Management of Pediatric Pulmonary Hypertension Using Remote Pulmonary Artery Pressure Sensor Monitoring

Background Management of pediatric pulmonary hypertension (PH) may require manipulation of multiple receptor sites to maximize response to medical therapy. Assessment of response typically occurs through imaging, labs, physical exam and recurrent cardiac catheterization, with anesthetic exposure to assess pulmonary artery pressures (PAP) and vascular resistance (PVR). We aimed to assess feasibility, safety and utility of remote PAP monitoring in pediatric PH patients. Methods We reviewed 4 pediatric patients with significant PH, each of whom underwent cardiac catheterization with pulmonary vasoreactivity testing and placement of a CardioMEMS remote PAP monitoring device. Results Four patients (P1-4: ages 5, 6, 8 and 10 years old) underwent CardioMEMS insertion without procedural complication. P1, P2 and P3 presented with unrepaired VSD;ASD with partial anomalous pulmonary venous return;and ASD and PDA, respectively, while P4 had prior repair of atrioventricular canal. Three patients had Down syndrome. All had elevated PAP and PVR. Mean left lower PA branch size was 7 mm. Mean PAP prior to therapy was 70 mm Hg for P1, 82 for P2, 93 for P3 and 30 for P4. All 4 patients required initiation of triple therapy for treatment of PH, with improvement or normalization of PAP by CardioMEMS, which also included surgical or catheter based intervention for 3 patients. Post-repair of P2, he was unable to be separated from cardiopulmonary bypass and was placed on ECMO. Right ventricular cardiac output improved over 2 weeks, with improvement of PAP determined through serial CardioMEMS. He was successfully decannulated, utilizing CardioMEMS in the OR. Two patients also developed COVID respiratory infections at home with CardioMEMS assessments allowing for oxygen and medication titration. Conclusion Remote PAP monitoring is feasible and appears safe in pediatric patients with adequate PA size. It allows for manipulation of medical therapy with real time knowledge of impact on PAP and can augment management during weaning of mechanical cardiac support. It may also augment decision-making in management of PH patients with developmental disabilities in whom traditional assessments may be more challenging.Copyright © 2023 American College of Cardiology Foundation

Covid-19 Induced Biventricular Takotsubo Cardiomyopathy

Background Takotsubo Cardiomyopathy (TTS) is a syndrome of transient LV dysfunction. Myocardial injury (MCI) has been reported in acute COVID-19 (C19) infections, however, the exact pathophysiology is unclear. Association of rising cardiac biomarkers with inflammatory markers suggests systemic inflammatory response in C19 infection in causing MCI. Case A 52-year-old AA male with history of HTN presents with complaint of worsening shortness of breath and atypical chest pain. Diagnosed with C19 and intubated due to respiratory failure. Chest pain workup included TTE which showed biventricular (BV) systolic dysfunction with apical ballooning and LVEF 25-30%. Left heart catheterization showed non-obstructing coronary disease. Repeat TTE 2 weeks later showed normal BV systolic function with LVEF greater than 55%. Decision-making BV TTS is associated with more hemodynamic instability than is isolated LV TTS. Mayo Clinic diagnostic criteria for TTS requires absence of obstructive CAD or plaque rupture. Rapid recovery of BV function is consistent with TTS with transient BV dysfunction. LV TTS is common in COVID-19 infections, but BV TTS is a less common complication of COVID. Conclusion Due to the propensity of C19 to cause hemodynamic instability it is important to not relate to a patient's instability to C19 alone. It is important to consider TTE in patients with C19, as the patient may be experiencing TTS. [Formula presented]Copyright © 2023 American College of Cardiology Foundation

Behavioral pediatrics: Mental health and management. Fifth edition

Pediatricians can provide a wide variety of care to children and adolescents with complex disorders, depending on their training as well as interests, but they need to work closely with professionals in psychiatry and psychology when dealing with complex issues in mental health disorders. Behavioral health screening is therefore an important task of pediatricians and behavioral pediatricians as they evaluate their pediatric patients. Section one looks at what is called special issues in mental health that include suicide/self-harm in pediatrics, childhood-onset schizophrenia, child abuse/maltreatment, mental health issues of chronic disorders (i.e., diseases of the cardiovascular system, the kidneys and the liver), and behavioral/emotional effects of COVID-19 on children/adolescents. Section two covers various aspects of substance use disorders (SUD) that include SUD neurobiology, substance use/abuse in adolescents, an overview on cannabis, psychosocial treatments of SUDs, pharmacologic management of SUDs, and pharmacology of tobacco abuse. Section three provides a critical look at mental health management that includes psychotherapeutic interventions (i.e., children, adolescents and families), behavioral/cognitive behavioral therapies and principles of psychopharmacologic management in pediatric persons. © 2022 by Nova Science Publishers, Inc.

BAMLANIVIMAB PLUS ETESEVIMAB for the TREATMENT of COVID-19 in PEDIATRIC PATIENTS

Background: There are no authorized or approved treatments in the US for COVID-19 in patients <12 years of age. SARS-CoV-2 neutralizing monoclonal antibodies bamlanivimab and etesevimab together (BAM+ETE) reduce COVID-19 related hospitalization and all-cause mortality in patients ≥12 years of age with mild to moderate COVID-19. Herein, we present the pharmacokinetic (PK), safety, and efficacy results from an open-label Phase III clinical trial addendum (BLAZE-1, NCT04427501) investigating weight-based dosing of BAM+ETE in pediatric patients at increased risk for severe COVID-19. Methods: A total of 91 pediatric patients (<18 years of age) were evaluated for PK. Pediatric patients weighing ≥40kg received 700mg BAM+1400mg ETE. Pediatric patients weighing less than 40kg received weight-based dosing to match the exposures observed in adults and adolescents (12 to <18 years of age) who received the authorized dose of 700mg BAM+1400mg ETE. Twenty additional adolescent patients (12 to <18 years of age) received BAM+ETE in controlled BLAZE-1 cohorts and were included in safety and efficacy analyses. All ambulatory patients had mild to moderate COVID-19 upon enrollment, at least one risk factor for severe COVID-19, and received treatment within 3 days of a positive SARS-CoV-2 test. The primary objective was to characterize the pharmacokinetics of weight-based dosing of BAM+ETE in pediatric patients. Results: Of the 111 pediatric patients who received BAM+ETE, the median age was 12 and age distribution was 12 to <18 (n=60), 6 to <12 (n=36), 2 to <6 (n=10), and 0 to <2 (n=5). Overall, 47.7% were female, 19.1% were Hispanic/Latino, and 62.4% were Black/African American. In patients receiving weight-based dosing, the AUC for both BAM and ETE in pediatric patients was similar (within 90% interval) to adults (Figure). For all pediatric patients, there were no reports of hospitalizations, serious adverse events, or deaths. At Day 7, pediatric patients had a change in viral load from baseline of-4.10 (normalized baseline viral load of 6.41) as compared to-3.65 (normalized baseline viral load of 6.75) in adult patients. The median time to complete symptom resolution was 5 days for all pediatric patients. Conclusion: The weight-based doses administered to pediatric patients provided similar drug exposures when compared to adult patients who received the authorized dose of 700 mg BAM+1400mg ETE. Treatment in pediatric patients was well-tolerated and resulted in favorable viral load reduction and symptom resolution.

Immune durability and protection against SARS-CoV-2 re-infection in Syrian hamsters.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a pandemic. As immunity to endemic human coronaviruses (i.e. NL63 or OC43) wanes leading to re-infection, it was unknown if SARS-CoV-2 immunity would also decline permitting repeat infections. Recent case reports confirm previously infected individuals can become re-infected; however, re-infection may be due to heterogeneity in the initial infection or the host immune response, or may be the result of infection with a variant strain that escapes pre-existing immunity. To control these variables, we utilized the Syrian hamster model to evaluate the duration of immunity and susceptibility to re-infection with SARS-CoV-2. Hamsters were given a primary mock or SARS-CoV-2 infection (culture media or 105 TCID50 USA/WA1/2020 isolate, respectively). Mock and SARS-CoV-2 infected hamsters were then given a secondary SARS-CoV-2 infection at 1, 2, 4, or 6 months post-primary infection (n = 14/time point/group). After the primary SARS-CoV-2 infection, hamsters developed anti-spike protein IgG, IgA, and neutralizing antibodies, and these antibodies were maintained for at least 6 months. Upon secondary SARS-CoV-2 challenge, previously SARS-CoV-2 infected animals were protected from weight loss, while all previously mock-infected animals became infected and lost weight. Importantly, despite having high titres of antibodies, one SARS-CoV-2 infected animal re-challenged at 4 months had a breakthrough infection with replicating virus in the upper and lower respiratory tract. These studies demonstrate immunity to SARS-CoV-2 is maintained for 6 months; however, protection may be incomplete and, even in the presence of high antibody titres, previously infected hosts may become re-infected.

Bamlanivimab+etesevimab for treatment of COVID-19 in high-risk ambulatory patients

Background: Patients with underlying medical conditions have a greater risk of developing severe COVID-19. Unlike vaccine-derived immunity which develops over time, administration of neutralizing monoclonal antibodies is an immediate, passive humoral immunotherapy, with the potential to reduce disease progression, emergency room visits, hospitalizations, and death. Methods: In this phase 3 portion of the BLAZE-1 trial, a high-risk ambulatory cohort of 1035 patients with mild-to-moderate COVID-19 were randomly assigned 1:1 to receive a single intravenous infusion of a neutralizing monoclonal antibody combination treatment consisting of 2800mg bamlanivimab+2800mg etesevimab together, or placebo, within 3 days of laboratory diagnosis. The primary outcome was overall patient clinical status, measured by the proportion of patients who experienced COVID-19-related hospitalization or death by any cause by Day 29. Results: 1035 patients were randomized and infused (mean age [SD];53.8 years [16.8], female (52%)). A 70% reduction in COVID-19-related hospitalization and death by any cause by Day 29 was observed in patients who received the bamlanivimab+etesevimab combination treatment (11/518 arm total) compared to those who received placebo (36/517 arm total) (Δ[95% CI]=-4.8[-7.4,-2.3])(p=0.0004). No deaths were observed among patients who received the combination treatment, 10 deaths were reported in the placebo group, at least 8 designated COVID-19-related. A significantly greater reduction in log10(viral load) from baseline at Day 7 was observed amongst patients who received bamlanivimab+etesevimab compared to placebo (Δ[95% CI]=-1.20[-1.46,-0.94])(p<0.00000001). The median time to sustained symptom resolution was shorter for those who received the combination treatment (days [95% CI]=8[7.0,8.0]) compared to those who received placebo (days [95% CI]=9[8.0,10.0])(p=0.007). Similar rates of adverse events were observed between placebo (60/517,11.6%) and combination treatment groups (69/518,13.3%). Conclusion: 2800mg bamlanivimab+2800mg etesevimab neutralizing monoclonal antibody combination therapy significantly reduced COVID-19- related hospitalizations and deaths amongst high-risk ambulatory patients and accelerated the decline in viral load and disease symptoms over time. This study confirms that early intervention with bamlanivimab + etesevimab greatly improves the clinical outcomes for high-risk ambulatory patients, and links reduction in nasopharyngeal viral load to clinically meaningful benefits.