Bioadaptor implant versus contemporary drug-eluting stent in percutaneous coronary interventions in Sweden (INFINITY-SWEDEHEART): a single-blind, non-inferiority, registry-based, randomised controlled trial.

BACKGROUND: Persistent non-plateauing adverse event rates in patients who underwent percutaneous coronary intervention (PCI) remain a challenge. A bioadaptor is a novel implant that addresses this issue by restoring the haemodynamic modulation of the artery, allowing cyclic pulsatility, vasomotion, and adaptative remodelling, by unlocking and providing dynamic support to the artery. We aimed to assess outcomes with the device versus a contemporary drug-eluting stent (DES) in a representative PCI population. METHODS: INFINITY-SWEDEHEART is a single-blind, non-inferiority, registry-based, randomised controlled study conducted in 20 hospitals in Sweden. Patients aged 18-85 years, with chronic or acute coronary syndrome ischaemic heart disease, with an indication for PCI, with up to three de novo lesions suitable for implantation with one single device per lesion, and successful pre-dilatation were identified via the Swedish Coronary Angiography and Angioplasty Registry and eligible for enrolment. Participants were randomly assigned (1:1), using block randomisation with random variation in block size and stratified by site, to either the DynamX bioadaptor (Elixir Medical, Milpitas, CA, USA) or a zotarolimus-eluting DES (Resolute Onyx and Onyx Trustar, Medtronic, Minneapolis, MN, USA). The primary endpoint was the device-oriented clinical endpoint of target lesion failure at 12 months (a composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target lesion revascularisation), assessed in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment, regardless of treatment received) who had either experienced an event up to 12 months or completed the trial up to 12 months. Non-inferiority was established if the upper limit of the two-sided 95% CI for the absolute risk difference was less than 4·2%. Powered secondary endpoints were landmark analyses from 6 months onwards for target lesion failure, target vessel failure (composite of cardiovascular death, target vessel myocardial infarction, and ischaemia-driven target vessel revascularisation), and target lesion failure for patients with acute coronary syndrome assessed in the ITT population). This study is registered with ClinicalTrials.gov, NCT04562805, and follow-up to 5 years is ongoing. FINDINGS: Between Sept 30, 2020, and July 11, 2023, 2399 patients were randomly assigned to receive the bioadaptor (n=1201) or DES (n=1198; ITT population). Median age was 69·5 years (IQR 61·2-75·6), 575 (24·0%) of 2399 patients were female, and 1824 (76·0%) were male (data on race and ethnicity were not collected), and 1838 (76·6%) patients presented with acute coronary syndrome. The primary endpoint of 12-month target lesion failure occurred in 28 (2·4%) of 1189 assessable patients in the bioadaptor group versus 33 (2·8%) of 1192 assessable patients in the DES group, with a risk difference of -0·41% (95% CI -1·94 to 1·11; pnon-inferiority<0·0001). In the prespecified landmark analysis from 6 months to 12 months, the Kaplan-Meier estimates of target lesion failure were 0·3% (with events in three of 1170 patients) in the bioadaptor group versus 1·7% (with events in 16 of 1176 patients) in the DES group (hazard ratio 0·19 [95% CI 0·06 to 0·65]; p=0·0079), of target vessel failure were 0·8% (events in eight of 1167) versus 2·5% (events in 23 of 1174; 0·35 [0·16 to 0·79]; p=0·011), and of target lesion failure in patients with acute coronary syndrome were 0·3% (events in two of 906) versus 1·8% (events in 12 of 895; 0·17 [0·04 to 0·74]; p=0·018). The rate of definite or probable device thrombosis, which was recorded as a safety outcome, was low and did not differ between groups (eight [0·7%] of 1201 in the bioadaptor group vs six [0·5%] of 1198 in the DES group; difference in event rates of 0·16% [95% CI -0·50 to 0·83]). INTERPRETATION: Among patients with coronary artery disease, including those with acute coronary syndrome, treatment with the bioadaptor was non-inferior to contemporary DES, showing potential to mitigate non-plateauing device-related events and improving outcomes in patients undergoing PCI. The additional planned follow-up will help to reinforce the clinical significance of the 1-year findings. FUNDING: Elixir Medical.

MFSD2A frameshift variant in Kerry Hill sheep with microcephaly.

Microcephaly is a rare neurodevelopmental disorder characterized by reduced skull circumference and brain volume that occurs sporadically in farm animals. We investigated an early-onset neurodegenerative disorder observed in seven lambs of purebred Kerry Hill sheep. Clinical signs included inability to stand or severe ataxia, convulsions, and early death. Diagnostic imaging and brain necropsy confirmed microcephaly. The pedigree of the lambs suggested monogenic autosomal recessive inheritance. We sequenced the genome of one affected lamb, and comparison with 115 control genomes revealed a single private protein-changing variant. This frameshift variant, MFSD2A: c.285dupA, p.(Asp96fs*9), represents a 1-bp duplication predicted to truncate 80% of the open reading frame. MFSD2A is a transmembrane protein that is essential for maintaining blood-brain barrier homeostasis and plays a key role in regulating brain lipogenesis. Human MFSD2A pathogenic variants are associated with a neurodevelopmental disorder with progressive microcephaly, spasticity, and brain imaging abnormalities (NEDMISBA, OMIM 616486). Here we present evidence for the occurrence of a recessively inherited form of microcephaly in sheep due to a loss-of-function variant in MFSD2A (OMIA 002371-9940). To the best of our knowledge, this is the first report of a spontaneous MFSD2A variant in domestic animals.

Fasciola hepatica soluble antigens (FhAg) induce ovine PMN innate immune reactions and NET formation in vitro and in vivo.

Fasciola hepatica causes liver fluke disease, a worldwide neglected and re-emerging zoonotic disease, leading to hepatitis in humans and livestock. In the pathogenesis, flukes actively migrate through liver parenchyma provoking tissue damage. Here, parasites must confront leukocytes of the innate immune system in vivo. Polymorphonuclear neutrophils (PMN) are the most abundant granulocytes and first ones arriving at infection sites. PMN may display neutrophil extracellular traps (NETs), consisting of nuclear DNA, decorated with histones, enzymes, and antimicrobial peptides. We investigated for the first time whether F. hepatica soluble antigens (FhAg) can also trigger NETosis and innate immune reactions in exposed ovine PMN. Thus, isolated PMN were co-cultured with FhAg and NET formation was visualized by immunofluorescence and scanning electron microscopy analyses resulting in various phenotypes with spread NETs being the most detected in vitro. In line, NETs quantification via Picogreen®-fluorometric measurements revealed induction of anchored- and cell free NETs phenotypes. Live cell 3D-holotomographic microscopy revealed degranulation of stimulated PMN at 30 min exposure to FhAg. Functional PMN chemotaxis assays showed a significant increase of PMN migration (p = 0.010) and intracellular ROS production significantly increased throughout time (p = 0.028). Contrary, metabolic activities profiles of FhAg-exposed PMN did not significantly increase. Finally, in vivo histopathological analysis on F. hepatica-parasitized liver tissue sections of sheep showed multifocal infiltration of inflammatory cells within liver parenchyma, and further fluorescence microscopy analyses confirmed NETs formation in vivo. Overall, we hypothesized that NET-formation is a relevant host defence mechanism that might have a role in the pathogenesis of fasciolosis in vivo.

Multiple-trait and structural equation modelling approaches to infer genetic relationships between tail length and weight traits in Merinoland sheep.

Tail docking is routinely conducted in long-tailed sheep breeds to prevent flystrike infections, but it is not in agreement with legal guidelines and animal welfare issues. Selection on short tails is a sustainable alternative in this regard, but side effects on other breeding goal traits are unclear. In consequence, the present study aimed to estimate genetic parameters for tail length (TL) at birth, birth weight (BW), weaning weight (WW) and postweaning weight (PWW) at the slaughtering date considering single-trait (STM), multiple-trait (MTM) and structural equation models (SEM) with different random effects, and accordingly, different covariance structures. The SEM considered time-lagged recursive relationships among response variables in three different pathways. The first path pertained to the effect of TL on WW and of WW on PWW. The second path reflected the effect of BW on WW and of WW on PWW. The third path was the recursive effect of TL on PWW. The phenotypic data consisted of 2803 records for TL, 13,042 records for BW, 1556 records for WW and 3986 records for PWW from Merinoland lambs. Lambs were born in the period from 1995 to 2021 and kept at the university Gießen research station, Germany, with their naturally long tails. Genetic statistical model evaluation based on Bayesian and Akaike's information criteria suggested models simultaneously considering direct genetic, maternal genetic and maternal permanent environmental effects and respective covariances. For statistical models including the same random effects and covariance structures, SEM were superior over MTM. The direct heritability for TL from the best-fitting STM was 0.60 ± 0.08, indicating the potential for genetic reduction of tail length within a few generations. For growth traits, the direct heritabilities ranged from 0.16 ± 0.03 for BW to 0.31 ± 0.09 for PWW. The maternal heritabilities were 0.03 ± 0.03 for TL, 0.12 ± 0.02 for BW, 0.04 ± 0.03 for WW and 0.07 ± 0.03 for PWW, reflecting small, but the non-significant influence of uterine characteristics on the tail development. The direct genetic correlations between TL and all weight traits were positive and very similar to MTM and SEM but reflected antagonistic genetic relationships from a breeding perspective. Oppositely, the structural equation coefficients reflecting trait associations phenotypically were negative (favourable) for the time-lagged effects of TL on WW and on PWW. As an explanation, lambs with long and woolly tails have an increased risk for contamination with dirt and dust causing infections, which in turn impairs the body weight development. In conclusion, breeding on short tails should consider trait-associated environmental risk factors, for example, disease susceptibility, which can be mimicked via SEM approaches.

Downregulation of testicular function in the goat by altrenogest.

BACKGROUND: The present study investigated whether the administration of the progestin altrenogest provides noninvasive, temporary, and reversible suppression of gonadal function in the goat as a potential alternative to chirurgical castration, which is related with irreversibility, risks of complications till death of the animal and welfare issues. Eight sexually mature Peacock goats were randomly divided into two groups. The experimental group was administered altrenogest (0.088 mg/kg) orally once daily for 7 weeks. The remaining four goats received an oral glucose solution and served as the control group. After completing the administration period, the reversibility of the medication was evaluated for another 7 weeks (observation phase). The treatment effects were assessed by clinical examination; ultrasound examination of the testes, including one-dimensional grayscale analysis, blood testosterone levels, analysis of semen parameters and libido. At the end of the observation period, the animals were castrated and the testicles were examined histologically. RESULTS: Altrenogest treatment had no significant effect on the physical development of the goats, the sonographic appearance of the testes, the gray values measured in the ultrasound images, or the blood testosterone levels. The effects of treatment on the testicular and semen parameters varied widely in the experimental animals; the testicle volume was significantly lower and the number of pathologically altered sperm in the ejaculate was significantly higher in treated animals. CONCLUSION: These findings indicate that daily altrenogest administration at a dose of 0.088 mg/kg does not reliably suppress gonadal function in the goat.

Bivalirudin versus Heparin Monotherapy in Myocardial Infarction.

BACKGROUND: The comparative efficacy of various anticoagulation strategies has not been clearly established in patients with acute myocardial infarction who are undergoing percutaneous coronary intervention (PCI) according to current practice, which includes the use of radial-artery access for PCI and administration of potent P2Y12 inhibitors without the planned use of glycoprotein IIb/IIIa inhibitors. METHODS: In this multicenter, randomized, registry-based, open-label clinical trial, we enrolled patients with either ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) who were undergoing PCI and receiving treatment with a potent P2Y12 inhibitor (ticagrelor, prasugrel, or cangrelor) without the planned use of glycoprotein IIb/IIIa inhibitors. The patients were randomly assigned to receive bivalirudin or heparin during PCI, which was performed predominantly with the use of radial-artery access. The primary end point was a composite of death from any cause, myocardial infarction, or major bleeding during 180 days of follow-up. RESULTS: A total of 6006 patients (3005 with STEMI and 3001 with NSTEMI) were enrolled in the trial. At 180 days, a primary end-point event had occurred in 12.3% of the patients (369 of 3004) in the bivalirudin group and in 12.8% (383 of 3002) in the heparin group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.10; P=0.54). The results were consistent between patients with STEMI and those with NSTEMI and across other major subgroups. Myocardial infarction occurred in 2.0% of the patients in the bivalirudin group and in 2.4% in the heparin group (hazard ratio, 0.84; 95% CI, 0.60 to 1.19; P=0.33), major bleeding in 8.6% and 8.6%, respectively (hazard ratio, 1.00; 95% CI, 0.84 to 1.19; P=0.98), definite stent thrombosis in 0.4% and 0.7%, respectively (hazard ratio, 0.54; 95% CI, 0.27 to 1.10; P=0.09), and death in 2.9% and 2.8%, respectively (hazard ratio, 1.05; 95% CI, 0.78 to 1.41; P=0.76). CONCLUSIONS: Among patients undergoing PCI for myocardial infarction, the rate of the composite of death from any cause, myocardial infarction, or major bleeding was not lower among those who received bivalirudin than among those who received heparin monotherapy. (Funded by the Swedish Heart-Lung Foundation and others; VALIDATE-SWEDEHEART ClinicalTrialsRegister.eu number, 2012-005260-10 ; ClinicalTrials.gov number, NCT02311231 .).

ß-blockers after myocardial infarction and 1-year clinical outcome - a retrospective study.

BACKGROUND: Long term ß-blocker therapy after myocardial infarction (MI) reduces mortality and recurrent MI but evidence for this treatment predates contemporary acute coronary care. ß-blocker treatment is a key quality of care indicator in the Swedish national quality register for acute coronary care, Riks-HIA. Between 2011 and 2015 a declining number of MI-patients discharged with a ß-blocker from the coronary care unit (CCU) at Helsingborg and other hospitals was reported. This retrospective observational study aimed to investigate the causes for discharge without a ß-blocker and relate it to outcome, compared to patients discharged with a ß-blocker. METHODS: MI-patients registered in Riks-HIA discharged without ß-blocker during 2011-2015 (no-ß-group) and a control group (ß-group) comprised of patients discharged with ß-blocker treatment between January 1 to December 31, 2013, were matched by RIKS-HIA criteria for ß-blocker use. Clinical characteristics, date of death, readmission for MI, other cardiovascular events were collected from Riks-HIA and medical records. RESULTS: The no-ß-group included 141 patients, where 65.2% had a justified reason for non-ß-blocker use. The ß-group included 206 patients. There was no difference in cardiovascular risk factor profile. There were a trend towards a higher number of readmissions for MI in the no-ß-group was (n = 8 (5.7%) vs n = 2 (1.0%), p = 0.02), but not mortality (6 (4.3%) vs 2 (1.0%), p = 0.07) and combined readmission for angina pectoris, heart failure, arrhythmias or stroke/TIA (n = 23 (16.3%) vs n = 25 (12.1%), p = 0.27). CONCLUSION: A majority of the patients in the no-ß-group had a justified absence of a ß-blocker. ß-blocker treatment post-MI showed a trend towards fewer readmissions for MI. But important quality information is lacking to make a firm conclusion of the effect on outcome.

Mechanical chest compressions for cardiac arrest in the cath-lab: when is it enough and who should go to extracorporeal cardio pulmonary resuscitation?

BACKGROUND: Treating patients in cardiac arrest (CA) with mechanical chest compressions (MCC) during percutaneous coronary intervention (PCI) is now routine in many coronary catheterization laboratories (cath-lab) and more aggressive treatment modalities, including extracorporeal CPR are becoming more common. The cath-lab setting enables monitoring of vital physiological parameters and other clinical factors that can potentially guide the resuscitation effort. This retrospective analysis attempts to identify such factors associated with ROSC and survival. METHODS: In thirty-five patients of which background data, drugs used during the resuscitation and the intervention, PCI result, post ROSC-treatment and physiologic data collected during CPR were compared for prediction of ROSC and survival. RESULTS: Eighteen (51%) patients obtained ROSC and 9 (26%) patients survived with good neurological outcome. There was no difference between groups in regards of background data. Patients arriving in the cath-lab with ongoing resuscitation efforts had lower ROSC rate (22% vs 53%; p = 0.086) and no survivors (0% vs 50%, p = 0.001). CPR time also differentiated resuscitation outcomes (ROSC: 18 min vs No ROSC: 50 min; p = 0.007 and Survivors: 10 min vs No Survivors: 45 min; p = 0.001). Higher arterial diastolic blood pressure was associated with ROSC: 30 mmHg vs No ROSC: 19 mmHg; p = 0.012). CONCLUSION: Aortic diastolic pressure during CPR is the most predictive physiological parameter of resuscitation success. Ongoing CPR upon arrival at the cath-lab and continued MCC beyond 10-20 min in the cath-lab were both predictive of poor outcomes. These factors can potentially guide decisions regarding escalation and termination of resuscitation efforts.

Prasugrel 5 mg inhibits platelet P-selectin and GPIIb-IIIa expression in very elderly and non elderly: results from the GENERATIONS trial, a pharmacodynamic study in stable CAD patients.

UNLABELLED: Platelet P-selectin and activated glycoprotein IIb-IIIa (GPIIb-IIIa) are markers of platelet activation and mediates platelet aggregation. Prasugrel (Pras) 5 mg may be used in very elderly (VE) acute coronary syndrome (ACS) patients undergoing PCI, but its effect on platelet P-selectin and activated GPIIb-IIIa in those patients is not known. Stable ACS patients, VE (78 ± 5 years, n = 23) and non-elderly (NE) (55 ± 5 years, n = 22) were randomized to Pras (5 or 10 mg) or clopidogrel (Clop) 75 mg during three 12-day periods. Platelet activation markers were measured by flow cytometry on unstimulated or stimulated (adenosine diphosphate (ADP) 20 µM) platelets, before and after each dosing period. RESULTS: At baseline there was no difference in platelet activation markers, either unstimulated or ADP-stimulated, between NE and VE. Pras 5 mg reduced both ADP-stimulated platelet P-selectin and activated GPIIb-IIIa in VE (p < 0.01 for both analyses) and NE (p < 0.001 and p < 0.05, respectively). Clop 75 mg had a similar effect as Pras 5 mg but did not significantly reduce activated GPIIb-IIIa in VE. Prasugrel 10 mg resulted in decreased platelet activation in both age groups compared to Clop 75 mg (p < 0.01). CONCLUSIONS: In VE and NE-patients, Pras 5 mg inhibited platelet P-selectin expression similar to Clop 75 mg and Pras 10 mg. Prasugrel 10 mg inhibited platelet P-selectin expression better than Clop 75 mg. Prasugrel 10 mg and 5 mg, but not Clop 75 mg, significantly inhibited activated GPIIb-IIIa in VE. This platelet reactivity data support the use of Pras 5 mg for VE patients.

Repeated epinephrine doses during prolonged cardiopulmonary resuscitation have limited effects on myocardial blood flow: a randomized porcine study.

BACKGROUND: In current guidelines, prolonged cardiopulmonary resuscitation (CPR) mandates administration of repeated intravenous epinephrine (EPI) doses. This porcine study simulating a prolonged CPR-situation in the coronary catheterisation laboratory, explores the effect of EPI-administrations on coronary perfusion pressure (CPP), continuous coronary artery flow average peak velocity (APV) and amplitude spectrum area (AMSA). METHODS: Thirty-six pigs were randomized 1:1:1 to EPI 0.02 mg/kg/dose, EPI 0.03 mg/kg/dose or saline (control) in an experimental cardiac arrest (CA) model. During 15 minutes of mechanical chest compressions, four EPI/saline-injections were administered, and the effect on CPP, APV and AMSA were recorded. Comparisons were performed between the control and the two EPI-groups and a combination of the two EPI-groups, EPI-all. RESULT: Compared to the control group, maximum peak of CPP (Pmax) after injection 1 and 2 was significantly increased in the EPI-all group (p = 0.022, p = 0.016), in EPI 0.02-group after injection 2 and 3 (p = 0.023, p = 0.027) and in EPI 0.03-group after injection 1 (p = 0.013). At Pmax, APV increased only after first injection in both the EPI-all and the EPI 0.03-group compared with the control group (p = 0.011, p = 0.018). There was no statistical difference of AMSA at any Pmax. Seven out of 12 animals (58%) in each EPI-group versus 10 out of 12 (83%) achieved spontaneous circulation after CA. CONCLUSION: In an experimental CA-CPR pig model repeated doses of intravenous EPI results in a significant increase in APV only after the first injection despite increments in CPP also during the following 2 injections indicating inappropriate changes in coronary vascular resistance during subsequent EPI administration.

Higher body weight patients on clopidogrel maintenance therapy have lower active metabolite concentrations, lower levels of platelet inhibition, and higher rates of poor responders than low body weight patients.

Body weight is a predictor of clopidogrel response. However, no prospective studies have compared pharmacodynamic (PD) and pharmacokinetic (PK) data based on body weight. We compared PD and PK effects of clopidogrel 75 mg in low body weight (LBW, <60 kg) and higher body weight (HBW, ≥60 kg) patients with stable coronary artery disease. LBW (n = 34, 56.4 ± 3.7 kg) and HBW (n = 38, 84.7 ± 14.9 kg) aspirin-treated patients received clopidogrel 75 mg for 10-14 days. The area under the concentration-time curve of active metabolite (Clop-AM) calculated through the last quantifiable concentration up to 4 h postdose, AUC(0-tlast), was calculated by noncompartmental methods. Light transmission aggregometry (LTA) (maximum platelet aggregation and inhibition of platelet aggregation to 20 µM adenosine diphosphate (ADP), and residual platelet aggregation to 5 µM ADP), VerifyNow(®) P2Y12 reaction units (PRU), and vasodilator-associated stimulated phosphoprotein phosphorylation platelet reactivity index (VASP-PRI) were performed. Mean AUC(0-tlast) was lower in HBW than LBW patients: 12.8 versus 17.9 ng h/mL. HBW patients had higher platelet reactivity as measured by LTA (all p ≤ 0.01), PRU (207 ± 68 vs. 152 ± 57, p < 0.001), and VASP-PRI (56 ± 18 vs. 39 ± 17, p < 0.001). More HBW patients exhibited high on-treatment platelet reactivity (HPR) using PRU (35 vs. 9%) and VASP-PRI (65 vs. 27%). Body weight correlated with PRU and VASP-PRI (both p < 0.001), and inversely with log transformed AUC(0-tlast) (p < 0.001). In conclusion, HBW patients had lower levels of Clop-AM, and higher platelet reactivity and rates of HPR than LBW subjects, contributing to their suboptimal response to clopidogrel.

First detection of autochthonous Lamanema chavezi infections in llamas (Lama glama) in Europe.

Lamanema chavezi is one of the most pathogenic nematode species of South American camelids (SAC), with a homoxenous life cycle involving enterohepatic migration of its larvae in the host. So far, it has been found in the Americas and New Zealand. The first autochthonous L. chavezi infections in SAC in Europe are reported here. On a SAC farm in Germany, a 15-month-old male llama with a short history of diarrhoea died in September 2017, followed nine months later by a three-year-old female llama with a history of emaciation, apathy, anorexia, anaemia and tetraparesis with retained sensorium. Both animals were born and raised on the farm, which had imported three llamas directly from Chile 4-14 years earlier. At necropsy, the main lesions in both cases were numerous white-yellow to dark red foci, up to 3 mm in size, close to the Glisson's capsule and deep in the parenchyma of the liver. Histologically, the livers showed haemorrhagic tracks by and with nematode larvae and a necro-haemorrhagic to fibrinous inflammation with a predominantly lymphohistiocytic infiltration. The larvae were 30-50 µm in diameter and had external longitudinal cuticular ridges. Larvae extracted from unfixed liver tissue were 1800-2000 µm long and about 80 µm in diameter, with a terminal spine at the posterior end, which is characteristic of female L. chavezi stages. The ribosomal DNA including the almost complete 18S rRNA gene, the first internal transcribed spacer, the 5.8S RNA gene, the second internal transcribed spacer (ITS) and the partial 28S rRNA gene from isolated larvae were amplified using nematode-specific oligonucleotide primers and then sequenced. The assembled nematode sequence of 3448 bp showed an identity of 99.4% to previously published L. chavezi sequences in the BLASTN search. Low numbers of L. chavezi-like eggs were found in the faeces of seven (29%) of 24 llamas and alpacas in the herd, including some farm-born crias, tested two years after the last fatal case. The results show for the first time that L. chavezi has not only been imported into Europe from South America, but has also completed its life cycle locally, resulting in autochthonous infections of SAC. This was also suspected to be the cause of the fatal disease in two llamas.

Mycoplasma mycoides subspecies capri, an uncommon mastitis and respiratory pathogen isolated in a German flock of goats.

Mycoplasma mycoides ssp. capri (Mmc) is one of the etiological microorganisms of contagious agalactia, which is among the diseases causing the highest economical losses in small ruminants. We report a disease outbreak in a German flock that led to significant suffering of goats characterized by mastitis, arthritis, pleuropneumonia and sudden deaths. Mmc was persistently isolated from many animals both from milk, and from a number of different swab and tissue samples. A number of closely related Mycoplasma spp. have to be taken into consideration to rule out important animal epizootics listed by European Animal Health Law and the World Organisation for Animal Health (WOAH). Some goats developed cross-reacting antibodies against Mycoplasma mycoides ssp. mycoides. Although Mmc is believed to be an uncommon microorganism in Germany, this study highlights that veterinarians should consider this pathogen in their work during herd health monitoring in Central Europe. Although eradication was not fully achieved, autogenous vaccination significantly seemed to improve animal health and welfare.

Bivalirudin versus heparin in ST and non-ST-segment elevation myocardial infarction-Outcomes at two years.

BACKGROUND: The registry-based randomized VALIDATE-SWEDEHEART trial (NCT02311231) compared bivalirudin vs. heparin in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI). It showed no difference in the composite primary endpoint of death, MI, or major bleeding at 180 days. Here, we report outcomes at two years. METHODS: Analysis of primary and secondary endpoints at two years of follow-up was prespecified in the study protocol. We report the study results for the extended follow-up time here. RESULTS: In total, 6006 patients were enrolled, 3005 with ST-segment elevation MI (STEMI) and 3001 with Non-STEMI (NSTEMI), representing 70 % of all eligible patients with these diagnoses during the study. The primary endpoint occurred in 14.0 % (421 of 3004) in the bivalirudin group compared with 14.3 % (429 of 3002) in the heparin group (hazard ratio [HR] 0.97; 95 % confidence interval [CI], 0.85-1.11; P = 0.70) at one year and in 16.7 % (503 of 3004) compared with 17.1 % (514 of 3002), (HR 0.97; 95 % CI, 0.96-1.10; P = 0.66) at two years. The results were consistent in patients with STEMI and NSTEMI and across major subgroups. CONCLUSIONS: Until the two-year follow-up, there were no differences in endpoints between patients with MI undergoing PCI and allocated to bivalirudin compared with those allocated to heparin. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02311231.

Frequency and Characterisation of Anomalies and Fractures of the Caudal Spine in Sheep with Undocked Tails.

As tails are often docked within the first days of life, studies investigating tail malformations and injuries in sheep do not exist thus far. To address this gap in the literature, this research aimed to analyse the occurrence of vertebral anomalies and fractures in the tail within an undocked Merinoland sheep population. At 14 weeks of age, the caudal spines of 216 undocked Merinoland lambs was radiographically examined, and tail length and circumference were measured. Anomalies were documented and statistical correlation and model calculations were performed. The occurrence of block vertebrae was observed in 12.96% and wedged vertebrae in 8.33% of the sample. Of the animals, 59 (27.31%) exhibited at least one vertebral fracture, which were observed in the middle and caudal third of the tail. A significant correlation was found between the occurrence of fractures and tail length (r = 0.168) and number of vertebrae (r = 0.155). Conversely, the presence of block and wedged vertebrae was not significantly correlated with tail length, circumference, or number of vertebrae. Only the sex showed significant differences in the probability of axis deviation. These results emphasize the importance of breeding for short tails to avoid fractures.

[Phenotyping the sheep tail - Presentation of characterization methods in the context of breeding for short-tailedness]. / Phänotypisierung des Schafschwanzes ­ Darstellung von Methoden zur Charakterisierung im Rahmen der Zucht auf Kurzschwänzigkeit.

OBJECTIVE: In order to establish targeted breeding for short-tailedness, a suitable method must initially be found that allows phenotyping of the sheep tail beyond tail length. In this study, in addition to assessing body measurements, more advanced studies such as ultrasonography and radiology were performed on the caudal spine of sheep for the first time. The objective of this work was to analyze the physiological variation of tail lengths and vertebrae within a merino sheep population. It also aimed to validate the use of sonographic gray scale analysis and perfusion measurement on the sheep tail. MATERIAL AND METHOD: Tail length and circumference in centimeters were measured in 256 Merino lambs on the first or second day of life. At 14 weeks of age the caudal spine of these animals was examined radiographically. Sonographic gray scale analysis and measurement of the perfusion velocity of the caudal artery mediana were also performed in a portion of the animals. RESULTS: The tested method of measurement showed a standard error of 0,08 cm and a coefficient of variation of 0,23% for tail length and 0,78% for tail circumference. The animals had a mean tail length of 22,5±2,32 cm and a mean tail circumference of 6,53±0,49 cm. The mean caudal vertebrae count for this population was 20,4±1,6. The use of a mobile radiographic unit is well suited for imaging the caudal spine in sheep. It was demonstrated that the caudal median artery could be imaged for measurement of perfusion velocity (cm/s), and sonographic gray-scale analysis also showed good feasibility. The mean gray scale value is 19,74±4,5 and the modal value for the most commonly found gray scale pixels is 191,53±120,2. The mean perfusion velocity for the caudal artery mediana is 5,83±3,04 cm/s. CONCLUSION: The results show that the methods presented are well suited for further characterization of the ovine tail. For the first time, gray values for the tail tissue and the perfusion velocity of the caudal artery mediana were determined.

Prognostic value of early sustained ventricular arrhythmias in ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention: A substudy of VALIDATE-SWEDEHEART trial.

Background: Prognostic assessment of ventricular tachycardia (VT) or ventricular fibrillation (VF) in ST-segment elevation myocardial infarction (STEMI) is based mainly on distinguishing between early (<48 hours) and late arrhythmias, and does not take into account its time distribution with regard to reperfusion, or type of arrhythmia. Objective: We analyzed the prognostic value of early ventricular arrhythmias (VAs) in STEMI with regard to their type and timing. Methods: The prespecified analysis of the multicenter prospective Bivalirudin versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarctionin Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease evaluated according to Recommended Therapies Registry Trial included 2886 STEMI patients undergoing primary percutaneous coronary intervention (PCI). VA episodes were characterized regarding their type and timing. Survival status at 180 days was assessed through the population registry. Results: Nonmonomorphic VT or VF was observed in 97 (3.4%) and monomorphic VT in 16 (0.5%) patients. Only 3 (2.7%) early VA episodes occurred after 24 hours from symptom onset. VA was associated with higher risk of death (hazard ratio 3.59; 95% confidence interval [CI] 2.01-6.42) after adjustment for age, sex, and STEMI localization. VA after PCI was associated with an increased mortality compared with VA before PCI (hazard ratio 6.68; 95% CI 2.90-15.41). Early VA was associated with in-hospital mortality (odds ratio 7.39; 95% CI 3.68-14.83) but not with long-term prognosis in patients discharged alive. The type of VA was not associated with mortality. Conclusion: VA after PCI was associated with an increased mortality compared with VA before PCI. Long-term prognosis did not differ between patients with monomorphic VT and nonmonomorphic VT or VF, but events were few. VA incidence during 24 to 48 hours of STEMI is negligibly low, thus precluding assessment of its prognostic importance.

Epididymis incision as a method to collect epididymal sperm cells in alpacas.

BACKGROUND: Epididymal sperm can be collected post-castration or post-mortem. This method has already been described for alpaca (Vicugna pacos), but little data are available on success rate and the influence of diluent on it. OBJECTIVE: The aim was to investigate the effectiveness of epididymis incision as an extraction method. METHOD: Post-castration epididymides (n = 78) were incised and semen was collected from cut surfaces. Further sperm were flushed with two semen extenders. For the left epididymis, a diluent without animal proteins and for the right, a diluent with egg yolk was utilised. Collected sperms were immediately spermatologically examined. RESULTS: Due to incorrect measurements, the samples of seven epididymides were not analysed. An evaluation was possible in 58 samples. Average density was 108.80 ± 83.28 million/mL and motility was 53.30 ± 18.17%. On average, 76.70 ± 11.60% of the sperm were vital in eosin-stained specimens. In the hypoosmotic swelling test, an average of 69.50 ± 10.48% of the sperm had an intact plasma membrane. Semen extender had no effect on spermatological parameters (p > 0.05). Overall success rate of sperm recovery was 83%. Extraction of epididymal sperm was possible in 68.80% of the 2-year-old males. The 13 epididymides from which no sperm recovery was possible were histologically examined and for 10, there was no histological evidence of sperm. The corrected success rate was 95.60%. CONCLUSION: Testicular volume (p = 0.0453), but not age (p = 0.62), had an effect on the probability of obtaining sperm.