Population-based study of the sensitivity of axillary ultrasound imaging in the preoperative staging of node-positive invasive lobular carcinoma of the breast.

BACKGROUND: Preoperative staging of the axilla is important to allow decisions regarding neoadjuvant treatment and the management of the axilla. Invasive lobular carcinoma metastases are difficult to detect because of the infiltrative pattern of the nodal spread. In this study the sensitivity of preoperative axillary staging between invasive lobular (ILC) and ductal (IDC) carcinoma was compared. METHODS: All women diagnosed with pure ILC or IDC in the West of Scotland in 2012-2014 were identified from a database maintained prospectively within the Managed Clinical Network. Pretreatment axillary ultrasound imaging (AUS), core biopsy and fine-needle aspiration cytology (FNAC) results were compared between ILC and IDC. RESULTS: Some 602 women with ILC and 4199 with IDC had undergone axillary surgery, of whom 209 and 1402 respectively had nodal metastases. Pretreatment AUS sensitivity was significantly lower in ILC than in IDC (32·1 versus 50·1 per cent respectively, P < 0·001; OR 0·47, 95 per cent c.i. 0·34 to 0·64). Core biopsy had equally high sensitivity of 86 per cent in both subtypes; however, FNAC was significantly less sensitive in both ILC (55 per cent; P = 0·003) and IDC (75·6 per cent; P = 0·006). Multivariable analysis revealed that cT3-4 status and symptomatic presentation were both significant in predicting nodal metastasis in patients with ILC and false-negative AUS findings (OR 3·77, 95 per cent c.i. 1·69 to 8·42, P = 0·001; and OR 1·92, 1·24 to 2·98, P = 0·003, respectively). CONCLUSION: AUS is inferior in detecting axillary node metastasis in ILC compared with IDC. Women with cT3-4 lobular carcinoma may benefit from ultrasound-guided axillary biopsy regardless of the ultrasonographic appearance of the nodes.

Design of a simplified histopathologic model for gastrointestinal inflammation in dogs.

Significant interobserver variability in the diagnostic interpretation of endoscopic gastrointestinal (GI) specimens exists even with the use of World Small Animal Veterinary Association (WSAVA) standardization criteria. Chi-square analyses compared the extent of pathologists' agreement for microarchitectural features of inflammation in endoscopic specimens obtained from 253 animals of the original WSAVA study. Patterns of agreement between pathologists were classified as broad (3/4 pathologists agreed), dichotomous (2/4 pathologists agreed), or divergent (no agreement between pathologists). The simplified model for GI inflammation was based on those parameters for which the pathologists had either broad or minimally divergent opinions of histopathologic significance. In this model, the parameters chosen were as follows: gastric parameters (intraepithelial lymphocytes [IELs], lamina propria [LP] infiltrates, and mucosal fibrosis), duodenal parameters (villus atrophy, epithelial injury, IELs, crypt changes, and LP infiltrates), and colonic parameters (epithelial injury, crypt dilation, fibrosis, LP infiltrates, and goblet cell depletion). Preliminary data using this simplified model showed excellent correlation between pathologists in defining the presence and extent of GI inflammation in dogs.

Practice leadership and active support in residential services for people with intellectual disabilities: an exploratory study.

BACKGROUND: We hypothesised that a key factor determining the quality of active support was 'practice leadership' - provided by the first-line manager to focus staff attention and develop staff skills in providing direct support to enable people with intellectual disabilities to have a good quality of life. This exploratory study focused on what levels of practice leadership were found and its role in explaining variation in active support. METHOD: Relevant aspects of management, including practice leadership, were assessed by questionnaires administered to staff in residential settings alongside observational measures of active support and resident engagement in meaningful activity. Relationships between these variables were explored using regression and post hoc group comparisons. RESULTS: There was wide variation, with average levels of practice leadership being low, though improving over the period studied. Practice leadership had a significant impact on active support, but was fully mediated by the effect of quality of management. When the quality of management was higher better practice leadership did produce a significant difference in active support. However, higher quality of management on its own did not produce better active support. CONCLUSIONS: A number of limitations are acknowledged and further research is required. Practice leadership appears to be an important factor in enabling staff to provide active support but as part of generally good management. Given the rather low levels found, attention needs to be given to the training, career development and support of practice leaders and also to how to protect their time from their many other responsibilities.

Natural Heterobilharzia americana infection in horses in Texas.

The schistosome Heterobilharzia americana infects dogs, raccoons, and other mammals in the southeastern United States. Migration of eggs into the liver results in parasitic granulomas with varying degrees of fibrosis and inflammation. Recently, hepatic parasitic granulomas in horses were shown to be caused by H. americana infection. In the present study, samples of liver from 11 of 12 horses with hepatic granulomas identified at necropsy (n = 11) or surgical biopsy (n = 1) were used for DNA extraction, polymerase chain reaction amplification and sequencing using primers specific for a portion of the H. americana small subunit ribosomal RNA gene. A polymerase chain reaction amplicon of the correct size was produced from the extracted DNA in 8 of the 11 horses. Amplicons from 5 of the 8 positive horses were sequenced and had 100% identity with H. americana. In all but 2 of the 12 horses, Heterobilharzia was not responsible for the primary clinical disease, and the hepatic granulomas were considered an incidental finding.

Immobilised teicoplanin does not demonstrate antimicrobial activity against Staphylococcus aureus.

Antibacterial bone biomaterial coatings appeal to orthopaedics, dentistry and veterinary medicine. Achieving the successful, stable conjugation of suitable compounds to biomaterial surfaces is a major challenge. A pragmatic starting point is to make use of existing, approved antibiotics which are known to remain functional in a stationary, immobilised state. This includes the macrocyclic glycopeptide, teicoplanin, following the discovery, in the 1990's, that it could be used as a chiral selector in chromatographic enantiomeric separations. Importantly teicoplanin works at the level of the bacterial cell wall making it a potential candidate for biomaterial functionalisations. We initially sought to functionalise titanium (Ti) with polydopamine and use this platform to capture teicoplanin, however we were unable to avoid the natural affinity of the antibiotic to the oxide surface of the metal. Whilst the interaction between teicoplanin and Ti was robust, we found that phosphate resulted in antibiotic loss. Before contemplating the covalent attachment of teicoplanin to Ti we examined whether a commercial teicoplanin stationary phase could kill staphylococci. Whilst this commercially available material could bind N-Acetyl-L-Lys-D-Ala-D-Ala it was unable to kill bacteria. We therefore strongly discourage attempts at covalently immobilising teicoplanin and/or other glycopeptide antibiotics in the pursuit of novel antibacterial bone biomaterials.

Lysophosphatidic acid and calcitriol co-operate to promote human osteoblastogenesis: requirement of albumin-bound LPA.

Lysophosphatidic acid (LPA), a pleiotropic signalling lipid is assuming growing significance in osteoblast biology. Although committed osteoblasts from several mammalian species are receptive to LPA far less is known about the potential for LPA to influence osteoblast formation from their mesenchymal progenitors. An essential factor for both bone development and post-natal bone growth and homeostasis is the active metabolite of vitamin D3, calcitriol (D3). Previously we reported how a combination of LPA and D3 synergistically co-operated to enhance the differentiation of immature human osteoblasts. Herein we provide evidence for the formation of human osteoblasts from multiple, primary human bone marrow derived stromal (stem) cells (hBMSCs). Importantly osteoblast development from hBMSCs only occurred when LPA was administered as a complex with albumin, its natural carrier. Collectively our findings support a co-operative role of LPA and D3 in osteoblastogenesis, findings which may aid the development of novel treatment strategies for bone repair.

Cerebral and renal phaeohyphomycosis in a dog infected with Bipolaris species.

Mycotic meningoencephalitis in dogs may manifest as a primary disease of the central nervous system or as a part of disseminated infection. Fungi belonging to the genus Bipolaris are saprophytic plant pathogens and can cause disease in humans. The authors report a case of Bipolaris infection in a dog with granulomatous meningoencephalitis, nephritis, and vasculitis. The clinical and histological features resembled those of the more common aspergillosis, thus warranting confirmation by molecular methods. Polymerase chain reaction and sequence analysis identified Bipolaris from the brain lesion, indicating its involvement in the disease. To the authors' knowledge, this is the first reported case of meningoencephalitis caused by this fungus in a domestic animal.

Oncoplastic breast surgery: A guide to good practice.

Oncoplastic Breast Surgery has become standard of care in the management of Breast Cancer patients. These guidelines written by an Expert Advisory Group; convened by the Association of Breast Surgery (ABS) and the British Association of Plastic, Reconstructive and Aesthetic Surgeons (BAPRAS), are designed to provide all members of the breast cancer multidisciplinary team (MDT) with guidance on the best breast surgical oncoplastic and reconstructive practice at each stage of a patient's journey, based on current evidence. It is hoped they will also be of benefit to the wide range of professionals and service commissioners who are involved in this area of clinical practice.

Multicentric squamous cell carcinoma in situ associated with papillomavirus in a ferret.

A 6-year-old castrated male ferret presented with multiple black and tan proliferative skin lesions. Histologically, the lesions were characterized by multifocal plaques of irregular epidermal hyperplasia and full-thickness dysplasia, with loss of normal epithelial stratification, loss of nuclear polarity, and rare eosinophilic intranuclear inclusion bodies in the superficial layers of the epidermis. Immunohistochemical staining with a monoclonal antibody against papillomaviruses was strongly immunoreactive. Ultrastructurally, large numbers of hexagonal viral particles approximately 50 nm were observed within the nuclei of dysplastic superficial keratinocytes. To the authors' knowledge, this is the first report of a ferret multicentric squamous cell carcinoma in situ associated with papillomavirus.

Effect of tissue processing on assessment of endoscopic intestinal biopsies in dogs and cats.

BACKGROUND: Prior studies failed to detect significant association between hypoalbuminemia and small intestinal lesions. HYPOTHESIS: Use of pictorial templates will enhance consistency of interpathologist interpretation and identification of intestinal lesions associated with hypoalbuminemia. ANIMALS: Tissues from 62 dogs and 25 cats examined as clinical cases at 7 referral veterinary practices in 4 countries. METHODS: Retrospective, observational study. Histopathology slides from sequential cases undergoing endoscopic biopsy were examined by 4 pathologists by pictorial templates. Changes for 9 microscopic features were recorded as normal, mild, moderate or severe, and 2- and 4-point scales were tested for consistency of interpretation. Logistic regression models determined odds ratios (OR) of histologic lesions being associated with hypoalbuminemia while kappa statistics determined agreement between pathologists on histologic lesions. RESULTS: There was poor agreement (kappa = -0.013 to 0.3) between pathologists, and institution of origin of slides had effect (kappa = 1.0 for 3 of 4 lesions on slides from Institution 5) on agreement between pathologists on selected histologic features. Using 2 point as opposed to 4-point grading scale increased agreement between pathologists (maximum kappa = 0.69 using 4-point scale versus maximum kappa = 1.0 using 2-point scale). Significant association (P = .019- .04; 95% OR = 3.14-10.84) between lacteal dilation and hypoalbuminemia was found by 3 pathologists. CONCLUSIONS AND CLINICAL IMPORTANCE: Substantial inconsistency between pathologists remains despite use of pictorial template because of differences in slide processing. Distinguishing between mild and moderate lesions might be important source of the disagreement among pathologists.

'It's pretty hard with our ones, they can't talk, the more able bodied can participate': staff attitudes about the applicability of disability policies to people with severe and profound intellectual disabilities.

BACKGROUND: The level of resident's adaptive behaviour and staff facilitative practices are key sources of variation in outcomes for residents in community-based residential services. The higher the resident support needs the poorer their outcome. Although substantial investment has been made in values-based training for staff, their attitudes and the impact of these on practice is largely unexplored. METHOD AND FINDINGS: The first study used ethnographic and action research methods to examine the daily lives of 25 residents with severe and profound intellectual disabilities (ID), who lived in five small group homes, and the attitudes of the staff supporting them. Thematic analysis of the data led to a proposition that although staff accept principles of inclusion, choice and participation for people with ID in general, they do not consider it feasible to apply these to the people with severe and profound ID to whom they provide support. The findings from a second study that used a group comparison design and administered a short questionnaire about staff attitudes to 144 direct-care staff and first-line managers working in disability services confirmed this hypothesis. CONCLUSIONS: The study suggests more focused attention is needed to staff understanding the values embedded in current policies and their application to people with more severe disabilities.

Zirconia toughened alumina ceramic foams for potential bone graft applications: fabrication, bioactivation, and cellular responses.

Zirconia toughened alumina (ZTA) has been regarded as the next generation orthopedic graft material due to its excellent mechanical properties and biocompatibility. Porous ZTA ceramics with good interconnectivity can potentially be used as bone grafts for load-bearing applications. In this work, three-dimensional (3D) interconnected porous ZTA ceramics were fabricated using a direct foaming method with egg white protein as binder and foaming agent. The results showed that the porous ZTA ceramics possessed a bimodal pore size distribution. Their mechanical properties were comparable to those of cancellous bone. Due to the bio-inertness of alumina and zirconia ceramics, surface bioactivation of the ZTA foams was carried out in order to improve their bioactivity. A simple NaOH soaking method was employed to change the surface chemistry of ZTA through hydroxylation. Treated samples were tested by conducting osteoblast-like cell culture in vitro. Improvement on cells response was observed and the strength of porous ZTA has not been deteriorated after the NaOH treatment. The porous 'bioactivated' ZTA ceramics produced here could be potentially used as non-degradable bone grafts for load-bearing applications.

Histopathological standards for the diagnosis of gastrointestinal inflammation in endoscopic biopsy samples from the dog and cat: a report from the World Small Animal Veterinary Association Gastrointestinal Standardization Group.

The characterization of inflammatory change in endoscopic biopsy samples of the gastrointestinal mucosa is an increasingly important component in the diagnosis and management of canine and feline gastrointestinal disease. Interpretation has hitherto been limited by the lack of standard criteria that define morphological and inflammatory features, and the absence of such standardization has made it difficult, if not impossible, to compare results of retrospective or prospective studies. The World Small Animal Veterinary Association (WSAVA) Gastrointestinal Standardization Group was established, in part, to develop endoscopic and microscopical standards in small animal gastroenterology. This monograph presents a standardized pictorial and textual template of the major histopathological changes that occur in inflammatory disease of the canine and feline gastric body, gastric antrum, duodenum and colon. Additionally, a series of standard histopathological reporting forms is proposed, to encourage evaluation of biopsy samples in a systematic fashion. The Standardization Group believes that the international acceptance of these standard templates will advance the study of gastrointestinal disease in individual small companion animals as well as investigations that compare populations of animals.

Effect of sample quality on the sensitivity of endoscopic biopsy for detecting gastric and duodenal lesions in dogs and cats.

BACKGROUND: The quality of histopathology slides of endoscopic biopsies from different laboratories varies, but the effect of biopsy quality on outcome is unknown. HYPOTHESIS: The ability to demonstrate a histologic lesion in the stomach or duodenum of a dog or cat is affected by the quality of endoscopic biopsy samples submitted. More endoscopic samples are needed to find a lesion in poor-quality tissue specimens. ANIMALS: Tissues from 99 dogs and 51 cats were examined as clinical cases at 8 veterinary institutions or practices in 5 countries. METHODS: Histopathology slides from sequential cases that underwent endoscopic biopsy were submitted by participating institutions. Quality of the histologic section of tissue (inadequate, marginal, adequate), type of lesion (lymphangiectasia, crypt lesion, villus blunting, cellular infiltrate), and severity of lesion (normal, mild, moderate, severe) were determined. Sensitivity of different quality tissue samples for finding different lesions was determined. RESULTS: Fewer samples were required from dogs for diagnosis as the quality of the sample improved from inadequate to marginal to adequate. Duodenal lesions in cats displayed the same trend except for moderate duodenal infiltrates for which quality of tissue sample made no difference. Gastric lesions in dogs and mild gastric lesions in cats had the same trend, whereas the number of tissue samples needed to diagnose moderately severe gastric lesions in cats was not affected by the quality of tissue sample. CONCLUSIONS AND CLINICAL IMPORTANCE: The quality of endoscopically obtained tissue samples has a profound effect on their sensitivity for identifying certain lesions, and there are differences between biopsies of canine and feline tissues.

Abnormal cancellous bone collagen metabolism in osteoarthritis.

Biochemical investigations into the pathogenesis of osteoarthritis have, for the last two decades, concentrated on the mechanisms involved in the destruction of the articular cartilage. Although bone changes are known to occur, the biochemistry of the collagenous matrix within osteoarthritic bone has received scant attention. We report that bone collagen metabolism is increased within osteoarthritic femoral heads, with the greatest changes occurring within the subchondral zone. Collagen synthesis and its potential to mineralize were determined by the carboxy-terminal propeptide content and alkaline phosphatase activity, respectively. These data supported elevated new matrix formation. Our finding of a three- to fourfold increase in TGF-beta in osteoarthritic bone indicates that this might represent a stimulus for the increased collagen synthesis observed. Of additional significance is the hypomineralization of deposited collagen in the subchondral zone of osteoarthritic femoral heads, supporting a greater proportion of osteoid in the diseased tissue. The cross-linking of collagen was similar to that observed for controls. In addition, the degradative potential of osteoarthritic bone was considerably higher as demonstrated by increased matrix metalloproteinase 2 activity, and again the greater activity was associated with the subchondral bone tissue. The polarization exhibited in the metabolism of bone collagen from osteoarthritic hips might exacerbate the processes involved in joint deterioration by altering joint morphology. This in turn may alter the distribution of mechanical forces to the various tissues, to which bone is a sensitive responder. Bone collagen metabolism is clearly an important factor in the pathogenesis of osteoarthritis and certainly warrants further biochemical study.

Alkaline phosphatase binds tenaciously to titanium; implications for biological surface evaluation following bone implant retrieval.

Enhancing the performance and longevity of titanium (Ti) implants continues to be a significant developmental theme in contemporary biomaterials design. Our specific focus pertains to the surface functionalisation of Ti using the bioactive lipid, lysophosphatidic acid (LPA) and certain phosphatase-resistant analogues of LPA. Coating survivorship to a plethora of testing regimens is required to align with due regulatory process before novel biomaterials can enter clinical trials. One of the key acceptance criteria is coating retention to the physical stresses experienced during implantation. In assessing coating stability to insertion into porcine bone we found that a subsequent in vitro assessment to confirm coating persistence was masked by abundant alkaline phosphatase (ALP) contamination adsorbed to the metal surface. Herein we report that ALP can bind to Ti in a matter of minutes by simply immersing Ti samples in aqueous solutions of the enzyme. We strongly discourage the in vitro monitoring of osteoblast and stromal cell ALP expression when assessing bioactive coating survivorship following Ti implant retrieval form native bone tissue.

Oncoplastic breast conservation surgery is oncologically safe when compared to wide local excision and mastectomy.

BACKGROUND: Support for the oncological safety of oncoplastic breast conservation surgery (OBCS) is mostly based on evidence comparing recurrence rates after OBCS to wide local excision (WLE). However, OBCS is often indicated for larger cancers and oncological results should also be compared to patients treated with mastectomy. In this study we compared recurrence and survival following OBCS, mastectomy and WLE. METHODS: Patients treated with OBCS between 2009 and 2012 were identified from a prospectively maintained database. For comparison, consecutive patients treated with WLE or mastectomy with or without immediate reconstruction (Ms ± IR) over the same time period were identified. Histological variables of patients were compared using Fisher Exact or Chi squared tests, and recurrence and survival were compared using Kaplan-Meier and Cox regression survival analysis. RESULTS: 980 patients' data were analysed (OBCS: n = 104; WLE: n = 558; Ms ± IR: n = 318). Tumour size, grade, nodal status, ER, and PR expression of patients treated with OBCS were all significantly more adverse compared with patients treated with WLE (p < 0.001). These histological variables were similar in patients treated with Ms ± IR and OBCS. 5-year local recurrence rates were similar in all three groups (WLE: 3.4 per cent, OBCS: 2 per cent, Ms ± IR: 2.6 per cent; log rank = 0.973), while distant recurrence rates were higher after Ms ± IR and OBCS (Ms ± IR:13.1 per cent, OBCS:7.5 per cent, WLE:3.3 per cent; log rank: p < 0.001). CONCLUSION: OBCS is oncologically safe in patients even when histological results are similar to patients treated with Ms ± IR.

Lysophosphatidic acid cooperates with 1alpha,25(OH)2D3 in stimulating human MG63 osteoblast maturation.

Osteoblast maturation is partly controlled by the interaction of 1alpha,25(OH)(2)D(3) (D3), an active metabolite of Vitamin D, with other growth factors. The first reports describing the in vitro effect of D3 on human osteoblast differentiation performed experiments in the presence of serum. One potentially exciting candidate that might help explain the D3 responses observed for osteoblasts cultured with serum is lysophosphatidic acid (LPA). Drawn to the possibility that D3 and serum borne LPA might interact to induce osteoblast maturation we co-treated human cells with D3 and serum in the presence of Ki16425, an LPA receptor antagonist. Ki16425 inhibited osteoblast maturation as determined by markedly reduced alkaline phosphatase (ALP) expression. We subsequently found that LPA and D3 acted synergistically in generating mature osteoblasts and that this differentiation response could be inhibited using pertussis toxin, implying an important role of Galphai signal transduction. Furthermore, we found evidence for a dependency on both mitogen activated protein kinase kinase (MEK) and Rho associated coiled kinase (ROCK) for LPA and D3 stimulated maturation.

High-Grade Myxoid Liposarcoma (Round Cell Variant) in a Dog.

A 10-year-old, neutered male, Basset hound had a 26 × 21 × 21 cm infiltrative mass on the left abdominal wall that did not extend into the peritoneal cavity based on radiographs and abdominal computed tomography. Cytological examination revealed moderate numbers of neoplastic round cells, which frequently contained numerous round, clear, cytoplasmic vacuoles. Histologically, the tumour was composed of two morphologically distinct cell populations forming a continuum of heterogeneously differentiated cells. The primary spindle-shaped population formed streams with abundant, lightly eosinophilic, alcian blue-positive, myxoid matrix. The second population was arranged in sheets and had a round cell appearance. Scattered within both populations were neoplastic cells containing variably sized, intracytoplasmic, osmium tetroxide-positive vacuoles (lipid). Multifocal large pools of mucin formed pseudocysts, and numerous small capillaries were present throughout the neoplasm. According to the current World Health Organization veterinary classification of liposarcomas, this neoplasm had morphological features of both the myxoid and pleomorphic variants of liposarcoma; however, it was analogous to the recently defined high-grade myxoid liposarcoma in man. Myxoid liposarcoma with round cells has not been described previously in dogs. This case highlights the need to potentially re-evaluate the current classification of liposarcomas in animals.

Chitinase 3-like 1 expression by human (MG63) osteoblasts in response to lysophosphatidic acid and 1,25-dihydroxyvitamin D3.

Chitinase 3-like 1, otherwise known as YKL-40, is a secreted glycoprotein purported to have a role in extracellular matrix metabolism. The first mammalian cell type found to express YKL-40 was the human osteosarcoma-derived osteoblast, MG63. In that first study the active vitamin D3 metabolite, 1,25-dihydroxycholecalciferol (1,25D), stimulated YKL-40 expression, thereby indicating that a vital factor for skeletal health promoted YKL-40 synthesis by bone forming cells. However, when these MG63 cells were exposed to 1,25D they were also exposed to serum, a rich source of the pleiotropic lipid mediator, lysophosphatidic acid (LPA). Given that 1,25D is now known to co-operate with selected growth factors, including LPA, to influence human osteoblast differentiation we hypothesised that 1,25D and LPA may work together to stimulate osteoblast YKL-40 expression. Herein we report that 1,25D and LPA synergistically promote YKL-40 expression by MG63 cells. Inhibitors targeting AP1, MEK, Sp1 and STAT3 blunted the expression of both alkaline phosphatase and YKL-40 by MG63 cells in response to co-stimulation with 1,25D and LPA. Other ligands of the vitamin D receptor also co-operated with LPA in driving YKL-40 mobilisation. Collectively our findings highlight another important role of 1,25D and LPA in the regulation of human osteoblast function.