Low molecular weight 35 kDa hyaluronan fragment HA35 in the treatment of bone metastasis pain: A case report.

RATIONALE: Late-stage cancer patients often experience severe pain due to bone metastasis, caused by structural damage and cancer-induced inflammation. Hyaluronan, known to alleviate pain by blocking the TRVP1 calcium channel, faces limitations due to its high molecular weight. However, 35 kDa low molecular weight hyaluronan fragment (HA35) have shown promise in relieving various pains, including cancer-related pain. Nonetheless, evidence regarding their efficacy in bone metastasis pain remains scarce. PATIENTS CONCERNS: A 52-year-old female with a rectal malignant tumor and multiple secondary tumors in the sacrum and lungs, accompanied by bone metastasis pain. Despite undergoing radiotherapy, her pain relief was unsatisfactory. Before treatment with HA35, her numerical rating scale score was 10, severely affecting her sleep, appetite, and daily activities. DIAGNOSES: The patient was diagnosed with rectal malignant tumor with multiple metastases, presenting symptoms such as sacral metastasis pain, anal pain, lower limb pain, and anterior abdominal pain. Sacral metastasis pain and lower limb pain indicated a clear diagnosis of bone metastasis pain. INTERVENTIONS: Treatment involved subcutaneous injection into the deep fat tissue layer of the abdomen. A subcutaneous injection of 100 mg/5 mL of HA35 was administered once into the deep fat tissue of the abdomen, with subsequent injections repeated every 3 days. OUTCOMES: Following 1 injection, the patient's pain score decreased to 6 points within 20 minutes, providing 40% pain relief. After 40 minutes, the score further dropped to 4 points, with 60% pain relief. After 50 injections, pain was consistently controlled at around 3 points. LESSONS SUBSECTIONS: Subcutaneous injection of HA35 into the abdominal fat tissue effectively alleviates pain in cancer and bone metastasis patients resistant to conventional treatments. Additionally, it helps alleviate anxiety and fatigue, and improves diet and sleep, thereby offering crucial palliative care for advanced cancer patients.

Predictors of Patient-Reported Outcomes After Hyaluronic Acid Injections: Effect of Expectations and Psychological Stress.

INTRODUCTION: Hyaluronic acid (HA) injections are a common nonsurgical treatment of knee osteoarthritis (OA). Patient expectations and psychological stress are believed to affect outcomes after orthopaedic procedures. METHODS: This was a prospective cohort study seeking to identify factors predictive of greater patient-reported outcomes after HA injections, particularly expectations and psychological stress. 250 patients receiving a series of HA injections for knee OA were enrolled, with 196 being included for analysis. Demographics, surgical history, and preoperative Kellgren-Lawrence severity scores were collected, and patients completed the Knee Osteoarthritis Outcome Score (KOOS) questionnaire, a modified KOOS questionnaire assessing their 6-month postinjection expectations, and the Perceived Stress Scale before the first injection. Outcomes were assessed at 3 weeks and 3 and 6 months after the final injection. RESULTS: KOOS scores improved from preinjection to 6-month follow-up but did not meet patients' expectations or minimal clinically important difference. Expectations correlated with 6-month KOOS pain, activities of daily living, sport, and quality of life subscales (ρ = 0.19 to 0.34), but not the symptom subscale (P = 0.10). Expectations (ρ = 0.31 to 0.37), younger age (ρ = -0.17 to -0.18), and greater perceived stress (ρ = 0.23) correlated with greater improvement from baseline KOOSs. Lower body mass index (ρ = -0.19 to -0.22), male sex (ρ = -0.17), and greater preinjection function (ρ = 0.37 to 0.46) correlated with greater 6-month outcomes. Stress measured on the Perceived Stress Scale did not correlate with 6-month KOOSs (P ≥ 0.27). Lower Kellgren-Lawrence severity score was weakly associated with greater 6-month KOOS activities of daily living and sport scores (ρ = -0.15 to -0.16) and greater improvement in the KOOS symptom score (ρ = -0.15). DISCUSSION: This study identified that higher expectations, lower body mass index, younger age, male sex, lower radiographic severity, greater preinjection function, and greater perceived stress are associated with greater patient outcomes after HA injection. Physicians should consider these factors when counseling patients with knee OA about viscosupplementation. STUDY TYPE: Prospective Cohort Study (Level of Evidence II).

Improved new bone formation capacity of hyaluronic acid-bone substitute compound in rat calvarial critical size defect.

BACKGROUND: Bone loss of residual alveolar ridges is a great challenge in the field of dental implantology. Deproteinized bovine bone mineral (DBBM) is commonly used for bone regeneration, however, it is loose and difficult to handle in clinical practice. Hyaluronic acid (HA) shows viscoelasticity, permeability and excellent biocompatibility. The aim of this study is to evaluate whether high-molecular-weight (MW) HA combined with DBBM could promote new bone formation in rat calvarial critical size defects (CSDs). MATERIALS AND METHODS: Rat calvarial CSDs (5 mm in diameter) were created. Rats (n = 45) were randomly divided into 3 groups: HA-DBBM compound grafting group, DBBM particles only grafting group and no graft group. Defect healing was assessed by hematoxylin-eosin staining and histomorphometry 2, 4 and 8 weeks postop, followed by Micro-CT scanning 8 weeks postop. Statistical analyses were performed by ANOVA followed by Tukey's post hoc test with P < 0.05 indicating statistical significance. RESULTS: All rats survived after surgery. Histomorphometric evaluation revealed that at 2, 4 and 8 weeks postop, the percentage of newly formed bone was significantly greater in HA-DBBM compound grafting group than in the other two groups. Consistently, Micro-CT assessment revealed significantly more trabecular bone (BV/TV and Tb.N) in HA-DBBM compound group than in the other two groups, respectively (P < 0.05). Moreover, the trabecular bone was significantly more continuous (Tb.Pf) in HA-DBBM compound group than in the other two groups, respectively (P < 0.05). CONCLUSION: HA not only significantly promoted new bone formation in rats calvarial CSDs but also improved the handling ability of DBBM.

Performance and Safety of Amino-Acid- and Hydroxyapatite Enriched-Hyaluronic Acid Intradermal Gel in Facial Skin Defects.

Background and Objectives: The facial skin defects associated with aging are common concerns in the aging population. Hyaluronic-acid-based intradermal gels have established themselves as safe and effective treatments for addressing these concerns. Recently developed enriched products aim to enhance the efficacy of these gels, yet their effectiveness lacks thorough validation in the existing literature. Materials and Methods: In this retrospective analysis, we investigated the outcomes of intradermal gel treatments in 103 patients with soft tissue defects. This study included three groups: 35 patients received amino-acid-enriched hyaluronic acid gel, another 35 were treated with hydroxyapatite-enriched hyaluronic acid gel, and the remaining 33 underwent hyaluronic acid treatment only. The efficacy of the treatments was assessed using the Global Aesthetic Improvement Scale (GAIS) score, while patient satisfaction was gauged through a detailed questionnaire. Any adverse event was monitored. Results: The treatments demonstrated remarkable efficacy, as evidenced by mean GAIS scores of 1.714 points for those treated with amino acid-enriched hyaluronic acid gel, 1.886 points for individuals receiving hydroxyapatite-enriched hyaluronic acid gel, and 1.697 for those treated with hyaluronic acid alone, all showing statistical significance (p < 0.0001). Patient satisfaction was very high. Significantly, there were no recorded instances of major adverse events. Conclusions: Hyaluronic gels, particularly those enriched with amino acids and hydroxyapatite, are effective and safe interventions for addressing facial skin aging defects. They serve as valuable tools in mitigating age-related blemishes and contribute to the overall improvement of skin aesthetics.

Can Hyaluronic Acid Combined with Chondroitin Sulfate in Viscosupplementation of Knee Osteoarthritis Improve Pain Symptoms and Mobility?

The objective of the present study was to assess the effect of intra-articular Hyaluronic acid (HA) and Chondroitin sulfate (CS) supplementation (Hialurom® Hondro (HH)) on pain symptoms and joint mobility. In total, 60 mg/mL sodium hyaluronate and 90 mg/mL CS were administered to 21 patients (17 females and 4 males) respecting the in-force requirements, excluding patients with some specific comorbidities. In addition to the clinical study (where the pain intensity (severity) and joint mobility were assessed), rheological characterization was conducted evaluating the following parameters: elastic modulus (G'), loss modulus (G″) oscillatory frequency (fc) at 0.5 Hz and 2.5 Hz, crossover frequency (fc), relaxation time (λ) where it was noticed that the addition of chondroitin sulfate (CS) to sodium hyaluronate (SH) significantly enhances and improves the viscoelastic properties, particularly at higher shear frequencies. A significant decrease in pain intensity felt by the subjects was found, from 7.48 (according to Wong-Baker scale)-pain close to 8 (the patient is unable to perform most activities), to more reduced values of 5.86-at 6 weeks after injection, 4.81-at 3 months after injection, and 5.24-at 6 months after injection, improvements in symptoms was fast and durable. Data related to the evolution of joint mobility show that at 6 weeks after injection, the mobility of joints increased by 17.8% and at 6 months by 35.61%. No serious adverse events were reported with undesired effects so that they would impose additional measures. Better resistance to enzymatic degradation and free radicals could be expected from the synergic combination of sodium hyaluronate and chondroitin sodium sulfate, this having a special importance for the patients, granting them the ability to perform more ample movements and reducing dependency on attendants, thus increasing quality of life.

Profhilo® Structura, Current Status and Future Perspectives: A Practical Review.

Hyaluronic acid (HA)-based injectables continue to grow in popularity and are used worldwide to improve facial changes associated with aging. Profhilo® Structura (IBSA Farmaceutici Italia, Lodi, Italy) is a novel HA-based product that uses nano hybrid complex of hyaluronic acid (NAHYCO)® technology to create hybrid cooperative complexes consisting of high and low molecular weight HA. Profhilo® Structura's high concentration (45 mg of total HA) and rheological properties (ie, viscosity [resistance to flow] and elasticity [stickiness]) have been specially formulated to restore facial adipose tissue. Because of their early involvement in the facial aging process, the superficial medial and lateral-temporal cheek fat compartments are good candidates for treatment. However, recommendations and guidelines are necessary to ensure that treatment is safe and effective. Three experts were invited to IBSA Farmaceutici Italia Srl to discuss clinical rationale, optimal injection techniques, and clinical outcomes for treating the superficial medial and lateral-temporal cheek fat compartments with Profhilo® Structura. These techniques were developed using patients presenting with either initial hypotrophy of fat compartments within the preauricular area (ie, sinkers) or jowl sagging due to hypotrophy within the preauricular and zygomatic areas (ie, saggers). Targeting these areas using the optimal injection site can maximize product diffusion and minimize the risk for vascular compromise. Targeting these areas also leads to lateral tightening and lipolifting effects due to adipose tissue restoration. The experts agreed that Profhilo® Structura is currently the first and only HA-based injectable treatment that can integrate and restore the adipose tissue in these affected fat compartments.

Clinical and Radiographic Evaluation of Intrabony Periodontal Defects Treated with Hyaluronic Acid or Enamel Matrix Proteins: A 6-Month Prospective Study.

PURPOSE: To compare the regenerative clinical and radiographic effects of cross-linked hyaluronic acid (xHyA) with enamel matrix proteins (EMD) at six months after regenerative treatment of periodontal intrabony defects. MATERIALS AND METHODS: Sixty patients presenting one intrabony defect each were randomly assigned into control (EMD) and test (xHyA) groups. Clinical attachment level (CAL) gain was the primary outcome, while pocket probing depth (PPD), gingival recession (REC), bleeding on probing (BOP), full-mouth plaque score (FMPS), full-mouth bleeding score (FMBS), and radiographic parameters such as defect depth (BC-BD), and defect width (DW) were considered secondary outcome variables. Parameters were recorded at baseline and after 6 months. RESULTS: At the 6-month follow-up, 54 patients were available for statistical analysis. In the control and test groups, the mean CAL gain was statistically significant in the intragroup comparison (p < 0.001). 48.1% of test sites showed a CAL gain ≤ 2 mm compared with 33.3% of control sites. The mean PPD reduction was statistically significant in the intragroup comparison in both groups (p < 0.001). The mean REC increase was similar in the two groups: 1.04 ± 1.29 mm vs 1.11 ± 1.22 mm (test vs control). The mean BC-BD, DW, FMPS, FMBS, and BOP changed statistically significantly only in the intragroup comparison, not in the intergroup comparison. CONCLUSION: Both treatments, EMD and xHyA, produced similar statistically significant clinical and radiographical improvements after six months when compared with baseline.

Treatment of Chronic Parastomal Ulceration with Silver Sulfadiazine and Hyaluronic Acid: Two Case Reports.

ABSTRACT: Skin complications in individuals with an ostomy are widely reported and can cause physical and emotional challenges in everyday life. Chronic parastomal skin complications can be difficult to heal and cause significant pain.Two patients presented to the stomal therapy clinic for treatment and were diagnosed with chronic parastomal skin ulceration. Following standard treatment of wound management, topical corticosteroid ointment, and appliance review, the ulcers either were not improving or had reoccurred. Treatment with a combination cream consisting of 0.2% hyaluronic acid and 1% silver sulfadiazine was initiated, and both patients demonstrated complete healing.Treatment of parastomal skin ulceration with dual-action cream 0.2% hyaluronic acid and 1% silver sulfadiazine was successful for these two patients, with a reduction in pain and purulent fluid noted throughout treatment, in addition to a reduced cost of treatment when compared with standard protocols.

Comparative efficacy of 0.1% and 0.15% Sodium Hyaluronate on lipid layer and meibomian glands following cataract surgery: A randomized prospective study.

PURPOSE: To compare the efficacy of a 0.15% HA with that of 0.1% HA eye drops for DES after cataract surgery. METHODS: This study was double blinded, randomized and prospective study, and conducted in 69 participants (70 eyes) from Pusan National University Yangsan Hospital and executed from February 1, 2022 to November 30, 2022. Participants were adult cataract patients with normal lid position, not suffering from any other ocular disease and not meet the exclusion cirteria of clinical trial. Participants were randomly divided into two groups: 35 participants (17 males and 18 females) in the 0.1% HA group and 34 participants (19 males and 15 females) in the 0.15% HA group, receiving treatment six times daily for 6 weeks following cataract surgery. Subjective and objective assessments were performed at preoperative and postoperative visits, including ocular surface disease index score, tear break up time, corneal staining score, Schirmer's I test score, lipid layer thickness), meiboscore, and biochemical analysis of the eye drops. RESULTS: Throughout the study, the postoperative ocular surface disease index score was significantly lower in the group receiving 0.15% hyaluronic acid than in the group receiving 0.1% hyaluronic acid. Additionally, the postoperative ocular surface disease index score showed a significant positive correlation with the postoperative use of 0.15% hyaluronic acid and the preoperative Schirmer's I test score. In multivariate analysis, treatment with 0.15% hyaluronic acid and the preoperative ocular surface disease index score were significant independent parameters affecting the postoperative ocular surface disease index score. CONCLUSION: The use of 0.15% hyaluronic acid is recommended for its potential advantages in alleviating symptoms following cataract surgery, making it a viable alternative to traditional 0.1% hyaluronic acid treatment. TRIAL REGISTRATION: ISRCTN95830348.

Advances in viscosupplementation and tribosupplementation for early-stage osteoarthritis therapy.

Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements that contain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.

Non-surgical interventions for treating osteoarthritis of the big toe joint.

BACKGROUND: Osteoarthritis (OA) affecting the first metatarsophalangeal joint (hallux rigidus) is common and painful. Several non-surgical treatments have been proposed; however, few have been adequately evaluated. Since the original 2010 review, several studies have been published necessitating this update. OBJECTIVES: To determine the benefits and harms of non-surgical treatments for big toe OA. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search was February 2023. SELECTION CRITERIA: We included randomised trials that compared any type of non-surgical treatment versus placebo (or sham), no treatment (such as wait-and-see) or other treatment. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. The major outcomes were pain, function, quality of life, radiographic joint structure, adverse events and withdrawals due to adverse events. The primary time point was 12 weeks. We used GRADE to assess the certainty of evidence. MAIN RESULTS: This update includes six trials (547 participants). The mean age of participants ranged from 32 to 62 years. Trial durations ranged from 4 to 52 weeks. Treatments were compared in single trials as follows: arch-contouring foot orthoses versus sham inserts; shoe-stiffening inserts versus sham inserts; intra-articular injection of hyaluronic acid versus saline (placebo) injection; arch-contouring foot orthoses versus rocker-sole footwear; peloid therapy versus paraffin therapy; and sesamoid mobilisation, flexor hallucis longus strengthening and gait training plus physical therapy versus physical therapy alone. Certainty of the evidence was limited by the risk of bias and imprecision. Meta-analysis was not performed due to the heterogeneity of interventions. We reported numerical data for the 12-week time point for the three trials that used a placebo/sham control group. Arch-contouring foot orthoses versus sham inserts One trial (88 participants) showed that arch-contouring foot orthoses probably lead to little or no difference in pain, function, or quality of life compared to sham inserts (moderate certainty). Mean pain (0-10 scale, 0 no pain) with sham inserts was 3.9 points compared to 3.5 points with arch-contouring foot orthoses; a difference of 0.4 points better (95% (CI) 0.5 worse to 1.3 better). Mean function (0-100 scale, 100 best function) with sham inserts was 73.3 points compared to 65.5 points with arch-contouring foot orthoses; a difference of 7.8 points worse (95% CI 17.8 worse to 2.2 better). Mean quality of life (-0.04-100 scale, 100 best score) with sham inserts was 0.8 points compared to 0.8 points with arch-contouring foot orthoses group (95% CI 0.1 worse to 0.1 better). Arch-contouring foot orthoses may show little or no difference in adverse events and withdrawal due to adverse events compared to sham inserts (low certainty). Adverse events (mostly foot pain) were reported in 6 out of 41 people with sham inserts and 4 out of 47 people with arch-contouring foot orthoses (RR 0.58, 95% CI 0.18 to 1.92). Withdrawals due to adverse events were reported in 0 out of 41 people with sham inserts and 1 out of 47 people with arch-contouring foot orthoses (Peto OR 6.58, 95% CI 0.13 to 331). Shoe-stiffening inserts versus sham inserts One trial (100 participants) showed that shoe-stiffening inserts probably lead to little or no difference in pain, function, or quality of life when compared to sham inserts (moderate certainty). Mean pain (0-100 scale, 0 no pain) with sham inserts was 63.8 points compared to 70.1 points with shoe-stiffening inserts; a difference of 6.3 points better (95% CI 0.5 worse to 13.1 better). Mean function (0-100 scale, 100 best function) with sham inserts was 81.0 points compared to 84.9 points with shoe-stiffening inserts; a difference of 3.9 points better (95% CI 3.3 worse to 11.1 better). Mean quality of life (0-100 scale, 100 best score) with sham inserts was 53.2 points compared to 53.3 points with shoe-stiffening inserts; a difference of 0.1 points better (95% CI 3.7 worse to 3.9 better). Shoe-stiffening inserts probably show little or no difference in adverse events (moderate-certainty) and may show little or no difference in withdrawal due to adverse events (low-certainty), compared to sham inserts. Adverse events (mostly foot pain, blisters, and spine/hip pain) were reported in 31 out of 51 people with sham inserts and 29 out of 49 people with shoe-stiffening inserts (RR 0.94, 95% CI 0.42 to 2.08). Withdrawals due to adverse events were reported in 1 out of 51 people with sham inserts and 2 out of 49 people with shoe-stiffening inserts (Peto OR 2.08, 95% CI 0.19 to 22.23). Hyaluronic acid versus placebo One trial (151 participants) showed that a single intra-articular injection of hyaluronic acid probably leads to little or no difference in pain or function compared to placebo (moderate certainty). Mean pain (0-100 scale, 0 no pain) with placebo was 72.5 points compared to 68.2 points with hyaluronic acid; a difference of 4.3 points better (95% CI 2.1 worse to 10.7 better). Mean function (0-100 scale, 100 best function) was 83.4 points with placebo compared to 85.0 points with hyaluronic acid; a difference of 1.6 points better (95% CI 4.6 worse to 7.8 better). Hyaluronic acid may provide little or no difference in quality of life (0-100 scale, 100 best score) which was 79.9 points with placebo compared to 82.9 points with hyaluronic acid; a difference of 3.0 better (95% CI 1.4 worse to 7.4 better; low certainty). There may be fewer adverse events with hyaluronic acid compared to placebo. Adverse events (mostly pain at the injection site) were reported in 43 out of 76 people with placebo compared with 27 out of 75 people with hyaluronic acid (RR 0.64, 95% CI 0.44 to 0.91; low certainty). No participants withdrew from either group due to adverse events. The effects on radiographic joint structure were not reported in any study. AUTHORS' CONCLUSIONS: The existing evidence regarding the benefits and harms of non-surgical treatments for big toe OA is limited. There is moderate-certainty evidence, based upon three single placebo/sham-controlled trials, that there are no clinically important benefits of arch-contouring foot orthoses, shoe-stiffening inserts, or a single intra-articular injection of hyaluronic acid. Further placebo-controlled trials are needed to evaluate the effectiveness of non-surgical treatments for big toe OA.

Early periodontal wound healing after chlorhexidine rinsing: a randomized clinical trial.

OBJECTIVES: This single-center randomized, parallel design, clinical trial with a 2-week follow-up involved patients affected by periodontitis undergoing periodontal surgery. The aim was to evaluate periodontal surgical wound healing with the use of chlorhexidine-based mouth rinses versus an untreated control group. MATERIALS AND METHODS: Periodontal surgery was performed following a standardized protocol. Patients were randomly prescribed i) chlorhexidine (CHX) + anti-discoloration system (ADS) + hyaluronic acid (HA), ii) CHX + ADS or iii) no treatment (control group). Plaque score, gingival inflammation, and Early Healing Index (EHI), assessing the degree of wound closure and the presence of fibrin and necrosis, were evaluated at 3, 7 and 14 days after surgery. RESULTS: In total, 33 patients were enrolled. Patients were comparable at baseline for all measured clinical parameters. At 3-days wound healing was significantly improved in all patients treated with CHX + ADS-based mouth rinses with a lower EHI score at the interdental papillae compared with control group (p < 0.01). CHX + ADS + HA group presented improved healing across all time points in terms of EHI, plaque containment, and gingival inflammation when compared to control group (p < 0.01). CONCLUSIONS: The usage of CHX-ADS following periodontal surgery improved early wound healing, reduced plaque accumulation and gingival inflammation. During the early post-operative period the adjunct of HA further improved soft tissue closure. CLINICAL RELEVANCE: This study aims at evaluating the response of gingival tissues to mouth rinsing with chlorhexidine and anti-discoloration system (CHX + ADS) or CHX + ADS + hyaluronic acid (CHX + ADS + HA) versus no rinse in terms of healing of the periodontal surgical wound. CHX + ADS mouth rinses enhanced early soft tissue closure after periodontal surgery and contributed to the reduction in plaque accumulation and gingival inflammation. The adjunct of HA may be beneficial especially in the early post-operative period. CHX + ADS administration following periodontal surgery may improve soft tissue healing in the first two post-operative weeks.

The efficacy of hyaluronic acid fragments with amino acid in combating facial skin aging: an ultrasound and histological study.

BACKGROUND: Various techniques have been employed in aesthetic medicine to combat skin aging, in particular that of the facial region. Hyaluronic acid is utilized to enhance moisture levels and extracellular matrix molecules. This study aims to histologically assess the effects of low molecular weight hyaluronic acid fragments combined with amino acids (HAAM) on facial skin rejuvenation through intradermal microinjections. METHODS: A total of twenty women, with an average age of 45 and ranging from 35 to 64 years old, participated in the study, including 8 in menopause and 12 in the childbearing age group. Mesotherapy was used to administer HAAM to the patients. Prior to and three months after the treatment, each patient underwent small circular punch biopsies. Ultrasound examinations were conducted using B-mode, capturing 2D images in longitudinal or transverse orientations with frequencies ranging from 5 to 13 Mega-hertz (MY LAB X8, ESAOTE, Genova, Italy). A total of 60 ultrasound examinations were taken, with 30 collected before treatment and 30 after treatment. RESULTS: The histological analysis demonstrates an increase in fibroblast activity resulting in the production of Type III reticular collagen, as well as an increased number of blood vessels and epidermal thickness. However, the analysis of ultrasound data before and after treatment showed no statistical difference in skin thickness in malar area, chin and mandibular angle. CONCLUSIONS: Histological assessments indicate that subcutaneous infiltration of HAAM has a substantial impact on the dermis of facial skin.

Hyaluronic acid as a pulpotomy material in primary molars: an up to 30 months retrospective study.

BACKGROUND: The aim of this retrospective study was to determine the long-term clinical and radiographic success of our previous randomized clinical trial and to compare the success of hyaluronic acid, with the widely used formocresol and ferric sulphate agents. METHODS: This retrospective study is the extension of the 1-year survey of our randomized clinical trial that had compared the effectiveness of a hyaluronic acid pulpotomy over formocresol and ferric sulphate pulpotomies and included clinical and radiographic evaluations with a follow-up period of over 24 months for 44 children who applied to our clinic between May 2019 and September 2019. Long-term clinical and radiographic data were obtained from the periodic files of our department, wherein each tooth's file was examined to identify any clinical and radiographic findings. Descriptive statistics and Pearson's chi-square tests were used to evaluate the data. Statistical significance was considered as p < 0.05. RESULTS: The clinical and radiographic success rates of the hyaluronic acid, formocresol, and ferric sulphate groups were not statistically different at > 24 months. None of the teeth in the hyaluronic acid group showed any clinical findings at > 24 months. CONCLUSIONS: Hyaluronic acid pulpotomies exhibited comparable success rates to formocresol and ferric sulphate materials spanning over 24 months examinations. Because of convenient accessibility and applicability of hyaluronic acid, it may be recommended as a promising alternative medicament for pulpotomy treatments of primary molars. However, further long-term follow-up human studies are needed to better understand the effect of hyaluronic acid on the dental pulp of human primary molars.

Assessment of the Feasibility of Objective Parameters as Primary End Points for Patients Affected by Knee Osteoarthritis: Protocol for a Pilot, Open Noncontrolled Trial (:SMILE:).

BACKGROUND: Osteoarthritis (OA) is a disabling condition that affects more than one-third of people older than 65 years. Currently, 80% of these patients report movement limitations, 20% are unable to perform major activities of daily living, and approximately 11% require personal care. In 2014, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) recommended, as the first step in the pharmacological treatment of knee osteoarthritis, a background therapy with chronic symptomatic slow-acting osteoarthritic drugs such as glucosamine sulfate, chondroitin sulfate, and hyaluronic acid. The latter has been extensively evaluated in clinical trials as intra-articular and oral administration. Recent reviews have shown that studies on oral hyaluronic acid generally measure symptoms using only subjective parameters, such as visual analog scales or quality of life questionnaires. As a result, objective measures are lacking, and data validity is generally impaired. OBJECTIVE: The main goal of this pilot study with oral hyaluronic acid is to evaluate the feasibility of using objective tools as outcomes to evaluate improvements in knee mobility. We propose ultrasound and range of motion measurements with a goniometer that could objectively correlate changes in joint mobility with pain reduction, as assessed by the visual analog scale. The secondary objective is to collect data to estimate the time and budget for the main double-blind study randomized trial. These data may be quantitative (such as enrollment rate per month, number of screening failures, and new potential outcomes) and qualitative (such as site logistical issues, patient reluctance to enroll, and interpersonal difficulties for investigators). METHODS: This open-label pilot and feasibility study is conducted in an orthopedic clinic (Timisoara, Romania). The study includes male and female participants, aged 50-70 years, who have been diagnosed with symptomatic knee OA and have experienced mild joint discomfort for at least 6 months. Eight patients must be enrolled and treated with Syalox 300 Plus (River Pharma) for 8 weeks. It is a dietary supplement containing high-molecular-weight hyaluronic acid, which has already been marketed in several European countries. Assessments are made at the baseline and final visits. RESULTS: Recruitment and treatment of the 8 patients began on February 15, 2018, and was completed on May 25, 2018. Data analysis was planned to be completed by the end of 2018. The study was funded in February 2019. We expect the results to be published in a peer-reviewed clinical journal in the last quarter of 2024. CONCLUSIONS: The data from this pilot study will be used to assess the feasibility of a future randomized clinical trial in OA. In particular, the planned outcomes (eg, ultrasound and range of motion), safety, and quantitative and qualitative data must be evaluated to estimate in advance the time and budget required for the future main study. Finally, the pilot study should provide preliminary information on the efficacy of the investigational product. TRIAL REGISTRATION: ClinicalTrials.gov NCT03421054; https://clinicaltrials.gov/study/NCT03421054. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/13642.

A review on revolutionizing ophthalmic therapy: Unveiling the potential of chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer in eye disease treatments.

Ocular disorders, encompassing both common ailments like dry eye syndrome and more severe situations for instance age-related macular degeneration, present significant challenges to effective treatment due to the intricate architecture and physiological barriers of the eye. Polysaccharides are emerging as potential solutions for drug delivery to the eyes due to their compatibility with living organisms, natural biodegradability, and adhesive properties. In this review, we explore not only the recent advancements in polysaccharide-based technologies and their transformative potential in treating ocular illnesses, offering renewed optimism for both patients and professionals but also anatomy of the eye and the significant obstacles hindering drug transportation, followed by an investigation into various drug administration methods and their ability to overcome ocular-specific challenges. Our focus lies on biological adhesive polymers, including chitosan, hyaluronic acid, cellulose, cyclodextrin, and poloxamer, known for their adhesive characteristics enhancing drug retention on ocular surfaces and increasing bioavailability. A detailed analysis of material designs used in ophthalmic formulations, such as gels, lenses, eye drops, nanofibers, microneedles, microspheres, and nanoparticles, their advantages and limitations, the potential of formulations in improving therapeutic outcomes for various eye conditions. Moreover, we underscore the discovery of novel polysaccharides and their potential uses in ocular drug delivery.

Anti-aging trends in Australia.

Anti-aging trends in Australia have changed considerably since the country emerged from the lockdowns associated with the SARS-Cov2 pandemic. People now rely on social media influencers for skin care advice and skin care products, including professional skin care treatments that can be purchased on Internet platforms. The quest for the perfect 'zoom face' led to a 300% rise in cosmetic procedures across Australia in the year to April 2021. People now want to use less products on their skin, while looking healthy and natural (termed 'skin minimalism'). The popularity of retinoid derivatives for preventing wrinkles has been superseded by non-irritating actives like hyaluronic acid (HA) and niacinamide that provide skin barrier protection, skin hydration, plumping and anti-inflammatory effects. Botulinum toxin injections remain the most popular non-surgical cosmetic procedure, followed by HA fillers, and biostimulators that promote the synthesis of collagen and give longer lasting but more gradual results than HA fillers. Laser resurfacing is widely used for epidermal resurfacing and skin tightening, as well as non-ablative lasers, intense pulsed light and radiofrequency or ultrasound skin tightening devices. Superficial chemical peels are still popular because they are relatively gentle, inexpensive, and require no downtime, whereas medium-to-deep chemical peels have largely been superseded by laser technology. However, the most efficient approach to prevent skin aging is adopting a healthy lifestyle and taking action against all factors of the skin aging exposome.

The Extended Utilization of Bulking Agents in Pediatric Urology.

PURPOSE OF REVIEW: Traditional surgical management for urinary incontinence and vesicoureteral reflux often requires complex reconstructive surgery and extended hospitalizations. Since the introduction of endoscopic bulking agents in 1973, there has been increasing interest in the use of endoscopic injection (EI) and bulking for the treatment of a variety of pediatric urologic disorders. The purpose of this review is to summarize the most recent literature addressing the use of bulking agents in pediatric urology. RECENT FINDINGS: The most recent literature has focused primarily on the use of EI of bulking agents at the bladder neck for the treatment of urinary incontinence. Other uses of EI of bulking agents has focused on the treatment of vesicoureteral reflux (VUR) in patients with anatomic abnormalities or treatment of incontinence catheterizable channels. The development of advanced techniques for endoscopic injection along with safe, stable bulking agents has allowed for the treatment of a variety of urologic conditions. This minimally invasive procedure offers an additional tool for the pediatric urologist's armamentarium in the treatment of urinary incontinence and VUR.

A clinical study of the local injection of a freshly manufactured 35 kDa hyaluronan fragment for treating chronic wounds.

This study manufactured a 35 kDa hyaluronan fragment (HA35) by enzymatically degrading high-molecular-weight HA using hyaluronidase PH20 derived from bovine testis. The research then examined the therapeutic efficacy of locally administered, tissue-permeable HA35 in alleviating chronic wounds and their associated neuropathic pain. For 20 patients with nonhealing wounds and associated pain lasting over three months, 100 mg of HA35 was injected daily into the healthy skin surrounding the chronic wound for 10 days. Self-assessments before and after treatment indicated that HA35 significantly enhanced wound healing. This was evidenced by the formation of fresh granulation tissue on the wounds (p < 0.0001); reduced darkness, redness, dryness, and damage in the skin surrounding the wounds (p < 0.0001), and a decrease in wound size (p < 0.001). Remarkably, HA35 injections alleviated pain associated with chronic wounds within 24 hours (p < 0.0001). It can be concluded that the low-molecular-weight hyaluronan fragment HA35 potentially enhances the immune response and angiogenesis during wound healing.