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1.
The effects of poloxamer and sodium alginate mixture (Guardix-SG®) on range of motion after axillary lymph node dissection: A single-center, prospective, randomized, double-blind pilot study.
Lee, SB, Gwark, SC, Kang, CM, Sohn, G, Kim, J, Chung, IY, Lee, JW, Kim, HJ, Ko, BS, Ahn, SH, et al
PloS one. 2020;(9):e0238284
Abstract
PURPOSE Restricted shoulder mobility is a major upper extremity dysfunction associated with lower quality of life and disability after breast cancer surgery. We hypothesized that a poloxamer and sodium alginate mixture (Guardix-SG®) applied after axillary lymph node dissection (ALND) would significantly improve shoulder range of motion (ROM) in patients with breast cancer. METHODS We conducted a double-blind, randomized, prospective study to evaluate the clinical efficacy and safety of Guardix-SG® for the prevention of upper extremity dysfunction after ALND. The primary outcome measure was shoulder ROM at baseline (T0) and 3 (T1), 6 (T2), and 12 months (T3) after surgery. Secondary outcome measures were the Disabilities of the Arm, Shoulder, and Hand score(DASH), pain associated with movement, which was assessed using a numeric rating scale, and lymphedema assessed using body composition analyzer. RESULTS A total of 83 women with breast cancer were randomly assigned to either the Guardix-SG® group or the control group. In the Guardix-SG® group (n = 37), Guardix-SG® was applied to the axillary region after ALND. In the control group (n = 46), ALND was performed without using Guardix-SG®. Comparing ROM for shoulder flexion before surgery (178.2°) and 12 months after surgery (172.3°), that was restored 12 months after surgery in the Guardix-SG® group, and there was no statistically significant difference between that at before surgery and 12 months after surgery (p = 0.182). No adverse effect was observed in either group. CONCLUSIONS The results of this study have shown that Guardix-SG® help improve shoulder ROM without causing adverse effects in patients who underwent breast cancer surgery. However, there was no statistically significant difference from the control group. A further large-scale study is needed to obtain a more conclusive conclusion. TRIAL REGISTRATION CRISKCT0003386; https://cris.nih.go.kr (20181207).
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2.
An autologous protein gel for soft tissue augmentation: in vitro characterization and clinical evaluation.
Fedyakova, E, Pino, A, Kogan, L, Eganova, C, Troya, M, Anitua, E
Journal of cosmetic dermatology. 2019;(3):762-772
Abstract
BACKGROUND The aging process affects all organs of the body, but the skin is the most visible indicator with a great psychosocial impact. As a consequence, many skin anti-aging strategies have been developed to minimize, postpone, and even reverse the aging process. Growth factors have been widely studied in skin wound healing as these polypeptides play an essential role in the complex process of tissue regeneration. Recently, a novel 3D injectable gel based on the autologous technology platelet rich in growth factor has been described. OBJECTIVES In this study, a comparison between hyaluronic acid (HA, the gold standard for skin rejuvenation), and this novel autologous formulation has been conducted. METHODS Rheological and mechanical properties were determined. The in vitro biological capacity of both treatments on human dermal fibroblasts proliferation, migration, chemotaxis, and extracellular matrix synthesis was also assessed. Additionally, a clinical evaluation of the autologous platelet gel treatment was performed by macrophotographs, ultrasound analyses, and clinical and patient surveys. RESULTS The autologous gel outperformed the general biomechanical properties of HA and kept an optimal viscoelastic gel-like behavior for soft tissue augmentation. Both formulations stimulated cell chemotaxis, migration, and type I collagen synthesis. The autologous gel induced a statistically higher cell proliferation. After the autologous formulation treatment, a soft tissue augmentation effect was also noticed along with an overall skin quality improvement in terms of hydration, elasticity, wrinkle reduction, and general satisfaction scores. CONCLUSIONS This novel injectable formulation has desirable mechanical and bioactive properties for 3D tissue regeneration and might offer a safe and effective treatment for depressed areas of the skin.
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3.
Safety and tolerability of intradiscal implantation of combined autologous adipose-derived mesenchymal stem cells and hyaluronic acid in patients with chronic discogenic low back pain: 1-year follow-up of a phase I study.
Kumar, H, Ha, DH, Lee, EJ, Park, JH, Shim, JH, Ahn, TK, Kim, KT, Ropper, AE, Sohn, S, Kim, CH, et al
Stem cell research & therapy. 2017;(1):262
Abstract
BACKGROUND Adipose tissue-derived mesenchymal stem cells (AT-MSCs) offer potential as a therapeutic option for chronic discogenic low back pain (LBP) because of their immunomodulatory functions and capacity for cartilage differentiation. The goal of this study was to assess the safety and tolerability of a single intradiscal implantation of combined AT-MSCs and hyaluronic acid (HA) derivative in patients with chronic discogenic LBP. METHODS We performed a single-arm phase I clinical trial with a 12-month follow-up and enrolled 10 eligible chronic LBP patients. Chronic LBP had lasted for more than 3 months with a minimum intensity of 4/10 on a visual analogue scale (VAS) and disability level ≥ 30% on the Oswestry Disability Index (ODI). The 10 patients underwent a single intradiscal injection of combined HA derivative and AT-MSCs at a dose of 2 × 107 cells/disc (n = 5) or 4 × 107 cells/disc (n = 5). Safety and treatment outcomes were evaluated by assessing VAS, ODI, Short Form-36 (SF-36), and imaging (lumbar spine X-ray imaging and MRI) at regular intervals over 1 year. RESULTS No patients were lost at any point during the 1-year clinical study. We observed no procedure or stem cell-related adverse events or serious adverse events during the 1-year follow-up period. VAS, ODI, and SF-36 scores significantly improved in both groups receiving both low (cases 2, 4, and 5) and high (cases 7, 8, and 9) cell doses, and did not differ significantly between the two groups. Among six patients who achieved significant improvement in VAS, ODI, and SF-36, three patients (cases 4, 8, and 9) were determined to have increased water content based on an increased apparent diffusion coefficient on diffusion MRI. CONCLUSIONS Combined implantation of AT-MSCs and HA derivative in chronic discogenic LBP is safe and tolerable. However, the efficacy of combined AT-MSCs and HA should be investigated in a randomized controlled trial in a larger population. TRIAL REGISTRATION ClinicalTrials.gov NCT02338271 . Registered 7 January 2015.
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4.
Viscoelastic substance in prefilled syringe as an etiology of Toxic Anterior Segment Syndrome.
Althomali, TA
Cutaneous and ocular toxicology. 2016;(3):237-41
Abstract
CONTEXT Toxic Anterior Segment Syndrome (TASS) is an acute postoperative inflammatory reaction in which a noninfectious substance enters the anterior segment and induces toxic damage to the intraocular tissues. OBJECTIVE To present etiologic investigation of two consecutive clusters of TASS. TASS outbreak and investigation: This paper presents two consecutive clusters of TASS in 15 of the 24 uneventful surgeries and the investigation carried out to find the etiology. After the occurrence of first cluster of TASS, sterilization-related etiology was explored; however, we did not find any lacunae in the sterilization and cleaning process in the operating theater (OT). Nevertheless, multiple changes in cleaning process were implemented. Still a second cluster of TASS was encountered in the following session of OT. Several other factors which include preservatives, hand gloves, intraocular lenses, medications/solutions, intraocular penetration of topically administered drugs, and viscoelastics were investigated as the possible etiology of the second consecutive cluster of TASS; however, most of them were ruled out. The newly introduced viscoelastic I-visc® 1.4% sodium hyaluronate (I medical, i-Medical Ophthalmic International GmbH, Heidelberg, Germany) was thought to be the most likely cause and was replaced with previously in use sodium hyaluronate 1.5% and lidocaine hydrochloride 1% (Visthesia, CZ, Germany) in the following session of OT. No further TASS incident was encountered after replacing the viscoelastic. CONCLUSION Investigation revealed that 1.4% sodium hyaluronate in prefilled syringe (PFS) (I-visc® 1.4%) was the etiologic factor of two consecutive clusters of TASS. While TASS due to residual denatured ophthalamic viscosurgical devices (OVDs) is a common knowledge, current study brings out that even disposable viscoelastic material supplied in PFSs can be an etiology of TASS. It is important to recognize that contamination of OVDs with endotoxins can occur at the time of manufacturing. Therefore, in the absence of appropriate guidelines for ophthalmic preparations, endotoxin limit for medical preparations (i.e. <0.5 endotoxin units/ml) must be considered during OVD manufacture.
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5.
Sodium hyaluronate and chondroitin sulfate replenishment therapy can improve nocturia in men with post-radiation cystitis: results of a prospective pilot study.
Gacci, M, Saleh, O, Giannessi, C, Detti, B, Livi, L, Monteleone Pasquetti, E, Masoni, T, Finazzi Agro, E, Li Marzi, V, Minervini, A, et al
BMC urology. 2015;:65
Abstract
BACKGROUND Radiotherapy is one of the treatment options for prostate cancer (PCa) but up to 25% of men report about severe nocturia (nocturnal voiding). The combination of hyaluronic acid (HA) and chondroitin sulfate (CS) resembles glycosaminoglycan (GAG) replenishment therapy. The aim of our study was to evaluate the impact of HA and CS on nocturia, in men with nocturia after PCa radiotherapy. METHODS Twenty-three consecutive patients with symptomatic cystitis after external radiotherapy for PCa were enrolled. Patients underwent bladder instillation therapy with HA and CS weekly for the first month and, afterwards, on week 6, 8 and 12. Nocturnal voiding frequency was assessed by item 3 (Q3) of the Interstitial Cystitis Symptoms Index (ICSI) and item 2 (Q2) of the Interstitial Cystitis Problem Index (ICPI). Data were analyzed with paired-samples T-test and adjusted for age. RESULTS Eighteen patients (78%) reported about nocturia. Pre- and post-treatment ICSI-Q3 was 2.13 ± 0.28 and 1.61 ± 0.21 (-24.4%, p = 0.001). With logistic regression analysis, both age and baseline ICSI-Q3 had a significant impact on nocturnal voiding frequency (r = 0.293, p = 0.011 and r = 0.970, p < 0.001). Pre- and post-treatment ICPI-Q2 was 1.87 ± 0.26 and 1.30 ± 0.25 (-30.5%, p = 0.016); logistic regression analysis was without significant findings. CONCLUSION Bladder instillation treatment with a combination of HA and CS was effective in reducing nocturnal voiding frequency in men with post-radiation bladder pain for PCa. Randomized, controlled trials with sham treatment are needed to confirm our result.
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6.
Proteomic analysis of osteoarthritic chondrocyte reveals the hyaluronic acid-regulated proteins involved in chondroprotective effect under oxidative stress.
Yu, CJ, Ko, CJ, Hsieh, CH, Chien, CT, Huang, LH, Lee, CW, Jiang, CC
Journal of proteomics. 2014;:40-53
Abstract
UNLABELLED Osteoarthritis (OA), the most common type of arthritis, is a degenerative joint disease. Oxidative stress is well known to play important roles in cartilage degradation and pathogenesis of OA. The intra-articular injection of hyaluronic acid (IAHA) is accepted as an effective clinical therapy for OA, but we do not yet fully understand the mechanisms underlying the effects of HA on OA chondrocytes under oxidative stress. Here, we show for the first time that IAHA significantly reduces the synovial fluid levels of hydrogen peroxide (H2O2) and superoxide (O2(-)) in patients with knee OA. We also demonstrate that HA suppresses H2O2-induced cell death in human OA chondrocytes. Proteomic approaches (2-DE combined with mass spectrometry) allowed us to identify 13 protein spots corresponding to 12 non-redundant proteins as HA-regulated proteins in OA chondrocytes under oxidative stress. The expression levels of three putative HA-regulated proteins (TALDO, ANXA1 and EF2) in control, H2O2-, HA- and HA/H2O2-treated OA chondrocytes were verified by Western blotting and the results indeed support the notion that HA acts in anti-oxidation, anti-apoptosis, and the promotion of cell survival. Our results collectively demonstrate the utility of proteomic approaches and provide new insights into the chondroprotective effects of HA on OA. BIOLOGICAL SIGNIFICANCE In the present study, we show for the first time that IAHA reduces the levels of H2O2 and O2(-) in synovial fluids from OA patients. We used primary cultured human OA chondrocytes as a model, treated cells with H2O2 to partly mimic their physiological conditions under oxidative stress, and examined the protection effects of HA. The proteomic approach allowed us to identify candidate proteins regulated by H2O2 and/or HA in OA chondrocytes. We found that proteins functioning in stress responses, apoptosis and protein synthesis were consistently regulated by HA in chondrocytes under oxidative stress. These novel results contribute to our understanding of the molecular mechanisms underlying HA-mediated chondroprotection.
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7.
Multivalent dendrimers presenting spatially controlled clusters of binding epitopes in thermoresponsive hyaluronan hydrogels.
Seelbach, RJ, Fransen, P, Peroglio, M, Pulido, D, Lopez-Chicon, P, Duttenhoefer, F, Sauerbier, S, Freiman, T, Niemeyer, P, Semino, C, et al
Acta biomaterialia. 2014;(10):4340-50
Abstract
The controlled presentation of biofunctionality is of key importance for hydrogel applications in cell-based regenerative medicine. Here, a versatile approach was demonstrated to present clustered binding epitopes in an injectable, thermoresponsive hydrogel. Well-defined multivalent dendrimers bearing four integrin binding sequences and an azido moiety were covalently grafted to propargylamine-derived hyaluronic acid (Hyal-pa) using copper-catalyzed alkyne-azide cycloaddition (CuAAC), and then combined with pN-modified hyaluronan (Hyal-pN). The dendrimers were prepared by synthesizing a bifunctional diethylenetriamine pentaacetic acid core with azido and NHBoc oligo(ethylene glycol) aminoethyl branches, then further conjugated with solid-phase synthesized RGDS and DGRS peptides. Azido terminated pN was synthesized by reversible addition-fragmentation chain transfer polymerization and reacted to Hyal-pa via CuAAC. Nuclear magnetic resonance (NMR), high performance liquid chromatography, size exclusion chromatography and mass spectroscopy proved that the dendrimers had well-defined size and were disubstituted. NMR and atomic absorption analysis confirmed the hyaluronan was affixed with dendrimers or pN. Rheological measurements demonstrated that dendrimers do not influence the elastic or viscous moduli of thermoresponsive hyaluronan compositions at a relevant biological concentration. Finally, human mesenchymal stromal cells were encapsulated in the biomaterial and cultured for 21days, demonstrating the faculty of this dendrimer-modified hydrogel as a molecular toolbox for tailoring the biofunctionality of thermoresponsive hyaluronan carriers for biomedical applications.
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8.
Intra-articular injections of hyaluronic acid in osteoarthritis of the subtalar joint: a pilot study.
Mei-Dan, O, Carmont, M, Laver, L, Mann, G, Maffulli, N, Nyska, M
The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons. 2013;(2):172-6
Abstract
We evaluated the efficacy of intra-articular viscosupplementation with sodium hyaluronate in the management of osteoarthritis of the subtalar joint. A total of 22 patients, aged 22 to 72 years (mean 53), with symptomatic subtalar joint osteoarthritis of 1 to 20 years' duration (mean 4.2) and a severity of Kellgren-Lawrence grade II to IV and Paley and Hall grade 1 to 3, were entered into the present study. Intra-articular injections of 10 mg sodium hyaluronate (Euflexxa) were administered weekly to the subtalar joint for 3 weeks. Clinical evaluations and objective scoring using the American Orthopaedic Foot and Ankle Society Ankle Hindfoot score, visual analog scale, maximum walking distance, pain frequency, and subjective global function were performed at baseline and 4, 12, and 28 weeks after treatment. Significant improvement occurred in the American Orthopaedic Foot and Ankle Society Ankle Hindfoot scores (baseline score 54.5, week 28 score 73.7; p < .01) and visual analog scale assessment (baseline pain, stiffness, and function score 5.4, 5.8, and 6.9; week 28 pain, stiffness, and function score 2.8, 3.1, and 3.8, respectively; p < .01). Global assessment showed improvement in 18 of 20 patients completing the study (p < .01). The tolerated walking distance significantly improved from 770 ± 886 m to 2,075 ± 1,500 m (p < .001). Improvement lasted for more than 6 months. Intra-articular injection of sodium hyaluronate should be considered in the conservative management of subtalar osteoarthritis.
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9.
Multicenter clinical trial on the performance and tolerability of the Hyaluronic acid-collagenase ointment for the treatment of chronic venous ulcers: a preliminary pilot study.
Gravante, G, Sorge, R, Giordan, N, Georgescu, SR, Morariu, SH, Stoicescu, I, Clatici, V
European review for medical and pharmacological sciences. 2013;(20):2721-7
Abstract
BACKGROUND Bed debridement is important to treat chronic wounds. Effective agents should remove the necrosis but protect the granulation tissue. We evaluated the performance and tolerability of a new composite ointment containing collagenase and hyaluronic acid for chronic venous ulcers. PATIENTS AND METHODS Subjects with class 6 venous ulcers (CEAP classification) of at least 6 months duration were prospectively recruited. The ointment was administered daily and follow-up visits were conducted on the fifth, 10th, 15th and 20th days. On each visit the necrotic area was measured with a grid. The moisture balance, odour, viability of non-necrotic areas and the presence of erythema were also assessed. Primary outcome was the percentage of subjects with complete debridement, secondary outcomes the time to complete healing, reduction of the lesion area, absence of necrotic tissue, presence of odor, erythema, hydration, any adverse events. RESULTS One hundred subjects were enrolled in four centres. All patients achieved complete debridement of the necrotic area and a significant reduction of the total ulcer area by day 20, while other parameters improved significantly over time. Only two patients experienced a transient leg oedema. CONCLUSIONS The combination of collagenase and hyaluronic acid is safe and effective for chronic venous ulcers.
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10.
Ultrasound-guided subacromial injections of sodium hyaluronate for the management of rotator cuff tendinopathy: a prospective comparative study with rehabilitation therapy.
Merolla, G, Bianchi, P, Porcellini, G
Musculoskeletal surgery. 2013;:49-56
Abstract
BACKGROUND Rotator cuff (RC) tendinopathy is a common cause of pain and shoulder dysfunction. The literature evidence suggests that a combination of overuse and extrinsic compression may induce chronic RC tendinopathy. Aim of the current study was to compare the results of subacromial sodium hyaluronate injections with rehabilitation therapy. MATERIALS AND METHODS We enrolled 48 patients (M/F: 26/22; mean age: 50 years; shoulder right/left: 29/19) with persistent shoulder pain for at least 4 months. Exclusion criteria were as follows: RC tear, calcifying tendinitis, glenohumeral instability, osteoarthritis, rheumatic diseases, physical therapy and/or injection in the previous 4 months, shoulder surgery, anesthetic nerve block, trauma, and severe medical diseases. The included subjects received either two ultrasound-guided subacromial hyaluronic acid (HA) injections (25 patients, HA group) at baseline and 14 days, or underwent rehabilitation therapy (23 patients, Physio group) including active shoulder mobilization, soft tissue stretching and humeral head positioner and propeller muscles strengthening for 30 days (3 sessions every week). Clinical assessment of shoulder function was performed with visual analog scale score for pain (0-100), Oxford Shoulder Score (OSS), and Constant-Murley Score (CS). Overall, patients were examined at baseline, week 2, week 4, week 12, and week 24. Statistical significance was set at 5 % (p < 0.05). RESULTS Reduction in overall pain in the HA group was statistically significant at week 2 (p < 0.05) week 4 (p < 0.05), week 12 comparing to baseline. Similarly, pain subscores (at night and with activity) were significantly lower at week 2 (p < 0.05), week 4 (p < 0.05), and week 12 (p < 0.05), respectively. In the Physio group, pain decreased significantly at week 2 (p < 0.05) but not maintained at week 4 (p > 0.05), week 12 (p > 0.05), and week 24 (p > 0.05). CS and OSS in the HA group increased significantly at week 2 (p < 0.05), week 4 (p < 0.05), and week 12 (p < 0.05). A non-statistically significant increase in clinical scores was found at week 24 (p > 0.05). A significant improvement of CS and OSS we found in the Physio group at week 2 (p < 0.05), but not at weeks 4, 12, and 24 (p > 0.05). CONCLUSIONS Subacromial HA injections could be an effective and safe alternative treatment for patients suffering from RC tendinopathy. We believe that the results of this study are encouraging but not lasting and we might suppose that a series of three to four subacromial sodium hyaluronate injections could provide good mid- and long-term clinical benefits.