Ti/Ta-based composite polysaccharide scaffolds for guided bone regeneration in total hip arthroplasty.

Guided bone regeneration can play an important role in orthopedic applications. This work presents the synthesis and characterization of composite scaffolds based on polysaccharides loaded with microparticles of titanium or tantalum as novel materials proposed for composite systems with promising characteristics for guided bone regeneration. Ti/Ta composite scaffolds were synthesized using chitosan and gellan gum as organic substrates and crosslinked with oxidized dextran resulting in stable inorganic-organic composites. Physico-chemical characterization revealed a uniform distribution of metal nanoparticles within the scaffolds that showed a release of metals lower than 5 %. In vitro biological assays demonstrated that Ta composites exhibit a 2 times higher ALP activity than Ti and a higher capacity to support the full differentiation of human mesenchymal stem cells into osteoblasts. These results highlight their potential for bone regeneration applications.

Advanced Hydrogel-Based Strategies for Enhanced Bone and Cartilage Regeneration: A Comprehensive Review.

Bone and cartilage tissue play multiple roles in the organism, including kinematic support, protection of organs, and hematopoiesis. Bone and, above all, cartilaginous tissues present an inherently limited capacity for self-regeneration. The increasing prevalence of disorders affecting these crucial tissues, such as bone fractures, bone metastases, osteoporosis, or osteoarthritis, underscores the urgent imperative to investigate therapeutic strategies capable of effectively addressing the challenges associated with their degeneration and damage. In this context, the emerging field of tissue engineering and regenerative medicine (TERM) has made important contributions through the development of advanced hydrogels. These crosslinked three-dimensional networks can retain substantial amounts of water, thus mimicking the natural extracellular matrix (ECM). Hydrogels exhibit exceptional biocompatibility, customizable mechanical properties, and the ability to encapsulate bioactive molecules and cells. In addition, they can be meticulously tailored to the specific needs of each patient, providing a promising alternative to conventional surgical procedures and reducing the risk of subsequent adverse reactions. However, some issues need to be addressed, such as lack of mechanical strength, inconsistent properties, and low-cell viability. This review describes the structure and regeneration of bone and cartilage tissue. Then, we present an overview of hydrogels, including their classification, synthesis, and biomedical applications. Following this, we review the most relevant and recent advanced hydrogels in TERM for bone and cartilage tissue regeneration.

Modification of the Polymer of a Bone Cement with Biodegradable Microspheres of PLGA and Loading with Daptomycin and Vancomycin Improve the Response to Bone Tissue Infection.

Chronic infections are one of the most serious adverse outcomes of prosthetic surgery. Prosthetic revision surgery using a bone cement loaded with antibiotics between the two stages of the surgery is commonly performed. However, this method often fails to reach the minimum inhibitory concentration and promotes antibiotic resistance, thus emphasizing the need for improving the current available therapies. MATERIALS AND METHODS: In this study, we performed a study of the in vivo response of a polymer-based construct of poly (lactic-co-glycolic acid) (PLGA) in the solid phase of Palacos R® in combination with vancomycin, daptomycin, and/or linezolid. To test its effectiveness, we applied an in vivo model, using both histological and immunohistochemical analyses to study the bone tissue. RESULTS: The presence of PLGA in the combination of vancomycin with daptomycin showed the most promising results regarding the preservation of bone cytoarchitecture and S. aureus elimination. Conversely, the combination of vancomycin plus linezolid was associated with a loss of bone cytoarchitecture, probably related to an increased macrophage response and inefficient antimicrobial activity. CONCLUSIONS: The modification of Palacos R® bone cement with PLGA microspheres and its doping with the antibiotic daptomycin in combination with vancomycin improve the tissue response to bone infection.

Prevention of Periprosthetic Joint Infection in Total Hip and Knee Replacement: One European Consensus.

Periprosthetic joint infection (PJI) is a devastating complication in total hip and knee replacement. Its prevention is key to decrease the incidence and avoid some consequences that seriously impact patients and health systems. In view of the variety of recommendations and guidelines, we decided to conduct an expert, peer-reviewed European consensus analysis about the pre-, intra-, and postoperative prevention of PJI. A multinational group of practicing orthopedic experts developed a series of 47 consensus statements in 6 main groups of intervention, and a 2-stage Delphi approach was launched with a threshold for agreement at 75% and for very high agreement at more than 90%. A total of 306 orthopedic surgeon responses were gathered from 9 countries. Consensus was reached for 42/47 statements, 31/47 of which achieved a very high consensus. Many preoperative actions gathered strong consensus, although areas like the use of alcoholic chlorhexidine or the timing of hair removal did not attain strong consensus, despite available evidence. Intra- and postoperative actions showed more variability regarding incise drapes, skin suturing techniques, and wound follow-up. This study confirms an important consensus among orthopedic surgeons across Europe in many areas well known to contribute to the prevention of PJI; however, there are still grounds for improvement.

Analysis of the Risk of Wear on Cemented and Uncemented Polyethylene Liners According to Different Variables in Hip Arthroplasty.

Wear debris in total hip arthroplasty is one of the main causes of loosening and failure, and the optimal acetabular fixation for primary total hip arthroplasty is still controversial because there is no significant difference between cemented and uncemented types for long-term clinical and functional outcome. To assess and predict, from a theoretical viewpoint, the risk of wear with two types of polyethylene liners, cemented and uncemented, a simulation using the finite element (FE) method was carried out. The risk of wear was analyzed according to different variables: the polyethylene acetabular component's position with respect to the center of rotation of the hip; the thickness of the polyethylene insert; the material of the femoral head; and the relationship of the cervical-diaphyseal morphology of the proximal end of the femur to the restoration of the femoral offset. In all 72 simulations studied, a difference was observed in favour of a cemented solution with respect to the risk of wear. With regard to the other variables, the acetabular fixation, the thickness of the polyethylene, and the acetabular component positioning were statistically significant. The highest values for the risk of wear corresponded to a smaller thickness (5.3 mm), and super-lateral positioning at 25 mm reached the highest value of the von Mises stress. According to our results, for the reconstruction of the acetabular side, a cemented insert with a thickness of at least 5 mm should be used at the center of rotation.

Preoperative clinical model to predict myocardial injury after non-cardiac surgery: a retrospective analysis from the MANAGE cohort in a Spanish hospital.

OBJECTIVES: To determine preoperative factors associated to myocardial injury after non-cardiac surgery (MINS) and to develop a prediction model of MINS. DESIGN: Retrospective analysis. SETTING: Tertiary hospital in Spain. PARTICIPANTS: Patients aged ≥45 years undergoing major non-cardiac surgery and with at least two measures of troponin levels within the first 3 days of the postoperative period. All patients were screened for the MANAGE trial. PRIMARY AND SECONDARY OUTCOME MEASURES: We used multivariable logistic regression analysis to study risk factors associated with MINS and created a score predicting the preoperative risk for MINS and a nomogram to facilitate bed-side use. We used Least Absolute Shrinkage and Selection Operator method to choose the factors included in the predictive model with MINS as dependent variable. The predictive ability of the model was evaluated. Discrimination was assessed with the area under the receiver operating characteristic curve (AUC) and calibration was visually assessed using calibration plots representing deciles of predicted probability of MINS against the observed rate in each risk group and the calibration-in-the-large (CITL) and the calibration slope. We created a nomogram to facilitate obtaining risk estimates for patients at pre-anaesthesia evaluation. RESULTS: Our cohort included 3633 patients recruited from 9 September 2014 to 17 July 2017. The incidence of MINS was 9%. Preoperative risk factors that increased the risk of MINS were age, American Status Anaesthesiology classification and vascular surgery. The predictive model showed good performance in terms of discrimination (AUC=0.720; 95% CI: 0.69 to 0.75) and calibration slope=1.043 (95% CI: 0.90 to 1.18) and CITL=0.00 (95% CI: -0.12 to 0.12). CONCLUSIONS: Our predictive model based on routinely preoperative information is highly affordable and might be a useful tool to identify moderate-high risk patients before surgery. However, external validation is needed before implementation.

Influence of Psychological Distress in Patients with Hypoallergenic Total Knee Arthroplasty. Treatment Algorithm for Patients with Metal Allergy and Knee Osteoarthritis.

The outcome in total knee arthroplasty (TKA) depends on multiples factors, among them is the psychological condition. In addition, up 15 to 30% of the patients that undergo TKA show little or no improvement after surgery, which implies the diagnosis of a painful TKA is a challenge for the orthopedic surgeon, who must rule out a possible metal allergy (MA). It is considered an exclusion diagnosis. Due to the complex relationship between psychological condition and MA, and according to the worse results in patients treated with a hypoallergenic TKA, we asked: (1). What degree of psychological distress (PD) is present in patients who have a hypoallergenic TKA, and how does it influence the results of quality of life (QoL) and functional capacity. (2). Can we develop a new algorithm for patients with a possible MA that improves the outcomes? A pragmatic clinical study was carried out that included patients who underwent hypoallergenic TKA during three consecutive years. Quality of life and functional capacity were measured with (Western Ontario McMaster Universities Osteoarthritis Index) WOMAC index, the Short Form 12 questionnaire (SF-12) questionnaire, and the The EQ-5D-5L questionnaire essentially consists of two pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS) (Euro-QoL-5D L-VAS (EQ5D)), in all patients. To assess PD, a Psychological Distress Score was developed. SPSS software was performed to statistical analysis, and Student´s test for independent variables with a p < 0.005 as statistically significant. A total of 72 anallergic TKAs in 64 patients were treated during this period; 31.3% of these patients showed features of PD before the surgery. According with the severity of the PD, 60% were classified as severe, 10% as moderate and 30% as mild. Patients with PD had statistically significant worse results on the final WOMAC, SF-12, and EQ5D questionnaires. The final scores of the physical subscale of the SF-12 and EQ5D showed better results in patients diagnosed by psychiatrist. Up to one third of the patients with hypoallergenic TKAs have PD, and their results are clearly inferior to those patients with MA without PD. When PD was diagnosed according with Psychological Distress Score, patients should be carefully assessed in order to determine if a specialist referral is recommended. According with our results, PD should be assessed either by the PCP or by us. If the PD is confirmed, a psychiatry referral is then requested for better preoperative management and treatment. We believe that this approach would lead to better TKA outcomes.

An integrative look at SARS­CoV­2 (Review).

SARS­CoV­2 is a newly discovered member of the betacoronaviruses and the etiological agent of the disease COVID­19. SARS­CoV­2 is responsible for the worldwide pandemic which has been taking place in 2020, and is causing a markedly higher number of infections and deaths compared to previous coronaviruses, such as SARS­CoV or MERS­CoV. Based on updated scientific literature, the present review compiles the most relevant knowledge of SARS­CoV­2, COVID­19 and the clinical and typical responses that patients have exhibited against this virus, discussing current and future therapies, and proposing strategies with which to combat the disease and prevent a further global threat. The aggressiveness of SARS­CoV­2 arises from its capacity to infect, and spread easily and rapidly through its tight interaction with the human angiotensin­converting enzyme 2 (ACE­2) receptor. While not all patients respond in a similar manner and may even be asymptomatic, a wide range of manifestations associated with COVID­19 have been described, particularly in vulnerable population groups, such as the elderly or individuals with other underlying conditions. The proper function of the immune system plays a key role in an individual's favorable response to SARS­CoV­2 infection. A hyperactivated response, on the contrary, could account for the more severe cases of COVID­19, and this may finally lead to respiratory insufficiency and other complications, such as thrombotic or thromboembolic events. The development of novel therapies and vaccines designed to control and regulate a proper immune system response will be key to clinical management, prevention measures and effective population screening to attenuate the transmission of this novel RNA virus.

Decrease of Quality of Life, Functional Assessment and Associated Psychological Distress in Patients with Hypoallergenic Total Knee Arthroplasty.

Total knee arthroplasty (TKA) is the final treatment for knee osteoarthritis, and 15-30% of patients show little or no improvement. This high percentage is related to aspects of the surgical technique, the selected implant, and specific patient characteristics. The aim of this study was to analyze whether there are differences in quality of life (QoL) and functional capacity among patients undergoing TKA with conventional implants compared to those treated with hypoallergenic oxinium implants. A pragmatic clinical study was carried out that included patients who underwent TKA between January 2013 and December 2015. During this period, 245 knees in 228 patients were treated. Eleven patients were excluded, leaving a sample of 161 conventionally treated knees, 72 knees treated with hypoallergenic implants, and one patient who received both implant types. In all patients, QoL and functional capacity were measured with the WOMAC index, the SF-12 questionnaire, and the Euro-Qol-5D L-VAS. We also assessed the psychological distress of each patient and related the findings to the functional results. The differences in QoL were tested using ANCOVA and propensity score matching (PSM) models adjusted for sex, age, weight, psychiatric history and associated complications. Patients who underwent TKA using conventional prostheses had significantly better scores on the total WOMAC index and in the pain domain (p < 0.05) than those who received hypoallergenic prostheses, but no significant differences were observed for the other domains in the ANCOVA. In contrast, with the PSM, we also found statistically significant differences in the difficulty domain of the WOMAC. Significant differences were found for the SF-12 mental health questionnaire results (p = 0.038), but the same did not occur for the physical health domain in the ANCOVA and PSM. We also found statistically significant differences in the Euro-Qol-5D index results (p = 0.041), but not in the VAS scale scores for the same questionnaire in the ANCOVA, and we did not find significant differences in either with the PSM. Patients with metal allergies and those who present psychological distress had WOMAC, SF-12, and Euro-Qol-5D results that were statistically significantly worse than those of patients who received conventional implants. Patients who underwent hypoallergic TKA had lower scores on the QoL and functional capacity scales than patients who received conventional Cr-Co implants. Additionally, patients with psychological distress had worse results on the questionnaires, and those with a metal allergy had even lower scores; the differences were statistically significant.

Type 2 Diabetes Mellitus Associated with Obesity (Diabesity). The Central Role of Gut Microbiota and Its Translational Applications.

Obesity is a condition of rising prevalence worldwide, with important socioeconomic implications, being considered as a growing public health concern. Frequently, obesity brings other complications in addition to itself-like Type 2 Diabetes Mellitus (T2DM)-sharing origin, risk factors and pathophysiological mechanisms. In this context, some authors have decided to include both conditions as a unique entity known as "diabesity". In fact, understanding diabesity as a single disease is possible to maximise the benefits from therapies received in these patients. Gut microbiota plays a key role in individual's health, and their alterations, either in its composition or derived products are related to a wide range of metabolic disorders like T2DM and obesity. The present work aims to collect the different changes reported in gut microbiota in patients with T2DM associated with obesity and their possible role in the onset, development, and establishment of the disease. Moreover, current research lines to modulate gut microbiota and the potential clinical translation derived from the knowledge of this system will also be reviewed, which may provide support for a better clinical management of such a complex condition.

Polylactic-co-glycolic acid microspheres added to fixative cements and its role on bone infected architecture.

Joint prostheses are an essential element to improve quality of life. However, prostheses may fail due to several factors, including the most frequent cause, Staphylococcus aureus infection. The identification of new fixing bone cements with less reactivity on bone tissue and an adequate response to infection remains a primary challenge. The aim of this study is to evaluate the response of bone tissue in rabbits after introduction of a hydroxyapatite-coated titanium rod with a commercial fixative cement (Palacos®) compared to a modified experimental cement (EC) containing polylactic-co-glycolic acid (PLGA) microspheres in the presence or absence of contaminating germs. This study used 20 New Zealand rabbits which were divided into four groups (n = 5) depending on the presence or absence of S. aureus and the use of commercial (Palacos®) or EC. A histological method, based on bone architecture damage, was proposed to evaluate from 1 to 9 the histological results and the response of the infected tissue. The macrophage response was also evaluated using monoclonal antibody RAM-11. The study showed better bone conservation with the use of EC with PLGA microspheres against the Palacos® commercial cement, including the noncontaminated and contaminated groups. © 2019 The Authors. Journal of Biomedical Materials Research Part B: Applied Biomaterials published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B:2517-2526, 2019.

Executive summary of management of prosthetic joint infections. Clinical practice guidelines by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC).

The incidence of prosthetic joint infection (PJI) is expected to increase in the coming years. PJI has serious consequences for patients, and high costs for the health system. The complexity of these infections makes it necessary to organize the vast quantity of information published in the last several years. The indications for the choice of a given surgical strategy and the corresponding antimicrobial therapy are specifically reviewed. The authors selected clinically relevant questions and then reviewed the available literature in order to give recommendations according to a pre-determined level of scientific evidence. The more controversial aspects were debated, and the final composition was agreed at an ad hoc meeting. Before its final publication, the manuscript was made available online in order that all SEIMC members were able to read it and make comments and suggestions.

Recurrent prosthetic joint infection due to Salmonella enteritidis: case report and literature review.

Prosthetic joint infection (PJI) due to Salmonella spp. is rare. We report a case of a recurrent prosthetic infection with involvement of two joints in a 72-year-old man and review the literature. The review of all cases previously reported and our case shows that conservative approach using antibiotics alone is insufficient to cure the infection. Prolonged antibiotic treatment and two-stage reconstruction with the use of joint spacer is the best choice for the treatment. Salmonella spp. should be considered as a cause of PJI, especially in patients with previous infections caused by this microorganism.

10 years results of an uncemented metaphyseal fit modular stem in elderly patients.

BACKGROUND: There are concerns with regard to the femoral fixation in cementless total hip arthroplasty in elderly patients. We report a retrospective analysis of clinical and radiological results of uncemented metaphyseal fit modular stem in elderly patients irrespective of anatomic characterstics of proximal femur. MATERIALS AND METHODS: This study reviews the outcomes of 60 primary hip replacements using a metaphyseal fit modular stem (third-generation Omniflex stem) conducted in 54 patients, of age 75 years or older. After a mean follow-up of 10,4 years, complete clinical and radiographic records were available for 52 hips of 48 patients. The patients were evaluated by Harris Hip Score (HHS). RESULTS: There was a significantly improved pain score and Harris Hip Score (41,6 to 83,2). Six stems (11.53%) were revised: four because of periprosthetic fracture; one stem was well fixed, but presented a large osteolytic lesion in the metaphyseal area and the last stem was revised because of aseptic loosening. Stem survival taking aseptic loosening as the end-point was 98%. Bone atrophy in the proximal femur caused by stress shielding was observed in 39 stems (75%), but there was no case of subtrochanteric stress shielding. Moreover, atrophy appeared within two years postoperatively, with no extension thereafter. CONCLUSIONS: We achieved good clinical and radiographic results by uncemented metaphyseal fit femoral stem regardless of patient's age and femoral canal type.

Prosthetic hip infection due to Brucella melitensis: case report and literature review.

Prosthetic joint infection (PJI) due to Brucella spp. is extremely rare. We report the case of a prosthetic hip infection due to Brucella melitensis in a 51-year-old male patient. The initial presentation was a gluteal abscess. There was radiographic evidence of implant loosening. The patient was cured after prolonged treatment with streptomycin, rifampicin, and doxycycline, followed by 2-stage exchange of the prosthesis. Brucella spp. should be considered in the differential diagnosis of PJI in countries where brucellosis is endemic. The review of all cases previously reported shows that a conservative approach using antibiotics alone can be followed in patients without signs of implant loosening. In contrast, prolonged antibiotic treatment and prosthetic joint revision should be considered in patients with evidence of implant loosening.

Injectable and self-curing composites of acrylic/bioactive glass and drug systems. A histomorphometric analysis of the behaviour in rabbits.

Injectable self-curing systems based on PMMA, phosphate-free bioactive glasses and the drug fosfosal, a phosphate derivative of salicylic acid with analgesic and moderate anti-inflammatory properties, have been tested in vivo to evaluate their biocompatibility. The model consisted of the injection of dough of cement into a defect created in the femur of rabbits, and the cure of the cement in situ after implantation. The biological response was studied in the short and long terms by macroscopic, radiological and histopathological examination, and quantitatively by histomorphometric and statistical analysis considering the most representative variables at the bone-cement interface: cement, bone marrow, newly formed bone and connective tissue. All bioactive formulations presented resorption of the cement at the end of the experiment in contrast to the control of PMMA, due to the presence of resorbable components. The presence or absence of the phosphate group added by the drug fosfosal influenced mainly on the new bone formation process. The cement formulated with bioactive glasses and in absence of fosfosal produced the maximum amount of neoformed bone at 2 weeks, and then it resorbed at 4 weeks to give a higher amount of neoformed bone at the end of the experiment, compared with the formulation containing only fosfosal. The presence of fosfosal and bioactive glass together affected the ossification process strongly. The osseous tissue was produced more gradually but it continuously increased giving rise to a more stable bone at the end of the experiment.