Search Results (43)

This prospective, single-arm, exploratory postmarketing study preliminarily evaluated the clinical response and plasma biomarker changes in 18 client-owned dogs with naturally occurring osteoarthritis (OA) treated with sodium hyaluronate (Bonharen). Patients received intravenous injections of Bonharen Intravenous at a dose of 0.15 mL/kg (1.3–1.6 mg/kg hyaluronic acid once a week for consecutive five weeks). Clinical parameters (lameness, joint pain, mobility, swelling) were assessed weekly and two weeks after the final dose was given via standardized scoring. The plasma concentrations of selected inflammatory, cartilage-related, and oxidative stress biomarkers were measured before treatment and two weeks after the final dose. Clinical improvement in lameness and/or joint pain on palpation was observed in nearly half of the patients. No clinical deterioration was recorded at any time point. Physical activity increased in all patients with reduced baseline activity. Significant decreases in the plasma levels of prostaglandin E₂, Δ17-6-keto prostaglandin F1α, malondialdehyde, and hyaluronan were detected, indicating reduced systemic inflammation and oxidative stress. In addition, an increase in plasma hydroxybutyrate and decrease in the collagen-breakdown marker prolyl-hydroxyproline were observed. No adverse effects were reported. These findings suggest that intravenous hyaluronic acid (Bonharen) may represent a safe and promising component to multimodal OA management in dogs and demonstrate the feasibility of integrating plasma biomarkers in canine OA studies. Full article

Post-traumatic lymphedema (PTL) is a chronic and often under-recognized sequela of soft tissue trauma, leading to persistent swelling, functional impairment, and increased risk of infection. While lymphedema is traditionally associated with oncologic interventions, growing evidence highlights the significant burden of PTL in trauma patients. This review provides a comprehensive analysis of the current understanding of PTL, including epidemiology, risk factors, pathophysiology, diagnostic modalities, and treatment strategies. PTL often occurs after high-impact musculoskeletal injuries (such as open fractures with significant soft tissue loss) or burns (especially if deep or circumferential). This risk is increased if injury occurs at critical areas of increased lymphatic density (such as anteromedial leg, medial knee, medial thigh, medial elbow, or medial arm). Advances in imaging techniques, including indocyanine green lymphography and magnetic resonance lymphangiography, have improved early detection and classification of PTL. Management approaches range from conservative therapies, such as complete decongestive therapy (CDT), to surgical interventions, including lymphaticovenous anastomosis (LVA), vascularized lymph node transfer (VLNT), and vascularized lymph vessel transfer (VLVT)/lymph-interpositional-flap transfer (LIFT). We report on our experience with two patients. At our center, we diagnose and stage PTL with ICG lymphography and trial CDT for 6 months. If there is no significant improvement, we recommend LVA. If there is insufficient improvement after 12 months, we recommend LIFT/repeat LVA/VLNT. We also treat open fractures with significant soft tissue defects with LIFT, as prophylaxis against PTL. PTL remains an underdiagnosed condition, necessitating increased awareness and intervention to prevent long-term disability. Full article

Background: Breast cancer-related lymphedema (BCRL) is a common and debilitating treatment-related adverse event that can profoundly impact quality of life and financial well-being. Although prospective surveillance and early intervention for BCRL have been shown to reduce the incidence and severity of this chronic condition, diagnostic accuracy of screening, programmatic utilization and efficacy vary widely. We describe the protocol for the BCRL Prospective Surveillance Model (PSM) and Early Intervention Program at the Dana-Farber Brigham Cancer Center that aims to address these issues by augmenting arm measurements (standard of care) with use of patient-reported outcome metrics (PROMs). Methods: Women with newly diagnosed stage I-III breast cancer at high risk for developing BCRL based on tumor and treatment characteristics are eligible for inclusion in our PSM care pathway, which uses both the Breast Cancer and Lymphedema Symptom Experience Index PROMs and arm measurements for screening. Screening begins prior to the initiation of neoadjuvant therapy and continues at regular intervals postoperatively. A positive screen, defined as new patient-reported arm swelling/heaviness and/or relative volume change (RVC) ≥ 5% in the affected limb, triggers consideration for multidisciplinary early intervention. Analysis: The BCRL detection rate will be compared to years previous to protocol development. PSM feasibility will be determined according to the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework. Efficacy of the PSM will be gauged by comparing change in patient-reported outcomes of interest and arm volume measurement pre and post early intervention. Feasibility will be determined by calculating the percentage of PSM-eligible individuals who complete all PSM activities in a 1-year span. Characteristics of participants versus non-participants in the target population will be compared. Furthermore, 1:1 semi-structured interviews with enrolled patients will be performed to understand facilitators and barriers to implementation. Conclusions: The findings from this study will be used to develop a standardized approach to PSM and early intervention that can be adapted to both resource-modest and resource-abundant healthcare infrastructures. Full article

Lipedema is a chronic, progressive adipose connective tissue disorder characterized by symmetrical, disproportionate fat accumulation, typically affecting the lower extremities and arms, accompanied by pain, swelling, and a sensation of heaviness. This study introduces intermediate Stages 1.5 and 2.5 to the established lipedema classification (Stages 1, 2 and 3), and other affected areas, based on physical examination, a questionnaire, and photographic documentation. Bioelectrical Impedance Spectroscopy (BIS) was employed to quantify total body water (TBW) across stages. A significant and linear increase in BMI was observed from Stage 1 to 3, correlating with increased reported pain and heaviness in the thighs, calves, and upper arms. Systemic symptoms of brain fog, debilitating fatigue, and hypothermia were significantly prevalent. TBW demonstrated a significant, stage-dependent increase in the lower extremities. Adipose tissue accumulation over the knees and feet significantly increased with lipedema stage. In contrast, shin involvement was evident in early stages and remained consistently elevated throughout later stages. Skeletal Muscle Mass (SMM) exhibited a significant increase across lipedema stages, positively correlating with fat mass (FM) in Stage 3. This study elucidates previously underrecognized clinical features and distribution patterns of lipedema, offering a refined staging system to improve understanding of its progression and burden. Full article

Background and Clinical Significance: Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disorder caused by mutations in the CYP27A1 gene, leading to impaired bile acid synthesis and systemic cholesterol deposition. The condition presents with a broad spectrum of symptoms affecting multiple organs and systems, including the eyes, central nervous system, tendons, and skeletal muscles. Due to its heterogeneous and often ambiguous clinical manifestations, CTX is frequently misdiagnosed or remains undiagnosed for years. Case Presentation: We report the case of a 37-year-old male who was admitted to our university hospital with a long-standing history of progressive muscle weakness in the arms and legs. His medical history revealed bilateral cataract surgery in childhood, cognitive decline, epilepsy, and bilateral round swellings of the Achilles tendons, suspected to be xanthomas. A clinical diagnosis of CTX was established, and sequencing analysis confirmed the presence of a homozygous pathogenic variant in the CYP27A1 gene. Despite the unavailability of chenodeoxycholic acid (CDCA) therapy in Bulgaria, symptomatic management was provided. Conclusions: This case underscores the diagnostic challenges associated with CTX and highlights the prolonged diagnostic journey faced by patients with rare neurogenetic disorders. It also emphasizes the need for increased awareness and early recognition of such conditions to improve patient outcomes. Full article

Hydrogel network structures play a crucial role in determining mechanical properties and have broad applications in biomedical and industrial fields. Therefore, their rational design is essential. Herein, we developed a Schiff base-crosslinked hydrogel through the reaction of Tetra-armed polyethylene glycol with aldehyde end groups (Tetra-PEG-CHO) and bovine serum albumin (BSA) under alkaline conditions. In addition, the Tetra-PEG-BSA hydrogel showed a rapid gelation time of around 11 s, much faster than that of the GLU-BSA, HT-BSA, and GDL-BSA hydrogels. It had high optical transmittance (92.92% at 600 nm) and swelling ratios superior to the other gels in different solutions, maintaining structural integrity even in denaturing environments such as guanidine hydrochloride and SDS. Mechanical tests showed superior strain at break (84.12 ± 0.76%), rupture stress (28.64 ± 1.21 kPa), and energy dissipation ability (468.0 ± 34.9 kJ·m⁻³), surpassing all control group hydrogels. MTT cytotoxicity assays indicated that cell viability remained >80% at lower concentrations, confirming excellent biocompatibility. These findings suggest that Tetra-PEG-BSA hydrogels may serve as effective materials for drug delivery, tissue engineering, and 3D printing. Full article

This study presents the development of thiol–maleimide/thiol–thiol double self-crosslinking hyaluronic acid-based (dscHA) hydrogels for use as dermal fillers. Hyaluronic acid with varying degrees of maleimide substitution (10%, 20%, and 30%) was synthesized and characterized, and dscHA hydrogels were fabricated using two molecular weights of four-arm polyethylene glycol (PEG10K/20K)–thiol as crosslinkers. The six resulting dscHA hydrogels demonstrated solid-like behavior with distinct physical and rheological properties. SEM analysis revealed a decrease in porosity with higher crosslinker MW and maleimide substitution. The swelling ratios of the six hydrogels reached equilibrium at approximately 1 h and ranged from 20% to 35%, indicating relatively low swelling. Degradation rates decreased with increasing maleimide substitution, while crosslinker MW had little effect. Higher maleimide substitution also required greater injection force. Elastic modulus (G′) in the linear viscoelastic region increased with maleimide substitution and crosslinker MW, indicating enhanced firmness. All hydrogels displayed similar creep-recovery behavior, showing instantaneous deformation under constant stress. Alternate-step strain tests indicated that all six dscHA hydrogels could maintain elasticity, allowing them to integrate with the surrounding tissue via viscous deformation caused by the stress exerted by changes in facial expression. Ultimately, the connection between the clinical performance of the obtained dscHA hydrogels used as dermal filler and their physicochemical and rheological properties was discussed to aid clinicians in the selection of the most appropriate hydrogel for facial rejuvenation. While these findings are promising, further studies are required to assess irritation, toxicity, and in vivo degradation before clinical use. Overall, it was concluded that all six dscHA hydrogels show promise as dermal fillers for various facial regions. Full article

Hydrogels have emerged as promising biomaterials due to their excellent performance; however, their biocompatibility, biodegradability, and absorbability still require improvement to support a broader range of medical applications. This paper presents a new biofunctionalized hydrogel based on in situ crosslinking between maleimide-terminated four-arm-poly(ethylene glycol) (4–arm–PEG–Mal) and poly(ε-lysine) (ε–PL). The PEG/ε–PL hydrogels, named LG–n, were rapidly formed via amine/maleimide reaction by mixing 4–arm–PEG–Mal and ε–PL under physiological conditions. The corresponding dry gels (DLG–n) were obtained through a freeze-drying technique. ¹H NMR, FT–IR, and SEM were utilized to confirm the structures of 4–arm–PEG–Mal and LG–n (or DLG–n), and the effects of solid content on the physicochemical properties of the hydrogels were investigated. Although high solid content could increase the swelling ratio, all LG–n samples exhibited a low equilibrium swelling ratio of less than 30%. LG–7, which contained moderate solid content, exhibited optimal compression properties characterized by a compressive fracture strength of 45.2 kPa and a deformation of 69.5%. Compression cycle tests revealed that LG–n demonstrated good anti-fatigue performance. In vitro degradation studies confirmed the biodegradability of LG–n, with the degradation rate primarily governing the drug (ceftibuten) release efficiency, leading to a sustained release duration of four weeks. Cytotoxicity tests, cell survival morphology observation, live/dead assays, and hemolysis tests indicated that LG–n exhibited excellent cytocompatibility and low hemolysis rates (<5%). Furthermore, the broad-spectrum antibacterial activity of LG–n was verified by an inhibition zone method. In conclusion, the developed LG–n hydrogels hold promising applications in the medical field, particularly as drug sustained-release carriers and wound dressings. Full article

A series of hybrid hydrogels of poly(ethylene glycol) (PEG) were synthesized using gelatin as a crosslinker and investigated for controlled delivery of the first-generation cephalosporin antibiotic, Cefazedone sodium (CFD). A commercially available 4-arm-PEG–OH was first modified to obtain four-arm-PEG–succinimidyl glutarate (4-arm-PEG–SG), which formed the gelatin–PEG composite hydrogels (S_nN_m) through crosslinking with gelatin. To regulate the drug delivery, S_nN_m hydrogels with various solid contents and crosslinking degrees were prepared. The effect of solid contents and crosslinking degrees on the thermal, mechanical, swelling, degradation, and drug release properties of the hydrogels were intensively investigated. The results revealed that increasing the crosslinking degree and solid content of S_nN_m could not only enhance the thermal stability, swelling ratio (SR), and compression resistance capacity of S_nN_m but also prolong the degradation and drug release times. The release kinetics of the S_nN_m hydrogels were found to follow the first-order model, suggesting that the transport rate of CFD within the matrix of hydrogels is proportional to the concentration of the drug where it is located. Specifically, S₁N₁-III showed 90% mass loss after 60 h of degradation and a sustained release duration of 72 h. The cytotoxicity assay using the MTT method revealed that cell viability rates of S₁N₁ were higher than 95%, indicating excellent cytocompatibility. This study offers new insights and methodologies for the development of hydrogels as biomedical composite materials. Full article

Wireless soft miniature robots have been studied for biomedical applications. However, the wireless soft miniature robots developed so far are mainly composed of synthetic polymers that do not guarantee biocompatibility and biodegradability. Additionally, current soft robots have limitations in demonstrating mobility in narrow spaces, such as blood vessels within the body, by using their flexible body. This study proposes a wireless hybrid-actuated soft miniature robot for biomedical applications. The proposed soft miniature robot consists of biodegradable chitosan and magnetic nanoparticles (MNPs) and is fabricated into an eight-arm shape by laser micromachining. The soft miniature robot can implement hydrogel swelling and magnetic-actuated shape morphing by using the difference in MNP density and magnetic field responsiveness within the robot body, respectively. Furthermore, the soft miniature robot can be guided by external magnetic fields. As feasibility tests, the soft miniature robot demonstrated on-demand pick-and-place motion, grasping a bead, moving it to a desired location, and releasing it. Furthermore, in an in-channel mobility test, the flexible body of the soft miniature robot passed through a tube smaller in size than the robot itself through magnetically actuated shape morphing. These results indicate that the soft miniature robot with controllable shape change and precise magnetic-driven mobility can be a minimally invasive surgical robot for disease diagnosis and treatment. Full article

Objective: This study aims to evaluate the safety and immunogenicity of the SKYVaricella vaccine in healthy Vietnamese children aged 12 months to 12 years. Methods: This open-label, single-arm study involved 201 children divided into two groups: 60 children aged 12 months to 5 years and 141 children aged 6 to 12 years. Safety was assessed through immediate reactions, solicited adverse events within 7 days, and unsolicited events up to Day 42. Immunogenicity was evaluated by seroconversion rates (SCR) and geometric mean titer (GMT) increments using fluorescent antibody-to-membrane antigen (FAMA) on the day of vaccination (D0) and 42 days after vaccination (D42). Results: All participants completed the follow-up. Immediate adverse events included pain (8.0%), redness (8.0%), and swelling (20.9%) at the injection site. Within 7 days, pain (17.9%) and swelling (12.4%) were mild and self-resolving. Unsolicited adverse events were infrequent and mild. Both age groups achieved 100% SCR. GMT of varicella-zoster virus antibodies increased from 1.37 (SD 1.97) at D0 to 18.02 (SD 2.22) at D42, a 13.12-fold rise. No Grade 3 adverse events were observed. Conclusion: The SKYVaricella vaccine shows a robust immunogenic response and favorable safety profile in Vietnamese children aged 12 months to 12 years. These findings endorse its potential inclusion in pediatric vaccination programs as a reliable preventive option against varicella. Full article

In recent years, hydrogel-based wearable flexible electronic devices have attracted much attention. However, hydrogel-based sensors are affected by structural fatigue, material aging, and water absorption and swelling, making stability and accuracy a major challenge. In this study, we present a DN-SPEZ dual-network hydrogel prepared using polyvinyl alcohol (PVA), sodium alginate (SA), ethylene glycol (EG), and ZnSO₄ and propose a self-calibration compensation strategy. The strategy utilizes a metal salt solution to adjust the carrier concentration of the hydrogel to mitigate the resistance drift phenomenon to improve the stability and accuracy of hydrogel sensors in amphibious scenarios, such as land and water. The ExpGrow model was used to characterize the trend of the ∆R/R₀ dynamic response curves of the hydrogels in the stress tests, and the average deviation of the fitted curves $\overline{ϵ}$ was calculated to quantify the stability differences of different groups. The results showed that the stability of the uncompensated group was much lower than that of the compensated group utilizing LiCl, NaCl, KCl, MgCl₂, and AlCl₃ solutions ($\overline{ϵ}$ in the uncompensated group in air was 276.158, 1.888, 2.971, 30.586, and 13.561 times higher than that of the compensated group in LiCl, NaCl, KCl, MgCl₂, and AlCl₃, respectively; $\overline{ϵ}$ in the uncompensated group in seawater was 10.287 times, 1.008 times, 1.161 times, 4.986 times, 1.281 times, respectively, higher than that of the compensated group in LiCl, NaCl, KCl, MgCl₂ and AlCl₃). In addition, for the ranking of the compensation effect of different compensation solutions, the concentration of the compensation solution and the ionic radius and charge of the cation were found to be important factors in determining the compensation effect. Detection of events in amphibious environments such as swallowing, robotic arm grasping, Morse code, and finger–wrist bending was also performed in this study. This work provides a viable method for stability and accuracy enhancement of dual-network hydrogel sensors with strain and pressure sensing capabilities and offers solutions for sensor applications in both airborne and underwater amphibious environments. Full article

We present a case of a healthy young male professional water polo player who presented with swelling and pain in the upper arm and elbow after vigorous exercise. Diagnostic workup included an MRI and dynamic duplex ultrasound, which revealed compression of the axillary vein by a hypertrophic pectoralis minor muscle without thrombosis, constituting McCleery syndrome. This is a rare entity within the multiple thoracic outlet syndrome aetiologies. Taking a detailed history and physical examination complemented with diagnostic imaging are vital to the diagnosis. Afterward, the patient was treated with multimodal physical therapy and fully recovered and even exceeded his previous training and play level. Full article

Background: Even minor adverse reactions after total hip replacement (THR), including lymphedema, postoperative leg swelling, and blood loss, compromise patient comfort in times of minimally invasive fast-track surgery. Compression dressings are commonly used in surgical practice to reduce swelling or blood loss. However, the use of spica hip compression dressings after primary THR is controversial, and prospective studies are lacking. Methods: We conducted a prospective, single-center, two-arm, randomized controlled trial (RCT) of patients undergoing THR for primary osteoarthritis. A total of 324 patients were enrolled; 18 patients were excluded, and 306 patients were finally analyzed. Leg swelling as primary endpoint was measured pre- and postoperatively with a rotating 3D infrared body scanner. Secondary endpoints were transfusion rate and blood loss, estimated by Nadler and Gross formulas. Results: Postoperative leg swelling was lower in the compression group (241 ± 234 mL vs. 307 ± 287 mL; p = 0.01), even after adjustment for surgery time and Body-Mass-Index (BMI) (p = 0.04). Estimated blood loss was also lower in the compression group on the first (428 ± 188 mL vs. 462 ± 178 mL; p = 0.05) and third (556 ± 247 mL vs. 607 ± 251 mL; p = 0.04) postoperative days and leveled off on the fifth postoperative day, but lost significance after adjustment for BMI and surgery time. Neither group received a transfusion. Conclusions: Compression dressing after THR in the context of minimally invasive surgery slightly reduces leg swelling, but has no effect on blood loss or blood transfusion rate. So, this method could not generally be recommended in primary hip replacement. Full article

A three-arm, randomized, placebo-controlled clinical study was conducted to assess the impact of lyophilized pineapple extract with titrated bromelain (Brome-Inf^®) and purified bromelain on pain, swelling, trismus, and quality of life (QoL) following the surgical extraction of the mandibular third molars. Furthermore, this study examined the need for Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) by comparing their effects with a placebo group. This study enrolled 42 individuals requiring the extraction of a single mandibular third molar under local anesthesia. The patients were randomly assigned to receive Brome-Inf^®, purified bromelain, or a placebo orally, initiating treatment on the day of surgery and continuing for the next 7 days. The primary outcome measured was the requirement for NSAIDs in the three groups. Pain, swelling, and trismus were secondary outcome variables, evaluated postoperatively at 1, 3, and 7 days. This study also assessed the comparative efficacy of freeze-dried pineapple extract and single-component bromelain. Ultimately, the placebo group showed a statistically higher need for ibuprofen (from days 1 to 7) at the study’s conclusion (p < 0.0001). In addition, reductions in pain and swelling were significantly higher in both the bromelain and pineapple groups (p < 0.0001 for almost all patients, at all intervals) than in the placebo group. The active groups also demonstrated a significant difference in QoL compared to the placebo group (p < 0.001). A non-significant reduction in trismus occurred in the treatment groups compared to the placebo group. Therefore, the administration of pineapple extract titrated in bromelain showed significant analgesic and anti-edema effects in addition to improving QoL in the postoperative period for patients who had undergone mandibular third molar surgery. Moreover, both bromelain and Brome-Inf^® supplementation reduced the need for ibuprofen to comparable extents, proving that they are good alternatives to NSAIDs in making the postoperative course more comfortable for these patients. A further investigation with larger samples is necessary to assess the pain-relieving and anti-inflammatory impacts of the entire pineapple phytocomplex in surgical procedures aside from mandibular third molar surgery. Full article