Surgical Repair of a Left Main Coronary Artery to Right Ventricle Fistula in a Neonate.

We describe the case of a newborn male with a large fistula from the left main coronary artery to the right ventricle. This case illustrates a rare congenital coronary artery fistula and its successful surgical management in the neonatal period.

Vascular thrombosis after pediatric liver transplantation: Is prevention achievable?

Background: Vascular thromboses (VT) are life-threatening events after pediatric liver transplantation (LT). Single-center studies have identified risk factors for intra-abdominal VT, but large-scale pediatric studies are lacking. Methods: This multicenter retrospective cohort study of isolated pediatric LT recipients assessed pre- and perioperative variables to determine VT risk factors and anticoagulation-associated bleeding complications. Results: Within seven postoperative days, 31/331 (9.37%) patients developed intra-abdominal VT. Open fascia occurred more commonly in patients with VT (51.61 vs 23.33%) and remained the only independent risk factor in multivariable analysis (OR = 2.84, p = 0.012). Patients with VT received more blood products (83.87 vs 50.00%), had significantly higher rates of graft loss (22.58 vs 1.33%), infection (50.00 vs 20.60%), and unplanned return to the operating room (70.97 vs 16.44%) compared to those without VT. The risk of bleeding was similar (p = 0.2) between patients on and off anticoagulation. Conclusions: Prophylactic anticoagulation did not increase bleeding complications in this cohort. The only independent factor associated with VT was open fascia, likely a graft/recipient size mismatch surrogate, supporting the need to improve surgical techniques to prevent VT that may not be modifiable with anticoagulation.

Bivalirudin anticoagulation for cardiopulmonary bypass during cardiac surgery.

INTRODUCTION: Heparin is the primary anticoagulant for cardiopulmonary bypass (CPB) support during cardiac surgery. While widely used, ∼2% of cardiac surgery patients develop heparin-induced thrombocytopenia (HIT) and 4-26% develop heparin resistance. Bivalirudin is an alternative anticoagulant mainly used for percutaneous coronary interventions. Given the challenges associated with heparin anticoagulation, we conducted a review to explore the use of bivalirudin for CPB surgery. METHODS: PubMed and Embase scoping review included 2 randomized controlled trials, a retrospective comparison study, 3 pilot studies, and 30 case reports. To provide a contemporary series, we searched for articles published from 2010 to 2023. Our review included studies from both adult and pediatric populations. RESULTS: While data is limited, bivalirudin seems to supply similar effectiveness and safety as heparin for CPB anticoagulation. Across the three comparative studies, the heparin cohorts had a 0-9% mortality rate and 0-27% rate of major bleeding/reoperation compared to a 0-3% mortality and 0-6% major bleeding/reoperation rate for the bivalirudin cohorts. Bivalirudin was successfully used as an anticoagulant in a wide range of CPB surgeries (e.g., heart transplants, ventricular assisted device placements, and valve repairs). Successful patient outcomes were reported with bivalirudin infusion of ∼2 mg/kg/hour, activated clotting time monitoring (target >400 s or 2.5× baseline), use of cardiotomy suctions, minimization of stagnant blood, and post-bypass modified ultrafiltration. CONCLUSION: Bivalirudin is a safe and effective anticoagulant for CPB, especially for patients with HIT or heparin resistance. Further comparative research is called for to optimize bivalirudin utilization for CPB during cardiac surgery.

Pericardiectomy for Successful Treatment of Constrictive Pericarditis in a Pediatric Patient.

A 15-year-old girl with history of asthma and obesity presented with recurrent anasarca without systolic heart failure or significant renal disease. She was diagnosed with constrictive pericarditis and successfully underwent pericardiectomy with pericardial stripping and a waffle procedure. (Level of Difficulty: Advanced.).

Cardiac transplantation in adult congenital heart disease: a narrative review.

Background and Objective: As more children with congenital heart disease survive to adulthood, adult congenital heart disease (ACHD) prevalence will increase (currently ~1 million US patients). Heart failure (HF) accounts for 26-42% of ACHD deaths. The rate of ACHD heart transplantations (ACHD HTx) is also increasing. We describe the ACHD HTx recipient/candidate cohort, analyze ACHD HTx outcomes, identify ACHD HTx specific challenges, and discuss opportunities to better serve more patients with ACHD HF. Methods: PubMed literature search including articles published from 2010-2023. Reviewed 89 studies, 67 included. Our search focused on the challenges of ACHD HTx and potential solutions. Key Content and Findings: ACHD HTx recipients are young [median age 35 years, interquartile range (IQR): 24-46 years]. 87-95% of ACHD HTx recipients had prior cardiac surgery. The most common underlying diagnoses include transposition of the great arteries (31%) and Fontan/Glenn circulation (28%). 63% of listed ACHD HTx candidates received a transplant within one year of listing. Post-transplant 1-year survival is 80%, 5-year survival 74%, and 10-year survival 59%. There are 4 unique ACHD HTx challenges: (I) difficulty in assessing pulmonary hypertension, resulting in some centers selecting oversized donor hearts. However, selecting oversized hearts does not improve post-operative mortality and could prolong waitlist time. (II) Increased immunologic sensitization, increasing rejection risk. Desensitization therapy has enabled sensitized HTx recipients to enjoy outcomes similar to non-sensitized recipients. (III) Procedural complexity with ~30% of cases requiring additional surgical reconstruction. Detailed multidisciplinary planning, extensive imaging, and transferring the patient into the operating room early can help manage the complexities and reduce organ ischemic time. (IV) Increased intraoperative bleeding due to patients' surgical histories and circulatory collaterals. Preoperative collateral coil embolization and select utilization of hypothermic circulatory arrest can help reduce bleeding. Additional Fontan specific challenges include extensive great artery repair, liver failure, plastic bronchitis, and protein loss enteropathy. Finally, given limited donor heart availability, mechanical circulatory support is a promising technology for patients with ACHD HF. Conclusions: The prevalence of ACHD HTx is slowly but steadily increasing. The operational complexity of ACHD HTx can be managed, and the majority of recipients have excellent outcomes (59% 10-year survival).

Antithrombin III supplementation during neonatal and pediatric extracorporeal membrane oxygenation.

BACKGROUND: Bleeding and thrombosis are common extracorporeal membrane oxygenation (ECMO) complications associated with increased mortality. Heparin is the most commonly used ECMO anticoagulant, employed in 94% of cases. Reduced antithrombin III (AT3) levels could decrease heparin effectiveness. Neonates have inherently lower levels of AT3 than adults, and pediatric patients on ECMO can develop AT3 deficiency. One potential approach for patients on ECMO with AT3 deficiency is exogenous AT3 supplementation. However, there is conflicting data concerning the use of AT3 for pediatric and neonatal patients on ECMO. METHODS: We analyzed the Bleeding and Thrombosis during ECMO database of 514 neonatal and pediatric patients on ECMO. We constructed daily regression models to determine the association between AT3 supplementation and rates of bleeding and thrombosis. Given the physiological differences between pediatric patients and neonates, we constructed separate models for each. RESULTS: AT3 administration was associated with increased rates of daily bleeding among pediatric (adjusted odds ratio [aOR] 1.59, p < 0.01) and neonatal (aOR 1.37, p = 0.04) patients. AT3 supplementation did not reduce the rate of thrombosis for either pediatric or neonatal patients. CONCLUSION: AT3 administration was associated with increased rates of daily bleeding, a hypothesized potential complication of AT3 supplementation. In addition, AT3 supplementation did not result in lower rates of thrombosis. We recommend clinicians utilize caution when considering supplementing patients on ECMO with exogenous AT3.

Anti-Xa testing for pediatric and neonatal patients on extracorporeal membrane oxygenation.

INTRODUCTION: To determine if anti-Xa testing is associated with improved outcomes for patients <19-years-old on ECMO. METHODS: We evaluated the clinical benefit of anti-Xa heparin monitoring utilizing the Bleeding and Thrombosis during ECMO (BATE) database of 514 patients <19-years-old. The BATE database includes incidences of bleeding, thrombosis, and mortality. The database also describes anti-coagulation test utilization. We grouped and analyzed patients based on ECMO indication (cardiac, respiratory, or extracorporeal cardiopulmonary resuscitation [E-CPR]) and age (neonatal vs pediatric). We constructed multivariable logistic regression models to analyze the impact of anti-Xa testing on mortality, bleeding, and thrombosis in each group. RESULTS: Across the entire population, anti-Xa testing did not have a significant effect on the incidence of mortality (43% with anti-Xa testing vs 49% without), bleeding (68% vs 74%), or thrombosis (37% vs 39%). However, among cardiac indicated patients on ECMO (n = 207), anti-Xa testing was significantly associated with reduced odds ratio (OR) of mortality (adjusted OR 0.527, p = .040) and bleeding (adjusted OR 0.369, p = .021). In addition, among neonatal patients on ECMO (n = 264), anti-Xa testing was associated with a significant reduction in the odds ratio of bleeding (adjusted OR 0.534, p = .046). CONCLUSION: Anti-Xa testing is associated with improved outcomes among cardiac indicated and neonatal patients on ECMO. Additional research to find the optimal heparin monitoring regimen is needed to better support these critically ill patients. In the interim, we recommend clinicians consider utilizing anti-Xa assays as part of their heparin monitoring plan for neonatal and cardiac indicated patients on ECMO.

Critical Care and Mechanical Ventilation Practices Surrounding Liver Transplantation in Children: A Multicenter Collaborative.

OBJECTIVES: We aimed to determine which characteristics and management approaches were associated with postoperative invasive mechanical ventilation (IMV) and with a prolonged course of IMV in children post liver transplant as well as describing the utilization of critical care resources. DESIGN: Retrospective, multicenter, cohort study of children who underwent an isolated liver transplantation between January 2017 and December 2018. SETTING: Twelve U.S., pediatric, liver transplant centers. PATIENTS: Three hundred thirty children post liver transplant admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Six patients died in our cohort. The median length of PICU stay was 4.5 days (interquartile range [IQR], 2.9-8.2 d). Most patients were initially monitored with arterial catheters (96%), central venous pressures (95%), and liver ultrasound (93%). Anticoagulation (80%), blood product administration (52.4%), and vasoactive agents (23.0%) were commonly used therapies in the first 7 days. In multivariable logistic regression analysis, age (adjusted odds ratio [aOR] 0.9 [0.86-0.95]), open fascia (aOR 7.0 [95% CI, 2.6-18.9]), large center size (aOR 4.3 [95% CI 2.2-8.3]), and higher Model for End-Stage Liver Disease/Pediatric End-Stage Liver Disease scores (aOR 1.04 [95% CI, 1.01-1.06]) were associated with postoperative IMV. In multivariable logistic regression analysis, postoperative day 0 peak inspiratory pressure (PIP) (aOR 1.2 [95% CI, 1.1-1.3]), large center size (aOR 2.9 [95% CI, 1.6-5.4]), and age (aOR 0.89 [95% CI, 0.85-0.95]) were associated with length of IMV greater than 24 hours. Length of IMV greater than 24 hours was associated with bleeding complications ( p = 0.03), infections ( p = 0.03), graft loss ( p = 0.02), and reoperation ( p = 0.03). CONCLUSIONS: Younger age, preoperative hospitalization, large center size, and open fascia are associated with use of IMV, and younger age, large center size, and postoperative day 0 PIP are associated with prolonged IMV on multivariable analysis. Longer IMV is associated with negative outcomes, making it an important clinical marker.

Use of bivalirudin for anticoagulation in pediatric extracorporeal membrane oxygenation (ECMO).

This study describes the use of bivalirudin in children on extracorporeal membrane oxygenation (ECMO). Pediatric patients receiving bivalirudin were compared to patients receiving heparin as the anticoagulant on ECMO. Data was collected for children under 18 years of age supported by ECMO from January 2016 to December 2019. Data collected included demographics, diagnosis, ECMO indication, type, and duration, indication for bivalirudin use, dose range, activated partial thromboplastin time (aPTT) levels, minor and major bleeding, hemolysis, and mortality. Forty pediatric patients received ECMO; eight received bivalirudin primarily for anticoagulation. The median age was 4 months (IQR 0.5, 92) in the heparin cohort, 0.6 months (IQR 0.0, 80.0) in the primary bivalirudin cohort. The indication for ECMO was respiratory in 5 patients (18%) in the heparin group versus 6 (75%) in the primary bivalirudin group, cardiac in 18 (67%) in heparin versus 1 (12.5%) in primary bivalirudin, and extracorporeal-cardiopulmonary resuscitation (E-CPR) in 4 (15%) in heparin versus 1 (12.5%) in primary bivalirudin. Bivalirudin was the initial anticoagulant for eight patients (66.6%) while three (25%) were switched due to concern for heparin-induced thrombocytopenia (HIT) and one (8%) for heparin resistance. The median time to achieve therapeutic aPTT was 14.5 hours compared to 12 hours in the heparin group. Sixty-five percent of aPTT values in the bivalirudin and 44% of values in the heparin group were in the therapeutic range in the first 7 days. Patients with primary bivalirudin use had significantly lower dose requirement at 12 (p = 0.003), 36 (p = 0.007), and 48 (p = 0.0002) hours compared to patients with secondary use of bivalirudin. One patient (12.5%) had major bleeding, and two patients (25%) required circuit change in the primary bivalirudin cohort. Bivalirudin may provide stable and successful anticoagulation in children. Further large, multicenter studies are needed to confirm these findings.

Volumetric Capnography in Pediatric Extracorporeal Membrane Oxygenation: A Case Series.

The kinetics of carbon dioxide elimination (VCO 2 ) may be used as a surrogate for pulmonary blood flow. As such, we can apply a novel use of volumetric capnography to assess hemodynamic stability in patients requiring extracorporeal membrane oxygenation (ECMO). We report our experience of pediatric patients requiring ECMO support who were monitored using volumetric capnography. We describe the use of VCO 2 and its association with successful decannulation. This is a prospective observational study of pediatric patients requiring ECMO support at The Children's Hospital at Montefiore from 2017 to 2019. A Respironics NM3 monitor was applied to each patient. Demographics, hemodynamic data, blood gases, and VCO 2 (mL/min) data were collected. Data were collected immediately prior to and after decannulation. Over the course of the study period, seven patients were included. Predecannulation VCO 2 was higher among patients who were successfully decannulated than nonsurvivors (109 [35, 230] vs. 12.4 [7.6, 17.2] mL/min), though not statistically significant. Four patients (57%) survived without further mechanical support; two (29%) died, and one (14%) was decannulated to Berlin. Predecannulation VCO 2 appears to correlate with hemodynamic stability following decannulation. This case series adds to the growing literature describing the use of volumetric capnography in critical care medicine, particularly pediatric patients requiring ECMO. Prospective studies are needed to further elucidate the use of volumetric capnography and optimal timing for ECMO decannulation.

Implementation of a Critical Care Asthma Pathway in the PICU.

OBJECTIVES: Acute asthma management has improved significantly across hospitals in the United States due to implementation of standardized care pathways. Management of severe acute asthma in ICUs is less well studied, and variations in management may delay escalation and/or deescalation of therapies and increase length of stay. In order to standardize the management of severe acute asthma in our PICU, a nurse- and respiratory therapist-driven critical care asthma pathway was designed, implemented, and tested. DESIGN: Cross-sectional study of severe acute asthma at baseline followed by implementation of a critical care asthma pathway. SETTING: Twenty-six-bed urban quaternary PICU within a children's hospital. PATIENTS: Patients 24 months to 18 years old admitted to the PICU in status asthmaticus. Patients with severe bacterial infections, chronic lung disease, heart disease, or immune disorders were excluded. INTERVENTIONS: Implementation of a nurse- and respiratory therapist-driven respiratory scoring tool and critical care asthma pathway with explicit escalation/deescalation instructions. MEASUREMENTS AND MAIN RESULTS: Primary outcome was PICU length of stay. Secondary outcomes were time to resolution of symptoms and hospital length of stay. Compliance approached 90% for respiratory score documentation and critical care asthma pathway adherence. Severity of illness at admission and clinical baseline characteristics were comparable in both groups. Pre intervention, the median ICU length of stay was 2 days (interquartile range, 1-3 d) with an overall hospital length of stay of 4 days (interquartile range, 3-6 d) (n = 74). After implementation of the critical care asthma pathway, the ICU length of stay was 1 day (interquartile range, 1-2 d) (p = 0.0013; n = 78) with an overall length of stay of 3 days (interquartile range, 2-3.75 d) (p < 0.001). The time to resolution of symptoms was reduced from a median of 66.5 hours in the preintervention group to 21 hours in the postintervention compliant group (p = 0.036). CONCLUSIONS: The use of a structured critical care asthma pathway, driven by an ICU nurse and respiratory therapist, is associated with faster resolution of symptoms, decreased ICU, and overall hospital lengths of stay in children admitted to an ICU for severe acute asthma.

Longitudinal Echocardiographic Assessment of Coronary Arteries and Left Ventricular Function following Multisystem Inflammatory Syndrome in Children.

Myocardial dysfunction and coronary artery dilation have been reported in the acute setting of severe acute respiratory syndrome coronavirus disease-2-related multisystem inflammatory syndrome in children. Through a longitudinal echocardiographic single-center study of 15 children, we report the short-term outcomes of cardiac dysfunction and coronary artery dilation in severe acute respiratory syndrome coronavirus disease-2-related multisystem inflammatory syndrome in children.

Lactic Acidosis Secondary to Thiamin Deficiency Following Autologous Stem Cell Transplantation.

A 22-month-old female with high-risk neuroblastoma completed 5 cycles of chemotherapy then underwent high-dose chemotherapy with autologous stem cell rescue (ASCR). Parenteral nutrition was administered from day +2 following ASCR, as she was unable to tolerate nasogastric feeds because of grade IV mucositis and vomiting. On day +12, she developed worsening metabolic acidosis with above reportable levels of lactic acid. Given the patient's well clinical appearance and paucity of evidence of end-organ dysfunction on physical examination and on laboratory studies, there was high suspicion that the patient's lactic acidosis did not result from tissue hypoxia and was, in fact, a type B lactic acidosis. Thiamin was empirically administered, with rapid improvement in lactic acidosis. Thiamin deficiency was later confirmed by laboratory studies drawn prior to thiamin administration.

Acute Kidney Injury in Pediatric Acute Respiratory Distress Syndrome.

OBJECTIVES: To describe the incidence of and risk factors for acute kidney injury (AKI) in children with acute respiratory distress syndrome (ARDS) and study the effect of AKI on patient outcomes. DESIGN: A single-center retrospective study. SETTING: A tertiary care children's hospital. PATIENTS: All patients less than 18 years of age who received invasive mechanical ventilation (MV) and developed ARDS between July 2010 and July 2013 were included. Acute kidney injury was defined using p-RIFLE (risk, injury, failure, loss, and end-stage renal disease) criteria. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fifteen children met the criteria and were included in the study. Seventy-four children (74/115, 64%) developed AKI. The severity of AKI was risk in 34 (46%) of 74, injury in 19 (26%) of 74, and failure in 21 (28%) of 74. The presence of AKI was associated with lower Pao 2 to Fio 2 (P/F) ratio (P = .007), need for inotropes (P = .003), need for diuretics (P = .004), higher oxygenation index (P = .03), higher positive end-expiratory pressure (PEEP; P = .01), higher mean airway pressure (P = .008), and higher Fio 2 requirement (P = .03). Only PEEP and P/F ratios were significantly associated with AKI in the unadjusted logistic regression model. Patients with AKI had a significantly longer duration of hospital stay, although there was no significant difference in the intensive care unit stay, duration of MV, and mortality. Recovery of AKI occurred in 68% of the patients. A multivariable model including PEEP, P/F ratio, weight, need for inotropes, and need for diuretics had a better receiver operating characteristic (ROC) curve with an AUC of 0.75 compared to the ROC curves for PEEP only and P/F ratio only for the prediction of AKI. CONCLUSIONS: Patients with ARDS have high rates of AKI, and its presence is associated with increased morbidity and mortality.

Pediatric Acute Respiratory Distress Syndrome (PARDS) in Children With Pulmonary Contusion.

OBJECTIVE: There is paucity of data about prevalence of pediatric acute respiratory distress syndrome (PARDS) in children with pulmonary contusion (PC). We intend to evaluate PC in children with chest trauma and the association between PC and PARDS. DESIGN: Retrospective review of Institutional Trauma Registry for patients with trauma. SETTING: Level 1 trauma center. PATIENTS: Age 18 years and younger with a diagnosis of PC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of the 1916 children with trauma, 50 (2.6%) had PC. Patients with PC and PARDS had lower Glasgow Coma Scale (GCS) score (7 [3-15] vs 15 [15-15], P = .0003), higher Injury Severity Scale (ISS) score (29 [22-34] vs 19 [14-22], P = .004), lower oxygen saturations (96 [93-99] days vs 99 [98-100] days, P = .0009), higher FiO2 (1 [1-1] vs 0.21 [0.21-0.40], P < .0001), lower oxygen saturation/FiO2 (S/F) ratios (97 [90-99] vs 457 [280-471], P < .0001), need for invasive mechanical ventilation (IMV; 86% vs 23%, P < .0001), and mortality (28% vs 0%, P = .006) compared to those without PARDS. Forty-two percent (21/50) of patients needed IMV, of these 61% (13/21) had PARDS. Patients who needed IMV had significantly lower GCS score (8 [3-11] vs 15 [15-15], P < .0001), higher ISS score (27 [22-34] vs 18 [14-22], P = .002), longer length of stay (LOS; 7.5 [4-14] days vs 3.3 [2-5] days, P = .003), longer hospital LOS (18 [7.0-25] vs 5 [4-11], P = .008), higher PARDS rate (62% vs 7%, P < .0001), and lower S/F ratios (99 [94-190] vs 461 [353-471], P < .0001) compared to those who did not require IMV. Lower GCS score was independently associated with both PARDS and need for IMV. CONCLUSIONS: Pediatric ARDS in children with PC is independently associated with lower GCS score, and its presence significantly increased morbidity and mortality. Further larger studies are needed to explore association of lower GCS and higher injury score in children with PARDS and PC.

The Practice and Complications of Midline Catheters: A Systematic Review.

OBJECTIVE: Midline catheters are considered "midway" regarding vascular access. The objective of this systematic review was to explore the current practice, dwell time, and complication rates of midline catheters. DESIGN: Systematic review. SETTING: Search on four databases, PubMed, CINAHL, Scopus, and Embase, were conducted for English language articles published after the year 2000. MEASUREMENTS AND MAIN RESULTS: A total of 987 articles were identified, of which 31 manuscripts met the inclusion criteria and were selected for review. Quality assurance was performed based on the Newcastle-Ottawa score. Average dwell time and complication rates were calculated for studies involving adult patients and adjusted for sample size. This analysis included data from the placement of 18,972 midline catheters across five countries. Aside from two randomized control trials, most of the studies analyzed were cohort studies. One pediatric and two neonatal studies were included. The average dwell time was 16.3 days (n = 4,412). The adjusted mean infection rate was 0.28/1,000 catheter days, with 64% of studies not reporting any infection with midline catheter. The failure rate of midline catheters was 12.5%. Adjusted average rates of other significant complications included the following: deep vein thrombosis (4.1%), dislodgement (5.0%), occlusion (3.8%), phlebitis (3.4%), and infiltration (1.9%). CONCLUSIONS: The dwell times and failure rates of midline catheters compare favorably against published data on other types of catheters. Their infection rates are also lower than the reported rates of central venous catheters; however, they have a higher rate of mechanical complications. Active surveillance of infections due to midline catheters is recommended. More data are needed from pediatric and neonatal populations.

ECMO support in SARS-CoV2 multisystem inflammatory syndrome in children in a child.

In this report, we describe the case of a 5-year-old male with SARS-CoV-2 associated MIS-C with progressive respiratory failure and vasoplegic shock requiring extracorporeal support. At presentation, reverse transcription-polymerase chain reaction (RT-PCR) testing for SARS-CoV-2 was negative, however, SARS-CoV2 antibody testing was positive. Multiple inflammatory markers and cardiac biomarkers were elevated. Echocardiogram demonstrated mildly depressed left ventricular function and no coronary anomalies noted. The patient required mechanical ventilation, vasopressors, and eventually extracorporeal membrane oxygenation (ECMO) for profound circulatory shock and progressive respiratory failure. During his clinical course, recovery of cardiac function was demonstrated however, a middle cerebral artery infarct and left frontal subarachnoid hemorrhage was suffered which ultimately the patient succumbed to. To the best of our knowledge, this is the youngest previously healthy child who had multi-system hyperinflammatory syndrome requiring ECMO support and the first case of SARS-CoV-2 related pediatric stroke.Clinical Trial Registration: None.