Performance and microbiological safety testing after multiple use cycles and hydrogen peroxide sterilization of a 5-mm vessel-sealing device.

OBJECTIVE: To evaluate the functional and microbiological safety of a single-use laparoscopic vessel-sealing device in a multiuse setting. STUDY DESIGN: Ex vivo study. SAMPLE POPULATION: Twelve 5-mm LigaSure Maryland jaw devices. METHODS: Handsets underwent repeated test cycles until failure. The handset packaging was opened, and handsets were agitated in phosphate-buffered saline (PBS). The PBS was removed, centrifuged, and submitted for culture. Canine ovariectomy was simulated on cadaveric tissue, after which vascular seal quality was evaluated by pressure testing of sealed porcine carotid arteries. The handsets were cleaned and sterilized with hydrogen peroxide gas and repackaged. RESULTS: Mean ± SD cycles to failure was 7.7 ± 2.8, with a minimum of 4 and a maximum of 12 use cycles achieved. Eleven of the 12 handsets failed by failure of handset activation after depression of the activation trigger. Only 1 handset failed to hold an adequate vascular seal under 300 mm Hg of pressure. No handset exhibited positive bacterial culture at any cycle. CONCLUSION: The sterilization method used in this study resulted in an excellent microbiological safety profile. Most of the handsets failed by activation button failure. CLINICAL SIGNIFICANCE: Under the conditions of this study, hydrogen peroxide sterilization achieved microbiological safety. Handsets can successfully be reused until activation button failure without negative effects on the vascular seal or increased risk of infection to the patient.

Strength limits in mesoscaled 3Y-TZP ceramics for micro-surgical instruments.

Micro-surgical instruments are a new application for mesoscale ceramics formed using the lost mold-rapid infiltration forming (LM-RIF) process. Instrument strength and reliability are the foremost concerns for this sensitive application. It is hypothesized that increasing grain size can improve the damage tolerance of the parts associated with the transformation toughening in the 3Y-TZP material, while retaining high strength. In this work, mesoscale bend bars (314 × 22 × 18 µm) of 3Y-TZP fabricated using the LM-RIF process were heat treated at 1400 °C for 1 h, 8 h, or 16 h, respectively, to obtain samples with different grain sizes. Strength tests were performed under three-point bending and results were evaluated using Weibull statistics. Fractographic and confocal Raman spectroscopic analyses were carried out to interpret the data. Experimental findings showed that the characteristic strength decreased with increasing grain size contrary to the damage tolerance hypothesis. An Orowan-Petch model was recalled to correlate the strength with the flaw size to grain size ratio. At fine grain sizes the strength was controlled by the flaws introduced by the LM-RIF process, whereas at large grain sizes the strength become more grain size controlled. Although larger-grained samples did have a higher propensity to transform, and thus increase toughening, exaggerated grain growth in some of the specimens tested caused an additional flaw population which led to an overall lower strength. Finally, based on the experimental observations and fracture mechanics considerations, we believe that an upper bound of ∼2.5 GPa exists for the strength of mesoscale as-fabricated 3Y-TZP ceramic parts.

Manuka honey and methylglyoxal increase the sensitivity of Staphylococcus aureus to linezolid.

The continued emergence and global spread of bacterial antibiotic resistance has fuelled the search for novel antimicrobial agents and resistance-modifying compounds. Manuka honey has both antimicrobial properties and the ability to increase the efficacy of FDA-approved antibiotic drugs. Compared to other types of honey, manuka honey contains elevated levels of methylglyoxal (MGO), a small molecule that contributes to its antibacterial activity. Manuka honey has shown particular promise for the treatment of antibiotic-resistant Gram-positive organisms such as methicillin-resistant Staphylococcus aureus. Linezolid is an oxazolidinone antibiotic used in the treatment of infections caused by a range of Gram-positive pathogens. Here, we demonstrate that manuka honey, as well as MGO in isolation, increases the sensitivity of S. aureus to linezolid in both agar diffusion and broth microdilution assays. This synergistic interaction is mediated in part by increased intracellular accumulation of linezolid in the presence of MGO. SIGNIFICANCE AND IMPACT OF THE STUDY: Manuka honey is widely recognized for its antimicrobial activity. Our study adds to the growing body of evidence that manuka honey and its active ingredient, methylglyoxal (MGO), can also function as antibiotic adjuvants. In this study, we provide the first report of synergy between MGO and linezolid against Staphylococcus aureus. Both manuka honey and purified MGO significantly increased the sensitivity of S. aureus to linezolid.

Use of 3D printer technology to facilitate surgical correction of a complex vascular anomaly with esophageal entrapment in a dog.

A 10 week old female intact Staffordshire terrier was presented with a total of five congenital cardio-thoracic vascular anomalies consisting of a patent ductus arteriosus (PDA) with an aneurysmic dilation, pulmonic stenosis, persistent right aortic arch, aberrant left subclavian artery and persistent left cranial vena cava. These abnormalities were identified with a combination of echocardiogram and computed tomography angiography (CTA). The abnormalities were associated with esophageal entrapment, regurgitation, and volume overload of the left heart with left atrial and ventricular enlargement. A 2 cm diameter aneurysmic dilation at the junction of the PDA, right aortic arch and aberrant left subclavian artery presented an unusual surgical challenge and precluded simple circumferential ligation and transection of the structure. A full scale three dimensional model of the heart and vasculature was constructed from the CTA and plasma sterilized. The model was used preoperatively to facilitate surgical planning and enhance intraoperative communication and coordination between the surgical and anesthesia teams. Intraoperatively the model facilitated spatial orientation, atraumatic vascular dissection, instrument sizing and positioning. A thoracoabdominal stapler was used to close the PDA aneurysm prior to transection. At the four-month postoperative follow-up the patient was doing well. This is the first reported application of new imaging and modeling technology to enhance surgical planning when approaching correction of complex cardiovascular anomalies in a dog.

Leukemia-cell proliferation and disease progression in patients with early stage chronic lymphocytic leukemia.

The clinical course of patients with recently diagnosed early stage chronic lymphocytic leukemia (CLL) is highly variable. We examined the relationship between CLL-cell birth rate and treatment-free survival (TFS) in 97 patients with recently diagnosed, Rai stage 0-II CLL in a blinded, prospective study, using in vivo 2H2O labeling. Birth rates ranged from 0.07 to 1.31% new cells per day. With median follow-up of 4.0 years, 33 subjects (34%) required treatment by NCI criteria. High-birth rate was observed in 44% of subjects and was significantly associated with shorter TFS, unmutated IGHV status and expression of ZAP70 and of CD38. In multivariable modeling considering age, gender, Rai stage, expression of ZAP70 or CD38, IGHV mutation status and FISH cytogenetics, only CLL-cell birth rate and IGHV mutation status met criteria for inclusion. Hazard ratios were 3.51 (P=0.002) for high-birth rate and 4.93 (P<0.001) for unmutated IGHV. The association between elevated birth rate and shorter TFS was observed in subjects with either mutated or unmutated IGHVs, and the use of both markers was a better predictor of TFS than either parameter alone. Thus, an increased CLL birth rate in early stage disease is a strong predictor of disease progression and earlier treatment.

Surgical treatment of dorsal hemivertebrae associated with kyphosis by spinal segmental stabilisation, with or without decompression.

This retrospective case series examined the effectiveness of spinal segmental stabilisation, with or without decompression, in nine dogs with neurological deficits associated with dorsal hemivertebrae. Data on signalment, preoperative neurological status, imaging findings, surgical techniques and outcome were evaluated. All cases occurred in young or adult, small-breed dogs with neurological signs ranging from progressive moderate pelvic limb ataxia to non-ambulatory paraparesis. Six dogs also showed urinary and faecal incontinence. In each dog, one or more dorsal thoracic hemivertebra(e) were detected by radiography and MRI. In all dogs, hemivertebra(e) were associated with kyphosis and reduced vertebral canal diameter. All dogs were surgically managed with spinal segmental stabilisation, using Steinmann pins and orthopaedic wires and/or sutures attached to the spinous processes. Three dogs also underwent additional decompressive surgery. Post-operative follow-up ranged from 1.5 to 5.5 years. Immediate or delayed post-operative complications occurred in three dogs, including implant migration or loosening. Eight dogs showed long-term gait improvement, with resolution of incontinence if previously present. At 2-6 years post-surgery, four dogs were neurologically normal, three had mild residual ataxia, one had moderate ambulatory paraparesis, and one dog relapsed 3.5 years after surgery, resulting in severe paraparesis. Spinal segmental stabilisation techniques, with or without decompression, can result in satisfactory outcomes in small dogs with hemivertebrae and mild to moderate neurological signs. Further adaptations might be required to avoid implant loosening and allow continued growth in immature dogs.

A review of local antibiotic implants and applications to veterinary orthopaedic surgery.

In the face of increasing incidence of multi-drug resistant implant infections, local antibiotic modalities are receiving increased attention for both infection prophylaxis and treatment. Local antibiotic therapy that achieves very high antibiotic drug concentrations at the site of the implant may represent an avenue for treatment of biofilm-forming bacterial pathogens. Randomized controlled trials in human patients have demonstrated an infection risk reduction when antibiotic-impregnated cement is used for infection prophylaxis in implanted joint prostheses, and when a gentamicin-impregnated collagen sponge is used for infection prophylaxis in midline sternotomy. The other modalities discussed have for the most part yet to be evaluated in randomized controlled trials in veterinary or human patients. In general, the in vivo pharmacokinetics and appropriate dosing profiles for local antibiotic modalities have yet to be elucidated. Toxicity is possible, and attention to the dose applied is warranted.

Long bone fracture as a complication following external skeletal fixation: 11 cases.

OBJECTIVES: To report on a series of dogs and cats with long bone fractures that occurred as a direct consequence of linear external skeletal fixation (ESF) application. METHODS: Retrospective study. Data from the medical records and radiographs of canine (n = 4) and feline (n = 7) cases were collected from three referral and three first opinion practices in the UK (1999 to 2011). RESULTS: Long bone fractures occurred following the application of linear ESF either while the ESF was in situ or after removal. All fractures occurred through either a pin tract or an empty drill hole. Pins associated with ESF-related fracture tended to be in the higher end of the recommended size range. The majority of cases had additional complicating factors such as multiple injuries, revision surgery, poor owner compliance with postoperative exercise restriction and the presence of empty drill holes. CLINICAL SIGNIFICANCE: In cases with features that could complicate outcome, careful attention should be paid to recommendations for ESF application. Leaving empty drill holes is suboptimal. The retrospective nature of the study, low numbers of, and diversity amongst, cases should be taken into consideration when interpreting the results from this study.

Distribution and persistence of topical clotrimazole after sinus infusion in normal canine cadavers.

OBJECTIVES: To determine the in vitro persistence of clotrimazole 1% cream in the canine frontal sinus and to evaluate the distribution of clotrimazole solution over the sino-nasal mucosa using a previously described surgical treatment protocol for canine nasal aspergillosis. METHODS: Two canine skulls were used to monitor the persistence of clotrimazole cream in the lateral frontal sinus at 37°C. The distribution of irrigation solution around the frontal sinus compartments and nasal cavity was determined using six canine cadaver heads by trephining either the lateral or both the lateral and rostral compartments of the frontal sinus. Stain was added to the sinus irrigation solution before visually inspecting the sagittally sectioned heads. RESULTS: Clotrimazole cream persisted in the frontal sinus for at least 96 hours. The nasal cavity mucosa was completely stained in 8 of 12 sides and almost completely stained in the remaining 4 of 12 sides. Flushing irrigation solution through the lateral compartment of the frontal sinus resulted in inadequate staining of the rostral compartment but medicating both the lateral and rostral compartments resulted in complete coating of all frontal sinus mucosa in eight of eight sides. CLINICAL SIGNIFICANCE: Clotrimazole cream has the potential to be retained in the frontal sinus for several days and is distributed effectively in normal canine cadavers. Medicating both the rostral and lateral compartments of the frontal sinus may be indicated in some clinical cases.

Salter-Harris type III fractures of the distal humerus in two dogs.

Salter-Harris type III fractures of the distal humerus in a four-month-old male Labrador Retriever and a male crossbreed dog (estimated to be 3.5-months-old) are reported. Both fractures were treated with open reduction and interfragmentary compression by lag screw fixation. Both fractures healed and full limb use was regained at four weeks postoperatively. The occurrence of this unusual fracture type may be related to the physeal closure pattern of the distal humeral physis, and a different mechanism of injury compared to the more common Salter-Harris type IV fracture seen in this region.

Low central venous oxygen saturation is associated with increased mortality in critically ill dogs.

OBJECTIVES: To investigate relationships between central venous oxygen saturation (ScvO(2)) and survival to hospital discharge in dogs. Central venous oxygen saturation is an accessible measure of the balance between systemic oxygen delivery and consumption. METHODS: Prospective observational cohort study, enrolling 126 client-owned dogs with central venous catheters. Central venous oxygen saturation was measured over the 24 hours following intensive care unit admission. Poor outcome was defined as death or euthanasia performed for moribund status. Regression analysis identified independent predictors of non-survival and physiologic parameters associated with central venous oxygen saturation. Area under the receiver operator curve analysis identified a cut-off point of central venous oxygen saturation, below which central venous oxygen saturation decrease was associated with increased mortality risk. RESULTS: Mortality risk was 30·9%. Low central venous oxygen saturation was associated with poor outcome (P<0·05). Area under the receiver operator curve analysis selected a central venous oxygen saturation of 68% as the point below which a fall in central venous oxygen saturation was associated with increased mortality risk. For each 10% drop in central venous oxygen saturation below 68%, odds of non-survival increased by 2·66 times (P=0·0002, 95% confidence interval of odds ratio=1·45 to 4·85). Central venous oxygen saturation was equivalent to lactate in predicting non-survival. Predictors of central venous oxygen saturation (packed cell volume, mean arterial blood pressure, fever, % arterial haemoglobin saturation as measured by pulse oximeter) were consistent with hypothesised physiologic mechanisms. CLINICAL SIGNIFICANCE: Central venous oxygen saturation was a strong mortality predictor. Further work is needed to determine if therapy targeting central venous oxygen saturation can reduce mortality in canine intensive care unit patients.

The Feline Acute Patient Physiologic and Laboratory Evaluation (Feline APPLE) Score: a severity of illness stratification system for hospitalized cats.

BACKGROUND: Scores allowing objective stratification of illness severity are available for dogs and horses, but not cats. Validated illness severity scores facilitate the risk-adjusted analysis of results in clinical research, and also have applications in triage and therapeutic protocols. OBJECTIVE: To develop and validate an accurate, user-friendly score to stratify illness severity in hospitalized cats. ANIMALS: Six hundred cats admitted consecutively to a teaching hospital intensive care unit. METHODS: This observational cohort study enrolled all cats admitted over a 32-month period. Data on interventional, physiological, and biochemical variables were collected over 24 hours after admission. Patient mortality outcome at hospital discharge was recorded. After random division, 450 cats were used for logistic regression model construction, and data from 150 cats for validation. RESULTS: Patient mortality was 25.8%. Five- and 8-variable scores were developed. The 8-variable score contained mentation score, temperature, mean arterial pressure (MAP), lactate, PCV, urea, chloride, and body cavity fluid score. Area under the receiver operator characteristic curve (AUROC) on the construction cohort was 0.91 (95% CI, 0.87-0.94), and 0.88 (95% CI, 0.84-0.96) on the validation cohort. The 5-variable score contained mentation score, temperature, MAP, lactate, and PCV. AUROC on the construction cohort was 0.83 (95% CI, 0.79-0.86), and 0.76 (95% CI, 0.72-0.84) on the validation cohort. CONCLUSIONS AND CLINICAL IMPORTANCE: Two scores are presented enabling allocation of an accurate and user-friendly illness severity measure to hospitalized cats. Scores are calculated from data obtained over the 1st 24 hours after admission, and are diagnosis-independent. The 8-variable score predicts outcome significantly better than does the 5-variable score.

Risk factors for medial meniscal injury in association with cranial cruciate ligament rupture.

OBJECTIVES: To determine the significant risk factors for medial meniscal injury in naturally occurring cranial cruciate ligament rupture and to quantify the risk using multivariate analysis. METHODS: A retrospective case control study was performed of dogs that had undergone surgery for cranial cruciate ligament rupture. Data recorded included patient signalment (age, breed and sex), the duration of the lameness, the extent of the cranial cruciate ligament rupture (complete or partial) and the condition of the medial meniscus. Logistic regression was used to analyse the relationship between these variables and tears in the medial meniscus. RESULTS: One hundred and sixty-one of 443 stifles (36·3%) in 366 dogs had a medial meniscal tear. The risk of a medial meniscal tear was increased by 12·9 times in association with complete cranial cruciate ligament rupture (OR 12·9; 95% CI 6·8 to 24·2), by approximately 2·6% for each additional week of lameness (OR 1·026; 95% CI 1·009 to 1·043) and by approximately 1·4% for each additional kilogram of bodyweight (OR 1·014; 95% CI 1·000 to 1·028). Golden retrievers and Rottweilers were at increased risk and West Highland white terriers were at reduced risk of medial meniscal tears compared with Labrador retrievers. CLINICAL SIGNIFICANCE: To minimise the risk of medial meniscal tears, surgical stabilisation should not be unnecessarily delayed.

The acute patient physiologic and laboratory evaluation (APPLE) score: a severity of illness stratification system for hospitalized dogs.

BACKGROUND: Objective risk stratification models are used routinely in human critical care medicine. Applications include quantitative and objective delineation of illness severity for patients enrolled in clinical research, performance benchmarking, and protocol development for triage and therapeutic management. OBJECTIVE: To develop an accurate, validated, and user-friendly model to stratify illness severity by mortality risk in hospitalized dogs. ANIMALS: Eight hundred and ten consecutive intensive care unit (ICU) admissions of dogs at a veterinary teaching hospital. METHODS: Prospective census cohort study. Data on 55 management, physiological, and biochemical variables were collected within 24 hours of admission. Data were randomly divided, with 598 patient records used for logistic regression model construction and 212 for model validation. RESULTS: Patient mortality was 18.4%. Ten-variable and 5-variable models were developed to provide both a high-performance model and model maximizing accessibility, while maintaining good performance. The 10-variable model contained creatinine, WBC count, albumin, SpO(2) , total bilirubin, mentation score, respiratory rate, age, lactate, and presence of free fluid in a body cavity. Area under the receiver operator characteristic (AUROC) on the construction data set was 0.93, and on the validation data set was 0.91. The 5-variable model contained glucose, albumin, mentation score, platelet count, and lactate. AUROC on the construction data set was 0.87, and on the validation data set was 0.85. CONCLUSIONS AND CLINICAL IMPORTANCE: Two models are presented that enable allocation of an accurate and user-friendly illness severity index for dogs admitted to an ICU. These models operate independent of primary diagnosis, and have been independently validated.

Relationship between pharyngeal conformation and otitis media with effusion in Cavalier King Charles spaniels.

Otitis media with effusion (OME) is a common incidental finding in otherwise normal Cavalier King Charles spaniels (CKCS). In this study, measurements made on MRI were used to determine whether there was an association between OME and brachycephalic conformation. The results confirm that association and also demonstrate that, in CKCS, greater thickness of the soft palate and reduced nasopharyngeal aperture are significantly associated with OME. These results suggest that auditory tube dysfunction and OME may represent a previously overlooked consequence of brachycephalic conformation in dogs.

Illness severity scores in veterinary medicine: what can we learn?

Illness severity scores are gaining increasing popularity in veterinary medicine. This article discusses their applications in both clinical medicine and research, reviews the caveats pertaining to their use, and discusses some of the issues that arise in appropriate construction of a score. Illness severity scores can be used to decrease bias and confounding and add important contextual information to research by providing a quantitative and objective measure of patient illness. In addition, illness severity scores can be used to benchmark performance, and establish protocols for triage and therapeutic management. Many diagnosis-specific and diagnosis-independent veterinary scores have been developed in recent years. Although score use in veterinary research is increasing, the scores available are currently underutilized, particularly in the context of observational studies. Analysis of treatment effect while controlling for illness severity by an objective measure can improve the validity of the conclusions of observational studies. In randomized trials, illness severity scores can be used to demonstrate effective randomization, which is of particular utility when group sizes are small. The quality of veterinary scoring systems can be improved by prospective multicenter validation. The prevalence of euthanasia in companion animal medicine poses a unique challenge to scores based on a mortality outcome.

Cardiac myxosarcoma with adrenal adenoma and pituitary hyperplasia resembling Carney complex in a dog.

A 9-year-old female Golden Retriever was presented with an acute onset of progressive respiratory distress. Echocardiography revealed a left atrial mass that limited blood flow from the pulmonary veins. The pathological evaluation revealed a left atrial ossifying myxosarcoma, bilateral adrenocortical adenomas, multifocal pituitary hyperplasia with expression of adrenocorticotrophic hormone, and multiple pituitary Rathke's cleft cysts. These pathologic findings are similar to those described in Carney complex, a familial human syndrome characterized by cardiac myxoma and extracardiac tumors associated with mutations in the protein kinase A regulator gene PRKAR1A. Mutations were not detected in PRKAR1A exons in the present case.

Gastrointestinal foreign bodies in dogs and cats: a retrospective study of 208 cases.

OBJECTIVES: To establish predilection sites of obstruction and to investigate clinical factors associated with a poor outcome. METHODS: A retrospective study of 208 consecutive cases over a 48-month period from first-opinion practice. RESULTS: Overall, 91 per cent of cases recovered with higher survival rates from discrete foreign bodies (94 per cent in dogs and 100 per cent in cats) as opposed to linear foreign bodies (80 per cent in dogs and 63 per cent in cats). English bull terriers, springer spaniels, Staffordshire bull terriers, Border collies and Jack Russell terriers were over-represented. In dogs, 63 per cent of obstructions occurred in the jejunum but foreign objects were encountered at all points along the gastrointestinal tract. A longer duration of clinical signs, the presence of a linear foreign body and multiple intestinal procedures were associated with significantly increased mortality. Neither the degree of obstruction (partial or complete) nor the location of the foreign body was shown to have a significant influence on survival. CLINICAL SIGNIFICANCE: Prompt presentation, diagnosis and surgical intervention improve the outcome of gastrointestinal obstruction by foreign bodies. At surgery, the minimal number of intestinal procedures should be performed to restore the integrity of the alimentary tract.

The efficacy of small cell foundation as a varroa mite (Varroa destructor) control.

Due to a continuing shift toward reducing/minimizing the use of chemicals in honey bee colonies, we explored the possibility of using small cell foundation as a varroa control. Based on the number of anecdotal reports supporting small cell as an efficacious varroa control tool, we hypothesized that bee colonies housed on combs constructed on small cell foundation would have lower varroa populations and higher adult bee populations and more cm(2) brood. To summarize our results, we found that the use of small cell foundation did not significantly affect cm(2) total brood, total mites per colony, mites per brood cell, or mites per adult bee, but did affect adult bee population for two sampling months. Varroa levels were similar in all colonies throughout the study. We found no evidence that small cell foundation was beneficial with regard to varroa control under the tested conditions in Florida.

NK resistance of tumor cells from multiple myeloma and chronic lymphocytic leukemia patients: implication of HLA-G.

Exploiting the antitumor effect of natural killer (NK) cells has regained interest in light of data from preclinical and clinical work on the potential of alloreactive NK cells. Multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) represent the two most prevalent adult hematological malignancies in the western hemisphere. To evaluate the role of NK cells in the immune surveillance and their therapeutic potential for CLL and MM, tumor cell susceptibility to NK-mediated killing was investigated. Results show relative resistance of tumor cells from CLL as well as MM (73 and 70% of the patients, respectively) to NK-mediated killing. To gain insight into molecular mechanisms of this resistance, the expression of the tolerogenic HLA-G molecule in CLL and MM and its relevance to susceptibility to NK-mediated killing were investigated. HLA-G transcript was found in tumor cells from 89% (n=19) of CLL and 100% (n=9) of MM patients examined. HLA-G1 surface expression was observed in CLL and was very low or undetectable in MM. Notably, blocking of HLA-G1 with specific antibody on CLL samples increased their susceptibility to NK-mediated killing, demonstrating that HLA-G participates in protecting CLL cells from NK-mediated killing and may thus contribute to their immune escape in vivo.