Performance of the American Heart Association/American College of Cardiology/Heart Rhythm Society versus European Society of Cardiology guideline criteria for hospital admission of patients with syncope.

BACKGROUND: Current American College of Cardiology/American Heart Association/Heart Rhythm Society (ACC/AHA/HRS) and European Society of Cardiology (ESC) guidelines recommend different strategies to avoid low-yield admissions in patients with syncope. OBJECTIVE: The purpose of this study was to directly compare the safety and efficacy of applying admission criteria of both guidelines to patients presenting with syncope to the emergency department in 2 multicenter studies. METHODS: The international BASEL IX (BAsel Syncope EvaLuation) study (median age 71 years) and the U.S. SRS (Improving Syncope Risk Stratification in Older Adults) study (median age 72 years) were investigated. Primary endpoints were sensitivity/specificity for the adjudicated diagnosis of cardiac syncope (BASEL IX only) and 30-day major adverse cardiovascular events (30d-MACE). RESULTS: Among 2560 patients in the BASEL IX and 2085 in SRS studies, ACC/AHA/HRS and ESC criteria recommended admission for a comparable number of patients in BASEL IX (27% vs 28%), but ACC/AHA/HRS criteria less often in SRS (19% vs 32%; P <.01). Recommendations were discordant in ∼25% of patients. In BASEL IX, sensitivity for cardiac syncope and 30d-MACE among patients without admission criteria was comparable for ACC/AHA/HRS and ESC criteria (64% vs 65%, P = .86; and 67% vs 71%, P = .15, respectively). In SRS, sensitivity for 30d-MACE was lower with ACC/AHA/HRS (54%) vs ESC criteria (88%; P <.001). Similarly, specificity for cardiac syncope and 30d-MACE in BASEL IX was comparable for both guidelines, but in SRS the ACC/AHA/HRS guidelines showed a higher specificity for 30d-MACE than the ESC guidelines. CONCLUSION: ACC/AHA/HRS and ESC guidelines showed disagreement regarding admission for 1 in 4 patients and had only modest sensitivity, all indicating possible opportunities for improvements.

Corrigendum: Extracorporeal Shock Wave Therapy Enhances the In Vitro Metabolic Activity and Differentiation of Equine Umbilical Cord Blood Mesenchymal Stromal Cells.

[This corrects the article DOI: 10.3389/fvets.2020.554306.].

Terminal Syme Amputation of the Great Toe in the Pediatric Population.

BACKGROUND: In the pediatric population, chronic ingrown toenails (onychocryptosis) can cause infection (paronychia), debilitating pain, and may be unresponsive to conservative treatments. Following multiple failed interventions, a terminal Syme amputation is one option for definitive treatment of chronic onychocryptosis. This procedure involves amputation of the distal aspect of the distal phalanx of the great toe with complete removal of the nail bed and germinal center, preventing further nail growth and recurrence. METHODS: A retrospective review was performed to determine outcomes of a terminal Syme amputation in the pediatric population. Inclusion criteria included treatment of onychocryptosis involving terminal Syme amputation with a minimum follow-up of 1 year. The medical record was reviewed to assess previous failed treatment efforts, perioperative complications, radiographic outcomes, and the need for additional procedures. RESULTS: From 1984 to 2017, 11 patients (13 halluces) with onychocryptosis were treated with a terminal Syme amputation. There were no intraoperative complications. One hallux had a postoperative infection requiring antibiotics as well as partial nail regrowth following the terminal Syme procedure that required subsequent removal of the residual nail. Following partial nail ablation, the patient had no further nail growth. An additional patient also developed a postoperative infection requiring oral antibiotic treatment. All patients returned to full weight-bearing physical activities within 6 weeks of surgery. CONCLUSIONS: Terminal Syme amputation was successful in treating pediatric patients who have recalcitrant onychocryptosis and paronychia. There was little functional consequence following terminal Syme amputation of the great toe in this patient population, making it an effective salvage procedure. LEVEL OF EVIDENCE: Level IV-retrospective comparative study.

Meta-Fish-Lib: A generalised, dynamic DNA reference library pipeline for metabarcoding of fishes.

The accuracy and reliability of DNA metabarcoding analyses depend on the breadth and quality of the reference libraries that underpin them. However, there are limited options available to obtain and curate the huge volumes of sequence data that are available on public repositories such as NCBI and BOLD. Here, we provide a pipeline to download, clean and annotate mitochondrial DNA sequence data for a given list of fish species. Features of this pipeline include (a) support for multiple metabarcode markers; (b) searches on species synonyms and taxonomic name validation; (c) phylogeny assisted quality control for identification and removal of misannotated sequences; (d) automatically generated coverage reports for each new GenBank release update; and (e) citable, versioned DOIs. As an example we provide a ready-to-use curated reference library for the marine and freshwater fishes of the U.K. To augment this reference library for environmental DNA metabarcoding specifically, we generated 241 new MiFish-12S sequences for 88 U.K. marine species, and make available new primer sets useful for sequencing these. This brings the coverage of common U.K. species for the MiFish-12S fragment to 93%, opening new avenues for scaling up fish metabarcoding across wide spatial gradients. The Meta-Fish-Lib reference library and pipeline is hosted at https://github.com/genner-lab/meta-fish-lib.

Use of a surgical safety checklist after implementation in an academic veterinary hospital.

OBJECTIVE: To determine the use and barriers to uptake of a surgical safety checklist (SSC) after implementation in a veterinary teaching hospital. STUDY DESIGN: Voluntary online survey and retrospective study. SAMPLE POPULATION: All personnel actively involved in the Ontario Veterinary College Health Sciences Centre small animal surgery service between October 2, 2018 and June 28, 2019. METHODS: Surgical case logs and electronically initiated SSC were reviewed to calculate checklist use. The sample population was surveyed to identify factors and barriers associated with use of the SSC. Participants were allowed 1 month to respond, and five reminder emails were sent. RESULTS: Forth-one of 50 (82%) participants completed the survey. The SSC was used in 374 of 784 (47.7%) surgeries. Use rates declined over sequential three-month intervals (P < .0001). Twenty-six of 41 (63%) respondents overestimated checklist use. Staff attitudes were largely supportive of the SSC, with 29 of 41 respondents suggesting mandatory application. Forgetfulness, hierarchal concerns, timing issues, perceived delays in care, lack of clarity regarding roles, and inadequate training were identified as obstacles to use of the SSC. CONCLUSION: The SCC tested in this study was used in approximately half of the surgical procedures performed after its implementation. Hospital personnel were supportive of the SSC; forgetting to use the SSC was the most common barrier identified by respondents (24/41 [59%]). CLINICAL SIGNIFICANCE: The SSC implementation experience and user feedback described here should be taken into consideration to improve design and implementation of future SSC.

Extracorporeal Shock Wave Therapy Enhances the In Vitro Metabolic Activity and Differentiation of Equine Umbilical Cord Blood Mesenchymal Stromal Cells.

Extracorporeal shock wave therapy (ESWT) has been shown to induce different biological effects on a variety of cells, including regulation and stimulation of their function and metabolism. ESWT can promote different biological responses such as proliferation, migration, and regenerations of cells. Recent studies have shown that mesenchymal stromal cells (MSCs) secrete factors that enhance the regeneration of tissues, stimulate proliferation and differentiation of cells, and decrease inflammatory and immune reactions. Clinically, the combination of these two therapies has been used as a treatment for tendon and ligament lesions in horses; however, there is no scientific evidence supporting this combination of therapies in vivo. Therefore, the objectives of the study were to evaluate the effects of ESWT on equine umbilical cord blood mesenchymal stromal cells (CB-MSCs) proliferative, metabolic, migrative, differentiation, and immunomodulatory properties in vitro. Three equine CB-MSC cultures from independent donors were treated using an electrohydraulic shock wave generator attached to a water bath. All experiments were performed as triplicates. Proliferation, viability, migration and immunomodulatory properties of the cells were evaluated. Equine CB-MSCs were induced to evaluate their trilineage differentiation potential. ESWT treated cells had increased metabolic activity, showed positive adipogenic, osteogenic, and chondrogenic differentiation, and showed higher potential for differentiation toward the adipogenic and osteogenic cell fates. ESWT treated cells showed similar immunomodulatory properties to none-ESWT treated cells. Equine CB-MSCs are responsive to ESWT treatment and showed increased metabolic, adipogenic and osteogenic activity, but unaltered immunosuppressive properties. In vivo studies are warranted to determine if synergistic effects occur in the treatment of musculoskeletal injuries if ESWT and equine CB-MSC therapies are combined.

Body composition of medium to giant breed dogs with or without cranial cruciate ligament disease.

OBJECTIVE: To describe the body composition of dogs with or without cranial cruciate ligament (CCL) disease. STUDY DESIGN: Cross-sectional. ANIMALS: Adult dogs in which CCL disease was diagnosed (n = 30) and adult dogs without clinical signs of orthopedic disease (n = 30). METHODS: Body weight, body condition score, and muscle condition score (MCS) were recorded. Body composition of the whole body and pelvic limbs were assessed by dual-energy x-ray absorptiometry. Body condition score, whole body, and pelvic limb body composition measurements were compared by using general linear mixed-model analysis of variance. Muscle condition score between groups was assessed by using a Mann-Whitney U test, while paired data were analyzed by using a Wilcoxon signed-rank test. RESULTS: Body fat percentage (P < .0001) was higher in affected dogs (38.78% ± 1.40) than in control dogs (27.49% ± 1.24). Affected dogs had lower MCS (1.90 ± 0.13, P < .0001) compared with control dogs (2.77 ± 0.08). The affected pelvic limb of affected dogs contained less lean soft tissues (P < .0001) but more fat (P = .0451) compared with the contralateral pelvic limb. CONCLUSION: Dogs with CCL disease were overweight compared with the control group. CLINICAL SIGNIFICANCE: Dogs that are overweight may be predisposed to developing CCL disease. Body composition changes in the pelvic limbs should be considered when managing the care of these dogs.

Contributing factors to surgical site infection after tibial plateau leveling osteotomy: A follow-up retrospective study.

OBJECTIVE: To identify factors associated with surgical site infection (SSI) after tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Retrospective case series. ANIMALS: Dogs (n = 541) that underwent TPLO (n = 659). METHODS: Medical records of dogs that underwent TPLO from 2011-2018 were reviewed. Data collected included perioperative and postoperative antimicrobial administration, stifle inspection, duration of surgery and anesthesia, comorbidities, and development of SSI including timing, microbiological investigation, and implant removal. Referring veterinarians were contacted for all dogs without a recorded return visit. Risk factors for SSI were assessed by using a multivariable logistic regression model built by using a stepwise approach. RESULTS: Surgical site infection was documented in 71 of 659 (11%) TPLO, with methicillin-resistant Staphylococcus pseudintermedius accounting for 20 of 71 (28%) infections. Protective factors against SSI included administration of postoperative antimicrobials (odds ratio [OR] 0.263; 95% CI = 0.157, 0.442) and timing of preoperative antimicrobial administration. Preoperative antimicrobial timing was protective against SSI when it was administered more than 60 minutes before the first incision compared with administration within 30 minutes (OR 0.275; 95% CI = 0.112, 0.676) or within 60 minutes (OR 0.419; 95% CI = 0.189, 0.929) of the first incision. CONCLUSION: Early administration of perioperative antimicrobials and postoperative antimicrobial administration were protective against SSI after TPLO. CLINICAL SIGNIFICANCE: Antimicrobials can influence the risk of SSI after TPLO. Perioperative and postoperative antimicrobial administration timing should be considered to reduce SSI.

In vitro elution of amikacin and Dispersin B from a polymer hydrogel.

OBJECTIVE: To characterize the in vitro elution of amikacin and Dispersin B (ß-N-acetylglucosaminidase) in a degradable hydrogel. STUDY DESIGN: In vitro, prospective study. METHODS: Amikacin (group A; 40 mg/mL), Dispersin B (group D; 70 µg/mL), or combined amikacin and Dispersin B (group AD; 40 mg/mL and 70 µg/mL, respectively) were added to a hydrogel. Ten aliquots per group were incubated in phosphate-buffered saline that was exchanged at 1, 4, 8, 12, and 24 hours and then once daily for 10 days. Eluted amikacin and Dispersin B were quantitated by using an amikacin reagent kit and a Dispersin B enzyme-linked immunosorbent assay kit, respectively. Time point drug concentrations were compared between groups by using repeated-measures analysis of variance, and total drug elution was compared by using an area under the curve calculation. RESULTS: Amikacin alone, Dispersin B alone, and amikacin and Dispersin B combined together underwent rapid elution in the first 24 hours, followed by a gradual decrease over 10 days. The concentration of Dispersin B eluted in group D was higher at 1 day and lower from day 5 to day 10 compared with that in group AD. The concentration of amikacin eluted in group A was higher at 1, 4, and 8 hours and on day 10 and lower on day 1 compared with that in group AD. The total elution of amikacin was greater from group AD compared with that from group A (P = .02). CONCLUSION: Combining amikacin and Dispersin B had an affect on the total elution of amikacin but not Dispersin B. CLINICAL SIGNIFICANCE: The combination of amikacin and Dispersin B in a degradable hydrogel could allow local treatment of complex infections without the requirement for multiple invasive procedures.

Risk Stratification of Older Adults Who Present to the Emergency Department With Syncope: The FAINT Score.

STUDY OBJECTIVE: Older adults with syncope are commonly treated in the emergency department (ED). We seek to derive a novel risk-stratification tool to predict 30-day serious cardiac outcomes. METHODS: We performed a prospective, observational study of older adults (≥60 years) with unexplained syncope or near syncope who presented to 11 EDs in the United States. Patients with a serious diagnosis identified in the ED were excluded. We collected clinical and laboratory data on all patients. Our primary outcome was 30-day all-cause mortality or serious cardiac outcome. RESULTS: We enrolled 3,177 older adults with unexplained syncope or near syncope between April 2013 and September 2016. Mean age was 73 years (SD 9.0 years). The incidence of the primary outcome was 5.7% (95% confidence interval [CI] 4.9% to 6.5%). Using Bayesian logistic regression, we derived the FAINT score: history of heart failure, history of cardiac arrhythmia, initial abnormal ECG result, elevated pro B-type natriuretic peptide, and elevated high-sensitivity troponin T. A FAINT score of 0 versus greater than or equal to 1 had sensitivity of 96.7% (95% CI 92.9% to 98.8%) and specificity 22.2% (95% CI 20.7% to 23.8%), respectively. The FAINT score tended to be more accurate than unstructured physician judgment: area under the curve 0.704 (95% CI 0.669 to 0.739) versus 0.630 (95% CI 0.589 to 0.670). CONCLUSION: Among older adults with syncope or near syncope of potential cardiac cause, a FAINT score of zero had a reasonably high sensitivity for excluding death and serious cardiac outcomes at 30 days. If externally validated, this tool could improve resource use for this common condition.

Alveolar echinococcosis in an Ontario dog resembling an hepatic abscess.

A boxer dog was evaluated because of lethargy, vomiting, and abdominal pain. Ultrasonography revealed multiple cystic structures in the abdomen. Exploratory laparotomy revealed 3 well-encapsulated hepatic masses and abdominal effusion with suppurative inflammation. Collectively, these findings suggested the hepatic masses were most likely abscesses. However, histologic examination of the hepatic masses revealed multi-cystic structures, consistent with alveolar echinococcosis. The diagnosis was confirmed by DNA sequencing. The dog was treated with daily albendazole, but within a few weeks exhibited adverse side effects. After 6 months, the dog's condition deteriorated, and it was euthanized.

Échinococcose alvéolaire ressemblant à un abcès hépatique chez un chien en Ontario. Un chien de race boxer fut évalué à cause de léthargie, vomissements, et douleur abdominale. Une échographie révéla de multiples structures kystiques dans l'abdomen. Une laparotomie exploratoire révéla trois masses hépatiques bien encapsulées et une effusion abdominale avec inflammation suppurative. Collectivement, ces données suggéraient que les masses hépatiques étaient fort probablement des abcès. Toutefois, l'examen histologique des masses hépatiques révéla des structures multi-kystiques, compatibles avec une échinococcose alvéolaire. Le diagnostic fut confirmé par séquençage d'ADN. Le chien fut traité avec de l'albendazole quotidiennement, mais en quelques semaines il montra des signes d'effets adverses. Après 6 mois la condition du chien se détériora et il fut euthanasié.(Traduit par Dr Serge Messier).

Do High-sensitivity Troponin and Natriuretic Peptide Predict Death or Serious Cardiac Outcomes After Syncope?

OBJECTIVES: An estimated 1.2 million annual emergency department (ED) visits for syncope/near syncope occur in the United States. Cardiac biomarkers are frequently obtained during the ED evaluation, but the prognostic value of index high-sensitivity troponin (hscTnT) and natriuretic peptide (NT-proBNP) are unclear. The objective of this study was to determine if hscTnT and NT-proBNP drawn in the ED are independently associated with 30-day death/serious cardiac outcomes in adult patients presenting with syncope. METHODS: A prespecified secondary analysis of a prospective, observational trial enrolling participants ≥ age 60 presenting with syncope, at 11 United States hospitals, was conducted between April 2013 and September 2016. Exclusions included seizure, stroke, transient ischemic attack, trauma, intoxication, hypoglycemia, persistent confusion, mechanical/electrical invention, prior enrollment, or predicted poor follow-up. Within 3 hours of consent, hscTnT and NT-proBNP were collected and later analyzed centrally using Roche Elecsys Gen 5 STAT and 2010 Cobas, respectively. Primary outcome was combined 30-day all-cause mortality and serious cardiac events. Adjusting for illness severity, using multivariate logistic regression analysis, variations between primary outcome and biomarkers were estimated, adjusting absolute risk associated with ranges of biomarkers using Bayesian Markov Chain Monte Carlo methods. RESULTS: The cohort included 3,392 patients; 367 (10.8%) experienced the primary outcome. Adjusted absolute risk for the primary outcome increased with hscTnT and NT-proBNP levels. HscTnT levels ≤ 5 ng/L were associated with a 4% (95% confidence interval [CI] = 3%-5%) outcome risk, and hscTnT > 50 ng/L, a 29% (95% CI = 26%-33%) risk. NT-proBNP levels ≤ 125 ng/L were associated with a 4% (95% CI = 4%-5%) risk, and NT-proBNP > 2,000 ng/L a 29% (95% CI = 25%-32%) risk. Likelihood ratios and predictive values demonstrated similar results. Sensitivity analyses excluding ED index serious outcomes demonstrated similar findings. CONCLUSIONS: hscTnT and NT-proBNP are independent predictors of 30-day death and serious outcomes in older ED patients presenting with syncope.

Clinical outcomes following prenatal diagnosis of asymmetric ventriculomegaly, interhemispheric cyst, and callosal dysgenesis (AVID).

OBJECTIVES: When identified prenatally, the imaging triad of asymmetric ventriculomegaly, interhemispheric cyst, and dysgenesis of the corpus callosum (AVID) can indicate a more serious congenital brain anomaly. In this follow-up series of 15 fetuses, we present the neurodevelopmental outcomes of a single institution cohort of children diagnosed prenatally with AVID. METHODS: Our fetal ultrasound database was queried for cases of AVID between 2000 and 2016. All available fetal MR imaging studies were reviewed for the presence of (a) interhemispheric cysts or ventricular diverticula and (b) dysgenesis or agenesis of the corpus callosum. Clinical records were reviewed for perinatal management, postnatal surgical management, and neurodevelopmental outcomes. RESULTS: Fifteen prenatal cases of AVID were identified. Twelve were live-born and three pregnancies were terminated. Of the 12 patients, 11 underwent neurosurgical intervention. Of the eight patients surviving past infancy, seven of eight have moderate to severe neurodevelopmental delays or disabilities, encompassing both motor and language skills, and all have variable visual abnormalities. CONCLUSION: In our cohort of 15 prenatally diagnosed fetuses with AVID, eight survived past infancy and all have neurodevelopmental disabilities, including motor and language deficits, a wide range of visual defects, craniofacial abnormalities, and medical comorbidities.

Predictors of Clinically Significant Echocardiography Findings in Older Adults with Syncope: A Secondary Analysis.

BACKGROUND: Syncope is a common reason for visiting the emergency department (ED) and is associated with significant healthcare resource utilization. OBJECTIVE: To develop a risk-stratification tool for clinically significant findings on echocardiography among older adults presenting to the ED with syncope or nearsyncope. DESIGN: Prospective, observational cohort study from April 2013 to September 2016. SETTING: Eleven EDs in the United States. PATIENTS: We enrolled adults (=60 years) who presented to the ED with syncope or near-syncope who underwent transthoracic echocardiography (TTE). MEASUREMENTS: The primary outcome was a clinically significant finding on TTE. Clinical, electrocardiogram, and laboratory variables were also collected. Multivariable logistic regression analysis was used to identify predictors of significant findings on echocardiography. RESULTS: A total of 3,686 patients were enrolled. Of these, 995 (27%) received echocardiography, and 215 (22%) had a significant finding on echocardiography. Regression analysis identified five predictors of significant finding: (1) history of congestive heart failure, (2) history of coronary artery disease, (3) abnormal electrocardiogram, (4) high-sensitivity troponin-T >14 pg/mL, and 5) N-terminal pro B-type natriuretic peptide >125 pg/mL. These five variables make up the ROMEO (Risk Of Major Echocardiography findings in Older adults with syncope) criteria. The sensitivity of a ROMEO score of zero for excluding significant findings on echocardiography was 99.5% (95% CI: 97.4%-99.9%) with a specificity of 15.4% (95% CI: 13.0%-18.1%). CONCLUSIONS: If validated, this risk-stratification tool could help clinicians determine which syncope patients are at very low risk of having clinically significant findings on echocardiography. REGISTRATION: ClinicalTrials.gov Identifier NCT01802398.

Predictors of Short-Term Outcomes after Syncope: A Systematic Review and Meta-Analysis.

INTRODUCTION: We performed a systematic review and meta-analysis to identify predictors of serious clinical outcomes after an acute-care evaluation for syncope. METHODS: We identified studies that assessed for predictors of short-term (≤30 days) serious clinical events after an emergency department (ED) visit for syncope. We performed a MEDLINE search (January 1, 1990 - July 1, 2017) and reviewed reference lists of retrieved articles. The primary outcome was the occurrence of a serious clinical event (composite of mortality, arrhythmia, ischemic or structural heart disease, major bleed, or neurovascular event) within 30 days. We estimated the sensitivity, specificity, and likelihood ratio of findings for the primary outcome. We created summary estimates of association on a variable-by-variable basis using a Bayesian random-effects model. RESULTS: We reviewed 2,773 unique articles; 17 met inclusion criteria. The clinical findings most predictive of a short-term, serious event were the following: 1) An elevated blood urea nitrogen level (positive likelihood ratio [LR+]: 2.86, 95% confidence interval [CI] [1.15, 5.42]); 2); history of congestive heart failure (LR+: 2.65, 95%CI [1.69, 3.91]); 3) initial low blood pressure in the ED (LR+: 2.62, 95%CI [1.12, 4.9]); 4) history of arrhythmia (LR+: 2.32, 95%CI [1.31, 3.62]); and 5) an abnormal troponin value (LR+: 2.49, 95%CI [1.36, 4.1]). Younger age was associated with lower risk (LR-: 0.44, 95%CI [0.25, 0.68]). An abnormal electrocardiogram was mildly predictive of increased risk (LR+ 1.79, 95%CI [1.14, 2.63]). CONCLUSION: We identified specific risk factors that may aid clinical judgment and that should be considered in the development of future risk-prediction tools for serious clinical events after an ED visit for syncope.

Diagnostic accuracy and clinical outcomes associated with prenatal diagnosis of fetal absent cavum septi pellucidi.

BACKGROUND: Absence of the cavum septi pellucidi (CSP) on prenatal imaging is historically associated with additional anomalies; however, recent cases of isolated absent CSP have also been identified. This study seeks to assess the accuracy of prenatal imaging in evaluating isolated absent CSP and to describe the spectrum of clinical outcomes. METHODS: This is a retrospective observational study of all prenatally diagnosed absent CSP cases between 2011 and 2016 at our institution. Cases with additional structural parenchymal abnormalities were excluded. Clinical outcomes were abstracted from available records. RESULTS: We identified 15 cases of prenatally diagnosed isolated absent CSP. All patients were initially diagnosed on ultrasound (US) and 11/15 patients had fetal magnetic resonance imaging (MRI) confirming the diagnosis. Prenatal US and MRI were concordant in all cases. Of the continuing pregnancies, 2 neonatal deaths occurred related to extreme prematurity. Two cases of septo-optic dysplasia were identified in our cohort. DISCUSSION: In this study, fetal MRI and US had a high degree of accuracy with concordant postnatal imaging. Our study is similar to other case series suggesting that a range of clinical outcomes is possible with isolated absent CSP, but long-term patient follow up is necessary.

Single-Domain Antibody-Functionalized pH-Responsive Amphiphilic Block Copolymer Nanoparticles for Epidermal Growth Factor Receptor Targeted Cancer Therapy.

Biocompatible antibody-nanoparticle conjugates have attracted interest as anticancer agents due to their potential to selectively target therapeutic agents at disease sites. However, new formulation and conjugation approaches are urgently needed to improve their uniformity for clinical applications. Here, a pH-responsive benzaldehyde-functionalized poly[oligo(ethylene glycol) methacrylate-st-para-formyl phenyl methacrylate]-b-poly[2-(diisopropyl)aminoethyl methacrylate] [P(OEGMA-st-pFPMA)-b-PDPA] block copolymer, prepared by reversible addition-fragmentation chain transfer polymerization, produced PEGylated nanoparticles (pH ∼ 7.4) by a single emulsion-solvent evaporation formulation approach. Efficient site-specific attachment of an aminooxy-functionalized anti-EGFR single-domain antibody (sdAb) on these benzaldehyde-decorated nanoparticles is achieved by oxime bond formation. These nanoconjugates can specifically bind EGFR (modified ELISA) and have enhanced uptake over nonfunctionalized controls in EGFR-positive HeLa cells. Encapsulation of rhodamine 6G dye and its dispersion upon cellular uptake, consistent with nanoparticle stability loss at pH < 5.7, prove their ability to facilitate triggered release in endosomal compartments and highlight their potential for use as next-generation antibody-drug nanoconjugates for therapeutic drug delivery.

Comparison of methicillin-resistant Staphylococcus pseudintermedius adherence to 2 canine limb salvage endoprosthesis implants.

The objective of our study was to compare adhesion of methicillin-resistant Staphylococcus pseudintermedius (MRSP) to stainless steel (SS) and to tantalum (TA) canine limb salvage endoprosthesis implants in an in vitro experimental study. The median of the mean log10 colony forming units/mL for adherent MRSP was 4.96 (range: 4.63 to 6.33) for the TA endoprosthesis and 4.31 (range: 3.86 to 5.05) for the SS endoprosthesis (P = 0.009). Although the trabecular and porous design of the TA endoprosthesis provides mechanical benefits over the SS endoprosthesis, it may increase the risk of developing infection due to higher levels of bacterial adherence.

Comparaison de l'adhérence deStaphylococcus pseudintermediusrésistant à la méthicilline à deux implants d'endoprothèse pour sauver des membres canins. L'objectif de notre étude consistait à comparer l'adhésion de Staphylococcus pseudintermedius résistant à la méthicilline (MRSP) à des implants d'endoprothèse en acier inoxydable (AI) et en tantale (TA) pour sauver des membres canins lors d'une étude expérimentale in vitro. La médiane des moyennes en log10 des unités formatrices de colonies/mL pour le MRSP adhérent était de 4,96 (écart : de 4,63 à 6,33) pour l'endoprothèse TA et 4,31 (écart : de 3,86 à 5,05) pour l'endoprothèse d'AI (P = 0,009). Même si la conception trabéculaire et poreuse de l'endoprothèse de TA offre des avantages mécaniques par rapport à l'endoprothèse d'AI, elle peut accroître le risque de développer une infection en raison des taux supérieurs d'adhérence bactérienne.(Traduit par Isabelle Vallières).

Characterization and Immunomodulatory Effects of Canine Adipose Tissue- and Bone Marrow-Derived Mesenchymal Stromal Cells.

BACKGROUND: Mesenchymal stromal cells (MSC) hold promise for both cell replacement and immune modulation strategies owing to their progenitor and non-progenitor functions, respectively. Characterization of MSC from different sources is an important and necessary step before clinical use of these cells is widely adopted. Little is known about the biology and function of canine MSC compared to their mouse or human counterparts. This knowledge-gap impedes development of canine evidence-based MSC technologies. HYPOTHESIS AND OBJECTIVES: We hypothesized that canine adipose tissue (AT) and bone marrow (BM) MSC (derived from the same dogs) will have similar differentiation and immune modulatory profiles. Our objectives were to evaluate progenitor and non-progenitor functions as well as other characteristics of AT- and BM-MSC including 1) proliferation rate, 2) cell surface marker expression, 3) DNA methylation levels, 4) potential for trilineage differentiation towards osteogenic, adipogenic, and chondrogenic cell fates, and 5) immunomodulatory potency in vitro. RESULTS: 1) AT-MSC proliferated at more than double the rate of BM-MSC (population doubling times in days) for passage (P) 2, AT: 1.69, BM: 3.81; P3, AT: 1.80, BM: 4.06; P4, AT: 2.37, BM: 5.34; P5, AT: 3.20, BM: 7.21). 2) Canine MSC, regardless of source, strongly expressed cell surface markers MHC I, CD29, CD44, and CD90, and were negative for MHC II and CD45. They also showed moderate expression of CD8 and CD73 and mild expression of CD14. Minor differences were found in expression of CD4 and CD34. 3) Global DNA methylation levels were significantly lower in BM-MSC compared to AT-MSC. 4) Little difference was found between AT- and BM-MSC in their potential for adipogenesis and osteogenesis. Chondrogenesis was poor to absent for both sources in spite of adding varying levels of bone-morphogenic protein to our standard transforming growth factor (TGF-ß3)-based induction medium. 5) Immunomodulatory capacity was equal regardless of cell source when tested in mitogen-stimulated lymphocyte reactions. Priming of MSC with pro-inflammatory factors interferon-gamma and/or tumour necrosis factor did not increase the lymphocyte suppressive properties of the MSC compared to untreated MSC. CONCLUSIONS/SIGNIFICANCE: No significant differences were found between AT- and BM-MSC with regard to their immunophenotype, progenitor, and non-progenitor functions. Both MSC populations showed strong adipogenic and osteogenic potential and poor chondrogenic potential. Both significantly suppressed stimulated peripheral blood mononuclear cells. The most significant differences found were the higher isolation success and proliferation rate of AT-MSC, which could be realized as notable benefits of their use over BM-MSC.

Internal hemipelvectomy for treatment of obstipation secondary to pelvic malunion in 3 cats.

Pelvic fractures are a common injury in cats, and both surgical and conservative management approaches have been described. One of the major complications of pelvic fractures managed conservatively is narrowing of the pelvic canal. Severe pelvic canal narrowing can result in constipation and subsequent megacolon. The purpose of this case series is to describe the long-term outcome for 3 cats with obstipation treated with internal hemipelvectomy because of megacolon secondary to pelvic canal narrowing after conservative management. All cats had a good functional outcome of the affected limb. Two cats required ongoing medical management for recurrent constipation. Overall, internal hemipelvectomy offers good long-term limb function; however, its success in relieving clinical signs of constipation requires additional research.

Hémipelvectomie interne pour le traitement de la constipation opiniâtre secondaire à un cal vicieux pelvien chez 3 chats. Les fractures pelviennes sont une blessure commune chez les chats et les approches chirurgicales et prudentes ont toutes deux été décrites. L'une des complications majeures des fractures pelviennes gérées de manière prudente consiste à raccourcir le canal pelvien. Un rétrécissement sévère du canal pelvien peut se traduire par la constipation et un mégacôlon subséquent. Le but de cette série de cas consiste à décrire le résultat à long terme pour 3 chats souffrant de constipation opiniâtre traitée par une hémipelvectomie interne en raison d'un mégacôlon secondaire au rétrécissement du canal pelvien après une gestion prudente. Tous les chats ont obtenu de bons résultats fonctionnels du membre affecté. Deux chats ont nécessité une gestion médicale permanente pour une constipation opiniâtre. En général, l'hémipelvectomie interne offre une bonne fonction du membre, mais son succès dans le soulagement des signes cliniques de la constipation exige de la recherche additionnelle.(Traduit par Isabelle Vallières).