Modular titanium alloy neck adapter failures in hip replacement - failure mode analysis and influence of implant material

<p>Abstract</p> <p>Background</p> <p>Modular neck adapters for hip arthroplasty stems allow the surgeon to modify CCD angle, offset and femoral anteversion intraoperatively. Fretting or crevice corrosion may lead to failure of such a modular device due to high loads or surface contamination inside the modular coupling. Unfortunately we have experienced such a failure of implants and now report our clinical experience with the failures in order to advance orthopaedic material research and joint replacement surgery.</p> <p>The failed neck adapters were implanted between August 2004 and November 2006 a total of about 5000 devices. After this period, the titanium neck adapters were replaced by adapters out of cobalt-chromium. Until the end of 2008 in total 1.4% (n = 68) of the implanted titanium alloy neck adapters failed with an average time of 2.0 years (0.7 to 4.0 years) postoperatively. All, but one, patients were male, their average age being 57.4 years (36 to 75 years) and the average weight 102.3 kg (75 to 130 kg). The failures of neck adapters were divided into 66% with small CCD of 130° and 60% with head lengths of L or larger. Assuming an average time to failure of 2.8 years, the cumulative failure rate was calculated with 2.4%.</p> <p>Methods</p> <p>A series of adapter failures of titanium alloy modular neck adapters in combination with a titanium alloy modular short hip stem was investigated. For patients having received this particular implant combination risk factors were identified which were associated with the occurence of implant failure. A Kaplan-Meier survival-failure-analysis was conducted. The retrieved implants were analysed using microscopic and chemical methods. Modes of failure were simulated in biomechanical tests. Comparative tests included modular neck adapters made of titanium alloy and cobalt chrome alloy material.</p> <p>Results</p> <p>Retrieval examinations and biomechanical simulation revealed that primary micromotions initiated fretting within the modular tapered neck connection. A continuous abrasion and repassivation process with a subsequent cold welding at the titanium alloy modular interface. Surface layers of 10 - 30 μm titanium oxide were observed. Surface cracks caused by fretting or fretting corrosion finally lead to fatigue fracture of the titanium alloy modular neck adapters. Neck adapters made of cobalt chrome alloy show significantly reduced micromotions especially in case of contaminated cone connection. With a cobalt-chromium neck the micromotions can be reduced by a factor of 3 compared to the titanium neck. The incidence of fretting corrosion was also substantially lower with the cobalt-chromium neck configuration.</p> <p>Conclusions</p> <p>Failure of modular titanium alloy neck adapters can be initiated by surface micromotions due to surface contamination or highly loaded implant components. In the present study, the patients at risk were men with an average weight over 100 kg. Modular cobalt chrome neck adapters provide higher safety compared to titanium alloy material.</p

The Effects of Tamoxifen on Plasma Lipoprotein(a) Concentrations: Systematic Review and Meta-Analysis

Introduction: Tamoxifen is a selective estrogen receptor modulator widely used in the treatment of breast cancer. Tamoxifen therapy is associated with reduced circulating low-density lipoprotein cholesterol and increased triglycerides, but its effects on other lipids are less-well studied. Aims: We aimed to investigate the effect of tamoxifen on circulating concentrations of lipoprotein(a) (Lp(a)) through systematic review and meta-analysis of available randomized controlled trials (RCTs) and observational studies. Methods: This study was registered in the PROSPERO database (CRD42016036890). Scopus, Medline and EMBASE were searched from inception until 22nd March 2016 to identify studies investigating the effect of tamoxifen on Lp(a) values in humans. Results: Meta-analysis of 5 studies with 284 participants suggested a significant reduction of Lp(a) levels following tamoxifen treatment (weighted mean difference [WMD]: -3.53 mg/dL, 95% confidence interval [CI]: -6.53, -0.53, p=0.021). When studies were categorized according tamoxifen dose, there was a significant effect in the subset of studies with administered doses ≥20 mg/day (WMD: -5.05 mg/dL, 95% CI: -7.86, -2.23, p<0.001), but not in the subset with doses <20 mg/day (WMD: -1.41 mg/dL, 95% CI: -5.13, 2.31, p=0.458). With respect to duration of treatment, a greater effect was observed in subgroup of studies administering tamoxifen for <12 weeks (WMD: -4.01 mg/dL, 95% CI: -7.84, -0.18, p=0.04) versus the subgroup of studies lasting ≥12 weeks (WMD: -2.48 mg/dL, 95% CI: -5.50, 0.53, p=0.107). Conclusions: Meta-analysis suggested a significant reduction of Lp(a) levels following tamoxifen treatment. Further well-designed trials are required to validate these results

Funktionelle Charakterisierung eines spermienspezifischen Na+/H+ Austauschers

Sekundär aktive Austauscher sind membranständige Proteine, die den elektrochemischen Gradienten eines Ions nutzen, um den Transport anderer Ionen oder Substrate über die Zellmembran zu ermöglichen. Natrium/Protonen (Na+/H+) Austauscher der Solute Carrier 9 (SLC9) Familie spielen dabei eine Rolle in einer Vielzahl von physiologischen Prozessen. Ein bis heute rätselhaftes Mitglied der SLC9 Familie ist der spermienspezifische Austauscher SLC9C1. Es ist bis heute nicht bekannt, ob SLC9C1 ein funktionstüchtiger Na+/H+ Austauscher ist. SLC9C1 besitzt eine einzigartige dreiteilige Struktur; eine Austauscher (NHE) Domäne, eine Spannungssensordomäne (VSD) sowie eine Bindestelle für zyklische Nukleotide (CNBD). VSDs und CNBDs sind funktionelle Proteindomänen, die man bereits in anderen Proteinen gefunden hat, VSDs überwiegend in Ionenkanälen, aber auch in einer spannungsabhängigen Phosphatase, CNBDs in Proteinkinasen, Transkriptionsfaktoren, und auch in Ionenkanälen. SLC9C1 ist das erste Mitglied der SLC Familie, in dem solche Proteindomänen gefunden wurden. Im Rahmen meiner Arbeit habe ich diesen phylogenetischen Hybrid untersucht. Als Modellprotein diente dazu SLC9C1 des Seeigels Strongylocentrotus purpuratus (SpSLC9C1). Durch den Einsatz pH sensitiver Fluoreszenzfarbstoffe in der Elektrophysiologie konnte ich zeigen, dass SpSLC9C1 ein funktionstüchtiger Na+/H+ Austauscher ist. Hyperpolarisierende Spannungssprünge aktivieren sowohl Gating Ströme der VSD als auch den sekundär aktiven Na+/H+ Austausch. Ich konnte die Spannungsabhängigkeit der Austauschaktivität bestimmen, sowie zeigen, dass cAMP, aber nicht cGMP, die Spannungsabhängigkeit der Gating Ströme und der Austauschaktivität moduliert. Mutationen in der NHE Domäne, der CNBD und der VSD verhinderten jeweils den Na+/H+ Austausch bzw. die Modulation durch cAMP oder beeinflussten die Gating Ströme. Ein Antikörper bestätigte die Expression von SLC9C1 in S. purpuratus Spermien. Mithilfe von spannungs , pH und Na+ sensitiven Fluoreszenzfarbstoffen in S. purpuratus Spermien konnte ich zeigen, dass SpSLC9C1 auch in Spermien durch Hyperpolarisation aktiviert wird. Der Na+/H+ Austausch alkalisiert das Flagellum nach der Lockstoffstimulation und ermöglicht dem Spermium die chemotaktische Navigation.The solute carrier SLC9C1 is a Na+/H+-exchanger gated by an S4-type voltage-sensor and cyclic-nucleotide binding Secondary active exchangers are membrane bound proteins that use the electrochemical gradient of ions to transport other ions or substrates across cell membranes. Within these proteins, sodium/proton (Na+/H+) exchangers of the Solute Carrier 9 (SLC9) family play a crucial role in a number of physiological processes. A so far enigmatic member of this family is the sperm specific exchanger SLC9C1. No evidence exists up to today that SLC9C1 is a functional Na+/H+ exchanger. SLC9C1 features a unique tripartite structure; an exchanger (NHE) domain, a voltage sensing domain (VSD) as well as a cyclic nucleotide binding domain (CNBD). VSDs and CNBDs are protein domains that are found in a variety of proteins, VSDs mainly in ion channels but also in a voltage sensitive phosphatase, CNBDs in protein kinases, transcription factors and also ion channels. SLC9C1 is the first member of the SLC9 family in which these protein domains was found. During my thesis, I investigated this phylogenetic hybrid. As a model protein, I chose SLC9C1 from the sea urchin Strongylocentrotus purpuratus (SpSLC9C1). By using a pH sensitive fluorescence dye within an electrophysiological setup, I could show that SpSLC9C1 is indeed a functional Na+/H+ exchanger. Hyperpolarizing voltage steps evoked both gating currents and secondary active Na+/H+ exchange. I could determine the voltage dependence of exchanger activation. Furthermore, I looked into the action of cyclic nucleotides such as cGMP and cAMP on SpSLC9C1. Cyclic AMP, but not cGMP affected the voltage dependence of both gating currents and exchange activity. Mutations in the NHE domain, CNBD and VSD abolished Na+/H+ exchange, cAMP modulation or affected voltage gating, respectively. An antibody was raised to confirm SLC9C1 expression in S. purpuratus sperm. By using voltage , pH and Na+ sensitive fluorescent dyes together with a rapid mixing device, I could show that SpSLC9C1 in sperm activates during hyperpolarization. The Na+/H+ exchange alkalizes the flagellum upon stimulation with the chemoattractant and allows chemotactic navigation

NACA Technical Notes

Note presenting a flight investigation made on three nonrotating full-scale propeller spinners at free-stream Mach numbers of 0.70 to 0.96 to determine the surface-pressure distribution and the magnitude and radial extent of the influence of each spinner on the local flow field. Results regarding surface static-pressure distributions and radial variation of local Mach number along the blade center line are provided