Background In kinematic alignment in TKA, the aim is to match the implant’s position to the pre-arthritic anatomy of an individual patient, in contrast to the traditional goal of neutral mechanical alignment. However, there are limited mid-term, comparative data for survivorship and functional outcomes for these two techniques. Questions/purposes In the setting of a randomized, controlled trial at 5 years, is there a difference between kinematic alignment and mechanical alignment in TKA in terms of (1) patient-reported outcome measures, (2) survivorship free from revision or reoperation, and (3) the incidence of radiographic aseptic loosening? Methods In the initial study, 99 primary TKAs for osteoarthritis were randomized to either the mechanical alignment (n = 50) or kinematic alignment (n = 49) group. Computer navigation was used in the mechanical alignment group, and patient-specific cutting blocks were used in the kinematic alignment group. At 5 years, 95% (48 of 50) of mechanical alignment and 96% (47 of 49) of kinematic alignment TKAs were available for follow-up. Knee function was assessed using the Knee Society Score (KSS), VAS, Oxford Knee Score (OKS), WOMAC, Forgotten Joint Score (FJS) and EuroQol 5D. Survivorship free from reoperation (any reason) and revision (change or addition of any component) was determined via Kaplan-Meier analysis. Radiographs were assessed for signs of aseptic loosening (as defined by the presence of progressive radiolucent lines in two or more zones) by a single blinded observer. Results At 5 years, there were no differences in any patient-reported outcome measure between the two groups. For example, the mean OKS did not differ between the two groups (kinematic alignment: 41.4 ± 7.2 versus mechanical alignment: 41.7 ± 6.3; difference -0.3 [95% confidence interval - 3.2 to 2.5]; p = 0.99). At 5 years, survivorship free from reoperation was 92.2 (95% CI 80.4 to 97.0) for mechanical alignment and 89.7 (95% CI 77.0 to 95.6) for kinematic alignment (log rank test; p = 0.674), survivorship free from revision was 94.1 (95% CI 82.9 to 98.1) for mechanical alignment and 95.9 (95% CI 84.5 to 99.0) for kinematic alignment (log rank test; p = 0.681). At 5 years, one patient demonstrated radiographic aseptic loosening for the mechanical alignment group; no cases were identified for the kinematic alignment group. Conclusions We found no mid-term functional or radiographic differences between TKAs with mechanical alignment or kinematic alignment. The anticipated improvements in patient-reported outcomes with kinematic alignment were not realized. Because kinematic alignment results in a high proportion of patients whose tibial components are inserted in varus, loosening remains a potential long-term concern. Given the unknown impact on long-term survivorship of the substantial alignment alterations with kinematic alignment, our findings do not support the routine use of kinematic alignment outside of a research setting. Level of Evidence Level I, therapeutic study.

Fat accumulates in bone marrow (BM) of patients with diabetes. In this study, we investigated the mechanisms and consequences of this phenomenon. BM mesenchymal stromal cells (BM-MSCs) from patients with type 2 diabetes (T2D) constitutively express adipogenic markers and robustly differentiate into adipocytes (ADs) upon in vitro induction as compared with BM-MSCs from subjects without diabetes. Moreover, BM-ADs from subjects with T2D (T2D BM-ADs) paracrinally stimulate a transcriptional adipogenic program in BM-MSCs. Antagonism of MCP-1, a chemokine pivotally expressed in T2D BM-ADs, prevented the T2D BM-AD secretome from converting BM-MSCs into ADs. Mechanistic validation of human data was next performed in an obese T2D mouse model. Systemic antagonism of MCP-1 improved metabolic control, reduced BM fat, and increased osteocyte density. It also indirectly re-established the abundance of long-term versus short-term hematopoietic stem cells. We reveal a diabetic feedback loop in which ) BM-MSCs are constitutively inclined to make ADs, and) mature BM-ADs, via secreted MCP-1, relentlessly fuel BM-MSC determination into new fat. Pharmacological inhibition of MCP-1 signaling can contrast this vicious cycle, restoring, at least in part, the balance between adipogenesis and hematopoiesis in BM from subjects with T2D.

ObjectivesModular junctions are ubiquitous in contemporary hip arthroplasty. The head-trunnion junction is implicated in the failure of large diameter metal-on-metal (MoM) hips which are the currently the topic of one the largest legal actions in the history of orthopaedics (estimated costs are stated to exceed $4 billion). Several factors are known to influence the strength of these press-fit modular connections. However, the influence of different head sizes has not previously been investigated. The aim of the study was to establish whether the choice of head size influences the initial strength of the trunnion-head connection.Materials and MethodsTi-6Al-4V trunnions (n = 60) and two different sizes of cobalt-chromium (Co-Cr) heads (28 mm and 36 mm; 30 of each size) were used in the study. Three different levels of assembly force were considered: 4 kN; 5 kN; and 6 kN (n = 10 each). The strength of the press-fit connection was subsequently evaluated by measuring the pull-off force required to break the connection. The statistical differences in pull-off force were examined using a Kruskal–Wallis test and two-sample Mann–Whitney U test. Finite element and analytical models were developed to understand the reasons for the experimentally observed differences.Results36 mm diameter heads had significantly lower pull-off forces than 28 mm heads when impacted at 4 kN and 5 kN (p < 0.001; p < 0.001), but not at 6 kN (p = 0.21). Mean pull-off forces at 4 kN and 5 kN impaction forces were approximately 20% larger for 28 mm heads compared with 36 mm heads. Finite element and analytical models demonstrate that the differences in pull-off strength can be explained by differences in structural rigidity and the resulting interface pressures.ConclusionThis is the first study to show that 36 mm Co-Cr heads have up to 20% lower pull-off connection strength compared with 28 mm heads for equivalent assembly forces. This effect is likely to play a role in the high failure rates of large diameter MoM hips.Cite this article: A. R. MacLeod, N. P. T. Sullivan, M. R. Whitehouse, H. S. Gill. Large-diameter total hip arthroplasty modular heads require greater assembly forces for initial stability. Bone Joint Res 2016;5:338–346. DOI: 10.1302/2046-3758.58.BJR-2016-0044.R1.

Aims/hypothesis Previous studies have shown that diabetes mellitus destabilises the integrity of the microvasculature in different organs by damaging the interaction between pericytes and endothelial cells. In bone marrow, pericytes exert trophic functions on endothelial cells and haematopoietic cells through paracrine mechanisms. However, whether bone marrow pericytes are a target of diabetes-induced damage remains unknown. Here, we investigated whether type 2 diabetes can affect the abundance and function of bone marrow pericytes. Methods We conducted an observational clinical study comparing the abundance and molecular/functional characteristics of CD146 + pericytes isolated from the bone marrow of 25 individuals without diabetes and 14 individuals with uncomplicated type 2 diabetes, referring to our Musculoskeletal Research Unit for hip reconstructive surgery. Results Immunohistochemistry revealed that diabetes causes capillary rarefaction and compression of arteriole size in bone marrow, without changing CD146 + pericyte counts. These data were confirmed by flow cytometry on freshly isolated bone marrow cells. We then performed an extensive functional and molecular characterisation of immunosorted CD146 + pericytes. Type 2 diabetes caused a reduction in pericyte proliferation, viability, migration and capacity to support in vitro angiogenesis, while inducing apoptosis. AKT is a key regulator of the above functions and its phosphorylation state is reportedly reduced in the bone marrow endothelium of individuals with diabetes. Surprisingly, we could not find a difference in AKT phosphorylation (at either Ser473 or Thr308) in bone marrow pericytes from individuals with and without diabetes. Nonetheless, the angiocrine signalling reportedly associated with AKT was found to be significantly downregulated, with lower levels of fibroblast growth factor-2 (FGF2) and C-X-C motif chemokine ligand 12 (CXCL12), and activation of the angiogenesis inhibitor angiopoietin 2 (ANGPT2). Transfection with the adenoviral vector carrying the coding sequence for constitutively active myristoylated AKT rescued functional defects and angiocrine signalling in bone marrow pericytes from diabetic individuals. Furthermore, an ANGPT2 blocking antibody restored the capacity of pericytes to promote endothelial networking. Conclusions/interpretation This is the first demonstration of pericyte dysfunction in bone marrow of people with type 2 diabetes. An altered angiocrine signalling from pericytes may participate in bone marrow microvascular remodelling in individuals with diabetes. Electronic supplementary material The online version of this article (10.1007/s00125-019-4865-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

The latest NICE guidance dictates that all patients undergoing lower-limb arthroplasty should be prescribed potent venous thromboembolic (VTE) prophylaxis. However, use of potent anti-thrombotics is likely to lead to increased post-operative wound ooze. Postoperative wound ooze is associated with increased risk of infection. This study used a prospective, consecutive, multi-surgeon sample of 110 patients undergoing primary total hip replacement (THR) and total knee replacement (TKR) prescribed either direct thrombin inhibitor (DTI) (n=51, 26 males: 25 females, age 69 ±18) or aspirin (n=59, 25 males: 34 females, age 69 ± 19). Hospital stay, body mass index (BMI), wound length and patient demographics were documented along with a daily assessment of wound ooze. The use of DTI's was associated with a significant increase in mean days to dryness in both THR (6.2 ± 0.98, 95% C.I. 5.2-7.1) and TKR (6.6 ± 1.89, 95% C.I. 4.7-8.5) compared to aspirin in THR (3.0 ± 1.03, 95% C.I 1.9-4.0) and TKR (3.4 ± 1.21, 95% C.I 2.2-4.6) with p-values of <0.0001 and 0.0024 for THR and TKR respectively. Age, gender and wound length were not found to be significant confounding variables. DTI's proven benefit in lowering venous thromboembolism when compared with aspirin needs to be balanced with their increased cost and increased duration of wound ooze.

Osteoarthritis (OA) and osteoporosis (OP) are historically considered to be inversely correlated but there may be an overlap between the pathophysiology of the two diseases. This study aimed to investigate the subchondral bone microarchitecture and matrix mineralization, and the association between them in OA and OP in relation to the degree of cartilage degeneration. Fifty-six osteochondral plugs were collected from 16 OA femoral heads. They were graded on a regional basis according to the stages of cartilage degeneration, as evaluated by a new macroscopic and a modified microscopic grading system. Twenty-one plugs were collected from seven femoral heads with OP. Plugs were scanned by microcomputed tomography and the microarchitectural and mineral properties were obtained for both subchondral plate and trabecular bone. Microarchitecture and material and apparent densities of subchondral bone in OP were similar to regions with early cartilage degeneration but different from regions with advanced cartilage degradation in OA femoral heads. Subchondral trabecular bone was more mineralized than subchondral plate in both OP and OA, and this compartmental difference varied by severity of cartilage degradation. Furthermore, the relationship among trabecular bone volume fraction, tissue mineral density, and apparent bone density was similar in OP and different stages of OA. Subchondral bone microarchitecture and mineral properties in OP are different from OA in a regionalized manner in relation to stages of cartilage degeneration. Both regional and compartmental differences at structural, material, and cellular levels need to be studied to understand the transition of OA subchondral bone from being osteoporotic to sclerotic.

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A 7-year-old, spayed female Domestic Longhair cat was evaluated for a 6-week history of coughing. Thoracic radiography revealed a pleural effusion. Thoracic ultrasound revealed a pleural effusion and a focal lung mass. The cat underwent exploratory thoracotomy and a total left pneumonectomy was performed. Histopathology and cultures revealed fungal pneumonia and pyothorax caused by Aspergillus fumigatus. Abdominal ultrasound, repeat thoracic radiography, urinalysis with culture, and retroviral screening failed to detect evidence of systemic disease. The cat's poorly regulated diabetes mellitus is suspected to be the predisposing factor allowing a fungal pulmonary infection to become established. At 18 months after surgery the cat was still disease-free. To our knowledge this is the first reported case of successful treatment of pulmonary aspergillosis in the cat.