Stage based recipient and donor outcome in twin-to-twin transfusion syndrome treated by fetoscopic laser surgery using Solomon technique.

OBJECTIVE: To evaluate twin survival stratified by Quintero stage in patients with twin-to-twin transfusion syndrome (TTTS) after Solomon laser treatment. METHODS: Single center cohort of consecutive twin pregnancies treated with Solomon laser for TTTS. Preoperative Quintero stage, perioperative characteristics and obstetric factors were related to neonatal survival of the recipient and donor at discharge. Determinants of twin survival were evaluated using univariate, logistic regression and cumulative survival probability analyses. RESULTS: Of 402 twins with TTTS, 80 (19.9%) had stage I, 126 (31.3%) stage II, 169 (42%) stage III and 27 (6.7%) stage IV. Post laser TAPS or recurrent TTTS occurred in 19 (4.7%) patients and 11 (2.7%) required repeat laser. Preterm premature rupture of membranes occurred in 150 (37.3%) patients and median gestational age of delivery 32+1 weeks. In 303 (75.4%) both twins were alive at discharge; [66 (82.5%) in stage I, 101 (80.2%) in stage II, 114 (67.5%) in stage III and 22 (81.5%) in stage IV, p=0.062]. Compared to recipients, donor survival was only lower in stage III (155 (91.7%) recipients vs 118 (69.8%) donors, Chi square 24.685, p<0.0001). Larger intertwin size discordance and umbilical artery (UA) end-diastolic velocity (EDV) determined donor demise (Nagelkerke R2 0.38, P<0.001). Overall, spontaneous post laser donor demise accounted for the majority (39.5%) of all losses. Cumulative donor survival decreased from 92% to 65% with size discordance >30% and 48% when UA EDV was absent (p<0.001). CONCLUSION: Solomon laser achieves TTTS resolution and double survival in a high proportion of cases. Recipient and donor survival is comparable unless there is significant size discordance and placental dysfunction. This degree of unequal placental sharing, typically found in stage III, is the primary factor preventing double survival due to a higher rate of donor demise. This article is protected by copyright. All rights reserved.

Three-dimensional ultrasound diagnosis of adenomyosis is not associated with adverse pregnancy outcome following single thawed euploid blastocyst transfer: prospective cohort study.

OBJECTIVES: The objectives of this study were (1) to assess the prevalence of ultrasound (US) features of adenomyosis in an infertile population undergoing in-vitro fertilization (IVF), (2) to define the inter- and intrarater agreement of three-dimensional (3D) US assessment of adenomyosis, and (3) to evaluate sonographic features of adenomyosis with respect to pregnancy outcome following transfer of a single thawed euploid blastocyst. METHODS: This was a prospective cohort study. Subjects scheduled to undergo a single thawed euploid blastocyst transfer between April and December 2017 at a large IVF center were eligible for inclusion. Enrolled subjects underwent endometrial preparation for frozen embryo transfer. 3D-US was performed on the day prior to embryo transfer, with images stored for subsequent evaluation. Subjects then underwent transfer of a single thawed euploid blastocyst, and pregnancy outcomes were collected. All 3D-US volumes were de-identified and reviewed independently by five reproductive endocrinologists/infertility specialists with expertise in gynecological US for the presence of seven sonographic features of adenomyosis: global uterine enlargement, myometrial wall asymmetry, heterogeneous echogenicity, irregular junctional zone, myometrial cysts, fan-shaped shadowing and ill-defined myometrial lesions. Adenomyosis was considered to be present if the majority of the reviewers noted at least one of the seven sonographic features. Inter- and intrarater agreement was evaluated using Fleiss's kappa. Clinical and cycle characteristics of subjects with and those without adenomyosis were compared. The primary outcome of interest was live birth rate. Secondary outcomes included clinical pregnancy rate and miscarriage rate. Logistic regression analysis was performed to account for potential confounders. RESULTS: A total of 648 subjects were included. The prevalence of adenomyosis on US was 15.3% (99/648). On retrospective chart review, very few patients with adenomyosis had symptoms. The inter- and intrarater agreement amongst five independent specialists conducting the 3D-US assessments of adenomyosis were poor (κ = 0.23) and moderate (κ = 0.58), respectively. Subjects with adenomyosis were older (37.1 vs 35.9 years, P = 0.02) and more likely to undergo a gonadotropin-releasing hormone agonist downregulation protocol when compared with those without adenomyosis (12.1% vs 5.1%, P = 0.02). Clinical pregnancy (80.0% vs 75.0%) and live birth (69.5% vs 66.5%) rates were similar between the groups. When adjusting for potential confounders, there was no difference in the rate of clinical pregnancy (adjusted odds ratio (aOR), 1.47 (95% CI, 0.85-2.56)), miscarriage (aOR, 1.3 (95% CI, 0.62-2.72)) or live birth (aOR, 1.28 (95% CI, 0.78-2.08)) between subjects with and those without adenomyosis. No individual sonographic marker of adenomyosis was predictive of pregnancy outcome. CONCLUSIONS: The inter-rater agreement of 3D-US assessment of adenomyosis is poor. Furthermore, sonographic markers of adenomyosis in asymptomatic patients may not be associated with altered pregnancy outcome following transfer of a single thawed euploid blastocyst. These findings suggest that routine screening for asymptomatic adenomyosis in an unselected infertile patient population undergoing frozen embryo transfer may not be warranted. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Antibody and cellular immune responses of naïve mares to repeated vaccination with an inactivated equine herpesvirus vaccine.

Equine herpesvirus type 1 (EHV-1) continues to cause severe outbreaks of abortions or myeloencephalopathy in horses despite widely used vaccination. The aim of this work was to determine the effects of frequent vaccination with an inactivated EHV vaccine on immune development in horses. Fifteen EHV-1 naïve mares were vaccinated a total of 5 times over a period of 8 months with intervals of 20, 60, 90 and 60 days between vaccine administrations. Total antibody and antibody isotype responses were evaluated with a new sensitive EHV-1 Multiplex assay to glycoprotein C (gC) and gD for up to 14 months after initial vaccination. Antibodies peaked after the first two vaccine doses and then declined despite a third administration of the vaccine. The fourth vaccine dose was given at 6 months and the gC and gD antibody titers increased again. Mixed responses with increasing gC but decreasing gD antibody values were observed after the fifth vaccination at 8 months. IgG4/7 isotype responses mimicked the total Ig antibody production to vaccination most closely. Vaccination also induced short-lasting IgG1 antibodies to gC, but not to gD. EHV-1-specific cellular immunity induced by vaccination developed slower than antibodies, was dominated by IFN-γ producing T-helper 1 (Th1) cells, and was significantly increased compared to pre-vaccination values after administration of 3 vaccine doses. Decreased IFN-γ production and reduced Th1-cell induction were also observed after the second and fourth vaccination. Overall, repeated EHV vaccine administration did not always result in increasing immunity. The adverse effects on antibody and cellular immunity that were observed here when the EHV vaccine was given in short intervals might in part explain why EHV-1 outbreaks are observed worldwide despite widely used vaccination. The findings warrant further evaluation of immune responses to EHV vaccines to optimize vaccination protocols for different vaccines and horse groups at risk.

Antibodies to OspC, OspF and C6 antigens as indicators for infection with Borrelia burgdorferi in horses.

REASONS FOR PERFORMING STUDY: Lyme disease is caused by Borrelia burgdorferi, which is transmitted by infected ticks (Ixodes spp.). Reports on Lyme disease in horses have increased in recent years. Nevertheless, the diagnosis of Lyme disease in horses is still challenging owing to its vague clinical presentation and the limitations of diagnostic tests. OBJECTIVES: This study used a new serological Lyme multiplex assay to examine antibody responses to 3 antigens of B. burgdorferi, outer surface protein (Osp) C, OspF and C6, and to verify their use as markers for early and late infection stages in horses. METHODS: Multiplex analysis of antibodies to OspC, OspF and C6 in equine patient sera (n = 191) was performed. A subset of the sera (n = 90) was also tested using a commercial C6-based Lyme test. RESULTS: Antibodies to OspF and C6 highly correlate as reliable markers of infection with B. burgdorferi in horses. Antibodies to OspC, which have been confirmed as early infection markers in man and dogs, were only detected in some patient sera, suggesting that OspC antibodies are indicators of early infection in horses. Commercial C6 testing identified most infected horses but also resulted in false positive and false negative interpretations. CONCLUSIONS: Serological multiplex testing is a rapid and quantitative diagnostic method to confirm infection with B. burgdorferi and to identify the stage of infection. In horses with risk of exposure and clinical signs, multiplex testing supports the diagnosis of Lyme disease. POTENTIAL RELEVANCE: Antimicrobial treatment of B. burgdorferi is time sensitive. Treatment success decreases with time of persistent infection, while the risk of developing chronic disease increases. The ability to identify early infection with B. burgdorferi provides practitioners and clinicians with a tool to improve the diagnosis of equine Lyme disease and make treatment decisions.

Prevention and treatment of pressure ulcers.

Pressure ulcer prevention and treatment remains a challenge for interprofessional teams in all health care sectors. Evidencebased pressure ulcer guidelines can be simplified with a bedside enabler utilizing the wound bed preparation paradigm. Key steps involve treatment of the cause, addressing patient-centered concerns, and administering local wound care (debridement, infection/ inflammation control, and moisture balance before considering advanced therapies with the edge effect). Optimal outcomes are achievable with a multi-disciplinary approach that supports patients and their circle of care, which is central to every evaluation and course of treatment decisions.

5-Lipoxygenase expression in benign and malignant canine prostate tissues.

5-Lipoxygenase (5-LO) is overexpressed in human prostate carcinomas (PCs), and its inhibition decreases proliferation and induces apoptosis in prostate cancer cell lines. We hypothesized that 5-LO would be overexpressed in canine PC compared with benign prostate tissue and may be important in the pathogenesis of the disease. Immunoblot analysis of canine PC and benign prostatic hyperplasia (BPH) tissues demonstrated 5-LO expression in both. 5-LO immunohistochemical staining was not significantly different within the stromal or epithelial components of canine primary PC, BPH or suppurative prostatitis, suggesting that differential expression of this enzyme does not occur in these conditions. The percentage of tumour cells expressing 5-LO was significantly lower in metastatic PC lesions compared with primary PC (P < 0.0001). This decreased expression may indicate down-regulation or altered expression of the enzyme with progression of canine PC to a metastatic phenotype.

A case of tracheal varices: an unusual but important cause of mural nodules in the trachea.

Tracheal varices (TV) are uncommon but can be an important source of massive or recurrent haemoptysis. We present a case of TV in a 32-year-old patient with a history of Glenn-Fontan surgery, for congenital tricuspid atresia, and portal hypertension owing to cardiac cirrhosis. We discuss TV presenting as tracheal nodules in the presence of extensive mediastinal collateral circulation.

Antioxidant network expression abrogates oxidative posttranslational modifications in mice.

Antioxidant enzymatic pathways form a critical network that detoxifies ROS in response to myocardial stress or injury. Genetic alteration of the expression levels of individual enzymes has yielded mixed results with regard to attenuating in vivo myocardial ischemia-reperfusion injury, an extreme oxidative stress. We hypothesized that overexpression of an antioxidant network (AON) composed of SOD1, SOD3, and glutathione peroxidase (GSHPx)-1 would reduce myocardial ischemia-reperfusion injury by limiting ROS-mediated lipid peroxidation and oxidative posttranslational modification (OPTM) of proteins. Both ex vivo and in vivo myocardial ischemia models were used to evaluate the effect of AON expression. After ischemia-reperfusion injury, infarct size was significantly reduced both ex vivo and in vivo, ROS formation, measured by dihydroethidium staining, was markedly decreased, ROS-mediated lipid peroxidation, measured by malondialdehyde production, was significantly limited, and OPTM of total myocardial proteins, including fatty acid-binding protein and sarco(endo)plasmic reticulum Ca(²+)-ATPase (SERCA)2a, was markedly reduced in AON mice, which overexpress SOD1, SOD3, and GSHPx-1, compared with wild-type mice. These data demonstrate that concomitant SOD1, SOD3, and GSHPX-1 expression confers marked protection against myocardial ischemia-reperfusion injury, reducing ROS, ROS-mediated lipid peroxidation, and OPTM of critical cardiac proteins, including cardiac fatty acid-binding protein and SERCA2a.

Glutathione, cysteine, and ascorbate concentrations in clinically ill dogs and cats.

BACKGROUND: Oxidative stress plays a role in the pathogenesis of many systemic diseases. Hospitalized human patients are glutathione, cysteine, and ascorbate deficient, and antioxidant depletion has been correlated with poor clinical outcome. To date little is known about antioxidant concentrations in hospitalized veterinary patients. The purpose of this study was to determine whether ascorbate, cysteine, or glutathione depletion is present in ill dogs and cats compared with healthy controls. HYPOTHESIS: Clinically ill dogs and cats would be antioxidant depleted, and depletion would correlate with illness severity and clinical outcome. ANIMALS: Clinically ill client-owned dogs (n = 61) and cats (n = 37), healthy control dogs (n = 37) and cats (n = 33). METHODS: Prospective, observational, case control study. Erythrocyte reduced glutathione, plasma cysteine, and plasma ascorbate were quantified using high-performance liquid chromatography. RESULTS: Clinically ill dogs had significantly lower erythrocyte glutathione concentrations (1.22 mM, range 0.55-3.61) compared with controls (1.91 mM, range 0.87-3.51; P = .0004), and glutathione depletion correlated with both illness severity (P = .038) and mortality (P = .010). Cats had higher ascorbate concentrations when ill (10.65 microM, range 1.13-25.26) compared with controls (3.68 microM, range 0.36-13.57; P = .0009). CONCLUSIONS AND CLINICAL IMPORTANCE: Clinically ill dogs had decreased erythrocyte glutathione concentrations, which could be a marker of illness severity and prognostic of a poor outcome. Clinically ill cats had an unexpectedly high plasma ascorbate, which could represent a unique species response to oxidative stress.

Effects of firocoxib and tepoxalin on healing in a canine gastric mucosal injury model.

BACKGROUND: Little is known about the effect of dual cyclooxygenase (COX) and lipoxygenase inhibition on canine gastric mucosal healing. OBJECTIVE: This study compares the effects of putative dual COX and 5-lipoxygenase inhibition with that of COX-2 selective inhibition on gastric mucosal lesion healing in dogs. ANIMALS: Six normal adult mixed-breed research dogs. METHODS: Gastric body and pyloric lesions were induced by endoscopic biopsy. Dogs were treated with tepoxalin, firocoxib, or placebo for 7 days in a randomized 3-way crossover study design. Healing was evaluated on days 2, 4, and 7 of treatment by endoscopic lesion scoring. Eicosanoid concentrations in plasma and at the lesion margins were determined on days 2, 4, and 7. Repeated measures analyses were performed. All hypothesis tests were 2-sided with P < .05. Multiple comparisons were adjusted using Tukey's test. RESULTS: Significant treatment differences were noted in the pyloric lesion area measurements. Overall, the firocoxib group had larger lesions than the placebo (P= .0469) or tepoxalin (P= .0089) groups. Despite larger pyloric lesions in the firocoxib group, mucosal prostaglandin production did not differ significantly from placebo. In contrast, the tepoxalin group had significantly lower pyloric mucosal prostaglandin production compared with the firocoxib (P < .0001) or the placebo (P < .0001) groups but pyloric lesions were not significantly larger than those of the placebo group (P= .7829). CONCLUSION: COX-2 inhibition by firocoxib slowed wound healing by a mechanism independent of prostaglandin synthesis. Suppression of mucosal prostaglandin production by tepoxalin did not alter mucosal lesion healing compared with placebo.

Development of a methodology for successful multigeneration life-cycle testing of the estuarine sheepshead minnow, Cyprinodon variegatus.

Evaluation of effects on fish reproduction and development during chemical exposures lasting for multiple generations is sometimes limited by variable reproductive responses and the time required for the exposure. Established testing methods and the short life cycle of the sheepshead minnow, Cyprinodon variegatus, make this species particularly suitable for use in identifying potential impacts of contaminants in estuarine and marine environments. This study describes the refinement of life-cycle exposure methods that increased the reliability of reproduction in sheepshead minnows and reduced the time to maturation for larvae and juvenile fishes. A test of three spawning chamber designs, three sex ratios, and two photoperiods identified conditions that reduced the coefficient of variation in egg production from >100% to as little as 32%. The most reliable results were produced with groups of three female and two male fishes (all of similar size) when they were placed in a rectangular chamber and acclimated for 12 days. A test water temperature of 26.5 +/- 2 degrees C and a 14L:10D photoperiod resulted in fish producing a mean of 74 embryos per female per day, with a coefficient of variation of 31.8%. Egg fertility exceeded 90%, with a hatch rate of 95% for normal embryos (>or=80% yolk) and a hatch rate of or=2.7 cm standard length) was critical for spawning readiness. Adult fish were prepared for the spawning assessment by adding frozen brine shrimp to their diet. Results of these experiments provide methods that are of particular interest in assessment of endocrine-disrupting chemicals that are known to affect reproduction.

Leukotriene inhibition in small animal medicine.

Leukotrienes are important mediators of inflammatory and allergic conditions in people and are suspected to play an important role in tumorigenesis and tumor growth of several different tumor types. Based on this, researchers are making great progress in identifying novel pharmacologic targets for several human diseases. Leukotriene inhibition has resulted in therapeutic benefit in clinical trials involving people with osteoarthritis, allergic asthma, and atopic dermatitis. Despite this progress and the possibility that leukotriene inhibition may also play an important therapeutic role in veterinary patients, parallel advances have not yet been made in veterinary medicine. This article summarizes leukotriene function and synthesis. It also reviews the published literature regarding potential therapeutic applications of leukotriene inhibition in both human and veterinary medicine, focusing primarily on osteoarthritis, NSAID induced gastrointestinal mucosal damage, allergic asthma, atopic dermatitis, and cancer.

Detection of equine herpesvirus-1 in nasal swabs of horses by quantitative real-time PCR.

BACKGROUND: Early identification of inhalation-transmitted equine herpesvirus type 1 (EHV-1) infections has been facilitated by the availability of a number of real-time quantitative PCR (qPCR) tests. A direct comparison between nasal swab qPCR and traditional virus isolation (VI) requires a method for normalizing the qPCR samples and controlling for PCR inhibitors present in some clinical samples. OBJECTIVES: To quantify EHV-1 shedding in viral swabs using an internal control and to compare fast qPCR to VI for the detection of EHV-1 in nasal swabs from horses. ANIMALS: Fifteen horses experimentally infected with EHV-1. METHODS: Experimental study: Nasal swab samples were collected daily after experimental infection for up to 21 days. VI was performed by conventional methods. The DNA was prepared for qPCR with the addition of a known quantity DNA of Marek's disease virus as an internal control. qPCR was performed. RESULTS: The qPCR method detected virus up to day 21 after challenge, whereas VI detected virus only to day 5. The median Kaplan-Meier estimates for EHV-1 detection were 12 days for qPCR and 2 days for VI (P< .0001). When compared with VI, the sensitivity and specificity of qPCR were 97 (95% CI: 86-100) and 27% (95% CI: 20-35). CONCLUSIONS AND CLINICAL IMPORTANCE: We conclude that fast qPCR of nasal swab samples should be chosen for diagnosis and monitoring of herpesvirus-induced disease in horses. Recommended reference ranges of C(T) values are provided as well as justification of a minimum 10-day quarantine period.

No deterioration after 13 years in a stability study of a rabbit brain, plain, thromboplastin, RBT 1010, in rubber-stoppered ampoules.

RBT 1010, a rabbit brain thromboplastin, plain, was prepared at the Thrombosis Reference Centre, Withington Hospital, Manchester, in 1989. The batch has been stored at -20 degrees C, in rubber-stoppered ampoules, for 13 years. The material was unchanged after this time. This was confirmed in a stability study, in which the reagent was used to test the prothrombin times of a panel of plasmas stored in liquid nitrogen, one from a normal volunteer and two from stable anticoagulated patients. RBT 1010 was also tested in calibrations, according to World Health Organization recommendations, against the reference thromboplastin preparations CRM 149S and RBT 90.

Exercise-induced endocrine pathologies.

There has been a substantial increase in women practicing sports over the past 30 yr. While exercise provides many health benefits, there appears to be a unique set of risks associated with intense exercise for the female athlete. The female athlete triad encompasses these risks, including amenorrhea, osteoporosis and eating disorders. The incidence of menstrual irregularities including primary and secondary amenorrhea and shortened luteal phases is much higher among women partaking in athletics, specifically in sports requiring low body weight for performance and aesthetics. The hormone pattern seen in these amenorrheic athletes includes a decrease in GnRH pulses from the hypothalamus, which results in decreased pulsatile secretion of LH and FSH and shuts down stimulation of the ovary. The recently discovered hormone leptin may also play a large role as a significant mediator of reproductive function. The prevalence of eating disorders is high among female athletes who practice sports which emphasize leanness. Consequently, the cause of menstrual irregularities is not due to the exercise alone, but to chronic inadequate or restrictive caloric intake that does not compensate for the energy expenditure. The most dangerous risk associated with amenorrhea for the female athlete is the impact on the skeleton. Complications associated with amenorrhea include compromised bone density, failure to attain peak bone mass in adolescence and increased risk of stress fractures. The diagnosis of exercise-associated menstrual dysfunctions is one of exclusion. The most effective treatment is to decrease the intensity of the exercise and increase the nutritional intake. Hormone replacement has also been under investigation as a possible treatment.