Food insecurity in children with heart disease.

PURPOSE OF REVIEW: This review discusses the epidemiology of food insecurity (FI) and its consequences in children with congenital heart disease. We aimed to highlight current interventions to screen and address food insecurity in the context of pediatric cardiology and to offer strategies for providers to engage in this meaningful work. RECENT FINDINGS: Food insecurity is consistently associated with poor health outcomes in children. In the United States, 17.3% of households with children experience FI. Nonwhite and single-parent families are disproportionately affected. Interestingly, because of a low-quality diet, FI is associated with childhood obesity, putting affected children at increased risk for cardiovascular morbidity and mortality over time. Children with congenital heart disease are susceptible to poor outcomes due to unique altered metabolic demands, increased risk for growth impairment, frequent need for specialized feeding regimens, and additional morbidity associated with heart surgery in underweight children. SUMMARY: Today, the burden of screening for FI is most commonly placed on general pediatricians. Considering the importance of nutrition to cardiovascular health and general wellbeing, and the ease with which screening can be performed, pediatric cardiologists and other subspecialists should take a more active role in FI screening.

Safety of Continuing Anticoagulation Prior to Cardiac Catheterization in Pediatric Patients: A Los Angeles Center Experience.

This is the first report specifically describing outcomes of pediatric patients who underwent cardiac catheterization while on uninterrupted anticoagulation. One hundred forty-four cardiac catheterizations were identified that met inclusion criteria at our institution from 11/2014 to 10/2019. The median age and weight of the patients were 6.3 [0.01-20.9] years and 19.3 [2.1-172.5] kg, respectively. Seventy-eight (54%) catheterizations involved inpatients. The most common cardiac diagnoses among the cohort were single ventricle (n = 41), conotruncal defects (n = 37), and structurally normal heart (n = 16). The most common indications for anticoagulation were arterial/venous thrombus (n = 45), Fontan physiology (n = 32), and mechanical valve thrombus prophylaxis (n = 27). The anticoagulation medications used were warfarin (n = 57), heparin (n = 52), enoxaparin (n = 25), fondaparinux (n = 5), rivaroxaban (n = 2), and both heparin and warfarin (n = 3). Interventions were performed in 96 cases (67%). The median length of the procedure was 122.5 [15-760] minutes, and the median time to achieve hemostasis was 18.0 [range: 5-76, IQR: 13-25] minutes. Adverse events were present in 11 cases (7.6%), and of those only 2 cases (1.4%) were bleeding-related complications. Our single-center data suggest that performing cardiac catheterization on pediatric patients while on uninterrupted anticoagulation is safe and does not substantially increase the risk of bleeding complications based on a cohort of patients that varied in age, size, diagnosis, medical complexity, and type of intervention performed. Patients on warfarin therapy for a mechanical valve are most likely to benefit from this practice, as the ability to continue warfarin therapy avoids the need for bridging and other interruption-related complications.

Coronary Artery Changes in Patients with Multisystem Inflammatory Syndrome in Children: Los Angeles Experience.

We compared cardiac findings in patients with multisystem inflammatory syndrome in children and Kawasaki disease in the first 6 months of the 2020 coronavirus disease pandemic to patients with Kawasaki disease during 2016-2019. We saw a high rate of coronary aneurysms in 2020, with a similar rate of coronary involvement but greater volume and incidence of cardiac dysfunction compared with previous years.

Multi-Institution Evaluation of Sequential Gemcitabine and Docetaxel as Rescue Therapy for Nonmuscle Invasive Bladder Cancer.

PURPOSE: Rescue intravesical therapies for patients with bacillus Calmette-Guérin failure nonmuscle invasive bladder cancer remain a critical focus of ongoing research. Sequential intravesical gemcitabine and docetaxel therapy has shown safety and efficacy in 2 retrospective, single institution cohorts. This doublet has since been adopted as an intravesical salvage option at multiple institutions. We report the results of a multi-institutional evaluation of gemcitabine and docetaxel. MATERIALS AND METHODS: Each institution retrospectively reviewed all records of patients treated with intravesical gemcitabine and docetaxel for nonmuscle invasive bladder cancer between June 2009 and May 2018. Only patients with recurrent nonmuscle invasive bladder cancer and a history of bacillus Calmette-Guérin treatment were included in the analysis. If patients were disease-free after induction, maintenance was instituted at the treating physician's discretion. Posttreatment surveillance followed American Urological Association guidelines. Survival analysis was performed using the Kaplan-Meier method and risk factors for treatment failure were assessed with Cox regression models. RESULTS: Overall 276 patients (median age 73 years, median followup 22.9 months) received treatment. Nine patients were unable to tolerate a full induction course. One and 2-year recurrence-free survival rates were 60% and 46%, and high grade recurrence-free survival rates were 65% and 52%, respectively. Ten patients (3.6%) had disease progression on transurethral resection. Forty-three patients (15.6%) went on to cystectomy (median 11.3 months from induction), of whom 11 (4.0%) had progression to muscle invasion. Analysis identified no patient, disease or prior treatment related factors associated with gemcitabine and docetaxel failure. CONCLUSIONS: Intravesical gemcitabine and docetaxel therapy is well tolerated and effective, providing a durable response in patients with recurrent nonmuscle invasive bladder cancer after bacillus Calmette-Guérin therapy. Further prospective study is warranted.

Identifying an Oxygenation Index Threshold for Increased Mortality in Acute Respiratory Failure.

BACKGROUND: The objective of this work was to examine current oxygenation index (OI) data and outcomes using electronic medical record data to identify a specific OI value associated with mortality. METHODS: This study was a retrospective electronic medical record data review from the pediatric ICU of Phoenix Children's Hospital, with data mining for variables to calculate OIs on subjects age 1 month to 20 y mechanically ventilated > 24 h, excluding those with known intracardiac shunts or cyanotic heart disease. Age, length of hospital stay, duration of mechanical ventilation, and outcomes were also assessed. The Wilcoxon signed-rank test was used to compare continuous variables, receiver operating characteristic analysis was used in determining discriminant ability, and logistic regression was conducted to determine the odds ratio (OR) for risk of death with increasing OI. RESULTS: OI was calculated on 65 subjects, of whom 6 died (9%). The median maximum OI was 10 for all subjects, 17 for non-survivors, and 8 for survivors (P = .14 via Wilcoxon rank-sum test). ORs indicated a 2.4-fold increase in the odds of death (P = .09, 95% CI 0.9-6.6) for each increasing point in maximum OI. Mean OI OR revealed a 1.9-fold increase in the odds of death (P = .25, 95% CI 0.6-5.9). Receiver operating characteristic analysis indicated a higher discriminate ability for maximum OI (area under the curve = 0.68) than mean OI (area under the curve = 0.58). OI cut-points for mortality were established. Mortality was unchanged until maximum OI > 17, for which mortality nearly tripled at a value of 18% versus 6-7% for range 0-17. CONCLUSIONS: Limitations exist in obtaining serial OI values from current electronic medical records. Serial assessment of OI values may allow creation of alert values for increased mortality risk. Consideration of escalation of therapies for respiratory failure, such as high-frequency ventilation, inhaled nitric oxide, or extracorporeal membrane oxygenation may be warranted at lower OIs than historically reported.

The oxindole Syk inhibitor OXSI-2 blocks nigericin-induced inflammasome signaling and pyroptosis independent of potassium efflux.

The inflammasome is a caspase-1-activating complex that is implicated in a growing number of acute and chronic pathologies. Interest has increased in identifying small molecular inhibitors of inflammasome signaling because of its role in clinically relevant diseases. It was recently reported that the protein tyrosine kinase, Syk, regulates pathogen-induced inflammasome signaling by phosphorylating a molecular switch on the adapter protein ASC. However, several aspects of the role of Syk in inflammasome signaling and the effects of its inhibition remain unclear. The aim of the present study is to explore in detail the effects of the oxindole Syk inhibitor OXSI-2 on various aspects of nigericin-induced inflammasome signaling. Our results indicate that OXSI-2 inhibits inflammasome assembly, caspase-1 activation, IL-1ß processing and release, mitochondrial ROS generation, and pyroptotic cell death. Using a novel live cell potassium sensor we show that Syk inhibition with OXSI-2 has no effect on potassium efflux kinetics and that blockade of potassium efflux with extracellular potassium alters Syk phosphorylation. The effects of OXSI-2 identified in this study provide context for the role of Syk in inflammasome signaling and demonstrate its importance in oxidative signaling upstream of inflammasome activation and downstream of ion flux.