A clinical impact study of dermatologists' use of diagnostic gene expression profile testing to guide patient management.

Aim: Cutaneous melanocytic neoplasms with diagnostic and/or clinical ambiguity pose patient management challenges. Methods: Six randomized case scenarios with diagnostic/clinical uncertainty were described with/without a benign or malignant diagnostic gene expression profile (GEP) result. Results: Clinical impact was assessed by reporting the mean increase/decrease of management changes normalized to baseline (n = 32 dermatologists). Benign GEP results prompted clinicians to decrease surgical margins (84.2%). Malignant GEP results escalated surgical excision recommendations (100%). A majority (72.2%) reduced and nearly all (98.9%) increased follow-up frequency for benign or malignant GEP results, respectively. There was an overall increase in management plan confidence with GEP results. Conclusion: Diagnostic GEP tests help guide clinical decision-making in a variety of diagnostically ambiguous or clinicopathologically discordant scenarios.

Dermatologists' use of diagnostic gene expression profiles for personalized patient care. When your doctor takes a piece of a mole, that mole is looked at under the microscope by a pathologist. The pathologist is responsible for figuring out if the mole is dangerous or not. Dangerous moles are removed with surgery to make sure all the dangerous tissue is gone. Moles without a health threat are left alone. Sometimes figuring out how dangerous a mole is is difficult. The pathologist may not provide the doctor with enough information for them to know how to treat your mole. There is a test that can provide information on whether your mole is unsafe. This test is called diagnostic gene expression profiling or GEP. In this study, GEP is used to help doctors figure out how to treat a mole and how often the patient should be seen in the office for skin checks. With GEP, important changes in patient treatment were identified. These include the need for an additional surgery, how much healthy tissue should be removed during surgery and how often the patient should be seen in the office. For suspicious moles where the pathology report is unclear, GEP can provide information that leads to more appropriate and personalized patient care.

Ancillary diagnostic gene expression profile testing for ambiguous cutaneous melanocytic lesions helps optimize dermatologist recommendations for excision margin and follow-up.

Association of outcomes in point-of-care lung ultrasound for bronchiolitis in the pediatric emergency department.

BACKGROUND: Acute bronchiolitis (AB) is the most common lower respiratory tract infection in infants. Objective scoring tools and plain film radiography have limited application, thus diagnosis is clinical. The role of point-of-care lung ultrasound (LUS) is not well established. OBJECTIVE: We sought to characterize LUS findings in infants presenting to the pediatric ED diagnosed with AB, and to identify associations between LUS and respiratory support (RS) at 12 and 24 h, maximum RS during hospitalization, disposition, and hospital length of stay (LOS). METHODS: Infants ≤12 months presenting to the ED and diagnosed with AB were enrolled. LUS was performed at the bedside by a physician. Lungs were divided into 12 segments and scanned, then scored and summated (min. 0, max. 36) in real time accordingly: 0 - A lines with <3 B lines per lung segment. 1 - ≥3 B lines per lung segment, but not consolidated. 2 - consolidated B lines, but no subpleural consolidation. 3 - subpleural consolidation with any findings scoring 1 or 2. Chart review was performed for all patients after discharge. RS was categorized accordingly: RS (room air), low RS (wall O2 or heated high flow nasal cannula <1 L/kg), and high RS (heated high flow nasal cannula ≥1 L/kg or positive pressure). RESULTS: 82 subjects were enrolled. Regarding disposition, the mean (SD) LUS scores were: discharged 1.18 (1.33); admitted to the floor 4.34 (3.62); and admitted to the ICU was 10.84 (6.54). For RS, the mean (SD) LUS scores at 12 h were: no RS 1.56 (1.93), low RS 4.34 (3.51), and high RS 11.94 (6.17). At 24 h: no RS 2.11 (2.35), low RS 4.91 (3.86), and high RS 12.64 (6.48). Maximum RS: no RS 1.22 (1.31), low RS 4.11 (3.61), and high RS 10.45 (6.16). Mean differences for all dispositions and RS time points were statistically significant (p < 0.05, CI >95%). The mean (SD) hospital LOS was 84.5 h (SD 62.9). The Pearson correlation coefficient (r) comparing LOS and LUS was 0.489 (p < 0.0001). CONCLUSION: Higher LUS scores for AB were associated with increased respiratory support, longer LOS, and more acute disposition. The use of bedside LUS in the ED may assist the clinician in the management and disposition of patient's diagnosed with AB.

Diagnostic Yield of Cardiac Biomarker Testing in Predicting Cardiac Disease and Multisystem Inflammatory Syndrome in Children in the Pandemic Era.

OBJECTIVES: This study aimed to assess whether elevations in cardiac biomarkers are associated with pediatric cardiac diagnoses in the era of COVID-19 and multisystem inflammatory syndrome in children (MIS-C). STUDY DESIGN: This single-center retrospective study analyzed children with a troponin drawn in the emergency department or inpatient unit between April 21 and December 31, 2020. The primary outcome was the presence of a cardiac diagnosis or MIS-C. Relationships among demographics, complaint, cardiac diagnostics, and cardiac biomarkers were analyzed. RESULTS: Four hundred eighty-six patients (mean ± SD; age 13.1 ± 7.8 years; 46.7% women) met inclusion criteria, for whom a cardiac diagnosis (excluding MIS-C) was made in 27 (5.6%) patients, with MIS-C diagnosed in 14 (2.9%) patients. The sensitivity and specificity of an elevated initial high-sensitivity troponin T (hsTropT) value (>14 ng/L) in predicting the composite outcome of a cardiac diagnosis or MIS-C were 54% and 89%, respectively. Four percent of patients with negative initial troponin values were found to have a cardiac diagnosis or MIS-C. Multivariable regression analysis demonstrated that elevated hsTropT (>14 ng/L; odds ratio [OR] [95% confidence interval]: 4.9 [1.70-14.0]) and elevated N-terminal pro B-type natriuretic peptide values (>500 pg/mL; 6.4 [2.01-20.1]) were associated with increased odds of a cardiac diagnosis or MIS-C. CONCLUSIONS: Children with elevated cardiac biomarkers have increased odds of a cardiac diagnosis or MIS-C and warrant workup regardless of indication for testing. Although a negative hsTropT may reassure providers, further investigation is critical in developing algorithms to reliably exclude cardiac disease.

Response to Alpelisib in Clinically Distinct Pediatric Patients With PIK3CA -related Disorders.

PIK3CA -related disorders include vascular malformations, potential overgrowth of various tissues, limb abnormalities, disordered soft tissue, and/or fatty hyperplasia that often leads to significant morbidity. Alpelisib, a targeted inhibitor of p110α, an enzyme encoded by the PIK3CA gene, has demonstrated success in a cohort of patients with PIK3CA -driven overgrowth syndromes. We describe the clinical course of 2 pediatric patients treated with alpelisib under the Novartis Managed Access Program. Both patients, though clinically distinct, demonstrate improvements in overgrowth volumes/extent, function of their affected limb, and quality of life, without significant adverse effects after prolonged treatment.

Pediatric Non-Myofibroblastic Primitive Spindle Cell Tumors with ALK Gene Rearrangements and Response to Crizotinib.

We describe two poorly differentiated, non-myofibroblastic (SMA-, S100+, CD34±), spindle cell neoplasms with immunohistochemical positivity for ALK and with ALK gene rearrangements leading to PLEKHH2::ALK and CLTC::ALK fusions, respectively. ALK protein overexpression and/or gene fusions should be evaluated in poorly differentiated spindle cell neoplasms, even when there is an absence of a myofibroblastic phenotype. A positive ALK evaluation has therapeutic implications as both tumors responded to single-agent treatment with the tyrosine kinase inhibitor crizotinib.

Operational Innovation in the Provision of Pediatric Extracorporeal Membrane Oxygenation for Multisystem Inflammatory Syndrome in Children.

Treatment of multisystem inflammatory syndrome in children (MIS-C) can require significant critical care resources. Our aim is to alert mixed pediatric and adult hospitals worldwide of the possibility that pediatric and adult patients may simultaneously require cannulation to extracorporeal membrane oxygenation (ECMO) for MIS-C and severe COVID-19. We conducted a retrospective review of operations required to treat cardiogenic shock in 3 pediatric patients with a diagnosis of MIS-C admitted to a single medium-sized pediatric referral center located within a large academic medical center over a 14-day period. At this time, a large number of adult patients required ECMO for severe COVID-19 at our institution. Of the 11 pediatric patients who presented with MIS-C during the first surge of 2020, 2 patients required cannulation to venoarterial extracorporeal membrane oxygenation (VA-ECMO), and a third patient developed a life-threatening arrhythmia requiring transfer to a neighboring institution for consideration of VA-ECMO when our institution's ECMO capacity had briefly been reached. Pediatric referral centers located within institutions providing ECMO to adult patients with severe COVID-19 may benefit from frequent and direct communication with their adult and regional colleagues to devise a collaborative plan for safe and timely provision of ECMO to patients with MIS-C as the ongoing pandemic continues to consume this limited, lifesaving resource.

Point-of-Care Ultrasound for Central Venous Assessment in the Emergency Department: A Prospective Study Comparing the Femoral and Internal Jugular Veins.

OBJECTIVES: The objective of this study was to estimate the width, height, and depth of the femoral vein (FV) and internal jugular vein (IJV), both sites of potential central line placement in children, using point-of-care ultrasound. METHODS: This was a prospective observational study. Point-of-care ultrasound was used to measure the width, height, and depth of the right FV and IJV in 100 children. The primary outcome was a comparison of the widths of the FV and the IJV in the same child. Our primary hypothesis was that the IJV would be wider than the FV. Secondary outcome measures included comparison of the heights and depths the FV and IJV and description of vessel overlap frequency between the 2 sites. RESULTS: A total of 106 children were enrolled, with 6 subjects excluded, and equally divided into 5 age groups (0-30 days, 1-24 months, 2-5 years, 6-11 years, and 12-17 years). The FV/IJV width ratios (95% confidence interval) by age were 0.58 (0.49-0.68), 0.53 (0.43-0.66), 0.57 (0.49-0.67), 0.68 (0.55-0.85), and 0.73 (0.62-0.85), all P < 0.002. The FV/IJV height ratios were <1 in all age groups, with P < 0.003 in the 4 youngest age groups. The FV/IJV depth ratios were >1 in 6 to 11 years (P = 0.018) and 12 to 17 years (P < 0.001). CONCLUSIONS: The IJV was significantly wider and taller than the FV in the same child in all age groups. The FV was significantly deeper than the IJV in children 6 years and older. This supports the use of the IJV as a potential site when placing ultrasound-guided central lines in children.

Ventricular tachycardia after naloxone administration in an adolescent.

Naloxone is a medication with a largely benign safety profile that is frequently administered in the emergency department to patients presenting with altered mental status. Ventricular tachycardia has been reported after naloxone administration in adult patients with prior use of opiate or sympathomimetic medications. However, no such reports exist in the pediatric population or in patients who have no known history of opiate or sympathomimetic medication use. We describe a case of ventricular tachycardia after naloxone administration in a 17-year-old male with no known prior use of opiate or sympathomimetic agents who presented to the emergency department with altered mental status of unknown etiology. Emergency physicians may wish to prepare for prompt treatment of ventricular arrythmias when administering naloxone to pediatric patients presenting with altered mental status.

Distinguishing Features of Patients Evaluated for Multisystem Inflammatory Syndrome in Children.

OBJECTIVES: Given the significant overlap of multisystem inflammatory syndrome in children (MIS-C) with other common childhood illnesses presenting to the emergency department, extensive workup of this syndrome has become necessary. Nevertheless, little has been published on the factors differentiating MIS-C from other conditions in the acute care setting. We investigated differences in presentation and laboratory studies between suspected versus confirmed MIS-C patients. METHODS: This was a retrospective cohort study on patients 21 years or younger undergoing investigation for possible MIS-C at a single institution between April 21 and July 1, 2020. The primary outcome was diagnosis of MIS-C or an alternative final diagnosis. Clinical features and laboratory findings from initial presentation were collected and analyzed. RESULTS: A total of 106 patients (median, 4 years; 55.7% male) were included, of whom 17 (16%) of 106 met the criteria for MIS-C. Multisystem inflammatory syndrome in children patients were significantly more likely to report a coronavirus disease 2019 exposure (odds ratio (OR), 13.17 [3.87-44.9]), have gastrointestinal symptoms (OR, 3.81 [1.02-14.19]), and have a significantly higher odds of having abnormal laboratory values including high-sensitivity troponin T (OR, 13 [4.0-42.2]), N-terminal B-type natriuretic peptide (OR, 8.4 [2.3-30.1]), D-dimer (OR, 13 [1.6-103]), and ferritin (OR, 7.8 [2.2-27.2]). There were also differences between groups in inflammatory markers: C-reactive protein (median, 134.45 mg/L vs 12.6 mg/L; P < 0.05) and procalcitonin (1.71 ng/mL vs 0.14 ng/mL; P < 0.001). CONCLUSIONS: Higher elevations in key laboratory studies may help to distinguish between MIS-C patients and non-MIS-C patients presenting to the emergency department.

Pseudohyperkalemia and Pseudohyponatremia in Two Children with T-Cell Acute Lymphoblastic Leukemia.

Pseudohyperkalemia and pseudohyponatremia are phenomena in which hematologic disorders with high cell counts result in factitious electrolyte measurements that can result in inappropriate treatment. We describe 2 children with leukemia presenting with both disturbances to highlight the importance of correlating electrolyte results from plasma with those from whole blood before intervening.

Adult COVID-19 Patients Cared for in a Pediatric ICU Embedded in a Regional Biothreat Center: Disease Severity and Outcomes.

The objective of this study was to describe the clinical characteristics and outcomes of adult coronavirus disease 2019 (COVID-19) patients admitted to a pediatric intensive care unit (PICU), with assessment of respiratory clinical severity and outcomes when cared for by pediatric intensivists utilizing specific care processes. We conducted a retrospective cohort study of adult patients admitted to the 14-bed PICU of a quaternary referral center during the COVID-19 surge in Boston between April and June 2020. A total of 37 adults were admitted: 28 tested COVID-19 positive and 9 tested COVID-19 negative. Of the COVID-19-positive patients, 21 (75%), were male and 12 (60.7%) identified as Hispanic/Latino. Comorbidities in the patients included diabetes mellitus (39.3%), hyperlipidemia (39.3%), and hypertension (32.1%). Twenty-four (85.7%) required mechanical ventilation, in whom the lowest median ratio of arterial oxygen partial pressure to fractional inspired pressure was 161.5 (141.0 to 184.5), the median peak positive end-expiratory pressure (PEEP) was 14 (12.0 to 15.8) cmH2O and 15 (62.5%) underwent an optimal PEEP maneuver. Twelve (50%) patients were proned for a median of 3.0 (3.0 to 4.8) days. Of the 15 patients who were extubated, 3 (20%) required reintubation. Tracheostomy was performed in 10 patients: 3 after extubation failure and 7 for prolonged mechanical ventilation and weakness. Renal replacement therapy was required by 4 (14.3%) patients. There were 2 (7.1%) mortalities. We report detailed clinical outcomes of adult patients when cared for by intact pediatric critical care teams during the COVID-19 pandemic. Good clinical outcomes, when supported by adult critical care colleagues and dedicated operational processes are possible.

Cell-specific activation of RIPK1 and MLKL after intracerebral hemorrhage in mice.

Receptor-interacting protein kinase-1 (RIPK1) is a master regulator of cell death and inflammation, and mediates programmed necrosis (necroptosis) via mixed-lineage kinase like (MLKL) protein. Prior studies in experimental intracerebral hemorrhage (ICH) implicated RIPK1 in the pathogenesis of neuronal death and cognitive outcome, but the relevant cell types involved and potential role of necroptosis remain unexplored. In mice subjected to autologous blood ICH, early RIPK1 activation was observed in neurons, endothelium and pericytes, but not in astrocytes. MLKL activation was detected in astrocytes and neurons but not endothelium or pericytes. Compared with WT controls, RIPK1 kinase-dead (RIPK1D138N/D138N) mice had reduced brain edema (24 h) and blood-brain barrier (BBB) permeability (24 h, 30 d), and improved postinjury rotarod performance. Mice deficient in MLKL (Mlkl-/-) had reduced neuronal death (24 h) and BBB permeability at 24 h but not 30d, and improved post-injury rotarod performance vs. WT. The data support a central role for RIPK1 in the pathogenesis of ICH, including cell death, edema, BBB permeability, and motor deficits. These effects may be mediated in part through the activation of MLKL-dependent necroptosis in neurons. The data support development of RIPK1 kinase inhibitors as therapeutic agents for human ICH.

Measured CPAP in a Noninvasive Pediatric Airway and Lung Model.

BACKGROUND: Bronchiolitis is the most common cause of admission in children < 2 y of age in the United States. The standard of care involves supportive measures, including noninvasive interventions such as CPAP. CPAP is traditionally delivered through a full face mask; however, pediatric ICUs have been exploring the use of the RAM cannula by Neotech as a mode of CPAP delivery. The level of CPAP delivered via the RAM cannula is uncertain. We performed an in vitro study to determine the level of CPAP delivered via the RAM cannula utilizing a pediatric lung model. METHODS: Models of 7 sizes of pediatric upper airways, produced with a 3-dimensional printer, were connected to a breathing simulator. We applied each size of RAM cannula to weight-appropriate airway and lung compliance parameters, delivering pressures of 5, 7, and 10 cm H2O using a ventilator in the CPAP mode. Leaks of 0%, 20%, 40%, and 60% were generated to emulate a complete seal, a poor fit, and open-mouth breathing. The outcome measure was the difference in CPAP, referred to as "%leak effect," measured by the lung simulator relative to the CPAP set on the ventilator. RESULTS: We found that set CPAP of 5-10 cm H2O generated measured CPAP ranging from 2.6 to 9.7 cm H2O. For the set CPAP levels of 5, 7, and 10 cm H2O, the mean %leak effect values of measured CPAP from the set CPAP were -25%, -26%, and -25.7%, respectively. For each specific cannula-airway combination, increasing the set pressure and decreasing the air leak resulted in higher levels of CPAP delivered. CONCLUSIONS: The RAM cannula delivered varying amounts of CPAP, with a percent loss of approximately -25% depending on the level of leak in the system. With minimal leak, it is conceivable that the RAM cannula can be used to deliver clinically meaningful CPAP.

Respiratory Failure Leading to Intubation in the Setting of Flibanserin Ingestion in a Toddler.

The Psychiatric Consultation Service at Massachusetts General Hospital sees medical and surgical inpatients with comorbid psychiatric symptoms and conditions. During their twice-weekly rounds, Dr Stern and other members of the Consultation Service discuss diagnosis and management of hospitalized patients with complex medical or surgical problems who also demonstrate psychiatric symptoms or conditions. These discussions have given rise to rounds reports that will prove useful for clinicians practicing at the interface of medicine and psychiatry.