Indoxyl Sulfate Administration during Pregnancy Contributes to Renal Injury and Increased Blood-Brain Barrier Permeability.

Rates of pregnancy-related acute kidney injury (PR-AKI) have increased in the U.S over the past two decades, but how PR-AKI affects the blood-brain barrier (BBB) is understudied. AKI is associated with increased amounts of uremic toxins, like indoxyl sulfate (I.S), whose chronic administration leads to BBB and cognitive changes. This study's objective was to determine if (1) PR-AKI increases I.S and (2) if administration of I.S during pregnancy elicits renal injury and/or increases BBB permeability. From gestational day (GD) 11 to GD19, Sprague Dawley rats were given either 100 or 200 mg/kg body-weight dose of I.S. PR-AKI was induced on GD18 via 45 min bilateral renal ischemic reperfusion surgery. On GD18, metabolic cage metrics and metabolic waste was collected and on GD19 blood pressure, and BBB permeability (by Evan's Blue infusion) were measured. I.S and creatinine were measured in both urine and circulation, respectively. One-way ANOVA or student t-tests were performed using GraphPad Prism with a p < 0.05 significance. I.S and PR-AKI led to oliguria. I.S administration led to increased BBB permeability compared to normal pregnant and PR-AKI animals. These results suggest that I.S administration during pregnancy leads to increased BBB permeability and evidence of renal injury comparable to PR-AKI animals.

Biosimilar Perceptions Among Healthcare Professionals and Commercial Medical Benefit Policy Analysis in the United States.

BACKGROUND: Biosimilars represent a significant cost savings opportunity for the entire healthcare system. Despite efforts from the United States Food and Drug Administration, adoption has not been as successful as originally hoped. Perceived barriers to adoption of biosimilars have been described previously, but more knowledge is needed. Further, increased understanding is needed surrounding commercial payer preferences of biosimilars. METHODS: A survey to assess perceived barriers to biosimilar adoption was dispersed to healthcare leaders who work in health-systems, physician practices, and the pharmaceutical industry. Policies from the top 15 commercial payers, by covered lives, were reviewed to collect information surrounding coverage and preferred products to assess if perceptions from healthcare leaders align with payer policies. RESULTS: The largest number of responses (n = 76) came from health-systems (n = 56), followed by pharmaceutical manufacturers (n = 12), and physician practices (n = 8). Responses from each cohort aligned very closely with the composite results of the group. Responses surrounding safety and efficacy were high amongst all groups, while rebate increases to payers for reference products were of highest concern for adoption. United Healthcare had the most policies preferring biosimilars (6/7, 86%). Filgrastim-sndz (Zarxio), had the most preferred statuses for a biosimilar (10/15, 67%). The infliximab reference product had the most preferred statuses for a reference product (9/15, 60%). CONCLUSIONS: Findings from this study outline the greatest perceived barriers to adoption of biosimilars from a variety of different stakeholders. Rebates from reference product manufacturers to payers was the main deterrent for biosimilar use.

Relationship of hypothyroidism and immune response to pegylated IL-10/nivolumab.

Aim: We describe a case of an advanced disease non-small-cell lung cancer patient with low PD-L1 expression, but high tumor mutation burden (35 muts/Mb) who developed immune-related hypothyroidism and achieved subsequent partial response, while on clinical trial (NCT03382912) with nivolumab and PEGylated IL-10 (Pegilodecakin, ARMO BioSciences/Eli Lilly and Company, IN, USA). Results/conclusion: Results suggest positive antitumor activity to combination IL-10/nivolumab despite low PD-L1 expression but in likely relationship to high tumor mutation burden and in association with immune-mediated thyroid dysfunction in this case.

How to freak a Black & Mild: a multi-study analysis of YouTube videos illustrating cigar product modification.

Cigar smoking is increasingly common among adolescents who perceive cigars as less harmful than cigarettes. This perception of reduced harm is especially true for cigars that are user-modified by removing the tobacco binder through a process called 'freaking'. Little is known about 'freaking' and this multi-study, mixed-methods analysis sought to understand better the rationale and prevailing beliefs about this smoking practice using YouTube videos. In Study 1, we conducted a descriptive content analysis on the characteristics of 26 randomly sampled cigar product modification (CPM) videos posted during 2006-10. In Study 2, a thematic analysis was performed on the transcripts of commentary associated with each video to characterize viewers' comments about video content. Study 1 results revealed that 90% of videos illustrated a four-step CPM technique: 'Loosening the tobacco'; 'Dumping the tobacco'; 'Removing the cigar binder' and 'Repacking the tobacco'. Four themes related to the purpose of CPM were also derived from video content: 'Easier to smoke' (54%), 'Beliefs in reduction of health risks' (31%), 'Changing the burn rate' (15%) and 'Taste enhancement' (12%). Study 2 results concerning the content characteristics of video comments were categorized into three themes: 'Disseminating information/answering questions' (81%), 'Seeking advice/asking questions' (69%) and 'Learning cigar modification techniques' (35%). Favorable comments were more common (81%) compared to unfavorable (58%) and comment content suggested low-risk perceptions and poor understanding of smoking harms. These findings highlight a novel means for youth to access information concerning CPM that may have important implications for tobacco control policy and prevention.

Cigar use misreporting among youth: data from the 2009 Youth Tobacco Survey, Virginia.

INTRODUCTION: Researchers have suggested that adolescents' cigar use has increased beyond the rates being reported on tobacco use surveys. Differences in content knowledge and everyday colloquial expressions may be responsible for misreporting of cigar use. To determine whether cigar use is subject to systematic misreporting, we compared reports of general cigar use ("During the past 30 days, on how many days did you smoke cigars, little cigars, and cigarillos?") with reports of brand-specific use ("During the past 30 days, on how many days did you smoke Black & Milds?") among a statewide sample of adolescents in Virginia. METHODS: We examined data from 3,093 youth who completed the 2009 Virginia Youth Tobacco Survey to determine differences in the rate of misreported cigar use (ie, those who reported Black & Mild use but did not report cigar, little cigar, or cigarillo use) for youth with varying demographic profiles and conditions. RESULTS: More than one-half of Black & Mild users (57.3%) did not report general cigar use. Cigar use misreporting was most prevalent among older adolescents, blacks/African Americans, current users of cigarettes and hookah, and youth diagnosed with asthma. CONCLUSION: General cigar-use items on statewide surveys significantly underestimate the prevalence of youth cigar use. More comprehensive measures of cigar use may be beneficial in assessing tobacco use among groups most likely to misreport their tobacco use, such as African Americans and youth diagnosed with asthma.

Ethnic considerations in risk exposure and cigarette use vulnerability among eighth grade students in Virginia.

The purpose of this study was to examine risk exposure and cigarette use vulnerability among 4,559 8th grade students enrolled in Virginia public schools. The study used 2005 statewide data from the Community Youth Survey (CYS) which assessed risks and protective factors for substance use. The findings indicated that Asian youth reported the lowest exposure to community, family, school, and peer/individual risks, but were most vulnerable in terms of past 30-day cigarette use. African-American youth reported significantly greater risk exposure than did their counterparts on more than half of the risks examined; however, they were substantially less vulnerable to the effects of these risks in comparison to their White, Latino, and Asian peers. The findings are discussed with regard to prevention interventions for adolescents from different ethnic groups.

Pertussis with severe pulmonary hypertension and leukocytosis treated with extracorporeal membrane oxygenation.

Pertussis, or "whooping cough," is a highly communicable disease caused by the coccobacillus Bordetella pertussis. Pertussis remains one of the most common causes of death from infectious diseases worldwide. We describe a 5-week-old infant girl who presented with severe pertussis infection associated with extreme leukocytosis and required prolonged extracorporeal membrane oxygenation (ECMO). Nitric oxide therapy resolved the pulmonary hypertension, and she was successfully weaned from ECMO and discharged home after 3 months. We report successful application of ECMO for severe pertussis-induced respiratory failure despite multiple grave prognostic indicators (<1 year age, leukocytosis, pulmonary hypertension) and discuss the role of extracorporeal life support in treating pertussis.

Role of gastrointestinal hormones in neuroblastoma.

As a neuroendocrine tumor, neuroblastoma expresses various gastrointestinal (GI) hormones, such as vasoactive intestinal peptide, gastrin-releasing peptide (GRP), neurotensin, and somatostatin, which exert diverse cellular functions in neuroblastoma. In particular, we have recently found that GRP and its cell surface receptor, GRP-R, are abundantly expressed in neuroblastomas. Moreover, more advanced-stage neuroblastomas demonstrated an increased level of GRP-R, suggesting an important role of GRP in aggressive tumor behavior. This review describes the role of several GI hormones commonly expressed in neuroblastoma and discusses in depth the mitogenic actions of GRP in neuroblastoma. In addition, the molecular mechanisms involved in the GRP-induced stimulation of neuroblastoma cell growth are discussed. Our study results demonstrate a role of GRP as an autocrine/paracrine growth factor and elucidate involvement of specific intracellular signaling, the phosphatidylinositol 3-kinase pathway, in the growth regulation of neuroblastoma.