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The aim of the present study was to evaluate how much reduction in acetabular liner thickness could be tribologically acceptable in metal-on-vitamin-E diffused highly crosslinked ultra-high molecular weight polyethylene (Vit-E XLPE) bearings for total hip arthroplasty. We tested thick- (10.3 mm), moderate- (6.3 mm), and thin- (4.3 mm) Vit-E XLPE liners coupled with 28-mm cobalt-chromium femoral heads on a hip simulator to 5 million cycles, and peak contact stress was predicted based on mathematical modeling. Wear damage was also evaluated in terms of surface topology and morphology. Wear simulation demonstrated that the 2-4 mm thickness reduction (6.3 → 4.3 mm and 10.3 → 6.3 mm) did not significantly affect the wear rate for Vit-E XLPE liner, whereas 6-mm reduction (10.3 → 4.3 mm) significantly increased liner wear (by 309%) and head roughness (by 415%). This effect was attributed to a contact stress increase (by 24-41%). However, the wear rates for all thicknesses tested were much lower than those previously reported for thicker non-crosslinked materials. The original crystalline morphology was maintained in all liners after wear. Our results suggest that the 2-4 mm thickness reduction may be tribologically acceptable in Vit-E XLPE liners. However, more severe and longer term simulations are necessary to determine a minimum acceptable thickness.

Background Thymic malignancies are a heterogeneous group of rare cancers for which systemic chemotherapy is the standard treatment in the setting of advanced, recurrent or refractory diseases. Both environmental and genetic risk factors have not been fully clarified and few target-specific drugs have been developed for thymic epithelial tumors. A major challenge in studying thymic epithelial tumors is the lack of preclinical models for translational studies. Main body Starting from bioptic material of two consecutive recurrences of the same patient, we generated two patient-derived xenografts. The patient-derived xenografts models were characterized for histology by immunohistochemistry and mutations using next-generation sequencing. When compared to the original tumors resected from the patient, the two patient-derived xenografts had preserved morphology after the stain with hematoxylin and eosin, although there was a moderate degree of de-differentiation. From a molecular point of view, the two patient-derived xenografts maintained 74.3 and 61.8% of the mutations present in the human tumor of origin. Short conclusion The newly generated patient-derived xenografts recapitulate both the molecular characteristics and the evolution of the thymoma it derives from well, allowing to address open questions for this rare cancer.

Background Migraine and depression are highly prevalent and partly overlapping disorders that cause strong limitations in daily life. Patients tend to respond poorly to the therapies available for these diseases. OnabotulinumtoxinA has been proven to be an effective treatment for both migraine and depression. While many studies have addressed the effect of onabotulinumtoxinA in migraine or depression separately, a growing body of evidence suggests beneficial effects also for patients comorbid with migraine and depression. The current meta-analysis systematically investigates to what extent onabotulinumtoxinA is efficient in migraineurs with depression. Methods A systematic literature search was performed based on PubMed, Scopus and Web of Science from the earliest date till October $$30{th}$$ 30 th , 2020. Mean, standard deviation (SD) and sample size have been used to evaluate improvement in depressive symptoms and migraine using random-effects empirical Bayes model. Results Our search retrieved 259 studies, eight of which met the inclusion criteria. OnabotulinumtoxinA injections administered to patients with both chronic migraine and major depressive disorder led to mean reduction of $$- \;8.94$$ - 8.94 points (CI [$$- \;10.04, - \;7.84$$ - 10.04 , - 7.84 ], $$\hbox {p} < 0.01$$ p < 0.01 ) in the BDI scale, of $$- \;5.90$$ - 5.90 points (CI [$$- \;9.92, - \;1.88$$ - 9.92 , - 1.88 ], $$\hbox {p} < 0.01$$ p < 0.01 ) in the BDI-II scale and of $$- \;6.19$$ - 6.19 points (CI [$$- \;9.52, - \;2.86$$ - 9.52 , - 2.86 ], $$\hbox {p} < 0.01$$ p < 0.01 ) in the PHQ-9 scale, when evaluating depressive symptoms. In the case of the migraine-related symptoms, we found mean reductions of $$- \;4.10$$ - 4.10 (CI [$$- \;7.31, - \;0.89$$ - 7.31 , - 0.89 ], $$\hbox {p} = 0.01$$ p = 0.01 ) points in the HIT6 scale, $$- \;32.05$$ - 32.05 (CI [$$- \;55.96, - \;8.14$$ - 55.96 , - 8.14 ], $$\hbox {p} = 0.01$$ p = 0.01 ) in the MIDAS scale, $$- \;1.7$$ - 1.7 (CI [$$- \;3.27, - \;0.13$$ - 3.27 , - 0.13 ], $$\hbox {p} = 0.03$$ p = 0.03 ) points in the VAS scale and of $$- \;6.27$$ - 6.27 (CI [$$- \;8.48, - \;4.07$$ - 8.48 , - 4.07 ], $$\hbox {p} < 0.01$$ p < 0.01 ) migraine episodes per month. Comorbid patients showed slightly better improvements in BDI, HIT6 scores and migraine frequency compared to monomorbid patients. The latter group manifested better results in MIDAS and VAS scores. Conclusion Treatment with onabotulinumtoxinA leads to a significant reduction of disease severity of both chronic migraine and major depressive disorder in patients comorbid with both diseases. Comparative analyses suggest an equivalent strong effect in monomorbid and comorbid patients, with beneficial effects specifically seen for certain migraine features.

The outcome of kidney transplant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is still unclear. Here we describe the clinical characteristics, disease outcome, and risk factors for acute respiratory distress syndrome (ARDS) and death of a cohort of 53 kidney transplant patients with coronavirus disease 2019 (COVID-19). Eight of 53 have been handled as outpatients because of mild disease, on average with immunosuppression reduction and the addition of hydroxychloroquine and azithromycin; no patients required admission, developed ARDS, or died. Because of severe symptoms, 45/53 required admission: this cohort has been managed with immunosuppression withdrawal, methylprednisolone 16 mg/d, hydroxychloroquine, and antiviral drugs. Dexamethasone and tocilizumab were considered in case of ARDS. About 33% of the patients developed acute kidney injury, 60% ARDS, and 33% died. In this group, thrombocytopenia was associated to ARDS whereas lymphopenia at the baseline, higher D-dimer, and lack of C-reactive protein reduction were associated with risk of death. In the overall population, dyspnea was associated with the risk of ARDS and age older than 60 years and dyspnea were associated with the risk of death with only a trend toward an increased risk of death for patients on tacrolimus. In conclusion, SARS-CoV-2 infection may have a variable outcome in renal transplant patients, with higher risk of ARDS and death in the ones requiring admission.

The SARS-CoV-2 epidemic is pressuring health care systems worldwide. Disease outcomes in certain subgroups of patients are still scarce, and data are needed. Therefore, we describe here the experience of four dialysis centers of the Brescia Renal COVID task force. During March 2020, within an overall population of 643 hemodialysis patients, SARS-CoV-2 RNA positivity was detected in 94 (15%). At disease diagnosis, 37 of the 94 (39%) patients (group 1) were managed on an outpatient basis whereas the remaining 57 (61%) (group 2) required hospitalization. Choices regarding management strategy were made based on disease severity. In group 1, 41% received antivirals and 76% hydroxychloroquine. Eight percent died and 5% developed acute respiratory distress syndrome (ARDS). In group 2, 79% received antivirals and 77% hydroxychloroquine. Forty two percent died and 79% developed ARDS. Overall mortality rate for the entire cohort was 29%. History of ischemic cardiac disease, fever, older age (over age 70) and dyspnea at presentation were associated with the risk of developing ARDS whereas fever, cough and a C-reactive protein higher than 50 mg/l at disease presentation were associated with the risk of death. Thus, in our population of hemodialysis patients with SARS-CoV-2 infection, we documented a wide range of disease severity. The risk of ARDS and death is significant for patients requiring hospital admission at disease diagnosis., Graphical abstract

The outcome of SARS-CoV2 infection in patients who have received a kidney allograft and are being treated with immunosuppression is unclear. We describe 20 kidney transplant recipients (median age 59 years [inter quartile range 51-64 years], median age of transplant 13 years [9-20 years], baseline eGFR 36.5 [23-47.5]) with SARS-CoV2 induced pneumonia. At admission, all had immunosuppression withdrawn and were started on methylprednisolone 16 mg/day, all but one was commenced on antiviral therapy and hydroxychloroquine with doses adjusted for kidney function. At baseline, all patients presented fever but only one complained of difficulty in breathing. Half of patients showed chest radiographic evidence of bilateral infiltrates while the other half showed unilateral changes or no infiltrates. During a median follow-up of seven days, 87% experienced a radiological progression and among those 73% required escalation of oxygen therapy. Six patients developed acute kidney injury with one requiring hemodialysis. Six of 12 patients were treated with tocilizumab, a humanized monoclonal antibody to the IL-6 receptor. Overall, five kidney transplant recipients died after a median period of 15 days [15-19] from symptom onset. These preliminary findings describe a rapid clinical deterioration associated with chest radiographic deterioration and escalating oxygen requirement in renal transplant recipients with SARS-Cov2 pneumonia. Thus, in this limited cohort of long-term kidney transplant patients, SARS-CoV-2 induced pneumonia is characterized by high risk of progression and significant mortality.

The infection rate of total knee arthroplasty is still high, in spite of the high success of this surgical procedure. The use of an antibiotic-loaded temporary spacer made of poly(methyl methacrylate) (PMMA) has been proposed to treat infected knee arthroplasties. This study was aimed at comparatively investigating, on a molecular scale, two types of spacers from the same manufacturer (Spacer K and Vancogenx-space knee, Tecres, Italy), which differ for the added antibiotic (gentamicin sulphate in Spacer K and gentamicin sulphate + vancomycin hydrochloride in Vancogenx). Raman spectroscopy was used to gain more insights into the possible effects of the antibiotic on the spacer composition and polymer structure both in the new components and after in vivo use. Vancogenx was found to contain a lower residual MMA content than Spacer K (about 0.15% versus 0.4%). The former contained a higher amount of isotactic stereosequences than the latter, while the syndiotactic content (the prevailing component) was not significantly different in the two prostheses. The presence of vancomycin hydrochloride influenced not only the degree of polymerization and PMMA tacticity and crystallinity, but in turn also the wear behavior. Actually, Spacer K retrievals were found more affected by in vivo implantation than Vancogenx-space knee ones, revealing slight variations in polymer tacticity and crystallinity and relative radiopacifier content, besides release of MMA and additives of polymerization. However, these changes did not appear worrisome, due to the temporary nature of the prosthesis. In view of these results, the addition of vancomycin hydrochloride could offer an advantage, in spite of the higher costs requested and the potential risks of its unselective use.

Steroid minimization has always been one of the most desired goals regarding immunosuppressive therapy after renal transplantation. Following the introduction of cyclosporine different steroid-free protocols became available, but their implementation was limited due to the high risk of acute rejection. In the last few years, the use of a very low dose of prednisone (5 mg/day) has been deemed to guarantee a good balance between steroid toxicity and efficacy. However, high interpatient variability in prednisolone exposure prevented the standard low dose to be as safe as expected in all patients. Therefore, steroid side effects can still be observed in a variable percentage of patients. In this setting, the personalization of steroid dosage might prevent an over exposure to the drug, but this strategy is not available yet. Thus, steroid withdrawal remains the only available strategy to limit side effects. In the last 40 years, we learned that steroid free protocols are associated with a higher risk of acute rejection, but they do not reduce graft survival. Hence, patients at higher risk for acute rejection or recurrence of their primary renal disease are usually excluded from these protocols. Early steroid withdrawal (within 7 days after transplantation) has been widely used and also suggested by American guidelines. However, steroid withdrawal 3-4 months after transplantation has been preferred by many Authors and deemed equally efficient. In addition, early but not late steroid withdrawal should always be associated to induction therapy. Lastly, Tacrolimus plus Mycophenolic Acid has become the most used association in steroid minimization protocols.

Unicompartmental knee arthroplasty remains a challenge for orthopaedic surgeons because of its higher revision rate compare with the total knee arthroplasty. The hypothesis of this work is that the progression of osteoarthritis in unicompartmental knee prostheses is the natural history of the degenerative disease and a reason for reoperation. Most international joint registries consider this fact as a failure of the implant and a cause of revision. Annual joint registries were searched for progression of osteoarthritis in unicompartmental knee arthroplasty and reasons for their revisions. Current data from registries for unicompartmental knee indicate that the revision rate of such prostheses is overestimated. Considering osteoarthritis progression as the development of the existing disease and not as a failure of the implant, revision rate will be reduced. Registries, reports, and studies are needed to evaluate the progression of osteoarthritis as a cause of reoperation instead of a reason for revision, reducing unicompartmental revision rate and encouraging surgeons to implant more of them.

Background Dialysis and kidney transplant patients with moderate-severe COVID-19 have a high mortality rate, around 30%, that is similar in the two populations, despite differences in their baseline characteristics. In these groups, the immunology of the disease has been poorly explored. Methods Thirty-two patients on dialysis or with kidney transplant and SARS-CoV-2 infection requiring hospitalization (COV group) were included in our study. Lymphocyte subsets, dendritic cell (DC) counts and monocyte activation were studied. SARS-CoV-2 anti-spike/anti-nucleocapsid were monitored, and baseline cytokines and chemokines were measured in 10 patients. Results The COV group, compared to healthy subjects and uninfected dialysis/kidney transplant controls, showed lower numbers of CD4 + and CD8 + T cells, Natural-Killer (NK), B cells, plasmacytoid and myeloid DCs, while the proportion of terminally differentiated B-cells was increased. IL6, IL10, IFN-α and chemokines involved in monocyte and neutrophil recruitment were higher in the COV group, compared to uninfected dialysis/kidney transplant controls. Patients with severe disease had lower CD4 + , CD8 + and B-cell counts and lower monocyte HLA-DR expression. Of note, when comparing dialysis and kidney transplant patients with COVID-19, the latter group presented lower NK and pDC counts and monocyte HLA-DR expression. Up to 60 days after symptom onset, kidney transplant recipients showed lower levels of anti-spike antibodies compared to dialysis patients. Conclusions During SARS-CoV-2 infection, dialysis and kidney transplant patients manifest immunophenotype abnormalities; these are similar in the two groups, however kidney transplant recipients show more profound alterations of the innate immune system and lower anti-spike antibody response. Graphical abstract Supplementary Information The online version contains supplementary material available at 10.1007/s40620-021-01214-8.

Immune checkpoint inhibition induced a great step forward in the treatment of non-small cell lung cancer patients. In cancer immune microenvironment many checkpoints were studied and their involvement could represent a mechanism of resistance to cancer immunotherapy. For this reason, the inhibition of multiple immune checkpoints is under development. However, myeloid-derived suppressor cells (MDSC) and exhausted immune cells could limit the efficacy of cancer immunotherapy. We analyzed the variation of circulating immune suppressive-like cell subsets and exhausted immune cells in three non-small cell lung cancer patients treated with the combination of anti-CTLA-4 plus anti-PD-1 plus anti-LAG-3 at T0 (baseline), T1 (after 2 months) and T2 (after 4 months). We also describe the clinical and radiological course of the disease during this treatment in all three patients. We observed both clinical differences and changes in the composition of immune suppressive-like cell subsets and exhausted immune cells between the patients receiving the same schedule of treatment with immune checkpoint inhibitors. The study on a wider patient population and experimental model design could help to clarify the kinetics of these cell subpopulations with the perspective to find new targets for treatment or new biomarkers for resistance to cancer immunotherapy.

Articular cartilage (AC) is a specialized connective tissue able to provide a low-friction gliding surface supporting shock-absorption, reducing stresses, and guaranteeing wear-resistance thanks to its structure and mechanical and lubrication properties. Being an avascular tissue, AC has a limited ability to heal defects. Nowadays, conventional strategies show several limitations, which results in ineffective restoration of chondral defects. Several tissue engineering approaches have been proposed to restore the AC's native properties without reproducing its mechanical and lubrication properties yet. This work reports the fabrication of a bilayered structure made of gellan gum (GG) and poly (ethylene glycol) diacrylate (PEGDA), able to mimic the mechanical and lubrication features of both AC superficial and deep zones. Through appropriate combinations of GG and PEGDA, cartilage Young's modulus is effectively mimicked for both zones. Graphene oxide is used as a dopant agent for the superficial hydrogel layer, demonstrating a lower friction than the nondoped counterpart. The bilayered hydrogel's antiwear properties are confirmed by using a knee simulator, following ISO 14243. Finally, in vitro tests with human chondrocytes confirm the absence of cytotoxicity effects. The results shown in this paper open the way to a multilayered synthetic injectable or surgically implantable filler for restoring AC defects.

Background Migraine represents one of the most prevalent neurological conditions worldwide. It is a disabling condition with high impact on the working situation of migraineurs. Interestingly, gender-related differences regarding an association of migraine with important occupational characteristics has been hardly studied. Methods The current study scrutinizes gender-specific differences in the prevalence of migraine across a broad spectrum of occupational categories, shedding also light on associations with important job-related features such as shift work, job satisfaction, and physical activity. The study included data from 415 712 participants from the UK Biobank cohort, using the official ICD10 diagnosis of migraine and other health conditions as selection criteria. Prevalence ratios of migraineurs compared to healthy controls among different occupational categories and job-related variables were estimated using log-binomial regression analyses. Statistical models were adjusted for important sociodemographic features such as age, BMI, ethnicity, education and neuroticism. To better highlight specific differences between men and women we stratified by sex. Results We detected a differential prevalence pattern of migraine in relation to different job categories between men and women. Especially in men, migraine appears to be more prevalent in highly physically demanding occupations (PR 1.38, 95% CI [0.93, 2.04]). Furthermore, migraine is also more prevalent in jobs that frequently involve shift or night shift work compared to healthy controls. Interestingly, this prevalence is especially high in women (shift work PR 1.45, 95% CI [1.14, 1.83], night shift work PR 1.46, 95% CI [0.93, 2.31]). Conclusion Our results show that migraine is genderdependently associated with physically demanding jobs and shift working.

The effect of being obese on the long-term survival of total joint arthroplasty is persistently discussed. Considering only studies with large cohort of patients and meta-analysis, a high body mass index has been correlated with a higher incidence of complication but not univocally with a lower survival rate. In this study, we analyzed, retrospectively, the data of patients that received unicompartmental knee prostheses in order to examine if obesity has an effect on clinical outcomes.A retrospective multi-centre study was carried out on 4964 unicompartmental knee replacements between July 2000 and December 2016, the patients involved were 3976, with 988 bilateral cases. The patients were categorized into three groups: non-obese with a body mass index (BMI) 30 kg/mThe morbidly obese group was significantly younger and required a significantly longer operating time. No statistical significant differences were observed considering the BMI groups in terms of type of insert, type of tibial component, prosthetic condyle, and prosthesis fixation (p 0.05; chi-square test).Obese and morbidly obese patients have as much to gain from total knee replacement as non-obese patients.

Purpose Although total knee arthroplasty is a well-practiced surgical procedure, material properties and surface topography can contribute to the wear mechanisms and the implant failure. It has been advised that an increased femoral component's surface roughness of total knee prostheses may be a contributing factor to accelerated wear of the polyethylene menisci and eventually prosthesis failure. The aim of this study is to investigate the wear phenomena occurring on medial and lateral compartments of retrieved total knee arthroplasty in order to correlate the surface roughness vs. BMI, age at revision, and time in situ. Methods Qualitative visual analyses were performed on all the retrieved knee components to assess the damage due to the wear phenomena. Quantitative analysis includes surface characterization performed using optical apparatus to describe surface roughness and morphology on the retrieved femoral, tibial and polyethylene component. The Mann-Whitney statistical test was performed to correlate the medial vs. lateral condyle surface roughness of all explants with BMI, age at revision, and time in situ. Results Visual and topographical analysis showed damage along the entire zone of the sliding contact area. A statistical difference between medial and lateral condyle roughness was found on four prosthesis. No statistical significance was found between surface roughness measurements and patient BMI, age at revision, and time in situ. On the femoral components various scratches were observed in the anterior/posterior (AP) direction of all the fixed femoral components. A statistically significant difference between medial and lateral condyle was found on two mobile knee design (p = 0.03) and on two fixed design (p = 0.01). The results were discussed in the framework of the usual TKR loading conditions during the gait, and of knowledge on the bio-tribological behavior of the prosthetic joint. Conclusions The visual and topographical analysis showed consistent damage patterns with respect to the main movements to which the prosthetic components are subjected and no statistical significance was found between surface roughness measurements and patient BMI, age at revision, and time in situ.

Astrogliosis has a very dynamic response during the progression of spinal cord injury, with beneficial or detrimental effects on recovery. It is therefore important to develop strategies to target activated astrocytes and their harmful molecular mechanisms so as to promote a protective environment to counteract the progression of the secondary injury. The challenge is to formulate an effective therapy with maximum protective effects, but reduced side effects. In this study, a functionalized nanogel-based nanovector was selectively internalized in activated mouse or human astrocytes. Rolipram, an anti-inflammatory drug, when administered by these nanovectors limited the inflammatory response in A1 astrocytes, reducing iNOS and Lcn2, which in turn reverses the toxic effect of proinflammatory astrocytes on motor neurons in vitro, showing advantages over conventionally administered anti-inflammatory therapy. When tested acutely in a spinal cord injury mouse model, it improved motor performance, but only in the early stage after injury, reducing the astrocytosis and preserving neuronal cells.

Purpose Although total knee arthroplasty is one of the most successful and consolidated surgical procedure, the infection rate is still elevate. To treat infected knee arthroplasties, in the past years was approached a procedure that involved the implantation of an antibiotic-loaded temporary spacer. This spacer helps maintain an appropriate soft tissue envelope and the patients are able to walk during the interim period. This study investigated the tribological behavior of antibiotic-impregnated knee spacers under dynamic loading. Methods Three temporary spacer specimens were subjected to a cyclic test on a knee wear simulator for 500,000 walking cycles under a modified international guidelines (ISO 14243). During this test we address about the evaluation of the mechanical resistance and to quantify the wear rate of the devices. All the kinematics and the axial load were set to simulate more than six months of patient use. Results All the femoral and tibial specimens completed the 500,000 cycles without breakage. The wear patterns observed on the contact surfaces were similar over the specimens. Conclusions On the basis of the present data, the authors believe that the use of temporary antibiotic-impregnated knee spacers could be an effective wear-resistance temporary substitute of a total knee two-stage revision arthroplasty.

Total Knee Arthroplasty is a well-established surgical procedure performed to relieve pain and to restore function in knee osteoarthritis. A proper choice of the implant size is mandatory in order to guarantee the success of the implant and to respect the bone stock of tibial plateau and femoral condyles. The aim of this study was to investigate the combined effect of Body Mass Index and implant size on the wear damage of retrieved knee implants, a still debated subject. To this purpose, twelve total knee prostheses of the same design (NexGen, Zimmer, Warsaw, Indiana) but with different sizes were investigated. These prostheses were all cemented fixed bearing inserts and posterior stabilised. Roughness analyses were performed on femoral components to assess surface modifications. Micro-Raman spectroscopic characterization was performed on polyethylene inserts to evaluate crystallinity changes. A worsening of the surface and a nonhomogeneous aspect was observed in the prostheses characterized by a high ratio between preoperative Body Mass Index and implant size, which we called Ф factor. Delamination, a good indicator for polyethylene osteolysis, was more pronounced in the inserts having a high Ф than in those with a low Ф. Micro-Raman analyses showed more significant crystallinity changes in the prostheses of lower size, in agreement with the results previously obtained in vitro. The findings of the present study suggested that the Ф factor can be considered a predictor factor of the Total Knee Arthroplasty overall performance. Potentially, it could be used as a discriminating factor to redact Total Knee Arthroplasty outcome and prevent complications.

A new tendency in the field of wear testing of total knee replacements is represented by realistic simulations of various motor tasks of daily living (chair sitting and rising, squat, stair ascent, etc.). Various studies have shown in fact the limits of the ISO 14243 standards, in particular the concern about the ability of the level walking simulations to recreate the main wear mechanisms which occur on the knee implant during its in vivo lifespan. The recently proposed protocols for the simulation of these motor tasks still lack accuracy and consistency between the various degrees of freedom, which are necessary for a good replication of the mechanical behavior in a replaced knee. In the present study a realistic scenario for simulation of various motor tasks using a displacement controlled wear testing machine is presented. Stair climbing, chair sit/stand cycle, and squat cycle were analyzed through video-fluoroscopy in a population of knee replacement patients to extract flexion/extension and intra/extra rotation angles, together with anterior/posterior translation. Corresponding axial load data were arranged by gait analysis from a control population. The proposed protocol was tested on a displacement controlled wear simulator. Kinematic and load data revealed good consistency across subjects. The knee simulator showed an accurate reproduction of the various motion and load patterns, with average error lower than 5%. The obtained dataset for wear simulator, containing all the displacement and loading parameters for stair climbing, chair sit/stand and squat activities, is fully reported.

Purpose of review Automated external defibrillators require preshock interruptions in cardiopulmonary resuscitation (CPR) to perform rhythm analysis. Artifact filtering technology may provide the opportunity to visualize the underlying ECG trace during CPR. Moreover, a continuous ventricular fibrillation analysis may be performed such to prioritize CPR interventions, that is, chest compression or defibrillation. Recent findings Different ECG filtering techniques and ventricular fibrillation analysis algorithms to predict defibrillation outcome have been developed. Techniques to analyze ECG rhythm during CPR encompass two major solutions: adaptive filters for the suppression of chest compression artifacts and algorithms for a direct analysis of the artifact-contaminated ECG. The above methods achieve overall a high sensitivity of more than 99%, but an unacceptable specificity of less than 93%. Among the different ventricular fibrillation analysis approaches and defibrillation predictors, amplitude spectrum area has appeared as an independent predictor of defibrillation success, with an area under the receiver operating curve of 0.86. Summary The feasibility of ventricular fibrillation detection during CPR is a challenging issue that, if solved, would enable CPR to continue during the automated external defibrillator rhythm analysis. Furthermore, it would allow a continuous ventricular fibrillation analysis to optimize the timing of defibrillation and maximize the shock success.

Background and purpose — Little is known about the role of retained trunnions in revision hip arthroplasties, i.e., when only the femoral head is substituted. Wear (fretting corrosion) and ceramic head fractures are 2 poorly understood concerns related to use, and the role of adapter sleeves has not been defined. In this registry study we assessed the influence of sleeve interposition on re-revision rates in revision hip arthroplasties with retained stems. Confounding factors (demographics, implant-related features) and failures were also analyzed. Patients and methods — We conducted a registry study on 1,127 revised implants (retained trunnion and head exchange). In 26% of implants an adapter sleeve was interposed; in 74% no adapter sleeve was implanted. Demographic and implant-related features were investigated including a descriptive analysis of failures. Results — The mean follow-up of revised implants with and without the use of an adapter sleeve was 3.3 and 5.1 years, respectively. The implant survival without an adapter sleeve was significantly higher, 98.4% (95% CI 96.9–99.8) vs. 95.2% (CI 93.2–96.6) with an adapter sleeve at 5 years. No re-revisions due to adverse local tissue reactions or ceramic head fractures were reported. In order to overcome the different distribution of head materials and head sizes in the two cohorts, only Delta balls were investigated. Interpretation — Adapter sleeve interposition had a minor influence on the revision rates. No adverse local tissue reactions or head fractures occurred.

Ovarian mucinous tumors represent a group of rare neoplasms with a still undefined cell of origin but with an apparent progression from benign to borderline to carcinoma. Even though these tumors are different from the other histological subtypes of epithelial ovarian neoplasms, they are still treated with a similar chemotherapeutic approach. Here, we review its pathogenesis, molecular alterations, (differential) diagnosis, clinical presentation and current treatment, and how recent molecular and biological information on this tumor might lead to better and more specific clinical management of patients with mucinous ovarian carcinoma.

Wear and osteolysis continue to be the major reasons for revision surgery in Total Hip Arthroplasty. The introduction of the ceramic-on-ceramic bearings eliminates the problem of polyethylene wear debris. During the last 40 years, three generations of Biolox® ceramics were developed (Biolox®, Biolox® forte, and Biolox® delta), each better than the previous from the density, grain size and purity point of view. We conducted a retrieval study on 15 Biolox® femoral heads (Biolox®, Biolox® forte, and Biolox® delta) articulating against liners of the same type. Surface properties and residual stress were assessed using SEM, fluorescence and Raman spectroscopy. At SEM examination, the Biolox® delta retrievals showed a lower wear than the previous generations. The fluorescence measurements suggested different wear mechanisms in the three sets of retrievals. Micro-cracking was predominant in Biolox®, while in Biolox® forte and Biolox® delta a wider range of residual stress values was observed upon wear. Surface polishing was observed only in Biolox® and Biolox® forte. Raman spectroscopy of Biolox® delta femoral heads showed a progressive improvement in material composition. Wear induced a tetragonal to monoclinic transformation. The Raman results on the retrievals, here reported for the first time, allowed to validate the in vitro ageing protocols proposed in the literature to simulate the effects of the in vivo wear.

Context • Anecdotal evidence concerning a relationship between human illnesses and a full moon is frequently claimed by as many as 81% of mental health workers. Previous scientific investigations have studied only the full-moon phase and its possible effect on psychiatric presentations. However, information is limited about all 4 phases of the lunar cycle and their effects on different types of psychiatric disorders. Objective • This study primarily intended to evaluate the number of psychiatric presentations to a hospital's emergency department across all 4 phases of the lunar cycle. The secondary objective was to investigate the statistical differences among 5 categories of common mental disorders in relation to the 4 lunar phases. Design • This study was an observational analytic cohort study. Setting • The study took place in the emergency department of a 140-bed, community-teaching hospital. Participants • Participants were 1857 patients who were aged17 y and who had had a psychiatric component to a visit to the emergency department. Outcome Measures • Data from electronic medical records were collected for 41 consecutive months. The participants were divided into 5 diagnostic groups based on the Diagnostic and Statistical Manual of Mental Disorders, 5th ed (DSM-5). The study measured the number of psychiatric presentations for each group during the 4 National Aeronautics and Space Administration (NASA)-defined phases of the lunar cycle, and the study was statistically powered to detect small effects. Results • The following psychiatric presentations occurred: (1) 464 during the new moon; (2) 483 during the first quarter; (3) 449 during the full moon; and (4) 461 during the third quarter (4-group overall χ2, P = .89). Differences between the 5 diagnostic categories across the 4 lunar phases were not statistically significant (4-group overall χ2, P = .85 for the 5 diagnostic categories). Conclusions • Although many traditional and nontraditional providers believe in effects caused by the full moon based on casual observation or anecdotal evidence, this perception was not supported in the current study. Furthermore, no evidence demonstrated increased psychiatric presentations during the other 3 phases of the lunar cycle. The study found that the lunar cycle did not have an effect on the incidence of psychiatric presentations or on the DSM-5 categories. If lunar effects exist, they are probably small or infrequent, making them difficult to validate statistically. The current study's results, in concert with those of most other studies on the subject, provide evidence that should help dismiss misconceptions about the magnitude or frequency of lunar effects on psychiatric illnesses.

Improved wear resistance in total knee replacement (TKR) is a suitable goal. Whereas the use of metal components is well established, mechanical loosening in recently introduced ceramic components are a cause of concern. The scope of this work was to test in vitro whether ceramic TKR femoral components are more prone to mechanical loosening than metal ones. Composite femurs were implanted with commercially available TKR metal components, and with ceramic components having identical shape to the metal ones. Implanted femurs were tested on a knee simulator for up to 5 x 10(-6) cycles. Inducible micromotions and permanent migrations were recorded throughout the test. The cement layers were inspected for signs of damage or fracture. Micromotions and migrations were similar for metal and ceramic components: their magnitude and trend over time indicated that no implant was becoming loose. When there were statistically significant differences, the ceramic components were more stable than the metal ones. When the cement layers were inspected, a few short cracks were observed; most such cracks appeared during the first cycles, while no further damage occurred in the rest of the test. The type of damage found for both the metal and the ceramic components is compatible with well-fixed implants after long-term cycling. Altogether, no remarkable difference was found between the metal and ceramic components. Therefore, this study rejects the hypothesis that ceramic TKR femoral components are more prone to mechanical loosening. Although this study had a limited sample size, it provides novel pre-clinical indications about the potential of ceramic TKR femoral components.

The wear of the ultra-high-molecular-weight polyethylene (UHMWPE) tibial insert was determined using a four-station knee simulator. The bearings were subjected to flexion/extension (between 0 and 58 degrees ), anterior-posterior translation (between 0 and -5.2 mm), internal-external rotation (between -1.9 degrees and +5.7 degrees ), and a maximum axial load of 2.6 KN, as per ISO 14243-1,2,3. The wear tests were run at a frequency of 1.1 Hz for 5 million cycles, and the wear of the inserts (n = 3) was determined using the gravimetric method. The novelty of the study was a special setup developed to simulate, as realistically as possible, in vivo conditions; this involved fixing the femoral component to the distal end of a synthetic femur model by a qualified orthopedic surgeon using an approved method. After 5 million cycles, the mean weight losses were 11.16, 19.74, and 12.61 mg for specimens #1, #2, and #3, respectively. Visual and nondestructive inspections for each of the test specimens showed similar wear tracks and these were very similar to those seen on inserts retrieved after 2 years in vivo. These results show the efficacy of the new in vitro UHMWPE wear assessment method. Furthermore, a comparison between the present in vitro results and those reported in a relevant previous study provide some insight into the influence of the method used to fix the femoral component to the simulator on the wear magnitude and patterns of the tibial insert.

This study was aimed at determining the surface degradation occurred on retrieved ceramic and metallic heads, as well as the influence of the head surface quality on the wear of the polyethylene counterface. To this purpose, 14 ceramic and 14 metallic femoral heads retrieved at revision surgery were examined. Scanning electron microscopic analysis provided visual evidence that some metallic heads presented crescent wear more often than the ceramic ones; the former showed a higher volumetric loss (as determined by Coordinate Measuring Machine) than the latter, but less negative Rsk values. This apparent lack of correlation between volumetric loss (i.e., wear factor) and roughness data may be explained by considering that they are two temporally variant parameters. No significant differences were observed between the Ra values of the two sets of femoral heads. The cups articulating against metal heads were characterized by higher mean wear volumes than those articulating against alumina although this difference was not statistically significant; metal heads displayed significantly higher mean wear volumes than alumina heads. The micro-Raman analysis of the cup articulated against the most worn alumina femoral head showed an orthorhombic into monoclinic phase transformation that was not observed in the cups coupled to metal heads. The obtained results showed that the surface finishing of the femoral head (in terms of Rsk values) determined the morphological changes experienced by the ultra-high-molecular-weight polyethylene crystalline phase at the molecular level. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1374-1385, 2016.

Purpose Wear and survival of total joint replacements do not depend on the duration of the implant in situ, but rather on the amount of its use, i.e. the patient’s activity level. With this in mind, the present study was driven by two questions: (1) How does total knee replacement (TKR) respond to the simulation of daily highly demanding activities? (2) Are certain activities to be advised against or, on the contrary, useful to implanted patients, in order to reduce wear of TKR and its related problems? Methods One set of the same total knee prosthesis (TKP), equal in design and size, was tested on a three-plus-one knee joint simulator for two million cycles using a highly demanding daily load waveform, replicating a stair-climbing movement. The results were compared with a set of TKP previously tested with the ISO level walking task. A digital microscope was used to characterise the superficial structure of all the TKPs. Gravimetric and micro-Raman spectroscopic analyses were carried out on the polyethylene inserts. Visual comparison with in vivo explants was carried out. Results The average volumetric mass loss after two million cycles was 44±6 mm3. Microscope examinations showed some deep scratches along the flexion/extension movements for all the components. Also, the metallic backside surface showed intense non-linear scratches and the polyethylene counterface was characterised by some craters. A decrease in crystallinity, induced bymechanical stress was observed on all polyethylene components and was quantitatively confirmed by the orthorhombic fraction αo value. Conclusions The results of this study demonstrated that the forces and motion sustained by the knee are highly activitydependent. Moreover, this test confirmed that under more severe conditions, the material properties change according to a different wear mechanism and a decrease in crystallinity occurs. Loading characteristics for specific activities should be considered for the design of functional and robust TKRs.

Background Wear associated with hip components represents the main clinical problem in these patients, and it is important to develop new techniques for more accurate measurements of that wear. Currently, the gravimetric method is the gold standard for assessing mass measurements in preclinical evaluations. However, this method does not give other information such as volumetric loss or surface deviation. This work aimed to develop and validate a new technique to quantify ceramic volume loss from in vitro experiments using micro-computed tomography (micro-CT). Methods An alumina (BIOLOX® forte) femoral head (Ø = 28 mm) was used. Mass and volume loss were approached by gravimetric method (using a four decimal place digital microbalance) and by using Skyscan 1176 microtomographic system, respectively. Results Standard error and coefficient of variance of both gravimetric and experimental groups demonstrated the reliability of the micro-CT analysis technique. Conclusions In conclusion, the findings of the present study suggest that this new protocol could be considered an important tool for wear assessment and that we have found a reliable metrological protocol for volumetric analysis of ceramic femoral head prostheses, demonstrating that the micro-CT technique can be an important tool for wear assessment.

The combination of materials that still has highest wear resistance for total hip replacement is ceramic-on-ceramic. However, brittleness is a major concern for ceramics: in vivo and in vitro studies on ceramic hip prostheses correlate microseparation with hip noise, ceramic wear, or ceramic liner damage. Ceramic microseparation can lead to edge load, ceramic head wear, and squeaking. The aim of this in vitro study was to investigate whether different angles of inclination influence the wear pattern of alumina-on-alumina hip joints with micro-separation during the swing phase. We also evaluated the wear rate obtained from this in vitro investigation with retrieval specimens obtained at 13 years' mean follow-up. The study was performed using a 12-station hip joint wear simulator (Shore Western, Monrovia, CA, USA) under bovine calf serum used as lubricant. Wear was evaluated by the gravimetric method and the test length was set at two million cycles. After two million cycles, a volumetric loss of 0.11 ±0.03 mm3 and 0.12 ±0.06 mm3 was observed, respectively, for 23° and 63° angles of inclination. In particular, the results obtained in this work revealed an increase of about 12-fold compared to previous results without microseparation conditions. No significant differences were observed between the two different inclinations on the wear patterns of the acetabular cups with a level of significance of α = 0.5. The location and general shape of the stripes wear were similar for the retrieved and simulator balls.

Modification of knee joint wear simulation methods has included ‘anatomic attachment’ of unicondylar knee replacements (UKR) onto synthetic femurs with material properties and morphology similar to human femurs. The present study assesses the effect of such modification by comparing the damage patterns on UKR polyethylene inserts after in vitro simulation using standard and modified simulation methods with those on inserts retrieved after in vivo function. Three groups of UKR inserts were evaluated after retrieval (Explant Group, n = 17) or after knee joint wear simulation with the components attached to standard metal blocks (Standard Group, n = 6) or synthetic femurs (Anatomic Group, n = 6). All UKR had similar non-conforming articular surfaces. Articular damage patterns (mode, frequency, and area) were quantified using digital image photogrammetry. Although some common damage modes were noted, knee joint wear simulation with standard or ‘anatomic’ attachment did not generate damage pattern sizes similar to the explanted UKR. A focal damage pattern consistent with contact between the metal femoral articular surface and the polyethylene inserts was evident on all inserts, but only the Explant Group had evidence of dispersed damage dominated by abrasive modes. Synthetic femurs added complexity to the wear simulation without generating wear patterns substantially more similar to those observed on retrieved inserts.

Recent in vivo studies have identified variations in knee prosthesis function depending on prosthesis geometry, kinematic conditions, and the absence/presence of soft-tissue constraints after knee replacement surgery. In particular, unicondylar knee replacements (UKR) are highly sensitive to such variations. However, rigorous descriptions of UKR function through experimental simulation studies, performed under physiological force-controlled conditions, are lacking. The current study evaluated the long-term functional performance of a widely used fixed-bearing unicompartmental knee replacement, mounted in a bi-unicondylar configuration (Bi-UKR), utilizing a force-controlled knee simulator during a simulated (ISO 14243) walking cycle. The wear behaviour, the femoral—tibial kinematics, and the incurred damage scars were analysed. The wear rates for the medial and the lateral compartments were 10.27 ± 1.83 mg/million cycles and 4.49 ± 0.53 mg/million cycles, respectively. Although constant-input force-controlled loading conditions were maintained throughout the simulation, femoral—tibial contact point kinematics decreased by 65 to 68 per cent for average anterior/posterior travel and by 58 to 74 per cent for average medial/lateral travel with increasing cycling time up to 2 million cycles. There were no significant differences in damage area or damage extent between the medial and the lateral compartments. Focal damage scars representing the working region of the femoral component on the articular surface extended over a range of 16—21 mm in the anterior—posterior direction. Kinematics on the shear plane showed slight variations with increasing cycling time, and the platform exhibited medial pivoting over the entire test. These measures provide valuable experimental insight into the effect of the prosthesis design on wear, kinematics, and working area. These functional assessments of Bi-UKR under force-controlled knee joint wear simulation show that accumulated changes in the UKR articular conformity manifested as altered kinematics both for anterior/posterior translations and internal/external rotations.

Interest in the rheology and effects of interacting surfaces is as ancient as man. This subject can be represented by a recently coined word: tribology. This term is derived from the Greek word "tribos" and means the "science of rubbing". Friction, lubrication, and wear mechanism in the common English language means the precise field of interest of tribology. Wear of total hip prosthesis is a significant clinical problem that involves, nowadays, a too high a number of patients. In order to acquire further knowledge on the tribological phenomena that involve hip prosthesis wear tests are conducted on employed materials to extend lifetime of orthopaedic implants. The most basic type of test device is the material wear machine, however, a more advanced one may more accurately reproduce some of the in vivo conditions. Typically, these apparatus are called simulators, and, while there is no absolute definition of a joint simulator, its description as a mechanical rig used to test a joint replacement, under conditions approximating those occurring in the human body, is acceptable. Simulator tests, moreover, can be used to conduct accelerated protocols that replicate/simulate particularly extreme conditions, thus establishing the limits of performance for the material. Simulators vary in their level of sophistication and the international literature reveals many interpretations of the design of machines used for joint replacement testing. This paper aims to review the current state of the art of the hip joint simulators worldwide. This is specified through a schematic overview by describing, in particular, constructive solutions adopted to reproduce in vivo conditions. An exhaustive commentary on the evolution and actually existing simulation standards is proposed by the authors. The need of a shared protocol among research laboratories all over the world could lead to a consensus conference.

The wear of metal-on-metal bearings is affected by various design parameters, such as the clearance or surface roughness. It would be very useful to have a significant indicator of wear according to these design parameters, such as the Λ ratio. Three different batches of cast high- and low-carbon cobalt—chromium hip implants (28 mm, 32 mm, and 36 mm diameters) were tested in a hip joint simulator for 2 × 106 cycles. Bovine calf serum was used as lubricant, and the samples were weighed at regular intervals during the test. The predictive role of the Λ ratio on the wear behaviour was investigated. Three different configurations were tested to explore the wear rate for a broad range of Λ ratios. The results of these studies clearly showed that the femoral heads of 36 mm diameter had the best wear behaviour with respect to the other two smaller configurations tested. From a predictive point of view, the Λ ratios associated with the configurations tested could clearly indicate that the femoral heads of 36 mm diameter worked in the mixed-lubrication regime (Λ>1); all the smallest configurations (28 mm size) had λ< 1, thus showing their aptitude to work in the boundary lubrication regime, with substantially higher volume depletion due to wear. The Λ values associated with the 32 mm size varied in a range around 1 (0.95

Purpose The research questions of the present study were: (1) Is total knee prosthesis wear behaviour influenced by implant size, body weight and their combined effect? (2) Are these findings significant and helpful from a clinical point of view? Methods Two very different sizes of the same total knee prosthesis (TKP), previously tested with ISO 14243 parameters, were tested on a knee simulator for a further two million cycles using a modified ISO 14243 load waveform. Roughness examination was performed on the metallic components. Gravimetric and micro-Raman spectroscopic analyses were carried out on the polyethylene inserts. Results The average volumetric mass loss was 69 +/- 3 mm(3) and 88 +/- 4 mm(3) for smaller and bigger size, respectively. Bigger TKPs are little influenced by an increased load, while the wear trend of the smaller TKP showed a redoubled slope, and more significant morphology changes were observed. However, the two sizes seem to behave similarly when subjected to a load increase of 15 %; the slope of the volumetric mass loss trend was comparable for the two sets of inserts, which did not appear significantly different also at the molecular level. Roughness average parameters of the lateral femoral condyle support this evidence. Conclusions It can be asserted that the body weight and implant size are relevant to the understanding of TKP wear behaviour. A post-implantation body weight increase in a patient with smaller knee dimensions could results in more critical effects on prosthesis long-term performance.

Since 1979 the number of patients treated with femoral stems has continued to grow, as well as the number of stems with features similar to the Zweymuller prosthesis produced by different companies. Identification can be problematic in case requiring revision. In the present paper, we present an overview of morphometric differences between the different stem designs, which can be useful for radiologic identification in revision cases. By doing some research on the Internet of specialized sites and worldwide literature, we searched for all femoral stems agreeing with Zweymuller principles (cementless, straight, tapered, rectangular cross-sectioned femoral stems). We found 26 different stems from different companies producing or having produced in the past the Zweymuller-type femoral stems for hip prosthesis. Accurate preoperative identification of the Zweymuller femoral stem type may be of critical importance to eventual outcomes following revision surgery. Each manufacturer has different instruments specific to the removal of their primary implants, and ensuring they are available can simplify the revision procedure significantly. Exact pre-operative planning is also necessary for selecting the correct ball head in cases where a stem is well-fixed and can be left in situ. The commonly used notation "Eurocone 12/14" provides no information about the actual taper angle. Whenever the stem is left in situ, the exact specifications of the taper must therefore be obtained from the manufacturer in order to use a metal sleeve that precisely fits it and the ball head. Failure to do so may result in severe complications, such as metallosis. In cases where it is not possible to identify the taper angle, the surgeon may even consider removal of the stem, though this significantly increases the surgical procedure's invasiveness. Only a single, uniform standard taper, such as that offered until 1994 by CeramTec, can solve these issues in the future. The survival rate of the Zweymuller stems after ten years was 96 % and the complication rate was very low. Pre-operative identification of the femoral implant is of considerable importance for planning and correctly implementing revision procedures.

All-trans-retinoic acid (ATRA) is a natural compound proposed for the treatment/chemoprevention of breast cancer. Increasing evidence indicates that aberrant regulation of epithelial-to-mesenchymal transition (EMT) is a determinant of the cancer cell invasive and metastatic behavior. The effects of ATRA on EMT are largely unknown. In HER2-positive SKBR3 and UACC812 cells, showing co-amplification of the ERBB2 and RARA genes, ATRA activates a RARα-dependent epithelial differentiation program. In SKBR3 cells, this causes the formation/reorganization of adherens and tight junctions. Epithelial differentiation and augmented cell-cell contacts underlie the anti-migratory action exerted by the retinoid in cells exposed to the EMT-inducing factors EGF and heregulin-β1. Down-regulation of NOTCH1, an emerging EMT modulator, is involved in the inhibition of motility by ATRA. Indeed, the retinoid blocks NOTCH1 up-regulation by EGF and/or heregulin-β1. Pharmacological inhibition of γ-secretase and NOTCH1 processing also abrogates SKBR3 cell migration. Stimulation of TGFβ contributes to the anti-migratory effect of ATRA. The retinoid switches TGFβ from an EMT-inducing and pro-migratory determinant to an anti-migratory mediator. Inhibition of the NOTCH1 pathway not only plays a role in the anti-migratory action of ATRA; it is relevant also for the anti-proliferative activity of the retinoid in HCC1599 breast cancer cells, which are addicted to NOTCH1 for growth/viability. This effect is enhanced by the combination of ATRA and the γ-secretase inhibitor N-(N-(3,5-difluorophenacetyl)-l-alanyl)-S-phenylglycine t-butyl ester, supporting the concept that the two compounds act at the transcriptional and post-translational levels along the NOTCH1 pathway.

Knee wear simulators are meant to perform load cycles on knee implants under physiological conditions, matching exactly, if possible, those experienced at the replaced joint during daily living activities. Unfortunately, only conditions of low demanding level walking, specified in ISO-14243, are used conventionally during such tests. A recent study has provided a consistent knee kinematic and load data-set measured during stair climbing in patients implanted with a specific modern total knee prosthesis design. In the present study, wear simulation tests were performed for the first time using this data-set on the same prosthesis design. It was hypothesised that more demanding tasks would result in wear rates that differ from those observed in retrievals. Four prostheses for total knee arthroplasty were tested using a displacement-controlled knee wear simulator for two million cycles at 1.1 Hz, under kinematics and load conditions typical of stair climbing. After simulation, the corresponding damage scars on the bearings were qualified and compared with equivalent explanted prostheses. An average mass loss of 20.2±1.5 mg was found. Scanning digital microscopy revealed similar features, though the explant had a greater variety of damage modes, including a high prevalence of adhesive wear damage and burnishing in the overall articulating surface. This study confirmed that the results from wear simulation machines are strongly affected by kinematics and loads applied during simulations. Based on the present results for the full understanding of the current clinical failure of knee implants, a more comprehensive series of conditions are necessary for equivalent simulations in vitro.

Total hip replacement has become one of the most successful orthopaedic procedures. However, complications due to infections may give serious problems and have devastating consequences for the hip implant. The use of a temporary three-dimensional polymethylmethacrylate (PMMA) cement spacer may be an alternative to solve infections in hip implants, improving the lives of patients awaiting reimplantation. In order to evaluate their wear behaviour, five PMMA Spacer-G® femoral heads were tested against five post-mortem pelves in a hip joint simulator with bovine calf serum as lubricant. The surface of the worn spacers was characterized by scanning electron microscopy (SEM) analysis; all the samples revealed a similar morphology, showing areas characterized by different degrees of wear. Particle debris was isolated from the lubricant and PMMA particles and bone fractions were quantified. The amount of debris was found to be higher than where no-temporary prostheses were used. However, this result is acceptable since wear debris is removed by lavage irrigation when the Spacer-G® is explanted. On the basis of these data, it is considered that the use of the cement Spacer-G® could be a promising approach to the treatment of complicated infections of the hip joint. Therefore, Spacer-G® is worthy of further research.

Le moderne protesi monocompartimentali di ginocchio rappresentano una valida alternativa alla ricostruzione totale del ginocchio. E’ noto che variazioni nell’allineamento clinico possono portare ad una biomeccanica alterata e ad un'usura anormale. Lo scopo di questo studio era quello di valutare l'influenza, sul comportamento di usura, di due diverse interfacce di cementazione delle componenti femorale, mediante test su un simulatore di ginocchio. Sono stati esaminati dodici inserti commerciali GUR 1020 UHMWPE in articolazione con 12 componenti tibiali e femorali in cobalto-cromo-molibdeno ricoperti da un multi-strato di nitruro di cromo e da un ultimo strato di rivestimento ceramico in nitruro di zirconio ceramica in grado di bloccare gli ioni dal substrato. Sono state eseguite due prove di usura: nel primo test, ogni componente femorale è stato cementato ad incastro in un blocco metallico in grado di ospitarla; nella seconda prova, sono stati utilizzati dei femori in materiale sintetico composito sui quali sono state impiantate le componenti femorali, seguende le linee guida utilizzate nella tecnica chirurgica standard. Le due interfacce cementare hanno mostrato un comportamento significativamente differente all'usura, quantificata come perdita di peso media. Test al microscopio elettronico a scansione effettuato sulle componenti metalliche hanno mostrato macro e micro-pori di pochi micron in entrambe le configurazioni. Il modello osservato di usura a 3 milioni di cicli ha mostrato differenze tra i due metodi di fissazione per le componenti femorali.

Clinical and in vitro studies on ceramic hip prostheses correlate cup implant position with hip noise, ceramic wear, or ceramic liner damage. A ceramic cup malposition could lead to edge load, ceramic head wear, and squeaking. A noise of a ceramic hip could also be correlate with implant instability and liner damage. Aim of this study was to investigate the long-term wear behavior of 12 commercial alumina-on-alumina bearings under severe conditions: different angles of inclination (23°, 45°, and 63°) and the addition of third body particles (titanium and alumina powder) to address the effective role of cup position and ceramic particles on wear and hip noise. The study was performed using a 12-stations hip joint wear simulator (Shore Western, Monrovia) under bovine calf serum used as lubricant. Wear was evaluated by gravimetric method and the piezo-spectroscopic technique was used to evaluate the residual stress of the ceramic components and correlate this to the weight loss. After eight million cycles, we found that the inclination of the cup (63° in this study) was the most disadvantaged and it was correlated with a hip noise. Gravimetric measurements showed higher wear than the other configurations and these results were in agreement with the Photoluminescence investigation. In particular, the results obtained in this work revealed a residual stress state greater not only with respect to the other angles of inclination but also to two retrieved alumina acetabular cups with a 10 years follow-up. © 2009 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2009

Background To minimise wear of the meniscal component in total ankle replacement, a three-component artificial joint has recently been developed. This new prosthesis has convex spherical tibial and anticlastic talar metal components with non-anatomic but ligament-compatible shapes in the sagittal plane, and a fully conforming ultra-high-molecular-weight-polyethylene meniscal component inserted in between. The in vitro wear of meniscal components can be assessed using a four-station joint simulator. The study was aimed at comparing wear patterns obtained in vitro with those observed in implant retrievals with the same design. Methods The wear tests were run in a joint wear simulator at a frequency of 1.1 Hz for two million cycles. Three bearings within corresponding metal components were subjected to flexion/extension (range 0–58°), anterior–posterior translation (0–5.2 mm), internal–external rotation (−1.9° to +5.7°), and a maximum axial load of 2.6 KN. These conditions were taken from the most recent findings in ankle joint mechanics. Three prostheses of the same type were harvested from patients due to replacement failures not associated with the device, 24, 24 and 9 months, respectively, after implantation. The in vitro worn components and the three retrievals were analysed by using a scanning electron microscope, a Coordinate Measuring Machine, and micro-Raman spectroscopy. Findings Visual and microscopic observations, analyses, and Raman crystallinity-based measurements showed similarity between the patterns generated experimentally in the wear simulator and those seen in retrievals with similar wear life. Interpretation A joint wear simulator like the one used in this study, once configured properly, appears to be suitable to assess wear rates also in total ankle prostheses.

The impact of femoral head surface roughness on wear of gamma-irradiation sterilized (3 MRad in nitrogen, crosslinked) and nonsterilized (not crosslinked) UHMWPE acetabular cups has been evaluated. Gravimetric wear testing was performed in a hip joint simulator for 2 x 10(6) cycles. CoCrMo heads were used with different surface roughness (R(a) = 15 nm and R(a) = 400 nm). The surface roughness after wear test was unchanged for the roughened heads, whereas the initially smooth heads showed a few scratches. The roughened heads increased the wear of the acetabular cups 2-fold. The gamma-irradiated cups tested against rough heads underwent the highest wear. The absorption of water was highest for the gamma-irradiated cups (0.0204% compared to 0.0031% after 85 days). Raman spectroscopy showed small but significant crystallinity changes in the wear zone, where the gamma-irradiated cups with the most extensive abrasion increased in crystallinity, whereas the nonsterilized cups underwent a crystallinity decrease.

Success of total knee replacement (TKR) depends on the prosthetic design. Aseptic loosening of the femoral component is a significant failure mode that has received little attention. Despite the clinical relevance of failures, no protocol is available to test long-term implant—bone fixation of TKR in vitro. The scope of this work was to develop and validate a protocol to assess pre-clinically the fixation of TKR femoral components. An in vitro protocol was designed to apply a simplified but relevant loading profile using a 6-degrees-of-freedom knee simulator for 1 000 000 cycles. Implant—bone inducible micromotions and permanent migrations were measured at three locations throughout the test. After test completion, fatigue damage in the cement was quantified. The developed protocol was successfully applied to a commercial TKR. Additional tests were performed to exclude artefacts due to swelling or creep of the composite femur models. The components migrated distally; they tilted towards valgus in the frontal plane and in extension in the sagittal plane. The migration patterns were consistent with clinical roentgen-stereophotogrammetric recordings with TKR. Additional indicators were proposed that could quantify the tendency to loosen/stabilize. The type and amount of damage found in the cement, as well as the migration patterns, were consistent with clinical experience with the specific TKR investigated. The proposed pre-clinical test yielded repeatable results, which were consistent with the clinical literature. Therefore, its relevance and reliability was proved.

The precise measurement of leg length plays an important role in total hip arthroplasty. Leg length inequality occurs frequently after total hip arthroplasty and may cause patient discomfort. Current clinical methods used for measuring leg length are not accurate enough to meet the demands of precision required for hip replacement. The aim of this study was to examine the validity of determining leg length differences using an ultrasound system. The proposed system measures the distance between three points, in millimetres, so that the difference between preoperative and postoperative measurements gives an indication about the leg length. The mean ultrasound variation observed in in vitro measurements showed a relative error of 1.7% (range: 52-133 mm) that means a leg length inequality of about 0.4 mm (range: 52-133 mm). The method is non-invasive (ultrasound is not limited by radiation hazards), easy, quick to use, and can be used for standard clinical screening.

The pre-clinical validation of new joint prostheses is an important step in the development process of a new implant design. The high success rate of modern prostheses makes it very difficult to ensure that new designs will exhibit significant improvements combined with a risk of failure as low as that of the designs currently in use. This situation requires a systematic re-thinking of the pre-clinical validation protocols. We advocate that a careful combination of risk analysis, experimental and numerical modelling, and the use of statistical finite element analysis to generalize the results to a simulated population, can provide the level of confidence required by class 3 devices as the joint prostheses recently became. The proposed approach is illustrated using the validation of a cemented epiphyseal stem as an example.

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