To describe radiotherapy outcomes for canine infiltrative lipomas and provide detailed radiotherapy planning data.
24 dogs from 2000 to 2020.
In this retrospective study, dogs received 1 to 3 ...surgeries prior to conventionally fractionated radiotherapy for gross (18) or microscopic (8) infiltrative lipomas. Dogs received 45 to 51 Gray (Gy) in 15 to 20 daily fractions, with 71% of dogs receiving 48 Gy in daily 3-Gy fractions.
Masses were regionally located as follows: limbs (7), trunk (13), head/neck (4). At analysis, 16/24 dogs were deceased, 5/24 were alive (median follow-up for alive dogs: 1,216 days range, 741 to 1,870 days), and 3/24 were lost to follow-up. One living dog had progressive disease 923 days after completing conventionally fractionated radiotherapy and received another surgery. The estimated median overall survival (OS) after completing radiotherapy was 4.8 years (1,760 days; 95% CI, 1,215 to 2,777 days; range, 23 to 3,499 days) for any cause of death, and no patients were reported to have been euthanized or died from their tumor. No statistically significant difference was found for dogs based on gross versus microscopic disease (gross OS, 4.8 years vs microscopic OS, 3.6 years; P = .45). Furthermore, the number of surgeries before radiotherapy did not impact survival (P = .96). The survival difference between females (median OS, 7.6 years; 95% CI, 963 days to not reached) versus males (median OS, 4.6 years; 95% CI, 335 to 2,245 days; P = .05) was statistically significant, although 4/5 living dogs were female.
This study demonstrates lengthy survivals with radiotherapy, even with gross disease, for dogs with infiltrative lipomas.
The soils and food webs associated with mid to high elevation, forested, headwater streams in northeastern North America are potential hotspots for mercury (Hg) methylation and bioaccumulation, but ...are not well studied. Our goals were to quantify total Hg (THg) and methyl Hg (MeHg) concentrations in soils and terrestrial food webs associated with headwater streams of northern hardwood forests to identify predictors of small-scale spatial variation in Hg bioaccumulation. We sampled soil characteristics that promote Hg methylation including pH, sulfur and calcium content, and organic matter. To assess spatial variation, we sampled at high (~700 m asl) and mid elevations (~500 m asl), both adjacent to (<1 m) and away from (>75 m) three replicate headwater streams in each of two watersheds of the White Mountains region, New Hampshire, USA. Soils of these forested watersheds differed significantly in pH and the content of calcium, sulfur, organic matter and THg. Conditions for methylation were more favorable in the upland forest sites compared to streamside sites. Significant bioaccumulation of THg occurred in all measured components of the food web, including insects, spiders, salamanders, and birds. Trophic position, as determined by δ15N, was the best predictor of both THg and MeHg bioaccumulation across the sampled taxa and was also a better predictor than spatial location. However, the degree of bioaccumulation at which MeHg significantly affects animal behavior, reproduction or survival is unknown for most taxa in terrestrial habitats, particularly for invertebrates. These findings show that Hg methylation and bioaccumulation is not limited to areas traditionally classified as wetlands or to areas with exceptionally high THg inputs, but that it is a widespread and important phenomenon in the moist deciduous forests of eastern North America.
•Small-scale spatial variation in Hg bioaccumulation in a forest was investigated.•Soil chemistry was a good predictor of total Hg but not of MeHg bioaccumulation.•Methylation of Hg was greater in upland areas compared to streamside environments.•MeHg varied among taxa and was related to trophic position (δ15N) and location.•MeHg and bioaccumulation are important issues for forests of eastern North America.
The microbiome has clearly been established as a cutting-edge field in tumor immunology and immunotherapy. Growing evidence supports the role of the microbiome in immune surveillance, self-tolerance, ...and response to immune checkpoint inhibitors such as anti PD-L1 and CTLA-4 blockade (1-6). Moreover, recent studies including those using fecal microbial transplantation (FMT) have demonstrated that response to checkpoint immunotherapies may be conferred or eliminated through gut microbiome modulation (7, 8). Consequently, studies evaluating microbiota-host immune and metabolic interactions remain an area of high impact research. While observations in murine models have highlighted the importance of the microbiome in response to therapy, we lack sufficient understanding of the exact mechanisms underlying these interactions. Furthermore, mouse and human gut microbiome composition may be too dissimilar for discovery of all relevant gut microbial biomarkers. Multiple cancers in dogs, including lymphoma, high grade gliomas, melanomas and osteosarcoma (OSA) closely resemble their human analogues, particularly in regard to metastasis, disease recurrence and response to treatment. Importantly, dogs with these spontaneous cancers also have intact immune systems, suggesting that microbiome analyses in these subjects may provide high yield information, especially in the setting of novel immunotherapy regimens which are currently expanding rapidly in canine comparative oncology (9, 10). Additionally, as onco-microbiotic therapies are developed to modify gut microbiomes for maximal responsiveness, large animal models with intact immune systems will be useful for trialing interventions and monitoring adverse events. Together, pre-clinical mechanistic studies and large animal trials can help fully unlock the potential of the microbiome as a diagnostic and therapeutic target in cancer.
Individualized prediction of outcomes may help with therapy decisions for patients with non-small cell lung cancer. We developed a nomogram by analyzing 17 clinical factors and outcomes from a ...randomized study of sublobar resection for non-small cell lung cancer in high-risk operable patients. The study compared sublobar resection alone with sublobar resection with brachytherapy. There were no differences in primary and secondary outcomes between the study arms, and they were therefore combined for this analysis.
The clinical factors of interest (considered as continuous variables) were assessed in a univariate Cox proportional hazards model for significance at the 0.10 level for their impact on overall survival (OS), local recurrence-free survival (LRFS), and any recurrence-free survival (RFS). The final multivariable model was developed using a stepwise model selection.
Of 212 patients, 173 had complete data on all 17 risk factors. Median follow-up was 4.94 years (range, 0.04 to 6.22). The 5-year OS, LRFS, and RFS were 58.4%, 53.2%, and 47.4%, respectively. Age, baseline percent diffusing capacity of lung for carbon monoxide, and maximum tumor diameter were significant predictors for OS, LRFS, and RFS in the multivariable model. Nomograms were subsequently developed for predicting 5-year OS, LRFS, and RFS.
Age, baseline percent diffusing capacity of lung for carbon monoxide, and maximum tumor diameter significantly predicted outcomes after sublobar resection. Such nomograms may be helpful for treatment planning in early stage non-small cell lung cancer and to guide future studies.
Liver lymphatic vessels support liver function by draining interstitial fluid, cholesterol, fat, and immune cells for surveillance in the liver draining lymph node. Chronic liver disease is ...associated with increased inflammation and immune cell infiltrate. However, it is currently unknown if or how lymphatic vessels respond to increased inflammation and immune cell infiltrate in the liver during chronic disease. Here we demonstrate that lymphatic vessel abundance increases in patients with chronic liver disease and is associated with areas of fibrosis and immune cell infiltration. Using single-cell mRNA sequencing and multi-spectral immunofluorescence analysis we identified liver lymphatic endothelial cells and found that chronic liver disease results in lymphatic endothelial cells (LECs) that are in active cell cycle with increased expression of CCL21. Additionally, we found that LECs from patients with NASH adopt a transcriptional program associated with increased IL13 signaling. Moreover, we found that oxidized low density lipoprotein, associated with NASH pathogenesis, induced the transcription and protein production of IL13 in LECs both
and in a mouse model. Finally, we show that oxidized low density lipoprotein reduced the transcription of
and decreased lymphatic stability. Together these data indicate that LECs are active participants in the liver, expanding in an attempt to maintain tissue homeostasis. However, when inflammatory signals, such as oxidized low density lipoprotein are increased, as in NASH, lymphatic function declines and liver homeostasis is impeded.
Teamwork and communication skills are essential for the safe practice of cardiothoracic surgery. In this article, we will summarize the literature on teamwork and the culture of safety, and discuss ...how surgeons may directly improve the outcomes of their patients by addressing these factors.
Early diagnosis of cancer enhances treatment planning and improves prognosis. Many masses presenting to veterinary clinics are difficult to diagnose without using invasive, time-consuming, and costly ...tests. Our objective was to perform a preliminary proof-of-concept for the HT Vista device, a novel artificial intelligence-based thermal imaging system, developed and designed to differentiate benign from malignant, cutaneous and subcutaneous masses in dogs.
Forty-five dogs with a total of 69 masses were recruited. Each mass was clipped and heated by the HT Vista device. The heat emitted by the mass and its adjacent healthy tissue was automatically recorded using a built-in thermal camera. The thermal data from both areas were subsequently analyzed using an Artificial Intelligence algorithm. Cytology and/or biopsy results were later compared to the results obtained from the HT Vista system and used to train the algorithm. Validation was done using a "Leave One Out" cross-validation to determine the algorithm's performance.
The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the system were 90%, 93%, 88%, 83%, and 95%, respectively for all masses.
We propose that this novel system, with further development, could be used to provide a decision-support tool enabling clinicians to differentiate between benign lesions and those requiring additional diagnostics. Our study also provides a proof-of-concept for ongoing prospective trials for cancer diagnosis using advanced thermodynamics and machine learning procedures in companion dogs.
Thymectomy is often performed on the basis of computed tomography scan findings that are suspicious for thymoma. However, the final diagnosis may be a condition such as thymic hyperplasia or lymphoma ...for which thymectomy is not therapeutic. The present analysis was undertaken to determine the prevalence of a "nontherapeutic" thymectomy.
The Nationwide Inpatient Sample from 2000 through 2009 was queried to identify patients who underwent a thymectomy. Only adult patients who underwent a total thymectomy without other associated procedures were analyzed. Patients with a diagnosis of myasthenia were excluded. A nontherapeutic thymectomy was defined as a patient who underwent thymectomy with an International Classification of Diseases, Ninth Revision diagnosis code of lymphoma, thymic hyperplasia, thymic cyst, or other benign diseases of the thymus.
A total of 1,306 patients were identified. Overall, 72.2% (n = 943) of thymectomies were therapeutic and 27.8% (n = 363) were nontherapeutic. The most common diagnosis in the nontherapeutic group was thymic hyperplasia (n = 174). Mortality (0.32% versus 0%; p = 0.083) and overall complication rates (25% versus 17%; p < 0.001) were higher in the therapeutic group. Patients in the nontherapeutic group were younger (median age, 41 versus 56 years; p < 0.001) and more likely to undergo a video-assisted thoracoscopic surgery thymectomy (28% versus 19%; p = 0.085).
In this study, 27.8% of thymectomies were nontherapeutic, and most patients underwent an open approach. The most common benign diagnosis was thymic hyperplasia, a condition for which magnetic resonance imaging has a high predictive value. Consequently, further studies are warranted to determine the optimal evaluation of patients undergoing thymectomy for presumed thymoma.
Abstract Introduction Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially ...available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. Methods Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. Results From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR , KRAS , and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p = 0.024 for EGFR ) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p = 0.021 for EGFR ). Conclusions Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special tissue acquisition or manipulation.
The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study recruited 3624 pregnant women, most partners and 3542 eligible offspring. We hypothesise that early life physical and ...psychosocial environments, immunological, physiological, nutritional, hormonal and metabolic influences interact with genetics influencing allergic diseases, including asthma. Environmental and biological sampling, innate and adaptive immune responses, gene expression, DNA methylation, gut microbiome and nutrition studies complement repeated environmental and clinical assessments to age 5. This rich data set, linking prenatal and postnatal environments, diverse biological samples and rigorous phenotyping, will inform early developmental pathways to allergy, asthma and other chronic inflammatory diseases.
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