RESPONSE AND PHYSIOLOGIC OUTCOMES AFTER BUTORPHANOL, MIDAZOLAM, AND MEDETOMIDINE IMMOBILIZATION AND REVERSAL IN CAPTIVE REINDEER (RANGIFER TARANDUS).

Sedation, recovery response, and physiologic outcomes were evaluated in five captive reindeer (Rangifer tarandus) in Minnesota using a completely reversible immobilization protocol. Reindeer were immobilized with butorphanol (0.23-0.32 mg/kg), midazolam (0.23-0.32 mg/kg), and medetomidine (0.15 mg/kg) (BMM) via IM dart. Induction time (IT), recumbency time (DT), and recovery time (RT) were recorded. Temperature (T), respiratory rate (RR), pulse rate (PR), pulse oximetry (SpO2), arterial blood gas values including oxygen (PaO2), and carbon dioxide (PaCO2) tensions and lactate (Lac) were recorded preoxygen supplementation and 15 min postoxygen supplementation. Reversal was done using naltrexone (2.3-3.0 mg/kg), flumazenil (0.008-0.01 mg/kg) and atipamezole (0.62-0.78 mg/kg) (NFA) IM, limiting recumbency to 1 h. Median IT, DT, and RT were 5 min, 46 min, and 7 min, respectively. SpO2 (92 to 99%, P = 0.125), PaO2 (45.5 to 97 mmHg, P = 0.25), and PaCO2 (46.5 to 54.6 mmHg, P = 0.25) all increased, whereas Lac (3.02 to 1.93 mmol/L, P = 0.25) decreased between baseline and 15 min postoxygen supplementation, without statistical significance. BMM immobilization, and reversal with NFA provided rapid and effective immobilization and recovery, respectively. Oxygen supplementation mitigated hypoxemia in all reindeer.

INTRAOCULAR PRESSURES OF AQUARIUM-HOUSED COWNOSE RAYS (RHINOPTERA BONASUS) WITH NORMAL AND ABNORMAL OPHTHALMIC EXAMS.

Cownose rays (Rhinoptera bonasus) are common elasmobranchs in zoos and aquaria; however, there is a lack of published information regarding ocular findings in this species. Intraocular pressure (IOP) was measured in a total of 52 cownose rays (Rhinoptera bonasus) from two unrelated aquaria (n = 22 from A1, n = 30 from A2) using a TonoVet rebound tonometer on two settings (dog = D, and unidentified species = P) as part of a full ophthalmologic examination. Adult (n = 38) and juvenile (n = 14) rays were sampled out of water briefly in sternal recumbency. Intraocular pressure (mean ± SD [range]) in the D setting (9.10 ± 2.57 [4-18] mmHg) was higher than the P setting (5.21 ± 2.32 [0-12] mmHg) (P<0.001). Statistical analysis revealed no difference in IOP between right and left eyes, and no correlation between body weight and IOP. No differences in IOP between sex, age group, and location were identified in either setting. However, a significant difference was observed between levels of severity of corneal disease in IOP D setting (P=0.006) and P setting (P=0.024), and levels of severity of intraocular disease in IOP D setting (P=0.034) only. This study provides baseline IOP values using rebound tonometry in aquarium-housed cownose rays with apparent corneal and intraocular lesions and reveals that the D setting may be more sensitive in identifying IOP changes in eyes with intraocular disease.

CLINICAL AND HISTOPATHOLOGIC OCULAR FINDINGS IN AQUARIUM-HOUSED COWNOSE RAYS (RHINOPTERA BONASUS).

Cownose rays (Rhinoptera bonasus) are susceptible to ocular disease with their prominent globes, but despite being popular animals housed in aquaria, there is little published information about their normal ocular anatomy and common pathologic ocular findings. A total of 63 live cownose rays (CNR) from three unrelated, separately housed groups had ocular examinations, and 5 adult rays were selected for ocular ultrasound. All examinations were performed out of the water, and most without anesthesia. Clinical findings were described, categorized, and scored by severity. Sixty-two of 63 rays (123 eyes) had clinical abnormalities, including 110 eyes with corneal pathology (mild = 76, moderate/severe = 34) and 74 eyes with intraocular pathology (mild = 44, moderate/severe = 30). Grey-to-white corneal opacities were the most common pathology (n = 58 rays/100 eyes) followed by cataracts (n = 41 rays/58 eyes), then persistent (or dysplastic) pupillary membranes (n = 14 rays/15 eyes). Most pathologic findings appeared inactive, but one aquarium had several CNR with active ocular pathology. There was a significant association between the diagnosis of moderate/severe corneal and intraocular pathology with age (P = 0.008 and P = 0.014, respectively) and weight (P = 0.001 and P = 0.039, respectively), as well as moderate/severe corneal pathology and group sampled (P = 0.03). There were no other significant variables identified. Additionally, histopathology of 14 eyes (11 rays) from two different facilities were examined, with keratitis (n = 8) and uveitis (n = 2) as the most common lesions. This study shows a high prevalence of pathologic ocular findings in cownose ray eyes with heavier adults more likely to be affected than lighter juveniles. Comprehensive ocular evaluation is important in this species and serial ocular exams and future studies should be pursued to monitor ocular disease progression and better understand possible etiologies.

RABIES DIAGNOSIS AND RESPONSE TO VACCINATION IN SOUTHERN TAMANDUA (TAMANDUA TETRADACTYLA).

Rabies has rarely been described in Xenarthra, and rabies vaccine response has not been documented. A southern tamandua (Tamandua tetradactyla) presented with nonspecific clinical signs and was euthanatized. Subsequently, immunohistochemistry and RT-PCR confirmed a rabies diagnosis. Following these tests, a group of eight captive tamanduas were vaccinated with a killed rabies vaccine, and titers were measured at the time of vaccination and 23 d later. One animal had day 0 titers suggestive of previous vaccination or exposure. All animals had detectable neutralizing rabies virus antibody titers after vaccination, but one animal failed to meet the World Organization for Animal Health's definition for adequate vaccination (≥0.5 IU/ml), and two other animals had low antibody titers (0.56 and 0.6 IU/ml). Rabies should be considered as a possible cause of illness in tamanduas, and rabies vaccination may be a useful preventative measure when anthropic interaction through medical care or ambassador roles is occurring.

Does ORTO-15 produce valid data for 'Orthorexia Nervosa'? A mixed-method examination of participants' interpretations of the fifteen test items.

PURPOSE: Orthorexia Nervosa (ON) is defined as a pathological eating behaviour stemming from being "healthy" or "pure". Survey-based studies typically rely on the ORTO-15 questionnaire or its variations to detect orthorexia. However, frequent post-hoc adjustments to the ORTO-15 suggest psychometric problems. In this study, we explored people's cognitions about the ORTO-15 items to (1) identify problems specific to ORTO-15 items and (2) explore participants' understanding of ON symptoms. METHODS: Fifty adult participants (40% male, mean age = 34.0 ± 14.4 years) completed the ORTO-15, the Eating Attitudes Test (EAT-26) and the Obsessive-Compulsive Inventory-Revised edition (OCI-R). Qualitative data were collected using the modified "think aloud" protocol, which asked participants to 'verbalise' their responses to the ORTO-15 items. These qualitative responses were first analysed conjunctively with the quantitative responses; then subjected to thematic analysis. RESULTS: ORTO-15 identified 64% of the participants for orthorexic tendencies. In most cases (76%), participants reported no issues completing the ORTO-15. However, in some cases, qualitative responses differed from quantitative ones. When people encountered problems, it was because of poor psychometric construction: lack of clarity, ambiguous wording and multiple statements in a single item. Elaborations around the ORTO-15 items formed four major themes: "preoccupation with physical appearance", "control", "food is fuel" and "alone, not isolated". CONCLUSION: Even though in the majority of cases there were no issues with completing ORTO-15, thematic analysis revealed several discrepancies between our participants' perceptions of the ORTO-15 items and the previously proposed diagnostic criteria for ON. The results suggest that ORTO-15 is, at best, a mediocre screening tool for ON, which is sensitive to diet but fails to have sufficient level of specificity to detect the pathological stage. More accurate instruments are needed to further research on ON. LEVEL OF EVIDENCE: V (cross-sectional descriptive study with qualitative analysis).

Efficacy of a Modified Health Assessment Utilized on Two Genetically Distinct Stocks of Rainbow Trout.

The Rainbow Trout Oncorhynchus mykiss is a salmonid fish that is maintained in aquaculture facilities and used as a source of protein around the world. Veterinarians need accurate, efficient tools and straightforward assessments to evaluate the health status of fish, like Rainbow Trout, that are cultivated on farms. In this study, two genetically distinct broodstock lines of Rainbow Trout originally obtained from two different U.S. states but propagated at Rushing Waters Trout Farm (Palmyra, Wisconsin) were evaluated. Groups originating from both states (State A: n = 20; State B: n = 20) were surveyed with a modified health assessment in a prospective, randomized, single-blind study. The adapted health assessment included external and internal gross evaluations, skin scrapes, gill clips, intestinal scrapes, and calculated indices, including condition factor and the hepatosomatic index. Generally, there were few significant differences in health assessment values between State A and State B fish. When this information was presented to the producer, it was discovered that perceived differences between groups were due to management errors in calculated growth rates. The results of this study add validity to the use of standardized health assessments for evaluating fish within aquaculture.

COMPARISON OF SUBCUTANEOUS ADMINISTRATION OF ALFAXALONE-MIDAZOLAM-DEXMEDETOMIDINE WITH KETAMINE-MIDAZOLAM-DEXMEDETOMIDINE FOR CHEMICAL RESTRAINT IN JUVENILE BLUE POISON DART FROGS (DENDROBATES TINCTORIUS AZUREUS).

Blue poison dart frogs (Dendrobates tinctorius azureus) are commonly maintained in zoological institutions and are becoming popular in the pet trade industry. Sedation or light anesthesia is required for safe and effective handling of this species. In this study, the sedative effects of subcutaneously administered alfaxalone-midazolam-dexmedetomidine (AMD) (20, 40, 5 mg/kg, respectively) and ketamine-midazolam-dexmedetomidine (KMD) (100, 40, 5 mg/kg, respectively) were compared in a prospective, randomized, blinded, crossover study in juvenile blue poison dart frogs (n = 10). Both protocols were partially reversed 45 min after administration of either protocol with subcutaneously administered flumazenil (0.05 mg/kg) and atipamezole (50 mg/kg). Heart rate, pulmonic respiratory rate, various reflexes, and behavioral parameters were monitored after drug administration. Both protocols resulted in rapid loss of righting reflex [median (range): AMD, 5 min (5-5 min); KMD, 5 min (5-10 min)]. Time to complete recovery was similar with both protocols (mean ± SD: AMD, 97.5 ± 11.4 min; KMD, 96.5 ± 25.4 min). The AMD protocol resulted in pulmonic respiratory depression, whereas no significant difference in heart rate was found between the two protocols. All frogs were observed eating within 24 hr of chemical restraint. Gastric prolapses occurred in four frogs (AMD 3, KMD 1) that were easily reduced with a cotton-tip application. No other adverse reactions were observed. The results of this study provide two different subcutaneous chemical restraint protocols in juvenile blue poison dart frogs.

Adult autologous mesenchymal stem cells for the treatment of suspected non-infectious inflammatory diseases of the canine central nervous system: safety, feasibility and preliminary clinical findings.

BACKGROUND: Non-infectious inflammatory diseases of the canine central nervous system (CNS) are common idiopathic disorders grouped under the term meningoencephalomyelitis of unknown origin (MUO). Ante mortem diagnosis is achieved via assessment of clinical signs, magnetic resonance imaging (MRI), and cerebrospinal fluid (CSF) analysis, but the definitive diagnosis needs histopathological examination. MUO are mostly considered as autoimmune CNS disorders, so that suppressing the immune reaction is the best management method for patients. Mesenchymal stem cells (MSCs) are under investigation to treat autoimmune and degenerative disorders due to their immunomodulatory and regenerative properties. This study aims to verify the safety, feasibility, and efficacy of MSCs treatment in canine idiopathic autoimmune inflammatory disorders of the CNS. METHODS: Eight dogs presented with acute onset and rapid progression of multifocal neurological signs were selected to the study. In all patients' physical and neurological examinations, MRI and CSF analyses were performed. Clinical diagnosis in all cases was MUO. All selected dogs responded initially to immunosuppressive drugs (prednisone and a combination of prednisolone and cytosine arabinoside) but developed undesirable side effects. For all eight dogs, the owners considered euthanasia but accepted cell therapy as a last possibility. Autologous bone marrow MSCs (BMMSCs), isolated, cultured, and expanded, were administered by intrathecal (IT) injection in the cisterna magna intravenously (IV) and by intra-arterial (IA) injection in the right carotid artery. Adverse effects and clinical response were monitored for 6 months up to 2-year follow-up. RESULTS: The use of autologous BMMSCs in dogs with MUO was safe for IT, IV, and IA injections. No major short- or long-term adverse effects were registered. All the dogs presented early improvement in their general and neurological conditions, with particular effect on cervical pain. The group of dogs treated by IT+IA administration showed a shorter time of reaction to therapy compared to the group treated by IT+IV administration. CONCLUSIONS: MSCs treatment in dogs affected by MOU is safe and feasible. A larger group of dogs is needed to confirm these results as well as CNS histology in order to better understand the underlying mechanisms.

HIV-2 infection, end-stage renal disease and protease inhibitor intolerance: which salvage regimen?

Non-nucleoside reverse transcriptase inhibitors and enfuvirtide are ineffective against HIV-2 replication. These considerations may have particular significance in the formulation of second-line or salvage regimens for HIV-2 infection when resistance or toxicity precludes the use of protease inhibitors (PIs) or specific nucleoside analogues. We describe a case of a treatment-experienced patient with important limitations in therapeutic options dictated by the presence of HIV-2 infection, severe HIV nephropathy (requiring haemodialysis), intolerance to PIs and clinical contraindications to the use of some nucleoside analogues (anaemia, pancreatic toxicity and high cardiovascular risk). A three-drug regimen based on raltegravir, tenofovir disoproxil fumarate and lamivudine was given, with no major toxicity, good immunological response and complete viral suppression. Our case indicates that regimens based on integrase inhibitors could represent an effective alternative in PI-resistant or PI-intolerant patients with HIV-2, and that tenofovir disoproxil fumarate may be used in patients with end-stage renal disease requiring haemodialysis who cannot take other nucleoside analogues because of treatment-limiting adverse effects.

Comparison of Thermal and Mechanical Noxious Stimuli for Testing Analgesics in White's Tree Frogs (Litoria caerulea) and Northern Leopard Frogs (Lithobates pipiens).

Determining the clinical efficacy of analgesic drugs in amphibians can be particularly challenging. The current study investigated whether a thermal nociceptive stimulus is useful for the evaluation of analgesic drugs in 2 amphibian species. The objectives of this study were 2-fold: 1) compare 2 models of nociception (thermal and mechanical) using 2 frog species; White's Tree Frogs (Litoria caerulea; WTF) and Northern Leopard Frogs (Lithobates pipiens; NLF) after administration of saline or morphine sulfate; and 2) evaluate antinociceptive efficacy of morphine sulfate at 2 doses in a common amphibian research species, the NLF, using a mechanical stimulus. Neither WTF nor NLF displayed consistent drug-dependent changes in withdrawal responses to a noxious thermal stimulus applied using the Hargreaves apparatus, but NLF exposed to the noxious mechanical stimulus demonstrated a significant dose-dependent antinociceptive response to morphine sulfate. These results indicate that morphine is not antinociceptive in WTF, supporting previously reported results, and demonstrate the importance of using an appropriate experimental antinociceptive test in amphibians. Our data suggest that nociception in amphibian species may be best evaluated by using mechanical nociceptive models, although species differences must also be considered.

Early Treatment with Bamlanivimab Alone does not Prevent COVID-19 Hospitalization and Its Post-Acute Sequelae. A Real Experience in Umbria, Italy.

BACKGROUND AND OBJECTIVE: The use of monoclonal antibodies to the SARS-Cov-2 spike protein for early treatment of COVID-19 disease is being evaluated, with only phase 2 studies available to date. The emergency authorization of bamlanivimab monotherapy was obtained in November 2020 by the FDA and in March 2021 by Italian agency AIFA. Its use was then revoked in April 2021 by both. This study reports the results of bamlanivimab utilization in monotherapy in Umbria (Italian region) to verify whether, in a population with multiple risk factors, comparable results to the phase 2 BLAZE1 trial had been obtained. METHODS: Between March and April 2021, a retrospective observational study was performed on patients treated with bamlanivimab. Demographic and clinical characteristics before and after infusion were evaluated. Moreover, a telephone interview was conducted about 30 days after the infusion to evaluate the overall course. RESULTS: All patients had an early infection (mean 4±1.73 days), almost all by alpha variant (97%). No adverse events to treatment were observed. Altogether within 30 days, the hospitalization rate was 20%, 15% for COVID-19 related pathologies, versus 4% at 11 days in the BLAZE1 phase 2 study. In addition, worsening of some symptoms observed at baseline such as asthenia (77 vs. 51.3%), shortness of breath (38 vs. 23%) was registered, as well as the onset of non-restorative sleep (41%). CONCLUSION: The clinical outcome after bamlanivimab monotherapy was far below the expectation despite the patients had been infected by a theoretically sensitive viral variant.

Effect of High-Titer Convalescent Plasma on Progression to Severe Respiratory Failure or Death in Hospitalized Patients With COVID-19 Pneumonia: A Randomized Clinical Trial.

Importance: Convalescent plasma (CP) has been generally unsuccessful in preventing worsening of respiratory failure or death in hospitalized patients with COVID-19 pneumonia. Objective: To evaluate the efficacy of CP plus standard therapy (ST) vs ST alone in preventing worsening respiratory failure or death in patients with COVID-19 pneumonia. Design, Setting, and Participants: This prospective, open-label, randomized clinical trial enrolled (1:1 ratio) hospitalized patients with COVID-19 pneumonia to receive CP plus ST or ST alone between July 15 and December 8, 2020, at 27 clinical sites in Italy. Hospitalized adults with COVID-19 pneumonia and a partial pressure of oxygen-to-fraction of inspired oxygen (Pao2/Fio2) ratio between 350 and 200 mm Hg were eligible. Interventions: Patients in the experimental group received intravenous high-titer CP (≥1:160, by microneutralization test) plus ST. The volume of infused CP was 200 mL given from 1 to a maximum of 3 infusions. Patients in the control group received ST, represented by remdesivir, glucocorticoids, and low-molecular weight heparin, according to the Agenzia Italiana del Farmaco recommendations. Main Outcomes and Measures: The primary outcome was a composite of worsening respiratory failure (Pao2/Fio2 ratio <150 mm Hg) or death within 30 days from randomization. Results: Of the 487 randomized patients (241 to CP plus ST; 246 to ST alone), 312 (64.1%) were men; the median (IQR) age was 64 (54.0-74.0) years. The modified intention-to-treat population included 473 patients. The primary end point occurred in 59 of 231 patients (25.5%) treated with CP and ST and in 67 of 239 patients (28.0%) who received ST (odds ratio, 0.88; 95% CI, 0.59-1.33; P = .54). Adverse events occurred more frequently in the CP group (12 of 241 [5.0%]) compared with the control group (4 of 246 [1.6%]; P = .04). Conclusions and Relevance: In patients with moderate to severe COVID-19 pneumonia, high-titer anti-SARS-CoV-2 CP did not reduce the progression to severe respiratory failure or death within 30 days. Trial Registration: ClinicalTrials.gov Identifier: NCT04716556.

A case of severe cefepime-related neutropenia in a 15-year-old patient.

We describe the case of a 15-y-old boy with a post-surgical osteoarticular infection, who developed a severe neutropenia after 24 days of treatment with cefepime. Our report suggests that, although rare, severe neutropenia should be considered by clinicians when prescribing cefepime, especially if long-term therapy is expected.

Intra-Articular Administration of Autologous Micro-Fragmented Adipose Tissue in Dogs with Spontaneous Osteoarthritis: Safety, Feasibility, and Clinical Outcomes.

Similar to the disease affecting humans, osteoarthritis (OA) is a painful musculoskeletal condition affecting 20% of the adult canine population. Several solutions have been proposed, but the results achieved to date are far from being satisfactory. New approaches, such as intra-articular delivery of cells (including mesenchymal stromal cells), have been proposed. Among the many sources, the adipose tissue is considered very promising. We evaluated the safety, feasibility, and efficacy of a single intra-articular injection of autologous and micro-fragmented adipose tissue (MFAT) in 130 dogs with spontaneous OA. MFAT was obtained using a minimally invasive technique in a closed system and injected in the intra- and/or peri-articular space. Clinical outcomes were determined using orthopedic examination and owners' scores for up to 6 months. In 78% of the dogs, improvement in the orthopedic score was registered 1 month after treatment and continued gradually up to 6 months when 88% of the dogs improved, 11% did not change, and 1% worsened compared with baseline. Considering the owners' scores at 6 months, 92% of the dogs significantly improved, 6% improved only slightly, and 2% worsened compared with baseline. No local or systemic major adverse effects were recorded. The results of this study suggest that MFAT injection in dogs with OA is safe, feasible, and beneficial. The procedure is time sparing and cost-effective. Post injection cytological investigation, together with the clinical evidence, suggests a long-term pain control role of this treatment. The spontaneous OA dog model has a key role in developing successful treatments for translational medicine. Stem Cells Translational Medicine 2018;7:819-828.

[Trends in infective endocarditis in a medium-sized University Hospital in Italy: analysis of 232 cases]. / Aspetti epidemiologici e clinici delle endocarditi infettive in un Ospedale Universitario di medie dimensioni dell'Italia centrale: analisi di 232 casi.

The aim of this study was to evaluate the epidemiological and clinical characteristics of 232 cases of infective endocarditis (IE), admitted to the Clinica delle Malattie Infettive of Perugia Italy from 1973 to 2012. The analysis was retrospective until 2004. After this year, all the consecutive IE cases were included by utilizing the same prospective observational protocol of the Italian Study on Endocarditis (SEI). Out of 232 EI cases, 200 (86.2 %) were definite. Over the 40-year period, a statistically significant increase was observed in the patients' age, the rate of IE admissions and prosthetic device IEs. The rate of healthcare-associated IEs also increased in the last 10 years (p=NS). Diabetes mellitus was the most frequent comorbidity. There were no variations in the rate of S. aureus and streptococcal IEs. Central nervous system complications and surgery were reported in 19.4 percent and 29.3 percent of the cases, respectively. The in-hospital mortality was 18.9 percent. In conclusion, the epidemiological and clinical trends of this study are in agreement with the literature. The difference in S. aureus endocarditis, neurological complications and surgery rates may be due to the fact that this was a single centre and, for its first part, a retrospective study. A shared, multidisciplinary protocol may be useful to improve the outcome of patients with IE and its epidemiology.

Is estimated cardiovascular risk higher in HIV-infected patients than in the general population?

Cardiovascular disease (CVD) is an increasing concern for human immunodeficiency virus (HIV)-infected patients, and risk assessment is recommended in routine HIV care. The absolute cardiovascular risk in an individual is determined by several factors, and various algorithms may be applied. To date, few comparisons of HIV patients with persons of the same age from the general population have been conducted. We hypothesized that the calculated risk of CVD may be increased in HIV patients. The probability for acute coronary events within 10 y (Framingham Risk Score) and the probability for fatal cardiovascular disease (SCORE algorithm) were assessed in 403 consecutive HIV-positive subjects free from overt cardiovascular disease, as well as in 96 age- and gender-matched control subjects drawn from the general population living in the same geographical area. The average 10-y risk for acute coronary events (Framingham Risk Score) was 7.0%+/-5% in HIV subjects and 6.3%+/-5% in the control group (p =0.32). The 10-y estimated risk for cardiovascular mortality (SCORE algorithm) was 1.23%+/-2.3% and 0.83%+/-0.9%, respectively (p =0.01). The main contributor to the increased CVD risk was the high proportion of smokers, but not an increase in cholesterol level. In conclusion, a limited increase in estimated risk of CVD was found in HIV-infected patients compared to the general population. In HIV-infected individuals other factors of less value in the general population and not included in any cardiovascular algorithm might be important. In our patients intervention to modify traditional risk factors should be addressed primarily towards modifying smoking habits.