Effectiveness of Soluble CTLA-4-Fc in the Inhibition of Bone Marrow T-Cell Activation in Context of Indoleamine 2.3-Dioxygenase (IDO) and CD4+Foxp3+ Treg Induction.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease with systemic inflammation finally resulting in damaged joints. One of the RA development models suggests bone marrow (BM) as a place of inflammation development further leading to disease progression. We aimed to investigate the potential of CTLA-4-Fc molecule in inducing tolerogenic milieu in BM measured as indoleamine 2,3-dioxygenase (IDO) expression, CD4+Foxp3+ Treg induction, and T cell activation control. The expression of IDO-pathway genes was also examined in monocytes to estimate the tolerogenic potential in the periphery. Methods: Bone marrow mononuclear cells (BMMC) were stimulated by pro-inflammatory cytokines and CTLA-4-Fc. Next IDO expression, CD4+CD69+ and CD4+Foxp3+ percentage were estimated by PCR and FACS staining, respectively. Enzymatic activity of IDO was confirmed by HPLC in BM plasma and blood plasma. Genes expressed in IDO-pathway were analyzed by NGS in peripheral monocytes isolated from RA patients and healthy controls. Results: We found that CTLA-4-Fc and IFN-γ stimulation results in IDO production by BMMC. CTLA-4-Fc induced tryptophan catabolism can inhibit mitogen-induced CD4+ T cells activation without influencing CD8+ cells, but did not control CD25 nor Foxp3 expression in BM cells. Significantly higher expression of selected IDO-pathway genes was detected on peripheral monocytes isolated from RA as compared to healthy controls. Conclusion: This study sheds light on some immunosuppression aspects present or induced in BM. The potential of IDO-mediated pathways were confirmed in the periphery, what may represent the promising candidates for therapeutic strategies in RA.

An aggressive course of pyoderma gangrenosum mimicking bacterial osteomyelitis after open reduction and internal fixation of a distal radius fracture with a titanium plate.

Pyoderma gangrenosum (PG) is a rare condition characterized by the development of aseptic, non-healing skin ulcers. Any skin trauma, such as a surgical incision, can trigger an outbreak of lesions. Our case and literature review show that a physician should consider PG in every event of a non-healing, aseptic wound after surgery. The treatment of PG requires collaboration within a multidisciplinary team and immunosuppressive therapy is the first line of treatment, while surgical interventions should be avoided in the active stage of PG.

Identification of human-dependent routes of pathogen's transmission in a tertiary care hospital.

OBJECTIVES: The purpose of the study was to validate the risk of patients' exposure to pathogenic flora carried on hands of students, visitors, and patients themselves, analyzing its density and genera and to compare them with the microflora of healthcare workers (HCWs). PATIENTS AND METHODS: Between May and June 2018, five groups of participants were included. Each group consisted of eight individuals. Palmar skin imprints were obtained from dominant hands of doctors, nurses, students, visitors, and patients in orthopedics ward. Imprints were incubated at 37°C under aerobic conditions, and colony-forming units (CFU) on each plate were counted after 24, 48, and 72 h. Microorganisms were identified. RESULTS: Hands of doctors were colonized more often by Gram - positive non-spore-forming rods bacteria than hands of nurses (p<0.05). A higher number of Staphylococcus epidermidis CFUs was observed on doctors' than on nurses' hands (p<0.05), whereas Staphylococcus hominis was isolated from doctor's and patients' imprints, but was not from nurses' and students' imprints (p<0.05). Micrococcus luteus colonized patients' hands more often than students' (p<0.05), visitors' hands than doctors' (p<0.05), students' than nurses' (p<0.05), visitors' than nurses' (p<0.05) and patients' hands (p<0.05). Staphylococcus aureus (S. aureus) was isolated only from one doctor and one nurse (203 and 10 CFUs/25 cm2 ). Imprints taken from the hands of patients, students and visitors were S. aureus-free. No methicillin-resistant S. aureus (MRSA), vancomycin-resistant enterococci, nor expanded spectrum betalactamase-positive or carbapenemase-positive rods were isolated. The number of Gram-negative rods was the highest on visitors' hands, significantly differing from the number on patient's, doctor's, nurse's, and student's hands. Spore-forming rods from genus of Bacillus were isolated from representatives of all tested groups. Bacillus cereus occurred more commonly on visitors' hands than doctors' hands (p<0.05). CONCLUSION: Patients, students, and visitors may play the causal role in the spread of pathogenic bacteria, particularly spore-forming rods. Our study results confirm the effectiveness of educational activities, that is the hospital's hand hygiene program among HCWs, patients, and visitors. Hand hygiene procedures should be reviewed to put much more effort into reducing the impact of all studied groups on the transmission of infectious diseases.

Deformation of the Titanium Plate Stabilizing the Lateral Ankle Fracture Due to Its Overloading in Case of the Young, Obese Patient: Case Report Including the Biomechanical Analysis.

The number of overweight and obese patients in developed countries is gradually increasing. It was reported that 1287 (64%) out of 2007 adults operated on in 2017 had a body mass index (BMI) greater than 25 kg/m2, and 26.4% even greater than 30, while the BMI of the most obese patient was as high as 57.6 kg/m2. Such distressing statistics raised an issue related to the inadequate durability of implants used for the fixation of bone fractures. Implants for the lower-extremity fractures may not be durable enough to fit the requirements of overweight and obese patients. This case report presents the history of a 23-year-old obese male with a BMI of 38.7, who bent the angularly stabile titanium plate stabilizing his broken lateral ankle and torn distal tibiofibular syndesmosis. Biomechanical analysis showed that the maximal static bending moment registered during one-leg standing was equal to 1.55 Nm. This value was circa one-third of the maximally admissible bending moment for this particular plate (5.34 Nm) that could be transmitted without its plastic deformation. Since dynamic forces exceed static ones several (3-12) times during typical activities, such as walking, climbing the stairs, running, and jumping, unpredictable forces may occur and increase the risk of loosening, bending, and even breaking implants. None of these situations should have occurred for the typical patient's body mass of 75 kg, or even for the analyzed mass of the young patient (120 kg) who tried to avoid excessive loading during his daily routine. Subsequent implant bending and destabilization of the fracture shows that for the significantly high and still growing number of obese patients, a very strict physical regime should be recommended to prevent overabundant dynamic loads. On the other hand, the geometry of implants dedicated to these patients should be reconsidered.

Narrative Review of the Mechanism of Hip Prosthesis Dislocation and Methods to Reduce the Risk of Dislocation.

Total hip arthroplasty (THA) is one of the most effective surgical procedures. It improves quality of life, increases range of motion, and reduces pain in patients with hip joint degeneration. THA allows patients to return to everyday social and professional activities. Therefore, today it is the best approach to treatment of several chronic conditions affecting the hip joint, including advanced degenerative diseases, avascular necrosis, and some traumatic events. The aim of this study was to present the mechanism of hip prosthesis dislocation, associated risk factors, and the factors reducing the risk of dislocation, as well as its consequences and methods of risk minimization. Hip dislocation is a common complication following THA. It is responsible for up to 2% to 3% failures of primary replacements, increasing even to 10% in extreme cases of patients highly predisposed to this condition. In most cases, technical errors during implant placement are responsible for the incidence. The measures taken to prevent complications include activities aimed at correct implant insertion and the selection of the most appropriate type of implant for the patient, depending on individual needs. We summarized the current knowledge of implant dislocation to help surgeons understand the changes in biomechanics of the hip after its replacement and the impact of each particular element that participates in it. This knowledge can enable a surgeon choose the most favorable surgical method and the most appropriate implant to reduce the risk of implant dislocation.

Selected Clinical Features Fail to Predict Inflammatory Gene Expressions for TNF-α, TNFR1, NSMAF, Casp3 and IL-8 in Tendons of Patients with Rotator Cuff Tendinopathy.

The pathophysiology of rotator cuff tendinopathy is not fully understood, particularly in terms of the local inflammatory process. This study aimed to investigate the expression of selected molecules in the tumour necrosis factor (TNF)-α transduction pathway, including TNF-α, TNF receptor 1 (TNFR1), neutral sphingomyelinase activation associated factor (NSMAF), caspase 3 (Casp3), and interleukin (IL)-8, in patients with rotator cuff tendinopathy that had undergone surgical treatment. We included 44 participants that underwent arthroscopy, due to rotator cuff tendinopathy. Samples from the injured tendon were collected during arthroscopy, and RT-PCR was performed to determine gene expression. Pearson correlation analyses or U-Mann-Whitney test were performed to identify associations with the following parameters: sex, age at admission, body mass index, the presence of night pain, previous treatment (nonsteroidal anti-inflammatory drugs and/or steroids), medical history of the shoulder injury, upper subluxation of the humeral head, and the number of tendons injured. RT-PCR showed that the selected pro-inflammatory factors involved in the TNF-α signalling pathway expression levels were expressed in the tendon tissues. However, the levels of expression varied from patient to patient. Variations were over 250-fold for TNF-α, about 130-fold for TNFR1, NSMAF, and Casp3, and 1000-fold for IL-8. We could not confirm that any of the clinical parameters investigated were associated with the level of gene expression in the TNF-α pathway and IL-8.

The complexity of molecular processes in osteoarthritis of the knee joint.

Osteoarthritis (OA) is a common medical problem leading to chronic pain and physical disability among the world's population. Analyzing the molecular background of the degenerative arthritis creates the potential for developing novel targeted methods of treatment. Fifty samples of meniscus, anterior cruciate ligaments (ACLs) and articular surfaces were collected from patients who underwent total knee arthroplasty in 2016. Enzyme-linked immunosorbent assay was used to assess the levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF), transforming growth factor-ß1 and LUMINEX for MMP-1, MMP-2, MMP-3, MMP-9 and MMP-13. The collected data were correlated with the severity of radiological OA, demographic data and clinical scales. Strong positive correlations in the concentration of metalloproteinases and proinflammatory cytokines, TNF-α (MMP-2 and MMP-13) and IL-6 (MMP-13), were identified. MMP-13 had a positive correlation with the concentration of MMP-1, MMP-2 and MMP-9. Negative correlation coefficient exists between clinical conditions measured with the Western Ontario and McMaster Universities Osteoarthritis Index scale and the level of TNF-α and MMP-1. The TNF-α concentration was lower in the cartilage of the articular surface among patients who took non-steroidal anti-inflammatory drugs periodically. The decrease in MMP-2 in the cartilage of the articular surface corresponded with the severity of radiological OA on the Kellgren-Lawrence scale. Current treatment methods for OA do not stop disease progression. Identifying signaling pathways and molecular particles engaged in OA and their correlations with the patient's clinical condition brings new therapeutic possibilities.

Treatment of pathological fractures due to brown tumours in a patient with hyperparathyroidism and lack of parafibromin expression - A case report.

Brown tumours, known also as osteitis fibrosa cystica, are benign osteolytic lesions found in 5-15% of patients with hyperparathyroidism, and commonly located in mandibles, the shafts of long bones, the pelvis or ribs. As they compromise bone strength, pathological fractures can be a typical effect of their presence; but given the complex nature of the disease process in this case, such fractures require an interdisciplinary approach directed at orthopaedic treatment, plus management of the underlying hyperparathyroidism. In this paper, we present the case of a 36-year-old female patient with bilateral anophthalmia, hyperparathyroidism and nephrolithiasis, in whom a fall led to her sustaining a pathological fracture of the proximal third of the femoral shaft in the place of an osteolytic lesion, as well as second pathological fracture of the left patella also changed by multiple examples of such lesions. Parathyroidectomy on account of adenoma had been performed 2 weeks prior to the trauma. The femoral shaft fracture was treated surgically, the patella fracture conservatively, and a sample brown tumour was found in tissue. As the parathyroid showed no parafibromin expression, a diagnosis of HPT-JT (hyperparathyroidism and jaw tumour) was arrived at, with this condition given as caused by CDC73 mutation. This disease is able to account for brown tumours, hyperparathyroidism, benign or malignant tumours of kidneys, intestinal tract, and lungs. The approach combining treatment of the fractures with intervention over the parathyroid adenoma proved a successful one, with complete bone union ensuing, and no relapse into hyperparathyroidism 2 years on from the surgery. This case indicates the importance of an interdisciplinary approach to the treatment of brown tumours, as well as the necessity for a diagnosis to be extended when incidental brown tumours are found.

The outcomes of Ilizarov treatment in aseptic nonunions of the tibia stratified by treatment strategies and surgical techniques.

Nonunions of the tibia, particularly those located in the distal third of the bone, are relatively common in clinical practice. There is no gold standard for the treatment of nonunions of the tibia. The purpose of our study was to assess the results of treatment with the Ilizarov method in patients with aseptic nonunions of the tibia, depending on the employed treatment strategies and surgical techniques. A total of 75 patients with Ilizarov treatment of aseptic nonunions of the tibia were evaluated in the study. The patients's mean age at the beginning of treatment was 46 years. The mean follow-up period was 10 years and 11 months. The evaluated patients underwent either closed technique or open technique. The operators used one of two treatment strategies: neutral fixation without compression or continued compression. The following were assessed: rates of union, ASAMI bone scores, ASAMI functional scores, treatment time, complications, duration of hospital stay. Bone union was achieved in all of the 75 evaluated patients. The results of most analyses showed no significant differences in the assessed variables, except for the ASAMI functional scores, which were higher in the group of patients who underwent closed surgery (Me = 6.00 vs. Me = 4.00). We observed better ASAMI functional score outcomes in the patients who underwent closed fixation than in the open fixation group. The different surgical techniques and treatment strategies had no effect on the number of complications, rates of bone union, length of hospital stay, duration of Ilizarov treatment, or ASAMI bone scores. For managing nonunions of the tibia we recommend the technique of closed fixation without continued compression. The Ilizarov method in the treatment of nonunions of the tibia gives good outcomes.

Modified frailty index as a predictor of the long-term functional result in patients undergoing primary total hip arthroplasty.

OBJECTIVES: Total hip arthroplasty (THA) is a well-approved method for the treatment of end-stage osteoarthritis (OA). Due to rising life expectancy, elderly patients burdened with multimorbidity are subjected to THA. Some of these patients present significant depletion of physiological reserves, which is described as the frailty syndrome. This study aims to assess the influence of frailty on the THA outcomes in OA patients. MATERIAL AND METHODS: A single-center observational study was conducted to investigate the effect of frailty measured by the modified frailty index-5 (mFI-5) and modified frailty index-11 (mFI-11) on the long-term post-THA outcomes. The analysis included 597 initially screened patients subjected to unilateral, primary THA due to hip OA. The outcomes were assessed during a follow-up visit 3 years after THA. The primary outcome measures were patient-reported (the Western Ontario and McMaster Universities Osteoarthritis Index - WOMAC) and physician-reported scales (the Harris Hip Score - HHS). The secondary outcome measures were the length of hospital stay (LOS), pain complaints, complications, and satisfaction. A correlation analysis was performed (Spearman's R). RESULTS: Three hundred sixty-five patients met the eligibility criteria, including 57.26% women (n = 209) and 42.74% men (n = 156). The mean age was 65.11 ±12.12 years. Patients with high values of mFI-5 (r = 0.19; p < 0.05) and mFI-11 (r = 0.22; p < 0.01) achieved less satisfactory functional outcomes after THA (WOMAC). After age adjustment, mFI-11 (r = 0.17; p < 0.05) was a better predictor of functional outcome (WOMAC) than mFI-5 was (r = 0.15; p = 0.07). The mFI-5 (r = 0.25; p < 0.001) and mFI-11 (r = 0.29; p < 0.001) correlated with longer LOS. CONCLUSIONS: The modified frailty index-5 (mFI-5) and modified frailty index-11 (mFI-11) are useful tools to identify patients subjected to THA at a high risk of poor functioning after the procedure. They can be used in preoperative counseling before obtaining informed consent to support surgical decision-making. To our knowledge, this is the first study investigating the impact of the mFI on long-term postoperative functional results in OA treated with THA.

Bone marrow-derived from the human femoral shaft as a new source of mesenchymal stem/stromal cells: an alternative cell material for banking and clinical transplantation.

BACKGROUND: Mesenchymal stem/stromal cells (MSC) are commonly used in regenerative medicine. Among different tissues, iliac crest bone marrow (BM) represents the most exploited source, but its disadvantages are a painful aspiration procedure and low cell number. An alternative, readily available source of MSC for research would be beneficial for regenerative medicine development. This work aimed to propose a new source of bone marrow isolation in which the femoral shaft is taken during total hip arthroplasty (THA). METHODS: In preliminary experiments, three different gradient methods for cell separation (Ficoll-Paque 1.078 g/mL, 17% sucrose gradient, BM seeding fraction) were tested with regard to the time of primary culture, initial cell number, the phenotype, and morphology of MSC. Then human bone marrow MSC derived from two different sources, iliac crest aspirate (BM-MSCi) or femoral shaft (BM-MSCt), were analyzed in terms of cell number and colony-forming ability followed by differentiation potential of MSC into osteo-, chondro-, and adipogenic lineages as well as mRNA expression of a variety of cytokines and growth factors. RESULTS: Our studies showed that MSC isolated from the bone marrow of two different sources and cultured under appropriate conditions had similar characteristics and comparable propensity to differentiate into mesodermal cells. MSC derived from BM-MSCi or BM-MSCt expressed various growth factors. Interestingly, the expression of EGF, FGF, IGF, and PDGF-A was much higher in BM-MSCt than BM-MSCi. CONCLUSIONS: The results of our study demonstrate that human MSC isolated from the BM of the femoral shaft have similar biological characteristics as MSC derived from the iliac crest, suggesting the femoral shaft as a possible alternative source for mesenchymal stem/stromal cells.

An update on joint-specific outcome measures in total hip replacement.

This is the latest review of joint-specific tools used to evaluate patients undergoing total hip replacement (THR) surgery, which is an effective treatment for end-stage osteoarthritis. Due to the large number and multitude of scales and their variants used, a critical assessment of the available tools is necessary. In the article, we briefly describe six different clinical tools: the Western Ontario and McMaster Universities Osteoarthritis Index, the Hip Disability and Osteoarthritis Outcome Score, the Harris Hip Score, the Oxford Hip Score, the Mayo Hip Score, and the Rheumatoid and Arthritis Outcome Score. We present the advantages and constraints of the different outcome measures, providing a helpful resource of information for clinical trials and for everyday routine evaluation.

Heterotopic ossification and clinical results after total hip arthroplasty using the anterior minimally invasive and anterolateral approaches.

INTRODUCTION: Total hip arthroplasty (THA) is considered the gold standard in the treatment of advanced osteoarthritis of the hip. The aim of this study was to compare the incidence of heterotopic ossification (HO), the quality of life and the function in two groups of patients who underwent total hip arthroplasty (THA), performed using the anterior minimally invasive (MIS) and the anterolateral approaches. MATERIAL AND METHODS: Retrospective analysis of 597 patients who underwent THA in 2009-2013 was performed. In all 597 cohort data on medical history were retrieved. HO occurrence was recorded for 331 patients and was evaluated based on Brooker's scale in the X-ray scan. Functional and quality of life scores were obtained for 238 patients. The following scales were used for the survey: Harris Hip Score, Western Ontario and McMaster Universities Osteoarthritis Index, Visual Analogue Scale, and Hip and Knee Arthroplasty Satisfaction Scale. RESULTS: Patients operated on from the MIS approach had statistically significantly (p < 0.05) better results with all the clinical scales used, except the Visual Analogue Scale (p > 0.05). HO was slightly more common after the MIS approach (52.5%) compared to the anterolateral approach (49.76%), though the difference was not statistically significant (p > 0.05). CONCLUSIONS: The MIS approach was associated with better clinical and functional outcomes. In the aspect of HO, we were not able to show the superiority of the MIS approach in terms of incidence.

Surgical treatment outcomes of the Ilizarov and internal osteosynthesis methods in posttraumatic pseudarthrosis of the tibia-a retrospective comparative analysis.

INTRODUCTION: This study compared surgical treatment outcomes of the Ilizarov and internal osteosynthesis methods in posttraumatic pseudarthrosis of the tibia. MATERIAL AND METHODS: In a retrospective comparative study, 75 patients were treated with the Ilizarov technique for aseptic posttraumatic pseudarthrosis of the tibia in the period 2000-2016. We compared them with the 51 patients from the control group, treated for tibial bone union disturbances using internal osteosynthesis methods, i.e., internal-fixation plates and intramedullary nails. The study groups were compared in terms of the rates of union, time to union, and the baseline-to-postoperative difference in lower leg deformity. RESULTS: Union rate in the Ilizarov group was 100% and the control group was 51.92% (p < 0.001). The median time to union suggests that patients from the Ilizarov group needed a shorter time to achieve bone union (203.00 days vs. 271.00 days) (p = 0.091). The effect size in the Ilizarov group was larger both in terms of reducing both limb deformity and shortening (it is worth noting, however, that the Ilizarov treatment was used in patients with higher baseline values of both these parameters). We observed no significant difference in terms of time to union between the group of patients with at least one risk factor for disturbance in fracture healing and the group with no risk factors. The following risk factors were considered: diabetes mellitus, corticosteroid therapy, smoking, alcohol dependence, and advanced lower-extremity vascular disease (p = 0.827). DISCUSSION: Our study demonstrated a high effectiveness of the Ilizarov method in the treatment of aseptic posttraumatic pseudarthroses of the tibia. The Ilizarov method seems to be worth considering in all cases where either the patient or the nature of injury is associated with additional risk factors and whenever there is a need for leg deformity correction or leg elongation.

CD4+FOXP3+ T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired.

There is evolving evidence that dysregulation of immune homeostasis in the bone marrow (BM) adjacent to the inflamed joints is involved in the pathogenesis of. In this study, we are addressing the phenotype and function of regulatory T cells (Tregs) residing in the BM of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). BM and peripheral blood samples were obtained from RA and OA patients undergoing hip replacement surgery. The number and phenotype of Tregs were analyzed by flow cytometry and immunohistochemistry. The function of Tregs was investigated ex vivo, addressing their suppressive activity on effector T cells. [3H]-Thymidine incorporation assay and specific enzyme-linked immunosorbent assay were used for quantification of cell proliferation and pro-inflammatory (TNF, IFN-γ) cytokine release, respectively. Significantly lower numbers of CD4+FOXP3+ T cells were found in the BM of patients with RA compared to control patients with OA. High expression of CD127 (IL-7 receptor) and relatively low expression of CXCR4 (receptor for stromal cell-derived factor CXCL12) are characteristics of the CD4+FOXP3+ cells residing in the BM of RA patients. The BM-resident Tregs of RA patients demonstrated a limited suppressive activity on the investigated immune response. Our results indicate that the reduced number and impaired functional properties of CD4+FOXP3+ T cells present in the BM of RA patients may favor the inflammatory process, which is observed in RA BM.

Correlations between Vancouver type of periprosthetic femur fracture and treatment outcomes.

OBJECTIVE: Periprosthetic femur fractures are one of the most severe complications of total hip arthroplasty. METHODS: The aim of this study was to assess outcomes of periprosthetic femur fractures based on the Vancouver classifications of fractures. RESULTS: Sixty-four patients were enrolled into the study. Type B1 fractures were the most common - 33 cases. In comparison to patients with type B3 fracture, patients with type B1 fracture significantly less often experienced postoperative pain. CONCLUSION: Study shown that in the context of both objective outcomes of the operation and patient satisfaction, the most unfavourable prognosis is after type B3.

Comminuted fractures of the proximal humerus - principles of the diagnosis, treatment and rehabilitation.

Comminuted fractures of the proximal humerus impair shoulder function, resulting in more or less severe disability. They rank among the most frequent fractures in adults, with incidence increasing with age and the degree of bone loss (osteoporosis). Among all currently used methods of stabilization of proximal humeral fractures, the best outcomes are afforded by angularly-stable plate fixation and interlocking or reconstructive intramedullary nailing. Both methods produce comparable results enabling bone union and restoration of limb functionality. Nevertheless, in elderly patients with advanced bone loss, in whom anatomical reduction of bone fragments is difficult or impossible, stabilization questionable and patient cooperation in the postoperative rehabilitation impossible to enforce, arthroplasty should be considered. Non-displaced or minimally displaced fractures may be treated conservatively by immobilizing the limb in an orthosis for three weeks. Nevertheless, the recommendations for operative interventions are being broadened, as stabilization eliminates the need to immobilize the limb, thus not affecting the patient's professional and social activities, enabling immediate rehabilitation, reducing the risk of joint stiffness and shortening recovery time.

Survival of lymphocytes is not restricted by IDO-expressing fibroblast from rheumatoid arthritis patients.

Objective: Rheumatoid arthritis (RA) is characterized by expansion of fibroblast-like synoviocytes (FLS) in inflamed joints and activation of lymphocytes. Tryptophan (trp) is an essential amino acid indispensable for the biosynthesis of proteins and critical for survival of lymphocytes. Indoleamine 2,3-dioxygenase (IDO) that initiates the degradation of trp and tryptophanyl-tRNA synthetase (TTS) essential for tryptophan synthesis, regulate trp bioavailability. Here, we tested the hypothesis that triggered by cytokines, enhanced IDO activity modulate regulatory function of otherwise non-tolerogenic FLS isolated from RA patients. Materials and methods: IDO and TTS mRNA expression were evaluated by RT-PCR. IDO enzymatic activity was confirmed using HPLC. Resting or PHA-activated PBMC from healthy volunteers and RA patients were co-cultured with IDO expressing untreated (FLSC) or IFNγ-treated (FLSIFNγ) RA FLS. Lymphocyte survival and proliferation were evaluated by flow cytometry analysis and tritiated thymidine incorporation, respectively. Results: RA FLSIFNγ produce functionally active IDO and constitutively express TTS. RA FLSC and FLSIFNγ increased survival of resting lymphocytes in both studied groups, and decreased proliferation of healthy, but not RA, PBMC. Only FLSIFNγ diminished survival of activated CD3+CD4-, but not CD3+CD4+, healthy T cells and similar tendency was observed in rheumatoid cells. Importantly, IDO inhibitor, 1-methyl-DL-tryptophan (1-MT), failed to reverse this effect. PBMC, irrespective of their state (resting versus activated) or origin (healthy or RA), expressed high level of TTS mRNA. Conclusions: We suggest that RA FLS express functionally active IDO but control survival and expansion of healthy cells in IDO-independent mechanism and exert weaker, if any, suppressive effect on rheumatoid cells.

Use of Three-dimensional Printing and Patient-matched Implant in Total Hip Arthroplasty - a Case Study.

We present a case report of a 70-year-old female patient with a history of right hip dysplasia and total hip arthroplasty complicated by chronic periprosthetic hipction. Failure of oral antibiotic treatment was an indication for implant removal. A computed tomography scan performed during qualification for reimplantation revealed massive bone defects in the pelvis. A three-dimensional printed patient-specific anatomical model of the pelvis helped to determine the precise position and cup size in preoperative planning and prepare a patient-matched acetabulum. The custom-made endoprosthesis was implanted during revision arthroplasty.

Results of Treatment of Type 3 Acromioclavicular Joint Dislocation with Three Methods.

BACKGROUND: Rockwood Type III acromioclavicular joint injuries are treated both conservatively and surgically. There is still no consensus on an optimal fixation method. The aim of this study was to evaluate which of the surgical methods used in our Department produces the best outcomes in long-term follow-up. MATERIAL AND METHODS: The study involved 27 patients. Wire cerclage was used in 12 patients, 11 patients were operated on by the Ladermann method, and a hook plate was used in 4 patients. The patients were assessed at a late follow-up visit after a mean of 22 months post-operatively. The Constant Shoulder Scale (CSS), Oxford Shoulder Scale (OSS), and PROMIS v1.2 for the upper limb were used to assess the long-term effects of the treatment. RESULTS: There were no statistically significant differences between the Ladermann method and wire cerclage for the scales applied (p=0.98 at α=0.05). The functional CSS showed a significant advantage of the outcomes of the Lader-mann method and wire cerclage in comparison to the hook plate (p=0.014 and p=0.004, respectively, at α=0.05). The quality of life scales OSS and PROMIS showed no significant difference between the methods. CONCLUSIONS: 1. The outcomes of treatment with the Ladermann method and wire cerclage are excellent and com-parable with regard to both clinical outcomes and the quality of life. 2. The use of a hook plate may substantially contribute to worse clinical outcomes. 3. No considerable difference was found in the quality of life between the different groups, but a study involving a larger number of patients would be necessary for a complete evaluation.