Conservative treatment of a synovial cyst in a golden eagle (Aquila chrysaetos) with triamcinolone acetonide.

In human and veterinary medicine, the treatment of synovial cysts involves medical or surgical approach. When medical treatment is chosen, triamcinolone acetonide is one of the most used drugs. In this case, intracystic triamcinolone was administered for the treatment of a non-infectious elbow synovial cyst in a subadult female Golden eagle (Aquila chrysaetos), unable to fly. The bird was brought to a wildlife rescue center after an aerial fight with a conspecific. After the treatment, no clinically detectable adverse effects were noted and there was no recurrence within two weeks. Given the improvement of the clinical conditions and the recovery of flight ability, the animal was released back into the wild 17 days after administration of the drug.

Diagnosis and Surgical Treatment of a Renal Cyst Causing Unilateral Lameness in a Golden Eagle (Aquila chrysaetos).

This report describes the diagnosis and treatment of a benign renal cyst in an adult, female golden eagle (Aquila chrysaetos) presented for unilateral leg lameness. A cyst at the cranial division of the left kidney was diagnosed by computed tomography and was suspected of compressing the lumbosacral nerve plexus, resulting in limb lameness. The renal cyst was incompletely excised because the cyst wall was closely adhered to the kidney parenchyma and local blood supply. Fluid analysis and surgical biopsy of the cyst and left kidney confirmed the diagnosis of a benign renal cyst. No evidence of an infectious, inflammatory, or neoplastic etiology was noted. Postoperatively, the eagle's lameness resolved and the bird was ultimately released following recovery. During treatment for the renal cyst, the eagle was concurrently found to have increased serum titers on elementary body agglutination for Chlamydia psittaci and a positive titer for Aspergillus species antibody testing. The bird was administered doxycycline, azithromycin, and voriconazole for treatment of these potential pathogens prior to release. Unfortunately, the eagle was found dead 86 days postrelease due to an unknown cause. To the authors' knowledge, this is the first report of a golden eagle with a benign solitary renal cyst causing unilateral lameness secondary to nerve compression that was resolved with surgical excision.

A "One Arrow Three Eagle" Strategy to Improve CM-272 Primed Bladder Cancer Immunotherapy.

Immunotherapy using an immune-checkpoint blockade has significantly improved its therapeutic effects. CM-272, which is a novel epigenetic inhibitor of G9a, induces immunogenic cell death (ICD) for recovering the sensitivity to anti-PD-1 antibodies; however, the efficacy of CM-272 is greatly limited by promoting the transcription activity of HIF-1α to form a hypoxic environment. Here, a Fe3+ -based nanoscale metal-organic framework (MIL-53) is used to load CM-272 (ultra-high loading rate of 56.4%) for realizing an MIL-53@CM-272 nanoplatform. After entering bladder cancer cells, Fe3+ not only promotes the decomposition of H2 O2 into O2 for O2 -compensated sonodynamic therapy but reduces the high level of glutathione in the tumor microenvironment (TME) for enhancing reactive oxygen species, including ferroptosis and apoptosis. MIL-53 carriers can be degraded in response to the TME, accelerating the release of CM-272, which helps achieve the maximum effectiveness in an O2 -sufficient TME by attenuating drug resistance. Furthermore, MIL-53@CM-272 enhances dendritic cell maturation and synergistically combines it with an anti-programmed cell death protein 1 antibody during the study of immune-related pathways in the transcriptomes of bladder cancer cells using RNA-seq. This study presents the first instance of amalgamating nanomedicine with CM-272, inducing apoptosis, ferroptosis, and ICD to achieve the "one arrow three eagle" effect.

Postmortem Evaluation of Cardiac Valvular Disease in Bald Eagles (Haliaeetus leucocephalus) and a Golden Eagle (Aquila chrysaetos).

Limited data are available regarding cardiac diseases in birds of prey despite their prevalence in these avian species. Literature regarding valvular lesions in birds of prey is scarce and includes single reports of left atrioventricular valvular endocarditis in an adult, free-ranging, male bald eagle (Haliaeetus leucocephalus) and aortic valvular endocarditis in an adult, free-ranging, female red-tailed hawk (Buteo jamaicensis). The purpose of this study was to evaluate the prevalence, signalment, gross necropsy findings, and histologic lesions of valvular lesions in eagles. In this retrospective study, necropsy reports for 24 free-ranging and captive eagles were evaluated over a 15-year period (July 3, 2006-February 28, 2021). Six (25%; 95% confidence interval: 8.9-58.9) birds, 5 bald eagles and 1 golden eagle (Aquila chrysaetos), met the inclusion criteria. Five (83.3%) of the 6 birds had valvular degeneration, 2 (33.3%) had endocarditis, and Staphylococcus aureus was cultured from 1 (16.7%) of the endocarditis cases. The 6 eagles with valvular lesions were all captive adults. Four of the birds were female (66.7%), and the aortic and left atrioventricular valves were equally affected. Acute or chronic cerebral infarcts were present in all 6 birds. Valvular cardiac disease should be considered as a differential diagnosis in eagles exhibiting respiratory distress, neurologic signs, syncope, or in cases of sudden death.

Massive hepatic trematodosis in 5 juvenile bald eagles.

Hepatic trematodosis by opisthorchiid flukes has been reported sporadically in North American fish-eating raptors. Bald eagles (Haliaeetus leucocephalus) infected by these flukes often have various degrees of granulomatous cholangitis, pericholangitis, necrosis of adjacent hepatocytes, and subsequent hepatic fibrosis. Species identification has been complicated by the inability to dissect intact specimens from liver tissue. Between 2007 and 2018, 5 juvenile bald eagles with massive hepatic trematodosis were identified at autopsy. Histologically, flukes were non-spinous. Parasitologic identification revealed ventral suckers (80-93 µm diameter), and uteri containing golden, operculated eggs (~25.0 × 12.0 µm). An unfixed frozen liver sample of one eagle was analyzed by PCR and DNA sequencing targeting the large subunit rRNA, ITS region, and cox1 genes of the parasite. The fluke DNA sequences shared 99.6%, 98.4%, and 87.0% similarity, respectively, with Erschoviorchis anuiensis, a newly described opisthorchiid species infecting the liver and pancreas of fish-eating birds in Europe and Asia. Infection by E. anuiensis is highly pathogenic in several piscivorous bird species. The clinical significance of trematodosis in our 5 cases is uncertain because all birds had comorbidities.

Intralipid Emulsion Therapy for the Treatment of Suspected Toxicity in 2 Avian Species.

Intravenous lipid emulsion (ILE) therapy has shown promise as a treatment option for a variety of lipophilic toxins. Two birds presented for suspected ingestion of a toxic substance. A blue-and-gold macaw (Ara ararauna) presented after chewing a block of bromethalin rodenticide without overt clinical signs at the time of presentation. Additionally, a free-ranging bald eagle (Haliaeetus leucocephalus) was found weak and depressed near a municipal landfill after presumptive ingestion of pentobarbital. Both birds were treated with ILE therapy for potential intoxication without any adverse events. The macaw was clinically normal after 3 days of hospitalization and at a 1-week reevaluation. The eagle was transferred to a rehabilitation center after markedly improved mentation and strength and was released 7 days later. Clinicians should consider ILE therapy for the treatment of lipophilic toxicities; however, monitoring is recommended for persistent lipemia and other adverse effects that have been reported in the veterinary literature.

Lead, cadmium, and other trace elements in the liver of golden eagles and white-tailed eagles: recent data from Poland and a systematic review of previous studies.

The golden eagle (Aquila chrysaetos) and the white-tailed eagle (Haliaeetus albicilla), being apex predators and facultative scavengers, can bioaccumulate different environmental contaminants, including toxic elements that may adversely affect their health. We analyzed the levels of cadmium (Cd), lead (Pb), and other metals and metalloids, including arsenic (As), barium (Ba), beryllium (Be), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), magnesium (Mg), manganese (Mn), molybdenum (Mo), selenium (Se), thorium (Th), thallium (Tl), uranium (U), vanadium (V), and zinc (Zn) in liver samples taken from three golden eagles and 36 white-tailed eagles that were found dead across Poland to verify their exposure. We also used a systematic review to summarize the available literature data on Cd, Pb, and other studied elements in the liver of both eagle species. Analyses of trace elements in the liver samples of the Polish eagles revealed interspecific differences in Cd, Cu, and Mn and differences in Co, Mn, Tl, and Zn among study regions. All elements tested except Pb were below the suggested thresholds linked with adverse health effects in birds. The hepatic Pb found in almost half of all the tested individuals suggests environmental exposure to this toxic element. One of the tested white-tailed eagles had hepatic Pb above the threshold of sublethal poisoning. Although our results seem optimistic, as previous Polish studies showed a higher prevalence of birds with hepatic Pb exceeding the toxicity threshold, they indicate that exposure to this toxic metal could still pose an additional threat to the health of Polish eagles.

Survival Risk Prediction of Esophageal Squamous Cell Carcinoma Based on BES-LSSVM.

Esophageal squamous cell carcinoma (ESCC) is one of the highest incidence and mortality cancers in the world. An effective survival prediction model can improve the quality of patients' survival. In this study, ten indicators related to the survival of patients with ESCC are founded using genetic algorithm feature selection. The prognostic index (PI) for ESCC is established using the binary logistic regression. PI is divided into four stages, and each stage can reasonably reflect the survival status of different patients. By plotting the ROC curve, the critical threshold of patients' age could be found, and patients are divided into the high-age groups and the low-age groups. PI and ten survival-related indicators are used as independent variables, based on the bald eagle search (BES) and least-squares support vector machine (LSSVM), and a survival prediction model for patients with ESCC is established. The results show that five-year survival rates of patients are well predicted by the bald eagle search-least-squares support vector machine (BES-LSSVM). BES-LSSVM has higher prediction accuracy than the existing particle swarm optimization-least-squares support vector machine (PSO-LSSVM), grasshopper optimization algorithm-least-squares support vector machine (GOA-LSSVM), differential evolution-least-squares support vector machine (DE-LSSVM), sparrow search algorithm-least-squares support vector machine (SSA-LSSVM), bald eagle search-back propagation neural network (BES-BPNN), and bald eagle search-extreme learning machine (BES-ELM).

An appraisal of FDA approvals for adult solid tumours in 2017-2021: has the eagle landed?

In 2016, the then US President Barack Obama announced the Cancer Moonshot with a view to making 10 years' worth of progress in cancer prevention, diagnosis and treatment in only 5 years. This Perspective evaluates the FDA approvals of therapeutic agents for use in solid tumour oncology for the period 2017-2021 against the aspirations of the Cancer Moonshot. In the past 5 years, the FDA issued an unprecedented 161 new approvals of therapeutic agents for various indications in adult patients with solid tumours. However, less than a third (27%) of the newly approved medicines are supported by unequivocal evidence of an overall survival benefit; most are supported by positive signals from surrogate end points. Herein, the European Society for Medical Oncology Magnitude of Clinical Benefit Scale version 1.1 was used to evaluate the clinical value of the therapies granted FDA approval during the period 2017-2021. The results of this appraisal indicate a low level of clinical benefit for a substantial proportion (~20%) of the new indications, with most (~44%) providing intermediate benefit. The data suggest that, beyond increases in the sheer quantity of approvals, considerable improvement in the quality of the approved treatments is required to more confidently ensure that the clinical benefits are real and substantial enough to clearly justify the risks to patients.

A time-trend guided non-target screening study of organic contaminants in Baltic Sea harbor porpoise (1988-2019), guillemot (1986-2019), and white-tailed sea eagle (1965-2017) using gas chromatography-high-resolution mass spectrometry.

The rate of decline in regulated persistent organic pollutant (POP) concentrations in Baltic Sea biota has leveled off in recent years, with new contaminants frequently being discovered. There is, therefore, a need for comprehensive approaches to study occurrence and temporal trends of a wide range of environmental contaminants, including legacy POPs, contaminants of emerging concern (CECs), and new contaminants. In the current work, non-target screening (NTS) workflows were developed and used for, to the best of our knowledge, the first time-trend directed NTS of biota using gas chromatography-high-resolution mass spectrometry (GC-HRMS). To maximize contaminant coverage, both electron ionization (EI) and electron capture negative ion chemical ionization (ECNI) were used. The EI data were treated using highly automated workflows to find, prioritize, and tentatively identify contaminants with statistically significant temporal trends. The ECNI data were manually processed and reviewed prior to time-trend analysis. Altogether, more than 300 tentatively identified contaminants were found to have significant temporal trends in samples of Baltic guillemot, harbor porpoise, or white-tailed sea eagle. Significant decreases were found for many regulated chemicals, as could be expected, such as PCBs, polychlorinated terphenyls, chlorobenzenes, toxaphenes, DDT, other organochlorine pesticides, and tri- and tetra- bromodiphenyl ethers (BDEs). The rate of decline of legacy POPs agreed well with data reported from targeted analyses. Significant increases were observed for small polycyclic aromatic hydrocarbons, heptaBDEs, CECs, and terpenes and related compounds. The CECs included, among others, one plasticizer tributyl acetylcitrate (ATBC), two antioxidants 2,6-bis(1,1-dimethylethyl)phenol and 2,6-bis(tert-butyl)-4-(4-morpholinyl-methyl)phenol, and two compounds used in polymer production, trimethyl isocyanurate and 2-mercaptobenzothiazole, which had not previously been reported in biota. Their increased concentrations in biota indicate increased use and release. The increase in ATBC may be linked to increased use of it as a substitute for di-2-ethylhexyl phthalate (DEHP), which has been phased out over the last decade.

The eagle sign: a new preoperative MRI-based tool for predicting topographic correlation between craniopharyngioma and hypothalamus.

PURPOSE: Accurate prediction of topographical correlation between craniopharyngiomas (CPs) and hypothalamus is important for treatment. This study sought to develop a predicting tool based on preoperative-MRI through radiological-surgical-pathological-outcome analysis. MATERIALS AND METHODS: Third ventricle floor (TVF), mammillary bodies and cerebral peduncle were evaluated through preoperative-MRI. An eagle-head-like sign named "eagle sign" was observed. Normal TVF on sagittal-MRI was defined as the baseline. Variants of the sign were analyzed by comparing with the baseline and corresponding correlations of CPs with hypothalamus were verified using intraoperative records, histopathology and outcome evaluation. RESULTS: A total of 146 CPs patients, who undergone endoscopic endonasal procedure were divided into four groups based on the variants of "eagle sign". Group A: 24 patients with the upward sign; group B: 81 with the downward sign; group C: 21 with the anterior TVF upward sign and group D: 20 with the unidentifiable sign. Surgical-pathological analysis showed significant correlations between 95.8% CPs in group A and 95.2% in group C with tumor topography and tumor adherence to the hypothalamus. These CPs had their origins beneath the hypothalamus. In contrast, groups B and D, with hypothalamic origin, showed hypothalamic infiltration by tumor in 97.5% and 95% of cases in groups B and D, respectively. Outcomes of groups A and C were relatively better than groups B and D. Predictive sensitivity and specificity of "eagle sign" were more than 90%. CONCLUSION: "Eagle sign" is an accurate tool for predicting topographic correlations between CPs and hypothalamus with high sensitivity and specificity.

Pharmacokinetics of a Single Intramuscular Injection of Ceftiofur Crystalline Free Acid in Bald Eagles (Haliaeetus leucocephalus).

The objective of this study was to evaluate the pharmacokinetic properties of ceftiofur crystalline free acid (CCFA) administered intramuscularly at dosages of 10 and 20 mg/kg in bald eagles (BAEAs) (Haliaeetus leucocephalus). Ceftiofur crystalline free acid is a long-acting, injectable, third-generation cephalosporin antibiotic drug. A prospective, randomized, complete crossover design was used for this pharmacokinetic investigation. CCFA (10 or 20 mg/kg) was administered intramuscularly, and blood samples were obtained from 6 adult, nonreleasable, healthy BAEAs at predetermined sampling times. After a 4-week washout period, the protocol was repeated with each bird receiving the dose not given during the initial sample collection according to the randomized crossover design. Plasma ceftiofur free acid equivalents were quantified and data were analyzed by a noncompartmental pharmacokinetic approach. The mean observed peak plasma concentrations were 9.23 µg/mL and 15.08 µg/mL for 10 and 20 mg/kg CCFA IM administration, respectively. The mean observed time to maximum plasma concentration was 18 and 17.6 hours, and the mean terminal elimination half-life was 32.38 and 38.08 hours for intramuscular administration of 10 and 20 mg/kg CCFA, respectively, in the BAEAs. Reported minimum inhibitory concentrations of raptor bacterial isolates from a prior study was used to determine the target minimum inhibitory concentration of 1 µg/mL selected for this investigation. From the previously published information, a target plasma concentration of 4 µg/mL was determined for the CCFA in the BAEAs. From the results of this study, CCFA may be dosed every 60 and 110 hours at 10 mg/kg IM, and every 80 and 160 hours at 20 mg/kg IM in BAEAs.

Removal of foreign bodies from the proventriculus in a young golden eagle (Aquila chrysaetos).

This paper presents a clinical case report of a golden eagle (Aquila chrysaetos) with foreign bodies (stones) in its proventriculus. The case deals with the identification, management and removal of foreign objects identified in the gastrointestinal tract. A surgical removal by proventriculotomy under general anaesthesia was attempted. The surgery and the recovery were uneventful, and the follow-up after six months revealed no complications. To the best of our knowledge, there are no other reports of successful foreign body removal by proventriculotomy in the golden eagle.

Radiographic Reference Intervals of the Cardiac Silhouette Width in the Bald Eagle (Haliaeetus leucocephalus).

Radiograph imaging is an important diagnostic tool for assessing cardiac size in avian patients. The bald eagle (Haliaeetus leucocephalis), once on the United States Federal List of Endangered and Threatened Wildlife and Plants, is now a thriving species in the United States. However, there is surprisingly little information regarding bald eagle cardiac reference values obtained through radiographic imaging for use in assessment of cardiac disease in this species. This study was performed to establish reference values of cardiac size in the bald eagle. Ventrodorsal radiographic images were taken from 9 healthy birds obtained from a raptor rehabilitation facility. Cardiac silhouette width to thorax width, cardiac silhouette width to sternum width, cardiac silhouette width to hepatic silhouette width, and cardiac silhouette width to coracoid width were obtained. Ratios were calculated between the respective areas measured. The results showed that the cardiac silhouette averages 44%-52% of the thoracic width, 71%-86% of the sternal width, 94%-117% of the width of the hepatic silhouette, and 500%-920% of the coracoid width. In the individuals studied there was a strong correlation between cardiac silhouette width to thoracic and sternal width whereas cardiac width with hepatic and coracoid widths had a moderate to weak correlation respectively. The values obtained in this study can be used to radiographically assess the cardiac size of bald eagles, thus aiding in the diagnosis of cardiomegaly in this species.

Squamous cell carcinoma of the footpad with systemic metastasis in a captive crowned solitary eagle (Buteogallus coronatus).

Squamous cell carcinomas (SCC) are one of the most common tumors of the tegument that can have a misdiagnosis of chronic skin wounds. An adult captive crowned solitary eagle presented an indolent wound-like ulcer on the footpad and a fatal outcome. An infiltrating tumoral mass in the foot and multiple tumoral metastatic nodules in visceral organs were detected. The neoplasm was composed of atypical squamous cells with strong positivity for cytokeratin, "keratin pearl" structures, and marked invasion of tissues confirming a diagnosis of metastatic SCC. This might be the first report of an SSC with metastasis on the footpad in a captive Chaco eagle, which is one of the endangered species of birds of prey.

Acute toxoplasmosis and pox-viral dermatitis in a juvenile bald eagle (Haliaeetus leucocephalus) in New Brunswick, Canada.

Although birds of prey are commonly subclinically infected by Toxoplasma gondii tissue cysts, clinical disease is relatively rare in these species. The present report describes a rare case of fatal toxoplasmosis in a juvenile bald eagle in New Brunswick. Necropsy investigation revealed severe emaciation and poxviral dermatitis which partially obscured the palpebral fissures. Microscopically there was severe lymphoplasmacytic inflammation and necrosis of the lung that was associated with abundant protozoal tachyzoites. Infection with T. gondii was confirmed in the lung via immunohistochemistry and DNA sequencing. Key clinical message: Wildlife rehabilitation centers should be aware of the potential occurrence of acute clinical toxoplasmosis in stressed malnourished raptors.

Toxoplasmose aigu ë et dermatite à poxvirus chez un pygargue à tête blanche ( Haliaeetus leucocephalus ) au Nouveau-Brunswick, Canada. Bien que les oiseaux de proie soient fréquemment infectés de manière subclinique par des kystes tissulaires de Toxoplasma gondii, la maladie clinique est relativement rare chez ces espèces. Le présent rapport décrit un rare cas de toxoplasmose fatale chez un pygargue à tête blanche juvénile au Nouveau-Brunswick. La nécropsie a révélé une émaciation sévère et une dermatite à poxvirus qui obstruait partiellement les fissures palpébrales. L'examen microscopique révéla une inflammation lympho-plasmocytaire sévère et une nécrose du poumon qui fut associé à une abondance de tachyzoïtes d protozoaires. L'infection par T. gondii fut confirmée dans le poumon via immunohistochimie et séquençage de l'ADN.Message clinique clé :Les centres de réhabilitation de la faune devrait être averti de l'existence de toxoplasmose clinique aiguë chez des rapaces stressés et mal nourris.(Traduit par Dr Serge Messier).

Fecal sex steroids and reproductive behaviors in harpy eagles (Harpia harpyja).

Aiming to improve our reproductive knowledge of large birds of prey, behavioral data and fecal steroids were assessed in captive pairs of Harpy eagles, a keystone species that is monogamous and resides in the Neotropics year-round. Adult individuals exhibited different reproductive outcomes and a breeding season extending beyond summer solstice (5-9 months) suggests that harpy eagles may not be absolutely photorefractory. Comparisons among breeding stages in males revealed that mean androgen levels in courtship were higher than in copulation and incubation, but no differences were detected in fecal progestagens or estrogens. Females had higher mean estrogen concentrations in courtship and copulation, whereas mean progestagen levels peaked during egg laying. Mean androgen concentrations were not significantly different among breeding stages in females. Assessment of six egg-lay cycles from three females demonstrated that fecal estrogens peaked predominantly between 31 and 18 days before oviposition (-31 to -18 days), and then remained low until 45 days after laying the first egg (+45 days). In contrast, fecal progestagens raised mostly between -20 and +1 day, lowering to baseline concentrations by +3 days. To our knowledge, this is the first study to describe in detail endocrine and behavioral data regarding reproduction in tropical eagles, which may serve in the future as a reference to developing breeding programs.

Screening and Identification of Novel cGAS Homologues Using a Combination of in Vitro and In Vivo Protein Synthesis.

The cyclic GMP-AMP synthase (cGAS) catalyzes the synthesis of the multifunctional second messenger, cGAMP, in metazoans. Although numerous cGAS homologues are predicted in protein databases, the catalytic activity towards cGAMP synthesis has been proven for only four of them. Therefore, we selected five novel and yet uncharacterized cGAS homologues, which cover a broad range in the field of vertebrates. Cell-free protein synthesis (CFPS) was used for a pre-screening to investigate if the cGAS genes originating from higher organisms can be efficiently expressed in a bacterial expression system. As all tested cGAS variants were expressible, enzymes were synthesized in vivo to supply higher amounts for a subsequent in vitro activity assay. The assays were carried out with purified enzymes and revealed vast differences in the activity of the homologues. For the first time, the cGAS homologues from the Przewalski's horse, naked mole-rat, bald eagle, and zebrafish were proven to catalyze the synthesis of cGAMP. The extension of the list of described cGAS variants enables the acquisition of further knowledge about the structural and molecular mechanism of cGAS, potentially leading to functional improvement of the enzyme.

Successful, Full-Thickness Skin Graft in a Bald Eagle (Haliaeetus leucocephalus).

A subadult, male bald eagle (Haliaeetus leucocephalus) was evaluated after being found unable to fly, with large eschars on the dorsal head and right stifle. Because of the appearance and location, the lesions were believed to be caused by an electrical injury. Treatment included oral antibiotics, nonsteroidal anti-inflammatory drugs, pain medication, surgical debridement of the eschars, and trephining of the affected inner table of the cranium. A full-thickness skin graft was performed to expedite wound healing and minimize holding time. After 6 weeks, the bird had new feather growth on its dorsal head and was released. This is the first report, to our knowledge, of a nonmesh, full-thickness skin graft in an avian species. Full-thickness skin grafts should be considered as a surgical option in juvenile or adult avian patients with large dorsal head wounds.