Engineering approaches for innate immune-mediated tumor microenvironment remodeling.

Cancer immunotherapy offers transformative promise particularly for the treatment of lethal cancers, since a correctly trained immune system can comprehensively orchestrate tumor clearance with no need for continued therapeutic intervention. Historically, the majority of immunotherapies have been T cell-focused and have included immune checkpoint inhibitors, chimeric antigen receptor T cells, and T-cell vaccines. Unfortunately T-cell-focused therapies have failed to achieve optimal efficacy in most solid tumors largely because of a highly immunosuppressed 'cold' or immune-excluded tumor microenvironment (TME). Recently, a rapidly growing treatment paradigm has emerged that focuses on activation of tumor-resident innate antigen-presenting cells, such as dendritic cells and macrophages, which can drive a proinflammatory immune response to remodel the TME from 'cold' or immune-excluded to 'hot'. Early strategies for TME remodeling centered on free cytokines and agonists, but these approaches have faced significant hurdles in both delivery and efficacy. Systemic toxicity from off-target inflammation is a paramount concern in these therapies. To address this critical gap, engineering approaches have provided the opportunity to add 'built-in' capabilities to cytokines, agonists, and other therapeutic agents to mediate improved delivery and efficacy. Such capabilities have included protective encapsulation to shield them from degradation, targeting to direct them with high specificity to tumors, and co-delivery strategies to harness synergistic proinflammatory pathways. Here, we review innate immune-mediated TME remodeling engineering approaches that focus on cytokines, innate immune agonists, immunogenic viruses, and cell-based methods, highlighting emerging preclinical approaches and strategies that are either being tested in clinical trials or already Food and Drug Administration approved.

Pelvic vein embolization: an assessment of the readability and quality of online information for patients.

INTRODUCTION: Pelvic congestion syndrome is a controversial topic. Pelvic vein embolization is a minimally invasive treatment for pelvic congestion syndrome. We aimed to assess the quality of information available on the Internet and determine how accessible information provided by the main IR societies was to patients. MATERIALS AND METHODS: The most commonly used term relating to pelvic vein embolization was searched across the five most-used English language search engines, with the first 25 web pages returned by each engine included for analysis. Duplicate web pages, nontext content and web pages behind paywalls were excluded. Web pages were analyzed for quality and readability using validated tools: DISCERN score, JAMA Benchmark Criteria, HONcode Certification, Flesch Reading Ease Score, Flesch-Kincaid Grade Level, and Gunning-Fog Index. RESULTS: The most common applicable term was "Pelvic Vein Embolization". Mean DISCERN quality of information provided by websites is "fair". Flesh-Kincaid readability tests and Gunning-Fog Index demonstrated an average "college level" of reading ease. HON code certification was demonstrated in less than one third of web pages. Professional societies and scientific journals demonstrated the highest average JAMA and DISCERN scores, while for-profit organizations and healthcare providers demonstrated the lowest. Only information from 1 of 3 interventional societies was included in the first 25 search engine pages. CONCLUSION: The quality of information available online to patients is "fair" and outside of scientific journals the majority of web pages do not meet the JAMA benchmark criteria. These findings call for the production of high-quality and comprehensible content regarding interventional radiology, where physicians can reliably direct their patients for information.

Induction of labour postdates in primiparae using vaginal prostaglandin tablets.

The management of pregnancy after 40 completed weeks remains controversial because induction of labour has been, in the past, associated with an increase in the incidence of caesarean section. This study examined the use of vaginal prostaglandin tablets for the induction of labour in selected primiparae after forty one weeks of pregnancy. The outcome of prostaglandin induction in 118 consecutive patients was compared with the outcome in 90 consecutive patients who went into labour spontaneously at the same gestation before induction could be undertaken. The active management of labour was applied in both groups and, therefore, the management of labour was strictly standardised. There was no difference between the two groups in the mode of delivery. Nor was prostaglandin induction associated with an increased incidence of prolonged labour. In selected primiparae, the cautious use of vaginal prostaglandin tablets can induce labour successfully postdates without increasing the complications of labour. A larger study is required to examine the effects of the induction of labour at this gestation on the fetal outcome.

Active management of labor associated with a decrease in the cesarean section rate in nulliparas.

Active management of labor was introduced as the standard policy for the care of nulliparas in labor in a London maternity hospital. The basis of this management is, first, a strict diagnosis of labor and second, the early diagnosis and prompt treatment of dystocia. This study describes the outcome in 1000 consecutive nulliparas who were actively managed. In this multiracial population, active management was associated with a decrease in the cesarean section rate, without any evidence of an increase in perinatal mortality or morbidity. The results indicate that active management can be safely applied outside of Ireland to reduce the incidence of cesarean childbirth. It is suggested that this approach to the management of dystocia in labor be evaluated in the United States in a randomized controlled trial.

Obstetric outcome in first-time mothers aged 40 years and over.

This retrospective study examines the outcome of pregnancy after 28 weeks gestation in 100 consecutive, unselected primiparae who were aged 40 years or more. Antenatally, the incidence of hypertension was increased. There was an increased incidence of induction of labour and caesarean section. There were no maternal deaths and no evidence of an increase in maternal morbidity. After correction for congenital malformations, the perinatal mortality rate was not increased in these mothers. The incidence of Down's Syndrome was 4%, as expected. In general, the outcome of the pregnancy for the mother and her baby was satisfactory. Contrary to popular opinion, the results justify an optimistic approach to women about to become mothers for the first time in their forties, and the traditional high intervention rates may not be justified.