Multi-omic signatures of sarcoidosis and progression in bronchoalveolar lavage cells.

BACKGROUND: Sarcoidosis is a heterogeneous granulomatous disease with no accurate biomarkers of disease progression. Therefore, we profiled and integrated the DNA methylome, mRNAs, and microRNAs to identify molecular changes associated with sarcoidosis and disease progression that might illuminate underlying mechanisms of disease and potential biomarkers. METHODS: Bronchoalveolar lavage cells from 64 sarcoidosis subjects and 16 healthy controls were used. DNA methylation was profiled on Illumina HumanMethylationEPIC arrays, mRNA by RNA-sequencing, and miRNAs by small RNA-sequencing. Linear models were fit to test for effect of sarcoidosis diagnosis and progression phenotype, adjusting for age, sex, smoking, and principal components of the data. We built a supervised multi-omics model using a subset of features from each dataset. RESULTS: We identified 1,459 CpGs, 64 mRNAs, and five miRNAs associated with sarcoidosis versus controls and four mRNAs associated with disease progression. Our integrated model emphasized the prominence of the PI3K/AKT1 pathway, which is important in T cell and mTOR function. Novel immune related genes and miRNAs including LYST, RGS14, SLFN12L, and hsa-miR-199b-5p, distinguished sarcoidosis from controls. Our integrated model also demonstrated differential expression/methylation of IL20RB, ABCC11, SFSWAP, AGBL4, miR-146a-3p, and miR-378b between non-progressive and progressive sarcoidosis. CONCLUSIONS: Leveraging the DNA methylome, transcriptome, and miRNA-sequencing in sarcoidosis BAL cells, we detected widespread molecular changes associated with disease, many which are involved in immune response. These molecules may serve as diagnostic/prognostic biomarkers and/or drug targets, although future testing is required for confirmation.

Effect of video angle on detection of induced front limb lameness in horses.

BACKGROUND: Lameness examinations are commonly performed in equine medicine. Advancements in digital technology have increased the use of video recordings for lameness assessment, however, standardization of ideal video angle is not available yielding videos of poor diagnostic quality. The objective of this study was to evaluate the effect of video angle on the subjective assessment of front limb lameness. A randomized, blinded, crossover study was performed. Six horses with and without mechanically induced forelimb solar pain were recorded using 9 video angles including horses trotting directly away and towards the video camera, horses trotting away and towards a video camera placed to the left and right side of midline, and horses trotting in a circle with the video camera placed on the inside and outside of the circle. Videos were randomized and assessed by three expert equine veterinarians using a 0-5 point scoring system. Objective lameness parameters were collected using a body-mounted inertial sensor system (Lameness Locator®, Equinosis LLC). Interobserver agreement for subjective lameness scores and ease of grading scores were determined. RESULTS: Induction of lameness was successful in all horses. There was excellent agreement between objective lameness parameters and subjective lameness scores (AUC of the ROC = 0.87). For horses in the "lame" trials, interobserver agreement was moderate for video angle 2 when degree of lameness was considered and perfect for video angle 2 and 9 when lameness was considered as a binary outcome. All other angles had no to fair agreement. For horses in the "sound" trials, interobserver agreement was perfect for video angle 5. All other video angles had slight to moderate agreement. CONCLUSIONS: When video assessment of forelimb lameness is required, a video of the horse trotting directly towards the video camera at a minimum is recommended. Other video angles may provide supportive information regarding lameness characteristics.

Ultrasound-guided caudal cervical articular process arthrocentesis is accurate in live horses with and without arthropathy.

BACKGROUND: Cervical articular process joint (CAPJ) therapy is advocated for horses with neck disorders. Several ultrasound-guided CAPJ techniques have been described in cadaver studies with 72%-89% intra-articular injection accuracy; however, the CAPJ injection accuracy in clinical equine practice has not been extensively reported. OBJECTIVES: To describe a modified cranial approach for ultrasound-guided caudal CAPJ injections, to investigate the accuracy of this CAPJ injection technique in live horses, and to assess the effect of CAPJ injection location, laterality, operator, and radiographic CAPJ enlargement on injection accuracy. STUDY DESIGN: Retrospective case study. METHODS: Medical records of adult horses in which ultrasound-guided caudal (C4-T1) CAPJ injections were performed using a modified cranial approach between November 2006 and December 2020 were reviewed. Radiographic images of caudal cervical vertebrae were assessed by a blinded radiologist and the degree of CAPJ enlargement was graded using a previously described grading system (Rgrade 1-5b). Ultrasound-guided caudal CAPJ injection accuracy was determined by synovial fluid retrieval during an individual CAPJ injection. Statistical analysis was performed using mixed-effects multivariable logistic model to evaluate the association of CAPJ injection accuracy and the CAPJ injection location, Rgrade, laterality (right, left), and operator. RESULTS: The study included 149 horses with 177 hospital admissions. Synovial fluid was obtained from 586/658 (89.1%) caudal CAPJs using modified cranial ultrasound-guided approach for CAPJ injections. C6-C7 CAPJ injections had 7-fold higher likelihood (OR = 6.78, 95% CI: 1.67-27.52; p = 0.007) of synovial fluid retrieval compared with C4-C5 CAPJ injections. Operator, CAPJ injection side (left, right), and degree of radiographic CAPJ enlargement did not have significant effects on the success of synovial fluid retrieval from ultrasound-guided caudal CAPJ injections. MAIN LIMITATIONS: Retrospective study design. CONCLUSIONS: Intra-articular ultrasound-guided caudal CAPJ injections using a modified cranial approach can be performed accurately in live horses with and without CAPJ arthropathy.