The key regulators of the transcriptional response to hypoxia and inflammation (hypoxia inducible factor, HIF, and nuclear factor-kappa B, NF-κB, respectively) are evolutionarily conserved and share significant crosstalk. Tissues often experience hypoxia and inflammation concurrently at the site of infection or injury due to fluid retention and immune cell recruitment that ultimately reduces the rate of oxygen delivery to tissues. Inflammation can induce activity of HIF-pathway genes, and hypoxia may modulate inflammatory signaling. While it is clear that these molecular pathways function in concert, the physiological consequences of hypoxia-induced inflammation and how hypoxia modulates inflammatory signaling and immune function are not well established. In this review, we summarize known mechanisms of HIF and NF-κB crosstalk and highlight the physiological consequences that can arise from maladaptive hypoxia-induced inflammation. Finally, we discuss what can be learned about adaptive regulation of inflammation under chronic hypoxia by examining adaptive and maladaptive inflammatory phenotypes observed in human populations at high altitude. We aim to provide insight into the time domains of hypoxia-induced inflammation and highlight the importance of hypoxia-induced inflammatory sensitization in immune function, pathologies, and environmental adaptation.
The rates of immunizations for IBD patients receiving anti-TNF treatment were lower than recommended. Structured reminders for vaccinations and education for both patients and providers (older physicians in particular) may prove beneficial in improving immunization rates among immunocompromised IBD patients.
Drug shortages in the United States continue to be a significant problem that negatively impacts pediatric patients of all ages. These shortages have been associated with a higher rate of relapse among children with cancer, substitution of less effective agents, and greater risk for short- and long-term toxicity. Effective prevention and management of any drug shortage must include considerations for issues specific to pediatric patients; hence, the Pediatric Pharmacy Advocacy Group (PPAG) strongly supports the effective management of shortages by institutions caring for pediatric patients. Recommendations published by groups such as the American Society of Health-System Pharmacists and the American Society for Parenteral and Enteral Nutrition should be incorporated into drug shortage management policies. PPAG also supports the efforts of the Food and Drug Administration (FDA) to not only address but prevent drug shortages caused by manufacturing and quality problems, delays in production, and discontinuations. Prevention, mitigation, and effective management of drug shortages pose significant challenges that require effective communication; hence, PPAG encourages enhanced and early dialogue between the FDA, pharmaceutical manufacturers, professional organizations, and health care institutions.
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