Polydeoxyribonucleotide in the Treatment of Tendon Disorders, from Basic Science to Clinical Practice: A Systematic Review.

Polydeoxyribonucleotide (PDRN) is a proprietary and registered drug with several beneficial effects, including tissue repairing, anti-ischemic action, and anti-inflammatory properties. The present study aims to summarize the current evidence about PRDN's clinical effectiveness in the management of tendon disorders. From January 2015 to November 2022, OVID-MEDLINE®, EMBASE, Cochrane Library, SCOPUS, Web of Science, Google Scholar and PubMed were searched to identify relevant studies. The methodological quality of the studies was evaluated, and relevant data were extracted. Nine studies (two in vivo studies and seven clinical studies) were finally included in this systematic review. Overall, 169 patients (male: 103) were included in the present study. The effectiveness and safeness of PDRN has been investigated in the management of the following diseases: plantar fasciitis; epicondylitis; Achilles tendinopathy; pes anserine bursitis; chronic rotator cuff disease. No adverse effects have been recorded in the included studies and all the patients showed an improvement in clinical symptoms during the follow-up. PDRN are a valid emerging therapeutic drug in the treatment of tendinopathies. Further multicentric randomized clinical studies are needed to better define the therapeutic role of PDRN, especially in combined clinical protocols.

Targeting Adenosine Signalling in Knee Chondropathy: The Combined Action of Polydeoxyribonucleotide and Pulsed Electromagnetic Fields: A Current Concept Review.

Chondropathy of the knee is one of the most frequent degenerative cartilage pathologies with advancing age. Scientific research has, in recent years, advanced new therapies that target adenosine A2 receptors, which play a significant role in human health against many disease states by activating different protective effects against cell sufferance and damage. Among these, it has been observed that intra-articular injections of polydeoxyribonucleotides (PDRN) and Pulsed Electromagnetic Fields (PEMF) can stimulate the adenosine signal, with significant regenerative and healing effects. This review aims to depict the role and therapeutic modulation of A2A receptors in knee chondropathy. Sixty articles aimed at providing data for our study were included in this review. The present paper highlights how intra-articular injections of PDRN create beneficial effects by reducing pain and improving functional clinical scores, thanks to their anti-inflammatory action and the important healing and regenerating power of the stimulation of cell growth, production of collagen, and the extracellular matrix. PEMF therapy is a valid option in the conservative treatment of different articular pathologies, including early OA, patellofemoral pain syndrome, spontaneous osteonecrosis of the knee (SONK), and in athletes. PEMF could also be used as a supporting therapy after an arthroscopic knee procedure total knee arthroplasty to reduce the post-operative inflammatory state. The proposal of new therapeutic approaches capable of targeting the adenosine signal, such as the intra-articular injection of PDRN and the use of PEMF, has shown excellent beneficial results compared to conventional treatments. These are presented as an extra weapon in the fight against knee chondropathy.

Significant variations of dangerous exposures during COVID-19 pandemic in Italy: a possible association with the containment measures implemented to reduce the virus transmission.

BACKGROUND: In response to the COVID-19 health emergency, mass media widely spread guidelines to stop the virus transmission, leading to an excessive and unaware use of detergents and disinfectants. In Italy and in other countries this tendency caused a significant increase of exposures to these products in 2020. Evaluating data collected by the Italian Pavia Poison Centre (PPC), this study intends to examine the relationship between the COVID-19 lockdown and the variations of exposures to specific product categories possibly associated to the containment measures implemented. Simultaneously, this work shows the effectiveness of the European Product Categorisation System (EuPCS) in surveillance activities of dangerous chemicals. METHODS: Exposure cases managed by the PPC during March-May 2020 (lockdown) and during the same months of 2017-2018-2019 were compared. Differences in categorical variables were tested with the Chi-square test. The level of significance was set at Alpha = .05. The study included all EuPCS groups but specifically focused on cleaners, detergents, biocides and cosmetics. RESULTS: During the lockdown, calls from private citizens showed a highly significant increase (+ 11.5%, p < .001) and occupational exposures decreased (- 11.7%, p = .011). Among Cleaners, exposures to Bleaches slightly increased while Drain cleaning products went through a significant reduction (- 13.9%, p = .035). A highly significant increase of exposures to Disinfectants was observed (+ 7.7%, p = .007), particularly to those for surfaces (+ 6.8%, p = .039). Regarding Cosmetics, both handwashing soaps and gel products significantly increased (respectively: + 25.0, p = .016 and + 9.7%, p = .028). Among children 1-5 years, the statistical significance is reached with exposures to Dishwashing detergents (+ 13.1%, p = .032), handwashing soaps (+ 28.6%, p = .014) and handwashing gel products (+ 16.8%, p = .010). Contrarily, Liquid Laundry Detergent Capsules decreased in a highly significant manner (- 25%; p = .001). The general severity of exposures showed a highly significant decrease (Moderate: - 10.1%, p = .0002). CONCLUSIONS: This study investigated the relationship between the COVID-19 lockdown and the variations of exposures to some product categories related to the containment measures. The results obtained support any action to be taken by Competent Authorities to implement measures for a safer use of cleaners/disinfectants. This paper shows the benefit in applying the EuPCS to categorize products according to their intended use, though an extension of this system to products not covered by CLP Regulation may be a further advantage.

Towards Precision Medicine for Osteoarthritis: Focus on the Synovial Fluid Proteome.

Osteoarthritis (OA) is a joint degenerative disease that most affects old age. The study of proteomics in synovial fluid (SF) has the task of providing additional elements to diagnose and predict the progress of OA. This review aims to identify the most significant biomarkers in the study of OA and to stimulate their routine use. Some of the major components of the ECM, such as proteoglycan aggrecan and decorin, were found considerably reduced in OA. Some biomarkers have proved useful for staging the temporality of OA: Periostin was found to be increased in early OA, while CRTA1 and MMPs were found to be increased in late OA. In its natural attempt at tissue regeneration, Collagen III was found to be increased in early OA while decreased in late OA. Some molecules studied in other areas, such as ZHX3 (oncological marker), LYVE1, and VEGF (lymph and angiogenesis markers), also have been found to be altered in OA. It also has been recorded that alteration of the hormonal pathway, using a dosage of PPAR-γ and RETN, can influence the evolution of OA. IL-1, one of the most investigated biomarkers in OA-SF, is not as reliable as a target of OA in recent studies. The study of biomarkers in SF appears to be, in combination with the clinical and radiological aspects, an additional weapon to address the diagnosis and staging of OA. Therefore, it can guide us more appropriately towards the indication of arthroplasty in patients with OA.

A Gel-Based Proteomic Analysis Reveals Synovial α-Enolase and Fibrinogen ß-Chain Dysregulation in Knee Osteoarthritis: A Controlled Trial.

BACKGROUND: The identification of synovial fluid (SF) biomarkers that could anticipate the diagnosis of osteoarthritis (OA) is gaining increasing importance in orthopaedic clinical practice. This controlled trial aims to assess the differences between the SF proteome of patients affected by severe OA undergoing Total Knee Replacement (TKR) compared to control subjects (i.e., subjects younger than 35, undergoing knee arthroscopy for acute meniscus injury). METHODS: The synovial samples were collected from patients with Kellgren Lawrence grade 3 and 4 knee osteoarthritis undergoing THR (study group) and young patients with meniscal tears and no OA signs undergoing arthroscopic surgery (control group). The samples were processed and analyzed following the protocol defined in our previous study. All of the patients underwent clinical evaluation using the International Knee Documentation Committee (IKDC) subjective knee evaluation (main outcome), Knee Society Clinical Rating System (KSS), Knee injury and Osteoarthritis Outcome Score (KOOS), and Visual Analogue Scale (VAS) for pain. The drugs' assumptions and comorbidities were recorded. All patients underwent preoperative serial blood tests, including complete blood count and C-Reactive Protein (CRP). RESULTS: The synovial samples' analysis showed a significantly different fibrinogen beta chain (FBG) and alpha-enolase 1 (ENO1) concentration in OA compared to the control samples. A significant correlation between clinical scores, FBG, and ENO1 concentration was observed in osteoarthritic patients. CONCLUSIONS: Synovial fluid FBG and ENO1 concentrations are significantly different in patients affected by knee OA compared with non-OA subjects.

The Usefulness of Synovial Fluid Proteome Analysis in Orthopaedics: Focus on Osteoarthritis and Periprosthetic Joint Infections.

Synovial fluid (SF) is a viscous and mucinous substance produced by the synovium, a specialized connective tissue that lines diarthrodial joints. SF represents a source of disease-related proteins that could be used as potential biomarkers in several articular diseases. Based on these findings the study of SF has been gaining increasing importance, in recent years. This review aims to summarize the usefulness of synovial fluid in orthopaedics research and clinical practice, mainly focusing on osteoarthritis (OA) and periprosthetic joint infections (PJIs). Proteomics of the SF has shown the up-regulation of several components of the classic complement pathway in OA samples, including C1, C2, C3, C4A, C4B, C5, and C4 C4BPA, thus depicting that complement is involved in the pathogenesis of OA. Moreover, proteomics has demonstrated that some pro-inflammatory cytokines, namely IL-6, IL-8, and IL-18, have a role in OA. Several SF proteins have been studied to improve the diagnosis of PJIs, including alpha-defensin (Alpha-D), leukocyte esterase (LE), c-reactive protein (CRP), interleukin-6 (IL-6), calprotectin and presepsin. The limits and potentials of these SF biomarkers will be discussed.