Complications and cost of single-stage vs. two-stage bilateral unicompartmental knee arthroplasty: A case-control study.

BACKGROUND: Single-stage bilateral knee arthroplasty, even when unicompartmental, remains controversial, chiefly due to the risk of peri-operative complications. The primary objective of this study was to compare the short-term complication rate and cost of single- vs. two-stage bilateral unicompartmental knee arthroplasty (UCA). The secondary objective was to compare total hospital stay lengths and motion-range recovery. HYPOTHESIS: Single-stage bilateral UCA is a cost-saving alternative that is not associated with higher complication rates compared to two-stage bilateral UCA. MATERIAL AND METHOD: This single-centre retrospective comparative study included 70 patients of any age managed between 2010 and 2016. Among them, 44 (88 UKAs) had single-stage surgery (1S group) and 26 (52 UCAs) two-stage surgery (2S group). The two groups were comparable for age, body mass index, gender distribution, compartment replaced, ASA score, and Charlson comorbidity index. The following were evaluated: operative time, haemoglobin level before and after surgery, major and minor complication rates, motion-range recovery, and the radiographic hip-knee-ankle (HKA) angle. Costs were estimated based on the standard codes assigned to the procedures by the national statutory health insurance system (GHM 08C24 for knee arthroplasty to treat knee osteoarthritis and NFKA006 for unicompartmental tibio-femoral or femoro-patellar arthroplasty), modulated according to the concomitant diagnoses. RESULTS: No differences were found for the haemoglobin level change, time to motion-range recovery, or HKA angle. The complication rates per patient were not significantly different between the groups: major complications, 9.1% (n=4) in the 1S group and 15.4% (n=4) in the 2S group (p=1.00); minor complications, 4.5% (n=2) in the 1S group and 3.8% (n=1) in the 2S group (p=1.00). Cost of the total hospital stay was significantly higher in the 2S group than in the 1S group (11,766.7€) and 5626.4€, respectively; p<0.001). Mean total hospital stay duration per patient was 6.7 days with single-stage surgery and 13.4 days with two-stage surgery. DISCUSSION: Single-stage bilateral UCA is not associated with a higher rate of peri-operative complications compared to the two-stage alternative and is substantially less costly. Financial incentives from the healthcare authorities are warranted to increase the use of the single-stage procedure. LEVEL OF EVIDENCE: III, case-control study.

Retrospective evaluation of toceranib phosphate (Palladia®) toxicity in cats.

The purpose of this study was to describe the toxicity profile of toceranib phosphate in tumour bearing cats. Medical records were reviewed from seven institutions. Patients with incomplete medical records and those receiving concurrent chemotherapy or NSAIDs (non-steroidal anti-inflammatory) were excluded. Fifty-five cats met the inclusion criteria. Carcinoma was diagnosed in 55% of cases. Median oral toceranib dose was 2.7 mg kg-1 and was most commonly administered on Monday, Wednesday and Friday. Thrombocytopenia (16.3%) and neutropenia (9.1%) were the most common haematologic toxicities. Azotemia (14.5%) and alanine aminotransferase (ALT) elevations (7.2%) were the most frequently encountered biochemical alterations. Gastrointestinal (GI) toxicity was seen in 21.8% of cats, and was lower than previously reported in dogs. The results of this study showed that treatment of cats with toceranib is well-tolerated and toxicity is uncommon. Additional studies to define a more structured dosing schedule and to evaluate the efficacy of toceranib in the treatment of feline cancers are needed.

Do temperature variations at the bearing surface during gait affect polyethylene wear in Charnley low-friction arthroplasty of the hip? Simulator study comparing UHMWPE and highly cross-linked polyethylene.

INTRODUCTION: There are significant individual variations in the polyethylene (PE) wear of Charnley total hip arthroplasty (THA) in published studies. This could be in part related to variations in hip joint kinematics with abnormal heating at the metal/PE interface. The objectives of our hip simulator experiment were: (1) to measure PE wear as a function of hip kinematics and temperature variations at the interface; (2) to compare ultra-high molecular weight polyethylene (UHMWPE) to latest generation highly cross-linked PE (XLPE). HYPOTHESIS: Our hypothesis was that PE wear is correlated with temperature increases at the interface and thereby hip joint kinematics. MATERIAL AND METHODS: A simulator study was performed with four UHMWPE cups (Initiale™, Amplitude, Valence, France) and two XLPE cups (X3, Stryker, Kalamazoo, Michigan, USA) subjected to 5 million cycles each. The temperature at the femoral head/cup interface was measured every 500 cycles and implant dimensions were measured every 1 million cycles. RESULTS: The average temperature was 42°C for 1Hz and 50°C for 1.5Hz, no matter the type of PE tested. There was a large difference between UHMWPE and XLPE in their roughness, but no temperature variations or wear effects. Femoral head penetration after the first 1 million cycles was 0.18mm for the XLPE and 0.075mm UHMWPE on average. Between 1 and 5 million cycles, the penetration was less than 0.1mm per million cycles, with XLPE being similar to UHMPWE. DISCUSSION: Our study found a significant temperature increase at the bearing interface as a function of frequency. But there was no correlation between temperature variations and PE degradation. However, shear stresses were under-estimated because our simulator could not reproduce abduction and adduction movements. Our hypothesis was not confirmed because PE deformation was not correlated to temperature variations. XLPE was not better than UHMWPE in the particular conditions of this study. Simulator studies are limited because of the lack of standards on cycling and the simulator bath. LEVEL OF EVIDENCE: III-prospective case-control study in vitro.

Histology and clinical outcome of benign and malignant vascular lesions primary to feline cervical lymph nodes.

A novel form of primary feline hemangiosarcoma and additional cases of plexiform vascularization in the cervical lymph nodes are reported. Sixteen cases of feline lymphadenopathy attributed to abnormal vascular proliferation were identified and evaluated. Most of these lesions were diagnosed histologically as hemangiosarcoma. However, lesions of plexiform vascularization, with and without areas of putative malignant transformation, were also identified. Mean age of the cats was 11 years (range, 3-16 years) with most being domestic shorthair and medium hair (13). Two domestic long hair and 1 Maine Coon were identified. Excisional nodal biopsy was performed in 15 cases and incisional biopsy in 1 case. Six cats were euthanized due to their disease. Survival times ranged from ≤ 1 month to ≥ 30 months. We provide a new clinical differential for cervical lymphadenopathy in cats that is not widely recognized. Proper identification of primary nodal vascular lesions in cats will enable further characterization of clinical features and biologic behavior to determine specific therapy.

The use of megavoltage radiation therapy in the treatment of thymomas in rabbits: 19 cases.

An overall median survival time (MST) and prognostic factors in rabbits with thymomas treated with megavoltage radiation therapy (RT) were determined in this multi-institutional retrospective case analysis. Medical records for 19 rabbits with suspected or confirmed thymomas treated with RT were evaluated for data including signalment, haematological and serum biochemistry abnormalities, presence of pleural effusion, radiation plan, body weight, total radiation dose and institution administering RT. Statistical significance of these factors related to overall survival was assessed. An overall MST for all 19 rabbits was 313 days; exclusion of 3 rabbits that died acutely during the first 14 days of RT yielded a MST of 727 days. The only factor associated with a significantly decreased survival time was having a body weight lower than mean body weight of 1.57 kg. Radiation treatment-associated complications were infrequent and included radiation-induced myocardial failure, radiation pneumonitis and alopecia.

Platelet-derived microparticles on synthetic surfaces observed by atomic force microscopy and fluorescence microscopy.

Platelet activation on a thrombogenic surface includes the release of membrane-derived microparticles that provide catalytic sites for blood coagulation factors. Here, we describe a quantitative investigation on the production and dimensions of platelet-derived microparticles observed on glass and polyethylene under aqueous conditions, using atomic force microscopy (AFM) and complementary fluorescence microscopy. The results show that contact-activated platelet microparticles are not evenly distributed over a thrombogenic surface, but in clusters in close proximity to adherent platelets. The microparticles are localized near the platelet periphery, and in some cases appear to emanate from platelet pseudopodia, suggesting that formation may result from vesiculation of the pseudopodia. The microparticles measured 125 +/- 21 nm (n = 73) in the x-y dimensions and 5.2 +/- 3.6 nm in height. The results compared closely with 125 +/- 22 nm width and 4.1 +/- 1.6 nm height obtained for control preparations of thrombin activated microparticles, that were filtered and deposited on glass. Large differences between the measured widths and heights of adsorbed microparticles suggest that platelet microparticles may undergo spreading after attachment to a surface. The adsorbed microparticles expressed platelet membrane receptor GPIIb/IIIa, and many expressed the platelet activation marker P-selectin as determined by fluorescence microscopy. The high number distribution of procoagulant microparticles per unit area of surface compared with platelets suggests that platelet-derived microparticles provide a mechanistic route for amplifying thrombus formation on a thrombogenic surface.

Intermolecular force mapping of platelet surfaces on collagen substrata.

The interactions between plasma proteins and platelets are responsible for surface adsorption and activation of platelets, which leads to initiation of platelet-mediated thrombotic events at biomaterial surfaces. We are seeking to gain a fundamental understanding of these interactions. The atomic force microscope (AFM) has been used to create force maps across platelets adsorbed onto collagen substrata using peptide-modified probes. Combining the imaging and force-measuring capabilities of AFM, the force-mapping mode has been used to measure interactions of peptide-modified AFM probes with the surface. Observed differences in the force of adhesion are clearly evident in the platelet samples fixed in air, proving the ability of the AFM system to map adhesion. When this system is changed to a fluid environment we are no longer able to see such evident adhesion because of the membrane flexibility; instead the deformability of the surface is mapped. The specific interaction between the peptide sequence RGD and platelets was measured in a non-mapping mode of the AFM. Although this does not provide a force map, we can see significant differences between the forces measured on the substrate and those measured with a control hexapeptide.

Atomic force microscopy for characterization of the biomaterial interface.

The molecular processes that occur at the interface of an implanted biomaterial determines the host response, including phenomena such as protein adsorption, conformational changes, and subsequent interactions with cellular components. Until recently, such processes could not be observed directly. Over the past decade, atomic force microscopy (AFM) has provided mechanistic insights into the molecular level interactions that occur at the biomaterial interface. Several unique operational modes have been developed which utilize intermittent contact with the sample and decrease applied shear forces. These dynamic modes also can be used to study the role of different structural components on biomaterial micromechanical properties. Force detection techniques allow molecular level studies of individual receptor-ligand binding events, and force mapping for determining structure/function relationships. Advancements in tip manufacturing, image processing techniques, the use of model surfaces and labeling all have contributed to the advancement of the AFM as a state-of-the-art research instrument. In this report, we examine the applicability of the AFM to the study of biomaterials and cell/molecular interactions.

Three dimensional structure of human fibrinogen under aqueous conditions visualized by atomic force microscopy.

Fibrinogen plays a central role in surface-induced thrombosis. However, the interactions of fibrinogen with different substrata remain poorly understood because of the difficulties involved in imaging globular proteins under aqueous conditions. We present detailed three dimensional molecular scale images of fibrinogen molecules on a hydrophobic surface under aqueous conditions obtained by atomic force microscopy. Hydrated fibrinogen monomers are visualized as overlapping ellipsoids; dimers and trimers have linear conformations predominantly, and increased affinity for the hydrophobic surface compared with monomeric fibrinogen. The results demonstrate the importance of hydration on protein structure and properties that affect surface-dependent interactions.

Shear-dependent changes in the three-dimensional structure of human von Willebrand factor.

The three-dimensional tertiary structure of human von Willebrand Factor (vWF) on a hydrophobic surface under aqueous conditions and different shear stress regimes was studied by atomic force microscopy (AFM). vWF was imaged by AFM at molecular level resolution under negligible shear stress, under a local applied shear force (7.4 to 19 nN) using the AFM probe in contact mode scanning, and after subjecting vWF to a range of shear stress (0 to 42.4 dyn/cm2) using a rotating disk system. The results demonstrate that vWF undergoes a shear stress-induced conformational transition from a globular state to an extended chain conformation with exposure of intra-molecular globular domains at a critical shear stress of 35 +/- 3.5 dyn/cm2. The globular vWF conformation (149 nm by 77 nm and height 3.8 nm) is representative of native vWF after simple diffusion to the hydrophobic surface, followed by adhesion and some spreading. In a shear stress field above the critical value, protein unfolding occurs and vWF is observed in extended chain conformations oriented in the direction of the shear stress field with molecular lengths ranging from 146 to 774 nm and 3.4 nm mean height. The shear stress-induced structural changes to vWF suggest a close conformation-function relationship in vWF properties for thrombogenesis in regions of high shear stress.

Interactions of human von Willebrand factor with a hydrophobic self-assembled monolayer studied by atomic force microscopy.

Human von Willebrand Factor (vWF) was studied by atomic force microscopy under physiologic buffer on a hydrophobic octadecyltrichlorosilane self-assembled monolayer. The self-assembled monolayer deposited on glass was sufficiently smooth (root mean square roughness = 0.25 +/- 0.12 nm) to permit identification of adsorbed vWF. Adhesion of the protein to the hydrophobic substrate was sufficient to allow repeated scanning by the atomic force microscope probe, and images of vWF on a submolecular scale were obtained. The frictional force between the surface and the protein was sufficient to withstand an applied lateral force of 19 nN. This result shows that vWF experiences strong interaction with a hydrophobic surface in aqueous media. Statistical analysis of adsorbed vWF shows that the protein is composed of large globular domains with elliptical cross sections of average dimensions 56 +/- 24 nm (major axis) 26 +/- 19 nm (minor axis), and 2.8 +/- 1.0 nm (height). Further analysis of the major axis dimension shows that the molecular chain of vWF contains two statistically different populations of domain size. However, no sequence order of the different domains within the individual molecule was found. On the basis of our analysis of the globular domains, we present a model describing the three-dimensional structure of vWF protomer adsorbed on a hydrophobic surface in a physiologic solution.