Risk factors and outcomes of sudden cardiac arrest in pediatric heart transplant recipients.

BACKGROUND: Sudden cardiac arrest (SCA) is a prevailing cause of mortality after pediatric heart transplant (HT) but remains understudied. We analyzed the incidence, outcomes, and risk factors for SCA at our center. METHODS: Retrospective review of all pediatric HT patients at our center from January 1, 2009 to January 1, 2021. SCA was defined as an abrupt loss of cardiac function requiring cardiopulmonary resuscitation and/or mechanical circulatory support (MCS). Events that occurred in the setting of limited resuscitative wishes, or while on MCS were excluded. Patient characteristics and risk factors were analyzed. RESULTS: Fourteen of 254 (6%) experienced SCA at a median of 3 (1, 4) years post-HT. Seven (50%) events occurred out-of-hospital. Eleven (79%) died from their initial event, 2 (18%) after failure to separate from extracorporeal membrane (ECMO). In univariate analysis, black race, younger donor age, prior acute cellular rejection (ACR) episode, pacemaker and/or ICD in place, and pre-mortem diagnosis of allograft vasculopathy were associated with SCA (P = .003-0.02). In multivariable analysis, history of ACR, younger donor age, and black race retained significance. [OR = 6.3, 95% CI: 1.6-25.4, P = .01], [OR = 0.9, 95% CI: 0.8-1, P = .04], and [OR = 7.3, 95% CI: 1.1-49.9, P = .04], respectively. SCA occurred in 3 patients with a functioning ICD or pacemaker, which failed to restore a perfusing rhythm. CONCLUSIONS: SCA occurs relatively early after pediatric HT and is usually fatal. Half of events happen at home. Those who received younger donors, have a history of ACR, or are of black race are at increased risk. ICDs/pacemakers may offer limited protection.

Postoperative Acute Kidney Injury in Williams Syndrome Compared With Matched Controls.

OBJECTIVES: Cardiovascular manifestations occur in over 80% of Williams syndrome (WS) patients and are the leading cause of morbidity and mortality. One-third of patients require cardiovascular surgery. Renal artery stenosis (RAS) is common in WS. No studies have assessed postoperative cardiac surgery-related acute kidney injury (CS-AKI) in WS. Our objectives were to assess if WS patients have higher risk of CS-AKI postoperatively than matched controls and if RAS could contribute to CS-AKI. DESIGN: This was a retrospective study of all patients with WS who underwent cardiac surgery at our center from 2010 to 2020. The WS study cohort was compared with a group of controls matched for age, sex, weight, and surgical procedure. SETTING: Patients underwent cardiac surgery and postoperative care at Lucile Packard Children's Hospital Stanford. PATIENTS: There were 27 WS patients and 43 controls (31% vs 42% female; p = 0.36). Median age was 1.8 years (interquartile range [IQR], 0.7-3.8 yr) for WS and 1.7 years (IQR, 0.8-3.1 yr) for controls. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Postoperative hemodynamics, vasopressor, total volume input, diuretic administration, and urine output were collected in the first 72 hours. Laboratory studies were collected at 8-hour intervals. Multivariable analysis identified predictors of CS-AKI.Controlled for renal perfusion pressure (RPP) and vasoactive inotrope score (VIS), compared with controls, the odds ratio (OR) of CS-AKI in WS was 4.2 (95% CI, 1.1-16; p = 0.034). Higher RPP at postoperative hours 9-16 was associated with decreased OR of CS-AKI (0.88 [0.8-0.96]; p = 0.004). Increased VIS at hour 6 was associated with an increased OR of CS-AKI (1.47 [1.14-1.9]; p = 0.003). Younger age was associated with an increased OR of CS-AKI (1.9 [1.13-3.17]; p = 0.015). CONCLUSIONS: The OR of CS-AKI is increased in pediatric patients with WS compared with controls. CS-AKI was associated with VIS at the sixth postoperative hour. Increases in RPP and mean arterial pressure were associated with decreased odds of CS-AKI.

Development of consensus recommendations for the management of post-operative chylothorax in paediatric CHD.

OBJECTIVE: A standardised multi-site approach to manage paediatric post-operative chylothorax does not exist and leads to unnecessary practice variation. The Chylothorax Work Group utilised the Pediatric Critical Care Consortium infrastructure to address this gap. METHODS: Over 60 multi-disciplinary providers representing 22 centres convened virtually as a quality initiative to develop an algorithm to manage paediatric post-operative chylothorax. Agreement was objectively quantified for each recommendation in the algorithm by utilising an anonymous survey. "Consensus" was defined as ≥ 80% of responses as "agree" or "strongly agree" to a recommendation. In order to determine if the algorithm recommendations would be correctly interpreted in the clinical environment, we developed ex vivo simulations and surveyed patients who developed the algorithm and patients who did not. RESULTS: The algorithm is intended for all children (<18 years of age) within 30 days of cardiac surgery. It contains rationale for 11 central chylothorax management recommendations; diagnostic criteria and evaluation, trial of fat-modified diet, stratification by volume of daily output, timing of first-line medical therapy for "low" and "high" volume patients, and timing and duration of fat-modified diet. All recommendations achieved "consensus" (agreement >80%) by the workgroup (range 81-100%). Ex vivo simulations demonstrated good understanding by developers (range 94-100%) and non-developers (73%-100%). CONCLUSIONS: The quality improvement effort represents the first multi-site algorithm for the management of paediatric post-operative chylothorax. The algorithm includes transparent and objective measures of agreement and understanding. Agreement to the algorithm recommendations was >80%, and overall understanding was 94%.

The impact of plug-in fragrance diffusers on residential indoor VOC concentrations.

Plug-in fragrance diffusers are one of myriad volatile organic compound-containing consumer products that are commonly found in homes. The perturbing effects of using a commercial diffuser indoors were evaluated using a study group of 60 homes in Ashford, UK. Air samples were taken over 3 day periods with the diffuser switched on and in a parallel set of control homes where it was off. At least four measurements were taken in each home using vacuum-release into 6 L silica-coated canisters and with >40 VOCs quantified using gas chromatography with FID and MS (GC-FID-QMS). Occupants self-reported their use of other VOC-containing products. The variability between homes was very high with the 72 hour sum of all measured VOCs ranging between 30 and >5000 µg m-3, dominated by n/i-butane, propane, and ethanol. For those homes in the lowest quartile of air exchange rate (identified using CO2 and TVOC sensors as proxies) the use of a diffuser led to a statistically significant increase (p-value < 0.02) in the summed concentration of detectable fragrance VOCs and some individual species, e.g. alpha pinene rising from a median of 9 µg m-3 to 15 µg m-3 (p-value < 0.02). The observed increments were broadly in line with model-calculated estimates based on fragrance weight loss, room sizes and air exchange rates.

To Unifocalize or Not to Unifocalize?: A Comparison of Retroesophageal Versus Anterior Collaterals.

BACKGROUND: The anatomy of major aortopulmonary collateral arteries (MAPCAs) can be highly variable with regard to number, anatomic origin, course, and relationship to the native pulmonary arteries. Some MAPCAs travel behind the esophagus (retroesophageal) and bronchus before entering the lung parenchyma. This study compared the physiologic and surgical characteristics of retroesophageal vs anterior located MAPCAs. METHODS: This was a retrospective review of 42 patients who had 1 (n = 36) or 2 (n = 6) retroesophageal MAPCAs. These MAPCAs were then characterized as (1) single supply, meaning no connection to the pulmonary arteries; (2) dual supply, but inadequate connection to the distal pulmonary vascular bed; and (3) dual supply with adequate connection. RESULTS: The 42 patients presented with 187 MAPCAs, or 4.5 MAPCAs per patient. Of these, 48 MAPCAs were retroesophageal, including 40 that were single supply, 6 were dual supply with inadequate connection, and 2 had dual supply with adequate connection. On the basis of this anatomy and physiology, 96% of retroesophageal MAPCAs were unifocalized. For the 139 anterior MAPCAs, 89 were single supply, 15 were dual supply with inadequate connection, and 35 were dual supply with adequate connection; thus, 75% of anterior MAPCAs were unifocalized (P < .01 compared with retroesophageal MAPCAs). CONCLUSIONS: The data demonstrate that retroesophageal MAPCAs had very different anatomy and physiology compared with anterior MAPCAs. These results suggest that nearly every retroesophageal MAPCA should be unifocalized to incorporate the lung segments supplied.

Frequency of use of household products containing VOCs and indoor atmospheric concentrations in homes.

Volatile organic compounds (VOCs) are a key class of atmospheric emission released from highly complex petrochemical, transport and solvent sources both outdoors and indoors. This study established the concentrations and speciation of VOCs in 60 homes (204 individuals, 360 × 72 h samples, 40 species) in summer and winter, along with outdoor controls. Self-reported daily statistics were collected in each home on the use of cleaning, household and personal care products, all of which are known to release VOCs. Frequency of product use varied widely: deodorants: 2.9 uses home per day; sealant-mastics 0.02 uses home per day. The total concentration of VOCs indoors (range C2-C10) was highly variable between homes e.g. range 16.6-8150 µg m-3 in winter. Indoor concentrations of VOCs exceeded outdoor for 84% of households studied in summer and 100% of homes in winter. The most abundant VOCs found indoors in this study were n-butane (wintertime range: 1.5-4630 µg m-3), likely released as aerosol propellant, ethanol, acetone and propane. The cumulative use VOC-containing products over multiday timescales by occupants provided little predictive power to infer 72 hour averaged indoor concentrations. However, there was weak covariance between the cumulative usage of certain products and individual VOCs. From a domestic emissions perspective, reducing the use of hydrocarbon-based aerosol propellants indoors would likely have the largest impact.

Texting preferences in a Paediatric residency.

PURPOSE: Text messaging is ubiquitous among residents, but remains an underused educational tool. Though feasibility has been demonstrated, evidence of its ability to improve standardised test scores and provide insight on resident texting preferences is lacking. The authors set out to evaluate: (1) satisfaction with a hybrid question-and-answer (Q&A) texting format; and (2) pre-/post-paediatric in-training exam (ITE) performance. METHODS: A prospective study with paediatrics and internal medicine-paediatrics residents. Residents were divided into subgroups: adolescent medicine (AM) and developmental medicine (DM). Messages were derived from ITE questions and sent Monday-Friday with a 20 per cent variance in messages specific to the sub-group. Residents completed surveys gauging perceptions of the programme, and pre- and post-programme ITE scores were analysed. RESULTS: Forty-one residents enrolled and 32 (78%) completed a post-programme survey. Of those, 21 (66%) preferred a Q&A format with an immediate text response versus information-only texts. The percentage change in ITE scores between 2013 and 2014 was significant. Comparing subgroups, there was no significant difference between the percentage change in ITE scores. Neither group performed significantly better on either the adolescent or developmental sections of the ITE. Text messaging… remains an underused educational tool CONCLUSIONS: Overall, participants improved their ITE scores, but no improvement was seen in the targeted subgroups on the exam. Although Q&A texts are preferred by residents, further assessment is required to assess the effect on educational outcomes.

Gene expression changes induced by skin sensitizers in the KeratinoSens™ cell line: Discriminating Nrf2-dependent and Nrf2-independent events.

The KeratinoSens™ assay is an in vitro screen for the skin sensitization potential of chemicals. It is based on a luciferase reporter gene under the control of the antioxidant response element of the aldoketoreductase gene AKR1C2. The transferability, reproducibility, and predictivity of the KeratinoSens™ assay have been investigated in detail and it is currently under assessment at the European Center for Validation of Alternatives to animal testing (ECVAM). Here we investigate the sensitizer-induced gene expression in the KeratinoSens™ cell line at the mRNA level and discriminate Nrf2-dependent and Nrf2-independent events by using siRNA to better characterize this test system at the molecular level. The results show that (i) the sensitizer-induced luciferase signal in KeratinoSens™ cells is completely dependent on Nrf2. The same holds true for the luciferase induction observed for the false positive chemical Tween80, indicating that the false positive result is not due to recruitment of an alternative transcription factor. (ii) Luciferase induction parallels the induction of endogenous Nrf2-dependent genes, indicating that the luciferase signal is representative for the sensitizer-induced Nrf2-response. (iii) The induction by sensitizers of additional genetic markers related to heat shock proteins and cellular stress could be reproduced in the KeratinoSens™ cell line and they were shown to be Nrf2-independent. These results confirm that the KeratinoSens™ cell line is a rapid and adequate screening tool to assess the sensitizer-induced Nrf2-response in keratinocytes.