Immune urinary biomarkers predict infant cardiac surgery-associated acute kidney injury.

BACKGROUND: Acute kidney injury (AKI) occurs frequently after infant cardiac surgery and is associated with poor outcomes, including mortality and prolonged length of stay. AKI mechanisms are poorly understood, limiting therapeutic targets. Emerging data implicates dysregulated immune activation in post-cardiac surgery AKI development. We sought to identify immune-mediated AKI biomarkers after infant cardiopulmonary bypass (CPB)-assisted cardiac surgery. METHODS: A single-center prospective study of 126 infants less than 1 year old undergoing CPB-assisted surgery enrolled between 10/2017 and 6/2019. Urine samples were collected before CPB and at 6, 24, 48, and 72 h after surgery. Immune-mediated biomarkers were measured using commercial ELISA and Luminex™ multiplex kits. Based on subject age, neonatal KDIGO (< 1 month) or KDIGO criteria defined AKI. The Kruskal-Wallis rank test determined the relationship between urinary biomarker measurements and AKI. RESULTS: A total of 35 infants (27%) developed AKI. AKI subjects were younger, underwent more complex surgery, and had longer CPB time. Subjects with AKI vs. those without AKI had higher median urinary chemokine 10 (C-X-C motif) ligand levels at 24, 48, and 72 h, respectively: 14.3 pg/ml vs. 5.3 pg/ml, 3.4 pg/ml vs. 0.8 pg/ml, and 1.15 pg/ml vs. 0.22 pg/ml (p < 0.05) post-CPB. At 6 h post-CPB, median vascular cell adhesion protein 1 (VCAM) levels (pg/mL) were higher among AKI subjects (491 pg/ml vs. 0 pg/ml, p = 0.04). CONCLUSIONS: Urinary CXCL10 and VCAM are promising pro-inflammatory biomarkers for early AKI detection and may indicate eventual AKI therapeutic targets. A higher resolution version of the Graphical abstract is available as Supplementary information.

High-Dose Celecoxib for Pain After Pediatric Tonsillectomy: A Randomized Controlled Trial.

OBJECTIVE: Pediatric tonsillectomy causes significant postoperative pain. Newer nonsteroidal anti-inflammatory drugs such as celecoxib control pain without increasing bleeding risk, but in prior studies provided only modest pain reduction at standard doses. We aimed to determine if high-dose celecoxib (double the usual pediatric dose) is effective for pain, without increasing bleeding or other risks. STUDY DESIGN: Randomized double-blind trial. SETTING: Pediatric tertiary center. METHODS: Children aged 3 to 11 years undergoing total tonsillectomy were randomized to receive celecoxib (6 mg/kg/dose) or placebo, twice daily, for up to 10 days. All cases were supplemented with acetaminophen and oxycodone as needed. All participants and personnel were blinded to treatment group. Subjects recorded coanalgesic consumption, pain, diet, and activity. RESULTS: The celecoxib group (n = 68) consumed 0.72 mg/kg of oxycodone, as compared with 1.12 mg/kg in the placebo group (n = 62), a 36% difference that was not significant. However, multivariate analysis by treatment group, separate from pain levels, confirmed that this reduction was due to celecoxib treatment (P = .03). In subjects with more prolonged pain (n = 88), celecoxib reduced consumption by 52% (P = .02). Celecoxib showed greater benefit for subjects in the prolonged pain group than for those in the lesser pain group (P = .006). Incidence of adverse events was similar between groups. Minor hemorrhage occurred in 4.6% (5 placebo, 3 celecoxib). CONCLUSION: High-dose celecoxib is effective in controlling pain after tonsillectomy, with no adverse effects in this relatively small sample. It reduces narcotic consumption, and its impact appears greater in children with higher degrees of pain. Celecoxib can be considered an effective alternative to ibuprofen after tonsillectomy. This trial was registered at ClinicalTrials.gov: NCT02934191.

The Use of Lanreotide in the Treatment of Congenital Hyperinsulinism.

CONTEXT: Congenital hyperinsulinism (HI) results in severe, persistent hypoglycemia and is associated with high risk of neurodevelopmental deficits. Sixty percent of HI cases are unresponsive to diazoxide, the only Food and Drug Administration-approved drug. Somatostatin analogs are used off-label as second-line treatment; the long-acting somatostatin analogue, lanreotide, has been used to treat HI over the past decade. Existing reports are limited to small case series. OBJECTIVE: To assess the effectiveness and safety of lanreotide in individuals with HI. DESIGN: Retrospective cohort study of individuals with HI treated with lanreotide between 2015 and 2020. SETTING: The Congenital Hyperinsulinism Center at The Children's Hospital of Philadelphia. PATIENTS: Fifty-four individuals with hyperinsulinism treated with lanreotide. MAIN OUTCOME MEASURES: Fasting duration with plasma glucose > 70 mg/dL; frequency of lanreotide-associated side effects. RESULTS: The median duration of lanreotide therapy was 28.7 (2.8-64.5) months. Thirty-four patients (63%) had HI due to inactivating mutations of the adenosine 5'-triphosphate (ATP) sensitive potassium channel (KATP-HI), and 39% had undergone a pancreatectomy. Of 52 patients receiving other HI therapies, 22 (42%) were able to discontinue other treatments and were managed on lanreotide alone. Fasting duration with plasma glucose > 70 mg/dL was significantly longer during therapy with lanreotide compared to prior to lanreotide initiation (8.6 ±â€…6.5 vs 5.1 ±â€…4.7 hours, P = 0.001). The most common side effects were subcutaneous nodules (26%) and gallstones (11%). CONCLUSIONS: Lanreotide is a well-tolerated treatment for patients with HI. It results in a longer duration of fasting and a simplification of treatment regimens.

Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19-related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a postinfectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and evaluate associated risk factors. We classified patients into 1 of 3 groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (COVID-19, n = 426; MIS-C, n = 138; and asymptomatic SARS-CoV-2, n = 289) in 814 patients, there were 20 patients with thrombotic events (TEs; including 1 stroke). Patients with MIS-C had the highest incidence (9 [6.5%] of 138) vs COVID-19 (9 [2.1%] of 426) or asymptomatic SARS-CoV-2 (2 [0.7%] of 289). In patients with COVID-19 or MIS-C, a majority of TEs (89%) occurred in patients age ≥12 years. Patients age ≥12 years with MIS-C had the highest rate of thrombosis at 19% (9 of 48). Notably, 71% of TEs that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13 of 564), but it was 28% (5 of 18) in patients with TEs. Our findings may help inform pediatric thromboprophylaxis strategies.

Real-world use of emicizumab in patients with haemophilia A: Bleeding outcomes and surgical procedures.

INTRODUCTION: Emicizumab is a recombinant humanized bispecific antibody that bridges factor IXa and factor X to mimic the cofactor function of factor VIII. It is approved to prevent bleeding in patients with haemophilia A (HA). Outside of clinical trials, there is limited data on outcomes of patients treated with emicizumab, particularly in children without inhibitors. AIM: To report our experience treating patients with emicizumab, including (a) bleeding rates pre and postemicizumab, (b) peri-procedural management and outcomes and (c) serious drug-related adverse events. METHODS: Multicentre observational study in patients with HA who started emicizumab prior to 15 May 2019. Data collection continued until 15 October 2019 and included demographics, disease history, bleeding events, invasive procedures, thrombotic events and death. Annualized bleeding rates (ABR) prior to emicizumab were compared to postemicizumab. RESULTS: Ninety-three patients (including three females) met inclusion criteria, 19 with an active inhibitor. Median age was 8.6 years; patients <12 years without inhibitors (n = 49) accounted for the majority. ABR dropped from 4.4 (inhibitors) and 1.6 (non-inhibitors) to 0.4 (both groups) on emicizumab, P = .0012 and .0025, respectively. There were 28 minor (21 port removals) and two major procedures. Three patients received 1-2 doses of unplanned factor postoperatively to treat minor bleeding events. No patient discontinued therapy, and there were no thrombotic events or deaths. DISCUSSION: Our favourable clinical experience with emicizumab is similar to that reported in the clinical trials. Notably, this is the largest cohort of patients <12 years without inhibitors treated with emicizumab.

Exploring Impacts of Taxes and Hospitality Bans on Cigarette Prices and Smoking Prevalence Using a Large Dataset of Cigarette Prices at Stores 2001-2011, USA.

In the USA, little is known about local variation in retail cigarette prices; price variation explained by taxes, bans, and area-level socio-demographics, and whether taxes and hospitality bans have synergistic effects on smoking prevalence. Cigarette prices 2001-2011 from chain supermarkets and drug stores (n = 2973) were linked to state taxes (n = 41), state and county bar/restaurant smoking bans, and census block group socio-demographics. Hierarchical models explored effects of taxes and bans on retail cigarette prices as well as county smoking prevalence (daily, non-daily). There was wide variation in store-level cigarette prices in part due to differences in state excise taxes. Excise taxes were only partially passed onto consumers (after adjustment, $1 tax associated with $0.90 increase in price, p < 0.0001) and the pass-through was slightly higher in areas that had bans but did not differ by area-level socio-demographics. Bans were associated with a slight increase in cigarette price (after adjustment, $0.09 per-pack, p < 0.0001). Taxes and bans were associated with reduction in smoking prevalence and taxes had a stronger association when combined with bans, suggesting a synergistic effect. Given wide variation in store-level prices, and uneven state/county implementation of taxes and bans, more federal policies should be considered.