Accuracy of pin placement in the canine thoracolumbar spine using a free-hand probing technique versus 3D-printed patient-specific drill guides: An ex-vivo study.

OBJECTIVE To compare pin placement accuracy, intraoperative technique deviations, and duration of pin placement for pins placed by free-hand probing (FHP) or 3D-printed drill guide (3DPG) technique. SAMPLE POPULATION Four greyhound cadavers. METHODS Computed tomography (CT) examinations from T6-sacrum were obtained for determination of optimal pin placement and 3DPG creation. Two 3.2/2.4-mm positive profile pins were inserted per vertebra, one left and one right from T7-L7 (FHP [n = 56]; 3DPG [n = 56]) by one surgeon and removed for repeat CT. Duration of pin placement and intraoperative deviations (unanticipated deviations from planned technique) were recorded. Pin tracts were graded by two blinded observers using modified Zdichavsky classification. Descriptive statistics were used. RESULTS A total of 54/56 pins placed with 3DPGs were assigned grade I (optimal placement) compared with 49/56 pins using the FHP technique. A total of 2/56 pins placed with 3DPGs and 3/56 pins using the FHP technique were assigned grade IIa (partial medial violation). A total of 4/56 pins placed using the FHP technique were assigned grade IIIa (partial lateral violation). No pins were assigned grade IIb (full medial violation). Intraoperative technique deviations occurred with 6/56 pins placed using the FHP technique and no pins with 3DPGs. Overall, pins were placed faster (mean ± SD 2.6 [1.3] vs. 4.5 [1.8] min) with 3DPGs. CONCLUSIONS Both techniques were accurate for placement of spinal fixation pins. The 3DPG technique may decrease intraoperative deviations and duration of pin placement. CLINICAL RELEVANCE Both techniques allow accurate pin placement in the canine thoracolumbar spine. The FHP technique requires specific training and has learning curve, whereas 3DPG technique requires specific software and 3D printers

Contralateral Cruciate Survival in Dogs with Unilateral Non-Contact Cranial Cruciate Ligament Rupture

BACKGROUND: Non-contact cranial cruciate ligament rupture (CrCLR) is an important cause of lameness in client-owned dogs and typically occurs without obvious injury. There is a high incidence of bilateral rupture at presentation or subsequent contralateral rupture in affected dogs. Although stifle synovitis increases risk of contralateral CrCLR, relatively little is known about risk factors for subsequent contralateral rupture, or whether therapeutic intervention may modify this risk. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a longitudinal study examining survival of the contralateral CrCL in client-owned dogs with unilateral CrCLR in a large baseline control population (n = 380), and a group of dogs that received disease-modifying therapy with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline (n = 16), and were followed for one year. Follow-up in treated dogs included analysis of mobility, radiographic evaluation of stifle effusion and arthritis, and quantification of biomarkers of synovial inflammation. We found that median survival of the contralateral CrCL was 947 days. Increasing tibial plateau angle decreased contralateral ligament survival, whereas increasing age at diagnosis increased survival. Contralateral ligament survival was reduced in neutered dogs. Our disease-modifying therapy did not significantly influence contralateral ligament survival. Correlative analysis of clinical and biomarker variables with development of subsequent contralateral rupture revealed few significant results. However, increased expression of T lymphocyte-associated genes in the index unstable stifle at diagnosis was significantly related to development of subsequent non-contact contralateral CrCLR. CONCLUSION: Subsequent contralateral CrCLR is common in client-owned dogs, with a median ligament survival time of 947 days. In this naturally occurring model of non-contact cruciate ligament rupture, cranial tibial translation is preceded by development of synovial inflammation. However, treatment with arthroscopic lavage, intra-articular hyaluronic acid and oral doxycycline does not significantly influence contralateral CrCL survival

Effect of analgesic therapy on clinical outcome measures in a randomized controlled trial using client-owned dogs with hip osteoarthritis

BACKGROUND: Pain and impaired mobility because of osteoarthritis (OA) is common in dogs and humans. Efficacy studies of analgesic drug treatment of dogs with naturally occurring OA may be challenging, as a caregiver placebo effect is typically evident. However, little is known about effect sizes of common outcome-measures in canine clinical trials evaluating treatment of OA pain. Forty-nine client-owned dogs with hip OA were enrolled in a randomized, double-blinded placebo-controlled prospective trial. After a 1 week baseline period, dogs were randomly assigned to a treatment (ABT-116 – transient receptor potential vanilloid 1 (TRPV1) antagonist, Carprofen – non-steroidal anti-inflammatory drug (NSAID), Tramadol - synthetic opiate, or Placebo) for 2 weeks. Outcome-measures included physical examination parameters, owner questionnaire, activity monitoring, gait analysis, and use of rescue medication. RESULTS: Acute hyperthermia developed after ABT-116 treatment (P < 0.001). Treatment with carprofen (P ≤ 0.01) and tramadol (P ≤ 0.001) led to improved mobility assessed by owner questionnaire. Nighttime activity was increased after ABT-116 treatment (P = 0.01). Kinetic gait analysis did not reveal significant treatment effects. Use of rescue treatment decreased with treatment in the ABT-116 and Carprofen groups (P < 0.001). Questionnaire score and activity count at the end of treatment were correlated with age, clinical severity at trial entry, and outcome measure baseline status (S(R) ≥ ±0.40, P ≤ 0.005). Placebo treatment effects were evident with all variables studied. CONCLUSION: Treatment of hip OA in client-owned dogs is associated with a placebo effect for all variables that are commonly used for efficacy studies of analgesic drugs. This likely reflects caregiver bias or the phenomenon of regression to the mean. In the present study, outcome measures with significant effects also varied between groups, highlighting the value of using multiple outcome measures, as well as an a priori analysis of effect size associated with each measure. Effect size data from the present study could be used to inform design of future trials studying analgesic treatment of canine OA. Our results suggest that analgesic treatment with ABT-116 is not as effective as carprofen or tramadol for treatment of hip arthritis pain in client-owned dogs

Summary of two-way ANOVA results for load-induced periosteal bone formation in CGRPα and CGRPβ wildtype and knockout mice.

<p><b>Note</b>: NS - not significant. <i>P</i> values<0.15 are also reported. Treatments were Sham, Load, or Block + Load.</p><p>Summary of two-way ANOVA results for load-induced periosteal bone formation in CGRPα and CGRPβ wildtype and knockout mice.</p

Role of Calcitonin Gene-Related Peptide in Functional Adaptation of the Skeleton

<div><p>Peptidergic sensory nerve fibers innervating bone and periosteum are rich in calcitonin gene-related peptide (CGRP), an osteoanabolic neurotransmitter. There are two CGRP isoforms, CGRPα and CGRPβ. Sensory fibers are a potential means by which the nervous system may detect and respond to loading events within the skeleton. However, the functional role of the nervous system in the response of bone to mechanical loading is unclear. We used the ulna end-loading model to induce an adaptive modeling response in CGRPα and CGRPβ knockout mouse lines and their respective wildtype controls. For each knockout mouse line, groups of mice were treated with cyclic loading or sham-loading of the right ulna. A third group of mice received brachial plexus anesthesia (BPA) of the loaded limb before mechanical loading. Fluorochrome labels were administered at the time of loading and 7 days later. Ten days after loading, bone responses were quantified morphometrically. We hypothesized that CGRP signaling is required for normal mechanosensing and associated load-induced bone formation. We found that mechanically-induced activation of periosteal mineralizing surface in mice and associated blocking with BPA were eliminated by knockout of CGRPα signaling. This effect was not evident in CGRPβ knockout mice. We also found that mineral apposition responses to mechanical loading and associated BPA blocking were retained with CGRPα deletion. We conclude that activation of periosteal mineralizing surfaces in response to mechanical loading of bone is CGRPα-dependent <i>in</i><i>vivo</i>. This suggests that release of CGRP from sensory peptidergic fibers in periosteum and bone has a functional role in load-induced bone formation.</p></div

Relative contributions of mineralizing surface and mineral apposition rate to load-induced periosteal bone formation in CGRPα and CGRPβ wildtype and knockout mice.

<p><b>Note</b>: Ps.MS/BS - periosteal mineralizing surface; Ps.MAR - periosteal mineral apposition rate; Ps.BFR/BS - periosteal bone formation rate. Data are derived from the mean values for the right ulna, which has loaded or sham loaded depending on group assignment and represent ((Right limb Load-Right limb Sham)-Right limb Sham)*100. CGRPα mice were bred on a C57BL/6 background. CGRPβ mice were bred on a Swiss background.</p><p>Relative contributions of mineralizing surface and mineral apposition rate to load-induced periosteal bone formation in CGRPα and CGRPβ wildtype and knockout mice.</p

Load-induced periosteal bone formation responses are similar in CGRPβ wildtype and knockout mice.

<p>Overall, periosteal mineral apposition rate (Ps.MAR) in CGRPβ wildtype and knockout mice was significantly increased in the right ulna, when compared with the left ulna (<i>p</i><0.005). Few other significant treatment effects were identified. **<i>p</i><0.01; ***<i>p</i><0.001 versus left ulna in associated CGRPβ knockout mice. Sham – sham loaded group, Load – loaded group, Block + Load – Brachial plexus anesthesia treatment before loading. n = 16–20 mice/group.</p

Deletion of the CGRP gene had opposite effects on bone mineral density (BMD) in CGRPα and CGRPβ mice.

<p>BMD was decreased in CGRPα knockout mice (<i>p</i><0.05) and increased in CGRPβ knockout mice (<i>p</i> = 0.01), relative to their respective wildtype groups. In wildtype mice, BMD was decreased in Swiss background strain for the CGRPβ mice, relative to the C57BL/6 mice background strain for the CGRPα mice. C57BL/6 mice had a lower percentage body fat than Swiss mice (<i>p</i><0001). In Swiss mice, deletion of CGRPβ function was associated with increased lean body mass (<i>p</i><0.001). BMD was determined using a PIXImus densitometer, n = 5/group.</p

Adaptive periosteal bone responses in CGRPα wildtype and knockout mice are mainly influenced by changes in mineral apposition rate.

<p>Cyclic loading of the right ulna in CGRPα knockout mice, but not wild-type mice, induced significant changes in relative periosteal mineral apposition rate (Ps.rMAR). Blocking of periosteal relative mineral apposition rate (Ps.rMAR) and periosteal relative bone formation rate (Ps.rBFR/BS) by brachial plexus anesthesia (BPA) was also found in CGRPα knockout mice, but not wildtype mice. Sham – sham loaded group, Load – loaded group, Block + Load – BPA treatment before loading. n = 11–14 mice/group.</p

Fluorochome-labeled new bone formation in CGRPα wildtype and knockout mice.

<p>Cyclic loading of the right ulna in wildtype (<b>A</b>) and knockout mice (<b>B</b>) induced an adaptive response with increased periosteal bone formation (white arrows). Blocking of periosteal bone formation with responses was more evident in the CGRP<b>α</b> knockout mice. Bar = 110 µm. Cd, caudal; Cr, cranial; Lat, lateral; Med, medial. Sham – sham loaded group, Load – loaded group, Block + Load – BPA treatment before loading. n = 11–14 mice/group.</p