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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.
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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3.
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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4.
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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5.
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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6.
Efficacy of a spray compound containing a pool of collagen precursor synthetic aminoacids (l-proline, l-leucine, l-lysine and glycine) combined with sodium hyaluronate to manage chemo/radiotherapy-induced oral mucositis: preliminary data of an open trial.
Colella, G, Cannavale, R, Vicidomini, A, Rinaldi, G, Compilato, D, Campisi, G
International journal of immunopathology and pharmacology. 2010;(1):143-51
Abstract
Oral mucositis (OM) is a very frequent and potentially severe complication experienced by patients receiving chemotherapy and/or radiotherapy, which often leads to significant morbidity and mortality, and decreased quality of life, and is very costly. Despite its severity and prevalence, there is no standard recognised management today. The aim of this open clinical trial is to evaluate the efficacy and compliance of a new spray compound containing sodium hyaluronate (SH) and a pool of collagen precursor amino acids (AAs) combined with sodium hyaluronate (SH) to manage radio/chemotherapy-induced OM. Twenty-seven consecutive patients with OM were treated according to the manufacturers instructions. At time T0 (baseline before intervention), we evaluated the following parameters: (i) pain score (by linear visual analogue scale; 0100) and (ii) severity of OM scored according to WHO Mucositis scale. The treatment efficacy was evaluated on i) pain score, ii) clinical resolution index (CRI) and iii) patient compliance at times T01 (after 2 hours), T1 (after 24 hours), T2 (after 72 hours), T3 (after 7 days) and T4 (after 14 days). Results showed that painful symptoms were significantly reduced after only 2 hours of spray administration compared with baseline measurements (p less than 0.0001; z=-4.541). A progressive reduction of pain through the 2 weeks was also noted (p less than 0.0001). Patient lesions treated with SH-Asbased spray also significantly improved after 72 hours of treatment (p=0.0051; z=-2.803). During the two-week observation, all patients significantly improved from the baseline (p less than 0.0001) and progressively ameliorated their ability to swallow foods and liquids. The compliance of all patients to the product was very good, and at the end of the study there were no adverse effects. The results suggest that the SHAAs-based spray accelerates lesion healing and above all helps to manage mucositis pain, especially in terms of immediate pain relief (after 2 hours from application). Although further randomized controlled studies are recommended, our findings suggest that frequent applications of this spray may offer rapid and effective pain management, aiding faster mucosal wound healing.
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7.
[Influence of intra-articular injections of sodium hyaluronate on clinical features and synovial fluid nitric oxide levels of temporomandibular osteoarthritis].
Guarda Nardini, L, Oliviero, F, Ramonda, R, Ferronato, G
Reumatismo. 2004;(4):272-7
Abstract
OBJECTIVE This study was designed to assess the effect of intra-articular injection of sodium hyaluronate (SH) on clinical findings of temporomandibular osteoarthritis (OA) and on synovial fluid (SF) levels of nitric oxide (NO). METHODS Twenty seven patients (7 men, 20 women, mean (SD) age 53.9 (11.8) years) with OA of the temporomandibular joint were randomly allocated to receive an injection of either SH (2 ml, Hyalgan, Fidia SpA, Abano T., P.M. 500-700.000, 20 mg/2 ml; once a week for 5 weeks) or a Ringer's lactate solution (once a week for 3 weeks). Clinical evaluation was done before each procedure, and at 1 week, 1, 3 and 6 months post-injection. Intensity of temporomandibular joint pain, jaw function, maximal mouth opening and lateral jaw movements were recorded at each visit. NO was measured on SF collected by rinsing the joint with saline 1 ml before the treatment. RESULTS Injection of SH caused significant improvement in the main clinical symptoms until the last follow-up which was carried out 6 months after last injection. Among patients who received SH injection, those who reached a good outcome showed the lowest basal levels of NO. CONCLUSIONS The results of this study showed that intra-articular injections of SH lead to a lasting improvement in the clinical symptoms of temporomandibular OA. Furthermore, our findings suggest that low NO levels in SF are related to a better outcome of temporomandibular OA among patients treated with SH intra-articular injection.
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8.
Morphological analysis of articular cartilage biopsies from a randomized, clinical study comparing the effects of 500-730 kDa sodium hyaluronate (Hyalgan) and methylprednisolone acetate on primary osteoarthritis of the knee.
Guidolin, DD, Ronchetti, IP, Lini, E, Guerra, D, Frizziero, L
Osteoarthritis and cartilage. 2001;(4):371-81
Abstract
OBJECTIVE Histomorphometric study on cartilage samples taken from osteoarthritic human knees before and 6 months after intraarticular injections of a specific fraction (500-730 kDa) of hyaluronan. The results obtained with hyaluronan were compared with the results of methylprednisolone acetate treatment. METHODS Twenty-four subjects with primary osteoarthritis (OA) of the knee were considered. Eleven patients were treated with Hyaluronan (Hyalgan), 20 mg/2 ml once a week for 5 weeks) and 13 with methylprednisolone (Depo-Medrol, 40 mg/1 ml once a week for 3 weeks). At the time of baseline and after 6 months from the start of treatment, biopsies of cartilage were taken and processed for electron microscopy. Articular surface morphology, territorial matrix, chondrocyte number and ultrastructure were characterized by a set of morphometric parameters. Samples from 19 informed patients showing no arthroscopic sign of OA were also used for comparison. RESULTS Six months after hyaluronan treatment a significant reconstitution of the superficial layer were observed together with an improvement in chondrocyte density and territorial matrix appearance. Furthermore, chondrocytes appeared significantly improved in their metabolism, as indicated by the increased extension of the synthetic structures and mitochondria with respect to the organelles having catabolic or storage functions. Hyaluronan treatment produced results that were significantly superior to those delivered with Methylprednisolone in almost all the morphometric estimators. CONCLUSIONS These results cannot be explained simply by temporary restoration of the synovial fluid viscoelasticity, and provide further evidence that the specific fraction of hyaluronan used in this study is a useful tool in OA treatment, with a potential structure-modifying activity.