Exploring Health Care Disparities in Genetic Testing and Research for Hereditary Cardiomyopathy: Current State and Future Perspectives.

Background Hereditary cardiomyopathies are commonly occurring myocardial conditions affecting heart structure and function with a genetic or familial association, but the etiology is often unknown. Cardiomyopathies are linked to significant mortality, requiring robust risk stratification with genetic testing and early diagnosis. Hypothesis We hypothesized that health care disparities exist in genetic testing for hereditary cardiomyopathies within clinical practice and research studies. Methods In a narrative fashion, we conducted a literature search with online databases such as PubMed/MEDLINE, Google Scholar, EMBASE, and Science Direct on papers related to hereditary cardiomyopathies. A comprehensive analysis of findings from articles in English on disparities in diagnostics and treatment was grouped into four categories. Results Racial and ethnic disparities in research study enrollment and health care delivery favor White populations and higher socioeconomic status, resulting in differences in the development and implementation of effective genetic screening. Such disparities have shown to be detrimental, as minorities often suffer from disease progression to heart failure and sudden cardiac death. Barriers related to clinical genetic testing included insurance-related issues and health illiteracy. The underrepresentation of minority populations extends to research methodologies, as testing in ethnic minorities resulted in a significantly lower detection rate and diagnostic yield, as well as a higher likelihood of misclassification of variants. Conclusions Prioritizing minority-based participatory research programs and screening protocols can address systemic disparities. Diversifying research studies can improve risk stratification strategies and impact clinical practice.

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.

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 Umbilical Cord Tissue for Rotator Cuff Injuries.

Highly prone to injury, the rotator cuff greatly contributes to the stability and mobility of the shoulder. Clinicians prioritize conservative treatment, resorting to surgery only when necessary, although they are hindered by inherent limitations. Biological therapies, including perinatal tissue, such as umbilical cord (UC) tissue, hold promise for treating rotator cuff injuries (RCIs) in the field of regenerative medicine. This article qualitatively presents the in vitro, preclinical, clinical, and ongoing scientific literature exploring the application of UC tissue and associated mesenchymal stem cells in the context of RCIs. Employing the "Preferred Reporting Items for Systematic Reviews and Meta-analyses" guidelines, a systematic review was conducted. These studies have presented substantial evidence indicating that UC tissue and UC-derived mesenchymal stem cells are safe and potentially efficacious for managing RCIs, though more adequately powered randomized controlled trials are warranted to further establish efficacy and justify 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.

Allogenic Umbilical Cord Tissue as a Scaffold for Ankle Osteoarthritis.

Osteoarthritis (OA) of ankle followed by injury to the talus is one of the most common disorders of ankle. Traditional treatment modalities have limitations and do not address the etiopathogenetic cause of OA. Perinatal tissue-derived biologics such as umbilical cords have shown potential for musculoskeletal regenerative medicine applications. This article qualitatively presents the in vitro, pre-clinical, clinical, and ongoing scientific literature exploring the application of umbilical cord tissue in the context of ankle OA. We identified only one clinical study wherein allogenic umbilical cord tissue was applied as a scaffold to the degenerated cartilage in the subtalar synovial joint. Administration of umbilical cord tissue is safe and potentially efficacious in patients with ankle OA. However, more in vitro, pre-clinical studies and high-powered, multi-center, non-randomized and randomized controlled trials are warranted to further establish the safety and efficacy of umbilical cord to justify its clinical use in ankle OA patients.

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 Perinatal Tissue for Musculoskeletal Regenerative Medicine Applications: A Systematic Review.

Producing tremendous amounts of stress and financial burden on the global patient population and healthcare systems around the world, most current modalities of treatment for musculoskeletal ailments often do not address the etiopathogenetic causes of these disorders. Regenerative medicine for musculoskeletal disorders relies on orthobiologics derived from either allogenic or autologous sources. Multiple drawbacks are associated with autologous sources, including donor-site morbidity, a dearth of studies, and variability in both patient reported and clinical/functional outcomes. On the other hand, allogenic sources address several of these concerns, and continue to be a suitable source of mesenchymal stem cells (MSCs). This review qualitatively reports both the preclinical and clinical outcomes of publications studying the applications of umbilical cord (-derived Wharton's jelly), amniotic suspension allograft, amniotic membrane, and amniotic fluid in musculoskeletal medicine. A systematic review was conducted utilizing the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines on studies published between January 2010 and October 2022 that used allogeneic perinatal tissues. Further randomized controlled clinical studies are necessary to properly evaluate the safety and efficacy of these tissues in orthopedic surgery.

Allogenic perinatal tissue for musculoskeletal regenerative medicine applications: a systematic review protocol.

BACKGROUND: Musculoskeletal ailments impact the lives of millions of people, and at times necessitate surgery followed by physiotherapy, drug treatments, or immobilization. Regenerative musculoskeletal medicine has undergone enormous progress over the last few decades. Sources of tissues used for regenerative medicine purposes can be grouped into autologous or allogenic. Although autologous sources are promising, there is a wide range of limitations with the treatment, including the lack of randomized controlled studies for orthopaedic conditions, donor site morbidity, and highly variable outcomes for patients. Allogenic sources bypass some of these shortcomings and are a promising source for orthopaedic regenerative medicine applications. METHODS: A systematic search will be performed using PubMed, Elsevier, ScienceDirect, and Google Scholar databases for articles published in English before May 2022. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement and guidelines will be used. Studies will be eligible if they apply to acute and chronic orthopaedic musculoskeletal complications or animal or human disease models. Publications must include the use of MSCs and/or tissue obtained from amniotic/chorionic membrane, amniotic fluid, umbilical cord, and/or umbilical cord-derived Wharton's jelly as an intervention. Placebos, noninjury models, acute injury models, non-injury models, and gold standard treatments will be compared. The study selection will be performed by two independent reviewers using a dedicated reference management software. Data synthesis and meta-analysis will be performed separately for preclinical and clinical studies. DISCUSSION: The results will be published in relevant peer-reviewed scientific journals. Investigators will present results at national or international conferences. TRIAL REGISTRATION: The Protocol will be registered on PROSPERO international prospective register of systematic reviews prior to commencement.