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Purpose: Traumatic abdominal injury is associated with significant mortality, especially in hemodynamically unstable patients. Trauma management now supports more conservative surgical management with judicious non-operative management. The aim of this study is to use STAG data to characterize abdominal trauma outcomes, focusing on factors that may influence mortality., Methods: A retrospective analysis of prospectively collected STAG data was queried using AIS codes for Scottish abdominal trauma patients between 2011 and 2015. Patients were divided into non-survivor and survivor groups, reflecting mortality. Following this, outcomes and injury patterns of patients undergoing operative or non-operative management were compared between groups., Results: A total of 1226 were analyzed. The mean age of the cohort was 42.47 ± 19.42 years, with most patients suffering blunt injuries. Non-survivors had more severe injuries to the liver, diaphragm, pancreas, vasculature, and pelvis (p < 0.001, p = 0.005, p = 0.025, p < 0.001, and p < 0.001, respectively). Survivors more often received CT scanning (0.09 [0.03-0.27]) and underwent surgical intervention (57.4% vs 39.7%; p = 0.001). Non-survivors more often had a shorter time till operative intervention (2.6 h vs 6.3 h, p < 0.001)., Conclusions: About 7% of patients in the STAG registry display abdominal injury. Mortality was found to have strong associations with older age, hemodynamic instability, poor neurological status, and head and neck injury. Outcomes may improve with the anticipated creation of the Scottish Trauma System., (© 2019. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Mesenteric vascular disease carries a high risk of mortality and morbidity; however, due to obscure clinical presentation, it can be under-recognized. Currently, epidemiology of mesenteric vascular disease remains poorly defined. The aim of this study is to analyze changes in Scottish mortality rates from mesenteric vascular disease overtime., Methods: This is a retrospective, longitudinal population-based cohort study using data extracted from death certificates and Scottish Index of Multiple Deprivation. All deaths related to a vascular disorder of the intestines recorded as an underlying cause of death between 1979 and 2014 were identified using International Classification of Disease-9 or International Classification of Disease-10 code groups. Data included demographics and location of death. The residence postcodes were used to classify socio-economic status using the Scottish Index of Multiple Deprivation., Results: From 2,142,921 deaths over 36 years, 14,530 (0.7%) were due to mesenteric vascular disease with a median (interquartile range) age of 77 and a 2:1 female to male gender ratio. The mean ± standard deviation age significantly increased from 72.6 ± 12.1 in 1979 to 76.8 ± 11.1 in 2014 ( p  < 0.001, R 2  = 0.772). Males were consistently younger than females at the time of death. The two lowest Scottish Index of Multiple Deprivation categories accounted for half of the cohort, throughout the study period ( p  = 0.068). The adjusted death rate per 100,000 population increased from 7.6 in 1979 to 12.1 in 2014., Conclusions: The reported death rates of mesenteric vascular disease in Scotland between 1979 and 2014 have nearly doubled. Mesenteric vascular disease affects twice as many women as men and is associated with social deprivation. The increased reporting of mesenteric vascular disease is likely due to increased recognition and incidence. These implications should be considered when planning healthcare provision in Scotland.

Breast cancer is the most common cause of cancer-related deaths in women worldwide. Identification of reliable prognostic indicators and therapeutic targets is critical for improving patient outcome. Cancer in companion animals often strongly resembles human cancers and a comparative approach to identify prognostic markers can improve clinical care across species. Feline mammary tumors (FMT) serve as models for extremely aggressive triple negative breast cancer (TNBC) in humans, with high rates of local and distant recurrence after resection. Despite the aggressive clinical behavior of most FMT, current prognostic indicators are insufficient for accurately predicting outcome, similar to human patients. Given significant heterogeneity of mammary tumors, there has been a recent focus on identification of universal tumor-permissive stromal features that can predict biologic behavior and provide therapeutic targets to improve outcome. As in human and canine patients, collagen signatures appear to play a key role in directing mammary tumor behavior in feline patients. We find that patients bearing FMTs with denser collagen, as well as longer, thicker and straighter fibers and less identifiable tumor-stromal boundaries had poorer outcomes, independent of the clinical variables grade and surgical margins. Most importantly, including the collagen parameters increased the predictive power of the clinical model. Thus, our data suggest that similarities with respect to the stromal microenvironment between species may allow this model to predict outcome and develop novel therapeutic targets within the tumor stroma that would benefit both veterinary and human patients with aggressive mammary tumors., Competing Interests: The authors have declared that no competing interests exist.

With the recent development of novel, more potent cancer treatment, in particular, immune 'checkpoint inhibitors', cases of neurological immune-related adverse events are on the rise. Although rare, this includes Guillain-Barré Syndrome (GBS). We present the case of a 68-year-old male who was admitted with sudden onset of worsening neurological symptoms following immunotherapy treatment. These symptoms progressed quickly to respiratory failure requiring intubation and admission to the intensive care unit. He was thoroughly investigated and is believed to have an axonal neuropathy in the form of Miller Fisher Syndrome (MFS) variant of GBS, secondary to immunotherapy treatment. He was initially treated with intravenous immunoglobulin, and later, perhaps more effectively, with high dose steroids which significantly improved his symptoms. This case of checkpoint inhibitor-induced MFS is one of few in the literature and is an important reminder of the potential for new immunotherapeutic agents to cause significant neurotoxic effects. These should be promptly and thoroughly investigated, in particular, as the management of these patients can differ from standard treatments used in these conditions., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

An interesting and rare case where a longstanding multinodular goitre causes sudden onset symptoms of superior vena cava obstruction. The symptoms were caused by bilateral brachiocephalic vein compression against the first rib. The patient's symptoms included upper limb and facial swelling, whereas her lower limbs were not oedematous (figure 1). The patient underwent CT imaging which showed a multinodular retrosternal thyroid filling the space created by the first rib, sometimes known as the thoracic outlet. The goitre expanded sufficiently to compress the brachiocephalic vein on both sides as shown in figures 2 and 3. This prevented venous drainage from the upper limbs and head. The goitre was also large enough to cause deviation of the trachea although there was no airway compromise. This case is interesting as it is very rare for a benign condition such as a multinodular goitre to cause symptoms of superior vena cava obstruction., Competing Interests: Conflicts of Interest: None declared., (2016 BMJ Publishing Group Ltd.)

Feline small cell lymphoma is associated with greater response to treatment and survival when compared to large cell lymphoma. Treatment-associated toxicity, response to rescue chemotherapy and prognostic factors are largely unknown. This retrospective study was performed to identify treatment-associated toxicity, response to rescue chemotherapy and treatment outcome for cats diagnosed with small cell lymphoma of various anatomic locations. Medical records from 56 cats were evaluated. All cats were treated with glucocorticoid and chlorambucil with discontinuation of treatment recommended at 1 year if complete clinical response was documented. Chemotherapy toxicity was uncommon (33.9%) and generally mild. Grade III or IV hepatotoxicity was documented in 10.7% of patients. Overall response rate was 85.7% with glucocorticoid and chlorambucil. Median progression-free survival was 1078 days. Overall response rate for rescue chemotherapy was 59%. Reintroduction of prednisone and chlorambucil was associated with significantly longer survival than prednisone and lomustine (>1500 vs. 492 days, P  = 0.01). Median overall survival times for cats with lymphoma of the gastrointestinal tract was not significantly different from those with extra-intestinal disease locations (1148 vs. 1375 days, P  = 0.23). Median overall survival was 1317 days. Toxicity, other than hepatotoxicity was mild. Rescue chemotherapy with re-introduction of glucocorticoids and chlorambucil was most successful. Discontinuation of glucocorticoid and chlorambucil with subsequent reintroduction as rescue chemotherapy appears to be just as effective as continued administration in cats.

A 22-year-old, wild-caught male kori bustard (Ardeotis kori) developed a large, slow-growing subcutaneous mass over the keel. The mass was surgically debulked and histopathologically described as a myxosarcoma. Surgical dehiscence and concurrent local tumor regrowth, with no evidence of metastasis, occurred over the subsequent 3 months, necessitating 2 additional surgical procedures to close the wound. At 19 weeks after the initial procedure, a second debulking surgical procedure was performed, at which time carboplatin-impregnated matrix beads were placed in the lesion. Moderate local tumor regrowth was clinically appreciable 4 weeks after surgery, at which time an oral metronomic chemotherapeutic protocol consisting of daily cyclophosphamide (10 mg/m(2)) and meloxicam (0.1 mg/kg) was initiated. Four months later, the tumor was no longer palpable. While oral therapy was discontinued during the breeding season, mass regrowth was observed, and the mass was surgically debulked before reinitiating oral chemotherapy. Treatment was extended for over 1 year with no hematologic evaluation or serum biochemical abnormalities, and the bird otherwise remained clinically healthy. To our knowledge, this is the first report of a myxosarcoma in a bustard species and the first report of successful clinical application of metronomic chemotherapy in an avian species.

Background: Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy., Hypothesis: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone., Animals: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo)., Methods: Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated., Results: Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively (P= .15) and median survival times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03)., Conclusions and Clinical Importance: This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.

The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced a more aggressive form of the disease. Two hundred and fifty-eight dogs were evaluated (102 clinical and 156 necropsy cases). In the necropsy population, Rottweilers had a younger mean age at death (7.3 versus 9 years, P = 0.006). There were no significant differences between Rottweilers and other breeds in age at diagnosis, median disease-free interval or survival time. However, Rottweilers were more likely to have metastasis to the brain (7 versus 0%, P = 0.03). These results suggest that OSA in Rottweilers may have a different biological behaviour, but this study did not confirm that these differences were associated with a worse outcome.

Tissue transglutaminase II (TGase II) is a dual function protein with both transamidating and guanidine triphosphate (GTP)-binding capabilities. Previous studies have implicated TGase as a pro-apoptotic molecule; however, our recent findings indicate that TGase II may act as a survival factor in various cell types. The purpose of this study was to survey TGase II expression in normal tissue and spontaneous tumours of dogs and cats, by Western blotting and immunohistochemistry. Bladder, liver and adrenal gland exhibited prominent expression of TGase II while other tissues, including mammary gland, displayed limited expression and activity. TGase II GTP-binding in normal tissues was proportional to the level of expression in all tissues examined. Normal mammary tissue and that showing benign hyperplasia did not express TGase II. However, 11/25 (44%) of canine mammary carcinomas and 10/12 (83%) of feline mammary carcinomas strongly expressed TGase II in either a stromal, cellular or combined pattern. The pattern of expression was not related to the classification of mammary carcinoma (solid, tubulopapillary, complex or anaplastic), except that two anaplastic canine mammary carcinomas showed prominent TGase II expression. Two canine mammary carcinoma cell lines showed prominent TGase expression, and when the TGase activity was inhibited, the cells became more sensitive to doxorubicin-induced cell death. Thus, TGase II was significantly expressed in mammary cancers from dogs and cats and immunoreactivity of TGase II was similar to that reported in humans beings. The pro-survival effect of TGase II in canine mammary carcinoma cell lines was similar to that previously reported in humans patients.

Retinoic acid (RA) is a potent activator of tissue transglutaminase (TGase) expression, and it was recently shown that phosphoinositide 3-kinase (PI3K) activity was required for RA to increase TGase protein levels. To better understand how RA-mediated TGase expression is regulated, we considered whether co-stimulation of NIH3T3 cells with RA and epidermal growth factor (EGF), a known activator of PI3K, would facilitate the induction or increase the levels of TGase expression. Instead of enhancing these parameters, EGF inhibited RA-induced TGase expression. Activation of the Ras-ERK pathway by EGF was sufficient to elicit this effect, since continuous Ras signaling mimicked the actions of EGF and inhibited RA-induced TGase expression, whereas blocking ERK activity in these same cells restored the ability of RA to up-regulate TGase expression. However, TGase activity is not antagonistic to EGF signaling. The mitogenic and anti-apoptotic effects of EGF were not compromised by TGase overexpression, and in fact, exogenous TGase expression promoted basal cell growth and resistance to serum deprivation-induced apoptosis. Moreover, analysis of TGase expression and GTP binding activity in a number of cell lines revealed high basal TGase GTP binding activity in tumor cell lines U87 and MDAMB231, indicating that constitutively active TGase may be a characteristic of certain cancer cells. These findings demonstrate that TGase may serve as a survival factor and RA-induced TGase expression requires the activation of PI3K but is antagonized by the Ras-ERK pathway.

The purpose of this study was to compare the rates of fluoride release with time from 1 nonfluoridated and 3 fluoride-containing orthodontic bonding materials in distilled water and artificial saliva. Materials tested were Assure (Reliance Orthodontic Products, Itasca, Ill), Fuji Ortho LC (GC, Tokyo, Japan), Python (TP Orthodontics, LaPorte, Ind), and Transbond XT (3M Dental Products, Monrovia, Calif). Ten specimens of each material type were stored in distilled water, and 10 of each type were stored in artificial saliva at 37 degrees C. Fluoride release was measured with an ion-specific electrode. Readings were taken periodically for a total time period of 6 months. At day 1, Assure released the most fluoride into distilled water (66.2 microg/cm(2)) and into artificial saliva (65.8 microg/cm(2)), followed by Fuji Ortho LC (25.9 microg/cm(2); 18.8 microg/cm(2)), Python (6.3 microg/cm(2); 4.2 microg/cm(2)), and Transbond (0.1 microg/cm(2); 0.1 microg/cm(2)). The fluoride release rates were highest during the first days of testing, declining to lower but more stable levels. At the end of 6 months, Fuji Ortho LC released the most fluoride (3.8 microg/cm(2); 3.5 microg/cm(2)) followed by Assure (3.1 microg/cm(2); 2.8 microg/cm(2)), Python (2.6 microg/cm(2); 1.7 microg/cm(2)), and Transbond (0.1 microg/cm(2); 0.1 microg/cm(2)). The type of storage medium did not dramatically affect fluoride release. The second part of the study, undertaken after a year of sample storage, tested the 20 samples of Assure for a further 2-week period, after exposure to running and still distilled water. Although fluoride release rates declined with time, they were still higher than the 1.5 microg/cm(2) level that is referenced as inhibiting decalcification of enamel in a clinical environment. Release rates were similar in running and still water at all time points. Throughout the 6-month period, all 3 fluoride-containing materials had rates of fluoride release that could theoretically inhibit decalcification of enamel.

The influence of dietary fat concentration and saturation on blastogenesis, cytotoxicity, antibody response and fatty acid composition of murine splenic lymphocytes was studied. Blastogenesis of lymphocytes from dietarily manipulated mice in response to alloantigens from control mice was significantly greater for those mice fed a diet containing minimal essential fatty acids (EFA) as the only fat source (EFA control) than those fed an EFA-deficient diet. When the dietary fat concentration was increased, blastogenic response decreased compared to the EFA control diet. Lymphocyte-mediated cytotoxicity against allogeneic melanoma cells was greater for mice receiving diets with EFA only than for those deficient in EFA. However, cytotoxicity responses of mice fed additional polyunsaturated fat (PUF) decreased as concentration increased, whereas responses of mice fet the saturated fat (SF) diets decreased only when the dietary fat concentration was greater than 8%. As compared to diets with EFA control, direct plaque-forming cell (PFC) response was decreased for mice fed high levels of PUF and increased for mice fed high levels of SF; however, no difference in the percentage of IgM-positive cells was observed. These changes in PFC response were inversely related to the levels of linoleic acid in the lymphocyte. Thus, high levels of dietary fat, and particularly PUF, suppress lymphocyte functions when EFA requirements are met, whereas low levels (EFA control) intensify these responses. EFA deficiency, however, suppress some lymphocyte responses. Thus, dietary lipids differentially modulate the levels of T- and B-cell responsiveness.

Dietary fat modulation of immune responsiveness was studied using a murine model subjected to prenatal and postnatal dietary manipulation. The weight of lymphoid associated organs, particularly the spleen, thymus and liver were significantly influenced by dietary fat saturation and concentration whereas other organs studied were not influenced by this manipulation. The serum immunoglobulins IgG1 and IgG2, but not IgM or IgA, increased in mice fed the polyunsaturated fat (PUF) diet as compared to the levels in those mice fed the saturated fat (SF) diet. While dietary manipulation generally did not influence the peripheral differential blood cell counts, the percentage of immunoglobulin positive splenic cells changed with dietary manipulation; the percentage of T cells, however, was not influenced by the experimental diets. In contrast, T-cell blastogenesis was influenced by both saturation and concentration of dietary fat whereas B-cell transformation was influenced by neither variable. Changes in T-cell responses were manifested through changes in the lymphocytes, and not cell numbers; PUF, particularly high levels, suppresses lymphocyte blastogenesis whereas low levels or a deficiency of PUF intensify this response. It is concluded that dietary fats influence the modulation and level of immune function.

Temporal changes in lymphocyte blastogenesis were studied using spleen cells from syngeneic melanoma-bearing and control mice fed various levels of purified diets containing 6, 10 or 30% casein. T-cell blastogenesis was stimulated by the presence of the tumor and these responses changed with the duration of feeding. In addition, protein concentration did not affect T-cell transformation but the level of energy intake influenced concanavalin A induced DNA synthesis. In contrast, the growing melanoma did not influence B-cell transformation whereas a very low level of dietary protein, a low level of energy intake and duration of the dietary manipulation influenced these cells. Tumor weights were generally not affected by the diet except in mice receiving a very low level of energy intake. Thus, we have found that B-cell responses were affected more than those of T-cells and that moderate protein deficiency did not enhance cellular immune responses in syngeneic tumor-bearing and control mice.