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A 38-year-old woman experienced a persistent dry cough and progressively worsening dyspnoea for 2 years. Spirometry testing revealed a moderate-to-severe restrictive abnormality. High-resolution chest computed tomography showed diffuse reticulonodular opacities. A lung biopsy disclosed alveolar parenchymal inflammation and fibrosis with bronchiolocentric features, prompting consideration of interstitial pneumonia. Following a thorough investigation of her occupational history and an on-site inspection, it was discovered that the patient had been grinding drill bits designed for printed circuit boards for 8 years, exposing her to hard metals. Mineralogical analyses confirmed excessive tungsten in urine, serum and hair, leading to a diagnosis of hard metal lung disease due to tungsten carbide-cobalt exposure. After discontinuing exposure and commencing corticosteroid therapy, her symptoms, pulmonary function and imaging showed modest improvement. This case highlights the significance of assessing occupational history in patients with interstitial pneumonia and understanding industrial hazards for accurate diagnosis and care., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society of Occupational Medicine. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

After almost three-quarters of a century during which contact dermatologists have often struggled to comprehend the relationship between metal allergy and failure of metal-alloy containing implant, it is possible to say that a relationship does exist, particularly for cobalt and chromium, but also for nickel. There is still debate as to whether allergy develops as a consequent of failure but thenceforth contributes to it, or whether sensitisation starts first and induces failure secondarily-opinion probably favours the first. Metal-on-polypropylene articulations were associated with few metal allergic problems but now are less favoured by orthopaedists due to plastic wear products causing osteolysis and pseudotumour formation through local inflammation. New metal alloys are regularly being introduced such that interested dermatologists need to stay on top of the situation. The jury is still out as to whether the recent favouring of titanium-containing alloys will confirm them to be more inert allergenically. Case reports do show some clinical reactions to titanium-containing implants and patch test series have inferred sometimes quite a high background rate of allergy, but interpretation must be tempered by the awareness that titanium salts on patch testing have a tendency to cause irritant reactions. Blood monitoring of metal ion values is now recommended in certain situations after joint replacement and increasing levels may be an indication that allergy with joint failure can develop, in which case patch testing is indicated, and suggested series are available. Predictive patch testing, whilst generally not recommended in the past, has been introduced into some protocols often by non-dermatologists, such that it is now needed for temporo-mandibular joint and Nuss bar insertion, and it can be anticipated that this may become more commonplace in the future. One of the major current deficits for patch testers is standardised guidance on which preparation or preparations to use for suspected titanium allergy. One suggestion is 0.5% titanium sulphate in petrolatum, though experience in at least one centre suggests the use of a battery of titanium salts might be desirable., (© 2023 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.)

Nickel is used in many cerebral endovascular treatment devices. However, nickel hypersensitivity is the most common metal allergy, and the relative risk of treatment in these patients is unknown. This retrospective analysis identified patients with nickel or metal allergies who underwent cerebral endovascular treatment with nickel-containing devices. Seven patients with nickel and/or other metal allergies underwent treatment with 9 nickel-containing devices. None experienced periprocedural complications. No patient received treatment with corticosteroids or antihistamines. At a mean clinical follow-up for all patients of 22.8 months (range, 10.5-38.0 months), no patients had symptoms attributable to nickel allergic reactions. The mean radiographic follow-up for all patients at 18.4 months (range, 2.5-37.5 months) showed successful treatment of the targeted vascular pathologies, with no evidence of in-stent stenosis or other allergic or hypersensitivity sequelae. The treatment of cerebrovascular lesions with a nickel-containing device resulted in no adverse outcomes among these patients and was safe and effective., (© 2023 by American Journal of Neuroradiology.)

Background: Wear particles-induced osteolysis is a major long-term complication after total joint arthroplasty. Up to now, there is no effective treatment for wear particles-induced osteolysis except for the revision surgery, which is a heavy psychological and economic burden to patients. A metabolite of gut microbiota, short chain fatty acids (SCFAs), has been reported to be beneficial for many chronic inflammatory diseases. This study aimed to investigate the therapeutic effect of SCFAs on osteolysis., Methods: A model of inflammatory osteolysis was established by applying CoCrMo alloy particles to mouse calvarium. After two weeks of intervention, the anti-inflammatory effects of SCFAs on wear particle-induced osteolysis were evaluated by Micro-CT analysis and immunohistochemistry staining. In vitro study, lipopolysaccharide (LPS) primed bone marrow-derived macrophages (BMDMs) and Tohoku Hospital Pediatrics-1 (THP-1) macrophages were stimulated with CoCrMo particles to activate inflammasome in the presence of acetate (C2), propionate (C3), and butyrate (C4). Western blotting, Enzyme-linked immunosorbent assay, and immunofluorescence were used to detect the activation of NLRP3 inflammasome. The effects of SCFAs on osteoclasts were evaluate by qRT-PCR, Western blotting, immunofluorescence, and tartrate-resistant acid phosphatase (TRAP) staining. Additionally, histone deacetylase (HDAC) inhibitors, agonists of GPR41, GPR43, and GPR109A were applied to confirm the underlying mechanism of SCFAs on the inflammasome activation of macrophages and osteoclastogenesis., Results: C3 and C4 but not C2 could alleviate wear particles-induced osteolysis with fewer bone erosion pits (P < 0.001), higher level of bone volume to tissue volume (BV/TV, P < 0.001), bone mineral density (BMD, P < 0.001), and a lower total porosity (P < 0.001). C3 and C4 prevented CoCrMo alloy particles-induced ASC speck formation and nucleation-induced oligomerization, suppressing the cleavage of caspase-1 (P < 0.05) and IL-1β (P < 0.05) stimulated by CoCrMo alloy particles. C3 and C4 also inhibited the generation of Gasdermin D-N-terminal fragment (GSDMD-NT) to regulate pyroptosis. Besides, C3 and C4 have a negative impact on osteoclast differentiation (P < 0.05) and its function (P < 0.05), affecting the podosome arrangement and morphologically normal podosome belts formation., Conclusion: Our work showed that C3 and C4 are qualified candidates for the treatment of wear particle-induced osteolysis., (© 2022. The Author(s).)

Introduction: For an inguinal hernia repair, meshes with a continuous memory frame made it more easy to position the mesh in the preperitoneal space by anterior approach. We present a case of a sigmoid perforation caused by a fractured nitinol ring of a Rebound HRD Shield mesh., Patients and Methods: A 29-years old sports instructor presented to the Emergency Department (ED) with a gnawing abdominal pain in the left lower quadrant. His past medical history noted an inguinal hernia repair on this side. A computed tomography scan showed a broken metal ring of the inguinal mesh perforating the sigmoid, so a laparoscopy was performed. The sigmoid was attached to the abdominal wall partially overlying the preperitoneal mesh and a part of the broken nitinol frame was found perforating the colon., Results: The memory ring of the Rebound mesh is made of nitinol. An alloy well-known in vascular surgery for stenting arteries with high bending and compression forces. In this setting, fracture due to fatigue has already been described, but it is not known in abdominal wall reconstruction. Our patients groin was subject to daily bending and compression forces resulting in breakage of the nitinol ring., Conclusion: Particularly in young athletic patients the nitinol ring will be subject to bending forces in the groin and prone to breakage. This can have potentially severe consequences given its location near abdominal organs and neurovascular structures. In our opinion, patients should be informed about the possibility of ring breakage and doctors should consider the risk-benefits well.

The local response of tissue triggered by implantation of degradable magnesium-based implant materials was investigated in vivo in a murine model. Pins (5.0 mm length by 0.5 mm diameter) made of Mg, Mg-10Gd, and Ti were implanted in the leg muscle tissue of C57Bl/6N mice (n = 6). Implantation was generally well tolerated as documented by only a mild short term increase in a multidimensional scoring index. Lack of difference between the groups indicated that the response was systemic and surgery related rather than material dependent. Longitudinal in vivo monitoring utilizing micro-computed tomography over 42 days demonstrated the highest and most heterogeneous degradation for Mg-10Gd. Elemental imaging of the explants by micro X-ray fluorescence spectrometry showed a dense calcium-phosphate-containing degradation layer. In order to monitor resulting surgery induced and/or implant material associated local cell stress, sphingomyelin based liposomes containing indocyanine green were administered. An initial increase in fluorescent signals (3-7 days after implantation) indicating cell stress at the site of the implantation was measured by in vivo fluorescent molecular tomography. The signal decreased until the 42nd day for all materials. These findings demonstrate that Mg based implants are well tolerated causing only mild and short term adverse reactions., (© 2021 The Authors. Journal of Biomedical Materials Research Part A published by Wiley Periodicals LLC.)

Bone defects and diseases are devastating, and can lead to severe functional deficits or even permanent disability. Nevertheless, orthopedic implants and scaffolds can facilitate the growth of incipient bone and help us to treat bone defects and diseases. Currently, a wide range of biomaterials with distinct biocompatibility, biodegradability, porosity, and mechanical strength is used in bone-related research. However, most orthopedic implants and scaffolds have certain limitations and diverse complications, such as limited corrosion resistance, low cell proliferation, and bacterial adhesion. With recent advancements in materials science and nanotechnology, metallic and metallic oxide nanoparticles have become the subject of significant interest as they offer an ample variety of options to resolve the existing problems in the orthopedic industry. More importantly, these nanoparticles possess unique physicochemical and mechanical properties not found in conventional materials, and can be incorporated into orthopedic implants and scaffolds to enhance their antimicrobial ability, bioactive molecular delivery, mechanical strength, osteointegration, and cell labeling and imaging. However, many metallic and metallic oxide nanoparticles can also be toxic to nearby cells and tissues. This review article will discuss the applications and functions of metallic and metallic oxide nanoparticles in orthopedic implants and bone tissue engineering., (© 2020 Wiley Periodicals LLC.)

Titanium alloys are widely used in the biomedical field due to their excellent resistance to corrosion, high mechanical strength/density ratio, low elastic modulus, and good biocompatibility. Niobium is a β-stabilizer element that has the potential to decrease elastic modulus and possesses excellent corrosion resistance. In this article, Ti-15Nb alloy was prepared via arc-melting, with the aim of using it in biomedical applications to replace implants that fail due to mechanical incompatibility with human bone. This Ti-15Nb alloy was structurally, chemically, and microstructurally characterized. Its mechanical properties were analyzed via Vickers microhardness and elastic modulus measurements. The cytotoxicity of the alloy was evaluated via direct and indirect MTT tests. In the direct MTT test, the cells were grown on alloy and in the indirect test, Ti-15Nb alloy extracts were prepared (1 g/1 mL at 310 K for 48 hours). The results of chemical composition showed that the alloy produced has good quality and low content of gaseous impurities, such as oxygen and nitrogen. The obtained results for structure and microstructure indicated the presence of the martensite α' phase. The microhardness of the Ti-15Nb alloy is superior to that of cp-Ti due to solid solution hardening, and the alloy has a better elastic modulus as compared to pure titanium. Cytotoxic effects were not observed. The Ti-15Nb alloy shows good results of mechanical properties and does not show cytotoxic effects. In addition, morphological variations were not found in the cells and good cell adhesion in all the studied conditions was observed. In general, the alloy proposed in this article has satisfactory characteristics as a biomedical material., (© 2019 International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.)

The purpose of the present study was to evaluate the mechanical strength and the absorption rate of WE43 material and to develop an absorbable metallic plate and screw for craniofacial application. The extruded WE43 plate and screw were evaluated using a LeFort I osteotomy canine model of 10 beagle dogs. Animals were divided into two groups: five dogs in the experimental group and five dogs in the control group. μCT was acquired at 4, 12, and 24 weeks. At 24 weeks after the operation, all animals were sacrificed, and histologic evaluation was performed. Swelling and gas formation were observed in three dogs in the experimental groups at 8 weeks. From 12 weeks, infraorbital fistula and inflammation were observed in three dogs in the experimental group, which gradually decreased and disappeared at 24 weeks. Other two dogs showed less gas formation at 12 weeks. The plates were completely absorbed, and gas formation was not observed at 24 weeks in these two dogs. New bone was well formed around the plates and screws in both groups. Histologic examination showed no specific differences between two groups. The mechanical strength of extruded WE43 was sufficient for mid-facial application. Plates and screws made with appropriately treated WE43 have the potential to be useful clinically., (© 2020 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc.)

Aims: To investigate the healing process and nickel release of the Hyperion occluder (Comed BV, Netherlands), as compared to the Amplatzer septal occluder (ASO) (St. Jude Medical Inc., St. Paul, MN, USA) in a chronic swine model., Background: Some long-term complications occurring after percutaneous atrial septal defect (ASD) closure may be partially associated with an inappropriate healing of the device and increased nickel release. There is no direct comparative study of different occluders for healing and nickel release., Methods: After percutaneous ASD creation, 12 pigs were implanted with 15 mm Hyperion ( n  = 6) and 15 mm ASO ( n  = 6) devices. After 1 month ( n  = 3 for each device) and 3 months ( n  = 3 for each device) of follow-up, device explantation was performed and healing was assessed using histopathological workup. Systemic and tissular nickel release was performed., Results: Implantation was successful in 100% without complications. Device coverage was observed as early as 1 month after implantation and was almost complete after 3 months. A granulation tissue with a predominantly mononuclear inflammatory reaction was observed in contact with nitinol wires while an inflammatory reaction was seen in contact with textile fibers. We found no statistically significant difference between the 2 devices whether for histological grading scores or systemic nickel release, regardless to follow-up duration., Conclusions: In this preclinical study, we demonstrated that Amplatzer septal occluder and Hyperion occluder were not significantly different for device healing and nickel release processes., Competing Interests: Z. J. received speaker honoraria and research grant from Abbott. J. B. T. and X. I. act as proctors for Abbott. The other authors have no conflicts of interest to declare., (Copyright © 2020 Zakaria Jalal et al.)

Objective: To assess in parous and nulliparous women, the efficacy, safety, and tolerability of a new, low-dose copper (175 mm) intrauterine contraceptive with a flexible nitinol frame provided in a preloaded applicator., Methods: Institutional review boards at 12 U.S. sites approved this commercially funded project. Patients met standard inclusion and exclusion criteria for a copper-based intrauterine device (IUD), generally consistent with the Centers for Disease Control and Prevention's U.S. Medical Eligibility Criteria for Contraceptive Use, 2016. Intrauterine device placement occurred at any day in the eligible patient's menstrual cycle after assuring she was not pregnant. The primary outcome measure assessed efficacy (measured by the Pearl Index) in this 1-year study with a 2-year extension. Secondary outcomes included placement success, ease of placement, safety as measured by adverse events, and tolerability assessed by discontinuation rate and bleeding and spotting patterns., Results: A total of 286 women provided 5,640 cycles evaluable for pregnancy. Patients averaged 27.1 years of age. Nulliparous women represented 60.8% of the patients. Over 36 months of observation, we identified two pregnancies (Pearl Index 0.46 [95% CI 0.06-1.67]) and 10 serious adverse events; none were study-related. Successful placement occurred in 283 participants (99.0%). Median (range) continuation times were 2.7 years (0-3.4). We identified five expulsions (1.8%), zero uterine perforations, and one report of pelvic inflammatory disease. Adverse events prompted 30 women (10.6%) to discontinue early in the first year of use with 23 (8.1%) discontinuing for issues of bleeding, pain, or both. Altogether, 107 (37.8%) completed 36 months of device use. Mean bleeding days per cycle decreased from 7.6 in cycle 1 to 5.2 in cycle 13., Conclusion: The novel, low-dose copper and nitinol IUD demonstrated high efficacy and safety in this phase 2 U.S. Food and Drug Administration trial and warrants further expanded study in a phase 3 clinical trial., Clinical Trial Registration: ClinicalTrials.gov, NCT02446821., Funding Source: Sebela Pharmaceuticals, Inc.

Wear and corrosion damage of biomedical alloys alters the structure and electrochemical properties of the surface heterogeneously. It was hypothesized that local regions on the same surface systematically differ from one another in terms of their impedance characteristics. To test this hypothesis, CoCrMo disks exposed to electrosurgical and inflammatory-species-driven damage were characterized using a localized impedance technique, nearfield electrochemical impedance spectroscopy (NEIS), to assess point-specific surface integrity in response to applied damage. It was found that electrosurgical damage, as may arise during primary arthroplasty and revision surgeries, and hydrogen peroxide concentrations of 5-10 mM significantly alter the corrosion susceptibility of the local surface compared to the as-polished CoCrMo surface. A CoCrMo retrieved neck taper (Goldberg score of 4) was scored in different local regions on the basis of visual appearance, and it was found that there is a direct relationship between increasing debris coverage and decreasing impedance, with the global surface impedance closest to the most severely scored local region. This noninvasive method, which uses a millielectrode configuration to test localized regions, can measure the heterogeneous electrochemical impedance of an implant surface and be tailored to assess specific damage and corrosion mechanisms revealed on retrieval surfaces.

Beta-type Ti-based alloys are promising new materials for bone implants owing to their excellent mechanical biofunctionality and biocompatibility. For treatment of fractures in case of systemic diseases like osteoporosis the generation of implant surfaces which actively support the problematic bone healing is a most important aspect. This work aimed at developing suitable approaches for electrodeposition of Sr-substituted hydroxyapatite (Srx-HAp) coatings onto Ti-45Nb. Potentiodynamic polarization measurements in electrolytes with 1.67 mmol/L Ca(NO 3 ) 2 , which was substituted by 0, 10, 50 and 100% Sr(NO 3 ) 2 , and 1 mmol/L NH 4 H 2 PO 4 at 333 K revealed the basic reaction steps for OH - and PO 4 3- formation needed for the chemical precipitation of Srx-HAp. Studies under potentiostatic control confirmed that partial or complete substitution of Ca 2+ - by Sr 2+ -ions in solution has a significant effect on the complex reaction process. High Sr 2+ -ion contents yield intermediate phases and a subsequent growth of more refined Srx-HAp coatings. Upon galvanostatic pulse-deposition higher reaction rates are controlled and in all electrolytes very fine needle-like crystalline coatings are obtained. With XRD the incorporation of Sr-species in the hexagonal HAp lattice is evidenced. Coatings formed in electrolytes with 10 and 50% Sr-nitrate were chemically analyzed with EDX mapping and GD-OES depth profiling. Only a fraction of the Sr-ions in solution is incorporated into the Srx-HAp coatings. Therein, the Sr-distribution is laterally homogeneous but non-homogeneous along the cross-section. Increasing Sr-content retards the coating thickness growth. Most promising coatings formed in the electrolyte with 10% Sr-nitrate were employed for Ca, P and Sr release analysis in Tris-Buffered Saline (150 mM NaCl, pH 7.6) at 310 K. At a sample surface: solution volume ratio of 1:200, after 24 h the amount of released Sr-ions was about 30-35% of that determined in the deposited Srx-HAp coating. In vitro studies with human bone marrow stromal cells (hBMSC) revealed that the released Sr-ions led to a significantly enhanced cell proliferation and osteogenic differentiation and that the Sr-HAp surface supported cell adhesion indicating its excellent cytocompatibility., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the incidence of contact dermatitis among workers in cemented carbide production enterprises. Methods: From October 1997 to October 2017, an occupational epidemiological survey was conducted on a large-scale cemented carbide production enterprise, and occupational health examinations were conducted for employees. 152 people were exposed to hard metal dust (hard metal raw material dust and alloy dust) . The employees in the work group were contact groups, and 142 employees in the non-dusting operation of the company were in the control group. A detailed retrospective survey of hard metal production workers with contact dermatitis history in the two groups was conducted to analyze the risk factors of contact dermatitis exposure to hard metal dust. Results: The incidence of allergic diseases in the exposed group was significantly higher than that in the control group. The difference was statistically significant (χ(2)=23.793, P <0.05) . The incidence of contact dermatitis in the exposed group was significantly higher than that in the control group. The difference was statistically significant (χ(2)=24.659, P <0.05) ; the changes of contact dermatitis in the contact group were mainly allergic contact dermatitis, and some showed irritative contact dermatitis; the operator had respiratory symptoms (including work-related nasal congestion, cough, wheezing) , difficulty breathing may be the influencing factors of contact dermatitis ( RR =2.60, 95% CI : 1.10-6.20, P <0.05) . Conclusion: Hard metal alloy enterprises are exposed to hard metal dust. The incidence of contact dermatitis is high in workers, and the occurrence of contact dermatitis may be associated with those with respiratory symptoms.

In this study, a comprehensive analysis of a novel zinc alloy osteosynthesis system in a canine mandibular fracture model is presented. The efficacy of the system was compared for PLLA (poly-l-lactic acid) and titanium materials using X-ray radiography, micro-CT tomography, undecalcified bone histomorphometry, and a three-point bending test. Histology, blood normal, blood biochemical, and serum zinc concentration tests were also performed to assess the biosafety of the zinc alloy osteosynthesis system. The degradability of the zinc alloy was evaluated using a micro-CT and scanning electron microscope during the 24-week post operation period. The results showed that zinc alloy possesses good mechanical properties that support fracture healing. Its uniform and slow corrosion leads to adequate degradation behavior in 24 weeks. Additionally, the zinc alloy proved to be biocompatible, indicating that this novel osteosynthesis system is safe for use in the body. The results of the study demonstrate that this zinc alloy-based osteosynthesis system is a promising candidate for a new generation of osteosynthesis systems, with further improvements required in the future., (Copyright © 2019 Acta Materialia Inc. All rights reserved.)

Bioresorbable metallic implants are considered to be a new generation of transient fixation devices, which provide strong mechanical support during healing as well as effective integration with the host bone tissues, free of secondary surgery. We evaluated the microstructures and mechanical properties of iron‑manganese alloys (Fe30Mn) with 0-, 5-, 10-, and 60-volume percent porosity, which was produced through ammonium bicarbonate (NH 4 HCO 3 ) decomposition. We also investigated the influence of porosity concentration on the corrosion rate and cytotoxicity of the alloy. The average value of maximum compressive strength was 2-fold greater in the 0-vol% scaffolds than that in 60-vol% scaffolds. Scaffolds with 60-vol% porosity exhibited the highest average value of corrosion rate in a potentiodynamic polarization test among the four groups. However, the group influenced cellular viability negatively in a subsequent cytotoxicity test. Fe30Mn scaffolds with 10-vol% NH 4 HCO 3 are considered promising resorbable scaffolds based on the results of compression tests, corrosion experiments and cytotoxicity studies., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: The occlusion devices used for repair of atrial septal defect and patent foramen ovale commonly contain nitinol, an alloy containing nickel. There are reports of nickel allergy in the context of intracardiac device implantation. Type IV delayed-type reactions likely predominate in intracardiac metal hypersensitivity, but there are potentially other mechanisms such as cytotoxic or innate immunity. Based on available literature to date, the significance of nickel allergy in intracardiac occluders remains unclear., Objective: The aim of the study was to investigate nickel allergy management strategies in intracardiac occluders., Methods: The American Contact Dermatitis Society facilitated distribution of a survey via e-mail to the members of its association, which included dermatologists and allergists/immunologists. A total of 70 individuals answered the survey., Conclusions: There was no consensus regarding the ability of patch testing to accurately determine allergic reactions within cardiac tissue. There was also no agreement on the criteria for patch testing in patients undergoing intracardiac implantation. However, most would inquire about a history of contact sensitivity to previously implanted devices. With a positive patch test, nickel-based intracardiac devices should be avoided, or the decision should be left to the discretion of the cardiologist.

Phenotype switching is a characteristic response of vascular smooth muscle cells (vSMCs) to the dynamic microenvironment and contributes to all stages of atherosclerotic plaque. Here, we immersed pure magnesium and AZ31 alloy in the completed medium under cell culture condition, applied the resultant leaching extracts to the isolated contractile rat aortic vSMCs and investigated how vSMCs phenotypically responded to the degradation of the magnesium-based stent materials. vSMCs became more proliferative and migratory but underwent more apoptosis when exposed to the degradation products of pure magnesium; while the AZ31 extracts caused less cell division but more apoptosis, thus slowing cell moving and growing. Noticeably, both leaching extracts dramatically downregulated the contractile phenotypic genes at mRNA and protein levels while significantly induced the inflammatory adhesive molecules and cytokines. Exogenously added Mg ions excited similar transformations of vSMCs. With the liberation or supplementation of Mg 2+ , the expression patterns of the pro-contractile transactivator myocardin and the pro-inflammatory transcriptional factor kruppel-like factor 4 (KLF4) were reversed. Overall, the degradation of the Mg-based materials would evoke a shift of the contractile vSMCs to an inflammatory phenotype via releasing Mg ions to induce a transition from the phenotypic control of vSMCs by the myocardin to that by the KLF4. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 988-1001, 2019., (© 2018 Wiley Periodicals, Inc.)

Biodegradable magnesium (Mg) alloys exhibit improved mechanical properties compared to degradable polymers while degrading in vivo circumventing the complications of permanent metals, obviating the need for surgical removal. This study investigated the safety and efficacy of Mg-Y-Zn-Zr-Ca (WZ42) alloy compared to non-degradable Ti6Al4V over a 14-week follow-up implanted as pins to fix a full osteotomy in rat femurs and as wires wrapped around the outside of the femurs as a cerclage. We used a fully load bearing model allowing implants to intentionally experience realistic loads without immobilization. To assess systemic toxicity, blood cell count and serum biochemical tests were performed. Livers and kidneys were harvested to observe any accumulation of alloying elements. Hard and soft tissues adjacent to the fracture site were also histologically examined. Degradation behavior and bone morphology were determined using micro-computed tomography scans. Corrosion occurred gradually, with degradation seen after two weeks of implantation with points of high stress observed near the fracture site ultimately resulting in WZ42 alloy pin fracture. At 14 weeks however, normal bone healing was observed in femurs fixed with the WZ42 alloy confirmed by the presence of osteoid, osteoblast activity, and new bone formation. Blood testing exhibited no significant changes arising from the WZ42 alloy compared to the two control groups. No recognizable differences in the morphology and more importantly, no accumulation of Mg, Zn, and Ca in the kidney and liver of rats were observed. These load bearing model results collectively taken, thus demonstrate the feasibility for use of the Mg-Y-Zn-Zr-Ca alloy for long bone fracture fixation applications.

Absorbable metallic implants have been under investigation for more than a century. Animal and human studies have shown that magnesium (Mg) alloys can be safely used in bioresorbable scaffolds. Several cardiovascular and orthopedic biodegradable metallic devices have recently been approved for use in humans. Bioresorbable Mg implants present many advantages when compared to bioabsorbable polymer or nonabsorbable metallic implants, including similar strength and mechanical properties as existing implant-grade metals without the drawbacks of permanence or need for implant removal. Imaging visibility is also improved compared to polymeric devices. Additionally, with Mg-based cardiovascular stents, the risk of late stent thrombosis and need for long-term anti-platelet therapy may be reduced as the host tissue absorbs the Mg degradation products and the morphology of the vessel returns to a near-normal state. Absorbable Mg implants present challenges in the conduct of preclinical animal studies and interpretation of pathology data due to their particular degradation process associated with gas production and release of by-products. This article will review the different uses of Mg implants, the Mg alloys, the distinctive degradation features of Mg, and the challenges confronting pathologists at tissue collection, fixation, imaging, slide preparation, evaluation, and interpretation of Mg implants.

Objective: To preliminarily investigate the feasibility of bioabsorption tracheal stenting for the therapeutic application of congenital tracheal stenosis (CTS)., Study Design: Experimental research., Setting: Shanghai Children Medical Center, National Children's Medical Center., Subjects and Methods: Five kinds of magnesium alloys with different compositions were studied in this paper, a patented Mg-Nd-Zn-Zr alloy series namely JDBM (JiaoDa BioMg) and four Mg-Ca-Zn alloys. The cytotoxicity of alloys was evaluated by the MTS ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) assay in rabbit tracheal epithelial cells. Specific magnesium alloys had been immersed in the cell culture medium for 24 h. The tracheal stents that were made of magnesium alloy were implanted into the trachea of New Zealand rabbits and the ablation of the stent was monitored by fiber bronchoscopy. The routine blood examination was conducted prior to and following the stent placement. The rabbits were euthanized following 2-3 months of stenting. H&E staining of the main organs was conducted and the induction of apoptosis of the tracheal tissues was monitored., Results: The cytotoxicity of the JDBM magnesium alloy was mild and lower than the remaining 4 alloys. The stents were placed successfully in five animals. The tracheal stents were successfully placed and gradually biodegradated as monitored by fiber bronchoscopy; no significant systemic inflammatory response was noted. No significant differences in the liver and/or kidney function prior to and following stent placement were noted. H&E staining indicated the absence of pathological changes in the trachea, liver, heart and/or kidney tissues. The apoptotic assay indicated that the apoptosis ratio of the tracheal tissues was comparable between rabbits with and without tracheal stenting., Conclusion: The results suggested the feasibility of bioabsorption stents made of biodegradable magnesium alloys using in patients with tracheal stenosis, especially in infants., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Hard metal lung disease (HMLD) is a pneumoconiosis caused by occupational exposure to hard metals such as tungsten carbide and cobalt, but the treatment strategies for HMLD have not been well established. A 68-year-old Japanese man with occupational history as a grinder of hard metals for 18 years referred to our hospital because of dry cough and dyspnea. A chest computed tomography (CT) on admission revealed centrilobular micronodules, ground-glass opacities, and reticular opacities in the peripheral zone of both lungs. Mineralogic analyses of lung tissues detected components of hard metals, such as tungsten, titanium and iron, and the same metals were also detected in the sample of the dust of his workplace. Thus, the patient was diagnosed as having HMLD based on occupational exposure history and radiologic and mineralogic analyses of the lung. Corticosteroid therapy was initiated, which resulted in partial improvements in his symptoms, radiological and pulmonary functional findings. In a review of the 18 case reports of HMLD treated with corticosteroids, including our case, the majority of patients (77.8%) showed favorable responses to corticosteroid treatment. Furthermore, the presence of fibrotic changes, such as reticular opacity, in radiological examinations was associated with the resistance to corticosteroids. In conclusion, the majority of patients with HMLD are expected to favorable response to corticosteroid treatment, whereas chest CT findings such as fibrotic changes may be predictive of the resistance of corticosteroid treatment. Lastly, proper prevention of hard metal exposure is most important as the first step.

Metal implants are biomaterials widely used in orthopedics. They are both used in osteosynthesis and arthroplasty. Their mechanical properties, biocompatibility and resistance to corrosion make them a widely used option in orthopedics. Alloys are the most commonly used metals in orthopedics. As far as physical traumas are concerned, implants such as screws, plates and/or nails are used for osteosynthesis as they ensure the stability of the fractured area and contribute to bone healing. Prostheses are used in arthroplasty to restore joint function for as long as possible. Contact between bone and the prosthesis induces bone remodeling at the interface between metal and bone even if the metal is recognized as biocompatible. Upon time, the interface between the metal implant and the bony tissue is continuously modified and adapted. Hip prosthesis is a typical example of intraosseous metal implant whose bone/implant interface has been extensively studied. Metal can be altered in vivo by different mechanisms including corrosion and fretting. An altered torque friction leads to wear debris that accumulate in the peri-prosthetic tissues causing metallosis., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Magnesium alloys have shown potential as biodegradable metallic materials for orthopaedic applications due to their degradability, and their resemblance to cortical bone and biocompatible degradation/corrosion products. However, the fast corrosion rate and the potential toxicity of their alloying element has limited the clinical application of Mg alloys. In the present study, a novel Mg‑2Zn‑0.5Nd alloy was prepared, and then the effects on the cell biological behaviour of the Mg‑2Zn‑0.5Nd alloy was compared with 317L stainless steel and titanium (Ti‑6Al‑4V) alloys as controls. The L6 cells were cultured in various leaching solutions. The proliferative effect of the Mg‑2Zn‑0.5Nd alloy was determined using the Cell Counting Kit‑8 assay method on the L6 cells. Also, the regulation of key intracellular signalling proteins was investigated in the L6 cells by the western blot analysis. The Mg‑2Zn‑0.5Nd alloy showed no cytotoxicity and induced higher levels of proliferation in the myoblast cell line L6 than the other alloys. Molecular analysis demonstrated that Mg‑2Zn‑0.5Nd had stimulatory effects on bone morphogenetic protein‑2 phosphorylation and on the activity of phosphorylated‑mammalian target of the rapamycin (mTOR), protein kinase B and forkhead box protein O1. Mg‑2Zn‑0.5Nd also had no effect on P38 activity. These results suggested that Mg‑2Zn‑0.5Nd is likely to promote myoblast cell proliferation by activating the mTOR signalling pathway.

The use of Central Venous Catheters (CVCs) commonly results in complications. Coatings with silver or metal alloys can reduce the risk associated with the use of CVC. We have evaluated the durability of a noble metal coated CVC (the Bactiguard Infectious Protection, BIP CVC) and compared with an uncoated CVC for clinical tolerability (Adverse Events, AEs) and performance, in order to create a baseline for a large future study. Patients undergoing major surgery, randomised at a 2:1 ratio to BIP CVC (n = 22) or standard CVC (n = 12), were catheterized 9 - 12 days, respectively. Adverse events, microbial colonization and metal release were measured., Findings: There were no AEs in the BIP CVC-group, but 5 AEs occurred in 4 patients (1 patient had 2 AEs) in the standard CVC-group, p = 0.011 (whereof 3 were catheter related). The BIP CVC showed an initial release of coating metals in blood (gold, silver and palladium), which rapidly decreased and were far below Permitted Paily Exposure (PDE) for chronical use. The levels of silver concentration were far below those needed to develop microbial resistance. The performance was equal, and there was no difference concerning microbial colonization, for the two CVCs., Conclusion: In this pilot study the BIP CVC had significantly lower AEs and showed a comparable performance to the standard CVC. The coating was durable throughout the study length (up to 16 days) and toxicological evaluation showed good safety margins. Larger studies are needed. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2337-2344, 2018., (© 2017 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc.)

Many cardiovascular device alloys contain nickel, which if released in sufficient quantities, can lead to adverse health effects. However, in-vivo nickel release from implanted devices and subsequent biodistribution of nickel ions to local tissues and systemic circulation are not well understood. To address this uncertainty, we have developed a multi-scale (material, tissue, and system) biokinetic model. The model links nickel release from an implanted cardiovascular device to concentrations in peri-implant tissue, as well as in serum and urine, which can be readily monitored. The model was parameterized for a specific cardiovascular implant, nitinol septal occluders, using in-vitro nickel release test results, studies of ex-vivo uptake into heart tissue, and in-vivo and clinical measurements from the literature. Our results show that the model accurately predicts nickel concentrations in peri-implant tissue in an animal model and in serum and urine of septal occluder patients. The congruity of the model with these data suggests it may provide useful insight to establish nickel exposure limits and interpret biomonitoring data. Finally, we use the model to predict local and systemic nickel exposure due to passive release from nitinol devices produced using a wide range of manufacturing processes, as well as general relationships between release rate and exposure. These relationships suggest that peri-implant tissue and serum levels of nickel will remain below 5 μg/g and 10 μg/l, respectively, in patients who have received implanted nitinol cardiovascular devices provided the rate of nickel release per device surface area does not exceed 0.074 μg/(cm 2  d) and is less than 32 μg/d in total., Statement of Significance: The uncertainty in whether in-vitro tests used to evaluate metal ion release from medical products are representative of clinical environments is one of the largest roadblocks to establishing the associated patient risk. We have developed and validated a multi-scale biokinetic model linking nickel release from cardiovascular devices in-vivo to both peri-implant and systemic levels. By providing clinically relevant exposure estimates, the model vastly improves the evaluation of risk posed to patients by the nickel contained within these devices. Our model is the first to address the potential for local and systemic metal ion exposure due to a medical device and can serve as a basis for future efforts aimed at other metal ions and biomedical products., (Published by Elsevier Ltd.)

Introduction: The purpose of this study was to evaluate the effect of different temperatures (0°C, 10°C, 22°C, 37°C, and 60°C) on the cyclic fatigue life of nickel-titanium (NiTi) files using a new fatigue test model in zirconium oxide., Methods: Three superelastic NiTi files (EndoSequence [Brasseler USA, Savannah, GA], ProFile [Dentsply Tulsa Dental Specialties, Tulsa, OK], and K3 [SybronEndo, Orange, CA]), and 3 heat-treated (K3XF [SybronEndo], Vortex [Dentsply Tulsa Dental Specialties], and HyFlex CM [Coltene-Whaledent, Allstetten, Switzerland]) NiTi files, all size 25/.04, were subjected to cyclic fatigue tests inside a novel, artificial ceramic canal with a curvature of 60° and a 5-mm radius. The model was immersed in water at 5 different preset temperatures. The number of cycles to failure (NCF) was recorded, and the fracture surface of the fragments was examined by a scanning electron microscope. The data were analyzed using 2-way analysis of variance with the significance level at 0.05., Results: When the temperature was reduced from 60°C to 0°C, the NCF significantly increased from over 2 to 10 times for the NiTi file groups (P < .01). K3XF had the highest fatigue resistance of all files at 0°C (P < .05). Vortex files had the highest NCF at 10°C-60°C. The NCF of heat-treated files was significantly higher than superelastic NiTi files at 10°C and 20°C (P < .05). There was no significant difference in the NCF of HyFlex CM at 0°C and 22°C. There was little difference in the fractographic appearance among different temperatures, except that the fraction area occupied by the dimple region of some instruments at 0°C was slightly smaller than at 60°C., Conclusions: Cooling down to low temperatures may be an interesting strategy to improve the fatigue resistance of rotary NiTi files., (Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Magnesium (Mg) alloys are considered promising materials for biodegradable medical devices; however, the initial effects and distribution of released Mg 2+ ions following implantation are unclear. This is addressed in the present study, using two types of Mg alloys implanted into rats. An in vitro immersion test was first carried out to quantify Mg 2+ ions released from the alloys at early stages. Based on these data, we performed an in vivo experiment in which large amounts of alloys were subcutaneously implanted into the backs of rats for 1, 5, 10, and 25 h. Mg 2+ accumulation in organs was measured by inductively coupled plasma mass spectrometry. In vivo, blood and urine Mg 2+ concentrations were higher in rats receiving the implants than in controls after 1 h; however, the levels were within clinically accepted guidelines. The Mg 2+ concentration in bone was significantly higher in the 25 h implanted group than in the other groups. Our results suggest that homeostasis is maintained by urinary excretion and bone accumulation of released Mg 2+ ions in response to sudden changes in Mg 2+ ion concentration in the body fluid in a large number of Mg alloy implants at the early stages.

Nickel-chromium(Ni-Cr) based alloys account for the majority of the porcelain-fused-to-metal fixed dental prostheses(PFM-FDPs) on account of their superior properties despite both nickel and chromium being known as human carcinogens. Understanding the genotoxicity and the cytotoxicity alongside the characteristics of corrosion behavior of the alloy is vital for understanding their biocompatibility. This study has evaluated whether the Ni-Cr based alloys corroded in artificial saliva by analyzing alloy decomposition at different pH levels and immersion durations(7, 14, 21, and 28 days) using inductively coupled plasma-optic emission spectrophotometry(ICP-OES). The principal aim of the study was to determine the possible genotoxicity and cytotoxicity using micronucleus(MN) and other nuclear anomaly frequencies [nuclear bud(NBUD), binucleated(BNC), condensed chromatin(CC), karyorrhectic(KhC), pyknotic(PC) and karyolytic(KC) cells] and various cytome parameters [basal cells(BC), differentiated cells(DF)] with the buccal epithelial cell(BEC) micronucleus cytome assay(BMCyt). This test was administered at 1 pre- and 3 post-treatment time points to 40 patients who underwent installation of PFM-FDPs made of Ni-Cr based alloy. Furthermore, at the final post-treatment time point, saliva cotinine levels were measured with salivary cotinine quantitative enzyme immunoassay(EIA) kit and information obtained by questionnaire prior to the first pre-treatment time point was confirmed. The highest greatest release of Ni and Cr ions were seen at pH 2.3. MN and micronucleated cell frequencies, and BNC cell frequencies were significantly elevated at post-treatment time points(p < 0.03). BC, CC, KhC, PC and KC cell frequencies however were not significantly different between pre-and post-treatment time points(p > 0.05). MN frequency was significantly lower in non-smokers than in current and former smokers(p < 0.001) at the pre-treatment time point. There was no significant correlation between the unit number of PFM-FDPs and MN frequencies. Our results revealed that Ni-Cr based alloys are prone to corrosion and that PFM-FDPs fabricated with Ni-Cr based alloys may induce genotoxic effects rather than cytotoxic effect., (Copyright © 2018 Elsevier B.V. All rights reserved.)

BACKGROUND Paeoniflorin (PF), a glucoside isolated from the dried root of Paeonia lactiflora Pall, has been reported to have a number of pharmacological properties, including immunity-regulation, anticancer activities, and neuroprotective effect. However, PF's pharmacological role in bone disorder has been seldom reported. Hence, this study was designed to investigate the effects of PF on osteoclast differentiation and osteolysis diseases. MATERIAL AND METHODS The bone marrow macrophages were isolated from C57BL/6 mice and incubated with RANK ligand (RANKL) and various concentrations of PF. After 5 days of incubation, tartrate-resistant acid phosphatase (+) cells and bone resorption pits were counted. Effects of PF on expression of osteoclast-specific protein and gene were investigated via Western blot, q-PCR, and immunofluorescence assay. The osteoprotective effect of PF in vivo was evaluated in a calvarial osteolysis model via micro-CT scan and histological stain. RESULTS In vitro, PF intervention inhibited osteoclast formation and resorption activity. PF also impaired RANKL-induced NF-κB phosphorylation and immigration to the nucleus. PF suppressed osteoclast-marker protein and gene expression. In vivo, PF inhibited cobalt-chromium-molybdenum alloy particle-induced osteolysis and reduced osteoclast number in tissue slice. CONCLUSIONS PF is a potential agent against osteolysis-related diseases caused by excessive osteoclast activity.

Introduction A standard osteosynthetic material for maxillofacial skeleton is titanium and its alloys. The convenience of degradable material is avoiding of second surgery in cases, where removal of the material is necessary. Magnesium biodegradable alloys have similar mechanic properties as cortical bone - reasonable corrosion and sufficient biologic properties. They might be used in facial skeleton fixation. Materials and methods The study included a total of 16 rabbits, and they were randomly divided into two groups. Each group received two screws (WE4 and titanium as a standard material) in artificially drilled defect into right tibia. Animals were euthanized at four-week intervals. Bone samples with implants underwent microfocus CT scans and were histologically examined. Results WE43 alloys showed fragmentation of the material on the 16th week - statistically significant volume loss was found between weeks 12 and 16. Bone healing around the WE43 screws was of similar quality as around titanium screws, and no adverse effect was noticed. Conclusion The study showed good quality of bone healing around WE43 implants. From this point of view, the WE43 alloy meets the requirements of osteosynthetic material for maxillofacial skeleton.

Nitinol alloy occluders are widely used in the transcatheter intervention treatment of congenital heart diseases like patent ductus arteriosus (PDA). However, nitinol alloy contains high levels of nickel, which can lead to toxic effects in the immune and hematopoietic systems if released in sufficient quantities. A new type of single-rivet occluder coated with nano-film has been developed to limit the release of nickel. In total, 23 patients were recruited and randomly assigned to the experimental group (n=12) with the new nano-film single-rivet occluders or the control group (n=11) with the traditional occluders. One case in the control group was lost to follow-up. The remaining 22 cases were followed up at 24 h, 7 days, 1 month, 3 months, and 6 months after the procedure. There were no statistically significant differences in routine blood test, alanine aminotransferase, creatinine, and troponin between the experimental and control groups. Serum nickel concentration in both two groups increased at 24 h after the procedure, peaked at 1 month, and returned to preoperative levels at 6 months. Serum nickel levels in the experimental group were significantly lower than in the control group at 24 h, 7 days, 1 month, and 3 months after the procedure. These data suggested that the nano-film coating effectively prevented nickel release from the new occluders, and therefore has a preferable safety profile.

Introduction: Literature on the potential release of trace elements following implantation of Zirconia-platelet toughened alumina (ZPTA) ceramic components is scant. The present study therefore analysed the in vitro and in vivo potential release of ions from ZPTA bearings., Material and Methods: An in vitro and in vivo study was conducted. The in vitro study compared leaching in bovine serum from two groups: ZPTA ceramic heads and Co-28Cr-6Mo alloy heads, both 28-mm diameter. A third group without implant served as reference group. An in vivo clinical study compared trace elements in the whole blood of patients with 36-mm diameter ZPTA ceramic-on-ceramic articulation after three and 12 months. A cohort of subjects without any prosthesis was used as control group. The release of ions was determined by high resolution-inductively coupled plasma-mass spectrometry., Results: In the in vitro experiment, significant differences (p ≤ 0.01) in trace element release for chromium, cobalt and molybdenum were found, with increased levels of ion release in the Co-28Cr-6Mo metal group. The very low detection limit for yttrium allowed detection of a small yttrium release from the ZPTA heads, which was not confirmed by the in vivo study. No significant difference between the groups was found for strontium, aluminium, and zirconium. In the in vivo study, no relevant differences in ion levels between the reference group without any implant and the study group were found at the three and 12-month follow-up., Conclusion: This study supports that ZPTA ceramic articulation components are safe in terms of ion release, and may be an excellent alternative to bearings based on Co-28Cr-6Mo alloys.

Context: There is growing interest in minimally invasive (MI) treatment options for male lower urinary tract symptoms (LUTS). Among these options, the temporary implantable nitinol device (TIND; Medi-Tate, Or Akiva, Israel) is a novel instrument used to alleviate symptoms by creating incisions in the prostate via mechanical stress., Objective: To review recent data for TIND as an MI procedure to improve LUTS., Evidence Acquisition: Medline, PubMed, the Cochrane Database, and Embase were screened for clinical trials, randomized controlled trials, and review articles on the use of TIND in patients with male LUTS., Evidence Synthesis: There are currently two studies available, one being a follow-up of the first pilot study. Both 12-mo and 36-mo results suggest at least medium-term effects of TIND in terms of symptom improvement (International Prostate Symptom Score, IPSS) and maximum urinary flow (Q max ). IPSS was improved by 41% after 12mo (p<0.001) and worsened only insignificantly after 36mo compared to baseline values. Q max increased by 4.4ml/s after 12mo (p<0.001) and did not decrease significantly after 36mo. Postoperative complications were mild and included urinary tract infection and urinary retention., Conclusions: Preliminary data suggest that TIND is a safe and effective MI technique for patients with male LUTS. Symptom relief and increase in urinary flow after 36mo are promising. However, long-term results are needed., Patient Summary: Various treatment options for male patients suffering from urinary voiding symptoms are emerging. TIND, a temporary implantable nitinol device, appears to be a safe option that improves symptoms without affecting sexuality., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: Based on a pooled analysis of data from an international study, evaluate total and cause-specific mortality among hardmetal production workers with emphasis on lung cancer., Methods: Study members were 32,354 workers from three companies and 17 manufacturing sites in five countries. We computed standardized mortality ratios and evaluated exposure-response via relative risk regression analysis., Results: Among long-term workers, we observed overall deficits or slight excesses in deaths for total mortality, all cancers, and lung cancer and found no evidence of any exposure-response relationships for lung cancer., Conclusions: We found no evidence that duration, average intensity, or cumulative exposure to tungsten, cobalt, or nickel, at levels experienced by the workers examined, increases lung cancer mortality risks. We also found no evidence that work in these facilities increased mortality risks from any other causes of death.

Background: Mortality pattern was determined in a cohort of 16,999 white and blue-collar workers in the Swedish hardmetal industry. Exposure assessment for cobalt is presented., Methods: A historical database (1970 to 2012) of personal and area measurements of cobalt, tungsten, and nickel in the Swedish hardmetal industry was created. Log linear and exponential modeling of cobalt concentrations based on time period, job, and site was performed, and cumulative and mean exposures were calculated., Results: Some 37% of the personal cobalt measurements exceeded 0.02 mg/m, mostly for powder production, pressing, and shaping. The log linear regression showed statistical differences (P < 0.05) between sites, time periods, and jobs. Some 1.6% of the cobalt cumulative exposures for blue-collar workers exceeded 0.4 mg/m years., Conclusion: Low levels of cumulative and mean exposures were determined.

Objective: To generate quantitative exposure estimates for use in retrospective occupational cohort mortality studies of the hardmetal industry., Methods: Job-exposure matrices (JEMs) were constructed for cobalt, tungsten, and nickel over the time period 1952 to 2014. The JEMs consisted of job class categories, based on job titles and processes performed, and exposure estimates calculated from available company industrial hygiene measurements., Results: Exposure intervals of one-half order magnitude were established for all three agents. Eight job classes had significantly decreasing time trends for cobalt exposure; no significant time trends were detected for tungsten or nickel exposures., Conclusions: The levels of exposures determined for this study were similar to or lower than those previously reported for the hardmetal industry during the 1952 to 2014 study period.

Objectives: To evaluate total and cause-specific mortality among hardmetal production workers with emphasis on lung cancer., Methods: Subjects were 7304 workers ever employed in one of eight US plants from 1952 to 2008. Vital status through 2012 was determined for 97% of subjects and cause of death for 98.3% of 1087 deaths. We computed standardized mortality ratios (SMRs) and evaluated exposure-response via relative risk regression analysis., Results: We observed overall deficits in deaths for total mortality, all cancers, and lung cancer and found no evidence of any exposure-response relationships for lung cancer., Conclusions: We found no evidence that exposure to tungsten, cobalt, or nickel, at levels experienced by the workers examined, increases lung cancer mortality risks. We also found no evidence that work in the US hardmetal industry increases mortality risks from any other causes of death.

Objective: This study retrospectively investigates causes of death among workers of a hardmetal plant in Austria., Methods: A retrospective cohort was formed of 1965 workers still employed in or after 1970. Follow-up was until end of 2014 based on national databases. Cobalt exposure was assessed through industrial hygiene data and urine analyses. Cox proportional hazards models were calculated for selected causes of death., Results: During 45,598 years of observation in total 177 deaths were observed. Forty-nine workers died from any cancer, 10 from lung cancer, and three from chronic obstructive pulmonary disease. Only the latter showed a significant association with cumulative exposure., Conclusions: Although this is a young study population with little power to detect subtle effects, at least it does not indicate a pronounced cancer risk among tungsten carbide workers due to cobalt.

Objective: The aim of this study was to characterize the mortality at two hardmetal production factories in the United Kingdom as part of an international study., Methods: Standardized mortality ratios (SMRs) were calculated on the basis of mortality rates for England and Wales, and local rates. A nested case-control study of lung cancer was undertaken., Results: The cohort comprised 1538 workers, with tracing complete for 94.4%. All-cause mortality was statistically significantly low for all cancers and nonmalignant respiratory disease, and for lung cancer was nonsignificantly low. The SMR for lung cancer for maintenance workers was elevated, based on only six deaths. The odds ratio for lung cancer per year of exposure to hardmetal was 0.93 (0.76 to 1.13)., Conclusions: In this small study, there is no evidence to support that working in the UK hardmetal manufacturing industry increased mortality from any cause including lung cancer.

: The cancer incidence was determined for 3713 workers from three plants from 1958 to 2011. The exposure measures were ever/never exposed, duration, cumulative, and mean cobalt concentrations.The incidence of all malignant neoplasms was increased at one plant, but standardized incidence ratio (SIR) was 0.96 for all workers. Lung cancer incidence was increased for all workers, SIR 1.38 (1.01 to 1.85). The lung cancer incidence was associated with shorter employment time and showed no exposure-response. There was decreased incidence for skin cancer. Increased lip cancer incidence found at one of the production plants might be related to diagnostic intensity.Lung cancer incidence showed no correlation to cobalt exposure based on internal comparison. The increased SIR for all workers might be associated with other factors.

Objective: The aim of this study was to investigate a cohort in German hardmetal industry, especially relationship between exposures to cobalt, with and without tungsten, and risks of total and cause-specific mortality., Methods: The cohort comprises blue-collar workers at three German plants who were employed in hardmetal processing. Individual cumulative exposures and long-term average concentrations were estimated for cobalt, nickel, tungsten, respirable, and inhalable dust. Standardized mortality ratios (SMRs) were calculated for external comparisons. Time-dependent multivariable Cox models were performed for internal analyses., Results: Elevated SMRs were found for all-cause, heart diseases, and nonmalignant respiratory diseases mortality, but not for lung cancer. Internal analyses did not show increased risks for any endpoints, and no exposure-response relationship was indicated., Conclusions: This study does not provide evidence for elevated lung cancer risks. Methodologic limitations, incomplete ascertainment of death causes in particular, impede conclusions about exposure effects.

Background: The mortality pattern was determined in a cohort of 16,999 white and blue-collar workers in the Swedish hardmetal industry, particularly for cobalt exposure and lung cancer., Methods: The mortality follow-up analysis in the Swedish Mortality register covered the period from 1952 to 2012. The exposure measures were ever/never exposed, duration of exposure, cumulative, and mean cobalt concentrations., Results: The mortality of all causes was significantly increased, highly associated with the short-term employed workers. A negative exposure-response was found for lung cancer and duration of exposure. An exposure-response was determined for cumulative and mean cobalt exposures analyzed by quartiles, but not for exposure classes. Internal comparison analysis using proportional hazard showed no exposure-response., Conclusions: The cohort lung cancer mortality showed no correlation to cobalt, nickel, or tungsten exposure.

A major limitation with current assessments of corrosion in metallic medical devices is the lack of correlation between in-vitro and in-vivo corrosion performance. Therefore, the objective of this study was to elucidate the relationship between pitting corrosion measured by breakdown potentials (E b ) in ASTM F2129 testing and corrosion resistance in-vivo. Four groups of Nitinol stents were manufactured using different processing methods to create unique surface properties. The stents were implanted into iliac arteries of minipigs for six months and explanted for corrosion analysis. Scanning electron microscopy and energy dispersive X-ray spectrometry analyses indicated that stents with a thick complex thermal oxide (420nm) and high corrosion resistance in-vitro (E b =975±94mV) were free from detectable corrosion in-vivo and exhibited no changes in Ni/Ti ratio when compared to non-implanted controls. This result was also found in mechanically polished stents with a thin native oxide (4nm; E b =767±226mV). In contrast, stents with a moderately thick thermal oxide (130nm) and low corrosion resistance in-vitro (E b =111±63mV) possessed corrosion with associated surface microcracks in-vivo. In addition, Ni/Ti ratios in corroded regions were significantly lower compared to non-corroded adjacent areas on explanted stents. When stents were minimally processed (i.e. retained native tube oxide from the drawing process), a thick thermal oxide was present (399nm) with low in-vitro corrosion resistance (E b =68±29mV) resulting in extensive in-vivo pitting. These findings demonstrate that functional corrosion testing combined with a detailed understanding of the surface characteristics of a Nitinol medical device can provide insight into in-vivo corrosion resistance., Statement of Significance: Nitinol is a commonly used material in the medical device industry. However, correlations between surface processing of nitinol and in-vivo corrosion has yet to be established. Elucidating the link between in-vivo corrosion and pre-clinical characterization can aid in improved prediction of clinical safety and performance of nitinol devices. We addressed this knowledge gap by fabricating nitinol stents to possess distinct surface properties and evaluating their corrosion susceptibility both in-vitro and after six months of in-vivo exposure. Relationships between stent processing, surface characterization, corrosion bench testing, and outcomes from explanted devices are discussed. These findings highlight the importance of surface characterization in nitinol devices and provide in-vitro pitting corrosion levels that can induce in-vivo corrosion in nitinol stents., (Published by Elsevier Ltd.)

Introduction: There exist a number of factors that affect the outcome of orthodontic treatment. These factors can be assessed by various gingival markers. One such maker is myeloperoxidase (MPO). Hence, we planned the present study to assess and compare the MPO activity in the gingival crevicular fluid (GCF) of subjects undergoing orthodontic treatment by different aligning arch wires., Materials and Methods: The present study included assessment of patients who underwent orthodontic treatment for crowding of anterior teeth. Diagnostic cast models of all the subjects were made for recording the irregularity index. All the subjects were randomly divided into three study groups with 15 patients in each group based on the type of nickel-titanium (NiTi) arch wires used. A collection of GCF samples was done in all the patients at various time intervals and it was sent to the laboratory for assessment of MPO activity. Activity of the MPO enzyme was expressed in terms of number of units per 100 μL. All the results obtained were compiled and analyzed by Statistical Package for the Social Sciences (SPSS) software., Results: We observed that nonsignificant results were obtained while comparing the mean age and mean gingival score in all the study groups. However, significant results were obtained on comparing the mean MPO enzymatic activity in all the study groups at different time intervals., Conclusion: Both superelastic NiTi and heat-activated NiTi generate optimal forces, which are necessary for higher metabolic response of the periodontal ligament., Clinical Significance: In the intimal stages of orthodontic treatment, both superelastic NiTi and heat-activated NiTi wires are superior in leveling and aligning the crowded teeth.

Magnesium (Mg)-based stents are extensively explored to alleviate atherosclerosis due to their biodegradability and relative hemocompatibility. To ensure the quality, safety and cost-efficacy of bioresorbable scaffolds and full utilization of the material tunability afforded by alloying, it is critical to access degradability and thrombosis potential of Mg-based alloys using improved in vitro models that mimic as closely as possible the in vivo microenvironment. In this study, we investigated biodegradation and initial thrombogenic behavior of Mg-based alloys at the interface between Mg alloys' surface and simulated physiological environment using a microfluidic system. The degradation properties of Mg-based alloys WE43, AZ31, ZWEK-L, and ZWEK-C were evaluated in complete culture medium and their thrombosis potentials in platelet rich plasma, respectively. The results show that 1) physiological shear stress increased the corrosion rate and decreased platelets adhesion rate as compared to static immersion; 2) secondary phases and impurities in material composition induced galvanic corrosion, resulting in higher corrosion resistance and platelet adhesion rate; 3) Mg-based alloys with higher corrosion rate showed higher platelets adhesion rate. We conclude that a microfluidic-based in vitro system allows evaluation of biodegradation behaviors and platelets responses of Mg-based alloys under specific shear stress, and degradability is related to platelets adhesion.

Cobalt exposure in the hard metal and bonded diamond tool industry is a well-established cause of ILD. The primary theories regarding the underlying mechanism of cobalt related ILD include an immunologic mechanism and an oxidant injury mechanism. Cobalt related ILD may present in subacute and chronic forms and often has associated upper respiratory symptoms. The evaluation begins with a thorough occupational history and includes PFTs, HRCT, and bronchoalveolar lavage. HRCT findings are nonspecific and may resemble NSIP, UIP, sarcoidosis, or HP. The finding of cannibalistic multinucleated giant cells is diagnostic provided there is a history of exposure and appropriate changes on imaging; however, when these cells are not found on lavage, lung biopsy is required for diagnosis. Giant cell interstitial pneumonia is the classic pathologic pattern, but cobalt related ILD may also present with pathologic findings of UIP, DIP, or HP. When cobalt related ILD is suspected, removal from exposure is the most important step in treatment. Case reports suggest that treatment with steroids results in symptomatic, physiologic, and radiographic improvement., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Titanium and titanium alloy are widely used as orthopedic implants for their favorable mechanical properties and satisfactory biocompatibility. The aim of the present study was to investigate the antibacterial effect and bone cell biocompatibility of a novel implant made with nanotubular anodized titanium coated with gentamicin (NTATi-G) through in vivo study in rabbits. The animals were divided into four groups, each receiving different kinds of implants, that is, NTATi-G, titanium coated with gentamicin (Ti-G), nanotubular anodized titanium uncoated with gentamicin (NTATi) and titanium uncoated with gentamicin (Ti). The results showed that NTATi-G implant prevented implant-related osteomyelitis and enhanced bone biocompatibility in vivo. Moreover, the body temperature of rabbits in NTATi-G and Ti-G groups was lower than those in Ti groups, while the weight of rabbits in NTATi-G and Ti-G groups was heavier than those in NTATi and Ti groups, respectively. White blood cell counts in NTATi-G group were lower than NTATi and Ti groups. Features of myelitis were observed by X-ray films in the NTATi and Ti groups, but not in the NTATi-G and Ti-G groups. The radiographic scores, which assessed pathology and histopathology in bone tissues, were significantly lower in the NTATi-G and Ti-G groups than those in the NTATi and Ti groups, respectively ( P <0.05). Meanwhile, explants and bone tissue culture demonstrated significantly less bacterial growth in the NTATi-G and Ti-G groups than in the NTATi and Ti groups, respectively ( P <0.01). The bone volume in NTATi-G group was greater than Ti-G group, and little bone formation was seen in NTATi and Ti groups., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Vascular anastomosis is the highlight of cardiovascular, transplant, and reconstructive surgery, which has long been performed by hand using a needle and suture. However, anastomotic thrombosis occurs in approximately 0.5-10% of cases, which can cause serious complications. To improve the surgical outcomes, attempts to develop devices for vascular anastomosis have been made, but they have had limitations in handling, cost, patency rate, and strength at the anastomotic site. Recently, indwelling metal stents have been greatly improved with precise laser metalwork through programming technology. In the present study, we designed a bare metal stent, Microstent, that was constructed by laser machining of a shape-memory alloy, NiTi. An end-to-end microvascular anastomosis was performed in SD rats by placing the Microstent at the anastomotic site and gluing the junction. The operation time for the anastomosis was significantly shortened using Microstent. Thrombus formation, patency rate, and blood vessel strength in the Microstent anastomosis were superior or comparable to hand-sewn anastomosis. The results demonstrated the safety and effectiveness, as well as the operability, of the new method, suggesting its great benefit for surgeons by simplifying the technique for microvascular anastomosis.