Long-term outcome and quality of life of dogs that developed neurologic signs after surgical treatment of a congenital portosystemic shunt: 50 cases (2005-2020).

OBJECTIVE: To determine survival time and quality of life of dogs that developed postattenuation neurologic signs (PANS) after surgical treatment of a single congenital portosystemic shunt and survived at least 30 days and identify whether neurologic signs present at the time of discharge would resolve or reoccur. ANIMALS: 50 client-owned dogs. PROCEDURES: Medical records were retrospectively reviewed, and follow-up data relating to neurologic signs and seizure activity were obtained. Owners were asked to complete a questionnaire related to the presence of neurologic signs, including seizures, and their dog's quality of life. RESULTS: Thirty of the 50 (60%) dogs had postattenuation seizures with or without other nonseizure neurologic signs, and 20 (40%) had neurologic signs other than seizures. Neurologic signs had fully resolved by the time of discharge in 24 (48%) dogs. Signs resolved in 18 of the remaining 26 (69%) dogs that still had PANS other than seizures at the time of discharge. Seizures reoccurred in 15 of the 30 dogs that had postattenuation seizures. Twenty-seven of 33 (82%) owners graded their dog's long-term (> 30 days after surgery) quality-of-life as high. Forty-five (90%) dogs survived > 6 months. Most (29/43 [67%]) neurologic signs (other than seizures) present at the time of hospital discharge resolved. CLINICAL RELEVANCE: Findings highlighted that survival times of > 6 months and a high QOL can be achieved in most dogs with PANS that survive at least 30 days. Most neurologic signs other than seizures resolved within 1 month postoperatively. Half of the dogs with postattenuation seizures had a reoccurrence.

Prognostic factors for short-term survival of dogs that experience postattenuation seizures after surgical correction of single congenital extrahepatic portosystemic shunts: 93 cases (2005-2018).

OBJECTIVE: To identify prognostic factors for short-term survival of dogs that experience seizures within 7 days after surgical correction of single congenital extrahepatic portosystemic shunts (cEHPSS). STUDY DESIGN: Multi-institutional retrospective study. SAMPLE POPULATION: Ninety-three client-owned dogs. METHODS: Medical records at 14 veterinary institutions were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 1, 2005 through February 28, 2018 and experienced postattenuation seizures (PAS) within 7 days postoperatively. Logistic regression analysis was performed to identify factors associated with 1-month survival. Factors investigated included participating institution, signalment, shunt morphology, concurrent/historical conditions, presence of preoperative neurologic signs, presence of preoperative seizures, aspects of preoperative medical management, surgical details including method and degree of shunt attenuation, type of PAS (focal only or generalized ± focal), drugs administered as part of the treatment of PAS, and development of complications during treatment of PAS. RESULTS: Thirty (32.3%) dogs survived to 30 days. Seventy-six (81.7%) dogs experienced generalized PAS. Factors positively associated with short-term survival included having a history of preoperative seizures (P = .004) and development of focal PAS only (P = .0003). Most nonsurvivors were humanely euthanized because of uncontrolled or recurrent seizures. CONCLUSION: Dogs that experienced PAS that had a history of preoperative seizures and those that experienced focal PAS only had significantly improved short-term survival. CLINICAL SIGNIFICANCE: The results of this study provide information that will help in the counseling of owners who seek treatment for PAS after surgical correction of cEHPSS. © 2020 The American College of Veterinary Surgeons.

Preliminary evaluation of an osteochondral autograft, a prosthetic implant, and a biphasic absorbable implant for osteochondral reconstruction in a sheep model.

OBJECTIVE: To determine the ability of three implants to enhance the healing of osteochondral defects: (1) a biphasic construct composed of calcium phosphate (CaP) and chitosan/cellulosic polymer, (2) a titanium-polyurethane implant, and (3) an osteochondral autograft. STUDY DESIGN: Experimental study. ANIMALS: Ten adult female sheep. METHODS: In five sheep, an 8-mm diameter osteochondral defect was created on the medial femoral condyle of a stifle and filled with a synthetic titanium-polyurethane implant. In five sheep, a similar defect was filled with an osteochondral autograft, and the donor site was filled with a biphasic construct combining CaP granules and a chitosan/cellulosic polymer. Sheep were monitored daily for lameness. Stifle radiographs and MRI were evaluated at 20 weeks, prior to animals being humanely killed. Surgical sites were evaluated with histology, microcomputed tomography, and scanning electron microscopy. RESULTS: Clinical outcomes were satisfactory regardless of the tested biomaterials. All implants appeared in place on imaging studies. Osteointegration of prosthetic implants varied between sites, with limited ingrowth of new bone into the titanium structure. Autografts and biphasic constructs were consistently well integrated in subchondral bone. All autografts except one contained a cartilage surface, and all biphasic constructs except one partially restored hyaline cartilage surface. CONCLUSION: Biphasic constructs supported hyaline cartilage and subchondral bone regeneration, although restoration of the articular cartilage was incomplete. CLINICAL IMPACT: Biphasic constructs may provide an alternative treatment for osteochondral defects, offering a less invasive approach compared with autologous grafts and eliminating the requirement for a prosthetic implant.

Effect of prophylactic treatment with levetiracetam on the incidence of postattenuation seizures in dogs undergoing surgical management of single congenital extrahepatic portosystemic shunts.

OBJECTIVE: To report the incidence of postattenuation seizures (PAS) in dogs that underwent single congenital extrahepatic portosystemic shunt (cEHPSS) attenuation and to compare incidence of PAS in dogs that either did or did not receive prophylactic treatment with levetiracetam (LEV). STUDY DESIGN: Multi-institutional retrospective study. POPULATION: Nine hundred forty dogs. METHODS: Medical records were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 2005 through July 2017 and developed PAS within 7 days postoperatively. Dogs were divided into 3 groups: no LEV (LEV-); LEV at ≥15 mg/kg every 8 hours for ≥24 hours preoperatively or a 60 mg/kg intravenous loading dose perioperatively, followed by ≥15 mg/kg every 8 hours postoperatively (LEV1); and LEV at <15 mg/kg every 8 hours, for <24 hours preoperatively, or continued at <15 mg/kg every 8 hours postoperatively (LEV2). RESULTS: Seventy-five (8.0%) dogs developed PAS. Incidence of PAS was 35 of 523 (6.7%), 21 of 188 (11.2%), and 19 of 228 (8.3%) in groups LEV-, LEV1, and LEV2, respectively. This difference was not statistically significant (P = .14). No differences between groups of dogs that seized with respect to investigated variables were identified. CONCLUSION: The overall incidence of PAS was low (8%). Prophylactic treatment with LEV according to the protocols that were investigated in our study was not associated with a reduced incidence of PAS. CLINICAL SIGNIFICANCE: Prophylactic treatment with LEV does not afford protection against development of PAS. Surgically treated dogs should continue to be monitored closely during the first 7 days postoperatively for seizures.

Human CD8+ cytotoxic T cell responses to adenovirus capsid proteins.

Adenoviruses (Ads) cause fatal disease in allogeneic stem cell transplant recipients, but there is no established therapy. Ad-specific CD8+ T cells were detected in PBMC from healthy adults at a mean frequency of 77 per 10(5) CD8+ T cells (range 8-260) by interferon-gamma ELISPOT and cytokine flow cytometry assays. CD8+ T cell lines from 7 of 7 donors exhibited MHC-class-I-restricted killing of targets expressing the capsid protein hexon. In contrast, cytotoxicity against the capsid proteins fiber and penton base was weaker or not detected. Two HLA-A2-restricted hexon epitopes and one HLA-B-restricted epitope were identified, all of which are adjacent to or overlap an HLA-DP4-restricted epitope in the highly conserved C-terminus. Thus, hexon is the immunodominant T cell target among capsid proteins and contains multiple C-terminal epitopes conserved among serotypes. These data support evaluation of donor lymphocyte infusions for treatment of Ad disease post-transplant.

The adenovirus capsid protein hexon contains a highly conserved human CD4+ T-cell epitope.

The immunogenicity of adenovirus vectors remains a major obstacle to their safe and efficacious use for gene therapy. In order to identify T-cell epitopes directly from adenoviruses, four viral protein sequences were screened for the well-characterized 9-mer HLA-A2 binding motif. Peripheral blood mononuclear cells (PBMC) from healthy adults were tested for responses to 17 selected viral peptides using a short-term interferon-gamma ELISPOT assay. Memory T-cell responses were identified to a single peptide derived from the major capsid protein hexon in 5 of 6 HLA-A2-positive donors. Unexpectedly, responses to this hexon peptide were also detected in 4 of 6 HLA-A2-negative donors, and responder cells were identified as CD4(+) T cells by immunomagnetic depletion experiments. A longer 15-mer peptide, H910-924, was identified as the optimal CD4(+) T-cell epitope. This hexon epitope induces strong proliferative T-cell responses that can be blocked by a monoclonal antibody against HLA-DR, and molecular HLA typing of donors suggests that the peptide response is restricted by multiple HLA-DR alleles. Additionally, quantitative analysis of responses to H910-924 and whole adenovirus reveals that the frequency of circulating CD4(+) T cells specific for this single hexon epitope (mean = 61 per 10(6) PBMC) represents up to one third of the total adenovirus-specific T-cell response. Finally, comparison of hexon sequences from over 20 different human adenovirus serotypes indicates that H910-924 is highly conserved. In most individuals, therefore, T-cell responses to this hexon epitope will be induced by all adenovirus vectors, including "gutted" vectors packaged with capsid proteins and vectors based on different serotypes.