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Pulmonary hypertension (PH) is a common comorbidity in dogs with myxomatous mitral valve disease (MMVD), and can induce various changes in the right heart, such as right ventricular (RV) hypertrophy, dilatation, and dysfunction. We hypothesized that RV function, not only systolic function but also diastolic function, could be worsened with PH progression. We aimed to compare RV systolic and diastolic function in dogs with MMVD. Twenty healthy dogs and sixty-eight dogs with MMVD were enrolled. Dogs with MMVD were classified into the probability of PH. Two-dimensional and Doppler echocardiographic indices for right heart and two-dimensional speckle tracking echocardiography indices were measured. The morphological indicators of the right heart were significantly higher only in the high probability of PH group. The RV strain, early-diastolic and systolic strain rates were significantly lower in the high probability of PH group than those in the low and intermediate probability of PH groups. Multivariate analysis showed that increased RV internal dimension normalized by body weight and RV myocardial performance index were significantly associated with the presence of right-sided congestive heart failure. Speckle tracking echocardiography-derived RV systolic and diastolic function were activated in the low and intermediate probability of PH groups. However, dogs with high probability of PH showed RV myocardial dysfunction and dilatation. Increased RV myocardial performance index and end-diastolic RV internal dimension normalized by body weight were significantly associated with the presence of right-sided congestive heart failure in dogs with MMVD.

Background Tricuspid annular plane systolic excursion (TAPSE) is a common right ventricular (RV) function indicator. However, TAPSE was not decreased in dogs with myxomatous mitral valve disease (MMVD) and postcapillary pulmonary hypertension (PH) because of its load, angle, and body weight dependency, and TAPSE was considered a preload‐dependent index. Objectives To evaluate the utility of TAPSE normalized by RV size in dogs with postcapillary PH. Animals Twenty healthy dogs and 71 MMVD dogs with or without PH. Methods In this prospective observational study, end‐diastolic RV internal dimension (RVIDd), end‐diastolic and end‐systolic RV area, and end‐diastolic RV wall thickness were measured as RV size indices. The TAPSE was measured using B‐mode and M‐mode methods. Normalized TAPSE was calculated by dividing TAPSE by each RV size index. The RV strain was obtained as the detailed RV function using 2‐dimensional speckle tracking echocardiography. All indices were compared among the PH severity groups and in the presence of right‐sided congestive heart failure (R‐CHF). Results Although nonnormalized TAPSE was higher with PH severity progression, each normalized TAPSE showed a significant decrease in the severe PH group (P

Purpose Recently, fecal microbiota transplantation (FMT) has been tested in veterinary medicine as a treatment option for multiple gastrointestinal (GI) diseases, such as inflammatory bowel disease (IBD). However, there are no reports of changes in the microbial diversity of fecal microbiome after treatment with FMT in canine IBD cases. Moreover, little is known about the long-term efficacy and safety of FMT treatment for dogs. Herein, we present a case of canine intractable IBD treated with repeated, long-term FMT. Patients and methods The patient was a 10-year-old, neutered, male, 4-kg Toy Poodle with a prolonged history of vomiting and diarrhea. Fecal examination for pathogens was negative. Despite treatment with multiple antibacterial and antidiarrheal agents, the patient showed no improvement. Endoscopic mucus sampling diagnosed a case of lymphocytic-plasmacytic duodenitis, ie, idiopathic IBD. Eventually, we performed periodic, long-term fecal microbiota transplantation of fresh donor feces collected from a 4-year-old, 32.8-kg, neutered male Golden Retriever by rectal enema. Additionally, we performed 16S rRNA sequence analysis, before and after FMT, to evaluate the microbiome diversity. Results Fecal microbiome diversity after FMT resembled that of the healthy donor dog’s fecal microbiome, before FMT, which led us to conclude that the fecal microbiome in our patient normalized with FMT. Moreover, the clinical symptoms improved remarkably with regard to the changes in the fecal microbiome. Additionally, we noted no observable side effects during FMT treatment. Conclusion This report indicates the efficacy and safety of long-term, periodic FMT for a case of canine IBD based on attenuation of clinical symptoms and changes in fecal microbiome diversity. Therefore, FMT could be chosen as a treatment option for IBD in canines in the future.

Congestive heart failure (CHF) is a life-threatening condition in cats with cardiomyopathy. We hypothesized that myocardial dysfunction may induce progression to CHF pathophysiology in cats with cardiomyopathy. However, no previous studies have evaluated the involvement of myocardial dysfunction in cats with CHF. In this study, we aimed to evaluate the relationship between CHF and myocardial function assessed using two-dimensional speckle-tracking echocardiography (2D-STE). Sixteen client-owned healthy cats and 32 cats with cardiomyopathy were enrolled in this study. Cats were classified into three groups: healthy cats, cardiomyopathy without CHF (CM group), and cardiomyopathy with CHF (CHF group). Left ventricular (LV) longitudinal and circumferential strains (SL and SC, respectively), and right ventricular (RV) SL were measured using 2D-STE. Logistic regression analysis was performed to assess the relationship between CHF and echocardiographic variables, including 2D-STE. Results comparing the healthy cats and CM vs. CHF groups showed that increased left atrial to aortic diameter ratio and decreased LV apical SC were significantly associated with the existence of CHF (odds ratio [95% confidence interval]: 1.40 [1.16–1.78] and 1.59 [1.06–2.36], respectively). Results comparing the CM vs. CHF group showed that increased end-diastolic RV internal dimension and decreased RV SL were significantly associated with the existence of CHF (odds ratio: 1.07 [1.00–1.13] and 1.34 [1.07–1.68], respectively). Left atrial enlargement and depressed LV apical myocardial function may be useful tools for predicting the progression to CHF in cats. Furthermore, RV enlargement and dysfunction may lead to the onset of CHF in asymptomatic cats with cardiomyopathy.

Post-capillary pulmonary hypertension (PH) is a life-threatening complication in dogs with myxomatous mitral valve disease (MMVD). An increase in pulmonary vascular resistance (PVR) is associated with post-capillary PH progression. In humans, PVR estimated by echocardiography (PVRecho) enables the non-invasive assessment of PVR in patients with PH. This study aimed to evaluate the clinical utility of PVRecho in dogs with MMVD, PH probability, and right-sided congestive heart failure (R-CHF). Dogs with MMVD and detectable tricuspid valve regurgitation were included in the study. Dogs were classified into three PH probability groups (low/intermediate/high) and according to the presence or absence of R-CHF. All dogs underwent echocardiographic measurements for right ventricular (RV) morphology and function. PVRecho was calculated by two methods using tricuspid valve regurgitation velocity and velocity–time integral of the pulmonary artery flow (PVRecho and PVRecho2). RV size indicators were significantly higher with a higher probability of PH. RV strain and velocity–time integral of the pulmonary artery flow in the high probability group were significantly lower than those in the other groups. Tricuspid valve regurgitation velocity, PVRecho, and PVRecho2 were significantly higher with an increase in PH probability. Logistic regression analysis revealed a significant association between the presence of R-CHF and increased PVRecho2 and end-diastolic RV internal dimension normalized by body weight. PVRecho and PVRecho2 showed significant differences among the PH probability groups. These non-invasive variables may be useful for the diagnosis and stratification of PH and the determination of the presence of R-CHF in dogs with MMVD.

Background: Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by an increase in pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. Right ventricle adapts to its pressure overload through various right ventricular (RV) compensative mechanisms: adaptive and maladaptive remodeling. The former is characterized by concentric hypertrophy and increased compensatory myocardial contractility, whereas the latter is distinguished by eccentric hypertrophy associated with impaired myocardial function.Objectives: To evaluate the RV adaptation associated with the increase of PAP using two-dimensional speckle tracking echocardiography.Animals: Seven experimentally induced PH models.Methods: Dogs were anesthetized and then a pulmonary artery catheter was placed via the right jugular vein. Canine models of PH were induced by the repeated injection of microspheres through the catheter and monitored pulmonary artery pressure. Dogs were performed echocardiography and hemodynamic measurements in a conscious state when baseline and systolic PAP (sPAP) rose to 30, 40, 50 mmHg, and chronic phase. The chronic phase was defined that the sPAP was maintained at 50 mmHg or more for 4 weeks without injection of microspheres.Results: Pulmonary artery to aortic diameter ratio, RV area, end-diastolic RV wall thickness, and RV myocardial performance index were significantly increased in the chronic phase compared with that in the baseline. Tricuspid annular plane systolic excursion was significantly decreased in the chronic phase compared with that in the baseline. The RV longitudinal strain was significantly decreased in the sPAP30 phase, increased in the sPAP40 and sPAP50 phases, and decreased in the chronic phase.Conclusions: Changes in two-dimensional speckle tracking echocardiography-derived RV longitudinal strain might reflect the intrinsic RV myocardial contractility during the PH progression, which could not be detected by conventional echocardiographic parameters.

Simple Summary The endomyocardial form of restrictive cardiomyopathy, a primary disorder of the myocardium, is one of the diseases with poor prognosis in cats. While two-dimensional speckle-tracking echocardiography has been known to identify myocardial deformations, its function relative to cats with the endomyocardial form of restrictive cardiomyopathy has yet to be characterized. We hypothesized that both the left and right myocardial functional abnormalities may occur in cats with the endomyocardial form of restrictive cardiomyopathy, causing this disease pathophysiology and clinical status. In the current study, cats were assessed for layer-specific myocardial function (whole, endocardial, and epicardial) in the left ventricular longitudinal and circumferential directions, and right ventricular longitudinal direction, via two-dimensional speckle-tracking echocardiography. Our study indicated that cats with restrictive cardiomyopathy have reduced left ventricular myocardial function. Notably, left ventricular systolic circumferential endocardial strain and circumferential endocardial-to-epicardial strain ratio were lower in cats with restrictive cardiomyopathy. Furthermore, some right ventricular myocardial deformations were also differerent in cats with restrictive cardiomyopathy. Myocardial function assessed by two-dimensional speckle-tracking echocardiography could reveal left and right myocardial dysfunction. Abstract The endomyocardial form of restrictive cardiomyopathy (EMF-RCM), a primary disorder of the myocardium, is one of the diseases with poor prognosis in cats. We hypothesized that both the left and right myocardial functional abnormalities may occur in cats with EMF-RCM, causing this disease pathophysiology and clinical status. Out of the 25 animals included in this study, 10 were client-owned cats with EMF-RCM, and 15 were healthy cats. In this study, cats were assessed for layer-specific myocardial function (whole, endocardial, and epicardial) in the left ventricular longitudinal and circumferential directions, and right ventricular longitudinal direction, via two-dimensional speckle-tracking echocardiography (2D-STE). Cats with EMF-RCM had depressed left ventricular myocardial deformations both in systole (whole longitudinal strain, epicardial longitudinal strain, and endocardial circumferential strain) and diastole (early and late diastolic longitudinal strain rates, and late diastolic circumferential strain rate) compared to controls. Furthermore, some right ventricular myocardial deformations (systolic longitudinal strain in epicardial layers, and endocardial-to-epicardial strain ratio) were significantly differerent in cats with EMF-RCM. Myocardial function assessed by 2D-STE could reveal left and right myocardial dysfunction.

Background Hypertrophic cardiomyopathy (HCM), a primary disorder of the myocardium, is the most common cardiac disease in cats. However, determination of layer-specific myocardial function with 2D speckle-tracking echocardiography in cats with asymptomatic HCM has not yet been reported. Objectives To quantitatively measure layer-specific myocardial function of asymptomatic cats with HCM. Animals Ten client-owned, asymptomatic cats with obstructive HCM and 13 healthy cats. Methods A retrospective, case-control study. Cats underwent assessment of layer-specific myocardial function (whole, endocardial, and epicardial) in the longitudinal and circumferential directions by using 2D speckle-tracking echocardiography. Results Longitudinal strains were significantly lower in cats with HCM than controls in the whole (-15.5% vs -19.1%), endocardial (-18.3% vs -21.8%), and epicardial (-13.1% vs -16.8%) layers. Circumferential strains in whole and epicardial layers also were significantly lower in cats with HCM as compared with controls (-15.0% vs -20.2% and - 4.4% vs -9.4%, respectively). However, no significant difference was found between cats with HCM and controls in the global circumferential strain in the endocardial layer (-31.2% vs -34.2%). The circumferential endocardial-to-epicardial strain ratio was significantly higher in cats with HCM than in controls (6.1 vs 3.5). Conclusions and clinical importance Layer-specific myocardial function assessed by 2D speckle-tracking echocardiography differed in asymptomatic cats with obstructive HCM compared to controls despite their apparently normal systolic function, as determined by conventional echocardiography. The maintained endocardial circumferential strain and higher circumferential endocardial-to-epicardial strain ratio may reflect compensation for occult systolic dysfunction in cats with obstructive HCM.

Background Egg allergy is one of the most common food allergies in children. To date, oral immunotherapy (OIT) has been considered as a promising treatment option for egg allergy. However, safety issues remain concerning severe adverse events requiring epinephrine injection. Hence, establishing a safer method to treat egg allergy would be beneficial. We report here two children with egg allergy who were safely treated with sublingual immunotherapy (SLIT) before transitioning to OIT. Case presentation Patient 1 was a 7-year-old girl and Patient 2 was a 5-year-old girl. Although OIT for egg had been attempted in both patients, severe anaphylactic symptoms were induced by ingesting only 0.1 g of heated whole egg. Therefore, SLIT was conducted with aqueous suspensions consisting of water and heated whole egg powder. Suspensions were administered sublingually, kept in the mouth for 2 min, and spat out immediately thereafter. SLIT was continued for 7 months for Patient 1 and 8 months for Patient 2 due to the exploratory character of the study. Afterwards, the patients successfully transferred to low-dose OIT with 1 g of heated whole egg (≒170 mg of egg protein) daily, and are continuing the therapy as of June 2020. As for adverse reactions, Patient 1 expressed oral cavity itchiness once at the beginning of SLIT. Patient 2 had no adverse reaction. The levels of antigen-specific IgE decreased in both patients after SLIT, and further decreased after switching to OIT. Conclusions Few clinical studies have evaluated the efficacy and safety of SLIT for egg allergy. Although the treatment was conducted in only two patients, our results have shown that SLIT is a promising treatment procedure for egg allergy. Further clinical trials will be needed to additionally assess the efficacy and safety of SLIT in children with food allergy.

Despite the accumulating evidences of the significance of humoral cancer immunity, its molecular mechanisms have largely remained elusive. Here we show that B-cell repertoire sequencing of 102 clinical gastric cancers and molecular biological analyses unexpectedly reveal that the major humoral cancer antigens are not case-specific neo-antigens but are rather commonly identified as ribonucleoproteins (RNPs) in the focal adhesion complex. These common antigens are shared as autoantigens with multiple autoimmune diseases, suggesting a direct molecular link between cancer- and auto-immunity on the focal adhesion RNP complex. This complex is partially exposed to the outside of cancer cell surfaces, which directly evokes humoral immunity and enables functional bindings of antibodies to cancer cell surfaces in physiological conditions. These findings shed light on humoral cancer immunity in that it commonly targets cellular components fundamental for cytoskeletal integrity and cell movement, pointing to a novel modality of immunotherapy using humoral immunological reactions to cancers., Atsumi et al. identify antigens to B-cell receptors isolated from gastric tumour samples. They find that focal adhesion-related protein complexes, several of which are also targets for autoimmune disease, are major humoral cancer antigens. These findings provide insights into humoral immunity in tumor environments.

SummaryCancer histological images contain rich biological and clinical information, but quantitative representation can be problematic and has prevented direct comparison and accumulation of large-scale datasets. Here we show that deep texture representations (DTRs) produced by a bilinear Convolutional Neural Network, express cancer morphology well in an unsupervised manner, and work as a universal encoder for cancer histology. DTRs are useful for content-based image retrieval, enabling quick retrieval of histologically similar images from optimally area selected datasets of 7,175 cases from The Cancer Genome Atlas. Via comprehensive comparison with driver and clinically actionable gene mutations, we have successfully predicted 309 combinations of genomic features and cancer types from hematoxylin and eosin-stained images at high accuracy (AUC > 0.70 and q < 0.02). With its mounting capabilities on accessible devices such as smartphones, DTR-based encoding for cancer histology has a potentially strong impact on global equalization for cancer diagnosis and targeted therapies.

In human medicine, fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridioides difficile infection. It has also been tested as a treatment for multiple gastrointestinal diseases, including inflammatory bowel disease (IBD). However, only a few studies have focused on the changes in the microbiome following FMT for canine IBD. Here, we performed FMT in nine dogs with IBD using the fecal matter of healthy dogs and investigated the subsequent changes in the fecal microbiome and clinical signs. In three dogs, the fecal microbiome was examined by 16S rRNA sequencing. Fusobacteria were observed at a low proportion in dogs with IBD. However, the post-FMT microbiome became diverse and showed a significant increase in Fusobacteria proportion. Fusobacterium was detected in the nine dogs by quantitative polymerase chain reaction. The proportion of Fusobacterium in the post-FMT fecal microbiome was significantly increased (p

The potential of mesenchymal stem cells (MSCs) to differentiate into nonmesodermal cells such as pancreatic beta cells has been reported. New cell-based therapy using MSCs for diabetes mellitus is anticipated as an alternative treatment option to insulin injection or islet transplantation in both human and veterinary medicine. Several protocols were reported for differentiation of MSCs into insulin-producing cells (IPCs), but no studies have reported IPCs generated from canine MSCs. The purpose of this study was to generate IPCs from canine adipose tissue-derived MSCs (AT-MSCs) in vitro and to investigate the effects of IPC transplantation on diabetic mice in vivo. Culturing AT-MSCs with the differentiation protocol under a two-dimensional culture system did not produce IPCs. However, spheroid-like small clusters consisting of canine AT-MSCs and human recombinant peptide μ-pieces developed under a three-dimensional (3D) culture system were successfully differentiated into IPCs. The generated IPCs under 3D culture condition were stained with dithizone and anti-insulin antibody. Canine IPCs also showed gene expression typical for pancreatic beta cells and increased insulin secretion in response to glucose stimulation. The blood glucose levels in streptozotocin-induced diabetic mice were decreased after injection with the supernatant of canine IPCs, but the hyperglycemic states of diabetic mice were not improved after transplanting IPCs subcutaneously or intramesenterically. The histological examination showed that the transplanted small clusters of IPCs were successfully engrafted to the mice and included cells positive for insulin by immunofluorescence. Several factors, such as the transplanted cell number, the origin of AT-MSCs, and the differentiation protocol, were considered potential reasons for the inability to improve the hyperglycemic state after IPC transplantation. These findings suggest that canine AT-MSCs can be differentiated into IPCs under a 3D culture system and IPC transplantation may be a new treatment option for dogs with diabetes mellitus.

Resting-state (rs) functional magnetic resonance imaging (fMRI) studies have revealed dysfunctional thalamocortical functional connectivity (FC) in schizophrenia. However, the relationship between thalamocortical FC and cognitive impairment has not been thoroughly investigated. We hypothesized that aberrant thalamocortical FC is related to attention deficits in schizophrenia. Thirty-eight patients with schizophrenia and 38 matched healthy controls underwent rs-fMRI and task fMRI while performing a Flanker task. We observed decreased left thalamic activation in patients with schizophrenia using task fMRI to determine the thalamic seed. A seed-based analysis using this seed was performed in the whole brain to assess differences in thalamocortical FC between the groups. Significantly worse performance was observed in the patient group. The rs-fMRI analysis revealed significantly increased FC between the left thalamus seed and the occipital cortices/postcentral gyri in patients when compared to controls. In the patient group, significant positive correlations were observed between the degree of FC from the left thalamus to the bilateral occipital gyri, which correspond to the visual cortex, and the Flanker effect. No significant correlation was detected in the control group. These results indicate that aberrant FC between the left thalamus and the visual cortex is related to attention deficits in schizophrenia.

Pain is a widely neglected symptom in patients with amyotrophic lateral sclerosis (ALS), even though it may be common and have a significant impact on the quality of life.The aim of this study was to determine the frequency and characteristics of pain and its treatment in ALS patients.A multicenter cross-sectional study.Eighty patients with ALS from eight hospitals.Data on demographics, functional status, and pharmacological treatment were collected. The Barthel Index (BI) was used to assess functional status. Pain was measured using the 0-5-point Wong-Baker FACES Pain Rating Scale.Pain was reported by 53.8% of ALS patients, and 36.3% reported receiving pain medication. Opioids were the drugs most commonly used to treat pain. The differences in pain frequency according to functional status were not statistically significant (p = 0.38). The pain intensity in patients whose functional status was total dependence (BI 0-20, 2.5 ± 1.2) was significantly worse than that in those with better functional status (BI 21-60, 1.4 ± 0.7; BI 61-99, 1.4 ± 0.5; p 0.01).Our study indicates that all patients with ALS have the potential to suffer from pain, the intensity of which increases with decreased functional status.

Motivation The aim of precision medicine is to harness new knowledge and technology to optimize the timing and targeting of interventions for maximal therapeutic benefit. This study explores the possibility of building AI models without precise pixel-level annotation in prediction of the tumor size, extrathyroidal extension, lymph node metastasis, cancer stage and BRAF mutation in thyroid cancer diagnosis, providing the patients’ background information, histopathological and immunohistochemical tissue images. Results A novel framework for objective evaluation of automatic patient diagnosis algorithms has been established under the auspices of the IEEE International Symposium on Biomedical Imaging 2017— A Grand Challenge for Tissue Microarray Analysis in Thyroid Cancer Diagnosis. Here, we present the datasets, methods and results of the challenge and lay down the principles for future uses of this benchmark. The main contributions of the challenge include the creation of the data repository of tissue microarrays; the creation of the clinical diagnosis classification data repository of thyroid cancer; and the definition of objective quantitative evaluation for comparison and ranking of the algorithms. With this benchmark, three automatic methods for predictions of the five clinical outcomes have been compared, and detailed quantitative evaluation results are presented in this paper. Based on the quantitative evaluation results, we believe automatic patient diagnosis is still a challenging and unsolved problem. Availability and implementation The datasets and the evaluation software will be made available to the research community, further encouraging future developments in this field. (http://www-o.ntust.edu.tw/cvmi/ISBI2017/). Supplementary information Supplementary data are available at Bioinformatics online.

Obinutuzumab is a novel glycoengineered, type-II anti-CD20 monoclonal antibody that was recently developed to treat follicular lymphoma (FL), the most prevalent subtype of indolent B-cell lymphoma. Several intensely hypermetabolic lesions (SUVmax: 40) were identified in the post-mediastinal and paraaortic lymph nodes by 18F-FDG-PET maximum-intensity projection images of a 58-year-old man who presented with systemic lymphadenopathy. A biopsy at the time of laparotomy definitively diagnosed grade 1 FL. The patient was given the recommended standard premedication, comprising acetaminophen (1000 mg), diphenhydramine (50 mg), and dexamethasone (20 mg), and then started on six cycles of obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). However, the patient developed severe hypotension and dyspnea about 15 min after starting obinutuzumab. It was difficult to differentiate between a possible allergic reaction and infusion-related reaction. A pleural effusion was drained to reduce the tumor burden, after which a single course of CHOP was started. Rituximab (R) was added 10 days later without incident, and the patient completed six cycles of the R-CHOP therapy without adverse events. We conclude that R-CHOP was safe for administration to patients who react to infused obinutuzumab. Such patients should be carefully monitored during R infusion, given the risk of cross-reactivity.

Background Inconsistency of treatment response in cats with obstructive hypertrophic cardiomyopathy is well recognized. We hypothesized that the difference in response to beta-blockers may be caused by myocardial functional abnormalities. This study was designed to compare myocardial function in cats with obstructive hypertrophic cardiomyopathy with and without response to beta-blockers. Twenty-one, client-owned, hypertrophic cardiomyopathy cats treated with carvedilol were analyzed. After carvedilol treatment, cats with decreased left ventricular outflow tract velocity were categorized as responders (n = 10); those exhibiting no response (no decrease in the left ventricular outflow tract velocity) were categorized as non-responders (n = 11). The cats were examined using layer-specific assessment of the myocardial function (whole, endocardial, and epicardial layers) longitudinally and circumferentially by two-dimensional speckle-tracking echocardiography, before and after carvedilol treatment. Results The non-responder cats had a significantly higher age, end-diastolic left ventricular posterior-wall thickness, peak velocity of left ventricular outflow tract, and dose of carvedilol than the responders (p = 0.04, p p p p p = 0.006). According to the multivariate analysis, circumferential strain in the epicardial layer was the only independent correlate of treatment response with carvedilol. Conclusions Myocardial function, assessed by two-dimensional speckle-tracking echocardiography, differed in cats with hypertrophic cardiomyopathy with and without response to beta-blockers. The determination of layer-specific myocardial function may facilitate detailed pathophysiologic assessment and treatment response in cats with hypertrophic cardiomyopathy.

BACKGROUND: Manually-assisted coughing and mechanical insufflation-exsufflation (MI-E) are commonly used in patients with Duchenne muscular dystrophy (DMD). Few studies have compared cough peak flow (CPF) with manually-assisted coughing to other methods, such as MI-E + manually-assisted coughing. In addition, few studies have reported the reliability of the measured CPF values. This study aimed to compare CPF with different cough-assistance methods and to examine the reliability of CPF data. METHODS: The study included 12 subjects with DMD (mean age, 34 ± 8 y). CPF, CPF + manually-assisted coughing (assisted CPF), maximum insufflation capacity (MIC) + CPF (MIC-CPF), MIC + manually-assisted coughing (MIC+assisted CPF), MI-E (MI-E–CPF), and MI-E + assisted CPF were measured. A spirometer was used to compare CPF measurements obtained with each of the cough-assist techniques. The reliability of the measured CPF values was analyzed using Bland-Altman analysis. RESULTS: CPF was 59 ± 34 L/min, assisted CPF was 113 ± 32 L/min, MIC-CPF was 170 ± 30 L/min, MIC+assisted CPF was 224 ± 62 L/min, MI-E–CPF was 199 ± 40 L/min, and MI-E + assisted CPF was 240 ± 38 L/min. A fixed and proportional bias was found in the CPF measurements made with the peak flow meter and the spirometer. The average 95% CI in the difference between peak flow meter, MI-E, and CPF obtained using the spirometer were −7.45 to −1.95 and −1.45 to 4.95, respectively. Test for correlation was r = 0.54 (P CONCLUSION: MI-E + assisted CPF was the highest. The CPF measured with the peak flow meter suggested underestimation.

BackgroundAs a large number of digital histopathological images have been accumulated, there is a growing demand of content-based image retrieval (CBIR) in pathology for educational, diagnostic, or research purposes. However, no CBIR systems in digital pathology are publicly available.ResultsWe developed a web application, the Luigi system, which retrieves similar histopathological images from various cancer cases. Using deep texture representations computed with a pre-trained convolutional neural network as an image feature in conjunction with an approximate nearest neighbor search method, the Luigi system provides fast and accurate results for any type of tissue or cell without the need for further training. In addition, users can easily submit query images of an appropriate scale into the Luigi system and view the retrieved results using our smartphone application. The cases stored in the Luigi database are obtained from The Cancer Genome Atlas with rich clinical, pathological, and molecular information. We tested the Luigi system by querying typical cancerous regions from four cancer types, and confirmed successful retrieval of relevant images.ConclusionsThe Luigi system will help students, pathologists, and researchers easily retrieve histopathological images of various cancers similar to those of the query image.

Case summary A 6-month-old female cat with a history of chronic regurgitation presented with weight loss. CT angiography (CTA) showed severe constriction of the oesophagus due to an aberrant right subclavian artery and Kommerell’s diverticulum. The cat was surgically treated and remained clinically normal. More than 1 year after surgery, the general condition of the cat was stable and body weight had increased. Relevance and novel information This case report describes the clinical findings and surgical management of a cat diagnosed with severe oesophageal constriction caused by an aberrant right subclavian artery with Kommerell’s diverticulum (markedly dilated origin of the aberrant right subclavian artery), which are rare vascular anomalies in veterinary medicine and specifically in cats. The Kommerell’s diverticulum compressed the oesophagus and contributed to the severe oesophageal constriction in this case. Preoperative CTA was useful in the diagnosis and treatment planning.

Case summary A 5-month-old intact female Scottish Fold cat was presented for cardiac evaluation. Careful auscultation detected a slight systolic murmur (Levine I/VI). The findings of electrocardiography, thoracic radiography, non-invasive blood pressure measurements and conventional echocardiographic studies were unremarkable. However, two-dimensional speckle tracking echocardiography revealed abnormalities in myocardial deformations, including decreased early-to-late diastolic strain rate ratios in longitudinal, radial and circumferential directions, and deteriorated segmental systolic longitudinal strain. At the follow-up examinations, the cat exhibited echocardiographic left ventricular hypertrophy and was diagnosed with hypertrophic cardiomyopathy using conventional echocardiography. Relevance and novel information This is the first report on the use of two-dimensional speckle tracking echocardiography for the early detection of myocardial dysfunction in a cat with hypertrophic cardiomyopathy; the myocardial dysfunction was detected before the development of hypertrophy. The findings from this case suggest that two-dimensional speckle tracking echocardiography can be useful for myocardial assessment when conventional echocardiographic and Doppler findings are ambiguous.

Objectives Hypertrophic cardiomyopathy, a primary disorder of the myocardium, is the most common cardiac disease in cats. However, determination of myocardial deformation with two-dimensional speckle-tracking echocardiography in cats with various stages of hypertrophic cardiomyopathy has not yet been reported. This study was designed to measure quantitatively multidirectional myocardial deformations of cats with hypertrophic cardiomyopathy. Methods Thirty-two client-owned cats with hypertrophic cardiomyopathy and 14 healthy cats serving as controls were enrolled and underwent assessment of myocardial deformation (peak systolic strain and strain rate) in the longitudinal, radial and circumferential directions. Results Longitudinal and radial deformations were reduced in cats with hypertrophic cardiomyopathy, despite normal systolic function determined by conventional echocardiography. Cats with severely symptomatic hypertrophic cardiomyopathy also had lower peak systolic circumferential strain, in addition to longitudinal and radial strain. Conclusions and relevance Longitudinal and radial deformation may be helpful in the diagnosis of hypertrophic cardiomyopathy. Additionally, the lower circumferential deformation in cats with severe hypertrophic cardiomyopathy may contribute to clinical findings of decompensation, and seems to be related to severe cardiac clinical signs. Indices of multidirectional myocardial deformations by two-dimensional speckle-tracking echocardiography may be useful markers and help to distinguish between cats with hypertrophic cardiomyopathy and healthy cats. Additionally, they may provide more detailed assessment of contractile function in cats with hypertrophic cardiomyopathy.

Background Cancer microenvironment plays a vital role in cancer development and progression, and cancer-stromal interactions have been recognized as important targets for cancer therapy. However, identifying relevant and druggable cancer-stromal interactions is challenging due to the lack of quantitative methods to analyze whole cancer-stromal interactome. Results We present CASTIN (CAncer-STromal INteractome analysis), a novel framework for the evaluation of cancer-stromal interactome from RNA-Seq data using cancer xenograft models. For each ligand-receptor interaction which is derived from curated protein-protein interaction database, CASTIN summarizes gene expression profiles of cancer and stroma into three evaluation indices. These indices provide quantitative evaluation and comprehensive visualization of interactome, and thus enable to identify critical cancer-microenvironment interactions, which would be potential drug targets. We applied CASTIN to the dataset of pancreas ductal adenocarcinoma, and successfully characterized the individual cancer in terms of cancer-stromal relationships, and identified both well-known and less-characterized druggable interactions. Conclusions CASTIN provides comprehensive view of cancer-stromal interactome and is useful to identify critical interactions which may serve as potential drug targets in cancer-microenvironment. CASTIN is available at: http://github.com/tmd-gpat/CASTIN. Electronic supplementary material The online version of this article (doi:10.1186/s12864-016-3207-z) contains supplementary material, which is available to authorized users.

Background Left ventricular torsional motion plays an important role for effective pump function. However, noninvasive clinical assessment of torsional deformations by two-dimensional speckle-tracking echocardiography (2D-STE) in dogs with myxomatous mitral valve disease (MMVD) has not been reported. Hypothesis Left ventricular torsion is determined by the native orientation of the helical myocardial fibers, such that it might provide better assessment of myocardial function than conventional methods. Animals Sixty-seven client-owned dogs with MMVD were classified into 3 classes based on the International Small Animal Cardiac Health Council classification and 16 weight- and age-matched healthy dogs. Methods Dogs were examined for myocardial deformations by 2D-STE and were evaluated for peak systolic rotation and rotation rate at each basal and apical view. Dogs also were evaluated for peak systolic torsion and torsion rate. Results Peak systolic torsion was higher in class II than in class I (P

Background There are some biomarkers for asthma diagnosis but they are often difficult in clinical use, particularly in pediatric cases. Periostin is an extracellular matrix protein, upregulated in response to IL-4 or IL-13. Serum periostin is expected to be used as a non-invasive biomarker for asthma diagnosis and management. Methods Twenty-eight children with asthma (BA) and 27 children without asthma (patients with pectus excavatum, etc. as control group) aged 6–16 years were included. Bronchial asthma was diagnosed according to International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Fractional exhaled nitric oxide (FeNO), lung function, blood eosinophil counts, total immunoglobulin E (IgE) levels, and serum periostin levels were assessed. Results were compared between BA and controls. Asthma diagnostic accuracies were calculated using receiver operating characteristics (ROC) curve analyses. Results Serum periostin levels in the BA group were significantly higher than those in the control group [medians (with interquartile ranges), 134.0 (116.3–166.3) vs. 112.0 (97.0–132.0) ng/ml; p = 0.012]. The area under the ROC curve (AUC) for periostin, FeNO, and eosinophil counts were 0.70, 0.72, and 0.84, respectively. After the exclusion of controls with pectus excavatum, AUC for periostin, forced expiratory volume in 1 s (FEV1), and maximum mid-expiratory flow rate (MMF) were 0.75, 0.74, and 0.80, respectively. Conclusion Serum periostin levels were significantly higher in children with asthma. ROC AUC values for periostin were equivalent to conventional biomarkers, including FeNO levels and lung function testing, indicating the utility of serum periostin levels in diagnosing asthma in children.

Objectives The objective of our study was to quantitatively measure systolic torsional deformations in cats with hypertrophic cardiomyopathy (HCM) and in controls. Animals Twenty-six client-owned cats with HCM and 14 healthy cats. HCM cats were categorized based on their symptoms (asymptomatic and symptomatic) and with or without left ventricular outflow tract obstruction (obstructive and non-obstructive). Methods The cats were examined for myocardial deformations using two-dimensional speckle-tracking echocardiography and were evaluated for peak systolic rotation and the rotation rate at each basal and apical view. Cats were also evaluated for the peak systolic torsion and torsion rate. Results The peak systolic apical rotation and torsion were higher in asymptomatic and symptomatic cats with HCM than in control cats. Also, the peak systolic apical rotation, apical rotation rate, torsion, and torsion rate were higher in cats with obstructive HCM than in control cats. Conclusions Myocardial torsional deformations assessed by two-dimensional speckle-tracking echocardiography may be useful for evaluating compensatory myocardial function of HCM.

Introduction Determine the usefulness of dyssynchrony indices derived from two-dimensional speckle tracking echocardiography for the detection of mechanical dyssynchrony in a canine model of left bundle branch block. Animals Ten healthy beagles. Materials and Methods Segmental, time–radial strain curves were obtained using two-dimensional speckle tracking echocardiography. The maximum difference and standard deviation of the time to peak radial strain for six predefined segments (MaxD-TpSR and 6SD-TpSR) were calculated, together with the left ventricular dyssynchrony by radial strain (DysSR), before and after ablation of the left bundle branch block. Receiver operating characteristic curve analysis was performed using dogs after ablation as positive controls. Results After ablation, all dogs showed multiple peaks in at least one segment on the time–radial strain curve, while all dyssynchrony indices increased significantly (MaxD-TpSR from 16.25 ± 16.04 [mean ± standard deviation] to 44.4 ± 26.18 ms, 6SD-TpSR from 7.59 ± 7.40 to 19.62 ± 11.91 ms, and DysSR from 4.20 ± 2.12 to 10.87± 2.92%, p

Despite extensive studies on clinical indices for the selection of patient candidates for cardiac resynchronization therapy (CRT), approximately 30% of selected patients do not respond to this therapy. Herein, we examined whether CRT simulations based on individualized realistic three-dimensional heart models can predict the therapeutic effect of CRT in a canine model of heart failure with left bundle branch block. In four canine models of failing heart with dyssynchrony, individualized three-dimensional heart models reproducing the electromechanical activity of each animal were created based on the computer tomographic images. CRT simulations were performed for 25 patterns of three ventricular pacing lead positions. Lead positions producing the best and the worst therapeutic effects were selected in each model. The validity of predictions was tested in acute experiments in which hearts were paced from the sites identified by simulations. We found significant correlations between the experimentally observed improvement in ejection fraction (EF) and the predicted improvements in ejection fraction (P

Radiological assessment was performed in cases with osteoarthritis (OA) of the ankle joints without definite origin, for example, trauma, infection etc. Among 25 OA cases unkown origin, 17 cases belonging to 8 males and 9 females ranging in age from 51 to 71 years (mean: 59.9yrs) were inversion types, 8 cases belonging to 2 males and 6 females ranging from 51 to 75 years (mean: 63.6yrs) were eversion types. Radiological mesurements were performed as follows, the basic line was drawn on the longitudinal axis of the distal third of the tibia, and the angle between this line and the mortise called ∠TAS on A-P view, called ∠TLS on lateral view, inclination of the articulus medio-malleoli on A-P view called ∠TMM. Measurements of normal material were parformed in 20 cases in the same manner. In normal material, ∠TAS was 89.2±3.0, ∠TLS was 81.2±4.1, ∠TMM was 23.8±5.9. In inverted OA, 86.6±3.5, 78.1±3.6, 78.1±3.6. In everted OA, 86.9±3.2, 76.1±3.8, 33.5±13.4. There were significant differences (p

Congenital absence of the tibia is a rare congenital anomaly causing marked shortening of the involved extremity.A long-term case of congenital absence of the tibia is reported. A 13-year-old boy entered our hospital for correction of his ankle and foot deformity, and lower leg lengthening using the I lizarov method. His absence belonged to the Ib type according to Jones' clssification.At 1 year and 2 months he had Brown's procedure and at 3 years of age ankle arthrodesis had been performed with remarkable equinovarus. Roentgenologically we can observe that his fibula widered and lergthened compared to normal.

We reported a case of the large fibular defect caused by osteomyelitis of fibula of a 20 years old male. He was hospitalized with the fractures of tibia and fibula in another hospital because of traffic accident. He was treated by osteosynthesis of tibia and fibula but suffered the large defect of the distal fibula (8cm long) with the equinovarus deformity due to osteomyelitis. We lengthened the fibula and then corrected the equinovarus deformity but was difficult to reduct the anterior dislocation of talus because of the narrowness of the ankle joint. So it can be thought that correction of the deformitry should be considered first before lengthening the fibula.

There are few reports to discuss the prognosis of the inferior instability of the shoulder. The purpose of this study is to compare the results of natural course and those of the pectoralis major transfer for the inferior instabilty. From 1975 to 1988, 48 patients were diagnosed as inferior instability of the shoulder and were followed from 2 to 11 years. According to the complaints, 19 patients were observed as natural course (natural group) and 29 patients (34 shoulders) were operated on (operated group), and there was no difference in the degree of instability between the two groups.All patients except two did not improve the inferior instability at their follow-up consultations (average, 4.3 years) in the natural group. And the two patients who were followed for 9.9 years and 11 years respectively, showed no instability. But the number of the patients who complain the feeling of subluxation were decreased among the natural group. The average instability of the operated group were improved from 38% to 16%. Four patients among the natural group and ten patints among the operated group did not complain at the follow-up. The number of patients who complained the shoulder stiffness were increased among the operated group at the follow-up. There were no osteoathrotic changes in the natural group.These results suggested that the operative indication should be made carefully for the patients who complain the shoulder stiffness and the feeling of subluxation of the shoulder.

We have studied the prognostic factors affecting the survival rate in 11 patients with chondrosarcoma. Of those, six died of multiple pulmonary metastases and the overall 5-year survival rate was 38.4%.The most significant prognostic factor was the histologic grade, and the 5-year survival rates in grade 1, 2, 3 were 100%, 0%, 25%, respectively. The location of the chondrosarcoma, and whether it was a peripheral or a central type, also seemed to be a good prognostic factor. The 5-year survival rate of the peripheral type was 66.7% as compared with 21.4% for the central type. Adjuvant therapy such as chemotherapy and irradiation had no effect on the survival rate.

Ninety-nine cases of supracondylar fracture of the humerus in children were followed-up from 1 to 13 years with an average length of 4 years and 2 months. Supracondylar fractures were classified by Holmberg's classification. They were treated by fixation with plaster cast, plaster cast after manipulation, percutaneous pinning or open reduction. We studied about the range of motion (R. O. M.) and varus or valgus deformity of the elbow after the treatment. Baumann's angle at reduction correlated well with carring angle at the last follow-up (correlation coeficient r=0.79). There were no relationship between the R. O. M. and deformity of the elbow and the degree of displacement of distal fragment after the treatment. The deformity and abnormal R. O. M. of the elbow were essentially caused by incomplete reduction. decrease of the tilting angle led to the limitation of flexion of the elbow. If the conservative treatment is not acceptable to get the good aligment, open reduction must be considered.

For osteoarthritis of the elbow, Kashiwagi-Outerbridge arthroplasty has been mainly employed at the Nagasaki University Hospital. This procedure however has several problems. The soft tissue in the anterior component cause flexion contracture and cannot be treated, also the osteophyte and loosebodies in the anterior parts cannot be eliminated completely, because its approach is a posterior one. Therefore, the anterior approach has been most often employed recently. In this paper, surgical techniques, results and indications are discussed. This procedure was employed in 5 elbows of 5 patients who had limitation of elbow flexion as a result of osteophytes of the coronoid process and loosebodies in the anterior parts. In two cases where they also involved the posterior element, an opening in the coronoid fossa was added. All patients were male and their ages averaged 39.4 years (range, 35 to 44 years). Preoperative range of motion, 99 degrees in flexion and -16 degrees in extension changed to 137 degrees in flexion and -5 degrees in extension on average following suvgery. Pain was eliminated in 4 cases and decreased in one case. Although there are some misgivings about using the anterior approach for the elbow, mainly because of possible injury to the nerve and vessels, such serious complications were not experienced in this series. The anterior approach for osteoarthritis of the elbow has many benefits, so this procedure is recommended.

Since May, 1986, Whiteside OrthoLoc Total Knee System was used in Twenty cases. Eleven cases (12 knees) who had had total knee replacement were followed-up for more than 3 months (ave. 6.7 months) after surgery. Nine cases (10 knees) had osteoarthritis (OA) and Two cases (2 knees) had rheumatoid arthritis (RA). Ten of the cases were female and 1 was male whose average age was 63.5 years.Using the criteria described by three universities, the clinical results were evaluated. The score was improved from 44.9±4.9 to 79.5±2.4 and roentgenographical results showed that FTA were improved from 187.8°±4.9° to 174.1°±2.6°.Good results were obtained in all cases, however, in some cases the small-size component was relatively small especially in its transverse diameter and it should be replaced in the near future.

It is well known that avascular necrosis of the talus may occur after fractures and dislocations of it. But the incidence of avascular necrosis is very low after fracture of the talus without displacement. In this report we describe a child with avascular necrosis of the talus after undisplaced fracture who had no treatment for fracture. This indicates that the proper treatment for talus fracture with or without displacement is necessary to avoid avascular necrosis of it.

The results of marginal excision and irradiation (3, 000-5, 000cGy) in 9 patients with liposarcoma of soft tissue were analyzed to determine the effectiveness of radiation therapy. Only one out of 9 patients, who received 3000cGy, developed a local recurrence at 3 years and 3 months after surgery. The 5-year actuarial local control rate was 84.7%, which was similar to that by radical and/or curative wide resection in soft tissue sarcomas. In addition, histological examination disclosed that a liposarcoma with preoperative radiation fell into almost necrosis.It suggests that the combination of conservative surgery and radiation therapy in the treatment of liposarcomas is of use to maintain a functional limb.

The response of osteosarcoma to preoperative treatment, which was classified by the degree of histologic tumor necrosis as good (4 cases), poor (5 cases) and fair (one case), was evaluated in 10 cases by using the value of serum alkaline phosphatase (sALP), conventional radiography, 99mTc-MDP scintigraphy, computed tomography (CT) and angiography before and after the treatment.All of the good responding cases showed the findings of a decreased uptake in 99mTc-MDP scintigraphy. A shrinkage of soft tissue mass on CT was seen in only 2 good responding cases. Angiography in 3 good and one fair cases revealed a decrease in tumor vascularity. The change of sALP value and radiographic findings were not correlated with the degree of histologic tumor necrosis.Therefore, 99mTc-MDF scintigraphy, CT and angiography would be of use for predicting the response of osteosarcoma to preoperative treatment.

Forty-nine patients who were hospitalized in Nagasaki University between February, 1977 and July, 1985, were examined in order to know the trend about the bacterial infections of bones and joints.Most of the bacillus in 37 cases of osteomyelitis and in 12 cases of pyogenic arthritis were staphylococcus aureus. There was a tendency of increase of the subacute and chronic types of osteomyelitis, and the pyogenic arthritis which was followed by puncture of the knee joint. Our results suggested that while diagnosing the osteomyelitis, the recognition of the existence of the subacute osteomyelitis is very important, and that we must pay more attention to prevent the iatrogenic infection.

An eighteen-year-old girl with Marfan syndrome, who was complicated with osteosarcoma of right humerus, was reported. She had the disorders of the skeleton (arachnodactyly, severe scoliosis and pectus excavatum), the eye (ectopia lentis and myopia) and the heart (mitral valve prolapse). According to these findings, she was diagnosed as Marfan syndrome by Pyeritz's criteria.In Nov. 1985, she felt right shoulder pain and swelling and radiograms showed the abnormal shadow in the right proximal humerus. Bone biopsy disclosed typical histological appearance of osteogenic sarcoma and forequater amputation was carried out on May 15, 1986.Relationship between the systemic disorders of the skeleton like Marfan syndrome and the occurrence of malignant bone tumor was discussed.

Tow cases, which might have been opportunistic infection in the early post-operative state, are reported in this paper.Case 1, a 60-year-old male, developed spticemia on the 22nd day after a synovectomy for suppurative arthritis of the left knee. He had a 13 years history of steroid medication following pituitary adenoma resection.Case 2, a 60-year-old, female, developed pueumonia 4 days after T. K. R.. The bacillus involved was strongly suspected to be a Legionella pneumophila. This patient's basic disease was rheumatoid arthritis.These two cases had similarities of situation, for example their general condition before the onset of infection and antibiotic medication after the operationo; these infections took a similar course. The number of aged patients who have complications following operations for basic diseases has been increasing in the orthopaedic field. We must always, therefore, pay attention to the possibility of the opportunistic infection in the management of such cases.

Twenty-one cases of osteosarcoma in the knee region were summarized in this series and the relation between clinicopathological findings and prognosis was studied. Treatment of those cases were divided into 3 groups as follows; group I (amputation, 3 cases), group II (adjuvant chemotherapy and amputation, 10 cases) and group III (high-dose radiotherapy with combination chemotherapy and surgical treatment, 8 cases) respectively. Ten cases of survival more than 4 years consisted of 5 of 10 cases in group II and 5 of 8 cases in group III. No significant differences of prognosis between groups II and III were recognized.According to radiological findings, 21 cases were classified into 3 types; osteolytic type (5 cases), sclerotic type (6 cases) and mixed type (10 cases), On the relation between radiological classification and prognosis, 5 cases of sclerotic type died. It suggests that sclerotic change in the roentgenogram is one of the poor prognostic findings.Histological classification of the cases in this series consisted of fibroblastic type (MFH-like, 5 cases), osteoblastic type (11 cases) and chondroblastic type (4 cases).The survival rate of fibroblastic type with severe cellular atypism is higher than that of osteoblastic type with mild atypism.