Citations

ImportanceRedirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding.ObjectiveTo examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm.Design, Setting, and ParticipantsThis is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks’ gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic).Main Outcomes and MeasuresThe primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks’ gestation, death and neurodevelopmental impairment at 22 to 26 months’ corrected age.ResultsOf the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type.Conclusions and RelevanceFor infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.

Abstract Background We aimed to determine if pre-existing immunocompromising conditions (ICCs) were associated with the presentation or outcome of patients with acute coronavirus disease 2019 (COVID-19) admitted for pediatric intensive care. Methods Fifty-five hospitals in 30 US states reported cases through the Overcoming COVID-19 public health surveillance registry. Patients <21 years admitted 12 March 2020–30 December 2021 to the pediatric intensive care unit (PICU) or high-acuity unit for acute COVID-19 were included. Results Of 1274 patients, 105 (8.2%) had an ICC, including 33 (31.4%) hematologic malignancies, 24 (22.9%) primary immunodeficiencies and disorders of hematopoietic cells, 19 (18.1%) nonmalignant organ failure with solid-organ transplantation, 16 (15.2%) solid tumors, and 13 (12.4%) autoimmune disorders. Patients with ICCs were older, had more underlying renal conditions, and had lower white blood cell and platelet counts than those without ICCs, but had similar clinical disease severity upon admission. In-hospital mortality from COVID-19 was higher (11.4% vs 4.6%, P = .005) and hospitalization was longer (P = .01) in patients with ICCs. New major morbidities upon discharge were not different between those with and without ICC (10.5% vs 13.9%, P = .40). In patients with ICCs, bacterial coinfection was more common in those with life-threatening COVID-19. Conclusions In this national case series of patients <21 years of age with acute COVID-19 admitted for intensive care, existence of a prior ICCs were associated with worse clinical outcomes. Reassuringly, most patients with ICCs hospitalized in the PICU for severe acute COVID-19 survived and were discharged home without new severe morbidities.

Abstract Introduction Intracavernosal injection (ICI) therapy for erectile dysfunction (ED) carries a risk of corporal fibrosis, potentially making placement of an inflatable penile prosthesis more difficult. Prostate cancer treatment may also induce corporal fibrosis. Objective To assess whether a history of ICI or prostate cancer treatment is associated with complications following IPP placement. Methods A retrospective cohort study of primary IPP cases from 2016–2021 across 16 institutions. Patients were stratified by history of ICI and between-group differences in risk factors were assessed. Multivariable logistic regression was used to assess for predictors of intraoperative complications, postoperative non-infectious complications and postoperative infection. Results A total of 2540 patients met inclusion criteria of which 781 (30.8%) had a history of ICI. Patients with a history of ICI tended to be older (mean 63 vs 64 years, p=0.002) and were more likely to have history of radical prostatectomy (21.0% vs. 32.1%, p<0.001) and/or radiation (5.51% vs 10.9%, p<0.001). On multivariable regression, a history of ICI, prostatectomy, and radiation were all significant predictors of intraoperative complications (OR 2.11, p=0.03; OR 2.27, p=0.03; OR 2.40, p=0.04, respectively). A history of ICI and patient age were predictors of non-infectious postoperative complications (OR 1.44, p=0.02, OR 1.02, p=0.004 respectively)). None of the variables were significant predictors of infection. Conclusions In men undergoing IPP placement, a history of ICI is associated with an increased risk of both intraoperative and postoperative, non-infectious complications. Prostate cancer treatment with radiation or surgery is independently associated with increased risk of intraoperative complications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: D.O. has served as a consultant for Coloplast, Intuitive Surgical, and Fidelis. P.P. has served as a consultant for Coloplast, Boston Scientific, and Urofill. M.S. has served as a consultant for Boston Scientific and Coloplast. J.S. has served as a consultant for Boston Scientific and Coloplast. F.A.Y. has served as a consultant for Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, and Acerus Pharma. M.S.G. has served as a consultant for Coloplast. The other authors disclose no conflicts.

Abstract Introduction Intracavernosal injection (ICI) therapy for erectile dysfunction (ED) carries a risk of corporal fibrosis, potentially making placement of an inflatable penile prosthesis more difficult. Prostate cancer treatment may also induce corporal fibrosis. Objective To assess whether a history of ICI or prostate cancer treatment is associated with complications following IPP placement. Methods A retrospective cohort study of primary IPP cases from 2016-2021 across 16 institutions. Patients were stratified by history of ICI and between-group differences in risk factors were assessed. Multivariable logistic regression was used to assess for predictors of intraoperative complications, postoperative non-infectious complications and postoperative infection. Results A total of 2540 patients met inclusion criteria of which 781 (30.8%) had a history of ICI. Patients with a history of ICI tended to be older (mean 63 vs 64 years, p=0.002) and were more likely to have history of radical prostatectomy (21.0% vs. 32.1%, p<0.001) and/or radiation (5.51% vs 10.9%, p<0.001). On multivariable regression, a history of ICI, prostatectomy, and radiation were all significant predictors of intraoperative complications (OR 2.11, p=0.03; OR 2.27, p=0.03; OR 2.40, p=0.04, respectively). A history of ICI and patient age were predictors of non-infectious postoperative complications (OR 1.44, p=0.02, OR 1.02, p=0.004 respectively)). None of the variables were significant predictors of infection. Conclusions In men undergoing IPP placement, a history of ICI is associated with an increased risk of both intraoperative and postoperative, non-infectious complications. Prostate cancer treatment with radiation or surgery is independently associated with increased risk of intraoperative complications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: D.O. has served as a consultant for Coloplast, Intuitive Surgical, and Fidelis. P.P. has served as a consultant for Coloplast, Boston Scientific, and Urofill. M.S. has served as a consultant for Boston Scientific and Coloplast. J.S. has served as a consultant for Boston Scientific and Coloplast. F.A.Y. has served as a consultant for Coloplast, Cynosure, Antares Pharma, Clarus Pharmaceuticals, and Acerus Pharma. M.S.G. has served as a consultant for Coloplast. The other authors disclose no conflicts.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and nearly 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16180. Catalytic receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, ion channels, nuclear hormone receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Introduction: Common genetic variation has been linked to an increased risk of developing dilated cardiomyopathy (DCM). However, the phenotypic profile, outcomes, and biological mechanisms by which such genetic background may predispose individuals to DCM are still unknown. Hypothesis: The primary objectives of this study were to develop a DCM polygenic risk score (PRS) based on prior case control-DCM GWAS and to apply this PRS to a well clinical characterized general population. Methods: The DCM-PRS was derived from 13 DCM risk alleles that were assayed in an unselected cohort (n=1897) of unrelated Olmsted County residents age >45 years who did not have a history of heart failure (HF) or CM and underwent physical examination, echocardiography, and blood analyses. Results: The entire population was equally divided into quartiles based on the DCM-PRS. No significant differences were present in terms of age (median 62 years) and sex (48% male). However, a significant correlation was detected between the DCM-PRS and left ventricle ejection fraction (LVEF) (Beta: -2.68, p<0.001), LV end-systolic diameter (Beta: 0.22, p<0.001), and LV end-diastolic diameter (Beta: 0.14, p=0.01). During a follow-up of 16 years (IQR: 15-17), 47 subjects developed DCM. Using a 3:1 non-DCM vs DCM matched cohort, a logistic regression analysis, found a significant correlation between median DCM-PRS and DCM development [OR=2.27 (1.06, 4.85), p=0.03]. However, there was no association between the DCM-PRS and HF biomarkers (aldosterone, natriuretic peptides, ST2, Galectin-3). Conclusions: DCM-PRS correlates with decreased LVEF, increased LV dimensions, and DCM development in a general population without significant differences in baseline clinical features. The absence of correlation between the DCM-PRS and available HF biomarkers suggests that this genetic background affects LV traits and DCM development independent of these biological mechanisms.

Introduction: Excess cardiomyocyte oxidative stress is a major metabolic abnormality in HTN and its progression to HF. Thus, therapies that reduce oxidative stress in the heart may lead to a reduction in CVD related adverse outcomes such as HF and death. Recently, we bioengineered a bispecific peptide NPA7 that co-activates the protective GC-A/cGMP and MasR/cAMP pathways. Previously we showed that NPA7 possesses cardiorenal protective properties. However, the antioxidant effects of NPA7 within the heart is unknown. Hypothesis: NPA7 protects human cardiomyocytes against oxidative stress through the GC-A/Mas Receptor-KEAP1-NRF2 pathway. Methods: HCMs were pretreated with PBS or NPA7 (10 uM) followed by 400 uM hydrogen peroxide (H2O2) to induce oxidative stress. Intracellular ROS was measured by dihydroethidium (DHE) staining and protein levels of KEAP1 and NRF2 via western blot. The ratio of GSH/GSSG were determined by using commercial kit. mRNA levels of G6PD, GCLC, GCLM and GSS in HCMs, which represents antioxidant capacity, were determined by real-time PCR. For knockdown experiments, HCMs were transfected with the siRNA target GC-A and MasR for 24 h and then treated with NPA7 and H2O2 for another 20 h. Results: H2O2 increased DHE staining level, which indicated elevated intracellular ROS levels within HCMs. Notably, treatment with NPA7 decreased DHE level and increased the ratio of GSH/GSSG in HCMs with H2O2. Furthermore, NPA7 significantly increased the mRNA level of NRF2 target genes (G6PD, GCLC, GCLM, GSS) through NRF2 activation and KEAP1 degradation, indicating that NPA7 activates KEAP1-NRF2 pathway, the upstream pathway that regulate antioxidant gene expression, in HCMs. Moreover, these effects were eliminated if GC-A and MasR were silenced by siRNA, thus supporting the protective antioxidant role of both GC-A and MasR. Conclusions: The present study establishes an antioxidant action of NPA7, a novel bispecific designer peptide, on H2O2-induced oxidative stress by the dual targeting of GC-A and MasR through the KEAP1-NRF2 signaling pathway in HCMs. These results advance NPA7 as an innovative therapeutic strategy targeting oxidative stress related to CVD.