Publications by authors named "Kim Stanley"

184 Publications

Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis.

PLoS One 2021 30;16(4):e0250944. Epub 2021 Apr 30.

Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Introduction: Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compared the concentrations of cerebrospinal fluid (CSF) and serum proteins between children who had TBM-related stroke and children with TBM without stroke.

Methods: We collected CSF and serum from 47 children consecutively admitted to the Tygerberg Academic Hospital in Cape Town, South Africa between November 2016, and November 2017, on suspicion of having TBM. A multiplex platform was used to measure the concentrations of 69 host proteins in CSF and serum from all study participants.

Results: After classification of study participants, 23 (48.9%) out of the 47 study participants were diagnosed with TBM, of which 14 (60.9%) demonstrated radiological arterial ischemic infarction. The levels of lipocalin-2, sRAGE, IP-10/ CXCL10, sVCAM-1, MMP-1, and PDGF-AA in CSF samples and the levels of D-dimer, ADAMTS13, SAA, ferritin, MCP-1/ CCL2, GDF-15 and IL-13 in serum samples were statistically different between children who had TBM-related stroke and children with TBM without stroke. After correcting for multiple testing, only the levels of sVCAM-1, MMP-1, sRAGE, and IP-10/ CXCL10 in CSF were statistically different between the two groups. CSF and serum protein biosignatures indicated stroke in children diagnosed with TBM with up to 100% sensitivity and 88.9% specificity.

Conclusion: Serum and CSF proteins may serve as biomarkers for identifying individuals with stroke amongst children diagnosed with TBM at admission and may guide us to understand the biology of stroke in TBM. This was a pilot study, and thus further investigations in larger studies are needed.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250944PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087017PMC
April 2021

Subsequent meniscal tears following tibial tuberosity advancement and tibial plateau leveling osteotomy in dogs with cranial cruciate ligament deficiency: An in vivo experimental study.

Vet Surg 2021 Jul 29;50(5):966-974. Epub 2021 Apr 29.

Department of Veterinary Surgery, College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.

Objective: To evaluate the short- and mid-term effects of tibial tuberosity advancement (TTA) and tibial plateau leveling osteotomy (TPLO) on subsequent meniscal tears.

Study Design: Experimental in vivo study.

Animals: Purpose-bred beagle dogs (n = 15).

Methods: For each dog, the cranial cruciate ligaments were transected; one limb underwent TTA and the other limb underwent TPLO. Orthopedic and radiographic examinations were performed preoperatively and at 12 and 32 weeks postoperatively. Gross evaluation of the stifle joint was performed after euthanasia at 12 (n = 10) and 32 (n = 5) weeks.

Results: Lameness scores were not different between TTA and TPLO limbs at any time point. Radiographic osteoarthritis scores of TTA stifles (1.33 ± 0.49) were higher than TPLO stifles (0.67 ± 0.49) (p = .002) at 12 weeks postoperatively, but there was no difference between groups at 32 weeks postoperatively. Subsequent medial meniscal tears occurred in 6/10 TTA stifles, and 0/10 TPLO stifles at 12 weeks postoperatively and in 5/5 TTA stifles, and 1/5 TPLO stifles at 32 weeks postoperatively. Subsequent lateral meniscal tears occurred in 4/5 TTA stifles at 32 weeks postoperatively. Medial meniscal total gross pathology score was higher in TTA than TPLO stifles. TTA stifles had more articular cartilage damage when compared with TPLO stifles at 32 weeks postoperatively.

Conclusion: In this within-dog experimental comparison, subsequent medial meniscal tears and cartilage injury was more prevalent following TTA when compared to TPLO.

Clinical Significance: In an experimental model, TPLO protects the medial meniscus and articular cartilage better than TTA in stifles with complete cranial cruciate ligament deficiency.
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http://dx.doi.org/10.1111/vsu.13648DOI Listing
July 2021

Validation and Optimization of Host Immunological Bio-Signatures for a Point-of-Care Test for TB Disease.

Front Immunol 2021 26;12:607827. Epub 2021 Feb 26.

Department of Science and Innovation - National Research Foundation (DSI-NRF) Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

The development of a non-sputum-based, point-of-care diagnostic test for tuberculosis (TB) is a priority in the global effort to combat this disease, particularly in resource-constrained settings. Previous studies have identified host biomarker signatures which showed potential, but there is a need to validate and refine these for development as a test. We recruited 1,403 adults presenting with symptoms suggestive of pulmonary TB at primary healthcare clinics in six countries from West, East and Southern Africa. Of the study cohort, 326 were diagnosed with TB and 787 with other respiratory diseases, from whom we randomly selected 1005 participants. Using Luminex technology, we measured the levels of 20 host biomarkers in serum samples which we used to evaluate the diagnostic accuracy of previously identified and novel bio-signatures. Our previously identified seven-marker bio-signature did not perform well (sensitivity: 89%, specificity: 60%). We also identified an optimal, two-marker bio-signature with a sensitivity of 94% and specificity of 69% in patients with no history of previous TB. This signature performed slightly better than C-reactive protein (CRP) alone. The cut-off value for a positive diagnosis differed for human immuno-deficiency virus (HIV)-positive and -negative individuals. Notably, we also found that no signature was able to diagnose TB adequately in patients with a prior history of the disease. We have identified a two-marker, pan-African bio-signature which is more robust than CRP alone and meets the World Health Organization (WHO) target product profile requirements for a triage test in both HIV-negative and HIV-positive individuals. This signature could be incorporated into a point-of-care device, greatly reducing the necessity for expensive confirmatory diagnostics and potentially reducing the number of cases currently lost to follow-up. It might also potentially be useful with individuals unable to provide sputum or with paucibacillary disease. We suggest that the performance of TB diagnostic signatures can be improved by incorporating the HIV-status of the patient. We further suggest that only patients who have never had TB be subjected to a triage test and that those with a history of previous TB be evaluated using more direct diagnostic techniques.
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http://dx.doi.org/10.3389/fimmu.2021.607827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952865PMC
July 2021

Higher SARS-CoV-2 seroprevalence in workers with lower socioeconomic status in Cape Town, South Africa.

PLoS One 2021 25;16(2):e0247852. Epub 2021 Feb 25.

DSI-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Department of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Background: Inequality is rife throughout South Africa. The first wave of COVID-19 may have affected people in lower socioeconomic groups worse than the affluent. The SARS-CoV-2 seroprevalence and the specificity of anti-SARS-CoV-2 antibody tests in South Africa is not known.

Methods: We tested 405 volunteers representing all socioeconomic strata from the workforce of a popular shopping and tourist complex in central Cape Town with the Abbott SARS-CoV-2 IgG assay. We assessed the association between antibody positivity and COVID-19 symptom status, medical history, and sociodemographic variables. We tested 137 serum samples from healthy controls collected in Cape Town prior to the COVID-19 pandemic, to confirm the specificity of the assay in the local population.

Results: Of the 405 volunteers tested one month after the first peak of the epidemic in Cape Town, 96(23.7%) were SARS-CoV-2 IgG positive. Of those who tested positive, 46(47.9%) reported no symptoms of COVID-19 in the previous 6 months. Seropositivity was significantly associated with living in informal housing, residing in a subdistrict with low income-per household, and having a low-earning occupation. The specificity of the assay was 98.54%(95%CI 94.82%-99.82%) in the pre-COVID controls.

Conclusions: There is a high background seroprevalence in Cape Town, particularly in people of lower socioeconomic status. Almost half of cases are asymptomatic, and therefore undiagnosed by local testing strategies. These results cannot be explained by low assay specificity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0247852PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7906413PMC
March 2021

Femorotibial joint kinematics in nine dogs treated with lateral suture stabilization for complete cranial cruciate ligament rupture.

J Am Vet Med Assoc 2021 Mar;258(5):493-501

Objective: To quantify 3-D femorotibial joint kinematics during ambulation in dogs with cranial cruciate ligament (CCL) rupture treated with lateral fabellotibial suture stabilization (LFTS).

Animals: 9 adult dogs (body weight, 15 to 35 kg [33 to 77 lb]) with unilateral complete CCL rupture.

Procedures: Digital 3-D bone models of the femur and fabellae and tibia and fibula were created from CT scans. Lateral fluoroscopic images of stifle joints were collected during treadmill walking before surgery and 6 months after LFTS. The LFTS was performed with nylon leader material secured with knots. Gait cycles were analyzed with a 3-D to 2-D image registration process. Femorotibial joint kinematics (craniocaudal translation, internal-external rotation, and flexion and extension angles) were compared among CCL-deficient stifle joints before LFTS, CCL-deficient stifle joints 6 months after LFTS, and unaffected contralateral (control) stifle joints. Owners and veterinarians subjectively assessed lameness by use of a visual analog scale and gait examination, respectively, at each time point.

Results: At midstance phase, medial cranial tibial translation decreased from 9.3 mm before LFTS to 7.6 mm after LFTS but remained increased when compared with control stifle joint values. Following LFTS, axial rotation and stifle joint flexion and extension angles were not significantly different from control stifle joints. On the owner survey, the median walking lameness score improved from 9.3 of 10 before surgery to 0.3 after surgery. On gait examination, median walking lameness score improved from 2 of 4 before surgery to 0 after surgery.

Conclusions And Clinical Relevance: Stifle joint instability was only slightly mitigated at 6 months following LFTS performed with knotted nylon leader material in medium to large dogs with CCL rupture, despite improvement in lameness.
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http://dx.doi.org/10.2460/javma.258.5.493DOI Listing
March 2021

Three-dimensional-printed custom guides for bipolar coxofemoral osteochondral allograft in dogs.

PLoS One 2021 9;16(2):e0244208. Epub 2021 Feb 9.

Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, Florida, United States of America.

The objective of this experimental study was to develop and evaluate a three-dimensionally printed custom surgical guide system for performing bipolar coxofemoral osteochondral allograft transplantation in dogs. Five cadaver dogs, weighing 20-38 kg were used in the study. Custom surgical guides were designed and three-dimensionally printed to facilitate accurate execution of a surgical plan for bipolar coxofemoral osteochondral allograft transplantation. Guide-assisted technique was compared to freehand technique in each cadaver. Surgical time was recorded and postoperative computed tomography and three-dimensional segmentation was performed. Femoral version and inclination angles, femoral neck length, and gap present at the femoral and acetabular donor-recipient interface was compared between the virtual surgical plan and postoperative outcome for both techniques. One-tailed paired t-test (P < .05) was used for statistical analysis. When compared to free-hand preparation, mean donor femoral preparation time was 10 minutes longer and mean recipient preparation time was 2 minutes longer when using guides (p = 0.011 and p = 0.001, respectively). No difference in acetabular preparation time was noted between groups. Gap volume at the acetabular and femoral donor-recipient interface was not different between groups. Mean difference between the planned and postoperative version angle was 6.2° lower for the guide group when compared to the freehand group (p = 0.025). Mean femoral neck length was 2 mm closer to the plan when using guides than when performing surgery freehand (p = 0.037). Accuracy for femoral angle of inclination was not different between groups. Custom surgical guides warrants consideration in developing bipolar coxofemoral osteochondral allograft transplantation as an alternative surgical technique for managing hip disorders in dogs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0244208PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872253PMC
July 2021

Calcium sulfate antibiotic-impregnated bead implantation for deep surgical site infection associated with orthopedic surgery in small animals.

Vet Surg 2021 May 25;50(4):748-757. Epub 2021 Jan 25.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.

Objective: To report the outcomes and complications associated with antibiotic-impregnated calcium sulfate beads for prevention and treatment of orthopedic-related surgical site infection (SSI) in companion animals.

Study Design: Retrospective case series.

Animals: Client-owned cats (n = 2) and dogs (n = 14).

Methods: Medical records of 16 cases in which implantation of antibiotic-impregnated calcium sulfate beads was performed for the prevention or treatment of SSI were reviewed. Information collected included signalment, prior surgery, reason for bead placement, antibiotics used, bacterial culture results, and clinical outcomes.

Results: Surgical site infection resolved in six of 10 animals treated therapeutically and did not occur in six of six animals treated prophylactically. Susceptibility of the causative bacteria to the antibiotic implanted was confirmed in five of six cases with resolved SSI treated therapeutically but in only one of four cases with unresolved SSI treated therapeutically. Complications directly related to bead placement were evident in only one case in which beads extruded from external skeletal fixator pin tracts 7 days after implantation. At final follow-up, 11 of 12 animals without SSI had satisfactory limb use and no clinical, cytologic, or radiographic evidence of infection.

Conclusion: Implantation was well tolerated. Resolution of SSI was inconsistent; however, when bacteria were susceptible to the antibiotic implanted, SSI resolved in all but one case.

Clinical Significance: Antibiotic-impregnated calcium sulfate beads could be considered for prevention or treatment of orthopedic SSI in small animals. A prospective clinical study is required to obtain additional information, including the value of preoperative bacterial culture.
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http://dx.doi.org/10.1111/vsu.13570DOI Listing
May 2021

What Is Your Diagnosis?

J Am Vet Med Assoc 2020 Nov;257(10):1007-1010

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http://dx.doi.org/10.2460/javma.2020.257.10.1007DOI Listing
November 2020

Human placenta-derived matrix with cancellous autograft and demineralized bone matrix for large segmental long-bone defects in two dogs with septic nonunion.

Vet Surg 2020 Dec 3;49(8):1618-1625. Epub 2020 Oct 3.

Department of Orthopedics and Rehabilitation, University of Florida, Gainesville, Florida.

Objective: To report the successful treatment of septic nonunion in two dogs with large segmental defects secondary to long-bone fractures by using a novel human placenta-derived matrix (hPM) as adjunct to fixation.

Animals: One 3-kg 9-year-old neutered male Yorkshire terrier with a distal antebrachial fracture and one 6-kg 4-year-old spayed female miniature pinscher with a distal humeral fracture.

Study Design: Short case series.

Methods: Both dogs presented for septic nonunion after internal fixation of Gustilo type II open diaphyseal fractures from dog bite injuries. During revision, debridement of nonviable bone resulted in segmental defects of 32% and 20% of the bone length for the antebrachial and humeral fractures, respectively. The antebrachial fracture was stabilized with a circular external fixator, and the humeral fracture was stabilized with biaxial bone plating. The fracture sites were not collapsed, and full length was maintained with the fixation. Autogenous cancellous bone graft and canine demineralized bone allograft were packed into the defects, and hPM was injected into the graft sites after closure.

Results: Radiographic union was documented at 8 weeks and 6 weeks for the antebrachial and humeral fractures, respectively. Both dogs became fully weight bearing on the affected limbs and returned to full activity.

Conclusion: Augmenting fixation with grafts and hPM led to a relatively rapid union in both dogs reported here.
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http://dx.doi.org/10.1111/vsu.13527DOI Listing
December 2020

Comparison of intestinal leak pressure between cadaveric canine and commercial synthetic intestinal tissue that did and did not undergo enterotomy.

Am J Vet Res 2020 Oct;81(10):827-831

Objective: To compare initial leak pressure (ILP) between cadaveric canine and synthetic small intestinal segments that did and did not undergo enterotomy.

Sample: Eight 8-cm grossly normal jejunal segments from 1 canine cadaver and eight 8-cm synthetic small intestinal segments.

Procedures: Intestinal segments were randomly assigned to undergo enterotomy (6 cadaveric and 6 synthetic segments) or serve as untreated controls (2 cadaveric and 2 synthetic segments). For segments designated for enterotomy, a 2-cm full-thickness incision was created along the antimesenteric border. The incision was closed in a single layer with 4-0 suture in a simple continuous pattern. Leak testing was performed with intestinal segments occluded at both ends and infused with dilute dye solution (999 mL/h) until the solution was observed leaking from the suture line or serosal tearing occurred. Intraluminal pressure was continuously monitored. The ILP at construct failure was compared between cadaveric and synthetic control segments and between cadaveric and synthetic enterotomy segments.

Results: Mean ± SD ILP did not differ significantly between cadaveric (345.11 ± 2.15 mm Hg) and synthetic (329.04 ± 24.69 mm Hg) control segments but was significantly greater for cadaveric enterotomy segments (60.77 ± 15.81 mm Hg), compared with synthetic enterotomy segments (15.03 ± 6.41 mm Hg).

Conclusions And Clinical Relevance: Leak testing should not be used to assess the accuracy or security of enterotomy suture lines in synthetic intestinal tissue. Synthetic intestinal tissue is best used for students to gain confidence and proficiency in performing enterotomies before performing the procedure on live animals.
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http://dx.doi.org/10.2460/ajvr.81.10.827DOI Listing
October 2020

Radiographic evaluation of patellar tendon length following corrective surgical procedures for medial patellar luxation in dogs.

PLoS One 2020 4;15(9):e0238598. Epub 2020 Sep 4.

Department of Small Animal Clinical Sciences, University of Florida College of Veterinary Medicine, Gainesville, Florida, United States of America.

Objective: To quantify changes in the patellar tendon length following surgical correction of medial patellar luxation in dogs and evaluate potential risk factors associated with patellar tendon elongation.

Study Design: Retrospective case series (n = 50).

Methods: Dogs that underwent surgery for medial patellar luxation correction and had 2-3 months follow up were included. Digital radiographs were utilized to quantify the patellar tendon length to patellar length ratio at various follow-up points. Odds ratio comparisons between potential risk factors associated with changes in patellar tendon length were performed.

Results: Post-operative patellar tendon lengthening of ≥ 5% was observed in 20% of stifles and post-operative patellar tendon shortening of ≥ 5% was observed in 22% of stifles at the 2-3 month follow up period. The risk factors including age, body weight, trochleoplasty and grade of medial patellar luxation were not significantly associated with risk of patellar tendon elongation. Patellar tendon lengthening was not associated with recurrence of luxation.

Conclusion: Patellar tendon lengthening and shortening can be observed in dogs following common medial patellar luxation corrective procedures in the short term follow up period. Patellar tendon lengthening does not appear to be associated with age, weight, trochleoplasty, grade of luxation, or risk of luxation recurrence.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0238598PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7473547PMC
October 2020

Host urine immunological biomarkers as potential candidates for the diagnosis of tuberculosis.

Int J Infect Dis 2020 Oct 12;99:473-481. Epub 2020 Aug 12.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, P.O. Box 241, Cape Town 8000, South Africa. Electronic address:

Objective: To investigate the potential of host urinary biomarkers as diagnostic candidates for tuberculosis (TB).

Methods: Adults self-presenting with symptoms requiring further investigation for TB were enrolled in Cape Town, South Africa. Participants were later classified as having TB or other respiratory diseases (ORD) using results from TB confirmatory tests. The concentrations of 29 analytes were evaluated in urine samples from participants using the Luminex platform, and their diagnostic potential was assessed using standard statistical approaches.

Results: Of the 151 study participants, 34 (22.5%) were diagnosed with TB and 26 (17.2%) were HIV-positive. Seven biomarkers showed potential as TB diagnostic candidates, with accuracy improving (in HIV-positives) when stratified according to HIV status (area under the receiver operating characteristics curve; AUC ≥0.80). In HIV-positive participants, a four-marker biosignature (sIL6R, MMP-9, IL-2Ra, IFN-γ) diagnosed TB with AUC of 0.96, sensitivity of 85.7% (95% confidence interval (CI) 42.1-99.6%), and specificity of 94.7% (95% CI 74.0-99.9%). In HIV-negatives, the most promising was a two-marker biosignature (sIL6R and sIL-2Ra), which diagnosed TB with AUC of 0.76, sensitivity of 53.9% (95% CI 33.4-73.4%), and specificity of 79.6% (95% CI 70.3-87.1%).

Conclusions: Urinary host inflammatory biomarkers possess TB diagnostic potential but may be influenced by HIV infection. The results of this study require validation in larger studies.
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http://dx.doi.org/10.1016/j.ijid.2020.08.019DOI Listing
October 2020

In vivo three-dimensional knee kinematics in goats with unilateral anterior cruciate ligament transection.

J Orthop Res 2021 May 13;39(5):1052-1063. Epub 2020 Jul 13.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, Florida.

Although the goat is an established animal model in anterior cruciate ligament (ACL) research, in vivo kinematics associated with ACL deficiency have not been previously described in this species. Three-dimensional knee kinematics were determined before and after unilateral ACL transection in eight goats. Fluoroscopic imaging of the knees during treadmill walking and force-platform gait analysis during over-ground walking were performed prior to ACL transection, and 2 weeks, 3 months, and 6 months after ACL transection. Transient lameness of the ACL-transected limb was noted in all goats but resolved by 3 months post-ACL transection. Increased extension of 8.7° to 17.0° was noted throughout the gait cycle in both the ACL-transected and the contralateral unaffected knees by 3 months post-ACL transection, in a bilaterally symmetric pattern. Peak anterior tibial translation increased by 3 to 6 mm after ACL transection and persisted over the 6-month study period. No changes in axial rotation or abduction angle were observed after ACL transection. Unilateral ACL deficiency in goats resulted in persistent kinematic alterations, despite the resolution of lameness by 3 months post-ACL transection.
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http://dx.doi.org/10.1002/jor.24795DOI Listing
May 2021

Association of aspirin and other non-steroidal anti-inflammatory drugs with bleeding complications in image-guided musculoskeletal biopsies.

Skeletal Radiol 2020 Nov 13;49(11):1849-1854. Epub 2020 Jun 13.

Department of Radiology, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, MA, 02215, USA.

Objective: To evaluate the safety of continuing aspirin and other non-steroidal anti-inflammatory drugs (NSAID) in patients undergoing image-guided musculoskeletal biopsies.

Material And Methods: Prior to October 2017, patients undergoing image-guided musculoskeletal biopsy had aspirin and NSAIDs withheld for the preceding 5-7 days. The policy changed in October 2017 based on new guidelines from the Society of Interventional Radiology such that aspirin and other NSAIDs were not withheld. A retrospective review of patient records was performed for all biopsies prior to and after the policy change to assess for differences in biopsy-related bleeding complications. Additional clinical and biopsy factors including age, gender, liver disease, coagulopathy, biopsy tissue type, and histological diagnosis were assessed.

Results: In the pre-policy change group, there were 1853 total biopsies with 43 biopsy-related bleeding complications (2.3%). Within this group, 362 patients were on aspirin with 7 bleeding complications (1.9%) and 260 patients were on NSAIDs with 5 bleeding complications (1.9%). There were 409 total biopsies in the post-policy change group and 7 bleeding complications (1.7%). Within this group, 71 patients were on aspirin with 1 bleeding complication (1.4%). No bleeding complications were recorded in patients on NSAIDs (0%). There was no significant difference in bleeding complication between the pre- and post-policy change groups overall (p = 0.58) and in patients on aspirin (p = 1.00) or other NSAIDs (p = 1.00).

Conclusion: Bleeding complications for musculoskeletal biopsies are rare. Leaving patients on aspirin or other NSAIDs during a musculoskeletal biopsy does not increase the incidence of bleeding complications.
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http://dx.doi.org/10.1007/s00256-020-03510-zDOI Listing
November 2020

Impact of Intermediate Hyperglycemia and Diabetes on Immune Dysfunction in Tuberculosis.

Clin Infect Dis 2021 01;72(1):69-78

Tuberculosis Centre and Department of Infection and Biology, London School of Hygiene and Tropical Medicine, London, United Kingdom.

Background: People with diabetes have an increased risk of developing active tuberculosis (TB) and are more likely to have poor TB-treatment outcomes, which may impact on control of TB as the prevalence of diabetes is increasing worldwide. Blood transcriptomes are altered in patients with active TB relative to healthy individuals. The effects of diabetes and intermediate hyperglycemia (IH) on this transcriptomic signature were investigated to enhance understanding of immunological susceptibility in diabetes-TB comorbidity.

Methods: Whole blood samples were collected from active TB patients with diabetes (glycated hemoglobin [HbA1c] ≥6.5%) or IH (HbA1c = 5.7% to <6.5%), TB-only patients, and healthy controls in 4 countries: South Africa, Romania, Indonesia, and Peru. Differential blood gene expression was determined by RNA-seq (n = 249).

Results: Diabetes increased the magnitude of gene expression change in the host transcriptome in TB, notably showing an increase in genes associated with innate inflammatory and decrease in adaptive immune responses. Strikingly, patients with IH and TB exhibited blood transcriptomes much more similar to patients with diabetes-TB than to patients with only TB. Both diabetes-TB and IH-TB patients had a decreased type I interferon response relative to TB-only patients.

Conclusions: Comorbidity in individuals with both TB and diabetes is associated with altered transcriptomes, with an expected enhanced inflammation in the presence of both conditions, but also reduced type I interferon responses in comorbid patients, suggesting an unexpected uncoupling of the TB transcriptome phenotype. These immunological dysfunctions are also present in individuals with IH, showing that altered immunity to TB may also be present in this group. The TB disease outcomes in individuals with IH diagnosed with TB should be investigated further.
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http://dx.doi.org/10.1093/cid/ciaa751DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823074PMC
January 2021

Caudal cruciate ligament disease in three Basset Hounds.

J Am Vet Med Assoc 2020 Apr;256(8):921-926

Case Description: 3 adult Basset Hounds were referred for evaluation of chronic, unilateral, pelvic limb lameness with no history of trauma.

Clinical Findings: On examination, all dogs had mild lameness of the affected limb; signs of pain were evident during manipulation of the stifle joint in the affected limb, along with effusion of that joint. No stifle joint instability was palpable. Radiographs were available for review for 2 of the 3 dogs. Effusion was confirmed radiographically, but severity of degenerative joint disease varied. Central intercondylar notch width ratios for the 2 dogs were 0.16 and 0.17, and tibial plateau angles were -10° and 15°; relative tibial tuberosity width was 1.1 for both dogs. Exploratory arthroscopy revealed moderate degeneration of the caudal cruciate ligament in all 3 dogs; the cranial cruciate ligaments were grossly normal.

Treatment And Outcome: Corrective osteotomy to increase the tibial plateau angle was performed in 1 dog, and the lameness resolved by 2 months after surgery. The 2 other dogs were managed without additional surgery. One dog was persistently lame. The other dog reportedly had normal limb function 2.5 years after undergoing exploratory arthroscopy.

Clinical Relevance: Morphological characteristics of the tibia in Basset Hounds may predispose to abnormal stresses on the caudal cruciate ligament. Isolated degeneration of the caudal cruciate ligament should be considered as a differential diagnosis for Basset Hounds with lameness originating from the stifle joint. Without direct inspection of the joint, caudal cruciate ligament disease could be confused for cranial cruciate ligament injury.
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http://dx.doi.org/10.2460/javma.256.8.921DOI Listing
April 2020

Intra-articular proximal jig pin placement during tibial plateau leveling osteotomy.

Open Vet J 2020 01 21;9(4):335-338. Epub 2019 Dec 21.

Department of Statistics, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, FL 32611, USA.

Background: During tibial plateau leveling osteotomy (TPLO), a TPLO jig is often used. For placement of the jig, one of the pins is placed slightly distal to the joint line. Erroneous pin placement may lead to intra-articular damage; however, the path of the pin tract has not been thoroughly investigated.

Aim: To document the rate and identify potential risk factors of intra-articular jig pin placement in dogs undergoing TPLO with the use of a TPLO jig.

Methods: Medical records and pre- and postoperative radiographs (2007-2017) of 696 dogs with TPLO performed with a jig were reviewed. Primary surgeon and tibial plateau angles (TPA) were recorded. Postoperative radiographs were evaluated and classified according to intra-articular jig pin placement. Medial tibial plateau jig pin placement was defined as a radiolucent tract on the osteochondral junction of the medial tibial plateau. Lateral tibial plateau placement was defined as a radiolucent tract within 3 mm of the medial tibial plateau with a pin trajectory penetrating the lateral tibial plateau. Rates of intra-articular jig pin placement were calculated, and associations between intra-articular jig pin placement and surgeon experience and TPA were assessed with a chi-squared test.

Results: Thirty-seven (5.32%) dogs had intra-articular placement of the jig pin. Seven dogs had medial tibial plateau jig placement, and 30 had lateral tibial plateau placement. There was no relationship between the TPA or surgeon level of experience and intra-articular placement of the pin.

Conclusion: This study serves as a reminder to be cautious when placing the proximal jig pin during TPLO to avoid intra-articular placement. In addition, guidelines for evaluating proximal jig pin placement on postoperative radiographs are provided.
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http://dx.doi.org/10.4314/ovj.v9i4.11DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971352PMC
January 2020

A Teenager With Cough, Weight Loss, and a Chest Wall Mass.

Clin Pediatr (Phila) 2020 05 22;59(4-5):522-528. Epub 2020 Jan 22.

University of California San Francisco-Fresno Branch, Fresno, CA, USA.

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http://dx.doi.org/10.1177/0009922819901006DOI Listing
May 2020

Intra-Articular Umbilical Cord Derived Mesenchymal Stem Cell Therapy for Chronic Elbow Osteoarthritis in Dogs: A Double-Blinded, Placebo-Controlled Clinical Trial.

Front Vet Sci 2019 20;6:474. Epub 2019 Dec 20.

Animal Cell Therapies, San Diego, CA, United States.

Intra-articular stem cell therapy may help alleviate lameness caused by osteoarthritis in dogs. Umbilical cord-derived stem cell (UMSC) therapy has not yet been investigated in a veterinary clinical study. We hypothesized that dogs treated with intra-articular UMSC will have improved limb function and quality of life when compared to dogs treated with a saline placebo injection. This was a prospective, double-blinded, placebo-controlled clinical trial in client-owned dogs with chronic elbow osteoarthritis with a follow-up time of 6 months. Dogs were assigned to receive intra-articular UMSC ( = 38) or a saline placebo intra-articular injection ( = 30). Outcome measures included the Canine Brief Pain Inventory score (CBPI) and peak vertical force (PVF) from force-platform gait analysis. Treatment was considered successful when there was a decrease in the Pain Severity Score of at least one and a decrease in the Pain Interference Score of at least one from baseline. Success rates and PVF were compared between groups. No adverse effects associated with UMSC were noted. Of the dogs completing the study, treatment success in the UMSC ( = 28) vs. placebo groups ( = 23) was observed in 54 vs. 28% of dogs at 1 month, 50 vs. 27% at 3 months, and 46 vs. 14% at 6 months, respectively. Success rate in the UMSC group was significantly higher than the placebo group at 1 and 6 months after treatment. However, no differences in PVF of the affected limb over time was observed in either group. Intra-articular UMSC for osteoarthritis may improve clinical signs based on owner observations.
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http://dx.doi.org/10.3389/fvets.2019.00474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932969PMC
December 2019

Correction of Excessive Tibial Plateau Angle and Limb Shortening in a Juvenile Dog Using a Hinged Circular Fixator Construct and Distraction Osteogenesis.

Case Rep Vet Med 2019 16;2019:1439237. Epub 2019 Nov 16.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, USA.

An 18-week-old Rhodesian Ridgeback puppy that was hit by a car sustained a Salter-Harris type III fracture of the left proximal tibial physis and ipsilateral diaphyseal femoral and tibial fractures. The diaphyseal fractures were successfully stabilized with bone plate fixation. Premature closure of the caudal aspect of the proximal tibial physis, secondary to the proximal physeal fracture, resulted in an excessively high tibial plateau angle (TPA) of 50° with a limb length discrepancy of 13% by 24 weeks of age. The deformity was addressed by performing a proximal tibial osteotomy and subsequent distraction osteogenesis to reduce the TPA while concurrently lengthening the crus. A radial osteotomy was performed in the proximal metaphyseal region and the hinged fixator was applied. Distraction was initiated the day following surgery at a rate of 1 mm per day as measured along the caudal cortex of the tibia with a rhythm of three distractions daily. Distraction was terminated 19 days postoperatively. Sequential distraction of the osteotomy resulted in 17 mm of tibial lengthening and a final TPA of 3°. The fixator was removed 52 days after application. Complications included wire tract inflammation involving the wires securing the proximal segment and a calcaneal fracture which required bone plate stabilization. The left pelvic limb was only 8% shorter than the right pelvic limb and the dog had only a subtle lameness 12 months after surgery. The hinged circular fixator construct allowed for both the reduction of the TPA and limb segment lengthening in this dog.
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http://dx.doi.org/10.1155/2019/1439237DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881767PMC
November 2019

Femorotibial kinematics in dogs treated with tibial plateau leveling osteotomy for cranial cruciate ligament insufficiency: An in vivo fluoroscopic analysis during walking.

Vet Surg 2020 Jan 28;49(1):187-199. Epub 2019 Nov 28.

Comparative Orthopaedics and Biomechanics Laboratory, College of Veterinary Medicine, University of Florida, Gainesville, Florida.

Objective: To determine the ability of tibial plateau leveling osteotomy (TPLO) to address abnormal femorotibial kinematics caused by cranial cruciate ligament (CCL) rupture during walking in dogs.

Study Design: Prospective, clinical.

Animals: Sixteen dogs (20-40 kg) with unilateral complete CCL rupture.

Methods: Lateral view fluoroscopy was performed during treadmill walking preoperatively and 6 months after TPLO. Digital three-dimensional (3D) models of the femora and tibiae were created from computed tomographic (CT) images. Gait cycles were analyzed by using a 3D-to-2D image registration process. Craniocaudal translation, internal/external rotation, and flexion/extension of the femorotibial joint were compared between preoperative and 6-month postoperative time points for the affected stifle and 6-month postoperative unaffected contralateral (control) stifles.

Results: In the overall population, CCL rupture resulted in 10 ± 2.2 mm (mean ± SD) cranial tibial translation at midstance phase, which was converted to 2.1 ± 4.3 mm caudal tibial translation after TPLO. However, five of 16 TPLO-treated stifles had 4.1 ± 0.3 mm of cranial tibial subluxation during mid-to-late stance phase, whereas 10 of 16 TPLO-treated stifles had 4.3 ± 0.4 mm of caudal tibial subluxation throughout the gait cycle. Overall, postoperative axial rotational and flexion/extension patterns were not different from control, but stifles with caudal tibial subluxation had more external tibial rotation during mid-to-late stance phase compared with stifles with cranial tibial subluxation.

Conclusion: TPLO mitigated abnormal femorotibial kinematics but did not restore kinematics to control values in 15 of 16 dogs during walking.

Clinical Significance: Tibial plateau leveling osteotomy reduces cranial tibial subluxation during walking, but persistent instability is common.
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http://dx.doi.org/10.1111/vsu.13356DOI Listing
January 2020

Percutaneous Pinning for Fracture Repair in Dogs and Cats.

Vet Clin North Am Small Anim Pract 2020 Jan 22;50(1):101-121. Epub 2019 Oct 22.

Clinic for Small Animal Surgery, Vetsuisse Faculty, University of Zurich, Zurich CH-8057, Switzerland.

This article describes the technique of percutaneous pinning in dogs and cats. Only acute fractures evaluated within the first 48 hours after trauma are selected for percutaneous pinning. Reduction is performed with careful manipulation of the fracture to minimize the trauma to the growth plate. After ensuring the fracture is reduced anatomically, smooth pins of appropriate size are inserted through stab incisions or through large-gauge needles. Depending on the anatomic location, the pins are cut flush with the bone or bent over. The main advantages of this technique are the minimal surgical trauma and lower perioperative morbidity.
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http://dx.doi.org/10.1016/j.cvsm.2019.09.001DOI Listing
January 2020

Percutaneous Plate Arthrodesis.

Vet Clin North Am Small Anim Pract 2020 Jan 22;50(1):241-261. Epub 2019 Oct 22.

Vetsuisse Faculty, University of Zurich, Winterthurerstrasse 258c, Zurich 8057, Switzerland.

Arthrodesis is an elective surgical procedure that aims at eliminating pain and dysfunction by promoting deliberate osseous fusion of the involved joint(s). Percutaneous plating can be used to perform carpal and tarsal arthrodeses in dogs and cats. After cartilage debridement is performed, the plate is introduced through separate plate insertion incisions made remote to the arthrodesis site and advanced along an epiperiosteal tunnel, and screws are inserted through the 3 existing skin incisions. The primary advantage of this technique is a decreased risk of soft-tissue complications, including postoperative swelling, ischemia, and wound dehiscence. Preliminary clinical results have been promising.
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http://dx.doi.org/10.1016/j.cvsm.2019.08.014DOI Listing
January 2020

Potential of Host Serum Protein Biomarkers in the Diagnosis of Tuberculous Meningitis in Children.

Front Pediatr 2019 25;7:376. Epub 2019 Sep 25.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa.

Tuberculous meningitis (TBM) is the most severe form of tuberculosis and results in high morbidity and mortality in children. Diagnostic delay contributes to the poor outcome. There is an urgent need for new tools for the rapid diagnosis of TBM, especially in children. We collected serum samples from children in whom TBM was suspected at a tertiary hospital in Cape Town, South Africa. Children were subsequently classified as having TBM or no TBM using a published uniform research case-definition. Using a multiplex cytokine array platform, we investigated the concentrations of serum biomarkers comprising biomarkers that were previously found to be of value in the diagnosis of adult pulmonary TB (CRP, SAA, CFH, IFN-γ, IP-10, Apo-AI, and transthyretin) plus other potentially useful host biomarkers as diagnostic candidates for TBM. Out of 47 children included in the study, 23 (48.9%) had a final diagnosis of TBM and six were HIV infected. A modified version of the adult 7-marker biosignature in which transthyretin was replaced by NCAM1, diagnosed TBM in children with AUC of 0.80 (95% CI, 0.67-0.92), sensitivity of 73.9% (95% CI, 51.6-89.8%) and specificity of 66.7% (95% CI, 44.7-84.4%), with the other six proteins in the signature (CRP, IFN-γ, IP-10, CFH, Apo-A1, and SAA) only achieving and AUC of 0.75 (95% CI, 0.61-0.90) when used in combination. A new childhood TBM specific 3-marker biosignature (adipsin, Aβ42, and IL-10) showed potential in the diagnosis of TBM, with AUC of 0.84 (95% CI, 0.73-0.96), sensitivity of 82.6% (95 CI, 61.2-95.0%) and specificity of 75.0% (95% CI, 53.3-90.2%) after leave-one-out cross validation. A previously described adult 7-marker serum protein biosignature showed potential in the diagnosis of TBM in children. However, a smaller childhood TBM-specific 3-marker signature demonstrated improved performance characteristics. Our data indicates that blood-based biomarkers may be useful in the diagnosis of childhood TBM and requires further validation in larger cohort studies.
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http://dx.doi.org/10.3389/fped.2019.00376DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773834PMC
September 2019

Large Animal Models for Anterior Cruciate Ligament Research.

Front Vet Sci 2019 29;6:292. Epub 2019 Aug 29.

Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainesville, FL, United States.

Large animal (non-rodent mammal) models are commonly used in ACL research, but no species is currently considered the gold standard. Important considerations when selecting a large animal model include anatomical differences, the natural course of ACL pathology in that species, and biomechanical differences between humans and the chosen model. This article summarizes recent reports related to anatomy, pathology, and biomechanics of the ACL for large animal species (dog, goat, sheep, pig, and rabbit) commonly used in ACL research. Each species has unique features and benefits as well as potential drawbacks, which are highlighted in this review. This information may be useful in the selection process when designing future studies.
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http://dx.doi.org/10.3389/fvets.2019.00292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6727067PMC
August 2019

Distinct serum biosignatures are associated with different tuberculosis treatment outcomes.

Tuberculosis (Edinb) 2019 09 12;118:101859. Epub 2019 Aug 12.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. Electronic address:

Biomarkers for TB treatment response and outcome are needed. This study characterize changes in immune profiles during TB treatment, define biosignatures associated with treatment outcomes, and explore the feasibility of predictive models for relapse. Seventy-two markers were measured by multiplex cytokine array in serum samples from 78 cured, 12 relapsed and 15 failed treatment patients from South Africa before and during therapy for pulmonary TB. Promising biosignatures were evaluated in a second cohort from Uganda/Brazil consisting of 17 relapse and 23 cured patients. Thirty markers changed significantly with different response patterns during TB treatment in cured patients. The serum biosignature distinguished cured from relapse patients and a combination of two clinical (time to positivity in liquid culture and BMI) and four immunological parameters (TNF-β, sIL-6R, IL-12p40 and IP-10) at diagnosis predicted relapse with a 75% sensitivity (95%CI 0.38-1) and 85% specificity (95%CI 0.75-0.93). This biosignature was validated in an independent Uganda/Brazil cohort correctly classifying relapse patients with 83% (95%CI 0.58-1) sensitivity and 61% (95%CI 0.39-0.83) specificity. A characteristic biosignature with value as predictor of TB relapse was identified. The repeatability and robustness of these biomarkers require further validation in well-characterized cohorts.
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http://dx.doi.org/10.1016/j.tube.2019.101859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6839616PMC
September 2019

The effect of tibial plateau leveling osteotomy on patellofemoral kinematics in dogs: An in vivo study.

Vet Surg 2020 Jan 2;49(1):207-213. Epub 2019 Aug 2.

Department of Mechanical and Aerospace Engineering, University of Florida, Gainesville, Florida.

Objective: To quantitatively evaluate patellofemoral (PF) kinematics during walking in dogs with cranial cruciate ligament (CrCL) deficiency treated by tibial plateau leveling osteotomy (TPLO).

Study Design: Longitudinal observational study.

Animals: Dogs with unilateral CrCL deficiency treated by TPLO (n = 10).

Methods: Horizontal beam fluoroscopic images of the stifles during treadmill walking were acquired 6 months after TPLO. Computed tomography was performed, and digitized bone models of both femurs and patellae were created. These digital models were superimposed over the fluoroscopic images with shape-matching software, and sagittal plane PF kinematics for TPLO-treated and normal contralateral stifles were calculated. Patellofemoral kinematics were described according to phase of gait cycle as well as relative to femorotibial flexion angle.

Results: In TPLO-treated stifles, there was an approximately 1-mm increase in cranial displacement of the patella (P < .05) compared with the normal stifle at equivalent femorotibial flexion angles between 120° and 140° and predominately during the stance phase. Proximal-distal translation and patellar flexion angle were mostly unaffected by TPLO when they were assessed according to either equivalent phase of gait cycle or femorotibial flexion angles.

Conclusion: In vivo PF kinematics in TPLO-treated stifles were subtly different from normal, characterized by slight cranial shifting of the patella relative to the trochlear groove.

Clinical Significance: The clinical significance of these results remains unknown. These results may provide further understanding into extensor mechanism abnormalities associated with TPLO.
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http://dx.doi.org/10.1111/vsu.13300DOI Listing
January 2020

Prospective evaluation of host biomarkers other than interferon gamma in QuantiFERON Plus supernatants as candidates for the diagnosis of tuberculosis in symptomatic individuals.

J Infect 2019 09 15;79(3):228-235. Epub 2019 Jul 15.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Po Box 241, Cape Town 8000, South Africa. Electronic address:

Background: There is an urgent need for new tools for the diagnosis of TB. We evaluated the usefulness recently described host biomarkers in supernatants from the newest generation of the QuantiFERON test (QuantiFERON Plus) as tools for the diagnosis of active TB.

Methods: We recruited individuals presenting at primary health care clinics in Cape Town, South Africa with symptoms requiring investigation for TB disease, prior to the establishment of a clinical diagnosis. Participants were later classified as TB or other respiratory diseases (ORD) based on the results of clinical and laboratory tests. Using a multiplex platform, we evaluated the concentrations of 37 host biomarkers in QuantiFERON Plus supernatants from study participants as tools for the diagnosis of TB.

Results: Out of 120 study participants, 35(29.2%) were diagnosed with active TB, 69(57.5%) with ORD whereas 16(13.3%) were excluded. 14(11.6%) of the study participants were HIV infected. Although individual host markers showed potential as diagnostic candidates, the main finding of the study was the identification of a six-marker biosignature in unstimulated supernatants (Apo-ACIII, CXCL1, CXCL9, CCL8, CCL-1, CD56) which diagnosed TB with sensitivity and specificity of 73.9%(95% CI; 51.6-87.8) and 87.6%(95% CI; 77.2-94.5), respectively, after leave-one-out cross validation. Combinations between TB-antigen specific biomarkers also showed potential (sensitivity of 77.3% and specificity of 69.2%, respectively), with multiple biomarkers being significantly different between TB patients, Quantiferon Plus Positive and Quantiferon Plus negative individuals with ORD, regardless of HIV status.

Conclusions: Biomarkers detected in QuantiFERON Plus supernatants may contribute to adjunctive diagnosis of TB.
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http://dx.doi.org/10.1016/j.jinf.2019.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6692655PMC
September 2019

Application of Cerebrospinal Fluid Host Protein Biosignatures in the Diagnosis of Tuberculous Meningitis in Children from a High Burden Setting.

Mediators Inflamm 2019 16;2019:7582948. Epub 2019 Apr 16.

DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Po Box 241, Cape Town 8000, South Africa.

Background: The diagnosis of tuberculous meningitis (TBM) especially in children is challenging. New tests are urgently needed for the diagnosis of the disease, especially in resource-limited settings.

Methods: We collected cerebrospinal fluid (CSF) samples from children presenting with symptoms requiring investigation for meningitis at a tertiary hospital in Cape Town, South Africa. Children were later classified as TBM or no TBM using published case definitions. Using a multiplex platform, we investigated the concentrations of biomarkers comprising a previously established 3-marker biosignature (VEGF, IL-13, and LL-37) and other potentially useful host biomarkers as diagnostic candidates for TBM.

Findings: Out of 47 children, age, 3 months to 13 years, 23 were diagnosed with TBM and six (16%) were HIV-infected. We validated the previously identified CSF biosignature (sensitivity of 95.7% (95% CI, 79.0-99.2%) and specificity of 37.5% (95% CI, 21.2-57.3%)). However, substitution of IL-13 and LL-37 with IFN- and MPO, respectively, resulted in improved accuracy (area under the ROC curve (AUC) = 0.97, 95% CI, 0.92-1.00, up to 91.3% (21/23) sensitivity and up to 100% (24/24) specificity). An alternative four-marker biosignature (sICAM-1, MPO, CXCL8, and IFN-) also showed potential, with an AUC of 0.97.

Conclusion: We validated a previously identified CSF biosignature and showed that refinement of this biosignature by incorporation of other biomarkers diagnosed TBM with high accuracy. Incorporation of these biomarkers into a point-of-care or bedside diagnostic test platform may result in the improved management of TBM in children.
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http://dx.doi.org/10.1155/2019/7582948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6501148PMC
December 2019

EDITORIAL.

Vet Surg 2019 06 6;48(S1):O5. Epub 2019 May 6.

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http://dx.doi.org/10.1111/vsu.13235DOI Listing
June 2019
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