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Objective: The aim of the present study was to quantify the amount of biologic debris present within disposable bipolar vessel sealing devices after each use for canine splenectomies and determine the aerobic bacterial load of the debris following instrument resterilization with ethylene oxide., Study Design: Prospective observational clinical study., Study Population: Client-owned dogs (n = 40) presenting to a single specialty hospital for open, routine, or emergency splenectomies., Methods: A total of 16 bipolar vessel sealing devices were randomly assigned to undergo one, two, three, or four splenectomies, manual hand cleanings, and ethylene oxide sterilizations before being dismantled. After final use and sterilization, each handset was agitated in phosphate-buffered saline before disassembly, which was submitted for aerobic culture. Following aseptic disassembly, all biological residue was photo-documented, collected, quantified using a subjective scoring system, and submitted for culture., Results: Biologic debris was present within the inner mechanics of all devices, specifically under the blade used for vessel transection. A linear increase in debris was not appreciated amongst devices used once versus devices used multiple times. None of the devices nor any of the biologic debris cultured positive following sterilization with ethylene oxide., Conclusion: The presence of biologic debris was documented after the initial use of disposable bipolar vessel sealing devices, but no devices or debris yielded positive culture results following ethylene oxide sterilization after splenectomies., Clinical Significance: Increased risk of iatrogenic surgical site contamination from reused vessel sealing devices is unlikely when they have been cleaned and sterilized with ethylene oxide after up to four splenectomy surgeries., (© 2024 American College of Veterinary Surgeons.)

Objective: To evaluate the effect of training with a high-fidelity surgical simulator on outcomes of live animals and students participating in a feline ovariohysterectomy teaching laboratory., Study Design: Nonrandomized controlled trial., Sample Population: Cats (n = 186) and students (n = 146)., Methods: Live animals were paired with student surgeons. Outcomes for animals and students were evaluated over two consecutive years before (year 1: NO SIM) and after (year 2: SIM) the introduction of a graded student teaching laboratory conducted on a high fidelity surgical simulator. Live animal surgical times and postoperative pain scores using the Glasgow Composite Measure Pain Scale - Feline acute pain scale as well as self-declared student confidence were assessed and the scores of the two groups were compared., Results: The duration of the live animal surgical procedure was on average 6 min shorter in the SIM group (p = .04). A pain score triggering intervention (> = 5/20) occurred less frequently in the SIM group (n = 1/82) than in the NO-SIM (n = 16/104) group (p < .01). Similarly, rescue analgesia was administered less frequently (4/82 vs 16/104, p = .03) in the SIM group. Student confidence prior to the live animal procedure was higher (median = 7/10 [IQR = 6-8]) in the SIM group than in the NO-SIM group (median = 6/10 [IQR = 4-7]) (p < .01)., Conclusion: Surgical simulator training prior to live animal procedures improves live animal outcomes and student confidence., Clinical Significance: Surgical simulator competency should be considered a prerequisite to participation in live animal teaching laboratories. This would improve both animal welfare and the student experience., (© 2023 American College of Veterinary Surgeons.)

Objective: To evaluate the effect of continuous positive airway pressure (CPAP) on respiratory function in the early postoperative period of brachycephalic dogs., Study Design: Prospective, randomized clinical trial., Animals: A total of 32 dogs., Methods: Dogs were assigned to recover with or without CPAP (control) and assessed at specific time points over 1 h. Treatment was discontinued for dogs with a CPAP tolerance score of 3 or more (from a range of 0-4). The primary outcome was pulse oximetry (SpO 2 ). Secondary outcomes were arterial O 2 pressure (PaO 2 )/FiO 2 ratio (PaO 2 /FiO 2 ), arterial CO 2 pressure (PaCO 2 ), and rectal temperature. For dogs that reached a CPAP tolerance score of 3 or more, only the data collected up to the time point before discontinuation were included in the analysis. The treatment effect (β) was analyzed using random effects models and the results were reported with 95% confidence intervals., Results: Dogs were assigned randomly to each protocol. Baseline characteristics in both groups were comparable. Arterial blood gases were obtained in seven control group dogs and nine CPAP group dogs. Treatment did not affect SpO 2 (β = -0.1, -2.1 to 2.0) but affected the PaO 2 /FiO 2 ratio (β = 58.1, 2.6 to 113.6), with no effects on PaCO 2 (β = -4.3, -10.5 to 1.9) or temperature (β = 0.4, -0.8 to 1.6)., Conclusion: In postoperative brachycephalic dogs, CPAP had no effect on SpO 2 but improved the PaO 2 /FiO 2 ratio in brachycephalic dogs postoperatively., Clinical Significance: Continuous positive airway pressure offers a valuable solution to improve gas exchange efficiency, a prevalent concern in postoperative brachycephalic dogs, with the potential to enhance overall outcomes., (© 2024 American College of Veterinary Surgeons.)

Objective: To develop and describe a minimally invasive technique for excisional biopsy of the axillary lymph nodes in dogs., Study Design: Descriptive cadaver and clinical case series., Animals: Four canine cadavers and three clinical patients., Methods: A 3D computed tomographic reconstruction of the canine axilla was used to identify an optimal avenue of approach to the lymph nodes. This approach was refined using endoscopic techniques in four cadavers (six procedures) and potential surgical hazards, landmarks, and the surgical time required for excisional biopsy of the nodes was recorded. The procedure was then performed in three clinical cases., Results: Axillary lymph node removal was achieved using an endoscopic technique with surgical times of 58 and 35 minutes in two of three clinical cases. The third case required conversion to an open approach after endoscopic identification of the node. No major complications were encountered., Conclusion: Excisional biopsy of the axillary lymph nodes can be performed successfully using a minimally invasive technique in the dog. Further investigation in clinical cases is needed to determine the risks and complications of this procedure., Clinical Significance: Minimally invasive excisional biopsy of the axillary lymph nodes in dogs can be performed and may have a role in assisting with staging and local disease control in oncologic cases., (© 2022 American College of Veterinary Surgeons.)

The timing of parturition is crucial for neonatal survival and infant health. Yet, its genetic basis remains largely unresolved. We present a maternal genome-wide meta-analysis of gestational duration (n = 195,555), identifying 22 associated loci (24 independent variants) and an enrichment in genes differentially expressed during labor. A meta-analysis of preterm delivery (18,797 cases, 260,246 controls) revealed six associated loci and large genetic similarities with gestational duration. Analysis of the parental transmitted and nontransmitted alleles (n = 136,833) shows that 15 of the gestational duration genetic variants act through the maternal genome, whereas 7 act both through the maternal and fetal genomes and 2 act only via the fetal genome. Finally, the maternal effects on gestational duration show signs of antagonistic pleiotropy with the fetal effects on birth weight: maternal alleles that increase gestational duration have negative fetal effects on birth weight. The present study provides insights into the genetic effects on the timing of parturition and the complex maternal-fetal relationship between gestational duration and birth weight., (© 2023. The Author(s).)

Background: We investigated Epstein-Barr virus (EBV) antibody kinetics in university freshmen who developed laboratory-documented primary EBV infection during prospective studies and correlated these kinetics with disease severity., Methods: EBV-naïve participants had blood collected periodically and sera tested for EBV-specific antibodies with line blot and enzyme immunoassays. The line blot assay contained EBNA-1, p18, p23, BZLF-1, p138, and p54 antigens; the enzyme immunoassay contained viral capsid antigen and EBNA-1. Severity of illness (SOI) was graded 0 (asymptomatic) to 6 (bedridden). Participants with maximum SOI scores 0-2 were compared with those whose maximum SOI scores were 3-6. Time to first antibody response was analyzed using the semi-parametric COX model., Results: A total of 201 sera from 38 college students collected before, during, and after primary EBV infection were tested. Earlier antibody responses correlated with milder symptoms. This was most pronounced for late-developing antibodies. The median time to development of p18 IgG was significantly earlier among low-SOI participants (64 days) than high-SOI patients (119 days; P = 0.0003).). Participants with mild disease developed EBNA-1 antibodies sooner than participants with more severe disease (125 days versus >270 days; P = 0.017). Participants with mild disease also showed more rapid loss of antibodies against IgG EA p138 and p54 ≥12 weeks post-infection (P = 0.012 and P = 0.026, respectively)., Conclusions: These data suggest that rapid antibody responses to EBV correlate with reduced severity of primary EBV infection., Competing Interests: Declaration of Competing Interest None of the authors has a financial conflict of interest or potential conflict of interest to declare., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 × 10-8) with GDM, mapping to/near MTNR1B (P = 4.3 × 10-54), TCF7L2 (P = 4.0 × 10-16), CDKAL1 (P = 1.6 × 10-14), CDKN2A-CDKN2B (P = 4.1 × 10-9) and HKDC1 (P = 2.9 × 10-8). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy., (© The Author(s) 2022. Published by Oxford University Press.)

Objective: To develop a scale to diagnose and assess the severity of postamputation pain (PAP) in dogs., Study Design: Single-center retrospective study., Animals: A total of 66 dogs that underwent thoracic or pelvic limb amputation and 139 dogs that underwent tibial plateau leveling osteotomy (TPLO) at a veterinary teaching hospital., Methods: An online survey regarding postoperative behavioral changes was sent to owners. Categorical, multiple-choice responses were entered into a univariable logistic regression model and tested for association with amputation using the Wald test. If p < 0.2, variables were forwarded to a multivariable logistic regression model for manual build. Model simplicity and predictive ability were optimized using the area under the receiver operating curve (AUROC) characteristic, and model calibration was assessed using the Hosmer-Lemeshow test. The selected model was converted to an integer scale (0-10), the Canine Postamputation Pain (CAMPPAIN) scale. Univariable logistic regression related each dog's calculated score to the probability of PAP., Results: Multivariable logistic regression identified four independent predictors of PAP (p < 0.05): 1) restlessness or difficulty sleeping, 2) episodes of panic or anxiety, 3) sudden vocalization, and 4) compulsive grooming of the residual limb. Score AUROC was 0.70 (95% confidence interval = 0.63-0.78) with good calibration (Hosmer-Lemeshow statistic p = 0.82). A score of 2 corresponded to a risk probability of 0.5. Taking a score ≥ 2 to indicate PAP, score specificity and sensitivity were 92.1% and 36.4%, respectively. When this score was used to diagnose PAP, prevalence was 36.4% (24/66) and 7.9% (11/139) in the amputation and TPLO groups, respectively., Conclusions and Clinical Relevance: Postamputation pain is characterized by specific postoperative behaviors and appears to affect approximately one-third of canine amputees. The CAMPPAIN scale generated from these data could facilitate diagnosis, treatment and further study of PAP but requires external validation., (Copyright © 2021 Association of Veterinary Anaesthetists and American College of Veterinary Anesthesia and Analgesia. Published by Elsevier Ltd. All rights reserved.)

Objective: To develop a population-derived, parsimonious, and objective risk stratification model for dogs following trauma and compare its predictive performance to the animal trauma triage (ATT) score., Design: Observational cohort study using data from the American College of Veterinary Emergency and Critical Care Veterinary Committee on Trauma (VetCOT) trauma registry acquired between September 2013 and October 2017., Setting: Nine Level I and Level II veterinary trauma centers., Animals: Nine hundred eighty-four dogs assessed within 24 h of traumatic injury., Interventions: None., Measurements and Main Results: Patient mortality was 10.8%. The VetCOT model was constructed based on 4 variables: plasma lactate and ionized calcium obtained within 6 h of admission, and presence or absence of clinical signs consistent with either head or spinal trauma. The VetCOT score had good discriminatory performance (AUROC = 0.87, 95% CI = 0.83-0.91) comparable to that of the 6 variable ATT score for the same population (area under the receiver operator characteristic [AUROC] = 0.87; 95% CI, 0.84-0.90). No statistical difference in discriminatory performance between the 2 scores was identified (P = 0.98). The VetCOT score showed good calibration on this population (Hosmer-Lemeshow test P = 0.93), whereas the ATT score failed to calibrate (P = 0.02) due to overprediction of mortality at low scores. Sensitivity and specificity for outcome of the VetCOT score at a risk probability cutoff of 0.5 for this population were 28.97% and 97.95%, respectively., Conclusions: The VetCOT score is a more parsimonious model with comparable discriminatory performance and superior calibration to the ATT score for risk stratification in dogs following trauma. Further prospective validation studies are required to confirm the discriminatory performance of the VetCOT score., (© Veterinary Emergency and Critical Care Society 2021.)

Objective: To describe the causes of intraoperative delays and the changes in delays and surgical workflow with the level of training of the primary surgeon., Study Design: Prospective observational study., Sample Population: Seventy-three small animal surgical procedures performed at an academic teaching institution between January 17, 2018 and April 10, 2018., Methods: Procedures (trainee = 37, faculty = 36) totaling 103.2 h were observed and video recorded. Operative time was allocated to the surgical approach, exploration, exposure, intervention, and closure phases. Suballocations were made to specific tasks within these categories (such as cutting or hemostasis). Intraoperative delays and reasons were recorded. Differences in use of time between trainee and faculty surgeons were analyzed., Results: Delays constituted 9.2% (±4.4) of the operative time, of which 6.5%(±3.6) were surgeon controlled and 2.6% (±2.7) were non-surgeon controlled. Surgeons preparing instrumentation outside of the operative field and retrieval of equipment from supply areas were the greatest contributors to delays. Intraoperative delays did not increase when the trainee was placed in the primary surgeon role (P = .78). During the approach faculty surgeons spent proportionally less time on hemostasis (P = .02), and during closure they spent less time suturing (P = .03) than trainees., Conclusion: Trainee surgeons did not have greater intraoperative delays. Delays were created when surgeons prepared their own instrumentation. Workflow differed between experts and trainees., Clinical Significance: Advancing a trainee surgeon into the primary role is unlikely to increase intraoperative delays, which can be reduced by the inclusion of trained scrub technicians. A focus on efficient hemostasis and fluidity when suturing may improve operative efficiency for surgical trainees., (© 2021 American College of Veterinary Surgeons.)

Objective: To determine whether catheterization of the common bile duct (CBD) is associated with outcome in dogs undergoing cholecystectomy for gallbladder mucocele and to determine whether this association is modified by the catheterization method., Study Design: Multi-institutional retrospective cohort study., Animals: Dogs (n = 252) that underwent cholecystectomy for gallbladder mucocele., Methods: Dogs were identified via electronic medical record review at four veterinary teaching hospitals. Baseline dog characteristics, surgical findings, and methods including normograde vs retrograde CBD catheterization, intraoperative outcomes, and postoperative outcomes and complications were recorded. Variables were compared between dogs with and without catheterization., Results: Catheterized dogs had higher American Society of Anesthesiologists scores (P = .04), higher total bilirubin (P = .01), and were more likely to have dilated CBD at the time of surgery (P < .01). Incidence of major and minor intraoperative complications was similar between the two groups. Surgical time was longer for the catheterized group (P = .01). The overall incidence of postoperative complications was similar between the groups; however, postoperative pancreatitis was associated with performing CBD catheterization (P = .01). This association was retained as an independent association in a multivariable model that addressed baseline group differences (P = .04). Likelihood of developing postoperative pancreatitis was not different between normograde and retrograde catheterization (P = .57)., Conclusion: Catheterization of the CBD was associated with development of postoperative pancreatitis. This was not influenced by the method of catheterization., Clinical Significance: The requirement for catheterization of the CBD during open cholecystectomy in dogs should be carefully considered, particularly in dogs without evidence of biliary obstruction because the procedure may induce postoperative pancreatitis., (© 2020 American College of Veterinary Surgeons.)

Evaluation of immune responses to adeno-associated virus (AAV)-mediated gene therapies prior to and following dose administration plays a key role in determining therapeutic safety and efficacy. This report describes up to 3 years of immunogenicity data following administration of valoctocogene roxaparvovec (BMN 270), an AAV5-mediated gene therapy encoding human B domain-deleted FVIII (hFVIII-SQ) in a phase 1/2 clinical study of adult males with severe hemophilia A. Patients with pre-existing humoral immunity to AAV5 or with a history of FVIII inhibitors were excluded from the trial. Blood plasma and peripheral blood mononuclear cell (PBMC) samples were collected at regular intervals following dose administration for assessment of humoral and cellular immune responses to both the AAV5 vector and transgene-expressed hFVIII-SQ. The predominant immune response elicited by BMN 270 administration was largely limited to the development of antibodies against the AAV5 capsid that were cross-reactive with other common AAV serotypes. No FVIII inhibitor responses were observed within 3 years following dose administration. In a context of prophylactic or on-demand corticosteroid immunosuppression given after vector infusion, AAV5 and hFVIII-SQ peptide-specific cellular immune responses were intermittently detected by an interferon (IFN)-γ and tumor necrosis factor (TNF)-α FluoroSpot assay, but they were not clearly associated with detrimental safety events or changes in efficacy measures., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: To compare the effect of sentinel lymph node (SLN) histology vs locoregional lymph node (LRLN) fine needle aspiration (FNA) cytology on assigned disease stage and adjunctive treatment recommendations and describe the incidence of anatomic disparity between the LRLN and SLN., Study Design: A pre-post study refers to a study design type in which subjects are compared pre and post the intervention of interest., Animals: Seventeen dogs undergoing primary excision of 20 cutaneous and subcutaneous mast cell tumors (MCT)., Methods: Client-owned dogs presenting to the Cornell University Hospital for Animals for surgical removal of a cytologically confirmed cutaneous or subcutaneous MCT >1 cm in diameter were enrolled. Cytological examination of FNA from the LRLN was compared with histology of the SLN. The SLN was identified by indirect computed tomographic lymphangiography (ICTL) after peritumoral injection of iopamidol and scanning at 1, 3, 5, 10, and 15 minutes. Histopathologic node score > 1 was considered metastatic. After case review by an oncologist, LRLN FNA cytology was compared with SLN histology for effect on changes in stage assignment and adjunctive treatment recommendations., Results: Mast cell tumors were graded as 2 low (n = 11), 2 high (n = 2), and subcutaneous (n = 7). Optimal scan timing was 10 minutes after injection of iopamidol. Sentinel lymph node differed anatomically from LRLN in 5 of 18 scans. Metastases were detected by histology in 9 of 20 SLN compared with in 1 of 20 FNA of LRLN (P = .001), changing stage and adjunctive treatment recommendations 8 of 20 tumors. Only 6 of 19 LRLN FNA samples were diagnostic., Conclusion: Sentinel lymph nodes were consistently identified with ICTL and differed from LRLN in one-quarter of tumors. Histopathological examination of SLN altered recommendations in half of the dogs compared with the previous standard of care., Clinical Significance: Indirect computed tomographic lymphangiography and SLN excision should be considered as a new standard for dogs with MCT., (© 2020 American College of Veterinary Surgeons.)

Strategies to mitigate watershed nitrogen export are critical in managing water resources. Green infrastructure (GI) has shown the ability to remove nitrogen from stormwater, but the removal mechanism is unclear. Denitrification removes nitrate from water permanently, making it the most desirable removal mechanism. The year-round field performance of a roadside infiltration GI practice (bioretention) in Northern Virginia was monitored to investigate the transport of nitrogen and the occurrence and contribution of denitrification. Stormwater runoff volumes, nitrogen concentrations, and nitrate isotope ratios (δ 15 N-NO 3 - and δ 18 O-NO 3 - ) were measured at the inlet and outlet of the bioretention during 24 storm events over 14 months. Nitrate concentration reductions (inlet vs. outlet) displayed seasonal trends, with higher reductions happening during warmer events and lower reductions or increases occurring during colder events. Cumulative bioretention nitrate and total dissolved nitrogen load reductions were 73% and 70%, respectively. Two out of 24 monitored events displayed denitrification isotope trends, indicating that although bioretention has denitrification potential, it is infrequent and other nitrogen removal mechanisms (i.e. infiltration and plant uptake) are primarily responsible for nitrogen surface effluent reductions. Only approximately 1.4% of the total reduced nitrate surface effluent load over the monitoring period was attributable to denitrification. Denitrification occurred during two of the largest monitored events, suggesting increased hydraulic retention time (HRT) promotes denitrification. Future GI designs should consider increasing HRT to encourage the important ecosystem service denitrification provides., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Obesity is common in the equine population and it has been associated with increased surgical morbidity and mortality in humans. The effect of increased body mass index (BMI) on the incidence of surgical site infections has not been investigated in horses., Objectives: To determine whether horses with increased body fat, as estimated by BMI, are more likely to develop post-operative complications, particularly incisional complications, following emergency ventral midline celiotomy., Study Design: Retrospective, multi-institutional clinical study., Methods: Medical records of horses >2 years old presenting with colic that underwent ventral midline celiotomy between January 2010 and September 2018 with follow-up of a minimum of 30 post-operative days were reviewed. Extracted data included signalment, operative details and outcome. BMI was calculated by dividing the patient's weight (kg) by the withers height squared (m 2 )., Results: In all, 287 horses fit inclusion criteria. Incisional complication prevalence was 23.7%. Horses with incisional complications had a higher BMI (median 203.6 kg/m 2 , IQR = 191.5-217.4) compared with those without (median 199.1 kg/m 2 , IQR = 184.7-210.2) (P = .03). Multi-variable analysis of the effects of age, sex, breed and presence of metabolic disease on the association between BMI and risk of incisional complications, identified a tendency towards increased risk with a higher BMI, but statistical significance decreased to P = .07. Breed had an association with BMI (P < .01), but not with incisional complication risk., Main Limitations: BMI as an estimate of body fat has limitations. Retrospective studies with reliance on owners reporting data and complete medical records is imperfect. When the data were subjected to multi-variable analysis, the trend towards an increased incidence of incisional complications in horses with higher BMI persisted but it was not statistically significant., Conclusion: Higher BMI may increase the risk for the development of incisional complications in horses following emergency ventral midline celiotomy., (© 2020 EVJ Ltd.)

Objective: To investigate associations among care errors, staffing, and workload in small animal ICUs., Design: Multicenter observational cohort study conducted between January 2017 and September 2018., Setting: Three small animal teaching hospital ICUs., Animals: None., Interventions: None., Measurements and Main Results: Data on patient numbers, illness severity (assesed via the acute patient physiologic and laboratory evaluation [APPLE] score), care burden, staffing levels, technician experience/education level, and care errors were collected at each study site. Care errors were categorized as major (unanticipated arrest or death; patient endangerment through IV line, arterial catheter, chest tube or other invasive device mismanagement, or errors in drug calculation/administration) or minor. Median patient:technician ratio was 4.3 (range: 1-18). Median patient illness severity was 15.1 (4.7-27.1) APPLE score units. A total of 221 major and 3,317 minor errors were observed over the study period. The odds of a major error increased by an average of 11% (odds ratio [OR] = 1.11; 95% confidence interval [CI], 1.02-1.20; P = 0.012) for each 1 patient increase in the patient:technician ratio after averaging by ICU location. The major error incident rate ratio was 2.53 (95% CI, 1.84-3.54; P < 0.001) for patient:technician ratios of >4.0 compared with ≤4.0. The odds of a major error increased by 0.5% per total unit APPLE score increase (OR = 1.005; 95% CI, 1.002-1.007; P < 0.001). The major error incident rate ratio was 1.71 (95% CI, 1.30-2.25; P < 0.001) for APPLE fast :technician ratios of >73 compared with ≤73. The odds of a major error decreased by 2% (OR = 0.98; 95% CI, 0.97-0.99; P = 0.01) for each year increase in total technician years of ICU work experience., Conclusions: Substantial reductions in major care errors may be achieved by maintaining ICU patient:technician ratios at ≤4. Technician experience and total unit burden of patient illness severity are also associated with error incidence, and should be taken into consideration when scheduling staff., (© Veterinary Emergency and Critical Care Society 2020.)

Winter deicing salt application has led to water quality impairment as stormwater carries salt ions (Na + and Cl - ) through watersheds. Green infrastructure (GI) is a promising urban stormwater management practice, but its efficacy in managing salt is unknown. GI is not yet designed to remove salt, but may have potential to mitigate its loading to surface waters. Two roadside infiltration-based GI practices in Northern Virginia (bioretention and bioswale) were monitored year-round over 28 precipitation events to investigate the transport of salt through modern stormwater infrastructure. Stormwater runoff volumes and concentrations of salt ions entering and exiting each GI were monitored to determine reductions of salt ions. Both the bioretention and bioswale significantly reduced effluent surface loads of Cl - and Na + (76% to 82%), displaying ability to temporarily retain and infiltrate salts and delay their release to surface waters. Changes in bioretention soil chemistry revealed a small percentage of Na + was stored long-term by ion exchange, but no long-term Cl - storage was observed. Limited soil storage along with groundwater observations suggest the majority of salt removed from stormwater by the bioretention infiltrates into groundwater. Infiltration GI can buffer surface waters from salt, but are also an avenue for groundwater salt loading., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: To determine whether conservative lateral surgical margins (equal to tumor diameter for tumors < 2 cm in diameter or 2 cm for larger tumors) were noninferior to wide (3-cm) lateral surgical margins for achieving tumor-free histologic margins following excision of grade I and II cutaneous mast cell tumors (MCTs) in dogs., Animals: 83 grade I and II MCTs excised with a deep surgical fascial margin and requisite lateral surgical margins from 68 dogs from 2007 to 2017. Tumors representing scar revision or local recurrence were excluded., Procedures: A pathology department database was searched to identify qualifying MCTs, and medical records were cross-referenced to obtain data regarding patients and tumors. Outcome (complete vs incomplete excision as histologically determined) was compared between conservative- and wide-margin groups. A noninferiority margin of ≥ 0.9 was used for the risk ratio (probability of complete excision for the conservative- vs wide-margin group), implying that noninferiority would be established if the data indicated that the true risk of complete excision with the conservative-margin approach was at worst 90% of that for the wide-margin approach., Results: The proportion of excised MCTs with tumor-free histologic margins was similar between the conservative- (43/46 [93%]) and wide- (34/37 [92%]) margin groups. There were no differences in tumor diameter or location between treatment groups. The risk ratio (1.02; 95% confidence interval, 0.89 to 1.19) met the criterion for noninferiority., Conclusions and Clinical Relevance: The conservative-margin approach appeared to be noninferior to the wide-margin approach for achieving tumor-free histologic margins in the dogs of this study, and its use could potentially reduce the risk of postoperative complications. ( J Am Vet Med Assoc 2020;256:567-572.

No licensed vaccine is available for prevention of EBV-associated diseases, and robust, high-throughput bioanalytical assays are needed to evaluate immunogenicity of gp350 subunit-based candidate EBV vaccines. Here we have developed an improved EBV-GFP based neutralization assay for such a vaccine's pre-clinical and clinical validation to measure EBV specific neutralizing antibodies in human donors. The supplementation of guinea pig complement of our previously published high-throughput EBV-GFP fluorescent focus (FFA)-based neutralization assay allowed the detection of complement-dependent neutralizing antibodies using a panel of heat-inactivated healthy human sera. Anti-gp350 antibody titers, which were evaluated using a previously optimized anti-gp350 IgG ELISA assay, were moderately correlated to the FFA-based neutralization titers. Overall, this improved high-throughput neutralization assay is capable of characterizing the serologic neutralizing antibody response to natural EBV infection, with applications in evaluating EBV antibody status in epidemiologic studies and immunogenicity of candidate gp350-subunit EBV vaccines in clinical studies., Competing Interests: Competing interests: HL, LG, RL, FZ, JCW, and GMH were employees and shareholders of AstraZeneca when the study was conducted; HHB had no competing interests.

Objective: To compare the effect of three methods of subcutaneous tissue closure on postoperative incisional complications and pain in cats., Study Design: Single-center, randomized, blinded, controlled trial conducted in a veterinary teaching hospital., Animals: Two hundred ninety-seven cats undergoing midline celiotomy for ovariohysterectomy (n = 280) or other abdominal procedure (n = 17)., Methods: Cats (n = 297) were assigned to one of three subcutaneous closure methods: simple continuous apposition with tacking to the rectus fascia (n = 108, quilting [Q] group); simple continuous apposition (SC; n = 94); no subcutaneous closure (NC; n = 95). Primary outcomes were incidence of seroma formation, postoperative pain, and surgical site infection or dehiscence. Active follow-up was obtained at 10 and 30 days postoperatively., Results: Baseline characteristics did not differ between groups. Seroma was less common in the Q group (13.0%) than in the NC (27.3%) and SC (25.9%) groups (P = .03). Compared with the other two groups, the relative risk of seroma formation in the Q group was 0.49 (95% CI = 0.28-0.86, P = .01). Median mechanical pain thresholds were higher (indicating greater comfort) in cats with subcutaneous sutures (Q and SC = 1.23 [interquartile range (IQR), 0.2-2.6 N], NC = 0.83 [IQR, 0-1.87 N], P = .04) on the day after surgery., Conclusion: Closing subcutaneous tissues with a quilting closure pattern reduced seroma formation in cats undergoing celiotomy., Clinical Significance: Placing a quilting suture pattern in the subcutaneous tissues after celiotomy is a simple low-cost measure that reduces seromas in cats. Abstaining from subcutaneous closure cannot be recommended because of increased seroma formation and pain., (© 2019 The American College of Veterinary Surgeons.)

Objective: To determine perioperative inadvertent hypothermia (PIH) incidence, risk factors, prevention methods, and effect of PIH prevention on anesthesia recovery times., Study Design: Nonrandomized controlled before-and-after trial., Animals: Dogs (n = 277) and cats (n = 20) undergoing open surgery., Methods: Incidence and risk factors for PIH (core temperature <96.8°F), existing thermal care practices, and recovery times were documented at baseline. For group 1, a thermal care bundle consisting of protocol-driven active warming combined with raised environmental temperatures (75°F) in induction rooms (IR) and operating rooms (OR) was implemented. Perioperative inadvertent hypothermia incidence and recovery times were recorded. For group 2, baseline active warming practices were resumed while environmental temperatures remained elevated., Results: Perioperative inadvertent hypothermia was associated with preoperative imaging (P = .039) and percentage clip area (P = .037). Perioperative inadvertent hypothermia decreased in group 1 (13.5%, n = 96, P < .001) and group 2 (13.0%, n = 100, P < .001) compared with baseline (35.6%, n = 101). Median time from anesthesia withdrawal to extubation decreased in group 1 (5 minutes, P = .028) and group 2 (5 minutes, P = .018) compared with baseline (7 minutes). Median time from anesthesia recovery to spontaneous food intake decreased in group 1 (6 hours, n = 92, P = .016) but not in group 2 (6.0 hours, n = 88, P = .060) compared with baseline (n = 94, 6.7 hours). No group differences in PIH risk factors were identified., Conclusion: Perioperative inadvertent hypothermia incidence was high but reducible by raising environmental temperatures alone or in combination with increased focus on active warming. Reductions in PIH shortened recovery times., Clinical Significance: Maintaining IR and OR temperatures at the standard-of-care for human pediatric surgery reduces PIH and may improve outcomes., (© 2019 The American College of Veterinary Surgeons.)

Objectives: To investigate veterinary technician burnout and associations with frequency of self-reported medical error, resilience, and depression and job-related risk factors., Design: Cross-sectional observational study using an anonymous survey conducted between November 2017 and June 2018., Setting: Four referral teaching hospitals in the United States and Canada., Subjects: A total of 344 veterinary technicians were invited to participate. Response rate was 95%. Overall 256 surveys were ultimately analyzed., Interventions: Burnout, depression, and resilience were measured using validated instruments. Respondents reported perceptions of workload, working environment, and medical error frequency. Associations between burnout and factors related to physical work environment, workload and schedule, compensation package, interpersonal relationships, intellectual enrichment, and exposure to ethical conflicts were analyzed., Measurements and Main Results: Burnout, characterized by high emotional exhaustion, depersonalization, and low sense of personal accomplishment was common, and was positively associated with perceived medical errors, desire to change career, and depression. Burnout levels on all 3 burnout subscales were higher in this population than previously reported for a contemporaneous group of trauma nurses working with human patients (P < 0.05). Burnout was negatively associated with resilience. Respondents' feelings of fear or anxiety around supervisor communications, perception that patient load was too high to allow for excellent patient care, and perceived lack of available assistance during sudden workload increases were all associated with burnout., Conclusions: Burnout in veterinary technicians is common and is associated with numerous undesirable outcomes. Work-related interventions to reduce burnout should focus on improving supervisor relationships and maintaining an appropriate patient:caregiver ratio., (© 2019 The Authors. Journal of Veterinary Emergency and Critical Care published by Wiley Periodicals, Inc. on behalf of Veterinary Emergency and Critical Care Society.)

Objective: To develop and validate a preoperative brachycephalic risk (BRisk) score that objectively and accurately predicts the risk of major complications or death in dogs undergoing corrective surgery for brachycephalic obstructive airway syndrome (BOAS)., Study Design: Retrospective multicenter cohort study., Sample Population: Score development n = 233 dogs, validation n = 50 dogs., Methods: Data were collected on signalment, medical history, reason for presentation, physical examination, and preoperative diagnostic findings. The primary outcome measures included risk of major complications (requirement for postoperative oxygen support for >48 hours or postoperative temporary/permanent tracheostomy) or death within the hospitalization period. The score was developed by using data from two centers and was validated in a third center. The 10-point BRisk score was modeled on breed, history of previous surgery, concurrent procedures, body condition score, airway status, and admission rectal temperature., Results: The score was associated with negative outcome (P < .0001) and discriminated well in both the construction (area under the receiver operator characteristic [AUROC] = 0.83) and validation groups (AUROC = 0.84). Dogs with scores >3 were 9.1 times more likely to have a negative outcome (95% CI = 3.9-21.2) compared with dogs with scores ≤3., Conclusion: The BRisk score developed from admission data in this study accurately rated the risk of negative outcome of dogs undergoing corrective surgery for BOAS., Clinical Significance: Preoperative determination of the BRisk score may assist triage, management of owner expectations, decision making regarding intervention selection, and characterization of populations in clinical research., (© 2019 The American College of Veterinary Surgeons.)

Objectives: To examine the Animal Trauma Triage (ATT) and modified Glasgow Coma Scale (mGCS) scores as predictors of mortality in injured cats., Design: Observational cohort study conducted September 2013 to March 2015., Setting: Nine Level I and II veterinary trauma centers., Animals: Consecutive sample of 711 cats reported on the Veterinary Committee on Trauma (VetCOT) case registry., Interventions: None., Measurements and Main Results: We compared the predictive power (area under receiver operating characteristic curve; AUROC) and calibration of the ATT and mGCS scores to their components. Overall mortality risk was 16.5% (95% confidence interval [CI], 13.9-19.4). Head trauma prevalence was 11.8% (n = 84). The ATT score showed a linear relationship with mortality risk. Discriminatory performance of the ATT score was excellent (AUROC = 0.87 [95% CI, 0.84-0.90]). Each ATT score increase of 1 point was associated with an increase in mortality odds of 1.78 (95% CI, 1.61-1.97, P < 0.001). The eye/muscle/integument category of the ATT showed the lowest discrimination (AUROC = 0.60). When this component, skeletal, and cardiac components were omitted from score calculation, there was no loss in discriminatory capacity compared with the full score (AUROC = 0.86 vs 0.87, respectively, P = 0.66). The mGCS showed fair performance overall for prediction of mortality, but the point estimate of performance improved when restricted to head trauma patients (AUROC = 0.75, 95% CI, 0.70-0.80 vs AUROC = 0.80, 95% CI, 0.70-0.90). The motor component of the mGCS showed the best predictive performance (AUROC = 0.71); however, the full score performed better than the motor component alone (P = 0.004). When assessment was restricted to patients with head injury (n = 84), there was no difference in performance between the ATT and mGCS scores (AUROC = 0.82 vs 0.80, P = 0.67)., Conclusion: On a large, multicenter dataset of feline trauma patients, the ATT score showed excellent discrimination and calibration for predicting mortality; however, an abbreviated score calculated from the perfusion, respiratory, and neurologic categories showed equivalent performance., (© Veterinary Emergency and Critical Care Society 2019.)

OBJECTIVE To describe outcomes for dogs after treatment of craniodorsal hip luxation with closed reduction and Ehmer sling placement and investigate potential risk factors for sling-associated tissue injury or reluxation of the affected hip at or near the time of sling removal. DESIGN Retrospective multicenter cohort study. ANIMALS 92 dogs. PROCEDURES Case information was solicited from 10 veterinary medical facilities through electronic communications. Data on patient demographic information, cause of injury, presence of concurrent injuries, details of Ehmer sling placement and management, and outcome at sling removal were collected. Data were analyzed for associations with outcomes. RESULTS 40 of 92 (43.5%) dogs had reluxation of the affected hip joint at or near the time of sling removal. Odds of reluxation occurring for dogs that had the initial injury attributed to trauma were 5 times those for dogs without known trauma (OR, 5.0; 95% confidence interval, 1.3 to 18.7). Forty-six (50%) dogs had soft tissue injuries secondary to sling use; 17 of these dogs had injuries classified as severe, including 1 dog that required limb amputation. Odds of severe sling injury for dogs that had poor owner compliance with home care instructions noted in the record, those that had the sling placed by an intern rather than a board-certified surgeon or resident, and those that were noted to have a soiled or wet bandage on ≥ 1 occasion were 12.5, 4.0, and 5.7 times those for dogs without these findings, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Placement of an Ehmer sling following closed reduction of a craniodorsal hip luxation had a low success rate and high complication rate.

Objective: To calculate a risk prediction model for hemangiosarcoma (HSA) diagnosis in dogs presenting with nontraumatic hemoabdomen., Design: Retrospective multicenter observational cohort study enrolling dogs presented 2003-2016., Setting: Five academic veterinary medical centers., Animals: A total of 406 dogs with nontraumatic hemoabdomen as the presenting complaint that underwent surgical exploration or necropsy and received a histological diagnosis. Overall, 219 dogs from 3 centers provided the data for model construction, and 187 dogs from 2 centers provided the population for external validation., Interventions: None., Measurements and Main Results: The risk score was modeled on 4 predictors: bodyweight (P = 0.01), total plasma protein (P < 0.01), platelet count (P < 0.01), and thoracic radiograph findings (P = 0.02). The incidence of HSA diagnosis was 36%, 76%, and 96% in the low risk (≤40), medium risk (41-55), and high risk (>55) score groups, respectively. The risk score AUROC was 0.85 (95% CI 0.79-0.90) on the construction population, and 0.77 (95% CI 0.70-0.84) on the validation population., Conclusions: The risk of HSA diagnosis in dogs presenting with nontraumatic hemoabdomen could be predicted using a simple risk score, which could aid in identification and treatment of dogs at lower risk for this diagnosis., (© Veterinary Emergency and Critical Care Society 2019.)

Adeno-associated virus (AAV)-based vectors are widely used for gene therapy, but the effect of pre-existing antibodies resulting from exposure to wild-type AAV is unclear. In addition, other poorly defined plasma factors could inhibit AAV vector transduction where antibodies are not detected. To better define the relationship between various forms of pre-existing AAV immunity and gene transfer, we studied valoctocogene roxaparvovec (BMN 270) in cynomolgus monkeys with varying pre-dose levels of neutralizing anti-AAV antibodies and non-antibody transduction inhibitors. BMN 270 is an AAV5-based vector for treating hemophilia A that encodes human B domain-deleted factor VIII (FVIII-SQ). After infusion of BMN 270 (6.0 × 10 13 vg/kg) into animals with pre-existing anti-AAV5 antibodies, there was a mean decrease in maximal FVIII-SQ plasma concentration (C max ) and AUC of 74.8% and 66.9%, respectively, compared with non-immune control animals, and vector genomes in the liver were reduced. In contrast, animals with only non-antibody transduction inhibitors showed FVIII-SQ plasma concentrations and liver vector copies comparable with those of controls. These results demonstrate that animals without AAV5 antibodies are likely responders to AAV5 gene therapy, regardless of other inhibiting plasma factors. The biological threshold for tolerable AAV5 antibody levels varied between individual animals and should be evaluated further in clinical studies.

Objectives: To measure two forms of attrition in a cohort of volunteer brain donors: Withdrawal during life and non-donation at death. To test whether cognitive impairment independently predicts attrition., Method: Attrition rates were calculated for all registered participants and for all brain donors who had completed a baseline and follow-up assessment of cognition, health, and lifestyle. Attrition reasons were described, and attrition rates were compared by gender, age group, and cognitive status. Multivariate logistic regression was used to identify the factors which independently predicted during life and at death., Results: A total of 3276 brain donors registered and 2307 (70.4%) remained in the cohort. Attrition rate overall was 5.9% for withdrawal and 13.8% for donation. Family disagreement and the brain bank not being informed of participant death were the most common reasons for withdrawal and donation attrition. Withdrawal was associated with having cognitive impairment (OR 2.0 95% CI 1.1-3.5), increased age (OR 3.1 95% CI 1.4-6.9), and lower education (OR 1.8 95% CI 1.2-2.8). Participants exhibiting cognitive decline between assessments were more likely to withdraw (OR 4.9 95% CI 1.7-13.6). Participants living alone were almost twice as likely to die without donating (OR 1.9 95% CI 1.1-3.3)., Conclusions: Attrition rates were relatively low, and consistent with other studies cognitive impairment, increased age, and less education predicted study withdrawal. Deaths of participants living alone were less likely to result in donation. Tailored, regular retention practices aimed at resolving family disagreement regarding donation decisions are required., (© 2018 John Wiley & Sons, Ltd.)

OBJECTIVE To identify risk factors associated with surgical site infection (SSI) in dogs following tibial plateau leveling osteotomy (TPLO). DESIGN Retrospective cohort study. ANIMALS 320 dogs that underwent unilateral or bilateral TPLO (n = 405 procedures) between 2007 and 2015 and were reexamined by a veterinarian at least once ≥ 8 weeks after the procedure. PROCEDURES Data were extracted from medical records regarding signalment, TPLO procedure details, medical history of dermatitis, and SSI status. Logistic regression was performed to identify factors associated with SSI development. RESULTS An SSI developed following 34 (8.4%; 95% confidence interval [CI], 6.1% to 11.5%) procedures. Prophylactic antimicrobial administration was provided following 36.8% (n = 149) of procedures. For 71 (17.5%) procedures, the dog had dermatitis at the time of surgery; 12 of these procedures involved dermatitis at the surgical site. The incidence of SSI following the 12 procedures for dogs with dermatitis at the surgical site was 16.7% (2/12 [95% CI, 3.3% to 54.3%]) and was 10.2% (6/59 [95% CI, 4.5% to 21.3%]) for dogs with dermatitis elsewhere; however, these differences in incidence were not significant. On multivariable analysis, German Shepherd Dogs (vs other breeds), meniscectomy (vs no meniscectomy), and attending surgeon having performed ≤ 20 (vs > 20) procedures during the study period were associated with increased odds of SSI. CONCLUSIONS AND CLINICAL RELEVANCE SSI following TPLO was associated with the German Shepherd breed, meniscectomy, and surgeon. Prospective studies are needed to investigate the mechanisms underlying these associations.

Objective: To evaluate the ability to assess laryngeal function and to diagnose unilateral laryngeal paralysis (uLP) via airway endoscopy and carbon dioxide (CO 2 ) stimulation., Study Design: Experimental study., Animals: Six healthy, adult beagles., Methods: Dogs were anesthetized with sevoflurane and dexmedetomidine. Laryngeal activity was observed via endoscopy placed through a laryngeal mask airway (LMA). The absolute and normalized glottic gap areas (AGGA and NGGA, respectively) and the glottic length (GL) were measured at inspiration and before and after surgically induced uLP. Measurements were obtained at eupnea and during hypercapnic hyperpnea produced by the administration of CO 2 . Values for each hemilarynx were also measured. Video recordings were observed by 2 surgeons who scored function as normal or uLP., Results: The AGGA and NGGA increased similarly during CO 2 administration in intact dogs and in dogs with uLP; the GL increased in dogs with uLP but not in intact dogs. The AGGA and NGGA of the intact hemilarynx increased more than those of the affected hemilarynx in dogs with uLP. uLP was correctly identified more frequently by observers at hypercapnic hyperpnea than during eupnea., Conclusion: The increase in AGGA and NGGA at peak inspiration during CO 2 administration was not limited by uLP, but asymmetry in hemilarynx AGGA and NGGA was observed in dogs with uLP. CO 2 administration facilitated the identification of uLP., Clinical Significance: Laryngeal endoscopy through an LMA coupled with administration of CO 2 in anesthetized dogs facilitates the observation of arytenoid function and may improve the diagnosis of naturally occurring mild laryngeal paralysis., (© 2018 The American College of Veterinary Surgeons.)

Objective: To examine the animal trauma triage (ATT) and modified Glasgow Coma Scale (mGCS) scores as predictors of mortality outcome (death or euthanasia) in injured dogs., Design: Observational cohort study conducted from September 2013 to March 2015 with follow-up until death or hospital discharge., Setting: Nine veterinary hospitals including private referral and veterinary teaching hospitals., Animals: Consecutive sample of 3,599 dogs with complete data entries recruited into the Veterinary Committee on Trauma patient registry., Interventions: None., Measurements and Main Results: We compared the predictive power (area under receiver operating characteristic [AUROC]) and calibration of the ATT and mGCS scores to their components. Overall mortality risk was 7.3% (n = 264). Incidence of head trauma was 9.5% (n = 341). The ATT score showed a linear relationship with mortality risk. Discriminatory performance of the ATT score was excellent with AUROC = 0.92 (95% confidence interval [CI] 0.91 to 0.94) and pseudo R 2 = 0.42. Each ATT score increase of 1 point was associated with an increase in mortality odds of 2.07 (95% CI = 1.94-2.21, P < 0.001). The "eye/muscle/integument" category of the ATT showed poor discrimination (AUROC = 0.55). When this component together with the skeletal and cardiac components were omitted from calculation of the overall score, there was no loss in discriminatory capacity (AUROC = 0.92 vs 0.91, P = 0.09) compared with the full score. The mGCS showed good performance overall, but performance improved when restricted to head trauma patients (AUROC = 0.84, 95% CI = 0.79-0.90, n = 341 vs 0.82, 95% CI = 0.79-0.85, n = 3599). The motor component of the mGCS showed the best predictive performance (AUROC = 0.79 vs 0.66/0.69); however, the full score performed better than the motor component alone (P = 0.002). When assessment was restricted to patients with head injury (n = 341), the ATT score still performed better than the mGCS (AUROC = 0.90 vs 0.84, P = 0.04)., Conclusions: In external validation on a large, multicenter dataset, the ATT score showed excellent discrimination and calibration; however, a more parsimonious score calculated on only the perfusion, respiratory, and neurological categories showed equivalent performance., (© Veterinary Emergency and Critical Care Society 2018.)

Objective: To evaluate long-term loading patterns using subchondral bone density (SBD) distribution of the tibial plateau after tibial plateau leveling osteotomy (TPLO) and tibial tuberosity advancement (TTA)., Study Design: Cross-sectional study., Animals: Adult (> 2 years), medium to large breed dogs (>20 kg) that had been treated with TPLO or TTA at least 1 year prior to the study were recruited. A normal cohort of similar age and weight dogs with normal physical and orthopedic examinations served as control., Methods: Dogs were sedated for computed tomography (CT) of the stifle, and DICOM (digital imaging and communications in medicine) files were processed for CT osteoabsorptiometry (CTOAM). Tibial plateaus were sampled at 6 zones, and CTOAM was used to determine regional and maximal areas of SBD as a marker of joint loading., Results: Data were collected on 48 stifles in 31 dogs (15 TPLO, 11 TTA, 22 control). Lower Hounsfield unit (HU) values were measured in the caudal and mid-region of the lateral tibial plateau after TPLO and compared to normal. HU values did not differ between joints treated with TTA and those in the control group., Conclusion: TPLO may alter stifle load distribution relative to the normal control group. There were no differences between TTA and the control group., Clinical Significance/impact: Despite ongoing osteoarthritis (OA) in dogs after surgical intervention for cranial cruciate disease, changes in tibial SBD are minor and may not correlate with clinical function., (© 2018 The American College of Veterinary Surgeons.)

Objective: To determine the influence of a quilting suture pattern tacking the subcutaneous tissues to the deep fascia on complications after midline celiotomy in dogs., Study Design: Single-center, randomized, blinded, controlled trial conducted in a veterinary teaching hospital., Animals: Four hundred thirty-two dogs undergoing midline celiotomy for ovariohysterectomy (n = 249) or other abdominal procedures (n = 183)., Methods: Dogs were randomly assigned to (1) a quilting group, subcutaneous tissue with apposition plus tacking to the rectus fascia or (2) a nonquilting group, with apposition of subcutaneous tissue without tacking. Randomization was stratified on hospital admitting service. Primary outcome was the incidence of incisional seroma. Secondary outcomes included postoperative pain the day after surgery and surgical site infection (SSI). Outcomes were assessed during the first 30 postoperative days., Results: No differences were detected between the quilting group (n = 183) and the nonquilting group (n = 175) in terms of illness severity, surgical procedure performed, surgeon's experience, duration of surgery, intraoperative complications, or methods of surgical closure other than the intervention under study. In an intent-to-treat analysis, the incidence of incisional seroma was lower in the quilting group (odds ratio = 0.30, 95% CI = 0.13-0.67, P = .004). Pain assessed 24 hours postoperatively was lower in the quilting group (P = .03). The incidence of SSI did not differ between groups., Conclusion: Tacking the subcutaneous tissues to the deep fascia is indicated to reduce seroma during celiotomy closure., (© 2017 The American College of Veterinary Surgeons.)

Brain banking has a long and distinguished past, contributing greatly to our understanding of human neurological and psychiatric conditions. Brain banks have been operationally diverse, collecting primarily end stage disease, with variable quality clinical data available, yet it is now recognized the most informative brain donations are from those in longitudinally studied cohorts. The Brains for Dementia Research (BDR) cohort and program was for planned brain donation across five UK brain banks and one donation point, with standardized operating procedures, following longitudinal clinical and psychometric assessments for people with no cognitive impairment as well as those with dementia. Lay representatives with experience of dementia were involved from inception of BDR and 74.5% of all enquiries about participation came through routes that were directly attributable to or influenced by lay representatives. Ten years after inception, this ongoing project has received over 700 brain donations from the recruited cohort of 3,276 potential brain donors. At cohort census for this paper, 72.2% of the living cohort have no cognitive impairment by assessment, whereas only 28.3% of the donated cohort were without cognitive impairment. It is important that brain banks are agile and reflect the changing needs of the research community, given that 'big data', readiness cohorts, and GWAS demand large sample numbers of highly characterized individuals to facilitate new approaches and understanding of pathological processes in dementia.

Objective: Test the feasibility of assessing cognition, psychiatric symptoms and daily living skills of potential brain donors by telephone and compare satisfaction and attitudes across telephone and face-to-face assessment., Method: Data were collected from 108 healthy participants from the Brains for Dementia Research cohort. Purposive sampling was used to assess feasibility and a randomised control trial design compared satisfaction and attitudes towards telephone and face-to-face assessment. Non-parametric tests were conducted to compare groups, and logistic regression was performed to assess the relationship between satisfaction and participant characteristics., Results: Of the 80 participants offered telephone assessment, 67 (83.8%) agreed, 2 (2.5%) had a significant hearing impairment, 4 (5.0%) had potential memory problems and 7 (8.7%) declined. On average, telephone assessments lasted 38 min and duration was negatively associated with Telephone Interview of Cognitive Status-Modified scores (p = 0.001) and positively associated with age (p = 0.040), Neuropsychiatric Inventory scores (p = 0.019), Geriatric Depression Scale (p = 0.035) and Global Deterioration Scale (p = 0.022). Satisfaction was high in respect to organisational and personal aspects; ratings did not differ significantly across telephone and face-to-face assessment groups and were not related to socio-demographic characteristics. Participants undergoing telephone assessment were significantly more likely to hold positive attitudes towards this mode of assessment., Conclusions: Telephone assessment is feasible, time-efficient and acceptable to healthy, potential brain donors. When used with other assessment modes and within the context of established contact, telephone assessment offers greater flexibility to researchers and participants and represents an effective mechanism for overcoming the challenges of growing, ageing cohorts and uncertain resources. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Prospective studies of antibodies to multiple Epstein-Barr virus (EBV) proteins and EBV neutralizing antibodies in the same individuals before, during, and after primary EBV infection have not been reported. We studied antibody responses to EBV in college students who acquired primary EBV infection during prospective surveillance and correlated the kinetics of antibody response with the severity of disease. Neutralizing antibodies and enzyme-linked immunosorbent assay (ELISA) antibodies to gp350, the major target of neutralizing antibody, reached peak levels at medians of 179 and 333 days after the onset of symptoms of infectious mononucleosis, respectively. No clear correlation was found between the severity of the symptoms of infectious mononucleosis and the peak levels of antibody to individual viral proteins or to neutralizing antibody. In summary, we found that titers of neutralizing antibody and antibodies to multiple EBV proteins increase over many months after primary infection with EBV., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

Vaccine prophylaxis with EBV glycoprotein 350 (gp350) subunit plus adjuvant has been demonstrated clinically to protect individuals against infectious mononucleosis (IM), but the specifications of the antigen required to elicit this protection has remained largely theoretical. Previous studies have shown that antibodies to gp350 comprise the principle component of EBV-neutralizing sera. Further, a murine monoclonal antibody against gp350 (clone 72A1) is able to prevent infection by the virus both in vitro and in vivo. In the present study, we identify the 72A1 epitope on recombinant gp350 antigen as the site required for binding to CD21 on human B cells. We also identify the need for conformational-dependence of the antigen to generate EBV-neutralizing antibodies in vivo. Further, we have characterized the glycosylation status and antigenicity profiles of both native and denatured CHO-produced soluble gp350 as well as non-glycosylated protein produced in Escherichia coli. Collectively our in vitro and in vivo data demonstrate the requirement for a conformationally accessible 72A1 epitope on gp350 to elicit EBV-neutralizing responses, and establish this as a critical attribute of this vaccine antigen. These data provide direction for commercial vaccine development, as the absence of this epitope on either E. coli-expressed or denatured gp350, may limit production and purification options for the antigen., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

A 2-year-old Labrador retriever dog was referred for evaluation of parasternal chronic draining sinus tracts associated with sternal osteomyelitis secondary to the presence of a residual wooden foreign body. The use of gentamicin-impregnated collagen sponges as adjunctive therapy to osteomyelitis treatment is reported herein.

Objective: To determine which type of surgical hand-tie trainee surgeons learn most readily in a laboratory setting, using a combination of audiovisual demonstration and one-on-one teaching., Study Design: Randomized controlled learning trial., Sample Population: Year 4 veterinary students in their 1st year of clinical training (n = 58)., Methods: Veterinary students entering clinical rotations were randomly allocated to 2 learning groups: 1-handed (28 students) or 2-handed (30 students) surgical ties. Knot tying technique was taught followed by three 15-minute practice sessions with student progress recorded by filming each student tying a square knot (2 throws). All 3 knot tying attempts were scored for technique and knot formation. Data on potential confounding factors between groups, including age and gender, were recorded., Results: There were no significant differences between group scores for each attempt (1st attempt P = .5; 2nd P = .2; 3rd P = .19). Initially, scores indicated more rapid learning in the 1-handed group but fewer individuals achieved a perfect technique and knot after 60 minutes of learning (29/30 for 2-handed; 24/28 for 1-handed group). The 1-handed group was the most error-prone (after 45 minutes P < .01; after 60 min P < .01)., Conclusions: Over 95% of students in the 2-handed group performed the technique and knot perfectly after 60 minutes learning time; were significantly less error-prone and fewer students continued to make corrected errors after 60 minutes. This evidence indicates that the 2-handed technique allows students to achieve success in a manageable teaching time., (© Copyright 2015 by The American College of Veterinary Surgeons.)

CD98 is expressed on several tissue types and specifically upregulated on fast-cycling cells undergoing clonal expansion. Various solid (e.g., nonsmall cell lung carcinoma) as well as hematological malignancies (e.g., acute myeloid leukemia) overexpress CD98. We have identified a CD98-specific mouse monoclonal antibody that exhibits potent preclinical antitumor activity against established lymphoma tumor xenografts. Additionally, the humanized antibody designated IGN523 demonstrated robust tumor growth inhibition in leukemic cell-line derived xenograft models and was as efficacious as standard of care carboplatin in patient-derived nonsmall lung cancer xenografts. In vitro studies revealed that IGN523 elicited strong ADCC activity, induced lysosomal membrane permeabilization and inhibited essential amino acid transport function, ultimately resulting in caspase-3 and -7-mediated apoptosis of tumor cells. IGN523 is currently being evaluated in a Phase I clinical trial for acute myeloid leukemia (NCT02040506). Furthermore, preclinical data support the therapeutic potential of IGN523 in solid tumors., (© 2014 UICC.)

Soft tissue sarcoma (STS) is a heterogenous tumor arising from the embryonic mesoderm represented by approximately 50 histological subtypes. Effective therapeutic intervention is lacking for recurrent, late stage and metastatic disease. CD39, a cell-surface ectonucleotidase, has previously been shown to be upregulated in hematological malignancies and various epithelial tumors, but not in STS. Here, we show by mass spectrometry and immunohistochemistry that CD39 is highly expressed in primary patient sarcoma samples. Moreover, CD39 nucleotidase activity is enhanced in fibrosarcoma compared with normal control cells. We demonstrate that an inhibitory monoclonal anti-CD39 antibody, abrogates CD39 enzymatic activity significantly and prolongs survival in a lethal metastatic patient-derived sarcoma model. Taken together, the data suggest CD39 is a novel therapeutic target for the treatment of STS.

Molecular characterization of events is an integral part of the advancement process during genetically modified (GM) crop product development. Assessment of these events is traditionally accomplished by polymerase chain reaction (PCR) and Southern blot analyses. Southern blot analysis can be time-consuming and comparatively expensive and does not provide sequence-level detail. We have developed a sequence-based application, Southern-by-Sequencing (SbS), utilizing sequence capture coupled with next-generation sequencing (NGS) technology to replace Southern blot analysis for event selection in a high-throughput molecular characterization environment. SbS is accomplished by hybridizing indexed and pooled whole-genome DNA libraries from GM plants to biotinylated probes designed to target the sequence of transformation plasmids used to generate events within the pool. This sequence capture process enriches the sequence data obtained for targeted regions of interest (transformation plasmid DNA). Taking advantage of the DNA adjacent to the targeted bases (referred to as next-to-target sequence) that accompanies the targeted transformation plasmid sequence, the data analysis detects plasmid-to-genome and plasmid-to-plasmid junctions introduced during insertion into the plant genome. Analysis of these junction sequences provides sequence-level information as to the following: the number of insertion loci including detection of unlinked, independently segregating, small DNA fragments; copy number; rearrangements, truncations, or deletions of the intended insertion DNA; and the presence of transformation plasmid backbone sequences. This molecular evidence from SbS analysis is used to characterize and select GM plants meeting optimal molecular characterization criteria. SbS technology has proven to be a robust event screening tool for use in a high-throughput molecular characterization environment., (© 2015 The Authors.)

Objective: To identify incidence and risk factors for surgical glove perforation in small animal surgery., Study Design: Observational cohort study., Sample Population: Surgical gloves (n = 2132) worn in 363 surgical procedures., Methods: All gloves worn by operative personnel were assessed for perforation at end-procedure using a water leak test. Putative risk factors were recorded by a surgical team member. Associations between risk factors and perforation were assessed using multivariable multi-level random-effects logistic regression models to control for hierarchical data structure., Results: At least 1 glove perforation occurred in 26.2% of procedures. Identified risk factors for glove perforation included increased surgical duration (surgery >1 hour OR = 1.79, 95% CI = 1.12-2.86), performing orthopedic procedures (OR = 1.88; 95% CI = 1.23-2.88), any procedure using powered instruments (OR = 1.93; 95% CI = 1.21-3.09) or surgical wire (OR = 3.02; 95% CI = 1.50-6.05), use of polyisoprene as a glove material (OR = 1.59, 95% CI = 1.05-2.39), and operative role as primary surgeon (OR = 2.01; 95% CI = 1.35-2.98). The ability of the wearer to detect perforations intraoperatively was poor, with a sensitivity of 30.8%., Conclusions: There is a high incidence of unrecognized glove perforations in small animal surgery., (© Copyright 2014 by The American College of Veterinary Surgeons.)

Objective: To investigate local and systemic pharmacokinetics of gentamicin after intra-articular implantation of a gentamicin impregnated collagen sponge (GICS) in the inflamed canine joint., Study Design: Descriptive repeated measures experimental study., Animals: Dogs (n = 9)., Methods: Stifle joint inflammation was caused by urate injection. Twenty-four hours later a GICS (gentamicin dose, 6 mg/kg) was arthroscopically implanted. Synovial fluid and plasma gentamicin concentrations were measured for 14 days after implantation, and pharmacokinetic parameters modeled using statistical moment analyses., Results: Intra-articular gentamicin concentrations fell to sub-MIC for Staphylococcus sp. (4 µg/mL) by 22.4 hours (95% CI: 18.6-26.2) after sponge implantation. Cmax synovial was 2397 µg/mL (95%CI: 1161-3634 µg/mL) at 1.2 hours (95%CI: 0.5-1.8 hours). Plasma gentamicin concentrations achieved levels of Cmax plasma  = 8.0 µg/mL (95%CI: 6.1-10.0 µg/mL) at 1.5 hours (95%CI: 0.8-2.1) after GICS placement and fell below target trough of 2.0 µg/mL by 5.6 hours (95%CI: 4.7-6.5 hours) after GICS placement., Conclusions: Intra-articular gentamicin concentration after GICS placement at an IV-equivalent dose reached high levels and declined rapidly. The maximum plasma levels attained were ∼1/3 of the recommended sub-toxic target for people after parenteral gentamicin administration., (© Copyright 2014 by The American College of Veterinary Surgeons.)