Epicondylar plate fixation of humeral condylar fractures in immature French bulldogs: 45 cases (2014-2020).

OBJECTIVES: The objective of this study was to report outcome and postoperative complications following stabilisation of humeral condylar fractures in skeletally immature French bulldogs with a transcondylar screw combined with locking or hybrid locking plates. MATERIALS AND METHODS: Medical records from one referral hospital were reviewed to identify skeletally immature French bulldogs with humeral condylar fractures treated with a transcondylar screw and epicondylar locking or hybrid locking plates crossing the distal humeral physis. RESULTS: Forty-five fractures in 41 different dogs with a mean age of 4 months (range 3.5 to 5) were identified. Six cases had complications: two (4.4%) minor and four (8.9%) major. Short-term clinical outcome was excellent in 35 (77.8%), good in nine (20%) and poor in one (2.2%) case. Forty-one of 45 fractures reached radiographic union without further surgical intervention; the remaining four cases reached union following revision surgery. Long-term owner assessed outcome by telephone interview was graded as excellent in all available cases (26 of 41 dogs). CLINICAL SIGNIFICANCE: This study suggests that the stabilisation of humeral condylar fractures in skeletally immature French bulldogs with combinations of a transcondylar screw and epicondylar locking or hybrid locking plates crossing the distal humeral physis was safe and led comparable outcomes and complication rates to previous reports.

Combined internal fixation and transarticular external skeletal fixation to treat traumatic patellar fractures in five dogs.

CASE HISTORY: Medical records of dogs (n = 5) that had been treated for patellar fracture with transarticular external skeletal fixation (TA-ESF) to augment internal fixation, at a single referral hospital in the United Kingdom between 2015 and 2017, were reviewed. CLINICAL FINDINGS AND TREATMENT: At presentation, two dogs had polar patellar fractures, two had comminuted fractures and one dog had a transverse fracture. The median age at the time of the surgery was 21 (min 8, max 132) months and the median body weight was 19.0 (min 8.3, max 28.6) kg. In all cases, TA-ESF (Type IA lateral triangulated or modified Type II) was used in combination with internal fixation with pins and/or orthopaedic wire, supported by nylon leader line (patella-to-tibia mattress suture) and/or absorbable suture in a locking loop and/or circum-patellar pattern. All cases had short-term (6-12 weeks) post-operative radiographic follow-up, which showed evidence of fracture healing in 2/5 cases. All TA-ESF were removed 6 or 7 weeks post-operatively and four dogs had minor complications related to TA-ESF. More than 2 years post-operatively, the owners of all dogs were contacted and questioned using the Liverpool Osteoarthritis in Dogs questionnaire regarding the mobility of their pet. Four of the five cases were re-examined to evaluate their long-term outcomes. Based on the results of goniometric measurement of stifle range of motion, subjective gait assessment and objective gait analysis with a pressure-sensitive walkway, all dogs showed a satisfactory outcome at the final follow-up. CLINICAL RELEVANCE: A combination of internal fixation and TA-ESF for stabilisation of traumatic patellar fractures is a valid treatment option. Further investigations with larger case numbers are necessary to evaluate success and complication rates.

Cognitive speed of processing and functional declines in older cancer survivors: an analysis of data from the ACTIVE trial.

It has been suggested that chemotherapy treatment for cancer may contribute to cognitive decline in older cancer survivors. This issue is particularly important given that subtle cognitive impairment, particularly in cognitive processing speed, can affect functional status and quality of life for older adults. Multivariate regression of data from a longitudinal randomized controlled trial of older adults revealed a trend towards decreased performance after cancer treatment with chemotherapy on several functional measures associated with processing speed (as compared with matched individuals who did not have cancer). Additional analyses revealed that a subset of the chemotherapy-treated adults demonstrated a reliable negative change on several measures of processing speed. While inconclusive, this hypothesis generating work suggests that cognitive dysfunction following cancer treatment may contribute to disability observed in older cancer survivors. Further research is needed to determine the significance of the relationship between cognitive and functional impairment in older cancer survivors.

Depletion of CD4+CD25+CD127lo regulatory T cells does not increase allergen-driven T cell activation.

BACKGROUND: It has been suggested that allergic diseases are caused by defective suppression of allergen-specific Th2 cells by CD4(+)CD25(+) regulatory T cells. However, such studies have been hampered by the difficulty in distinguishing regulatory T cells from CD25-expressing activated T cells. Recently, it was shown that conventional T cells expressed high levels of CD127, whereas regulatory T cells were CD127(lo), allowing discrimination between these distinct T cell subpopulations. OBJECTIVE: The aim of this study was to study whether the putative regulatory subset defined as CD4(+)CD25(+)CD127(lo) was involved in grass pollen-reactive T cell responses. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from allergic donors and non-atopic controls out of season. Grass pollen-induced cytokine production and proliferation were compared in cultures of undepleted cells and cells depleted of CD4(+)CD25(+), CD4(+)CD25(+)CD127(hi) or CD4(+)CD25(+)CD127(lo) T cells. RESULTS: Undepleted cell cultures from allergic patients showed significantly increased proliferation and Th2 cytokine production compared with non-atopic controls. Depletion of all CD25(+) T cells did not increase cytokine production or proliferation, and more importantly, no increase in Th2 cytokine production or proliferation was observed in cell cultures depleted of CD4(+)CD25(+)CD127(lo) cells (putative regulatory T cells) compared with undepleted PBMCs in both the allergic and the non-atopic group. CONCLUSION: Our study showed that T cells from grass pollen-allergic patients and non-atopic controls responded very differently to grass pollen extract, but this difference could not be explained by differences in regulatory T cell function. Further studies are needed to understand the importance of regulatory T cells in allergy.

Assay for monitoring in vitro selective depletion strategies in allogeneic stem cell transplantation.

BACKGROUND: GvHD is a serious and potentially life-threatening side-effect of allogeneic BMT, caused by alloreactive cells attacking normal host cells. A number of different approaches have been attempted to remove allo-activated cells from the graft prior to transplantation. When developing such assays, there is a need to control for unwanted removal of cells, as well as depletion efficiency related to activation kinetics. METHODS: The specific activation induced by the superantigens SEB and TSST-1 of T cells with defined Vbeta chains was utilized to follow activation of bystander cells and the kinetics of specific cellular activation by flow cytometry. RESULTS: The activation marker CD69 was up-regulated on bystander T cells, and was only transiently highly expressed on the specific T cells, making this marker unreliable for removal of alloreactive cells. In contrast, CD25 was found only on specifically activated T cells and was stably expressed over several days. However, it was not detected on all specific cells until day 6. Likewise, proliferation occurred only in T cells expressing the expected Vbeta chains, with all activated cells having undergone at least one cell cycle by day 4. DISCUSSION: In conclusion, our assay demonstrates that only temporary bystander activation occurs when polyclonally activating T cells by SEB or TSST-1, and that CD25, but not CD69, can be used for removal of specifically activated cells. Furthermore, this assay is useful for monitoring methods aiming at specific removal of cycling cells.

T cells from multiple sclerosis patients recognize multiple epitopes on Self-IgG.

The highly diversified variable regions of immunoglobulin (Ig) molecules contain immunogenic determinants denoted idiotopes. We have previously reported that T cells from multiple sclerosis (MS) patients recognize IgG from autologous cerebrospinal fluid (CSF), and mapped a T-cell epitope to an IgG idiotope. To test the ability of CSF IgG molecules to elicit a broad polyclonal T-cell response in MS, we have analysed T-cell responses in the blood and CSF against idiotope peptides spanning complementarity determining region (CDR) 3 and somatic mutations within the variable regions of monoclonal CSF IgG. Consistent with a diversified idiotope-specific T-cell repertoire, CD4(+) T cells from both patients recognized several idiotope peptides presented by HLA-DR molecules. Mutations were critical for T-cell recognition, as T cells specific for a mutated CDR1 peptide did not recognize corresponding germline-encoded peptides. One T-cell clone recognized both an idiotope peptide and the B-cell clone expressing this idiotope, compatible with endogenous processing and presentation of this idiotope by B cells. These results suggest that mutated CSF IgG from MS patients carry several T-cell epitopes, which could mediate intrathecal IgG production and inflammation in MS through idiotope-driven T-B-cell collaboration.

Plasmacytoid dendritic cells induce a distinct cytokine pattern in virus-specific CD4+ memory T cells that is modulated by CpG oligodeoxynucleotides.

Inherent properties of dendritic cell (DC) subsets are important in the regulation of naïve T-cell differentiation (e.g. Th1 versus Th2 cells), whereas effector memory T cells are believed to produce a fixed cytokine repertoire independent of the type of antigen presenting cell. Here we show that two distinct human DC subsets, plasmacytoid DC (PDC) and myeloid CD11c+ DC, induced autologous mumps virus-specific memory CD4(+) T cells to produce markedly different cytokine patterns upon antigen stimulation. PDC stimulated the T cells to produce gamma-interferon (IFN-gamma) and interleukin-(IL)-10, whereas CD11c+ DC induced lower levels of IFN-gamma, virtually no IL-10, but significant levels of IL-5. Analysis of intracellular cytokine production showed simultaneous production of IL-10 and IFN-gamma in mumps-specific T cells activated by PDC, a cytokine pattern similar to that described for Th1-like regulatory cells. Introduction of CpG oligodeoxynucleotides in PDC/T-cell co-cultures had synergistic effect on virus-dependent IFN-gamma production, whereas the other cytokines remained unchanged. Together, our results show that the type of DC involved in reactivation of previously primed T cells may have significant impact on the resulting cytokine response and suggest that targeting of viral antigens and adjuvant to specific DC subsets should be considered in the design of therapeutic antiviral vaccines.