epinephrine (epinephrine, Dey / EpiPen / epinephrine, Mylan)

Variability in Vasoactive Medication use Across Pediatric Intensive Care Units: A PICU Data Collaborative Study, 2010-2022.

Brown Stephanie R SR, Heneghan Julia A JA, Badke Colleen C, Dziorny Adam C AC et al.

ObjectiveUse of vasoactive medications is common in pediatric intensive care units (ICUs), however evidence to guide medication selection is limited likely resulting in practice variation. Our objective was to describe the use of vasoactive infusions across ICUs and sites.DesignRetrospective cohort study using the multi-institutional PICU Data Collaborative (PDC) database.SettingFour pediatric ICUs (PICUs) and three cardiac ICUs (CICUs) from the U.S. participating in the PDC.PatientsPatients admitted to a participating ICU between 2010 and 2022 who received a vasoactive infusion within 7 days of ICU admission.InterventionsNone.Measurements and Main ResultsA vasoactive infusion was administered within the first 7 days of admission in 16,959 (22%) out of a total of 75,953 ICU encounters. CICU encounters comprised 20% of all ICU encounters but 60% of those with a vasoactive infusion. The most frequently used vasoactive medications were milrinone (63%) and epinephrine (59%). We found a statistically significant difference in the frequency of each vasoactive infusion between PICU sites (P < 0.001) and between CICU sites (P < 0.001). The median peak vasoactive inotrope score (VIS) was 10 [IQR 5.5-20] and 8 [IQR 5-12.5] among PICU and CICU encounters respectively.ConclusionsWe found significant variability in the frequency of vasoactive infusion medication use between sites and type of ICU. Further investigation is needed to understand what impact this practice variability has on patient outcomes.

RETRACTION: Epinephrine Enhances the Response of Macrophages under LPS Stimulation.

Research International BioMed B

Reply to: Rhythm Specific or Phase Specific? Interpreting Epinephrine Associations in Non Shockable Cardiac Arrest.

Emoto Ryo R, Nishikimi Mitsuaki M

Mono-ADP-ribosylation-driven immunosuppression and cross-resistance to therapy through cancer cell intrinsic and extrinsic mechanisms.

Sun Yuchen Y, Tang Yingying Y, Singh Vivek T VT, Holczbauer Ágnes Á et al.

Mono-ADP-ribosylation (MARylation) is emerging as an important regulator of anti-cancer immunity and immunosuppressive tumor microenvironment (TME). Our previous studies showed that PARP11, one of several enzymes that facilitate MARylation, regulates the activities of intratumoral cytotoxic T lymphocytes (CTLs) and regulatory T cells (Tregs). Here, we demonstrate that stimuli such as adenosine, epinephrine, or glucagon-like peptide-1 (GLP1) induced PARP11 in cancer cells. Upregulation of PARP11 in cancer cells led to PARP11-mediated MARylation, ubiquitination, and accelerated degradation of MHC-I through the autophagy-lysosomal pathway. Induction of PARP11 protected cancer cells from killing by specific CTLs and stimulated tumor growth and progression. Genetic ablation of PARP11 attenuated MHC-I MARylation, ubiquitination, and interaction with autophagy receptors. Pharmacologic inhibition of PARP11 in pancreatic ductal adenocarcinoma (PDAC) cells restored their MHC-I levels, sensitized them to killing by CTLs, inhibited tumor growth, and impeded their initial resistance to chemotherapy and their acquired resistance to targeted therapy with RAS inhibitors. Moreover, inhibition of PARP11 prevented hyperprogressive disease in a mouse melanoma model treated with immune checkpoint inhibitors (ICBs), suggesting that PARP11 is a major therapeutically actionable driver of immunosuppression in tumors. Induction of PARP11 in the tumor microenvironment mediates immunosuppression. This study reports that PARP11-driven MARylation and ubiquitination of MHC-I in cancer cells drives immune evasion, tumor growth and resistance to therapies.