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.

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.

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.

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.

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.

[Survey among keepers of endangered sheep and goat breeds on the influence of wolves on animal husbandry]. / Befragung von Haltern von vom Aussterben bedrohten Schaf- und Ziegenrassen zum Einfluss des Wolfes auf die Tierhaltung.

OBJECTIVE: As Germany's wolf population is steadily becoming more widespread, conflicts with livestock owners are increasing. In this context, the wolves' impact on grazing livestock is of particular interest. The study aimed to investigate the wolves' influence on the husbandry of endangered sheep and goat breeds. Thus, livestock owners were interviewed about the types of measures taken to protect their herds against wolf predation. MATERIAL AND METHODS: A questionnaire consisting of 11 questions was published online by the "Gesellschaft zur Erhaltung alter und gefährdeter Haustierrassen e. V. (GEH)" and completed anonymously by 494 sheep and goat owners from all over Germany. RESULTS: 33 % of the endangered sheep breeds and 80 % of the endangered goat breeds are owned by fewer than ten of the livestock owners, who predominantly keep these animals as a hobby or as a supplementary source of income. The cessation of livestock husbandry by any of these owners may therefore have a significant negative impact on the continued existence of the breed in question. However, the mean herd sizes of the studbook breeds do not indicate any negative impact on animal numbers in recent years, although the majority of respondents consider their grazing livestock to be threatened by wolves. It is noteworthy that significantly more livestock owners situated far away from wolf habitats expressed the wish to discontinue their husbandry as opposed to those within range of wolf habitats. Preventative measures mentioned most frequently are fencing and enclosures as well as avoiding certain areas entirely. The use of guard dogs does not seem to play a major role. CONCLUSIONS: The abandonment of animal husbandry by individual farmers poses the risk of reducing breed diversity in small ruminants. Therefore, they need special protection, which must be taken into account when planning and defining compensation measures.

[Population structure of South American camelids in Germany]. / Populationsstruktur und Haltungsweisen von Neuweltkameliden in Deutschland sowie Fachkunde der Tierhalter.

OBJECTIVES: As part of the "Model- und Demonstrationsvorhaben Tierschutz (MuD-Tierschutz)-project, supported by the Federal Ministry of Food and Agriculture (BMEL), an animal owner survey was conducted to collect data on various aspects of keeping South American camelids (NWC). This publication covers the population structure of NWC in Germany. MATERIAL AND METHODS: 550 owners participated in the survey, of which 421 (76.5 %) completed the survey in full. The different sets of questions were evaluated using simple descriptive statistics. RESULTS: The participating farms divided up into 365 (66.4 %) alpaca, 89 (16.2 %) llama and 93 (16.9 %) farms which kept both animal species. Three farms failed to provide any information on the animal species. A total of 7739 NWC were recorded, including 6295 alpacas and 1444 llamas. The most popular breeds are the Huacaya alpaca and the Classic llama. Mares represent the greatest part of both the alpaca and the llama population (53.8 % of the alpaca and 45.0 % of the llama population). The herd size amounted to a mean of 14.9 animals of which the majority are kept in a constant group (56.6 %). Most owners stated, that they had acquired their animals within the past decade (84.1 % of alpaca and 62.6 % of llama husbandries). The majority of NWC are found in south-west Germany; in Bavaria, North Rhine-Westphalia and Baden-Wuerttemberg. These farms are typically hobby businesses (51.0 %), in most cases, the animals serve as hiking companions or their wool is processed (58.0 % and 52.3 %, respectively). 76.6 % of the animals possess an identification, most often by means of a microchip. 84.2 % of the farms stated, that they were registered at the local veterinary office. CONCLUSION: Based on the results of the present investigation, a significant increase in NWC husbandries and animal numbers is evident in recent years. The design of husbandry structures was evaluated by the present study, however, despite the existing registration obligation the exact number of the South American camelid population in Germany remains unknown. Systematic central recording under the supervision of an official body is therefore warranted.

[Importance of tail length in sheep and the breeding for short tails]. / Bedeutung der Schwanzlänge beim Schaf und Zucht auf Kurzschwänzigkeit.

Breeding for short tails in sheep may represent a good measure in order to avoid the continuation of tail docking in lambs. Since the ancestor of domestic sheep, the mouflon, has a short, narrow tail, it may be assumed that longer tails are a result of domestication. Previous studies on the heritability of tail length in domestic sheep were able to show values of 0.38 to 0.77, depending on the breed. Breeding for short tails must however ensure the avoidance of spinal malformations and those of neighboring structures. Until breeding progress is achieved, management measures may reduce the negative effects of long and woolly tails (e. g. myiasis, dermatitis). This includes prevention of diarrhea by balanced, ruminant-friendly feeding, a farm-specific and sustainable parasite management program as well as the deliberate shearing of uncut tails.

Suppression of reproductive function in juvenile rams by a slow-release gonadotropin-releasing hormone implant.

Background: Regarding animal welfare and reversible suppression of reproduction the need for alternatives to surgical castration, like slow-release gonadotropin-releasing hormone (GnRH) implants, is increasing. Aim: In this study, we evaluated whether the onset of puberty can be suppressed by implantation of a slow-release GnRH implant (4.7 mg deslorelin) in juvenile rams. Methods: Seven juvenile rams (3-5.5 months) were treated with the GnRH analog deslorelin to analyze the effects on testicular development, sonographic findings of testicular tissue, testosterone concentration in the blood, spermatogenesis, and sperm parameters from the epididymis after castration. Seven rams of the same age without an implant served as controls. Results: Follow-up examinations were conducted over 5 months, after which four rams per group were castrated. No significant group differences were found in the andrological parameters on the group level, but testicular development was suppressed in three rams in the treated group. Histological examination revealed spermatogenesis in the testicular tissue in three of four animals treated with a GnRH analog. Conclusion: The onset of puberty in juvenile rams cannot be reliably suppressed by using the slow-release GnRH implant Suprelorin®.

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.

Bivalirudin Versus Heparin Monotherapy in ST-Segment-Elevation Myocardial Infarction.

BACKGROUND: Bivalirudin was not superior to unfractionated heparin in patients with myocardial infarction (MI) treated with percutaneous coronary intervention and no planned use of GPI (glycoprotein IIb/IIIa inhibitors) in contemporary clinical practice of radial access and potent P2Y12-inhibitors in the VALIDATE-SWEDEHEART randomized clinical trial (Bivalirudin Versus Heparin in STEMI and NSTEMI Patients on Modern Antiplatelet Therapy-Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies Registry). METHODS: In this prespecified separately powered subgroup analysis, we included patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with the primary composite end point of all-cause death, MI, or major bleeding event within 180 days. RESULTS: Among the 6006 patients enrolled in the trial, 3005 patients with ST-segment-elevation MI were randomized to receive bivalirudin or heparin. The mean age was 66.8 years. According to protocol recommendations, 87% were treated with potent oral P2Y12-inhibitors before start of angiography and radial access was used in 90%. GPI was used in 51 (3.4%) and 74 (4.9%) of patients randomized to receive bivalirudin and heparin, respectively. The primary end point occurred in 12.5% (187 of 1501) and 13.0% (196 of 1504; hazard ratio [HR], 0.95 [95% CI, 0.78-1.17], P=0.64) with consistent results in all major subgroups. All-cause death occurred in 3.9% versus 3.9% (HR, 1.00 [0.70-1.45], P=0.98), MI in 1.7% versus 2.2% (HR, 0.76 [0.45-1.28], P=0.30), major bleeding in 8.3% versus 8.0% (HR, 1.04 [0.81-1.33], P=0.78), and definite stent thrombosis in 0.5% versus 1.3% (HR, 0.42 [0.18-0.96], P=0.04). CONCLUSIONS: In patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention with radial access and receiving current recommended treatments with potent P2Y12-inhibitors rate of the composite of all-cause death, MI, or major bleeding was not lower in those randomized to receive bivalirudin as compared with heparin. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

[Two cases of statin-induced immune-mediated necrotizing myopathy]. / Immunmedierad nekrotiserande myopati utlöst av statinbehandling.

Statin-induced immune-mediated necrotizing myopathy (IMNM) is a rare subtype of idiopathic inflammatory myopathy (IIM) that distinct from other types of IIM and statin-induced muscle symptoms, regarding clinic, diagnosis and treatment. The condition, characterized by symmetrical proximal muscle weakness and significantly increased creatine kinase (CK) levels, is persistent after statin discontinuation. Muscle biopsy shows necrotic muscle fibers and regeneration fibers with minimal inflammatory infiltrates. Over the past decade, an autoantibody to hydroxymethylglutaryl coenzyme A reductase (HMGCR) has been identified for the diagnosis of statin-associated IMNM. Optimal treatment strategy is unclear, but aggressive immunosuppression has shown to be effective. This case report describes two patients with statin-induced IMNM. The patients present with proximal muscle weakness, elevated CK levels, and are subsequently positive for anti-HMGCR autoantibodies with necrosis in muscle biopsy.

Clinical Impact of Intraprocedural Stent Thrombosis During Percutaneous Coronary Intervention in Patients Treated With Potent P2Y12 inhibitors - a VALIDATE-SWEDEHEART Substudy.

Background The clinical importance of intraprocedural stent thrombosis (IPST) during percutaneous coronary intervention in the contemporary era of potent oral P2Y12 inhibitors is not established. The aim of this study was to assess IPST and its association with clinical outcome in patients with myocardial infarction undergoing percutaneous coronary intervention with contemporary antithromboticmedications. Methods and Results The VALIDATE-SWEDEHEART study (Bivalirudin Versus Heparin in ST-Segment and Non-ST-Segment Elevation Myocardial Infarction in 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 6006 patients with myocardial infarction, treated with potent P2Y12 inhibitors during percutaneous coronary intervention. IPST, defined as a new or worsening thrombus related to a stent deployed during the procedure, was reported by the interventional cardiologist in 55 patients (0.9%) and was significantly associated with ST-segment elevation myocardial infarction presentation, longer stents, bailout glycoprotein IIb/IIIa inhibitors, and final Thrombolysis in Myocardial Infarction flow <3. The primary composite end point included cardiovascular death, myocardial infarction, out-of-laboratory definite stent thrombosis and target vessel revascularization within 30 days. Secondary end points were major bleeding and the individual components of the primary composite end point. Patients with versus without IPST had significantly higher rates of the primary composite end point (20.0% versus 4.4%), including higher rates of cardiovascular death, target vessel revascularization, and definite stent thrombosis, but not myocardial infarction or major bleeding. By multivariable analysis, IPST was independently associated with the primary composite end point (hazard ratio, 3.82; 95% CI, 2.05-7.12; P<0.001). Conclusions IPST is a rare but dangerous complication during percutaneous coronary intervention, independently associated with poor prognosis, even in the current era of potent antiplatelet agents. Future treatment studies are needed to reduce the rate of IPST and to improve the poor outcome among these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02311231.

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.