51%). Based on 83,821 rabbits with relevant breed information recorded, ear carriage was classified as lop-eared (57.05%) and erect-eared (42.95%). From a random sample of 3933 rabbits, the most prevalent disorders recorded overall were overgrown nail(s) (28.19%), overgrown molar(s) (14.90%) and obesity (8.82%). Compared to those with a mesaticephalic skull shape, brachycephalic rabbits had lower odds of obesity, anorexia and gastrointestinal stasis and higher odds of perineal faecal impaction, tear duct abnormality and haircoat disorder. Compared to erect-eared rabbits, lop-eared rabbits had higher odds of perineal faecal impaction and tear duct abnormality. LIMITATION: A large proportion of records with incomplete breed information hindered full analysis for breed-related and conformation-related attributes. CONCLUSION: Limited evidence for major links between skull shape or ear carriage conformations and overall disorder risk suggests that factors such as husbandry or even just living life as a domesticated species may be bigger drivers of common health issues in pet rabbits in the UK.

HAP-FAST: a feasibility study incorporating qualitative, mechanistic and costing sub-studies alongside a randomised pilot trial comparing chest x-ray to low-dose CT scan and empirical antibiotics to antibiotics guided by the BIOFIRE® FILM ARRAY® pneumonia plus panel in adults with suspected non-ventilator-associated hospital-cquired pneumonia.

INTRODUCTION: Non-ventilator-associated hospital-acquired pneumonia (nv-HAP) is the most common healthcare-associated infection (HCAI), is associated with high mortality and morbidity and places a major burden on healthcare systems. Diagnosis currently relies on chest x-rays to confirm pneumonia and sputum cultures to determine the microbiological cause. This approach leads to over-diagnosis of pneumonia, rarely identifies a causative pathogen and perpetuates unnecessary and imprecise antibiotic use. The HAP-FAST study aims to evaluate the feasibility of a randomised trial to evaluate the clinical impact of low-dose, non-contrast-enhanced thoracic CT scans and rapid molecular sputum analysis using the BIOFIRE® FILMARRAY® pneumonia plus panel (FAPP) for patients suspected with nv-HAP. METHODS AND ANALYSIS: The HAP-FAST feasibility study consists of a pilot randomised trial, a qualitative study, a costing analysis and exploratory analyses of clinical samples to investigate the immune-pathophysiology of HAP. Participants are identified and recruited from four acute hospitals in the Northwest of the UK. Using a Research Without Prior Consent model, the pilot trial will recruit 220 adult participants, with or without mental capacity, and with suspected HAP. HAP-FAST is a non-blinded, sequential, multiple assignment, randomised trial with two possible stages of randomisation: first, chest x-ray (CXR) or CT; second, if treated as nv-HAP, FAPP or standard microbiological processing alone (no FAPP). Pathogen-specific antibiotic guidance will be provided for FAPP results. Randomisation uses a web-based platform and followed up for 90 days. The feasibility of a future trial will be determined by assessing trial processes, outcome measures and patient and staff experiences. ETHICS AND DISSEMINATION: This study has undergone combined review by the UK NHS Research Ethics Committee and Health Research Authority. Results will be disseminated via peer-reviewed journals, via the funders' website and through a range of media to engage the public. TRIAL REGISTRATION NUMBER: NCT05483309.

Market Factors, Not Quality, Influence Reimbursement for Pancreaticoduodenectomy in an Era of Price Transparency.

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) price transparency rule tries to facilitate cost-conscious decision-making. For surgical services, such as pancreaticoduodenectomy (PD), factors mediating transparency and real-world reimbursement are not well described. METHODS: The Leapfrog Survey was used to identify United States hospitals performing PD. Financial and operational data were obtained from Turquoise Health and CMS Cost Reports. Chi-square tests and modified Poisson regression evaluated associations with reimbursement disclosure. Two-part logistic and gamma regression models estimated effects of hospital factors on commercial, Medicare, and self-pay reimbursements for PD. RESULTS: Of 452 Leapfrog hospitals, 295 (65%) disclosed PD hospital or procedure reimbursements. Disclosing hospitals were larger (beds > 200: 81.0% vs. 71.3%, p = 0.04), reported higher net margins (0.7% vs. - 2.1%, p = 0.04), more likely for-profit (26.1% vs. 6.4%, p < 0.001), and teaching-affiliated (82.0% vs. 65.6%, p < 0.001). Nonprofit status conferred hospitalization reimbursement increases of $8683-$12,329, while moderate market concentration predicted savings up to $5066. Teaching affiliation conferred reimbursement increases of $4589-$16,393 for hospitalizations and $644 for procedures. Top Leapfrog volume ratings predicted an increase of up to $7795 for only Medicare hospitalization reimbursement. CONCLUSIONS: Nondisclosure of hospital and procedural reimbursements for PD remains a major issue. Transparency was noted in hospitals with higher margins, size, and academic affiliation. Factors associated with higher reimbursement were non-profit status, academic affiliation, and more equitable market share. Reimbursement inconsistently tracked with PD quality or volume measures. Policy changes may be required to incentivize reimbursement disclosure and translate transparency into increased value for patients.

Current patterns of care and outcomes for dermatofibrosarcoma protuberans: An international multi-institutional collaborative.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a cutaneous sarcoma with an infiltrative growth pattern that makes it challenging to clear margins. High quality data regarding DFSP natural history, management, and outcomes are limited. METHODS: Data were retrospectively collected for adult DFSP patients who underwent resection at 10 institutions in eight countries. Demographics, tumor characteristics, treatment strategies, and outcomes were analyzed. RESULTS: Analysis included 347 patients consisting of young (median, 42 years), White (76.2%), males (54.2%) with truncal lesions (57.3%). The majority (76.8%) were symptomatic at presentation. Preoperative imaging was used in 55.9% of cases. Diagnosis was established with excisional biopsy in 50.9% versus incisional biopsy in 25.0% of cases. Despite planned margins of >1.0 cm in 67.4% of cases, only 69.0% of patients achieved R0 resection. Twenty-two percent of patients underwent at least one re-excision. R0 resection was achieved at a second procedure in 80.2% and a third procedure in 86.2%. Ultimately, R0 resection was feasible in 89.5% of all patients. Fibrosarcomatous transformation (FST) was observed in 12.6%. In total, 6.6% (N = 23) recurred (17 local, six distant). Of the six distant recurrences, 50.0% had FST. With a median follow-up of 47.0 months, disease-specific survival rate was 98.8%. In multivariable analysis, R0 margins at index resection were associated with wider circumferential margins and non-FST histology. CONCLUSIONS: In this international, multicenter collaborative, DFSP practice patterns were heterogeneous but achieved favorable recurrence rates and survival. Multiple excisions to clear margins remain commonplace and can inform future efforts to optimize margin selection.

Later-age neutering causes lower risk of early-onset urinary incontinence than early neutering-a VetCompass target trial emulation study.

There is growing evidence supporting clinically important associations between age at neutering in bitches and subsequent urinary incontinence (UI), although much of this evidence to date is considered weak. Target trial emulation is an innovative approach in causal inference that has gained substantial attention in recent years, aiming to simulate a hypothetical randomised controlled trial by leveraging observational data. Using anonymised veterinary clinical data from the VetCompass Programme, this study applied the target trial emulation framework to determine whether later-age neutering (≥ 7 to ≤ 18 months) causes decreased odds of early-onset UI (diagnosed < 8.5 years) compared to early-age neutering (3 to < 7 months). The study included bitches in the VetCompass database born from January 1, 2010, to December 31, 2012, and neutered between 3 and 18 months old. Bitches were retrospectively confirmed from the electronic health records as neutered early or later. The primary outcome was a diagnosis of early-onset UI. Informed from a directed acyclic graph, data on the following covariates were extracted: breed, insurance status, co-morbidities and veterinary group. Inverse probability of treatment weighting was used to adjust for confounding, with inverse probability of censoring weighting accounting for censored bitches. The emulated trial included 612 early-age neutered bitches and 888 later-age neutered bitches. A pooled logistic regression outcome model identified bitches neutered later at 0.80 times the odds (95% CI 0.54 to 0.97) of early-onset UI compared with bitches neutered early. The findings show that later-age neutering causes reduced odds of early-onset UI diagnosis compared with early-age neutering. Decision-making on the age of neutering should be carefully considered, with preference given to delaying neutering until after 7 months of age unless other major reasons justify earlier surgery. The study is one of the first to demonstrate successful application of the target trial framework to veterinary observational data.

Life tables of annual life expectancy and risk factors for mortality in cats in the UK.

OBJECTIVES: The aims of the present study were to generate the first life tables for the UK companion cat population overall as well as broken down by sex and breed status, and to quantify associations between mortality and traits such as sex, neuter status, breed status and body weight in relation to mortality. METHODS: Life table construction and modelling included data on 7936 confirmed deaths in cats under primary veterinary care at clinics participating in the VetCompass Programme in 2019. The life tables were built for cats overall, female and male cats, and crossbred and purebred cats. Multivariable generalised linear regression models were generated to explore the risk factors for a shortened lifespan. RESULTS: Life expectancy at age 0 for UK companion cats overall was 11.74 years (95% confidence interval [CI] 11.61-11.87). The probability of death at each year interval increased with age from year interval 3-4, with the probability value not exceeding 0.05 before year 9. Female cats (12.51 years; 95% CI 12.32-12.69) had a 1.33-year longer life expectancy than male cats (11.18 years; 95% CI 11.01-11.38) at age 0. Among the 12 breeds (including crossbred) analysed, Burmese and Birman had the longest life expectancy at year 0, showing 14.42 years (95% CI 12.91-15.93) and 14.39 years (95% CI 12.87-15.91), respectively. Sphynx had the shortest life expectancy at year 0 among the analysed breeds at 6.68 years (95% CI 4.53-8.83). Being entire, purebred and with a non-ideal body weight were significantly linked to a decreased lifespan. CONCLUSIONS AND RELEVANCE: The life tables presented here for companion cats in the UK overall, by sex, and by crossbred and purebred cats can contribute to a better understanding of the life trajectory of cats, helping with evidence-based decision-making for cat owners and the veterinary profession. We have also provided an updated life expectancy at age 0 for various cat breeds for 2019 and showed evidence of the association between non-ideal weight and a decreased lifespan.

Researcher, research thyself? Mapping the landscape of canine health and welfare research funding provided by UK not-for-profit organisations from 2012-2022.

BACKGROUND: Research into canine health and welfare is supported by Government, charitable and private UK funding organisations. However, there is no current overall visibility or coordination of these funding activities, potentially compromising optimal distribution of limited resources. This study aimed to survey UK canine health and welfare funding by not-for-profit funders between 2012 and 2022, providing a novel baseline analysis to inform future sector stakeholder priorities. RESULTS: Funding data were collected from 10 wide-scope funders (UK Government funding councils and medical charities), 18 animal-directed funders (organisations specifically concerned with animal health and welfare) and 81 breed community groups. These 109 UK funders together provided traceable canine-relevant funding of £57.8 million during the surveyed period, comprising 684 individual grant awards supporting over 500 separate research projects. Wide-scope funders contributed £41.2 million (71.2% of total funding); animal-directed organisations, £16.3 million (28.1% of total funding); and breed-specific groups, £370K (0.6% of total funding). Individual grants ranged from £2.3 million to £300. Funding patterns varied between sectors. Animal-directed funders provided £14.7 million of canine-relevant research funding that foregrounded the dog, 73% of all such funding; wide-scope funders provided £17.5 million of canine-relevant One Health research funding, 97% of all such funding. Customised metrics developed for this study assessed the 'benefit to the dog' and 'pathway to impact' of individual research projects. Overall, studies supported by animal-directed funders achieved significantly higher 'benefit to the dog' scores (Mann-Whitney U = 45235, p<0.001) and 'pathway to impact' scores (Mann-Whitney U = 43506.5, p<0.001) than those supported by wide-scope funders. CONCLUSION: The landscape of UK not-for-profit funding of canine health and welfare research is complex, with considerable variation between providers. Although wide-scope funders provide the majority of overall canine-relevant research funding, animal-directed funders provide the majority of canine-focused funding and support research with greater direct impact on canine welfare. Visibility of past funding patterns will enable stakeholders in this sector to make more informed decisions about future research. DEFINITIONS: To increase clarity, certain words and phrases are used in specific ways within the context of this paper. Animal-directed funders-Charities and other funding organisations whose remit primarily concerns animals or veterinary work Canine-focused research-Investigations where the primary purpose is to advance understandings of canine health and/or welfare Canine-relevant research-All research that is framed as advancing understandings of canine health and/or welfare as a primary or subsidiary purpose Institution-Refers to universities and other centres where research is carried out Organisation-Refers to funding bodies, including research councils, charities and other groups Research grant-A single funding event originating from one or more funders Research project-A cohesive piece of research concerning a particular topic; may involve multiple researchers and/or multiple research grants, in series or in parallel Wide-scope funders-Large organisations whose remit does not primarily concern animals, i.e. (in this dataset) UKRI councils and the Wellcome Trust.

Epidemiology of heat-related illness in dogs under UK emergency veterinary care in 2022.

BACKGROUND: Dogs are exposed to increasing environmental risk for developing heat-related illness (HRI), with 2022 recorded as the hottest year to date in the UK and most of Europe. METHODS: This study used VetCompass data to report the incidence risk, event fatality rate and canine risk factors for HRI in dogs presenting to Vets Now emergency care practices in the UK during 2022. RESULTS: From the clinical records of 167,751 dogs under care at Vets Now emergency clinics in 2022, 384 HRI events were identified. The 2022 incidence risk of HRI within the Vets Now caseload was 0.23% (95% confidence interval [CI]: 0.21%‒0.25%), with an event fatality rate of 26.56% (95% CI: 21.66%-32.25%). Multivariable analysis identified breed, age and sex/neuter status as risk factors for HRI. Brachycephalic dogs had 4.21 times the odds of HRI compared to mesocephalic dogs (95% CI: 3.22‒5.49, p < 0.001). LIMITATIONS: The clinical data used in this study were not primarily recorded for research and had some substantial levels of missing data (especially patient bodyweight). CONCLUSION: In order to protect canine welfare, improved long-term mitigation strategies are urgently needed to minimise HRI risk and associated fatality in UK dogs.

Contemporary trends and outcomes after liver transplantation and resection for intrahepatic cholangiocarcinoma.

BACKGROUND: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA. METHODS: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods stratified by management. Secondary analysis of patients undergoing transplant for CCA was performed with the United Network for Organ Sharing database. RESULTS: Of 2565 patients, 2412 (94.0%) underwent resection and 153 (5.96%) LT of whom 84 (54.9%) received neoadjuvant therapy. Utilization of LT remained between 3.9% and 7.8% annually. Unadjusted 5-year OS was higher for LT than resection (59.8% vs 39.9%, P = .0067), yet adjusted analysis revealed no significant difference in mortality (hazard ratio, 0.91; 95% CI, 0.66-1.27; P = .58). On secondary analysis including 437 patients with all subtypes of CCA, unadjusted 5-year OS was higher for non-CCA indications (79% vs 52%-54%, P < .001). CONCLUSION: Utilization of LT for iCCA remains low and many cases are likely incidental. Although partial hepatectomy remains the standard of care for patients with resectable disease, our findings suggest that highly selected patients with unresectable iCCA may achieve favorable outcomes after LT. Granular, prospective data are needed to identify patients most likely to benefit from transplant and allocate scarce liver grafts.