Clinical Outcomes of Collagenase Injections in Management of Dupuytren Contracture of the Proximal Interphalangeal Joint.

Purpose: Dupuytren contracture is characterized by the formation of cords and nodules in the palm. Surgical release has historically been the definitive treatment. Collagenase clostridium histolyticum (CCH) has been used successfully as an alternative to surgery. The treatment of proximal interphalangeal (PIP) contractures is the most challenging. The purpose of this study was to evaluate CCH treatment for Dupuytren contracture of the PIP joint. Methods: A retrospective chart review was performed for CCH treatment of Dupuytren contracture at a single institution from January 2010 to April 2023. Data collected included pretreatment/posttreatment total flexion contracture and adverse events. Contractures were analyzed both by severity (high >40° and low <40°) and type (isolated PIP; combined metacarpophalangeal and PIP). Results: A total of 304 patients with 470 PIP joints treated were included. Digits with isolated and combined contractures each had an average pre-CCH treatment contracture of 51 (±23) degrees. Postmanipulations the contractures were 6 (±13) and 7 (±16) degrees, respectively. Clinical success (<5° residual contracture) and improvement (>50% correction of contracture) were associated with low severity contractures at postmanipulation. There were 256 adverse events recorded (54.5%), including 187 skin tears (39.8%), 68 cases of lymphadenopathy (14.5%), and one injection site infection (0.2%). High severity and combined contractures were independently associated with an increased incidence of skin tears upon manipulation. Conclusions: Collagenase clostridium histolyticum treatment is effective for isolated or combined PIP joint contractures. Adverse events were associated with more severe contractures. Given the degree of improvement based on contracture severity, earlier intervention may provide better correction of contracture. Type of study/level of evidence: Therapeutic III.

Isolated bovine pancreatic islets as an alternate in vitro model for diabetes research.

Background & objectives Isolation of functional pancreatic islets for diabetes research and clinical islet transplantation stands as a big challenge despite the advancements in the field. In this context, the non-availability of human/animal tissues is one of the major impediments to islet-based research, which has tremendous scope for translation. The current study explores the feasibility of using the bovine pancreas as an alternative source to isolate pancreatic islets and assess its functionality for in vitro studies. Methods The bovine pancreas was collected from a registered slaughterhouse and transported in an ice-cold medium - Hank's Balanced Salt Solution (HBSS) to the laboratory. Islets were isolated by sequential collagenase digestion followed by a two-step filtration and purification by density gradient separation method. After isolation, islets were identified with dithizone staining and the islet function was assayed in vitro for assessing the dynamic insulin secretory function by monitoring the glucose-stimulated insulin secretion (GSIS), in response to low and high glucose. Staining techniques were also used to understand the cytoarchitecture of the bovine pancreas. Results The islet yield was 157±23 islets per gram of pancreas and was viable. The cold ischaemia time was reduced to 60-75 min. The islets released insulin with glucose stimulation. The insulin release was observed more with high glucose (28 mM) than with low glucose (2.8 mM). Dithizone staining confirmed the presence of islets after isolation and the size of islets ranged from 50 to 600 µm size. The mantled islets (islets with acinar tissue) were also noted with the pure islets in culture. Hematoxylin and eosin (H&E) and aldehyde- fuchsin showed islets interspersed in the acinar tissue of the bovine pancreas. Special stain defined the islets better than regular staining. Fluorescent and diaminobenzidine (DAB) staining with insulin, glucagon and somatostatin revealed the arrangement of the cells in each islet. The beta cells were majorly found in the islet core with alpha cells interspersed with the delta cells in the periphery. Interpretation & conclusions The isolation procedure described in this study yielded viable islets for in vitro studies which showed a differential response to glucose challenge, confirming their viability. We provide a simple and reproducible method for small-scale isolation of functional islets from the bovine pancreas. This model proffers the beginner a hands-on in islet experiments and helps to re-iterate the process that could be extrapolated to other pancreatic tissues as well as to expand on diabetes research.

High-fat diet-induced obesity exacerbated collagenase-induced tendon injury with upregulation of interleukin-1beta and matrix metalloproteinase-1.

AIMS: Obesity increases tendinopathy's risk, but its mechanisms remain unclear. This study examined the effect of high-fat diet (HFD)-induced obesity on the outcomes and inflammation of collagenase-induced (CI) tendon injury. METHODS: Mice were fed with standard chow (SC) or HFD for 12 weeks. Bacterial collagenase I or saline was injected over the patellar tendons of each mouse. At weeks 2 and 8 post-injection, the patellar tendons were harvested for histology, immunohistochemical staining, and gait analysis. The difference (Δ) of limb-idleness index (LII) at the time of post-injury and pre-injury states was calculated. Biomechanical test of tendons was also performed at week 8 post-injection. RESULTS: HFD aggravated CI tendon injury with an increase in vascularity and cellularity compared to SC treatment. The histopathological score (week 2: p = 0.025; week 8: p = 0.013) and ΔLII (week 2: p = 0.012; week 8: p = 0.005) were significantly higher in the HFD group compared to those in the SC group after CI tendon injury. Stiffness (saline: p = 0.003; CI: p = 0.010), ultimate stress (saline: p < 0.001; CI: p = 0.006), and Young's modulus (saline: p = 0.017; CI: p = 0.007) were significantly lower in the HFD group compared to the SC group at week 8 after saline or collagenase injection. HFD induced higher expression of IL-1ß (week 2: p = 0.010; week 8: p = 0.025) and MMP-1 (week 2: p = 0.010; week 8: p = 0.004) compared to SC treatment after CI tendon injury at both time points. CONCLUSIONS: HFD-induced obesity exacerbated histopathological, functional, and biomechanical changes in the CI tendon injury model, which was associated with an upregulation of IL-1ß and MMP-1.

Assessment of whole cartilage surface damage in an osteoarthritis rat model: the Cartilage Roughness Score (CRS) utilizing microcomputed tomography.

OBJECTIVE: This study aims to establish an accurate and robust imaging biomarker for pre-clinical osteoarthritis (OA) research, focusing on early detection of cartilage surface degeneration. METHOD: Using 50 male Wistar rats, this study aims to observe Collagenase Induced Osteoarthritis (CIOA) progression through microcomputed x-ray tomography (µCT), histopathological analysis, and gait analysis. A novel parameter, Cartilage Roughness Score (CRS), was developed for assessing cartilage structural damage from µCT data and was compared with histological OARSI Cartilage Degeneration Score (OARSI CDS). Additionally, as CRS maps the full surface, it was used to simulate the level of uncertainty in histological sampling. RESULTS: CRS and OARSI CDS have a linear relationship. CRS for healthy cartilage is 2.75 (95% CI: 1.14-4.36) and with every 1 unit increase in OARSI, CRS is expected to increase by 0.64 (95% CI: 0.35-0.92). Cartilage degeneration due to CIOA was evident in both histopathological scoring and CRS. However, only CRS was sensitive enough to show consistent damage progression from day 10 to day 60. Furthermore, our simulation for histological sampling suggested that up to 16 coronal slices with 200µm spacing would be needed to accurately represent the full extent of cartilage surface degeneration in a slice wise manner. Gait analysis showed changes solely at eight days post-collagenase injection, normalizing by day 60. CONCLUSION: The CRS analysis method emerges as a robust tool for cartilage surface damage assessment. This study demonstrates the potential of automatic 3D analysis over the traditional 2D histological approach when evaluating cartilage surface damage. DATA STATEMENT: Micro-computed tomography data is available via ida.fairdata.fi46 (https://doi.org/10.23729/f33d3ba8-01b8-47af-90dd-94b7c7861247).

Evaluation of Biotechnological Active Peptides Secreted by Saccharomyces cerevisiae with Potential Skin Benefits.

Biotechnological active peptides are gaining interest in the cosmetics industry due to their antimicrobial, anti-inflammatory, antioxidant, and anti-collagenase (ACE) effects, as well as wound healing properties, making them suitable for cosmetic formulations. The antimicrobial activity of peptides (2-10 kDa) secreted by Saccharomyces cerevisiae Ethanol-Red was evaluated against dermal pathogens using broth microdilution and challenge tests. ACE was assessed using a collagenase activity colorimetric assay, antioxidant activity via spectrophotometric monitoring of nitrotetrazolium blue chloride (NBT) reduction, and anti-inflammatory effects by quantifying TNF-α mRNA in lipopolysaccharides (LPS)-exposed dermal fibroblasts. Wound healing assays involved human fibroblasts, endothelial cells, and dermal keratinocytes. The peptides (2-10 kDa) exhibited antimicrobial activity against 10 dermal pathogens, with the Minimum Inhibitory Concentrations (MICs) ranging from 125 µg/mL for Staphylococcus aureus to 1000 µg/mL for Candida albicans and Streptococcus pyogenes. In the challenge test, peptides at their MICs reduced microbial counts significantly, fulfilling ISO 11930:2019 standards, except against Aspergillus brasiliensis. The peptides combined with MicrocareⓇ SB showed synergy, particularly against C. albicans and A. brasilensis. In vitro, the peptides inhibited collagenase activity by 41.8% and 94.5% at 250 and 1000 µg/mL, respectively, and demonstrated antioxidant capacity. Pre-incubation with peptides decreased TNF-α expression in fibroblasts, indicating anti-inflammatory effects. The peptides do not show to promote or inhibit the angiogenesis of endothelial cells, but are able to attenuate fibrosis, scar formation, and chronic inflammation during the final phases of the wound healing process. The peptides showed antimicrobial, antioxidant, ACE, and anti-inflammatory properties, highlighting their potential as multifunctional bioactive ingredients in skincare, warranting further optimization and exploration in cosmetic applications.

Towards the Use of Lichens as a Source of Bioactive Substances for Topical Applications.

The increasing incidence of dermatological diseases prompts the search for new natural methods of treatments, and lichens, with their special symbiotic structure, are a little-known and promising source of biologically active substances. Seven lichen species, Cladonia unicialis (L.) Weber ex F.H. Wigg. (Cladoniaceae), Evernia prunastri (L.) Ach. (Parmeliaceae), Hypogymnia physodes (L.) Nyl. (Parmaliaceae), Parmelia sulcata (Taylor) (Parmeliaceae), Physcia adscendens (Fr.) H. Olivier (Physciaceae), Pseudoevernia furfuracea (L.) Zopf (Parmeliaceae), and Xanthoria parietina (L.) Th. Fr. (Teloschistaceae), were used in our experiment. We identified different metabolites in the acetone extracts of all the lichen species. Based on the high-performance liquid chromatography analysis, the content of lichen substances in the extracts was evaluated. The impact of the individual lichen-specific reference substances, compared to the lichen extracts, on the viability of keratinocytes (HaCaT cell line) and fibroblasts (BJ cell line) and on the activity of selected skin-related enzymes was investigated. Our results revealed that only emodin anthrone at a concentration of 200 mg/L was cytotoxic to keratinocytes and fibroblasts in both cell viability assays. In turn, the C. uncialis extract was only cytotoxic to keratinocytes when used at the same concentration. The other tested treatments showed a positive effect on cell viability and no cytotoxicity or indeterminate cytotoxicity (shown in only one of the tests). Elastase and collagenase activities were inhibited by most of the lichen extracts. In turn, the individual lichen compounds (with the exception of evernic acid) generally had an undesirable stimulatory effect on hyaluronidase and collagenase activity. In addition, almost all the tested compounds and extracts showed anti-inflammatory activity. This suggests that some lichen compounds hold promise as potential ingredients in dermatological and skincare products, but their safety and efficacy require further study. The high cytotoxicity of emodin anthrone highlights its potential use in the treatment of hyperproliferative skin diseases such as psoriasis.

Long-Term Satisfaction With Collagenase Clostridium Histolyticum for Peyronie's Disease: Clinical Predictors and Side Effect Profile.

INTRODUCTION: Collagenase clostridium histolyticum (CCH) therapy for Peyronie's disease (PD) yields satisfaction rates of roughly 50% to 67% within 1 year of treatment completion, but little is known about long-term patient satisfaction. Our study aimed to identify clinical predictors of long-term satisfaction with CCH for PD and the impact of its side effect profile. METHODS: The Treatment Satisfaction Questionnaire for Medication (TSQM) survey was distributed to patients who received CCH for PD at a high-volume men's health academic center from 2009 to 2022. Through retrospective chart review, demographic and clinical data of the disease were collected. RESULTS: Of 242 eligible patients, 80 (32.9%) responded, with questionnaires completed at a median of 5.1 (interquartile range 2.4-6.7) years after the last CCH injection. Thirty-four (42.5%) respondents reported satisfaction with CCH therapy. Older age was associated with significantly greater side effect domain scores (P < .004 for all). Curvature degree, plaque diameter, and plaque volume before CCH treatment, the mean reduction, and the mean percent reduction in these parameters were not significantly correlated with TSQM totals. Patients with greater final curvature and plaque volume measured after CCH completion had significantly lower TSQM totals (Spearman's ρ = -0.36, -0.32; P < .04 for both). Ten (12.5%) patients with depression and 10 (12.5%) patients who proceeded to surgery exhibited significantly decreased TSQM totals (P < .04 for both). CONCLUSIONS: While a significant proportion of our cohort reported long-term satisfaction with CCH therapy, patient satisfaction with CCH therapy is multifaceted. Our findings can be used to better counsel and manage patient expectations of treatment outcomes before initiating CCH.

Coating Dormant Collagenase-Producing Bacteria with Metal-Anesthetic Networks for Precision Tumor Therapy.

Tumor malignancy highly depends on the stiffness of tumor matrix, which mainly consists of collagen. Despite the destruction of tumor matrix is conducive to tumor therapy, it causes the risk of tumor metastasis. Here, metal-anesthetic network-coated dormant collagenase-producing Clostridium is constructed to simultaneously destruct tumor matrix and inhibit tumor metastasis. By metal-phenolic complexation and π-π stacking interactions, a Fe3+-propofol network is formed on bacterial surface. Coated dormant Clostridium can selectively germinate and rapidly proliferate in tumor sites due to the ability of carried Fe3+ ions to promote bacterial multiplication. Intratumoral colonization of Clostridium produces sufficient collagenases to degrade tumor collagen mesh and the loaded propofol restrains tumor metastasis by inhibiting tumor cell migration and invasion. Meanwhile, the delivered Fe3+ ions are reduced to the Fe2+ form by intracellular glutathione, thereby inducing potent Fenton reaction to trigger lipid peroxidation and ultimate ferroptosis of tumor cells. In addition to a satisfactory safety, a single intratumoral injection of coated dormant Clostridium not only effectively retards the growth of established large primary tumors, but also significantly suppresses distal lung metastasis in two different orthotopic tumor models. This work proposes a strategy to develop advanced therapeutics for malignant tumor treatment and metastasis prevention.

MMP13 Expression and Activity Suggest Its Role in Bone Resorption in Ameloblastomas.

BACKGROUND: Ameloblastoma is a locally destructive benign odontogenic tumor. While the neoplastic cells of conventional ameloblastoma can infiltrate the connective tissue and bone, in unicystic ameloblastoma the epithelium is encapsulated. The mechanisms driving ameloblastoma's bone resorption remains unclear. METHODS: RNA sequencing (RNA-seq) was performed in a discovery cohort of conventional ameloblastoma, and pathway enrichment analysis was carried out. mRNA levels of MMP13, a gene associated with bone resorption, were assessed using RT-qPCR in a larger cohort of conventional ameloblastoma and in unicystic ameloblastoma. Zymogram gels and the immunoexpression profile of collagenase 3 (encoded by MMP13 gene) were evaluated as well. RESULTS: Enriched pathways related to bone mineralization and upregulation of MMP13 were observed in ameloblastomas. Collagenolytic activity of collagenase 3 was detected in the tumor lysates. Collagenase 3 immunopositivity was observed in ameloblastomatous epithelium infiltrating the fibrous capsule of unicystic ameloblastoma. At the tumor-bone interface, collagenase 3 expression was detected in stromal cells, osteoblasts, and osteocytes. CONCLUSION: The results indicate a potential involvement of MMP13 in ameloblastoma-related bone resorption and progression.

Creation of a Novel Classification System (PTNM) for Peyronie's Disease and Penile Curvature Using Evidence-Based Criteria.

PURPOSE: Our goal was to identify new Peyronie's disease (PD) subtypes, non-PD penile curvature classifications, and define active (acute) vs stable (chronic) phases of disease using evidence-based analyses. MATERIALS AND METHODS: A retrospective review was performed of 1098 men who presented with penile deformity, including subjective standardized and nonstandardized questionnaires and objective measures. A second cohort of 719 men who were sent a mailed survey was also utilized for the relapsing/remitting subtype. Statistical analyses were performed to identify clusters of disease characteristics representative of distinct PD and non-PD categorizations, including sensitivity/specificity analyses and subtype comparisons. RESULTS: Comparative analyses identified 4 distinct subtypes of PD: (1) classical and nonclassical, (2) calcifying-moderate/severe calcification, (3) progressive-subjective worsening following disease onset, and (4) relapsing/remitting-reactivation following ≥ 6 months of stability. Additional, non-PD categorizations included congenital (lifelong), maturational (developed around puberty), and trauma induced. Statistical analyses demonstrated unique profiles among each category. Penile pain was not found to be a reliable predictor for disease progression or stability. Stable phase disease (historically "chronic") was variably defined by subtype: classical (≥3 months); progressive, calcifying, or trauma induced (≥12 months + ≥3 months stable OR ≥6 months stable). Similarly, PD subtypes may be assigned at ≥ 3 months following disease onset. A PTNM staging system is proposed to help communicate disease states, in which P = PD component (Ca-calcifying, Cl-classical, P-progressive, R-relapsing/remitting, U-undifferentiated), T = trauma component (0-absent, 1-present), N = non-PD component (C-congenital, M-maturational, U-undifferentiated), and M = mode (0-stable, 1-active); for example, PClT1N0M0 = stable classical PD with prior trauma. CONCLUSIONS: The current study provides an evidence-based proposal for the establishment of new PD subtypes and non-PD curvature categorizations as well as a standardized definition for active vs stable phases of disease.

Successfully Nonsurgical Epidermoid Cyst Management with Recombinant Hydrolytic Enzymes: A Case Report.

Introduction: Epidermoid cysts (E.C.s), also known as sebaceous cysts, are benign asymptomatic subepidermal nodules filled with keratin material. These cysts originate from the follicular infundibulum, which when obstructed by keratin, results in cyst formation. Conventionally, E.C.s have been managed surgically with a high success rate and minimal complications. In this report, we present the successful resolution of an E.C. using a minimally invasive technique involving the intralesional injection of recombinant hydrolytic enzymes like hyaluronidase, collagenase, and lipase. Case Presentation: A 44-year-old woman with no significant medical history presented to the clinic with a mass on her right cheek that had been evolving for over 10 years. Skin and soft tissue ultrasound confirmed the presence of an E.C. of 9.3×6.6 × 9.3 mm. Owing to the size and location of the cyst, a decision was made to infiltrate the lesion with recombinant enzymes. Remarkably, significant clinical improvement was observed on Day 21, and complete dissolution of the E.C. occurred 40 days after the initial intervention. Importantly, no recurrences were observed during the 4-year follow-up period. Conclusion: Intralesional administration of hydrolytic enzymes represents an innovative technique in the management of E.C.s. However, further controlled studies are required to determine the efficacy and safety of this procedure.

Treatment utilization for Dupuytren's contracture in the United States is influenced by socioeconomic factors.

We examined whether treatment utilization for Dupuytren's contracture varied with the presence of adverse socioeconomic determinants of health in the United States. After propensity score matching, the presence of adverse socioeconomic determinants of health was associated with decreased treatment utilization.

Dupuytren's Contracture: Approach to Treatment and Counseling Patients in 2024.

Dupuytren disease is a progressive disease process that causes debilitating flexion contractures of the metacarpophalangeal and proximal interphalangeal joints. There are multiple interventions to choose from, ranging from minimally invasive techniques with little downtime to open surgical excision with a lengthy postoperative rehabilitation. Our understanding of the disease process continues to evolve. Depending on the extent of flexion contracture, needle aponeurotomy and collagenase injection have satisfactory results with moderate long-term efficacy. Surgical palmar fasciectomy continues to be the mainstay treatment of extensive contractures, with durable results.

Adjuvant Treatment with Celecoxib after Collagenase Injection for Dupuytren Contracture: A Double-Blind Randomised Controlled Trial.

Background: In patients with a high recurrence risk after treatment for Dupuytren contracture (DC) by Collagenase Clostridium histolyticum (CCH), adjuvant medical therapy may improve the outcome. Non-steroidal anti-inflammatory drugs have been used in the treatment of similar fibroproliferative processes. The aim of this study was to investigate if adjuvant anti-inflammatory medication could improve the outcome of CCH treatment for DC. Methods: In a prospective double blinded randomised trial, the effect of adjuvant peroral celecoxib on the outcome of DC treated with CCH was investigated in 32 patients with a high fibrosis diathesis. Primary outcome was the increase in Total Passive Extension Deficit (TPED)/ray. Secondary outcomes were the TPED of the individual finger joints, Tubiana index, Disability of Arm, Shoulder and Hand score (DASH) and visual analogue scale (VAS) for pain and satisfaction. Results: A significantly greater improvement in the celecoxib group for TPED and metacarpophalangeal contracture was found. For the proximal interphalangeal joint, the effect was much less pronounced. The VAS for pain and satisfaction were better at 6 and 12 weeks in the celecoxib group. The other outcome parameters did not significantly differ between both groups. Conclusions: Adjuvant peroral administration of celecoxib might improve the gain in TPED after treatment with CCH in patients with DC and a high fibrosis diathesis, with a beneficial effect up to 24 months. Level of Evidence: Level II (Therapeutic).

Validation of a rapid collagenase activity detection technique based on fluorescent quenched gelatin with synovial fluid samples.

BACKGROUND: Measuring collagenase activity is crucial in the field of joint health and disease management. Collagenases, enzymes responsible for collagen degradation, play a vital role in maintaining the balance between collagen synthesis and breakdown in joints. Dysregulation of collagenase activity leads to joint tissue degradation and diseases such as rheumatoid arthritis and osteoarthritis. The development of methods to measure collagenase activity is essential for diagnosis, disease severity assessment, treatment monitoring, and identification of therapeutic targets. RESULTS: This study aimed to validate a rapid collagenase activity detection technique using synovial fluid samples. Antibody microarray analysis was initially performed to quantify the levels of matrix metalloproteinase-9 (MMP-9), a major collagenase in joints. Subsequently, the developed gelatin-based test utilizing fluorescence measurement was used to determine collagenase activity. There was a significant correlation between the presence of MMP-9 and collagenase activity. In addition, Lower Limit of Detection and Upper Limit of Detection can be preliminary estimated as 8 ng/mL and 48 ng/mL respectively. CONCLUSIONS: The developed technique offers a potential point-of-care assessment of collagenase activity, providing real-time information for clinicians and researchers. By accurately quantifying collagenase activity, healthcare professionals can optimize patient care, improve treatment outcomes, and contribute to the understanding and management of joint-related disorders. Further research and validation are necessary to establish the full potential of this rapid collagenase activity detection method in clinical practice.

Isolation of the Stromal Vascular Fraction Using a New Protocol with All Clinical-Grade Drugs: From Basic Study to Clinical Application.

OBJECTIVE: The purpose of this study was to evaluate the yield, viability, clinical safety, and efficacy of the stromal vascular fraction (SVF) separated with a new protocol with all clinical-grade drugs. MATERIALS AND METHODS: SVF cells were isolated from lipoaspirate obtained from 13 participants aged from 30 to 56 years by using a new clinical protocol and the laboratory protocol. The cell yield, viability, morphology, mesenchymal stem cell (MSC) surface marker expression, and differentiation abilities of the SVF cells harvested from the two protocols were compared. Furthermore, three related clinical trials were conducted to verify the safety and efficiency of SVF cells isolated by the new clinical protocol. RESULTS: There were no significant differences in the yield, viability, morphology, and differentiation potential of the SVFs isolated with the clinical protocol and laboratory protocol. Adipose-derived mesenchymal stem cell (ASC) surface marker expression, including that of CD14, CD31, CD44, CD90, CD105, and CD133, was consistent between the two protocols. Clinical trials have demonstrated the effectiveness of the SVF isolated with the new clinical protocol in improving skin grafting, promoting mechanical stretch-induced skin regeneration and improving facial skin texture. No complications occurred. CONCLUSION: SVF isolated by the new clinical protocol had a noninferior yield and viability to that of the SVF separated by the laboratory protocol. SVFs obtained by the new protocol can be safely and effectively applied to improve skin grafting, promote mechanical stretch-induced skin regeneration, and improve facial skin texture. TRIAL REGISTRATION: The trials were registered with the ClinicalTrials.gov (NCT03189628), the Chinese Clinical Trial Registry (ChiCTR2000039317), and the ClinicalTrials.gov (NCT02546882). All the three trials were not patient-funded trials. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bias in published randomized trials that compare collagenase injection with percutaneous needle fasciotomy in the treatment of Dupuytren disease: a systematic review.

Purpose: Controversy exists regarding the comparative efficacy of collagenase injection and percutaneous needle fasciotomy in the treatment of Dupuytren contracture. The randomized controlled trials (RCTs) that have compared the two treatment methods have reported results mostly implying similar treatment efficacy, durability, and complications. We aimed to review these RCTs regarding methodical quality and risk of bias. Methods: We searched PubMed and Cochrane Library databases up to May 2023. All RCTs comparing collagenase injection with needle fasciotomy were included. Eligible articles were reviewed by two researchers, of whom one was blinded to each article's title, authors, year of publication, journal, and source of the studies. To assess methodical quality, we used the modified Jadad scale yielding a score of 0 (lowest quality) to 5 (highest quality). We assessed risk of bias with the Cochrane risk-of-bias tool (RoB 2). Results: Five studies were eligible, comprising 204 patients treated with collagenase injection and 209 patients treated with needle fasciotomy. The modified Jadad score ranged from 1 to 2 points in the five studies, and the overall risk of bias was high in all studies. Pretrial protocols could be retrieved for only two studies, revealing important discrepancies with the published articles. Conclusion: The published RCTs that have compared collagenase injection with needle fasciotomy in the treatment of Dupuytren contracture demonstrate a high risk of bias.

Upregulation of FABP4 induced inflammation in the pathogenesis of chronic tendinopathy.

Objectives: Excessive inflammation contributes to the pathogenesis of tendinopathy. Fatty acid binding protein 4 (FABP4) is a pro-inflammatory adipokine mediating various metabolic and inflammatory diseases. This study aimed to examine the expression of FABP4 and its association with the expressions of inflammatory cytokines in tendinopathy. The effects of a single injection of FABP4 on tendon pathology and inflammation were examined. The effect of FABP4 on the expressions of inflammatory cytokines and the effect of IL-1ß on the expression of FABP4 in tendon-derived stem/progenitor cells (TDSCs) were also investigated. Methods: 1) Clinical patellar tendinopathy samples, healthy hamstring tendon samples, and healthy patellar tendon samples, 2) rotator cuff tendinopathy samples and healthy hamstring tendon samples; and 3) Achilles tendons of mice after saline or collagenase injection (CI) were stained for FABP4, IL-1ß, IL-6, TNF-α and IL-10 by immunohistochemistry (IHC). For the rotator cuff tendinopathy samples, co-localization of FABP4 with IL-1ß and TNF-α was done by immunofluorescent staining (IF). Mouse Achilles tendons injected with FABP4 or saline were collected for histology and IHC as well as microCT imaging post-injection. TDSCs were isolated from human and mouse tendons. The mRNA expressions of inflammatory cytokines in human and mouse TDSCs after the addition of FABP4 was quantified by qRT-PCR. The expression of FABP4 in TDSCs isolated from rotator cuff tendinopathy samples and healthy hamstring tendon samples was examined by IF. Mouse Achilles TDSCs were treated with IL-1ß. The mRNA and protein expressions of FABP4 were examined by qRT-PCR and IF, respectively. Results: There was significant upregulation of FABP4 in the patellar tendinopathy samples and rotator cuff tendinopathy samples compared to their corresponding controls. FABP4 was mainly expressed in the pathological areas including blood vessels, hypercellular and calcified regions. The expressions of IL-1ß and TNF-α increased in human rotator cuff tendinopathy samples and co-localized with the expression of FABP4. Collagenase induced tendinopathic-like histopathological changes and ectopic calcification in the mouse Achilles tendinopathy model. The expressions of inflammatory cytokines (IL-1ß, IL-6, TNF-α, IL-10) and FABP4 increased in hypercellular region, round cells chondrocyte-like cells and calcified regions in the mouse Achilles tendons post-collagenase injection. A single injection of FABP4 in mouse Achilles tendons induced histopathological changes resembling tendinopathy, with increased cell rounding, loss of collagen fiber alignment, and additionally presence of chondrocyte-like cells and calcification post-injection. The expressions of IL1-ß, IL-6, TNF-α and IL-10 increased in mouse Achilles tendons post-FABP4 injection. FABP4 increased the expressions of IL10, IL6, and TNFa in human TDSCs as well as the expressions of Il1b, Il6, and Il10 in mouse TDSCs. Human tendinopathy TDSCs expressed higher level of FABP4 compared to healthy hamstring TDSCs. Besides, IL-1ß increased the expression of FABP4 in mouse TDSCs. Conclusion: In conclusion, an upregulation of FABP4 is involved in excessive inflammation and pathogenesis of tendinopathy. TDSCs is a potential source of FABP4 during tendon inflammation. Translation potential of this article: FABP4 can be a potential treatment target of tendinopathy.

Comparing collagenase and silver sulfadiazine in deep second-degree burn treatment.

The indications for collagenase ointment (CO) and its efficacy are not clearly established in the treatment of second-degree burn wounds. To evaluate the efficacy of CO versus silver sulfadiazine ointment (SSD) in the treatment of second-degree burn wounds. A total of 170 eligible patients with deep second-degree burns, aged 18-65 years, with injuries occurring within 48-96 h, and having a total wound area of less than 30% of the total body surface area were included from 5 centers in China. The primary outcome was the wound healing time, and the secondary outcomes were the clearance time of wound necrotic tissues, wound healing rate, and wound inflammation. The study included 85 patients in SSD group and 84 in CO group in the modified intention-to-treat (mITT) population. The median time of wound healing was comparable in both groups (10 days vs. 10.5 days P = 0.16). The time for wound necrotic tissue removal was significantly shortened by CO compared with SSD (5 vs. 10 days P < 0.01). Wound inflammation, pain, wound healing rate, and scar were compared with SSD (all P-values > 0.05). No adverse events, such as infection or allergic reactions to the drugs and materials used, were reported. Both CO and SSD could heal the burn wounds at 10 days of treatment. However, CO significantly shortened the time of wound necrotic tissue removal by 5 days. Trial Registration: ChiCTR2100046971.

Potential of Bioactive Protein and Protein Hydrolysate from Apis mellifera Larvae as Cosmeceutical Active Ingredients for Anti-Skin Aging.

This study aimed to extract bioactive proteins and protein hydrolysates from Apis mellifera larvae and assess their potential application in cosmetics as well as their irritation properties. The larvae were defatted and extracted using various mediums, including DI water, along with 0.5 M aqueous solutions of sodium hydroxide, ascorbic acid, citric acid, and hydrochloric acid. Subsequently, the crude proteins were hydrolyzed using the Alcalase® enzyme. All extracts underwent testing for antioxidant activities via the 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) and Griess assays. Anti-aging properties were evaluated in terms of anti-collagenase and anti-hyaluronidase effects. Irritation potential was assessed using the hen's egg chorioallantoic membrane (HET-CAM) test. The results revealed that the sodium hydroxide extraction showed promising outcomes in terms of yield, protein content, and effectiveness in inhibiting hyaluronidase, with the highest inhibition at 78.1 ± 1.5%, comparable to that of oleanolic acid. Conversely, crude protein extracted with ascorbic acid and its hydrolysate showed notable antioxidant and collagenase-inhibitory activities. Remarkably, their anti-collagenase effects were comparable to those of ascorbic acid and lysine. Additionally, it demonstrated safety upon testing with the CAM. In conclusion, the findings provided valuable insights into the utilization of A. mellifera larval proteins as active ingredients with a wide range of cosmeceutical applications, particularly due to their antioxidant, anti-aging, and low irritation properties, which hold significant promise for anti-skin wrinkles.