Aluminum Nanoparticles Affect Human Platelet Function In Vitro.

Endoprostheses are prone to tribological wear and biological processes that lead to the release of particles, including aluminum nanoparticles (Al NPs). Those particles can diffuse into circulation. However, the toxic effects of NPs on platelets have not been comprehensively analyzed. The aim of our work was to investigate the impact of Al NPs on human platelet function using a novel quartz crystal microbalance with dissipation (QCM-D) methodology. Moreover, a suite of assays, including light transmission aggregometry, flow cytometry, optical microscopy and transmission electron microscopy, were utilized. All Al NPs caused a significant increase in dissipation (D) and frequency (F), indicating platelet aggregation even at the lowest tested concentration (0.5 µg/mL), except for the largest (80 nm) Al NPs. A size-dependent effect on platelet aggregation was observed for the 5-20 nm NPs and the 30-50 nm NPs, with the larger Al NPs causing smaller increases in D and F; however, this was not observed for the 20-30 nm NPs. In conclusion, our study showed that small (5-50 nm) Al NPs caused platelet aggregation, and larger (80 nm) caused a bridging-penetrating effect in entering platelets, resulting in the formation of heterologous platelet-Al NPs structures. Therefore, physicians should consider monitoring NP serum levels and platelet activation indices in patients with orthopedic implants.

Overview of First-Line and Second-Line Pharmacotherapies for Osteoarthritis with Special Focus on Intra-Articular Treatment.

Osteoarthritis (OA) can be defined as the result of pathological processes of various etiologies leading to damage to the articular structures. Although the mechanism of degenerative changes has become better understood due to the plethora of biochemical and genetic studies, the drug that could stop the degenerative cascade is still unknown. All available forms of OA therapy are based on symptomatic treatment. According to actual guidelines, comprehensive treatment of OA should always include a combination of various therapeutic options aimed at common goals, which are pain relief in the first place, and then the improvement of function. Local treatment has become more common practice, which takes place between rehabilitation and pharmacological treatment in the hierarchy of procedures. Only in the case of no improvement and the presence of advanced lesions visible in imaging tests, should surgery be considered. Currently, an increasing number of studies are being published suggesting that intra-articular injections may be as effective or even more effective than non-steroidal anti-inflammatory drugs (NSAIDs) and result in fewer systemic adverse events. The most commonly used preparations are hyaluronic acid (HA), glucocorticosteroids (GS), and also platelet-rich plasma (PRP) in recent years. This review aims to present the mechanism of action and clinical effectiveness of different pharmacological options in relieving pain and improving functions in OA as well as the emerging approach in intra-articular treatment with PRP.

Minimally Invasive Cell-Based Therapy for Symptomatic Bone Marrow Lesions of the Knee: A Prospective Clinical Study at 1 Year.

Bone marrow lesions (BMLs) are typical findings in magnetic resonance imaging present in different pathologies, such as spontaneous insufficiency fractures, osteonecrosis, transient BML syndromes, osteoarthritis, and trauma. The etiology and evolution of BMLs in multiple conditions remain unclear. There is still no gold standard protocol for the treatment of symptomatic BMLs in the knee. The biologic augmentation by Osteo Core Plasty™ is a new treatment modality showing promising results reducing pain with the aim to stop the progression of the disease. The purpose of this prospective study is to report the clinical outcomes and safety of Osteo Core Plasty for the treatment of symptomatic BMLs in the knee. Fifteen patients with symptomatic BMLs of the knee treated with the Osteo Core Plasty technique were included and followed prospectively for a minimum of 12 months. Each patient was evaluated before the surgery and respectively at 6 and 12 months using the Tegner Score, Marx Score, the International Knee Documentation Committee, the Knee Injury and Osteoarthritis Outcome Score divided in pain, activity daily living and quality of life subscale, and the Visual Analog Scale for pain. All clinical scores except Tegner and Marx score showed an overall statistically significant improvement through the entire follow-up (P < 0.05) and a significant improvement (P < 0.05) between each follow-up period (T0 vs. T1; T0 vs. T2; T1 vs. T2). No complications were reported. These preliminary results confirm that biological subchondral bone augmentation by Osteo Core Plasty technique is a safe and effective minimally invasive treatment option for symptomatic BMLs in the knee at 1-year follow-up. There is still a need for high-quality randomized controlled trials studies and systematic reviews in the future to enhance further treatment strategies in preventing or treating BMLs of the knee.

The Influence of Body Mass Index on Growth Factor Composition in the Platelet-Rich Plasma in Patients with Knee Osteoarthritis.

BACKGROUND: An abnormally high body mass index is strongly associated with knee osteoarthritis. Usually, obese patients are excluded from clinical trials involving PRP intra-articular injections. Growth factors have been demonstrated to have a disease-modifying effect on KOA treatment, even though data on their influence on treatment effectiveness in obese patients are lacking. PURPOSE: To prospectively compare the level of selected growth factors including transforming growth factor-b (TGF-ß), epidermal growth factor (EGF), fibroblast growth factor, insulin-like growth factor-1 (IGF-1), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) in platelet-rich plasma (PRP) in obese patients and patients with normal BMI. METHODS: A total of 49 patients were included in the study according to inclusion and exclusion criteria. The groups strongly differed in body mass index (median values 21.6 vs. 32.15). Concentrations of growth factors were measured with an enzyme-linked immunosorbent assay. Statistical significance was determined with the Mann-Whitney U test. The compliance of the distribution of the results with the normal distribution was checked using the Shapiro-Wilk test separately for both groups. RESULTS: There were no statistically significant differences in median marker levels between groups. Statistically significant Pearson correlations were observed between IGF-1 serum level and age (weak negative, r = -0.294, p = 0.041) and gender (moderate positive, r = 0.392, 0.005). CONCLUSIONS: BMI does not influence the level of selected growth factors in patients with knee osteoarthritis. Obese and non-obese patients had similar compositions of PDGF, TGF-ß, EGF, FGF-2, IGF-1, and VEGF. PRP can be used in both groups with similar effects associated with growth factors' influence on articular cartilage.

Diagnosis and treatment of the most common neuropathies following knee injuries and reconstructive surgery - A narrative review.

The main nerves in the knee region are the tibial nerve, the common peroneal nerve, and the saphenous nerve. These three nerves innervate the lower leg and foot, providing sensory and motor function. The large sciatic nerve splits just above the knee to form the tibial and common peroneal nerves. The tibial nerve travels down in the posterior region, while the common peroneal nerve runs around the lateral side of the knee and runs down the front of the leg to the foot. Although all these nerves can be affected by injuries of the knee, the infrapatellar branch of the saphenous nerve (IPBSN) and the common peroneal nerve (CPN) are most affected. In this narrative review we focus on neuropathies associated with nerves located in the region of the knee joint in the context of their injuries and possible iatrogenic damage during reconstructive surgery.

The Effect of Platelet-Rich Plasma on the Intra-Articular Microenvironment in Knee Osteoarthritis.

Knee osteoarthritis (KOA) represents a clinical challenge due to poor potential for spontaneous healing of cartilage lesions. Several treatment options are available for KOA, including oral nonsteroidal anti-inflammatory drugs, physical therapy, braces, activity modification, and finally operative treatment. Intra-articular (IA) injections are usually used when the non-operative treatment is not effective, and when the surgery is not yet indicated. More and more studies suggesting that IA injections are as or even more efficient and safe than NSAIDs. Recently, research to improve intra-articular homeostasis has focused on biologic adjuncts, such as platelet-rich plasma (PRP). The catabolic and inflammatory intra-articular processes that exists in knee osteoarthritis (KOA) may be influenced by the administration of PRP and its derivatives. PRP can induce a regenerative response and lead to the improvement of metabolic functions of damaged structures. However, the positive effect on chondrogenesis and proliferation of mesenchymal stem cells (MSC) is still highly controversial. Recommendations from in vitro and animal research often lead to different clinical outcomes because it is difficult to translate non-clinical study outcomes and methodology recommendations to human clinical treatment protocols. In recent years, significant progress has been made in understanding the mechanism of PRP action. In this review, we will discuss mechanisms related to inflammation and chondrogenesis in cartilage repair and regenerative processes after PRP administration in in vitro and animal studies. Furthermore, we review clinical trials of PRP efficiency in changing the OA biomarkers in knee joint.

Relationship between long head of the biceps tendon histopathology and long-term functional results in smokers. A time to reevaluate the Bonar score?

AIM: The purpose of this study was to investigate whether there is an association between smoking, the extent of the degeneration process in the biceps tendinopathy, including cells and extracellular matrix (ECM) alterations, and long-term surgical results. METHODS: This study comprised 40 consecutive patients admitted for shoulder arthroscopy due to symptomatic biceps tendinopathy and classified into three groups based on smoking status: active smokers, former smokers, and non-smokers. According to the classical Bonar score criteria, the histopathologic evaluation of the harvested intra-articular portion of the tendon was done. The follow-up examination was based on the American Shoulder and Elbow Surgeons Score (ASES). RESULTS: A cohort of 32 patients was enrolled in the final follow-up examination; mean 37.56 months. Histopathological evaluation according to the classical Bonar score revealed degeneration of the tendinous tissue in each group but there was no correlation between the extent of degeneration, smoking indexes and the ASES. After revision of Bonar scale within the vascularity criterion, we found a correlation between the extent of degeneration of tendinous tissue, smoking data, ASES score, and the severity of rotator cuff injury. CONCLUSION: In this paper, we indicate the ambiguous role of the neovascularization in the biceps tendinopathy, and it was used for modification of the classical Bonar score. Consequently, recalculated, modified Bonar score was correlated positively with smoking indexes and functional outcomes. Furthermore, the morphological alterations of rotator cuff tendons also correlated positively with the extent of biceps tendon degeneration, measured according to the modified scoring system.

The Impact of Smoking on Clinical Results Following the Rotator Cuff and Biceps Tendon Complex Arthroscopic Surgery.

The purpose of this study was to investigate the association of smoking and functional outcomes after arthroscopic treatment of complex shoulder injuries: rotator cuff tears (RCTs) with biceps tendon (LHBT) tears. This retrospective case-control study has been conducted on a cohort of patients who underwent shoulder arthroscopy between 2015 and 2017 due to complex injury treatment. The outcomes were assessed using the American Shoulder and Elbow Surgeons Score (ASES), the University of California at Los Angeles (UCLA) Shoulder Score, need for non-steroid anti-inflammatory drugs (NSAIDs) consumption and the visual analog scale (VAS). Complications and changes in smoking status were also noted. A cohort of 59 patients underwent shoulder arthroscopy, due to complex LHBT pathology and RCTs, and were enrolled in the final follow-up examination; with mean duration of 26.03 months. According to smoking status, 27 of patients were classified as smokers, and the remaining 32 were non-smokers. In the examined cohort, 36 patients underwent the LHBT tenotomy and 23 tenodesis. We observed a relationship between smoking status and distribution of various RCTs (p < 0.0001). The mean postoperative ASES and UCLA scores were 80.81 and 30.18 in the smoker's group and 84.06 and 30.93 in the non-smoker's group, respectively. There were no statistically significant differences in pre/postoperative ASES and postoperative UCLA scores between smokers and non-smokers (p > 0.05). The VAS was significantly lower in the non-smokers' group (p = 0.0021). Multi-tendon injuries of the shoulder are a serious challenge for surgeons, and to obtain an excellent functional outcome, we need to limit the negative risk factors, including smoking. Furthermore, there is a significant association between smoking and the occurrence of massive rotator cuff tears, and the pain level measured by the VAS. Simultaneous surgical treatment of RC and LHBT lesions in the smoker population allowed us to obtain the functional outcomes approximated to non-smokers in the long-term follow-up. Of course, we cannot assert that smoking is the real cause of all complications, however, we may assume that this is a very important, negative factor in shoulder arthroscopy.

A 10-Year Follow-up on Arthroscopic Medial Plica Syndrome Treatments with Special Reference to Related Cartilage Injuries.

OBJECTIVE: The aim of this study was to evaluate the factors that can affect long-term results of arthroscopic resection of medial synovial plica of the knee. DESIGN: A total of 52 knees in 50 consecutive patients with medial plica syndrome (MPS) were enrolled to prospective study. Preoperatively the age, gender, level of activity, symptoms' duration, Lysholm knee scoring scale (LKSS), Q angle, range of motion (ROM), and quadriceps output torque (QOT) were recorded. The plica was then arthroscopically excised while plica morphological type and cartilage lesions (International Cartilage Repair Society [ICRS] classification) were registered. The postoperative evaluation was done after 1 month, 3 months, 6 months, 3 years, and 10 years. The final assessment after 10 years covered LKSS, ROM, QOT, and was enriched with functional tests: the single leg squat test (SLS), the modified Ober test (MO), and the manual palpation of the vastus medialis obliquus (VMO). RESULTS: The mean LKSS increased from 52 (15-85, SD 16.479) preoperative to 80 (48-100, SD 15.711) at final follow-up examination. A significant negative correlation was found between LKSS and the patients' age. Cartilage lesions higher than ICRS 1 significantly decreased the final LKSS. Results were significantly better in the subgroups with normal outcome of functional tests. CONCLUSIONS: Clinical results of arthroscopic plica resection are better in patients without coexisting cartilage lesions. Poor neuromuscular control may contribute to abnormal patella tracking, leading to both medial plica irritation and further cartilage deterioration.

Genetics in Cartilage Lesions: Basic Science and Therapy Approaches.

Cartilage lesions have a multifactorial nature, and genetic factors are their strongest determinants. As biochemical and genetic studies have dramatically progressed over the past decade, the molecular basis of cartilage pathologies has become clearer. Several homeostasis abnormalities within cartilaginous tissue have been found, including various structural changes, differential gene expression patterns, as well as altered epigenetic regulation. However, the efficient treatment of cartilage pathologies represents a substantial challenge. Understanding the complex genetic background pertaining to cartilage pathologies is useful primarily in the context of seeking new pathways leading to disease progression as well as in developing new targeted therapies. A technology utilizing gene transfer to deliver therapeutic genes to the site of injury is quickly becoming an emerging approach in cartilage renewal. The goal of this work is to provide an overview of the genetic basis of chondral lesions and the different approaches of the most recent systems exploiting therapeutic gene transfer in cartilage repair. The integration of tissue engineering with viral gene vectors is a novel and active area of research. However, despite promising preclinical data, this therapeutic concept needs to be supported by the growing body of clinical trials.

Cigarette smoking intensifies tendinopathy of the LHBT. A microscopic study after arthroscopic treatment.

Smoking has a damaging effect on the musculoskeletal system, which was presented by authors in the rotator cuff and Achilles tendons studies; however, there are a lack of data about the effect of smoking on disorders of the long head of the biceps tendon (LHBT), particularly at the microscopic level. The purpose of this study was to investigate the effect of the tobacco smoking on the histopathologic alterations of the LHBT. Thirty-six patients with preoperatively diagnosed tendinopathy of the LHBT were referred to the Orthopaedics Department. All patients underwent arthroscopic treatment with further macroscopic and microscopic evaluation of biceps tendon samples. The active and former smokers were characterised by more advanced degenerative process of the tendinous tissue; moreover, it was intensified in the group of former smokers. Subjects who smoke more than 20 cigarettes per day also had more advanced microscopic alterations. The most severe microscopic alterations occurred in the former smokers who used tobacco for more than 20 years. However, the non-smokers group revealed moderate degeneration in all LHBT samples. Tobacco smoking is an important risk factor of the LHBT disease, which essentially intensifies the degeneration of the tendinous tissue.

Intraoperative injuries during liver resection: analysis of 1,005 procedures.

PURPOSE: Risk of liver resection has been well investigated in many studies. However, the problem of intraoperative injuries is rarely mentioned. The aim of this study was to assess the incidence, the type, and management of intraoperative injuries during liver resection. METHODS: A total of 1,005 liver resections between 2004 and 2009 were included in this retrospective investigation. We analyzed the incidence of intraoperative injuries, risk factors, and an impact on patients' clinical outcome. RESULTS: The overall incidence of intraoperative injuries was 4.4% (44 of 1,005). Injuries of the diaphragm (1.6%, 16 of 1,005) and hepatocaval junction (1%, 10 of 1,005) were the most frequent. In multivariate analysis, tumor recurrence (p = 0.0199) and tumor size (p = 0.0317) were the only independent risk factors for diaphragm injuries, whereas the extent of resection (p = 0.0007) was the only independent risk factor for caval or hepatic vein injuries. Injuries of the inferior vena cava or hepatic veins significantly increased perioperative mortality (p = 0.0005). CONCLUSIONS: Minor injuries causing no significant complications were the most frequent. However, prevention and proper management of the rare injuries of hepatocaval junction are essential to avoid increased mortality in major liver resections.