Updates in current concepts in degenerative cervical myelopathy: a systematic review.

Background: The incidence of degenerative cervical myelopathy (DCM) has increased over the years due to an increasing aging population, yet there is a dearth of recent comprehensive data evaluating the multiple facets of this degenerative condition. Recent publications have highlighted the biochemistry and biomechanics of DCM, which are paramount to understanding the degenerative nature of the condition and selecting the most optimal treatment options for improved patient outcomes. In addition, there have been recent studies establishing the superiority of surgical to non-surgical treatments for DCM, which until now was a poorly substantiated claim that has permeated the medical field for decades. The authors of this systematic review sought to collect and assess available high quality peer reviewed data to analyze the nature of DCM and gain a better understanding for its treatment choices. Methods: PubMed and Cochrane Central Register of Controlled Trials were systematically searched on January 19, 2023 with date restrictions of 2015-2023 imposed. For initial data collection, five independent searches were completed using the following keywords: pathogenesis, pathophysiology, and epidemiology of DCM; cervical spondylotic myelopathy (CSM) and DCM recent developments; management and treatment for CSM and DCM; diagnosis and management of DCM; and pathophysiology of DCM. The results were screened for their application to DCM; any study that did not directly address DCM were identified and removed through abstract assessment, such studies included those pertaining to alternative fields including cardiology and psychiatry. Studies found relevant through full-text assessment and those published in English were included in this study and unpublished studies and studies found irrelevant based on titles and keywords were excluded from this study. The 115 articles that met criteria were critically appraised independently by the 2 reviewers and the principles of Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) were applied to assess the quality of evidence from each study. Results: A total of 352 studies resulted from the original search. There were 71 duplicate articles that were removed and a total of 281 articles were screened. 166 articles were then removed based on the exclusion/inclusion criteria, title, and abstract. Of the 138 articles that remained, a final list of 115 articles was created based on the reporting measures. Conclusions: DCM is a multifactorial disease that has the potential to impair neurological function and cause significant paralysis. Although the multiple facets of this disease have not been fully elucidated, there have been significant breakthroughs in understanding the mechanisms involved in this disease process. The use of complex imaging modalities, genetic sequencing, biomarkers, and pharmacological agents has provided insight into the factors involved in the progression of DCM, which has consequently cultivated more refined approaches for diagnosis and treatment of DCM.

Platform for the Delivery of Unformulated RNA In Vivo.

The successful delivery of RNA therapeutics is the gating hurdle to greater clinical translation and utility of this novel class of therapeutics. Delivery strategies today are limited and predominantly rely on lipid nanoparticles or conjugates, which can facilitate hepatic delivery but are poor for achieving uptake outside the liver. The ability to deliver RNA to other organs outside the liver in a formulation-agnostic approach could serve to unlock the broader potential of these therapies and enable their use in a broader set of disease. Here we demonstrate this formulation-agnostic delivery of two model siRNAs using low-frequency ultrasound to the gastrointestinal (GI) tract. Unformulated siRNAs targeting ß-catenin (Ctnnb 1) and Sjögren syndrome antigen B (SSB) genes were successfully delivered to colonic mucosa in mice, achieving robust knockdown of the target mRNA from whole-colon tissue samples. Indeed, the capacity to target and successfully suppress expression from genes underscores the power of this platform to rapidly deliver unformulated and unoptimized sequences against a range of targets in the GI tract.

Reducing the risk of venous thromboembolism following superficial endovenous treatment: A UK and Republic of Ireland consensus study.

OBJECTIVES: Venous thromboembolism is a potentially fatal complication of superficial endovenous treatment. Proper risk assessment and thromboprophylaxis could mitigate this hazard; however, there are currently no evidence-based or consensus guidelines. This study surveyed UK and Republic of Ireland vascular consultants to determine areas of consensus. METHODS: A 32-item survey was sent to vascular consultants via the Vascular and Endovascular Research Network (phase 1). These results generated 10 consensus statements which were redistributed (phase 2). 'Good' and 'very good' consensus were defined as endorsement/rejection of statements by >67% and >85% of respondents, respectively. RESULTS: Forty-two consultants completed phase 1. This generated seven statements regarding risk factors mandating peri-procedural pharmacoprophylaxis and three statements regarding specific pharmacoprophylaxis regimes. Forty-seven consultants completed phase 2. Regarding venous thromboembolism risk factors mandating pharmacoprophylaxis, 'good' and 'very good' consensus was achieved for 5/7 and 2/7 statements, respectively. Regarding specific regimens, 'very good' consensus was achieved for 3/3 statements. CONCLUSIONS: The main findings from this study were that there was 'good' or 'very good' consensus that patients with any of the seven surveyed risk factors should be given pharmacoprophylaxis with low-molecular-weight heparin. High-risk patients should receive one to two weeks of pharmacoprophylaxis rather than a single dose.

Ultra-rapid drug delivery in the oral cavity using ultrasound.

The delivery of therapeutics to the gastrointestinal (GI) mucosa remains primarily a function of diffusion and rapid delivery is a significant goal in drug delivery science. However, delivery is hindered by the molecular barrier properties of the mucosa, as well as environmental factors. We hypothesized that low-frequency ultrasound can overcome these barriers, achieving rapid delivery in an engineered, clinically-relevant system for buccal administration. The hand-held system enabled delivery of macromolecules in short, 60-s treatment times ex vivo. Tolerability of the prototype was demonstrated in awake, (unsedated) dogs. Finally, this technology enhanced the efficacy of the anti-inflammatory agent, budesonide, allowing for prophylactic treatment in a hamster model of oral inflammatory lesions in vivo. The capacity to deliver therapeutics in a targeted and rapid manner in a clinically-relevant form-factor presents an intriguing capability to expand the repertoire of therapeutics that can be applied topically in the mouth and beyond.