Is wear debris responsible for failure in alumina-on-alumina implants?: Clinical, histological, and laboratory investigations of 30 revision cases with a median follow-up time of 8 years

Background and purpose Ceramic-on-ceramic articulation is an attractive alternative to metal-on-polyethylene (PE) bearings, but little is known about the in vivo effects induced by dissemination of alumina wear debris in the periprosthetic tissues. We hypothesized that wear debris is not the main factor responsible for loosening and failure of the implant but that mechanical problems caused by incorrect surgical technique, prosthetic design, or trauma, may cause instability of the implants and result in production of wear debris

Idiopathic and secondary osteonecrosis of the femoral head show different thrombophilic changes and normal or higher levels of platelet growth factors

BACKGROUND AND PURPOSE: Thrombophilia represents a risk factor both for idiopathic and secondary osteonecrosis (ON). We evaluated whether clotting changes in idiopathic ON were different from corticosteroid-associated ON. As platelet-rich plasma has been proposed as an adjuvant in surgery, we also assessed whether platelet and serum growth factors were similar to those in healthy subjects. METHODS: 18 patients with idiopathic ON and 18 with corticosteroid-associated ON were compared with 44 controls for acquired and inherited thrombophilia. Platelet factor 4 (PF4), transforming growth factor-β1, platelet-derived growth factor-BB (PDGF-BB), and vascular endothelial growth factor were assayed in the supernatants of thrombin-activated platelets, in platelet lysates, and in serum from 14 ON patients and 10 controls. RESULTS: Idiopathic ON patients had higher plasminogen levels (median 118%) than controls (101%) (p = 0.02). Those with corticosteroid-associated ON had significantly higher D-dimer (333 ng/mL) and lower protein C levels (129%) than controls (164 ng/mL, p = 0.004; 160%, p = 0.02). The frequency of inherited thrombophilia was not different from the controls. No statistically significant differences were found between idiopathic and corticosteroid-associated ON. 20 of the 36 ON patients were smokers. (The controls were selected from smokers because nicotine favors hypercoagulability). ON patients had significantly higher serum PF4 levels (7,383 IU/mL) and PDGF-BB levels (3.1 ng/mL) than controls (4,697 IU/mL, p = 0.005; 2.2 ng/mL, p = 0.02). INTERPRETATION: Acquired hypercoagulability was common in both ON types, but the specific changes varied. The release of GF from platelets was not affected, providing a biological basis for platelet-rich plasma being used as an adjuvant in surgical treatment

Classification of Septic Shock Phenotypes Based on the Presence of Hypotension and Hyperlactatemia in Cats

open8noBackground: Three different phenotypes of septic shock based on changes in blood pressure and lactate are recognized in people. Dysoxic shock, representing the combination of fluid-refractory hypotension and hyperlactatemia, is characterized by greater disease severity and mortality compared to cryptic shock (hyperlactatemia alone) and vasoplegic shock (hypotension with normal blood lactate). Little is known about septic shock and specifically its phenotypes in cats. Objective: To analyze the characteristics and prognostic implications of three septic shock phenotypes in cats with sepsis. Methods: Cats with septic shock were prospectively included. Septic shock was defined by the presence of hypotension (mean blood pressure <60 mmHg) requiring vasopressor support and/or persistent hyperlactatemia (>4 mmol/L) and classified in three subgroups: dysoxic shock, vasoplegic shock and cryptic shock. Clinical and clinicopathological variables including APPLEfast and APPLEfull scores, occurrence of multi-organ dysfunction syndrome (MODS; presence of at least two dysfunctional organs simultaneously) and outcome were compared among subgroups. Cats with sepsis showing normal blood pressure and lactate concentrations hospitalized during the study period were included as uncomplicated sepsis, and compared to cats with septic shock for selected variables. Length of hospital stay and mortality were evaluated in the whole study population. Odds ratios for mortality were calculated using logistic regression analysis. Significance was set at P < 0.05. Results: The study enrolled 48 cats with uncomplicated sepsis and 37 cats with septic shock (dysoxic shock n = 17; vasoplegic shock n = 11; cryptic shock n = 7). Cats with dysoxic shock had significantly higher APPLEfast and APPLEfull scores compared to vasoplegic and cryptic shock. Mortality rates were not significantly different among cryptic (57%), dysoxic (65%) and vasoplegic shock (91%), while MODS occurrence was significantly lower in cats with cryptic shock (57%) compared to patients affected by dysoxic (94%) and vasoplegic (100%) shock. Cats with septic shock had higher frequency of MODS and greater mortality rate than cats with uncomplicated sepsis. Conclusion: Despite similar in-hospital mortality, cats with dysoxic and vasoplegic shock are characterized by having higher occurrence of multi- organ dysfunction compared to cats affected by cryptic shock. Results from this study suggest novel means of identifying high-risk subgroups of septic cats.openTroia R.; Buzzurra F.; Ciuffoli E.; Mascalzoni G.; Foglia A.; Magagnoli I.; Dondi F.; Giunti M.Troia R.; Buzzurra F.; Ciuffoli E.; Mascalzoni G.; Foglia A.; Magagnoli I.; Dondi F.; Giunti M

Insulin Receptor Isoform A and Insulin-like Growth Factor II as Additional Treatment Targets in Human Osteosarcoma

Abstract Despite the frequent presence of an insulin-like growth factor I receptor (IGFIR)-mediated autocrine loop in osteosarcoma (OS), interfering with this target was only moderately effective in preclinical studies. Here, we considered other members of the IGF system that might be involved in the molecular pathology of OS. We found that, among 45 patients with OS, IGF-I and IGFBP-3 serum levels were significantly lower, and IGF-II serum levels significantly higher, than healthy controls. Increased IGF-II values were associated with a decreased disease-free survival. After tumor removal, both IGF-I and IGF-II levels returned to normal values. In 23 of 45 patients, we obtained tissue specimens and found that all expressed high mRNA level of IGF-II and >IGF-I. Also, isoform A of the insulin receptor (IR-A) was expressed at high level in addition to IGFIR and IR-A/IGFIR hybrids receptors (HRA). These receptors were also expressed in OS cell lines, and simultaneous impairment of IGFIR, IR, and Hybrid-Rs by monoclonal antibodies, siRNA, or the tyrosine kinase inhibitor BMS-536924, which blocks both IGFIR and IR, was more effective than selective anti-IGFIR strategies. Also, anti–IGF-II-siRNA treatment in low-serum conditions significantly inhibited MG-63 OS cells that have an autocrine circuit for IGF-II. In summary, IGF-II rather than IGF-I is the predominant growth factor produced by OS cells, and three different receptors (IR-A, HRA, and IGFIR) act complementarily for an IGF-II–mediated constitutive autocrine loop, in addition to the previously shown IGFIR/IGF-I circuit. Cotargeting IGFIR and IR-A is more effective than targeting IGF-IR alone in inhibiting OS growth. [Cancer Res 2009;69(6):2443–52

Paracrine inhibition of osteoblast differentiation induced by neuroblastoma cells

The aim of our study was to investigate whether the defective function of osteogenic cells induced by neuroblastoma might play a role in the development of skeletal metastases. This mechanism has been extensively demonstrated for multiple myeloma, in which the blockage of osteoblast differentiation has been ascribed to the inhibitors of canonical Wingless pathway (Wnt), namely Dickkopf 1 (Dkk1). Our purpose was to verify if neuroblastoma cells derived from bone marrow metastases (SH-SY5Y, LAN1) or primaries (NB100, CHP212) hamper the differentiation of mesenchymal stem cells (hMSCs) into osteoblasts in a paracrine manner, and to test whether this ability depends on Dkk1 activity. We found that all neuroblastoma cells increased the proliferation of hMSCs collected from pediatric-aged donors, with a corresponding decrease in osteoblast differentiation markers, including alkaline phosphatase (ALP), analyzed as gene expression, enzymatic activity and number of ALP-positive colony forming units, osteoprotegerin (OPG) release, OPG and osteocalcin gene-expression. Dkk1 mRNA and protein were detectable in all cell lines, and the use of neutralizing anti-Dkk1 antibody reversed the effects induced by SH-SY5Y cells. Taken together, our results confirm that neuroblastoma hinders osteoblastogenesis, and that Dkk1 release seems to play a crucial role in blocking the differentiation of osteoprogenitor cells, though the ability to promote osteoclast activation remains an essential requirement for the development of skeletal metastases. Finally, our findings suggest that strategies regulating Wnt signaling and Dkk1 activity could be considered for adjuvant therapies in neuroblastoma metastasizing to the skeleton

Bilateral total hip arthroplasty in Morquio-Brailsford's Syndrome: a report of two cases

We report two cases of bilateral cementless total hip arthroplasty in two young women affected by Morquio-Brailsford syndrome. Morquio-Brailsford disease belongs to the mucopolysaccharidoses; it shows growth retardation with disproportional dwarfism. Usually patients are affected by a severe joint degeneration from their 2nd or 3rd decade. Young age, severe dysplasia, and joint size are the main technical problems for a total hip replacement. Accurate radiographic and CT planning allows the use of standard prostheses instead of custom-made ones