H-Wave® Device Stimulation for Chronic Neck Pain: A Patient-Reported Outcome Measures (PROMs) Study.

INTRODUCTION: Chronic neck pain (cNP) is one of the leading causes of disability worldwide, often being refractory to conventional forms of treatment. Various forms of electrical stimulation have been proposed to decrease pain and improve function. Patient-reported outcome measures (PROMs) for treatment of cNP have rarely been published. METHODS: An independent retrospective statistical analysis of PROMs data for users of H-Wave® device stimulation (HWDS), prospectively collected by the device manufacturer over a 4-year period, was conducted. Final surveys for 34,192 pain management patients were filtered for pain chronicity limited to 3-24 months and device use of 22-365 days, resulting in 11,503 patients with "all diagnoses"; this number was further reduced to 1482 patients with cNP, sprain, or strain. RESULTS: Neck pain was reduced by 3.13 points (0-10 pain scale), with significant (≥ 20%) relief in 86.6%. Function/activities of daily living (ADL) improved in 96.19%, while improved work performance was reported in 84.76%. Medication use decreased or stopped in 65.42% and sleep improved in 60.39%. Over 95% reported having expectations met or exceeded, service satisfaction, and confidence in device use, while no adverse events were reported. Subgroup analyses found positive benefit associations with longer duration of device use. CONCLUSION: Near-equivalent outcomes were self-reported by cNP HWDS patients as for (previously published) chronic low back pain (cLBP) patients. HWDS provided effective and safe cNP relief, improvements in function and ADL, along with additional benefits including decreased medication use, better sleep, and improved work performance.

Addressing cortex dysregulation in youth through brain health check coaching and prophylactic brain development.

The Carter Center has estimated that the addiction crisis in the United States (US), if continues to worsen at the same rate, may cost the country approximately 16 trillion dollars by 2030. In recent years, the well-being of youth has been compromised by not only the coronavirus disease 2019 pandemic but also the alarming global opioid crisis, particularly in the US. Each year, deadly opioid drugs claim hundreds of thousands of lives, contributing to an ever-rising death toll. In addition, maternal usage of opioids and other drugs during pregnancy could compromise the neurodevelopment of children. A high rate of DNA polymorphic antecedents compounds the occurrence of epigenetic insults involving methylation of specific essential genes related to normal brain function. These genetic antecedent insults affect healthy DNA and mRNA transcription, leading to a loss of proteins required for normal brain development and function in youth. Myelination in the frontal cortex, a process known to extend until the late 20s, delays the development of proficient executive function and decision-making abilities. Understanding this delay in brain development, along with the presence of potential high-risk antecedent polymorphic variants or alleles and generational epigenetics, provides a clear rationale for embracing the Brain Research Commission's suggestion to mimic fitness programs with an adaptable brain health check (BHC). Implementing the BHC within the educational systems in the US and other countries could serve as an effective initiative for proactive therapies aimed at reducing juvenile mental health problems and eventually criminal activities, addiction, and other behaviors associated with reward deficiency syndrome.

Identification of stress-induced epigenetic methylation onto dopamine D2 gene and neurological and behavioral consequences.

The D2 dopamine receptor (DRD2) gene has garnered substantial attention as one of the most extensively studied genes across various neuropsychiatric disorders. Since its initial association with severe alcoholism in 1990, particularly through the identification of the DRD2 Taq A1 allele, numerous international investigations have been conducted to elucidate its role in different conditions. As of February 22, 2024, there are 5485 articles focusing on the DRD2 gene listed in PUBMED. There have been 120 meta-analyses with mixed results. In our opinion, the primary cause of negative reports regarding the association of various DRD2 gene polymorphisms is the inadequate screening of controls, not adequately eliminating many hidden reward deficiency syndrome behaviors. Moreover, pleiotropic effects of DRD2 variants have been identified in neuropsychologic, neurophysiologic, stress response, social stress defeat, maternal deprivation, and gambling disorder, with epigenetic DNA methylation and histone post-translational negative methylation identified as discussed in this article. There are 70 articles listed in PUBMED for DNA methylation and 20 articles listed for histone methylation as of October 19, 2022. For this commentary, we did not denote DNA and/or histone methylation; instead, we provided a brief summary based on behavioral effects. Based on the fact that Blum and Noble characterized the DRD2 Taq A1 allele as a generalized reward gene and not necessarily specific alcoholism, it now behooves the field to find ways to either use effector moieties to edit the neuroepigenetic insults or possibly harness the idea of potentially removing negative mRNA-reduced expression by inducing "dopamine homeostasis."

Exosomes for the Management of Low Back Pain: A Review of Current Clinical Evidence.

Low back pain affects millions of people, creating an enormous financial burden on the global healthcare system. Traditional treatment modalities are short-lived and have shortcomings. Recently, orthobiologics, including extracellular vesicles or exosomes derived from mesenchymal stem cells, have markedly increased for managing musculoskeletal conditions. Here, the primary aim is to review the outcomes of clinical studies using extracellular vesicles or exosomes for treating low back pain. Numerous databases (Scopus, PubMed, Web of Science, Embase, and Google Scholar) were searched using terms for the intervention 'exosomes' and the treatment 'low back pain' for studies published in English to March 18, 2024. Articles utilizing exosomes for the management of low back pain were included. Articles not utilizing exosomes, not explicitly stating the presence of exosomes in their formulation, or not targeting low back pain were excluded. Two articles that met our pre-defined criteria were included in this review. The results showed that administering extracellular vesicles or exosomes is safe and potentially effective in patients suffering from low back pain. Yet, more sufficiently powered, multi-center, prospective, randomized, and non-randomized trials with longer follow-up are essential to assess the long-term safety and efficacy of extracellular vesicles or exosomes derived from various sources and to support its routine clinical use for managing low back pain.

Optimization of Polycaprolactone and Type I Collagen Scaffold for Tendon Tissue Regeneration.

Introduction Collagen synthesis is vital for restoring musculoskeletal tissues, particularly in tendon and ligamentous structures. Tissue engineering utilizes scaffolds for cell adhesion and differentiation. Although synthetic scaffolds offer initial strength, their long-term stability is surpassed by biological scaffolds. Combining polycaprolactone (PCL) toughness with collagen in scaffold design, this study refines fabrication via electrospinning, aiming to deliver enduring biomimetic matrices for widespread applications in musculoskeletal repair. Methods Electrospinning employed four solutions with varied collagen and PCL concentrations, dissolved in chloroform, methanol, and hexafluoro-2-propanol. Solutions were combined to yield 60 mg/mL concentrations with different collagen/PCL ratios. Electrospinning at 12-14kV voltage produced scaffolds, followed by vacuum-drying. Collagen coating was applied to PCL and 15% collagen/PCL scaffolds using a 0.1% collagen solution. SEM characterized fiber morphology, tensile testing was conducted to determine the mechanical properties of the scaffold, and Fourier-transform infrared (FTIR) spectroscopy analyzed scaffold composition. Atomic force microscopy (AFM) analyzed the stiffness properties of individual fibers, and a finite element model was developed to predict the mechanical properties. Cell culture involved seeding human bone marrow mesenchymal stem cells onto scaffolds, which were assessed through Alamar Blue assay and confocal imaging. Results Various scaffolds (100% PCL, PCL-15% collagen, PCL-25% collagen, PCL-35% collagen) were fabricated to emulate the extracellular matrix, revealing collagen's impact on fiber diameter reduction with increasing concentration. Tensile testing highlighted collagen's initial enhancement of mechanical strength, followed by a decline beyond PCL-15% collagen. FTIR spectroscopy detected potential hydrogen bonding between collagen and PCL. A finite element model predicted scaffold response to external forces which was validated by the tensile test data. Cell viability and proliferation assays demonstrated successful plating on all scaffolds, with optimal proliferation observed in PCL-25% collagen. Confocal imaging confirmed stem cell integration into the three-dimensional material. Collagen coating preserved nanofiber morphology, with no significant changes in diameter. Coating of collagen significantly altered the tensile strength of the scaffolds at the macro scale. AFM highlighted stiffness differences between PCL and collagen-coated PCL mats at the single fiber scale. The coating process did not significantly enhance initial cell attachment but promoted increased proliferation on collagen-coated PCL scaffolds. Conclusion The study reveals collagen-induced mechanical and morphological alterations, influencing fiber alignment, diameter, and chemical composition while emphasizing scaffolds' vital role in providing a controlled niche for stem cell proliferation and differentiation. The optimization of each of these scaffold characteristics and subsequent finite element modeling can lead to highly repeatable and ideal scaffold properties for stem cell integration and proliferation.

Effect of weight-adjusted antimicrobial antibiotic prophylaxis on postoperative dosage and surgical site infection incidence in total joint arthroplasty.

Surgical site infections (SSI) following total joint arthroplasty pose a significant concern for both providers and patients across the globe. Currently, administration of antimicrobial antibiotic prophylaxis is used throughout the world to reduce the incidence of SSI. However, the correct dosage and frequency of administration remains debatable. In this editorial, we emphasized the determination of the effect of administration of weight-adjusted antimicrobial antibiotic prophylaxis regime on the incidence of SSI and postoperative dosage reduction compared to the conventionally used regime during total joint arthroplasty. The results demonstrated similar efficacy between both regimes with respect to the incidence of SSI. In addition, weight-adjustment led to reduced postoperative dosage and has the potential to reduce chances of achieving lower therapeutic concentration, drug resistance, drug toxicity, and costs.

Management of rotator cuff injuries using allogenic platelet-rich plasma.

Rotator cuff injuries are a major cause of shoulder pain, affecting the quality of life and producing a significant burden on healthcare systems. Conservative management modalities are prioritized, resorting to surgery only when required. The field of regenerative medicine involving the use of biologics, such as platelet-rich plasma (PRP), has evolved and shown potential for managing rotator cuff injuries. Nonetheless, limitations including subpar outcomes have led clinicians to question the efficacy of autologous PRP. To circumvent this, the possibility of utilizing a standardized and well-characterized allogenic PRP for RCI has been explored. In this manuscript, we qualitatively present the evidence from in vitro, pre-clinical, clinical and ongoing studies investigating the applications of allogenic PRP in the context of rotator cuff disorders. Administration of allogenic PRP is safe and potentially efficacious to manage rotator cuff injuries, though more adequately powered randomized controlled trials with longer follow-ups are warranted to further establish the efficacy of allogenic PRP and justify its routine clinical use.

Autologous Protein Solution (APS) and Osteoarthritis of the Knee: A Scoping Review of Current Clinical Evidence.

Knees are the most regularly affected weight-bearing joints in osteoarthritis (OA), impacting millions of individuals across the globe. The incidence of knee OA will further rise with increasing rates of obesity and lifespan, resulting in a significant increase in the worldwide socioeconomic burden. Conventional therapies used to manage the symptoms associated with knee OA have limitations. Lately, there has been an increased interest in the use of autologous peripheral blood-derived orthobiologics (APBO), including autologous protein solution (APS), for the management of knee OA. Here, the primary objective is to summarize the outcomes of clinical studies involving APS for the treatment of knee OA. Several databases (Embase, Scopus, PubMed, and Web of Science) were searched using terms for the intervention "APS" and treatment "knee OA" for articles published in English until January 21, 2024. All clinical studies using APS as an intervention for the treatment of knee OA were included. Studies not utilizing APS alone or not aiming at the management of knee OA were excluded. Six clinical studies that met our predefined search terms and inclusion and exclusion criteria were included in this study. The results demonstrated that the intra-articular administration of APS is safe and efficacious in reducing pain and/or improving function in patients suffering from knee OA. However, more multicenter, randomized controlled trials involving active comparators, with adequate power and long-term follow-up along with post-market real-world studies in clinical practice are required to further assess the efficacy of APS and justify its regular clinical use for the management of knee OA.

Case Report: Portable handheld ultrasound facilitates intra-articular injections in articular foot pathologies.

Background: Intra-articular injections are commonly used to manage joint pathologies, including osteoarthritis. While conventional ultrasound (US) guidance has generally improved intra-articular injection accuracy, forefoot and midfoot joint interventions are still often performed without imaging guidance. This pilot study aims to evaluate the efficacy of office-based, portable ultrasound (P-US) guided intra-articular injections for forefoot and midfoot joint pain caused by various degenerative pathologies. Methods: A retrospective analysis was conducted on a series of consecutive patients who underwent P-US guided intra-articular injections following a chief complaint of forefoot or midfoot joint pain. Patients reported their pain levels using the Visual Analog Scale (VAS) pre-injection and at 3 months follow-up. The procedure was performed by an experienced foot and ankle surgeon using a linear array transducer for guidance, and a 25-gauge needle was used to inject a combination of 2 cc 1% lidocaine and 12 cc of Kenalog (40 mg/ml). Complications and pain scores were analyzed using a paired t-test and p < 0.05 was considered significant. Results: We included 16 patients, 31% male and 69% female with a mean age (±SD) of 61.31 (±12.04) years. None of the patients experienced immediate complications following the intervention. The mean pre-injection VAS score was significantly reduced from 5.21 (±2.04) to a mean of 0.50 (±1.32) at 3 months follow-up (P < 0.001). Thirteen patients reported complete resolution of pain at the 3-month follow-up. No adverse events were reported throughout the duration of the study. Conclusion: This pilot study suggests P-US-guided intra-articular injections offer a safe and effective method for managing forefoot and midfoot joint pain caused by various arthritic pathologies. Further research is warranted to establish the long-term efficacy and comparative effectiveness of P-US-guided injections in larger patient cohorts as compared to non-image guided injections.

Autologous Conditioned Plasma (ACP) and Osteoarthritis of the Knee: A Review of Current Clinical Evidence.

The primary objective of this study is to record the clinical outcomes of autologous conditioned plasma (ACP) for the treatment of knee osteoarthritis (OA) based on published literature. Multiple databases (PubMed, Embase, Web of Science and Scopus) were searched using terms for "knee OA" and the intervention "ACP" for articles published in English to January 4, 2024. All clinical studies using ACP for knee OA were included. Studies not utilizing ACP alone, i.e. used as an adjunct with other modalities or not focusing on the management of knee OA, were excluded. Five studies, three randomized controlled trials (RCTs) and two real-world post-market studies conducted in a clinical practice met the inclusion/exclusion criteria and were included in this study. All studies demonstrated statistically significant improvements in various patient-reported outcome measures (PROMs), however the studies performed in the clinical practice reported non-accomplishment of minimally clinically important difference (MCID). The results demonstrated the potential of ACP for management of knee OA, however the MCID was not achieved in real-world clinical settings. Thus, more adequately powered RCTs with longer follow-up as well as real-world post-market studies are warranted to establish long-term efficacy and justify routine clinical use, respectively, of ACP in patients suffering with knee OA.

Hyperacute Serum and Knee Osteoarthritis.

The knees are the most frequently affected weight-bearing joints in osteoarthritis (OA), impacting millions of people globally. With increasing life spans and obesity rates, the prevalence of knee OA will further mount, leading to a significant increase in the economic burden. The usual treatment modalities utilized to manage knee OA have shortcomings. Over the last decade, the field of regenerative medicine involving the use of biologics, such as autologous peripheral blood-derived orthobiologics, including hyperacute serum (HS), has evolved and shown potential for managing knee OA. In this manuscript, we qualitatively present the in vitro, pre-clinical, clinical, and ongoing studies investigating the applications of HS in the context of knee OA. Seven in vitro studies and one clinical study fit the scope of our manuscript. The results demonstrated that the administration of HS is potentially safe and efficacious in terms of increasing the viability of osteoarthritic chondrocytes, reducing pain and inflammation, and improving function in patients with knee OA. However, due to insufficient literature, pre-clinical studies to better understand the mechanism of action are required. In addition, adequately powered, multi-center, non-randomized, and randomized controlled trials with longer follow-up are warranted to establish the safety and efficacy of HS for the management of knee OA and to justify its clinical use.

H-Wave® Device Stimulation for Chronic Low Back Pain: A Patient-Reported Outcome Measures (PROMs) Study.

INTRODUCTION: Chronic low back pain (cLBP) is a problem globally, creating a tremendous economic burden. Since conventional treatments often fail, various forms of electrical stimulation have been proposed to improve function and decrease pain. Patient-reported outcome measures (PROMs) have not been adequately reported in the electrical stimulation literature. METHODS: A retrospective independent statistical analysis was conducted on PROMs data for users of H-Wave® device stimulation (HWDS) collected by the device manufacturer over a period of 4 years. Final surveys for 34,192 pain management patients were filtered for pain chronicity limited to 3-24 months and device use of 22-365 days, resulting in 11,503 patients with "all diagnoses"; this number was then reduced to 2711 patients with nonspecific cLBP, sprain, or strain. RESULTS: Reported pain was reduced by 3.12 points (0-10 pain scale), with significant (≥ 20%) relief in 85.28%. Function/activities of daily living (ADL) improved in 96.36%, while improved work performance was reported in 81.61%. Medication use decreased or stopped in 64.41% and sleep improved in 59.76%. Over 96% reported having expectations met or exceeded, service satisfaction, and confidence in device use, while no adverse events were reported. Subgroup analyses found positive associations with longer duration of device use, home exercise participation, and working, whereas older age and longer pain chronicity resulted in reduced benefit. Similar analysis of the larger all-diagnoses cohort demonstrated near-equivalent positive outcomes. CONCLUSION: Treatment outcomes directly reported by cLBP HWDS patients demonstrated profound positive effects on function and ADL, robust improvement in pain perception, and additional benefits like decreased medication use, better sleep, and improved work performance, representing compelling new evidence of treatment efficacy.

Wharton's jelly and osteoarthritis of the knee.

INTRODUCTION: The existing treatment modalities for knee osteoarthritis (OA) do not actually address the pathology. Biological therapies, including those using material derived from perinatal tissues, represent a ground-breaking approach to alleviating the symptoms of OA of the knee. SOURCE OF DATA: Current scientific literature published in PubMed (MEDLINE), Embase and Scopus databases. Trials registered in various clinical trial databases. AREAS OF AGREEMENT: Perinatal tissues including Wharton's jelly (WJ) and associated mesenchymal stem cells (MSCs) can be used for the management of knee OA. AREAS OF CONTROVERSY: The efficacy of WJ and associated MSCs in the management of knee OA is still controversial. GROWING POINTS: The use of WJ and associated MSCs in the management of knee OA is safe and appears to be effective. AREAS TIMELY FOR DEVELOPING RESEARCH: The present published evidence suggests that WJ tissue and associated MSCs offer an encouraging alternative for the management of knee OA. The published in vitro, preclinical and clinical investigations demonstrate the therapeutic potential of WJ and promote further research in this field to provide symptomatic relief to patients suffering from OA, aiming also to regenerate the osteoarthritic hyaline cartilage, with disease-modifying effects. Future adequately powered randomized controlled trials should be undertaken to establish whether WJ is helpful in the management of OA of the knee.

Allogenic Platelet-Rich Plasma for the Treatment of Adhesive Capsulitis.

Adhesive capsulitis (AC) is a common shoulder disorder leading to pain and restricted range of motion (ROM) and affects the patient's activities of daily living (ADL) and overall quality of life (QoL). Conservative therapies are prioritized, resorting to surgical intervention only when necessary. Unfortunately, these modalities have limitations and do not address the underlying pathological cause of AC. The use of autologous biologics, such as platelet-rich plasma (PRP), has evolved and shown promise for managing musculoskeletal (MSK) injuries, including AC. However, subpar functional outcomes have led clinicians to question the long-term efficacy of autologous PRP. To circumvent this, the possibility of utilizing a standardized and well-characterized allogenic PRP for AC has been explored. In this manuscript, we qualitatively present in vitro, pre-clinical, clinical, and ongoing studies investigating the varied applications of allogenic PRP for the management of AC. The results demonstrated that allogenic PRP acts in a pleiotropic manner and decreases pro-inflammatory cytokines only in the inflammatory condition. In addition, the administration of allogenic PRP is safe and potentially efficacious, in terms of reducing pain and improving range of motion, shoulder strength, and function, in non-surgical management of AC. Nonetheless, more pre-clinical studies and adequately powered, multicenter, prospective, non-randomized, and randomized controlled trials with longer follow-up are warranted to further establish the safety and efficacy of allogenic PRP and justify its routine clinical use.

Allogenic umbilical cord tissue for temporomandibular joint injuries.

The temporomandibular joint (TMJ) is crucial for functions of daily living such as mastication and articulation. Common TMJ issues include osteoarthritis, internal derangement, and myofascial pain dysfunction. Conservative methods such as physical therapy and medications are used, with surgical options such as arthroscopy and replacement for severe cases. Emerging regenerative medicine explores non-surgical treatments using human stem cells from umbilical cord derivatives, showing potential for tissue regeneration in TMJ disorders. A systematic search was conducted across PubMed, Embase, Scopus, and Web of Science databases, adhering to PRISMA guidelines, aiming to identify relevant articles published in English until August 2023. The search used specific terms to target in vitro, preclinical, and clinical studies on umbilical cord (UC)-derived tissue and mesenchymal stem cells (MSCs) for treating TMJ disorders. The search was extended to three clinical trial registries for on-going investigations related to UC tissue and MSCs for TMJ disorder management. The studies included in this article report the safety and efficacy profiles of allogenically acquired, umbilical cord-derived tissues and associated mesenchymal stem cells for temporomandibular joint ailments, future adequately powered, randomized controlled trials are warranted to conclusively justify the clinical use of this biologic therapy.