Comparison of DNA extraction methods for genotyping equine histidine-rich glycoprotein insertion/deletion polymorphisms using oral mucosa swabs and feces.

Previously, we demonstrated unique insertion/deletion polymorphisms of equine histidine-rich glycoprotein (eHRG) with five genotypes composed of 45-bp or 90-bp deletions in the histidine-rich region of eHRG in Thoroughbred horses. Although leukocytes are typically used to collect DNA for genotyping, blood sampling from animals is sometimes difficult and invasive. Moreover, the method for extracting DNA from blood leukocytes involves complicated steps and must be performed soon after blood sampling for sensitive gene analysis. In the present study, we performed eHRG genotyping using DNA, isolated from oral mucosa swabs collected by rubbing the mucosa on the underside of the upper lip of horses and 100 mg of freshly excreted feces obtained by scraping their surface. In the present study, we performed eHRG genotyping using DNA isolated from oral mucosa swabs and feces of horses (18 Thoroughbreds, 17 mixed breeds, 2 warm bloods), and compared the accuracy of this method with that of the method using DNA from leukocytes. The DNA derived from oral mucosa swabs was sufficient in quantity and quality for eHRG genotyping. However, DNA derived from fecal samples requires a more sensitive detection system because of contamination with non-horse DNA, and the test quality is low. Collection of oral mucosa swabs is less invasive than blood sampling; further, oral swabs can be stored for a longer period in a specified high-quality solution. Therefore, collecting DNA samples from oral mucosa swabs is recommended for the genetic analysis of not only horses but also other animals that are not accustomed to humans.

Renal pelvis cancer with initial symptoms of malignant gastric outlet obstruction.

Introduction: Gastric outlet obstruction caused by upper tract urothelial carcinoma is rare. Case presentation: A 78-year-old man presented to the hospital with nausea and vomiting. No hematuria was observed. Computed tomography revealed a tumor in the right renal pelvis and duodenal stenosis. Gastrojejunostomy was performed to treat the symptoms of the gastric outlet obstruction so that the patient could resume oral intake and outpatient chemotherapy. Chemotherapy was unsuccessful, and the patient died 9 months after the gastrojejunostomy. Histological assessment of an autopsy specimen revealed plasmacytoid urothelial carcinoma with direct infiltration of the duodenal wall, which caused the stenosis. Conclusion: Autopsy revealed a right renal pelvis cancer causing gastric outlet obstruction. Early gastrojejunostomy enabled oral intake and outpatient visits.

Hydrodissection performed safely with an injection catheter during robot-assisted radical prostatectomy.

To facilitate nerve preservation during robot-assisted radical prostatectomy (RP), hydrodissection (HD) using an injection catheter was performed. HD during RP is a nerve-sparing technique in which an epinephrine solution is injected into the lateral prostatic fascia to separate it from the prostatic capsule. Although the beneficial effects of HD on postoperative sexual function have been reported, HD has rarely been used in robot-assisted RP. The primary reason may be the potential benefits of robotic surgery, such as less bleeding, magnified surgical view, and fine movement of instruments; another possible reason is the difficulty of handling sharp needles in a narrow intra-abdominal surgical space of robot-assisted RP. For safe fluid injection, we performed HD using an injection catheter - commonly used for endoscopic upper gastrointestinal hemostasis - during robot-assisted RP. The required time to accomplish HD and the safety of the procedure were examined in 15 HD of 11 patients. Approximately 2 minutes (median, 118 seconds; interquartile range, 106-174 seconds) were needed for HD using the injection catheter. All patients had no complications, such as injuries to the intestine, vessels, or other organs. Postoperative bleeding did not occur in any patients. HD with an injection catheter enables surgeons to perform simple and safe nerve preservation during robot-assisted RP.

A case-control study of atypical guttural pouch empyema in Arabian foals.

BACKGROUND: Upper respiratory disease was reported over many seasons in Arabian foals on a single stud farm in the Middle East. Affected foals were noted to have mucopurulent nasal discharge, cough, fever and tachypnea. All affected foals had been empirically treated with a macrolide and rifampicin, by the referring veterinarian without improvement. On endoscopic examination, all affected foals had significant guttural pouch empyema (GPE). OBJECTIVES: (1) To document a previously unreported presentation of guttural pouch empyema (GPE) in a family of juvenile Arabian foals; (2) To document the cytological and microbial composition of the empyema; (3) To identify clinical signs significantly correlated with the presence of GPE, as predictors for the need for guttural pouch (GP) endoscopy; (4) To demonstrate successful resolution of the identified syndrome with mechanical GP lavage and evidence based antimicrobial use, improving antibiotic stewardship and the one-health approach to respiratory disease in this demographic of foals. METHODS: Evaluation and scoring of clinical signs, upper airway endoscopy and thoracic ultrasound were performed in 14 affected foals and 10 age-matched controls, followed by comparative tracheal and guttural pouch sputum culture and cytological evaluation. Therapeutic GP lavage was performed and response to therapy monitored. RESULTS: GPE, cranioventrally distributed ultrasonographic lesions and opportunistic pathogen infection suggested a primary lesion of GPE with aspiration of GP discharge into the lungs. GP lavage resolved the empyema and associated clinical signs in all cases. CONCLUSIONS: Cytological examination of tracheal and guttural pouch aspirates revealed a neutrophilic exudate with lipid-laden phagocytes, suggestive of engulfed milk. Bacteriology revealed a high prevalence of Streptococcus equi ssp. zooepidemicus admixed with other opportunistic pathogens. Streptococcus equi ssp. equi was not isolated in any case.

Unique insertion/deletion polymorphisms within histidine-rich region of histidine-rich glycoprotein in Thoroughbred horses.

Histidine-rich glycoprotein (HRG) is abundant plasma protein with various effects on angiogenesis, coagulation, and immune responses. Previously, we identified the base and amino acid sequences of equine HRG (eHRG) and revealed that eHRG regulates neutrophil functions. In this study, we first conducted a large-scale gene analysis with DNA samples extracted from 1700 Thoroughbred horses and identified unique insertion/deletion polymorphisms in the histidine-rich region (HRR) of eHRG. Here we report two types of polymorphisms (deletion type 1 [D1] and deletion type 2 [D2]) containing either a 45 bp or 90 bp deletion in the HRR of eHRG, and five genotypes of eHRG (insertion/insertion [II], ID1, ID2, D1D1, and D1D2) in Thoroughbred horses. Allele frequency of I, D1, and D2, was 0.483, 0.480, and 0.037 and the incidence of each genotype was II: 23.4%, ID1: 46.2%, ID2: 3.6%, D1D1: 23.1%, and D1D2: 3.7%, respectively. The molecular weights of each plasma eHRG protein collected from horses with each genotype was detected as bands of different molecular size, which corresponded to the estimated amino acid sequence. The nickel-binding affinity of the D1 or D2 deletion eHRG was reduced, indicating a loss of function at the site. eHRG proteins show a variety of biological and immunological activities in vivo, and HRR is its active center, suggesting that genetic polymorphisms in eHRG may be involved in the performance in athletic ability, productivity, and susceptibility to infectious diseases in Thoroughbred horses.

Novel quantitative software for automatically excluding red bone marrow on whole-body magnetic resonance imaging in patients with metastatic prostate cancer: A pilot study.

OBJECTIVES: To establish a novel quantitative method that automatically excludes the red bone marrow and accurately quantifies the tumor volume on whole-body magnetic resonance imaging using updated imaging software. To also evaluate the association between the quantified tumor volume and the prognosis of patients with metastatic prostate cancer. METHODS: This prospective analysis included patients diagnosed with metastatic hormone-sensitive or metastatic castration-resistant prostate cancer between 2017 and 2022. We developed an imaging software (Attractive BD_Score) that analyzed whole-body diffusion-weighted and in-phase and opposed-phase T1-weighted images to automatically exclude the red bone marrow. The quantified tumor volume was compared with that quantified by traditional whole-body diffusion-weighted imaging without red bone marrow exclusion. Prostate-specific antigen progression-free survival, time-to-pain progression, and overall survival were evaluated to assess the prognostic value of the quantified tumor volume. RESULTS: The quantified tumor volume was significantly smaller than that quantified by the traditional method in metastatic hormone-sensitive (median: 81.0 ml vs. 149.4 ml) and metastatic castration-resistant (median: 29.4 ml vs. 63.5 ml) prostate cancer. A highly quantified tumor volume was associated with prostate-specific antigen progression-free survival (p = 0.030), time-to-pain progression (p = 0.003), and overall survival (p = 0.005) in patients with metastatic hormone-sensitive prostate cancer and with poor prostate-specific antigen progression-free survival (p = 0.001) and time-to-pain progression (p = 0.005) in patients with metastatic castration-resistant prostate cancer. CONCLUSIONS: Our imaging method could accurately quantify the tumor volume in patients with metastatic prostate cancer. The quantified tumor volume can be clinically applied as a new prognostic biomarker for metastatic prostate cancer.

CD3+ T-Lymphocytic Coeliac-Mesenteric Ganglioneuritis Associated with Colonic Torsion and Inflammatory Bowel Disease in an Arabian Broodmare.

A 5-year-old Arabian broodmare with acute colic was diagnosed with lymphocytic ganglioneuritis of the coeliac-mesenteric ganglia and lymphocytic‒plasmacytic enterocolitis resembling inflammatory bowel disease. No significant pathogens were identified by aerobic culture or histopathological examination. The ganglia were multifocally infiltrated with small lymphocytes that were immunopositive for CD3 and negative for CD20 and CD79a antigens, indicating CD3+ T-lymphocyte-mediated coeliac-mesenteric ganglioneuritis. The findings suggest immune-mediated inflammatory bowel disease resulting in disturbance of the autonomic nervous system in the gastrointestinal tract, as in ulcerative colitis in humans. Histopathological features in this case differ from those of equine enteric dysautonomia and chronic intestinal pseudo-obstruction, which are characterized by neuronal degeneration and inflammation, respectively, and mostly affect the mural ganglion plexuses. To the best of our knowledge, this is the first report of CD3+ T-lymphocytic extramural enteric ganglioneuritis in equine inflammatory bowel disease.

Birth month associated with tracheal colonization of Rhodococcus equi in newborn foals on horse-breeding farms with sporadic rhodococcosis in Japan.

Tracheal washing fluid was collected from 170 foals at 28 and 35 d old from February to July in a foaling season on horse-breeding farms with sporadic rhodococcosis in Japan and was investigated by quantitative culture. The history of the 170 foals followed up for the next few months. The proportion of R. equi-positive foals at 28 and 35 d old was significantly increased according to the birth month. Furthermore, the mean number of R. equi in the tracheal washing fluid of each month group increased according to their birth month with the rise in outside temperature. During the follow-up observation, 9/30 foals (30.0 %) born in February showed the first clinical signs at 56 ± 8 d old, 21/61 foals (34.4 %) born in March showed the signs at 37 ± 3 d old, 15/49 foals (30.6 %) born in April showed the signs at 39 ± 2 d old, and 7/30 foals (23.3 %) born in May showed signs at 44 ± 3 d old. Two sick foals (6.7 %) born in February, 19 sick foals (31.1 %) born in March, 15 sick foals (30.6 %) born in April, and 6 sick foals (20.0 %) born in May showed a positive culture of R. equi at 28 or 35 d old. The present study revealed that birth month is associated with the initial colonization of R. equi in the trachea of newborn foals on farms with sporadic rhodococcosis in Japan. Therefore, birth month might be a risk factor for developing R. equi pneumonia in foals.

Histidine-Rich Glycoprotein Functions as a Dual Regulator of Neutrophil Activity in Horses.

Histidine-rich glycoprotein (HRG) is an abundant plasma protein that has been identified in most mammals. We first identified whole genome sequence of equine HRG (eHRG) and succeeded to purify eHRG from plasma of horses. Since HRG interacts with various ligands, this protein is thought to be involved in immune response, coagulation, and angiogenesis. Systemic inflammatory response syndrome (SIRS) is characterized as a non-specific, clinical, pro-inflammatory immune response that damage organs and tissues in the host. Recent reports revealed that blood HRG levels in human patients with SIRS are approximately 50% lower than those in healthy controls, indicating the use of HRG as a biomarker or treatment for SIRS. SIRS is also a serious issue in equine medicine. In this study, we investigated various effects of eHRG on neutrophil functions, including adhesion, migration, phagocytosis, reactive oxygen species (ROS) production, and lysosome maturation using neutrophils isolated from horses. Microscopic observation showed that the addition of eHRG to the culture diminished adhesion of neutrophils stimulated with LPS. Using the Boyden chamber technique, we showed that eHRG reduced neutrophil chemotaxis induced by recombinant human IL-8. Luminol-dependent chemiluminescence assay demonstrated that eHRG restrained the peak of LPS-promoted ROS production from neutrophils. In contrast, eHRG promoted phagocytic activity evaluated with uptake of fluorescent dye conjugated particles, as well as lysosomal maturation assessed using fluorescent staining for lysosomes of equine neutrophils. These results indicated that eHRG acts as a dual regulator of neutrophils in horses.

Short-term infusion of ultralow-dose dopamine in an adult horse with acute kidney injury: A case report.

Much is known regarding a good prognosis of acute kidney injury (AKI) is achieved with adequate, intensive, and early treatment, which leads to acceleration of the renal blood flow rate and associated urination. Low-dose dopamine (1 to 5 µg/kg bwt per min) is a treatment option for AKI in humans but remains controversial for use in horses because of the lack of extensive clinical trial data. A 19-year-old Westfalen horse gelding was referred to the Animal Medical Center with a 1-hour history of mild abdominal pain and anorexia after dressage exercise for 1 hour. Since elevated serum levels of blood urea nitrogen (BUN) and creatinine were found on days 4 and 5, the horse was diagnosed with AKI. In addition to basic hydration therapy with lactated Ringer's solution, we decided to use ultralow-dose dopamine because of the possibilities of the upregulation of dopamine receptors in the affected kidney and general large animal specificity of drug doses. Infusions with 0.04 and 0.02 µg/kg bwt per min for 1 hour on days 6 and 7, respectively, were effective in decreasing serum levels of BUN and creatinine accompanied with a diuretic effect. Thus, short-term infusion of ultralow-dose dopamine may be useful in controlling the renal blood flow rate and clinical conditions in horses with AKI.

Idiopathic multifocal myocardial atrophy with fibrosis and fatty infiltration involving Purkinje fibres in a 13-year-old Arabian broodmare: Histopathological features.

Myocardial atrophy with fibrosis and fatty infiltration involving the cardiac conduction system is relatively unusual in horses. We herein report of such a case in a 13-year-old Arabian broodmare that had spontaneously died on a paddock. An autopsy revealed multifocal myocardial atrophy with concomitant fibrosis and fatty infiltration in both the ventricles and interventricular septum. The Purkinje fibres in the ventricles and interventricular septum were surrounded by thick fibrous or adipose tissues adjacent to atrophic myocardial cells. Myocardial fibrosis and fatty infiltration were likely secondary to myocardial atrophy, occurring as a pathological response triggered by the repair of muscular wall injury. However, there were no major vascular pathologies (e.g. atherosclerosis and arteriosclerosis); hence, the pathogenesis of myocardial atrophy was unclear. There was no evidence of myocardial atrophy ̵ induced pathologies such as infarct, ischaemic lesions, myocardial degeneration, myocarditis and endocarditis. However, such an unusual histopathological pattern may be associated with rapid clinical deterioration and death.

Long-term chronological changes in urination status of patients who underwent ileal neobladder reconstruction at a single institution.

PURPOSE: This study aimed to investigate the long-term chronological changes in urination status of patients who underwent radical cystectomy (RC) followed by orthotopic ileal neobladder (ONB) reconstruction using the International Prostatic Symptoms Score (IPSS) and the Overactive Bladder Symptoms Score (OABSS). METHODS: This retrospective study focused on patients who underwent RC followed by ONB reconstruction and those who consented for IPSS, quality of life (QOL) based on urinary symptoms (IPSS-QOL), and OABSS assessments in the follow-up period. The patients were divided according to gender into the male group (M-group) and female group (F-group). All patients were evaluated using IPSS, IPSS-QOL, and OABSS every 3 months. The primary endpoint was to assess chronological changes in the urination status of patients who underwent ONB reconstruction after RC. RESULTS: The median age of the enrolled patients (n = 122) was 65 years and the median follow-up period was 92.0 months. The median voiding symptom score in IPSS after 10 years of surgery was significantly higher in the M-group than in the F-group. Contrarily, the F-group demonstrated a significantly higher median storage symptom score at 60-66 and 102-114 months than the M-group. The median OABSS scores were relatively higher in the F-group than in the M-group. CONCLUSIONS: Although long-term urinary function with ONB demonstrated acceptable results, dysfunctional voiding was observed > 10 years after surgery. Thus, the changes in long-term urinary function should be considered when deciding ONB.

Comparison of nivolumab plus ipilimumab with tyrosine kinase inhibitors as first-line therapies for metastatic renal-cell carcinoma: a multicenter retrospective study.

BACKGROUND: This study compared real-world outcomes of metastatic renal-cell carcinoma (mRCC) patients treated with tyrosine kinase inhibitors or nivolumab plus ipilimumab. METHODS: Using the International mRCC Database Consortium (IMDC), we retrospectively evaluated intermediate- and poor-risk mRCC patients who were treated with nivolumab plus ipilimumab (Nivo-Ipi), tyrosine kinase inhibitors (TKIs) as the first-line therapy between August 2015 and January 2020. We compared oncological outcomes between the Nivo-Ipi group and TKIs group using multivariate logistic regression analysis with the inverse probability of treatment weighting (IPTW) method. RESULTS: In this study 278 patients were included. There were 52 and 226 patients in the Nivo-Ipi and TKIs groups (sunitinib 97, axitinib 118, sorafenib 9, pazopanib 2), respectively. The median age in the Nivo-Ipi and TKIs groups were 69 and 67 years, respectively. There was no significant difference in age, performance status, history of nephrectomy, and the IMDC risk group distribution between the groups. The objective response rate was significantly higher in the Nivo-Ipi group (38%) than in the TKIs group (23%, P = 0.018). The IPTW-adjusted Cox regression analysis showed that a significantly longer progression-free survival (hazard ratio 0.60, P = 0.039) and overall survival (hazard ratio 0.51, P = 0.037) rates in the Nivo-Ipi group than those in the TKIs group. CONCLUSIONS: The oncological outcomes of patients receiving the first-line therapy of nivolumab plus ipilimumab in real-world practice were significantly improved in comparison with first-line TKIs therapy.

A Rapid Shift from Chronic Hyperoxia to Normoxia Induces Systemic Anaphylaxis via Transient Receptor Potential Ankyrin 1 Channels on Mast Cells.

Extensive activation of mast cells is the major switch that triggers systemic anaphylaxis, resulting in the subsequent release of anaphylactic mediators into circulation. We previously demonstrated that rapid changes in oxygen tension lead to mast cell degranulation, and the released tryptase triggers retinal angiogenesis in a murine oxygen-induced retinopathy model. However, whether a rapid shift from hyperoxia to normoxia (relative hypoxic stress) is a risk factor for systemic anaphylaxis remains unknown. In this study, we demonstrated that the relative hypoxia stress induces systemic mast cell activation via transient receptor potential ankyrin 1 (TRPA1) channels, which immediately leads to hypothermia and increased vascular permeability in adult mice. Although mast cell-deficient or TRPA1-deficient mice did not exhibit anaphylactic symptoms following a rapid sift to normoxia, preinjection with bone marrow-derived cultured mast cells (BMCMCs) derived from wild-type TRPA1-expressing mice restored anaphylactic responses. In addition, we found that the rapid reductions in oxygen tension in a culture atmosphere triggered the degranulation of BMCMCs derived from wild-type TRPA1-expressing mice but not that of BMCMCs derived from TRPA1-deficient mice. In human LAD2 mast cells, the relative hypoxic stress led to the degranulation, which was suppressed by the addition of a TRPA1 inhibitor. Gradual reductions from hyperoxia to normoxia led to no anaphylactic symptoms. Our results demonstrated that TRPA1-triggered mast cell degranulation is a novel pathway that induces anaphylactic shock without Ag-Ab reactions. These findings introduce a potential role for oxygen in inducing mast cell-dependent anaphylaxis and highlight the need to reconsider chronic pure oxygen therapy for anoxic diseases.

Efficacy and safety of first-line nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma: A multicenter retrospective study.

OBJECTIVES: To investigate the efficacy and safety of first-line nivolumab plus ipilimumab for patients treated with metastatic renal cell carcinoma. METHODS: We retrospectively evaluated 52 metastatic renal cell carcinoma patients who were treated with nivolumab plus ipilimumab between August 2015 and January 2020. Data on patient characteristics, treatment parameters and adverse events were obtained. Oncological outcomes were assessed according to the International Metastatic Renal Cell Carcinoma Database Consortium prognostic model. Furthermore, differences in treatment parameters between patients with objective response (responders) and non-responders were compared. RESULTS: The median age and follow-up periods were 69 years and 8.2 months, respectively. The 1-year progression-free survival and overall survival rates were 55% and 75%, respectively. The objective response rate was 39%, and it was significantly different between the International Metastatic Renal Cell Carcinoma Database Consortium intermediate- and poor-risk groups (52% vs 24%). We observed 36 (69%) any immune-related adverse events, and 19 (37%) severe immune-related adverse events (grades III-V). The International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and higher value of initial C-reactive protein (≥1.0 mg/dL) were significantly associated with non-responders. Patients with two factors (the International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group plus C-reactive protein ≥1.0 mg/dL) had a significantly poor overall survival than those with none or a single factor. CONCLUSIONS: In our experience, treatment response to nivolumab plus ipilimumab is comparable with that of the CheckMate 214 clinical trial, but the incidence of treatment-related adverse events is lower. The International Metastatic Renal Cell Carcinoma Database Consortium poor-risk group and initial C-reactive protein value might have a prognostic value for poor survival.

Impact of the Proportion of Biopsy Positive Core in Predicting Biochemical Recurrence in Patients with Pathological Pt2 and Negative Resection Margin Status after Radical Prostatectomy.

This study aimed to determine the prognostic factors associated with biochemical recurrence (BCR) after radical prostatectomy (RP) in patients with pathological T2 (pT2) prostate cancer (PCa) and negative resection margin (RM) status at a single institution. In this retrospective study, we examined 386 patients who were diagnosed with pT2 PCa with negative RM after RP. The length of the tumor was provided for each biopsy core and the overall percentage of PCa was calculated by a pathologist at our institution. We estimated the BCR-free survival (BRFS) in these patients. Univariate and multivariate analyses were performed using the Cox proportional hazard model to determine the risk factors of BCR. The median age of the participants was 68 years, and their initial prostate-specific antigen level was 6.55 ng/mL. The median follow-up period was 85.7 months. The 5-year BRFS rate of the participants was 89.0%. The 5-year BRFS rates were 89.8% in patients with a biopsy Gleason score of 6, 90.4% in those with 7, and 64.1% in those with ≥8 (P = 0.007). The BRFS rate was 93.3% in patients who had a biopsy positive core ≤20% and 82.0% in those who had ≥21% (P = 0.001). Based on the multivariate analysis, the proportion of biopsy positive core was significantly associated with BCR. The proportion of biopsy positive core may predict preoperative covariates in patients with pT2 PCa and negative RM status after RP.

Castration-resistant prostate cancer without metastasis at presentation may achieve cancer-specific survival in patients who underwent prior radical prostatectomy.

PURPOSE: Radical prostatectomy (RP) is relatively better oncological outcomes in patients with prostate cancer (PCa). However, the incidence of castration-resistant PCa (CRPC) and PCa-specific mortality in patients with biochemical recurrence (BCR) after RP remains unclear. The aim of this study was to evaluate the cancer-specific survival (CSS) in patients with CRPC after RP, in particular those who had metastases or not. METHODS: We retrospectively reviewed the data of 1582 consecutive patients who underwent RP between July 1996 and January 2019. The enrolled patients had histologically confirmed stage T1a-T3b PCa without lymph node involvement or distant metastasis. The endpoints were oncological outcomes, including CSS and BCR, in patients with PCa with or without metastases at the time of diagnosis with CRPC. RESULTS: A total of 1474 patients were enrolled in this study. By the end of the follow-up period, 352 patients (24.6%) in the enrolled patients had BCR after RP. A total of 42 patients (2.9%) developed CRPC and 18 (1.3%) had died of PCa. With regard to metastasis in patients who diagnosed CRPC, the 5-year CSS rate was 100% for nonmetastatic CRPC (nmCRPC) patients and 53.8% for metastatic CRPC (mCRPC) patients after RP. The 5-year CSS rate was 100% for nmCRPC patients and 27.1% for mCRPC patients after the diagnosis with CRPC. CONCLUSIONS: CRPC is one of the lethal causes with PCa death. However, nmCRPC may achieve relatively good prognosis in patients with PCa after RP.

Patterns of Rectal Temperature and Shipping Fever Incidence in Horses Transported Over Long-Distances.

Shipping Fever is a transport associated syndrome seen in equids and bovines transported during long distances. The microbial profile and clinical signs vary between species, and in horses it is characterized by pharyngeal commensal bacteria and aerosolized particulate matter invading the lower airway due to compromised mucocillary clearance mechanisms during transports. This leads to pyrexia, pulmonary parenchymal disease, inappetence, and in severe cases pleuropneumonia. It has been shown that the incidence of transport-related pyrexia in horses increases with travel time and distance, however, this incidence rate has been expressed as the cumulative number of horses showing pyrexia with the length of travel time during road transport (cumulative percentage), which does not accurately reflect the actual temperature fluctuations and their patterns in relation to shipping fever. This study aims to demonstrate the individual fluctuations of body temperature variations during transport, particularly febrile changes. 53 Anglo-Arab and Thoroughbred horses aged 23-30 months were transported by road over different distances and durations (36-61 h; 1,492-2,921 km) in 3 investigations carried out in the spring and mid-summer in the northern hemisphere. The results showed that the incidence of fever (characterized by rectal temperature >38.6°C) was highest from 20 to 49 h after the start of transport. Clinical signs of shipping fever was observed in 25 of the 53 horses (47.2%), of which 10 horses (18.9%) exhibited fever at the end of transportation and 15 horses (28.3%) did not. This showed that horses that develop shipping fever do not necessarily present with fever at the end of transportation. Necropsy of 20 horses performed immediately after transportation suggested that transport induced pneumonia, contributed to the onset of pyrexia. This finding supports the suggestion that measuring body temperature upon arrival to determine the presence or absence of shipping fever could result in missed diagnoses for some horses with subclinical pneumonia, and that taking multiple temperature measurements at intervals from 20 h of transportation is a simple method for not missing horses with subclinical pneumonia.

Neoadjuvant chemohormonal therapy followed by robot-assisted and minimum incision endoscopic radical prostatectomy in patients with high-risk prostate cancer: comparison of perioperative and oncological outcomes at single institution.

PURPOSE: Optimal management strategies for patients with high-risk prostate cancer (PCa) have not been established. This study aimed to estimate the impact of surgical procedures on perioperative and oncological outcomes in patients with high-risk PCa who received neoadjuvant chemohormonal therapy (CHT) prior to radical prostatectomy (RP). METHODS: In this retrospective study, we focused on patients with high-risk PCa who received neoadjuvant CHT followed by RP. The enrolled patients were divided into the following two groups according to surgical procedure: the robot-assisted RP (RARP) group and minimum incision endoscopic RP (MIE-RP) group. The primary endpoint was biochemical recurrence-free survival (BRFS). RESULTS: A total of 522 high-risk PCa patients were enrolled in this study. The median operating time was significantly shorter in the MIE-RP group than in the RARP group. The median estimated blood loss was significantly lower in the RARP group than in the MIE-RP group. The rates of positive surgical margins (PSMs) were not statistically significant in either group. During the follow-up period, biochemical recurrence (BCR) without clinical recurrence occurred in 60 (23.9%) patients in the MIE-RP group and 5 (1.8%) in the RARP group. The 5-year BRFS rate was 76.5% in the MIE-RP group and 97.6% in the RARP group (P < 0.001). On multivariate analysis, RARP, PSM, pathological T stage, and initial prostate-specific antigen were significantly associated with BCR. CONCLUSIONS: Neoadjuvant CHT with subsequent RARP may decrease the risk of BCR when compared to MIE-RP.

Significance of Serum N-glycan Profiling as a Diagnostic Biomarker in Urothelial Carcinoma.

BACKGROUND: The clinical diagnosis of urothelial carcinoma (UC) relies on invasive methods in patients with hematuria. Although more sensitive and noninvasive screening methods are required, a specific serum biomarker for UC is lacking. OBJECTIVE: To examine whether serum glycan-based biomarkers can be applied to UC detection. DESIGN, SETTING, AND PARTICIPANTS: Between April 1994 and June 2016, serum N-glycan concentrations were retrospectively measured in 212 patients with UC before treatment (UC group) and 212 pair-matched controls using glycoblotting and mass spectrometry. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: N-glycan levels were compared between the groups using receiver operating characteristic curves to select candidate N-glycans. We created an N-glycan score based on the combination of candidate N-glycans. The specificity and sensitivity of the candidate N-glycan score were evaluated using receiver operating characteristic curves. RESULTS AND LIMITATIONS: The N-glycan score was calculated using six N-glycans (m/z 1566, m/z 1687, m/z 1769, m/z 1871, m/z 2011, and m/z 2337) that were significantly associated with UC. The median N-glycan score was significantly higher in the UC group than in the pair-matched control group (5.0 vs 1.0, p<0.001). The N-glycan score correctly classified UC patients with a sensitivity, specificity, and area under the curve of 93%, 81%, and 0.95, respectively. The limitations of our study included its retrospective nature and nonclinical setting. CONCLUSIONS: Serum N-glycan content has the potential to be a specific and sensitive novel serum biomarker that may improve the accuracy of the detection for UC and reduce unnecessary invasive screening. Validation of this test in a large-scale prospective study is needed. PATIENT SUMMARY: Combination of serum N-glycan (N-glycan score) is a novel serum marker for urothelial carcinoma that is expressed by 93% of patients and thus is far more sensitive than classic urine cytology. Validation in a large patient cohort is needed.