TIMP-1 is an activator of MHC-I expression in myeloid dendritic cells with implications for tumor immunogenicity.

Immune checkpoint therapies (ICT) for advanced solid tumors mark a new milestone in cancer therapy. Yet their efficacy is often limited by poor immunogenicity, attributed to inadequate priming and generation of antitumor T cells by dendritic cells (DCs). Identifying biomarkers to enhance DC functions in such tumors is thus crucial. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), recognized for its influence on immune cells, has an underexplored relationship with DCs. Our research reveals a correlation between high TIMP1 levels in metastatic melanoma and increased CD8 + T cell infiltration and survival. Network studies indicate a functional connection with HLA genes. Spatial transcriptomic analysis of a national melanoma cohort revealed that TIMP1 expression in immune compartments associates with an HLA-A/MHC-I peptide loading signature in lymph nodes. Primary human and bone-marrow-derived DCs secrete TIMP-1, which notably increases MHC-I expression in classical type 1 dendritic cells (cDC1), especially under melanoma antigen exposure. TIMP-1 affects the immunoproteasome/TAP complex, as seen by upregulated PSMB8 and TAP-1 levels of myeloid DCs. This study uncovers the role of TIMP-1 in DC-mediated immunogenicity with insights into CD8 + T cell activation, providing a foundation for mechanistic exploration and highlighting its potential as a new target for combinatorial immunotherapy to enhance ICT effectiveness.

Localised erythema multiforme-like reaction confined to a region of clipper burn in a dog.

Localised erythema multiforme (LEM) is only reported to occur in humans and not in domestic species. This case report describes the clinical and histopathological features of LEM-like reaction in a dog, confined to a region of clipper burn.

L'érythème polymorphe localisé (LEM) n'est signalé que chez l'homme et non chez les animaux domestiques. Ce cas clinique décrit les caractéristiques cliniques et histopathologiques d'une réaction de type LEM chez un chien, localisé sur une région de brûlure de tondeuse.

El eritema multiforme localizado (LEM) sólo se ha descrito en seres humanos y no en especies domésticas. Este artículo describe un caso de un perro con una lesión confinada a una zona de quemadura por un rasurador cuyas características clínicas e histopatológicas fueron similares a LEM.

O eritema multiforme localizado (EML) é relatado apenas em humanos e não em animais domésticos. Este relato de caso descreve as características clínicas e histopatológicas de uma reação EML-símile em um cão, limitada a uma região de queimadura por lâmina de tosa.

Multiobjective optimization identifies cancer-selective combination therapies.

Combinatorial therapies are required to treat patients with advanced cancers that have become resistant to monotherapies through rewiring of redundant pathways. Due to a massive number of potential drug combinations, there is a need for systematic approaches to identify safe and effective combinations for each patient, using cost-effective methods. Here, we developed an exact multiobjective optimization method for identifying pairwise or higher-order combinations that show maximal cancer-selectivity. The prioritization of patient-specific combinations is based on Pareto-optimization in the search space spanned by the therapeutic and nonselective effects of combinations. We demonstrate the performance of the method in the context of BRAF-V600E melanoma treatment, where the optimal solutions predicted a number of co-inhibition partners for vemurafenib, a selective BRAF-V600E inhibitor, approved for advanced melanoma. We experimentally validated many of the predictions in BRAF-V600E melanoma cell line, and the results suggest that one can improve selective inhibition of BRAF-V600E melanoma cells by combinatorial targeting of MAPK/ERK and other compensatory pathways using pairwise and third-order drug combinations. Our mechanism-agnostic optimization method is widely applicable to various cancer types, and it takes as input only measurements of a subset of pairwise drug combinations, without requiring target information or genomic profiles. Such data-driven approaches may become useful for functional precision oncology applications that go beyond the cancer genetic dependency paradigm to optimize cancer-selective combinatorial treatments.

Progenitor cells in auricular cartilage demonstrate cartilage-forming capacity in 3D hydrogel culture.

Paramount for the generation of auricular structures of clinically-relevant size is the acquisition of a large number of cells maintaining an elastic cartilage phenotype, which is the key in producing a tissue capable of withstanding forces subjected to the auricle. Current regenerative medicine strategies utilize chondrocytes from various locations or mesenchymal stromal cells (MSCs). However, the quality of neo-tissues resulting from these cell types is inadequate due to inefficient chondrogenic differentiation and endochondral ossification, respectively. Recently, a subpopulation of stem/progenitor cells has been identified within the auricular cartilage tissue, with similarities to MSCs in terms of proliferative capacity and cell surface biomarkers, but their potential for tissue engineering has not yet been explored. This study compared the in vitro cartilage-forming ability of equine auricular cartilage progenitor cells (AuCPCs), bone marrow-derived MSCs and auricular chondrocytes in gelatin methacryloyl (gelMA)-based hydrogels over a period of 56 d, by assessing their ability to undergo chondrogenic differentiation. Neocartilage formation was assessed through gene expression profiling, compression testing, biochemical composition and histology. Similar to MSCs and chondrocytes, AuCPCs displayed a marked ability to generate cartilaginous matrix, although, under the applied culture conditions, MSCs outperformed both cartilage-derived cell types in terms of matrix production and mechanical properties. AuCPCs demonstrated upregulated mRNA expression of elastin, low expression of collagen type X and similar levels of proteoglycan production and mechanical properties as compared to chondrocytes. These results underscored the AuCPCs' tissue-specific differentiation potential, making them an interesting cell source for the next generation of elastic cartilage tissue-engineered constructs.

A Simultaneous Metabolic Profiling and Quantitative Multimetabolite Metabolomic Method for Human Plasma Using Gas-Chromatography Tandem Mass Spectrometry.

For the first time it is possible to simultaneously collect targeted and nontargeted metabolomics data from plasma based on GC with high scan speed tandem mass spectrometry (GC-MS/MS). To address the challenge of getting broad metabolome coverage while quantifying known biomarker compounds in high-throughput GC-MS metabolomics, we developed a novel GC-MS/MS metabolomics method using a high scan speed (20 000 Da/second) GC-MS/MS that enables simultaneous data acquisition of both nontargeted full scan and targeted quantitative tandem mass spectrometry data. The combination of these two approaches has hitherto not been demonstrated in metabolomics. This method allows reproducible quantification of at least 37 metabolites using multiple reaction monitoring (MRM) and full mass spectral scan-based detection of 601 reproducible metabolic features from human plasma. The method showed good linearity over normal concentrations in plasma (0.06-343 to 0.86-4800 µM depending on the metabolite) and good intra- and interbatch precision (0.9-16.6 and 2.6-29.6% relative standard deviation). Based on the parameters determined for this method, targeted quantification using MRM can be expanded to cover at least 508 metabolites while still collecting full scan data. The new simultaneous targeted and nontargeted metabolomics method enables more sensitive and accurate detection of predetermined metabolites and biomarkers of interest, while still allowing detection and identification of unknown metabolites. This is the first validated GC-MS/MS metabolomics method with simultaneous full scan and MRM data collection, and clearly demonstrates the utility of GC-MS/MS with high scanning rates for complex analyses.

A high-throughput method for liquid chromatography-tandem mass spectrometry determination of plasma alkylresorcinols, biomarkers of whole grain wheat and rye intake.

Plasma alkylresorcinols are increasingly analyzed in cohort studies to improve estimates of whole grain intake and their relationship with disease incidence. Current methods require large volumes of solvent (>10 ml/sample) and have relatively low daily sample throughput. We tested five different supported extraction methods for extracting alkylresorcinols from plasma and improved a normal-phase liquid chromatography coupled to a tandem mass spectrometer method to reduce sample analysis time. The method was validated and compared with gas chromatography-mass spectrometry analysis. Sample preparation with HybridSPE supported extraction was most effective for alkylresorcinol extraction, with recoveries of 77-82% from 100 µl of plasma. The use of 96-well plates allowed extraction of 160 samples per day. Using a 5-cm NH2 column and heptane reduced run times to 3 min. The new method had a limit of detection and limit of quantification equivalent to 1.1-1.8 nmol/L and 3.5-6.1 nmol/L plasma, respectively, for the different alkylresorcinol homologues. Accuracy was 93-105%, and intra- and inter-batch precision values were 4-18% across different plasma concentrations. This method makes it possible to quantify plasma alkylresorcinols in 100 µl of plasma at a rate of at least 160 samples per day without the need for large volumes of organic solvents.

The use of mass spectrometry for analysing metabolite biomarkers in epidemiology: methodological and statistical considerations for application to large numbers of biological samples.

Data quality is critical for epidemiology, and as scientific understanding expands, the range of data available for epidemiological studies and the types of tools used for measurement have also expanded. It is essential for the epidemiologist to have a grasp of the issues involved with different measurement tools. One tool that is increasingly being used for measuring biomarkers in epidemiological cohorts is mass spectrometry (MS), because of the high specificity and sensitivity of MS-based methods and the expanding range of biomarkers that can be measured. Further, the ability of MS to quantify many biomarkers simultaneously is advantageously compared to single biomarker methods. However, as with all methods used to measure biomarkers, there are a number of pitfalls to consider which may have an impact on results when used in epidemiology. In this review we discuss the use of MS for biomarker analyses, focusing on metabolites and their application and potential issues related to large-scale epidemiology studies, the use of MS "omics" approaches for biomarker discovery and how MS-based results can be used for increasing biological knowledge gained from epidemiological studies. Better understanding of the possibilities and possible problems related to MS-based measurements will help the epidemiologist in their discussions with analytical chemists and lead to the use of the most appropriate statistical tools for these data.

Cytokine and Growth Factor Concentrations in Canine Autologous Conditioned Serum.

OBJECTIVE: To compare cytokine and growth factor concentrations in canine autologous conditioned serum (ACS) to canine plasma. STUDY DESIGN: Experimental in vivo study. ANIMALS: Client-owned, adult dogs (n=22). METHODS: Blood collected from 16 medium to large breed dogs was used to produce ACS (Orthokine(®) vet irap 10 syringes) and citrated plasma (control). Canine-specific ELISA assays were run per manufacturers' instructions for interleukin (IL)-10, IL-4, tumor necrosis factor (TNF)-α, insulin-like growth factor (IGF)-1, fibroblast growth factor (FGF)-2, transforming growth factor (TGF)-ß1, IL-1ß, and interleukin-1 receptor antagonist (IL-1ra). Serum, in addition to plasma and ACS, was collected from an additional 6 dogs for TNF-α, IL-1ß, and IL-1ra analysis (total of 22 dogs). Data were analyzed for differences in each cytokine concentration using pairwise comparisons between ACS, plasma, and serum using Wilcoxon signed-rank tests. Significance was set at P<.05. RESULTS: There was a large variability in growth factor and cytokine concentrations in ACS and plasma for individual dogs. There were no significant differences in IL-10, TNF-α, IGF-1, FGF-2, and TGF-ß1 concentrations between ACS, plasma, and serum. The IL-1ß concentrations in ACS (median, range 46.3 pg/mL, 0-828.8) and IL-4 (0.0 pg/mL, 0-244.1) were significantly higher than plasma (36.6 pg/mL, 0-657.1 and 0.0 pg/mL, 0-0, respectively). The IL-1ra concentration in ACS (median, range 3,458.9 pg/mL, 1,243.1-12,089.0) was significantly higher than plasma (692.3 pg/mL, 422.5-1,475.6). The IL-1ra:IL-1ß ratio in ACS was significantly higher than plasma (39.9 vs. 7.2). CONCLUSION: IL-1ra concentrations in canine ACS were comparable to those published for people and horses and pro-inflammatory cytokines remained low in canine ACS.

Cefazolin concentration in surgically created wounds treated with negative pressure wound therapy compared to surgically created wounds treated with nonadherent wound dressings.

OBJECTIVE: To compare cefazolin concentrations in biopsied tissue samples collected from surgically created wounds treated with negative pressure wound therapy to those collected from surgically created wounds treated with nonadherent dressings. STUDY DESIGN: Prospective, controlled, experimental study. ANIMALS: Adult female spayed Beagles (n = 12). METHODS: Full thickness cutaneous wounds were created on each antebrachium (n = 24). Immediately after surgery, cefazolin (22 mg/kg intravenously [IV]) was administered to each dog and continued every 8 hours during the study. The right wound was randomly assigned to group I or group II whereas the wound on the contralateral antebrachium was assigned to the other group. Group I wounds were treated with negative pressure wound therapy (NPWT) and group II wounds were treated with nonadherent dressings for 3 days. Dressings were changed and tissue biopsies obtained from wound beds at 24 hours intervals for both groups. Cefazolin wound tissue and plasma concentrations were measured by liquid chromatography mass spectrometry (LC-MS/MS). Blood samples for measuring plasma cefazolin concentrations were collected before biopsy sampling. At the time of surgery and at each subsequent bandage change, wound beds were swabbed and submitted for aerobic and anaerobic culture. RESULTS: After initiating cefazolin treatment, wound tissue antibiotic concentrations between treatment groups were not significantly different at any sampling time. Similarly, after initiating cefazolin treatment, plasma cefazolin concentrations were not significantly different at any sampling time for individual dogs. CONCLUSIONS: Using a canine experimental model, NPWT treatment of surgically created wounds does not statistically impact cefazolin tissue concentrations when compared with conventional nonadherent bandage therapy.

AutonoMS: Automated Ion Mobility Metabolomic Fingerprinting.

Automation is dramatically changing the nature of laboratory life science. Robotic lab hardware that can perform manual operations with greater speed, endurance, and reproducibility opens an avenue for faster scientific discovery with less time spent on laborious repetitive tasks. A major bottleneck remains in integrating cutting-edge laboratory equipment into automated workflows, notably specialized analytical equipment, which is designed for human usage. Here we present AutonoMS, a platform for automatically running, processing, and analyzing high-throughput mass spectrometry experiments. AutonoMS is currently written around an ion mobility mass spectrometry (IM-MS) platform and can be adapted to additional analytical instruments and data processing flows. AutonoMS enables automated software agent-controlled end-to-end measurement and analysis runs from experimental specification files that can be produced by human users or upstream software processes. We demonstrate the use and abilities of AutonoMS in a high-throughput flow-injection ion mobility configuration with 5 s sample analysis time, processing robotically prepared chemical standards and cultured yeast samples in targeted and untargeted metabolomics applications. The platform exhibited consistency, reliability, and ease of use while eliminating the need for human intervention in the process of sample injection, data processing, and analysis. The platform paves the way toward a more fully automated mass spectrometry analysis and ultimately closed-loop laboratory workflows involving automated experimentation and analysis coupled to AI-driven experimentation utilizing cutting-edge analytical instrumentation. AutonoMS documentation is available at https://autonoms.readthedocs.io.

Bead size has a greater effect on in vitro elution from antimicrobial-impregnated calcium sulfate beads than drug concentration.

OBJECTIVE: To compare the elution characteristics of amikacin-impregnated calcium sulfate (CaSO4) beads based on different drug concentrations and bead size configurations. SAMPLE: Six groups of amikacin-impregnated CaSO4 beads and one negative control group. PROCEDURES: Amikacin-impregnated CaSO4 beads were formed with either 500 mg (low-concentration) or 1 g (high-concentration) of amikacin per 15 g CaSO4 hemihydrate powder. The number of beads necessary to approximate 150 mg of amikacin for each of the 3 bead sizes (3 mm, 5 mm, and 7 mm) at both low and high concentrations were placed in 6 mL of phosphate-buffered saline. The saline was sampled at 14 time points over 28 days. Amikacin concentrations were determined using liquid chromatography-mass spectrometry. RESULTS: Smaller beads reached higher mean peak concentrations than larger beads (P < .0006). Peak concentrations for the low- and high-concentration groups were 20.5 mg/mL and 27.4 mg/mL, 13.1 mg/mL and 14.0 mg/mL, and 8.85 mg/mL and 6.75 mg/mL for the 3 mm, 5 mm, and 7 mm beads, respectively. Bead size also affected the length of therapeutic duration, lasting 6 days for the 3 mm and 5 mm beads and 9 days for the 7 mm beads. However, this was only statistically evident among the high-concentration beads (P < .044). Antimicrobial concentration within the same bead sizes did not affect elution. CLINICAL RELEVANCE: Amikacin-impregnated CaSO4 beads achieved extreme supratherapeutic eluent concentrations. While additional studies are needed, bead size significantly affected elution with smaller beads reaching higher peak concentrations and 7 mm, high-concentration beads demonstrating a longer therapeutic duration than smaller beads.

High-throughput metabolomics for the design and validation of a diauxic shift model.

Saccharomyces cerevisiae is a very well studied organism, yet ∼20% of its proteins remain poorly characterized. Moreover, recent studies seem to indicate that the pace of functional discovery is slow. Previous work has implied that the most probable path forward is via not only automation but fully autonomous systems in which active learning is applied to guide high-throughput experimentation. Development of tools and methods for these types of systems is of paramount importance. In this study we use constrained dynamical flux balance analysis (dFBA) to select ten regulatory deletant strains that are likely to have previously unexplored connections to the diauxic shift. We then analyzed these deletant strains using untargeted metabolomics, generating profiles which were then subsequently investigated to better understand the consequences of the gene deletions in the metabolic reconfiguration of the diauxic shift. We show that metabolic profiles can be utilised to not only gaining insight into cellular transformations such as the diauxic shift, but also on regulatory roles and biological consequences of regulatory gene deletion. We also conclude that untargeted metabolomics is a useful tool for guidance in high-throughput model improvement, and is a fast, sensitive and informative approach appropriate for future large-scale functional analyses of genes. Moreover, it is well-suited for automated approaches due to relative simplicity of processing and the potential to make massively high-throughput.

Target-specific compound selectivity for multi-target drug discovery and repurposing.

Most drug molecules modulate multiple target proteins, leading either to therapeutic effects or unwanted side effects. Such target promiscuity partly contributes to high attrition rates and leads to wasted costs and time in the current drug discovery process, and makes the assessment of compound selectivity an important factor in drug development and repurposing efforts. Traditionally, selectivity of a compound is characterized in terms of its target activity profile (wide or narrow), which can be quantified using various statistical and information theoretic metrics. Even though the existing selectivity metrics are widely used for characterizing the overall selectivity of a compound, they fall short in quantifying how selective the compound is against a particular target protein (e.g., disease target of interest). We therefore extended the concept of compound selectivity towards target-specific selectivity, defined as the potency of a compound to bind to the particular protein in comparison to the other potential targets. We decompose the target-specific selectivity into two components: 1) the compound's potency against the target of interest (absolute potency), and 2) the compound's potency against the other targets (relative potency). The maximally selective compound-target pairs are then identified as a solution of a bi-objective optimization problem that simultaneously optimizes these two potency metrics. In computational experiments carried out using large-scale kinase inhibitor dataset, which represents a wide range of polypharmacological activities, we show how the optimization-based selectivity scoring offers a systematic approach to finding both potent and selective compounds against given kinase targets. Compared to the existing selectivity metrics, we show how the target-specific selectivity provides additional insights into the target selectivity and promiscuity of multi-targeting kinase inhibitors. Even though the selectivity score is shown to be relatively robust against both missing bioactivity values and the dataset size, we further developed a permutation-based procedure to calculate empirical p-values to assess the statistical significance of the observed selectivity of a compound-target pair in the given bioactivity dataset. We present several case studies that show how the target-specific selectivity can distinguish between highly selective and broadly-active kinase inhibitors, hence facilitating the discovery or repurposing of multi-targeting drugs.

Canine spinal nephroblastoma: long-term outcomes associated with treatment of 10 cases (1996-2009).

OBJECTIVE: To report clinical outcome associated with treatment of canine spinal cord nephroblastoma (CSN). STUDY DESIGN: Case series. ANIMALS: Dogs (n=10) with histopathologically confirmed CSN. METHODS: Records of dogs with CSN were reviewed and clinicopathologic, diagnostic imaging, treatment, outcome, and survival data were collected. RESULTS: CSN resulted in clinical signs of chronic, progressive T3-L3 myelopathy in young, large breed dogs, with an overrepresentation of German Shepherd Dogs (n=4). All CSN were located between T9 and L2. Dogs treated with cytoreductive surgery (n=6) or radiotherapy (1) survived longer (median, 374 days; range, 226-560 days) than dogs treated palliatively (3; median, 55 days; range, 38-176 days). Tumors confined to an intradural-extramedullary (ID-EM) location were associated with superior survival (n=6; median, 380 days; range, 176-560 days) than tumors with intramedullary (IM) involvement (n=4; median, 140 days; range, 38-269 days). Treatment resulted in temporary improvement in neurologic function in 9 dogs, including all dogs treated surgically, but local disease progression resulted in death of 8 dogs. CONCLUSIONS: Results of this observational study suggest that surgical cytoreduction and radiotherapy are effective at improving survival in dogs with CSN, and that ID-EM tumors may be associated with a more favorable prognosis than IM neoplasms.

Rectus abdominis muscle flap for repair of prepubic tendon rupture in 8 dogs.

The clinical use and outcome of the rectus abdominis muscle flap to repair prepubic hernias were evaluated retrospectively. Medical records (2002-2007) of 8 dogs that had a rectus abdominis muscle flap to repair traumatic prepubic tendon rupture were reviewed. Only minor donor site complications were noted, including self-limiting ventral and hind-limb swelling. No long-term complications including recurrence of hernia were noted. The results of this study indicate that the rectus abdominis muscle flap is a clinically useful option for repairing prepubic tendon rupture in dogs.

Zurich Cementless Dual Mobility Cup for Canine Total Hip Prosthesis: Implant Characteristics and Surgical Outcome in 105 Cases.

Dislocation after total hip arthroplasty (THA) remains a troublesome complication, and a source of frustration for the owner and the surgeon. The dislocation rate of hip prostheses in dogs is reported to range from 4 to 15%, representing the most common short-term complication. This is especially true in large and giant breed dogs, usually requiring revision surgery. With the increase in the number of THA being performed in veterinary surgery, reducing or preventing complications such as postoperative THA dislocation will be of paramount importance. The Zurich cementless dual mobility (DM) system allows impingement-free range of angulation of 80 to 132 degrees between the ceramic head and the polyether ether ketone (PEEK) cup when combined with the range of the PEEK cup in the outer metal cup. In this article, we review the use of the DM cup in THA in large and giant breed dogs, in terms of its history, biomechanics, outcomes and complications based on 105 cases.

Biofabrication of a shape-stable auricular structure for the reconstruction of ear deformities.

Bioengineering of the human auricle remains a significant challenge, where the complex and unique shape, the generation of high-quality neocartilage, and shape preservation are key factors. Future regenerative medicine-based approaches for auricular cartilage reconstruction will benefit from a smart combination of various strategies. Our approach to fabrication of an ear-shaped construct uses hybrid bioprinting techniques, a recently identified progenitor cell population, previously validated biomaterials, and a smart scaffold design. Specifically, we generated a 3D-printed polycaprolactone (PCL) scaffold via fused deposition modeling, photocrosslinked a human auricular cartilage progenitor cell-laden gelatin methacryloyl (gelMA) hydrogel within the scaffold, and cultured the bioengineered structure in vitro in chondrogenic media for 30 days. Our results show that the fabrication process maintains the viability and chondrogenic phenotype of the cells, that the compressive properties of the combined PCL and gelMA hybrid auricular constructs are similar to native auricular cartilage, and that biofabricated hybrid auricular structures exhibit excellent shape fidelity compared with the 3D digital model along with deposition of cartilage-like matrix in both peripheral and central areas of the auricular structure. Our strategy affords an anatomically enhanced auricular structure with appropriate mechanical properties, ensures adequate preservation of the auricular shape during a dynamic in vitro culture period, and enables chondrogenically potent progenitor cells to produce abundant cartilage-like matrix throughout the auricular construct. The combination of smart scaffold design with 3D bioprinting and cartilage progenitor cells holds promise for the development of clinically translatable regenerative medicine strategies for auricular reconstruction.

Computed tomographic and cross-sectional anatomic characterization of myofascial compartments and soft tissue spaces in the manus in cadavers of dogs without forelimb disease.

OBJECTIVE: To characterize the computed tomographic (CT) and cross-sectional anatomic features of myofascial compartments and soft tissue spaces in the manus of cadavers of dogs without forelimb disease. ANIMALS: 33 cadavers of adult medium- to large-breed dogs without forelimb disease. PROCEDURES: Forelimbs were removed from the cadavers within 4 hours after euthanasia or within 6 hours after thawing from initial freezing. Specimens were then frozen for variable periods and thawed for approximately 16 hours before use. Each manus of 60 forelimbs underwent CT before and after injection of a radiopaque, blue-staining contrast medium into locations where soft tissue spaces and myofascial compartments were predicted (on the basis of pilot study data [6 forelimbs]). Two veterinary radiologists reviewed CT images and recorded the presence or absence of a discrete space or compartment at each injection site. Each manus was subsequently dissected or sectioned transversely. Locations of blue-staining contrast medium accumulation were compared with locations of contrast enhancement in CT images. Anatomic structures within each soft tissue space or myofascial compartment were described. RESULTS: 13 soft tissue spaces and 5 myofascial compartments were identified in the manus. Three myofascial structures that were examined were determined not to be compartments. CONCLUSIONS AND CLINICAL RELEVANCE: Knowledge of soft tissue spaces and myofascial compartments are used to map the likely spread of disease in the hands and feet of humans. Thus, understanding the locations and extent of similar structures in the canine manus may improve the effectiveness of surgical interventions in dogs with injury or inflammation of this region of the forelimb.

Modeling of the spread of infection in the interdigital spaces of the manus in limbs from clinically normal dogs.

OBJECTIVE: To determine whether the pattern of extension of modeled infection from the interdigital web spaces in dogs is predictable and whether the distribution differs among initial injury sites. SAMPLE POPULATION: Thawed frozen forelimbs from 23 cadavers of previously healthy adult medium- to large-breed dogs. PROCEDURES: The manus of each forelimb was evaluated by use of computed tomography (CT) before and after injection of radiopaque blue-staining contrast medium into the interdigital web spaces. Two veterinary radiologists reviewed the CT images and recorded the extent of contrast medium from each site. Each manus was dissected or sectioned transversely after imaging, and the extent of contrast medium accumulation was recorded and compared with locations of CT contrast enhancement. The Fisher exact test was performed to determine whether the pattern of contrast medium extension differed by injection site. RESULTS: Injections made in the interdigital web spaces of the canine manus led to unique and predictable patterns of extension into the surrounding soft tissues. That pattern of extension primarily involved the soft tissues of the digits. CONCLUSIONS AND CLINICAL RELEVANCE: In humans, knowledge of common extension patterns from infected soft tissue spaces is used to predict the spread of disease within the hand and develop surgical plans that will minimize patient illness. Identification of the common sites of disease spread from the interdigital web spaces in dogs may help improve surgical planning and treatment for infection in the manus.