Mesenchymal Stromal Cells and Platelet-Rich Plasma Promote Tendon Allograft Healing in Ovine Anterior Cruciate Ligament Reconstruction

Purpose The effect of bone marrow mesenchymal stromal cells (BMSCs) and platelet-rich plasma (PRP) on tendon allograft maturation in a large animal anterior cruciate ligament (ACL) reconstruction model was reported for the first time. It was hypothesised that compared with non-augmented ACL reconstruction, BMSCs and PRP would enhance graft maturation after 12 weeks and this would be detected using magnetic resonance imaging (MRI). Methods Fifteen sheep underwent unilateral tendon allograft ACL reconstruction using aperture fixation and were randomised into three groups (n = 5). Group 1 received 10 million allogeneic BMSCs in 2 ml fibrin sealant; Group 2 received 12 ml PRP in a plasma clot injected into the graft and bone tunnels; and Group 3 (control) received no adjunctive treatment. At autopsy at 12 weeks, a graft maturation score was determined by the sum for graft integrity, synovial coverage and vascularisation, graft thickness and apparent tension, and synovial sealing at tunnel apertures. MRI analysis (n = 2 animals per group) of the signal–noise quotient (SNQ) and fibrous interzone (FIZ) was used to evaluate intra-articular graft maturation and tendon–bone healing, respectively. Spearman’s rank correlation coefficient (r) of SNQ, autopsy graft maturation score and bone tunnel diameter were analysed. Results The BMSC group (p = 0.01) and PRP group (p = 0.03) had a significantly higher graft maturation score compared with the control group. The BMSC group scored significantly higher for synovial sealing at tunnel apertures (p = 0.03) compared with the control group. The graft maturation score at autopsy significantly correlated with the SNQ (r = − 0.83, p < 0.01). The tunnel diameter of the femoral tunnel at the aperture (r = 0.883, p = 0.03) and mid-portion (r = 0.941, p = 0.02) positively correlated with the SNQ. Conclusions BMSCs and PRP significantly enhanced graft maturation, which indicates that orthobiologics can accelerate the biologic events in tendon allograft incorporation. Femoral tunnel expansion significantly correlated with inferior maturation of the intra-articular graft. The clinical relevance of this study is that BMSCs and PRP enhance allograft healing in a translational model, and biological modulation of graft healing can be evaluated non-invasively using MRI

Electroconvulsive Therapy Practice Changes in Older Individuals Due to COVID-19: Expert Consensus Statement

© 2020 American Association for Geriatric Psychiatry The ubiquitous coronavirus 2019 (COVID-19) pandemic has required healthcare providers across all disciplines to rapidly adapt to public health guidelines to reduce risk while maintaining quality of care. Electroconvulsive therapy (ECT), which involves an aerosol-generating procedure from manual ventilation with a bag mask valve while under anesthesia, has undergone drastic practice changes in order to minimize disruption of treatment in the midst of COVID-19. In this paper, we provide a consensus statement on the clinical practice changes in ECT specific to older adults based on expert group discussions of ECT practitioners across the country and a systematic review of the literature. There is a universal consensus that ECT is an essential treatment of severe mental illness. In addition, there is a clear consensus on what modifications are imperative to ensure continued delivery of ECT in a manner that is safe for patients and Northwell Health, while maintaining the viability of ECT services. Approaches to modifications in ECT to address infection control, altered ECT procedures, and adjusting ECT operations are almost uniform across the globe. With modified ECT procedures, it is possible to continue to meet the needs of older patients while mitigating risk of transmission to this vulnerable population

Advances in exosome therapies in ophthalmology–From bench to clinical trial

During the last decade, the fields of advanced and personalized therapeutics have been constantly evolving, utilizing novel techniques such as gene editing and RNA therapeutic approaches. However, the method of delivery and tissue specificity remain the main hurdles of these approaches. Exosomes are natural carriers of functional small RNAs and proteins, representing an area of increasing interest in the field of drug delivery. It has been demonstrated that the exosome cargo, especially miRNAs, is at least partially responsible for the therapeutic effects of exosomes. Exosomes deliver their luminal content to the recipient cells and can be used as vesicles for the therapeutic delivery of RNAs and proteins. Synthetic therapeutic drugs can also be encapsulated into exosomes as they have a hydrophilic core, which makes them suitable to carry water-soluble drugs. In addition, engineered exosomes can display a variety of surface molecules, such as peptides, to target specific cells in tissues. The exosome properties present an added advantage to the targeted delivery of therapeutics, leading to increased efficacy and minimizing the adverse side effects. Furthermore, exosomes are natural nanoparticles found in all cell types and as a result, they do not elicit an immune response when administered. Exosomes have also demonstrated decreased long-term accumulation in tissues and organs and thus carry a low risk of systemic toxicity. This review aims to discuss all the advances in exosome therapies in ophthalmology and to give insight into the challenges that would need to be overcome before exosome therapies can be translated into clinical practice

Clinical Characteristics and Treatment Patterns of Children and Adults With IgA Nephropathy or IgA Vasculitis: Findings From the CureGN Study

Introduction: The Cure Glomerulonephropathy Network (CureGN) is a 66-center longitudinal observational study of patients with biopsy-confirmed minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, or IgA nephropathy (IgAN), including IgA vasculitis (IgAV). This study describes the clinical characteristics and treatment patterns in the IgA cohort, including comparisons between IgAN versus IgAV and adult versus pediatric patients. Methods: Patients with a diagnostic kidney biopsy within 5 years of screening were eligible to join CureGN. This is a descriptive analysis of clinical and treatment data collected at the time of enrollment. Results: A total of 667 patients (506 IgAN, 161 IgAV) constitute the IgAN/IgAV cohort (382 adults, 285 children). At biopsy, those with IgAV were younger (13.0 years vs. 29.6 years, P < 0.001), more frequently white (89.7% vs. 78.9%, P = 0.003), had a higher estimated glomerular filtration rate (103.5 vs. 70.6 ml/min per 1.73 m2, P < 0.001), and lower serum albumin (3.4 vs. 3.8 g/dl, P < 0.001) than those with IgAN. Adult and pediatric individuals with IgAV were more likely than those with IgAN to have been treated with immunosuppressive therapy at or prior to enrollment (79.5% vs. 54.0%, P < 0.001). Conclusion: This report highlights clinical differences between IgAV and IgAN and between children and adults with these diagnoses. We identified differences in treatment with immunosuppressive therapies by disease type. This description of baseline characteristics will serve as a foundation for future CureGN studies

Glutathione-Related Antioxidant Defense System in Elderly Patients Treated for Hypertension

The purpose of this study was to analyze glutathione antioxidant defense system in elderly patients treated for hypertension. Studies were carried out in the blood collected from 18 hypertensive and 15 age- and sex-matched controls, all subjects age over 60. Hypertensives were on their usual antihypertensive treatment at the time of blood collection. The concentration of glutathione (GSH) in whole blood and activities of glutathione peroxidase (GPx-1), glutathione transferase (GST), and glutathione reductase (GR) in erythrocytes were measured. The data from patients and controls were compared using independent-samples t test. P value of 0.05 and less was considered statistically significant. We observed increased glutathione-related antioxidant defense in treated hypertensive elderly patients (HT) when compared with healthy controls (C). Mean GSH concentration was significantly higher in HT when compared with C: 3.1 ± 0.29 and 2.6 ± 0.25 mmol/L, respectively, P < 0.001. Mean activity of GR was significantly higher in HT group if compared with C: 83.4 ± 15.25 U/g Hb versus 64.2 ± 8.26 U/g Hb, respectively, P < 0.001. Mean activity of GST was significantly higher in HT group compared with C: 3.0 ± 0.60 mmol CDNB-GSH/mgHb/min and 2.6 ± 0.36 mmol CDNB-GSH/mgHb/min, respectively, P < 0.05. No difference in GPx activity was observed between two groups. These results show that glutathione-related antioxidant defense system was enhanced in elderly hypertensive patients treated for their conditions. This suggests important role of glutathione system in blood pressure regulation. Alterations in concentration and activity of antioxidants observed during antihypertensive medication are likely to be related to the effect of the treatment on NO bioavailability

Monitoring quality and coverage of harm reduction services for people who use drugs: a consensus study.

BACKGROUND AND AIMS: Despite advances in our knowledge of effective services for people who use drugs over the last decades globally, coverage remains poor in most countries, while quality is often unknown. This paper aims to discuss the historical development of successful epidemiological indicators and to present a framework for extending them with additional indicators of coverage and quality of harm reduction services, for monitoring and evaluation at international, national or subnational levels. The ultimate aim is to improve these services in order to reduce health and social problems among people who use drugs, such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection, crime and legal problems, overdose (death) and other morbidity and mortality. METHODS AND RESULTS: The framework was developed collaboratively using consensus methods involving nominal group meetings, review of existing quality standards, repeated email commenting rounds and qualitative analysis of opinions/experiences from a broad range of professionals/experts, including members of civil society and organisations representing people who use drugs. Twelve priority candidate indicators are proposed for opioid agonist therapy (OAT), needle and syringe programmes (NSP) and generic cross-cutting aspects of harm reduction (and potentially other drug) services. Under the specific OAT indicators, priority indicators included 'coverage', 'waiting list time', 'dosage' and 'availability in prisons'. For the specific NSP indicators, the priority indicators included 'coverage', 'number of needles/syringes distributed/collected', 'provision of other drug use paraphernalia' and 'availability in prisons'. Among the generic or cross-cutting indicators the priority indicators were 'infectious diseases counselling and care', 'take away naloxone', 'information on safe use/sex' and 'condoms'. We discuss conditions for the successful development of the suggested indicators and constraints (e.g. funding, ideology). We propose conducting a pilot study to test the feasibility and applicability of the proposed indicators before their scaling up and routine implementation, to evaluate their effectiveness in comparing service coverage and quality across countries. CONCLUSIONS: The establishment of an improved set of validated and internationally agreed upon best practice indicators for monitoring harm reduction service will provide a structural basis for public health and epidemiological studies and support evidence and human rights-based health policies, services and interventions