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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Clinical efficacy of multiple intra-articular injection for hip osteoarthritis.

Aims: Intra-articular (IA) injection may be used when treating hip osteoarthritis (OA). Common injections include steroids, hyaluronic acid (HA), local anaesthetic, and platelet-rich plasma (PRP). Network meta-analysis allows for comparisons between two or more treatment groups and uses direct and indirect comparisons between interventions. This network meta-analysis aims to compare the efficacy of various IA injections used in the management of hip OA with a follow-up of up to six months. Methods: This systematic review and network meta-analysis used a Bayesian random-effects model to evaluate the direct and indirect comparisons among all treatment options. PubMed, Web of Science, Clinicaltrial.gov, EMBASE, MEDLINE, and the Cochrane Library were searched from inception to February 2023. Randomized controlled trials (RCTs) which evaluate the efficacy of HA, PRP, local anaesthetic, steroid, steroid+anaesthetic, HA+PRP, and physiological saline injection as a placebo, for patients with hip OA were included. Results: In this meta-analysis of 16 RCTs with a total of 1,735 participants, steroid injection was found to be significantly more effective than placebo injection on reported pain at three months, but no significant difference was observed at six months. Furthermore, steroid injection was considerably more effective than placebo injection for functional outcomes at three months, while the combination of HA+PRP injection was substantially more effective at six months. Conclusion: Evidence suggests that steroid injection is more effective than saline injection for the treatment of hip joint pain, and restoration of functional outcomes.

High-molecular-weight Hyaluronan Administration Inhibits Bone Resorption and Promotes Bone Formation in Young-age Osteoporosis Rats.

Osteoporosis poses a significant global health concern, affecting both the elderly and young individuals, including athletes. Despite the development of numerous antiosteoporotic drugs, addressing the unique needs of young osteoporosis patients remains challenging. This study focuses on young rats subjected to ovariectomy (OVX) to explore the impact of high-molecular-weight hyaluronan (HA) on preventing OVX-induced osteoporosis. Twenty-four rats underwent OVX, while 12 underwent sham procedures (sham control group). Among the OVX rats, half received subcutaneous injections of HA (MW: 2700 kDa) at 10 mg/kg/week into their backs (OVX-HA group), whereas the other half received saline injections (0.5 ml/week) at the same site (OVX-saline group). OVX-HA group exhibited significantly higher percentages of osteoclast surface (Oc. S/BS), osteoblast surface per bone surface (Ob. S/BS), and bone volume/tissue volume (BV/TV) compared with OVX-saline group at the same age. The proportions of Ob. S/BS and BV/TV in the OVX-HA group closely resembled those of the sham control group, whereas the proportion of Oc. S/BS in the OVX-HA group was notably higher than that in the sham control group. In summary, the administration of HA significantly mitigated bone resorption and enhanced bone formation, suggesting a crucial role for HA in the treatment of young adult osteoporosis.

A comparative analysis of 3D bioprinted gelatin-hyaluronic acid-alginate scaffold and microfracture for the management of osteochondral defects in the rabbit knee joint.

OBJECTIVES: This study aims to compare the radiological, biomechanical, and histopathological results of microfracture treatment and osteochondral damage repair treatment with a new scaffold product produced by the three-dimensional (3D) bioprinting method containing gelatin-hyaluronic acid-alginate in rabbits with osteochondral damage. MATERIALS AND METHODS: A new 3D bioprinted scaffold consisting of gelatin, hyaluronic acid, and alginate designed by us was implanted into the osteochondral defect created in the femoral trochlea of 10 rabbits. By randomization, it was determined which side of 10 rabbits would be repaired with a 3D bioprinted scaffold, and microfracture treatment was applied to the other knees of the rabbits. After six months of follow-up, the rabbits were sacrificed. The results of both treatment groups were compared radiologically, biomechanically, and histopathologically. RESULTS: None of the rabbits experienced any complications. The magnetic resonance imaging evaluation showed that all osteochondral defect areas were integrated with healthy cartilage in both groups. There was no significant difference between the groups in the biomechanical load test (p=0.579). No statistically significant difference was detected in the histological examination using the modified Wakitani scores (p=0.731). CONCLUSION: Our study results showed that 3D bioprinted scaffolds exhibited comparable radiological, biomechanical, and histological properties to the conventional microfracture technique for osteochondral defect treatment.

A randomized controlled clinical trial of concentrated growth factor combined with sodium hyaluronate in the treatment of temporomandibular joint osteoarthritis.

OBJECTIVE: To investigate the effect of concentrated growth factor (CGF) combined with sodium hyaluronate (SH) on temporomandibular joint osteoarthritis (TMJOA). METHODS: Sixty patients with TMJOA who were diagnosed by cone-beam computed tomography (CBCT) between March 2020 and March 2023 at the Stomatological Hospital of Xi'an Jiaotong University were randomly divided into a control group (n = 30) and an experimental group (n = 30). The patients in the experimental group were treated with CGF + SH, and those in the control group were treated with SH only. The visual analogue scale (VAS) score indicating pain in the temporomandibular joint (TMJ) area; the Helkimo Clinical Dysfunction Index (Di); and changes in condylar CBCT at the first visit and 2 weeks, 3 months and 6 months after treatment were recorded. The CBCT data of the patients in the experimental and control groups were collected, and the three-dimensional CBCT image sequences were imported into Mimics Medical 19.0 software in DICOM format for condylar reconstruction. RESULTS: The VAS scores at 2 weeks, 3 months and 6 months after treatment were significantly lower in the experimental group than in the control group (P < 0.05), and the pain in the experimental group was significantly relieved. The Di was significantly lower in the experimental group than in the control group (P < 0.05), and the clinical function of the TMJ improved. After treatment, the CBCT score was significantly lower in the experimental group than in the control group (P < 0.05), and the condylar bone cortex was obviously repaired. Observation of the condylar bone cortex by three-dimensional reconstruction showed the same results as those obtained by CBCT. CONCLUSION: CGF combined with SH is effective in the treatment of TMJOA and can improve muscle pain, TMJ pain, Impaired TMJ function, Impaired range of movement, Pain on movement of the mandible and promote bone repair. THE REGISTRATION NUMBER (TRN): ChiCTR2400082712. THE DATE OF REGISTRATION: April 5, 2024.

Conservative treatment of Peyronie's disease: a guide.

PURPOSE: To review the literature on the topic, to suggest a common line of treatment applicable across a wide community of specialists, and to contribute in maintaining the high level of interest in this disease. METHODS: A comprehensive and exhaustive review of the literature was performed, identifying hundreds of articles on the topic. RESULTS: Peyronie's disease is a condition that has been recognized, studied, and treated for centuries; despite this, if one excludes surgery in cases in which the deformity is stable, no clear treatment (or line of treatment) is available for complete relief of signs and symptoms. Treatment options were divided into local, oral, and injection therapy, and a wide variety of drugs, remedies, and options were identified. CONCLUSIONS: Low-intensity extracorporeal shock wave therapy, vacuum therapy, penile traction therapy, phosphodiesterase type 5 inhibitors, hyaluronic acid, and collagenase of Clostridium histolyticum may be recommended only in specific contexts. Further studies on individual options or potential combinations are required.