Plastic waste in major orthopaedic surgical procedures: descriptive and sources of improvement.

PURPOSE: The healthcare industry is a significant contributor to single-use plastic waste, particularly in the operating room (OR). This study aims to assess the volume of plastic waste generated during total hip, knee, and shoulder arthroplasty in the OR and identify areas for improvement. METHOD: A prospective transversal study at a tertiary hospital was conducted. All total knee arthroplasty (TKA), total hip arthroplasty (THA), and reverse shoulder arthroplasty (RSA) from April to July 2021 were included. The weight of plastic used during patient preparation, anaesthesia, and the surgical procedure was recorded. To calculate the environmental impact, a calculator generated by the United States Environmental Protection Agency (U.S. EPA) was used. RESULTS: A total of 68 surgeries were included. The mean weight of plastic used in total was 7.3 kg (SD 0.48), with the highest yielding procedure being TKA. It generated a mean of 7.63 kg (SD 0.28), followed by THA at 7.28 kg (SD 0.43), and RSA at 6.87 kg (SD 0.47). Various scenarios were simulated to evaluate the potential impact of reducing plastic waste. Substituting plastic wrapping with recyclable materials could save 159.6 kg of CO2 emissions per 100 prostheses. Eliminating non-essential equipment and adopting reusable fabric drapes also showed a significant potential. CONCLUSION: The findings highlight the need for environmentally sustainable practices in the OR. In this way, the healthcare sector can contribute to a cleaner and greener world without compromising patient safety.

MAPK pathway and B cells overactivation in multiple sclerosis revealed by phosphoproteomics and genomic analysis.

Dysregulation of signaling pathways in multiple sclerosis (MS) can be analyzed by phosphoproteomics in peripheral blood mononuclear cells (PBMCs). We performed in vitro kinetic assays on PBMCs in 195 MS patients and 60 matched controls and quantified the phosphorylation of 17 kinases using xMAP assays. Phosphoprotein levels were tested for association with genetic susceptibility by typing 112 single-nucleotide polymorphisms (SNPs) associated with MS susceptibility. We found increased phosphorylation of MP2K1 in MS patients relative to the controls. Moreover, we identified one SNP located in the PHDGH gene and another on IRF8 gene that were associated with MP2K1 phosphorylation levels, providing a first clue on how this MS risk gene may act. The analyses in patients treated with disease-modifying drugs identified the phosphorylation of each receptor's downstream kinases. Finally, using flow cytometry, we detected in MS patients increased STAT1, STAT3, TF65, and HSPB1 phosphorylation in CD19+ cells. These findings indicate the activation of cell survival and proliferation (MAPK), and proinflammatory (STAT) pathways in the immune cells of MS patients, primarily in B cells. The changes in the activation of these kinases suggest that these pathways may represent therapeutic targets for modulation by kinase inhibitors.

Immune tolerance in multiple sclerosis and neuromyelitis optica with peptide-loaded tolerogenic dendritic cells in a phase 1b trial.

There are adaptive T-cell and antibody autoimmune responses to myelin-derived peptides in multiple sclerosis (MS) and to aquaporin-4 (AQP4) in neuromyelitis optica spectrum disorders (NMOSDs). Strategies aimed at antigen-specific tolerance to these autoantigens are thus indicated for these diseases. One approach involves induction of tolerance with engineered dendritic cells (tolDCs) loaded with specific antigens. We conducted an in-human phase 1b clinical trial testing increasing concentrations of autologous tolDCs loaded with peptides from various myelin proteins and from AQP4. We tested this approach in 12 patients, 8 with MS and 4 with NMOSD. The primary end point was the safety and tolerability, while secondary end points were clinical outcomes (relapses and disability), imaging (MRI and optical coherence tomography), and immunological responses. Therapy with tolDCs was well tolerated, without serious adverse events and with no therapy-related reactions. Patients remained stable clinically in terms of relapse, disability, and in various measurements using imaging. We observed a significant increase in the production of IL-10 levels in PBMCs stimulated with the peptides as well as an increase in the frequency of a regulatory T cell, known as Tr1, by week 12 of follow-up. In this phase 1b trial, we concluded that the i.v. administration of peptide-loaded dendritic cells is safe and feasible. Elicitation of specific IL-10 production by peptide-specific T cells in MS and NMOSD patients indicates that a key element in antigen specific tolerance is activated with this approach. The results warrant further clinical testing in larger trials.

Predicting disease severity in multiple sclerosis using multimodal data and machine learning.

BACKGROUND: Multiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity. METHODS: We have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseline and 2 years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells. Predictors of clinical outcomes were searched using Random Forest algorithms. Assessment of the algorithm performance was conducted in an independent prospective cohort of 271 MS patients from a single centre. RESULTS: We found algorithms for predicting confirmed disability accumulation for the different scales, no evidence of disease activity (NEDA), onset of immunotherapy and the escalation from low- to high-efficacy therapy with intermediate to high-accuracy. This accuracy was achieved for most of the predictors using clinical data alone or in combination with imaging data. Still, in some cases, the addition of omics data slightly increased algorithm performance. Accuracies were comparable in both cohorts. CONCLUSION: Combining clinical, imaging and omics data with machine learning helps identify MS patients at risk of disability worsening.

Total hip replacement with an uncemented Wagner cone stem for patients with congenital hip dysplasia.

PURPOSE: The purpose of this study was to review retrospectively the cases operated upon in our department in recent years with a Wagner stem and a small socket in cases of Crowe I or II dysplastic hips. METHODS: We conducted a retrospective clinical radiological review of 30 hips diagnosed with hip dysplasia Crowe I or II treated in our centre between 2002 and 2008. All of them were treated with a Wagner cone stem and a small Trilogy acetabulum (Zimmer ®). RESULTS: There were 15 men and 11 women with 13 left and 17 right femurs. Mean follow-up was 43.44 months (range 14-87). Eight patients were Crowe I type and 22 were Crowe II type. Merlé d'Aubigne score pre-operatively was 12.23 and at the last follow-up was 15.54. Mean leg length inequality was 1.79 and after surgery it was 0.69 cm. Complications included three infection and three dislocations (two of them in the same patient). CONCLUSIONS: The use of a Wagner stem is a good option to correct the different deformities in the proximal femur in these cases. A small socket allows a correct relocation of the acetabulum in a dysplastic socket with good bone coverage.

Prediction of combination therapies based on topological modeling of the immune signaling network in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a major health problem, leading to a significant disability and patient suffering. Although chronic activation of the immune system is a hallmark of the disease, its pathogenesis is poorly understood, while current treatments only ameliorate the disease and may produce severe side effects. METHODS: Here, we applied a network-based modeling approach based on phosphoproteomic data to uncover the differential activation in signaling wiring between healthy donors, untreated patients, and those under different treatments. Based in the patient-specific networks, we aimed to create a new approach to identify drug combinations that revert signaling to a healthy-like state. We performed ex vivo multiplexed phosphoproteomic assays upon perturbations with multiple drugs and ligands in primary immune cells from 169 subjects (MS patients, n=129 and matched healthy controls, n=40). Patients were either untreated or treated with fingolimod, natalizumab, interferon-ß, glatiramer acetate, or the experimental therapy epigallocatechin gallate (EGCG). We generated for each donor a dynamic logic model by fitting a bespoke literature-derived network of MS-related pathways to the perturbation data. Last, we developed an approach based on network topology to identify deregulated interactions whose activity could be reverted to a "healthy-like" status by combination therapy. The experimental autoimmune encephalomyelitis (EAE) mouse model of MS was used to validate the prediction of combination therapies. RESULTS: Analysis of the models uncovered features of healthy-, disease-, and drug-specific signaling networks. We predicted several combinations with approved MS drugs that could revert signaling to a healthy-like state. Specifically, TGF-ß activated kinase 1 (TAK1) kinase, involved in Transforming growth factor ß-1 proprotein (TGF-ß), Toll-like receptor, B cell receptor, and response to inflammation pathways, was found to be highly deregulated and co-druggable with all MS drugs studied. One of these predicted combinations, fingolimod with a TAK1 inhibitor, was validated in an animal model of MS. CONCLUSIONS: Our approach based on donor-specific signaling networks enables prediction of targets for combination therapy for MS and other complex diseases.

Impact of treatment on cellular immunophenotype in MS: A cross-sectional study.

OBJECTIVE: To establish cytometry profiles associated with disease stages and immunotherapy in MS. METHODS: Demographic/clinical data and peripheral blood samples were collected from 227 patients with MS and 82 sex- and age-matched healthy controls (HCs) enrolled in a cross-sectional study at 4 European MS centers (Spain, Italy, Germany, and Norway). Flow cytometry of isolated peripheral blood mononuclear cells was performed in each center using specifically prepared antibody-cocktail Lyotubes; data analysis was centralized at the Genoa center. Differences in immune cell subsets were assessed between groups of untreated patients with relapsing-remitting or progressive MS (RRMS or PMS) and HCs and between groups of patients with RRMS taking 6 commonly used disease-modifying drugs. RESULTS: In untreated patients with MS, significantly higher frequencies of Th17 cells in the RRMS population compared with HC and lower frequencies of B-memory/B-regulatory cells as well as higher percentages of B-mature cells in patients with PMS compared with HCs emerged. Overall, the greatest deviation in immunophenotype in MS was observed by treatment rather than disease course, with the strongest impact found in fingolimod-treated patients. Fingolimod induced a decrease in total CD4+ T cells and in B-mature and B-memory cells and increases in CD4+ and CD8+ T-regulatory and B-regulatory cells. CONCLUSIONS: Our highly standardized, multisite cytomics data provide further understanding of treatment impact on MS immunophenotype and could pave the way toward monitoring immune cells to help clinical management of MS individuals.

Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation.

The development of neuroprotective therapies is a sought-after goal. By screening combinatorial chemical libraries using in vitro assays, we identified the small molecule BN201 that promotes the survival of cultured neural cells when subjected to oxidative stress or when deprived of trophic factors. Moreover, BN201 promotes neuronal differentiation, the differentiation of precursor cells to mature oligodendrocytes in vitro, and the myelination of new axons. BN201 modulates several kinases participating in the insulin growth factor 1 pathway including serum-glucocorticoid kinase and midkine, inducing the phosphorylation of NDRG1 and the translocation of the transcription factor Foxo3 to the cytoplasm. In vivo, BN201 prevents axonal and neuronal loss, and it promotes remyelination in models of multiple sclerosis, chemically induced demyelination, and glaucoma. In summary, we provide a new promising strategy to promote neuroaxonal survival and remyelination, potentially preventing disability in brain diseases.

[The tutor-professor, transformer of professional practice]. / El profesor-tutor. Stransformador de la práctica profesional.

The emerging conceptualization of the teaching-learning process brings with it a modification in the teaching role of a university professor. To think of the function of a tutor-professor from a complex perspective will help professors to develop underneath this paradigm, facilitating the construction of thinking in integrated networks having different types of knowledge which substitute fragmented and lineal knowledge characteristic to positivist thinking. From a complex paradigm, learning acquires a new sense. The complex viewpoint is rich in matrixes, complacent with diversity capable to integrate difficulties. The final objective of teaching is to accompany a student as he/she discovers and interprets reality. The most important function of a tutor is to permit a student to construct himself/herself by means of reflexive dialogue with the student's own learning experience. The tutor's role should enable a student to make use of his/her own speech, offering secure places where a student can find his/her appropriate spot, and where the pressure of an exam becomes more a stimulus to learn than a difficulty for his/her development.

[Exercise prescription: indications, dosage and side effects]. / Prescripción de ejercicio físico: indicaciones, posología y efectos adversos.

The prescription of exercise is particularly useful for preventing premature death from all causes, ischemic heart disease, stroke, hypertension, colon and breast cancer, type 2 diabetes, metabolic syndrome, obesity, osteoporosis, sarcopenia, functional dependence and falls in the elderly, cognitive impairment, anxiety and depression. This benefit is observed in both sexes and increases with the volume or intensity of exercise. These benefits are obtained through moderate aerobic exercise for at least 30 minutes 5 days per week or vigorous exercise for at least 20 minutes 3 days a week. It is recommended to add a minimum of 2 nonconsecutive days, each week, to practice 8-10 exercises that develop the strength of most muscle groups (arms, shoulders, chest, abdomen, back, hips and legs). It is also advisable to spend 2 sessions of 10 minutes per week to practice 8-10 exercises that maintain the flexibility of most groups of muscles and tendons. The exercise may involve musculoskeletal injuries and cardiovascular risk, but the benefit outweighs the risk.

Functional and quality-of-life results of displaced and nondisplaced proximal humeral fractures treated conservatively.

OBJECTIVES: Functional and quality-of-life outcomes of conservatively treated proximal humeral fractures. DESIGN: Prospective study. SETTING: University orthopedic department at a hospital. PATIENTS/PARTICIPANTS: Seventy consecutive patients between the ages of 60 and 85 years. INTERVENTION: Conservative treatment. MAIN OUTCOME MEASUREMENTS: Functional outcome measured according to the Constant score, quality of life assessed using EuroQol-5D, and fracture pattern analyzed with x-ray and computed tomography scan. RESULTS: : All fractures consolidated uneventfully with no loss of reduction in either group. Four-part fractures obtained the worst functional results (33.66) followed by three-part fractures (54.64) and finally two-part fractures (65.88 and 71). Mild pain was expected in three- and four-part fractures, whereas two-part fractures achieved near complete pain relief. Nondisplaced fractures obtained a final Constant score of 73.58 and displaced fractures a score of 59.41 with significant differences in all Constant score items with the exception of external rotation. Although patients older than 75 years scored lower (54.63) than those younger than 75 years (70.83), there was no difference in the quality-of-life perception. CONCLUSION: Conservative treatment of proximal humeral fractures in those patients older than age 75 years provides good pain relief with limited functional outcome. Despite limited functional outcome, this appears to have no effect on the quality-of-life perception in the population studied. Four-part fractures present the worst results and treatment options may need to be discussed with the patient to adjust treatment to patient expectations.

In vivo evaluation of 3-dimensional polycaprolactone scaffolds for cartilage repair in rabbits.

BACKGROUND: Cartilage tissue engineering using synthetic scaffolds allows maintaining mechanical integrity and withstanding stress loads in the body, as well as providing a temporary substrate to which transplanted cells can adhere. PURPOSE: This study evaluates the use of polycaprolactone (PCL) scaffolds for the regeneration of articular cartilage in a rabbit model. STUDY DESIGN: Controlled laboratory study. METHODS: Five conditions were tested to attempt cartilage repair. To compare spontaneous healing (from subchondral plate bleeding) and healing due to tissue engineering, the experiment considered the use of osteochondral defects (to allow blood flow into the defect site) alone or filled with bare PCL scaffold and the use of PCL-chondrocytes constructs in chondral defects. For the latter condition, 1 series of PCL scaffolds was seeded in vitro with rabbit chondrocytes for 7 days and the cell/scaffold constructs were transplanted into rabbits' articular defects, avoiding compromising the subchondral bone. Cell pellets and bare scaffolds were implanted as controls in a chondral defect. RESULTS: After 3 months with PCL scaffolds or cells/PCL constructs, defects were filled with white cartilaginous tissue; integration into the surrounding native cartilage was much better than control (cell pellet). The engineered constructs showed histologically good integration to the subchondral bone and surrounding cartilage with accumulation of extracellular matrix including type II collagen and glycosaminoglycan. The elastic modulus measured in the zone of the defect with the PCL/cells constructs was very similar to that of native cartilage, while that of the pellet-repaired cartilage was much smaller than native cartilage. CONCLUSION: The results are quite promising with respect to the use of PCL scaffolds as aids for the regeneration of articular cartilage using tissue engineering techniques.