The Update on Instruments Used for Evaluation of Comorbidities in Total Hip Arthroplasty.

INTRODUCTION: It is a well-established fact that concomitant diseases can affect the outcome of total hip arthroplasty (THA). Therefore, careful preoperative assessment of a patient's comorbidity burden is a necessity, and it should be a part of routine screening as THA is associated with a significant number of complications. To measure the multimorbidity, dedicated clinical tools are used. METHODS: The article is a systematic review of instruments used to evaluate comorbidities in THA studies. To create a list of available instruments for assessing patient's comorbidities, the search of medical databases (PubMed, Web of Science, Embase) for indices with proven impact on revision risk, adverse events, mortality, or patient's physical functioning was performed by two independent researchers. RESULTS: The initial search led to identifying 564 articles from which 26 were included in this review. The measurement tools used were: The Charlson Comorbidity Index (18/26), Society of Anesthesiology classification (10/26), Elixhauser Comorbidity Method (6/26), and modified Frailty Index (5/26). The following outcomes were measured: quality of life and physical function (8/26), complications (10/26), mortality (8/26), length of stay (6/26), readmission (5/26), reoperation (2/26), satisfaction (2/26), blood transfusion (2/26), surgery delay or cancelation (1/26), cost of care (1/26), risk of falls (1/26), and use of painkillers (1/26). Further research resulted in a comprehensive list of eleven indices suitable for use in THA outcomes studies. CONCLUSION: The comorbidity assessment tools used in THA studies present a high heterogeneity level, and there is no particular system that has been uniformly adopted. This review can serve as a help and an essential guide for researchers in the field.

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.

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.

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.

Challenges and Controversies in Human Mesenchymal Stem Cell Therapy.

Stem cell therapy is being intensely investigated within the last years. Expectations are high regarding mesenchymal stem cell (MSC) treatment in translational medicine. However, many aspects concerning MSC therapy should be profoundly defined. Due to a variety of approaches that are investigated, potential effects of stem cell therapy are not transparent. On the other hand, most results of MSC administration in vivo have confirmed their safety and showed promising beneficial outcomes. However, the therapeutic effects of MSC-based treatment are still not spectacular and there is a potential risk related to MSC applications into specific cell niche that should be considered in long-term observations and follow-up outcomes. In this review, we intend to address some problems and critically discuss the complex nature of MSCs in the context of their effective and safe applications in regenerative medicine in different diseases including graft versus host disease (GvHD) and cardiac, neurological, and orthopedic disorders.

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.

Increased serum levels of progranulin (PGRN) in patients with haemophilic arthropathy.

Haemophilia A and B are rarely occurring X chromosome-linked congenital coagulation disorders dominated by spontaneous joint bleedings and chronic synovitis, leading to development of haemophilic arthropathy (HA). Progranulin (PGRN) is a growth factor with anti-inflammatory and immunomodulatory properties. PGRN is an important molecule in the pathogenesis of osteoarthritis (OA) and rheumatological disorders. This study was aimed at investigating the potential role of PGRN in the mechanisms underlying the pathogenesis of HA. The serum levels of PGRN were measured by enzyme-linked immunosorbent assay (ELISA) in patients with end-stage knee joint HA (n = 20) and end-stage primary knee joint OA (n = 20) who met the inclusion and exclusion criteria. The clinical and radiological assessment of disease severity was evaluated by the Knee Society Score (KSS) and Kellgren-Lawrence scale. Median PGRN levels in HA patients was 349.1 ng/mL (232.8-415.6 ng/mL) and in OA patients 148.3 ng/mL (112.1-275.3 ng/mL) with statistically significant differences between both groups (P < 0.015). Further analysis revealed no correlation between PGRN levels and any of the patient demographics and clinical parameters. This study demonstrates increased PGRN serum levels in patients with HA and provides new insights into the mechanisms underlying the pathogenesis of HA indicating a new potential target for therapeutic intervention.

Challenges of heterotopic ossification-Molecular background and current treatment strategies.

Heterotopic ossification (HO) is an abnormal formation of mature lamellar bone within extraskeletal soft tissues, such as muscles, tendons, and ligaments. This process is thought to be induced by inflammation associated with tissue injuries. HO is classified using two subtypes: resulting from injury or genetically inherited. HO formation is associated with polytrauma patients with traumatic brain injuries and spinal cord injuries. Moreover, HO is also considered to be a post-operative risk factor in some orthopaedic procedures. In this review, we summarize our current understanding of the pathology of different types of HO and discuss its current and future therapies. Thus far, research has revealed cellular and molecular pathways leading to HO formation and proposed several possible mechanisms leading to HO and conserved signalling pathways common in the different HO subtypes. Non-steroidal anti-inflammatory drug treatment and localized low-dose irradiation are currently the only available prophylactic treatments for HO. However, they are not always effective and do not target the osteogenic processes directly. New therapeutic strategies targeting the pathological processes of HO, such as bone morphogenetic protein (BMP) inhibitors like noggin, BMP type 1 receptor inhibitor, and nuclear retinoid acid receptor-gamma (RARγ) agonists, are currently being investigated. In-depth understanding of the HO pathological process could help to develop effective therapeutic strategies.

The Use of Type I Collagen Cross-Linked C-Telopeptide (CTX-1) as a Biomarker Associated with the Formation of Periprosthetic Ossifications Following Total Hip Joint Arthroplasty.

The aim of this study was to determine the co-occurrence of heterotopic ossifications (HO) and elevated bone biomarkers level (urine type I collagen cross-linked C-telopeptide - CTX-1, serum alkaline phosphatase - ALP) and assess the effectiveness of pharmacological prophylaxis of HO. The study group consisted of (N=54) patients qualified for total hip arthroplasty. In N=19 (35%) patients new HO were formed (48th week vs to baseline). On baseline, the mean CTX-1 value in the HO (-) patients was 8.60+/-5.37 ug/mmol vs HO (+) 11.73+/-6.02 ug/mmol (p<0,05). On the 5th day after the surgery, the mean value in HO (-) patients was 8.45+/-4.04 ug/mmol vs HO (+)14.46+/- 5.91 ug/mmol (p<0,05). The mean increase in CTX-1 levels in HO (+) patients' vs HO (-) compared to the initial value was 21% vs 47%. Correlation between CTX-1 concentration on the 5th day and the appearance of new ossifications (r=0.48, p<0.05) was demonstrated. In group covered by prophylaxis diclofenac 150 mg for 6 weeks, HO assessment in Brooker's scale was on average 0.78 points lower than in the group without prophylaxis and 0.89 points lower than in the group without prophylaxis and no risk factors of HO (p<0,05). The study also reported a correlation between the corrected ALP concentration in the 12th week and HO (r=0.59, p<0.05).

Influence of diabetes on tissue healing in orthopaedic injuries.

Diabetes is a group of metabolic diseases characterized by hyperglycaemia resulting from the defective action or secretion of insulin. Chronic hyperglycaemia can lead to the damage, dysfunction and failure of various organs. In the context of complications of healing and orthopaedic rehabilitation, vascular (microangiopathy) and nerve (neuropathy) disorders deserve particular attention. About 12% of the patients admitted to orthopaedic departments have diabetes. Studies indicate that there is an indisputable link between diabetes and: an increased risk of fractures, the difficult healing of injuries of bones, ligaments and musculotendinous. It appears that one of the main reasons for this is non-enzymatic glycosylation (glycation) of collagen molecules, a phenomenon observed in the elderly and diabetic populations, as it leads to the formation of advanced glycation end products (AGEs). Collagen is one of the major connective tissue components, and is therefore part of ligaments, tendons and bones. AGEs affect the weakening of its structure and biomechanical properties, and thus also affects the weakening of the structure and properties of the above-mentioned tissues. The aim of the study is to undertake an overview of the current knowledge of the impact of diabetes on the risk of some injuries and subsequent healing and rehabilitation of patients following orthopaedic injuries.