Sensitivity and specificity of microRNA-122 for liver disease in dogs.

BACKGROUND: Current tests for diagnosing liver disease in dogs are sub-optimal. MicroRNA-122 (miR-122) is a sensitive and specific biomarker of liver injury in humans and rodents. Circulating miR-122 could have utility in identifying dogs with liver disease. OBJECTIVE: Establish the reference interval for miR-122 in healthy dogs and determine performance in a range of dog breeds with liver disease and control animals with non-liver disease. ANIMALS: Stored serum from 120 healthy dogs, 100 dogs with non-liver diseases, and 30 dogs with histologically confirmed liver disease was analyzed. METHODS: Retrospective study. Medical records of dogs with liver disease, non-liver disease and healthy dogs were reviewed. Serum miR-122 concentrations were measured by PCR and compared with the characteristics of the dogs and their conventional clinical measurements. RESULTS: In healthy dogs the 2.5th, 50th, and 97.5th quartiles of miR-122 were 110 (90% CI 80-114), 594 (505-682), and 3312 (2925-5144) copies/µL, respectively. There was no difference between healthy dogs and dogs with non-liver disease (median ± IQR: healthy dogs 609 [327-1014] copies/µL; non-liver disease 607 [300-1351] copies/µL). miR-122 was higher in dogs with liver disease (11 332 [4418-20 520] copies/µL, P < .001 compared to healthy dogs). miR-122 identified dogs with liver disease with high accuracy (receiver operating characteristic area under curve for comparison with healthy dogs: 0.93 [95% CI 0.86-0.99]). The upper limit of normal for healthy dogs (3312 copies/µL) had a sensitivity of 77% and specificity of 97% for identifying liver disease. CONCLUSION AND CLINICAL IMPORTANCE: Liver disease can be sensitively and specifically diagnosed in dogs by measurement of miR-122.

Attending a social event and consuming alcohol is associated with changes in serum microRNA: a before and after study in healthy adults.

PURPOSE: Circulating microRNAs represent a reservoir for biomarker discovery. Our objective was to profile the change in human circulating microRNA associated with recreational use of alcohol at a social event. MATERIAL AND METHODS: Blood was collected from healthy volunteers (N = 16) before and after recreational consumption of alcohol (ethanol). Biochemistry, hematology and ethanol measurements were performed. The change in the serum small RNA fraction was quantified by RNA sequencing. RESULTS: Blood ethanol was undetectable at study entry in all subjects [<10 mg/dL]. After consuming alcohol the median concentration was 89 mg/dL [IQR: 71-138. Min-max 20-175]. There were no changes in biochemistry and hematology parameters. Serum RNA sequencing identified 1371 small RNA species (1305 microRNAs). There were significant increases [adjusted p-value <0.05, fold increase 2 or more] in 265 microRNAs, around a fifth of the total [median fold increase 2.3 [IQR: 2.1-2.5; Max: 3.7]]. miR-185-5p decreased following alcohol exposure [adjusted p-value <0.05, fold decrease 2 or more]. CONCLUSIONS: The microRNA composition of human serum is dynamic and environmental factors may have a significant impact. Within its context of use the fold change 'signal' of a microRNA must be large enough to negate the risk of false results due to background 'noise'.

Scaphoid screw fixation perpendicular to the fracture plane: Comparing volar and dorsal approaches.

INTRODUCTION: To percutaneously fixate a midwaist scaphoid fracture, both volar and dorsal approaches are considered valid options although they may have different screw insertion angles relative to the scaphoid fracture plane influencing fixation stability. In this virtual simulation study, we investigated the accessibility of placing a screw perpendicularly to the fracture plane in transverse and horizontal oblique scaphoid midwaist fracture models and compared standard volar and dorsal approaches. MATERIAL AND METHODS: Computed tomography scans of 38 healthy wrists were used to obtain virtual 3-dimensional wrist models in flexion and extension. In case the trapezium in volar approach or the distal radius in dorsal approach obstructed the screw axis perpendicular to the fracture plane, an alternative non-obstructed screw axis was chosen as close as possible to the perpendicular axis. The deviation angle between the best possible non-obstructed screw placement and true perpendicular screw placement was quantified. RESULTS: For transverse fractures, the average deviation angle (±standard deviation) was 8° (±5°) in volar approach, and 0° (±0°) in dorsal approach. For horizontal oblique fractures, these angles were 40° (±6°) and 14° (±8°), respectively. DISCUSSION: In our simulations, compared to the volar approach, the dorsal approach provided the most precise screw placement perpendicular to the fracture plane, with the largest differences for horizontal oblique fractures. When taken in addition to screw purchase, thread engagement and protrusion risk, information about screw orientation may help surgeons in deciding between percutaneous approaches in scaphoid surgery on which there is currently no consensus. LEVEL OF EVIDENCE: N/A.

Comparing radial styloid size between osteoarthritic and healthy wrists: a pathoanatomical three-dimensional study.

Radial styloid pointing due to spur formation is considered an early sign of osteoarthritis, but is sometimes difficult to distinguish from normal anatomic variation. In this pathoanatomical study we used three-dimensional imaging techniques to evaluate quantitatively whether the styloid size is larger in wrists with scaphoid non-union than in healthy wrists. We compared these findings with duration of the non-union and with the scaphoid non-union advanced collapse classification, which was based on radiographic assessment of the general level of wrist osteoarthritis. In 31 patients, the injured styloid was consistently larger than the contralateral healthy styloid. In 74% of the patients this pathoanatomical difference (maximum 5 mm) exceeded anatomical left-to-right variation in styloid size (maximum 2 mm), indicating significant pointing. Increased styloid pointing was associated with older non-unions, and with more severe osteoarthritis. Three-dimensional styloid pointing analysis is an objective method to assess osteoarthritic progression. Combining traditional qualitative evaluation and quantitative measurements may improve the classification of wrist osteoarthritis. LEVEL OF EVIDENCE: IV.

Analysis of deformity in scaphoid non-unions using two- and three-dimensional imaging.

UNLABELLED: Pre-operative assessment of the deformity in scaphoid non-unions influences surgical decision-making. To characterize deformity, we used three-dimensional computed tomographic modelling in 28 scaphoid non-unions, and quantified bone loss, dorsal osteophyte volume and flexion deformity. We further related these three-dimensional parameters to the intrascaphoid and capitate-lunate angles, and stage of scaphoid non-union advanced collapse assessed on conventional two-dimensional images and to the chosen surgical procedure. Three-dimensional flexion deformity (mean 26°) did not correlate with intrascaphoid and capitate-lunate angles. Osteophyte volume was positively correlated with bone loss and stage of scaphoid non-union advanced collapse. Osteophyte volume and bone loss increased over time. Three-dimensional modelling enables the quantification of bone loss and osteophyte volume, which may be valuable parameters in the characterization of deformity and subsequent decision-making about treatment, when taken in addition to the clinical aspects and level of osteoarthritis. TYPE OF STUDY/LEVEL OF EVIDENCE: Level IV.