Adrenal insufficiency in pediatric kidney transplantation recipients.

BACKGROUND: Immunosuppression of pediatric kidney transplant (PKT) recipients often includes corticosteroids. Prolonged corticosteroid exposure has been associated with secondary adrenal insufficiency (AI); however, little is known about its impact on PKT recipients. METHODS: This was a retrospective cohort review of PKT recipients to evaluate AI prevalence, risk factors, and adverse effects. AI risk was assessed using morning cortisol (MC) and diagnosis confirmed by an ACTH stimulation test. Potential risk factors and adverse effects were tested for associations with MC levels and AI diagnosis. RESULTS: Fifty-one patients (60.8% male, age 7.4 (IQR 3.8, 13.1) years; 1 patient counted twice for repeat transplant) were included. Patients at risk for AI (MC < 240 nmol/L) underwent definitive ACTH stimulation testing, confirming AI in 13/51 (25.5%) patients. Identified risk factors for AI included current prednisone dosage (p = .001), 6-month prednisone exposure (p = .02), daily prednisone administration (p = .002), and rejection episodes since transplant (p = .001). MC level (2.5 years (IQR 1.1, 5.1) post-transplant) was associated with current prednisone dosage (p < .001), 6-month prednisone exposure (p = .001), daily prednisone administration (p = .006), rejection episodes since transplant (p = .003), greater number of medications (ß = -16.3, p < .001), 6-month hospitalization days (ß = -3.3, p = .013), creatinine variability (ß = -2.4, p = .025), and occurrence of acute kidney injury (ß = -70.6, p = .01). CONCLUSION: Greater corticosteroid exposure was associated with a lower MC level and confirmatory diagnosis of AI noted with an ACTH stimulation test. Adverse clinical findings with AI included greater medical complexity and kidney function lability. These data support systematic clinical surveillance for AI in PKT recipients treated with corticosteroids.

A Pediatric Case of Reninoma Presenting with Paraneoplastic SIADH.

INTRODUCTION: A reninoma (juxtaglomerular cell tumour) is a rare cause of secondary hypertension that can present with headaches alongside the triad of severe hypertension, hypokalemia, and metabolic alkalosis. CASE PRESENTATION: We describe a case of a 15-year-old previously healthy girl who presented with headaches and hypertensive urgency who had severe hypokalemia, moderate hyponatremia and elevated aldosterone and renin levels. Abdominal ultrasound and MRI with contrast revealed a unilateral mass localized to the right kidney. Despite treatment of her hypertension, she had persistent hyponatremia with clinical euvolemia which was consistent with the paraneoplastic syndrome of inappropriate antidiuretic hormone secretion (SIADH). She underwent radical nephrectomy which normalized her blood pressure and aldosterone and renin values. The pathology findings were consistent with a reninoma with a mitotic rate of 1-2 mitoses per 10 high power fields. DISCUSSION/CONCLUSION: Hypertension in the pediatric age group requires work-up to rule out secondary causes. The classic triad of hypertension, hypokalemia, and metabolic alkalosis warrants assessment for aldosterone-mediated hypertension which can be a result of a renin-producing tumour. Curative approach requires surgical resection of the tumour. Reninomas may rarely manifest with a paraneoplastic phenomenon including SIADH, as seen in our case. Although reninomas are benign tumours, there are also a few reports of malignant transformation and metastases. Features uncommon in reninomas such as mitotic activity warrant long-term surveillance.

Cardiac Magnetic Resonance Findings of Coronavirus Disease 2019 (COVID-19) Vaccine-Associated Myopericarditis at Intermediate Follow-Up: A Comparison with Classic Myocarditis.

OBJECTIVE: To report intermediate cardiac magnetic resonance (CMR) findings of coronavirus disease 2019 (COVID-19) vaccine-associated myopericarditis (C-VAM) and compare with classic myocarditis. STUDY DESIGN: Retrospective cohort study including children diagnosed with C-VAM from May 2021 through December 2021 with early and intermediate CMR. Patients with classic myocarditis from January 2015 through December 2021 and intermediate CMR were included for comparison. RESULTS: There were 8 patients with C-VAM and 20 with classic myocarditis. Among those with C-VAM, CMR performed at a median 3 days (IQR 3, 7) revealed 2 of 8 patients with left ventricular ejection fraction <55%, 7 of 7 patients receiving contrast with late gadolinium enhancement (LGE), and 5 of 8 patients with elevated native T1 values. Borderline T2 values suggestive of myocardial edema were present in 6 of 8 patients. Follow-up CMRs performed at a median 107 days (IQR 97, 177) showed normal ventricular systolic function, T1, and T2 values; 3 of 7 patients had LGE. At intermediate follow-up, patients with C-VAM had fewer myocardial segments with LGE than patients with classic myocarditis (4/119 vs 42/340, P = .004). Patients with C-VAM also had a lower frequency of LGE (42.9 vs 75.0%) and lower percentage of left ventricular ejection fraction <55% compared with classic myocarditis (0.0 vs 30.0%), although these differences were not statistically significant. Five patients with classic myocarditis did not receive an early CMR, leading to some selection bias in study design. CONCLUSIONS: Patients with C-VAM had no evidence of active inflammation or ventricular dysfunction on intermediate CMR, although a minority had persistent LGE. Intermediate findings in C-VAM revealed less LGE burden compared with classic myocarditis.

Neurodevelopmental Outcomes in Children with Congenital Heart Disease: Ten Years After the American Heart Association Statement.

Even before birth, children with congenital heart disease (CHD) are at risk for neurodevelopmental concerns, with additional insults occurring as part of their treatment course and from subsequent exposures to socioeconomic stressors. With multiple affected neurodevelopmental domains, individuals with CHD face lifelong cognitive, academic, psychological, and quality-of-life difficulties. Early and repeated neurodevelopmental evaluation is key to receiving appropriate services. However, obstacles at the level of the environment, provider, patient, and family can make the completion of these evaluations difficult. Future neurodevelopmental endeavors should aim to evaluate CHD-specific programs, their effectiveness, and barriers to access.

Adverse Cutaneous Drug Reactions at a Rural-Based Tertiary Health-Care Center in Gujarat: An Eleven Year Study.

Background: An adverse cutaneous drug reaction (ACDR) is an undesirable change in structure and function of the skin, its appendages, or mucous membranes due to drugs. Aims and Objectives: To study the demographic details, clinical patterns, mucocutaneous involvement, causality, and the offending drugs causing ACDR. Materials and Methods: In this observational study, we have seen 2,96,544 patients in the skin department at a rural-based tertiary health-care hospital, out of which 728 cases were diagnosed to have ACDR from a time span of April 2010 to March 2021. The causality assessment system WHO-UMC (World Health Organization Collaborating Centre for International Drug Monitoring, the Uppsala Monitoring Centre), the Naranjo probability scale, and Hartwigs score were calculated for patients. Results: Out of 728 cases, males were 371 (50.96%); most common age group was 21-30 years (25.13%). The most common presenting complaint was erythematous rash (21.29%). Antimicrobials (n = 345, 47.39%) were the most common drug group. Most common mucosa involved was oral mucosa and most common pattern of reaction seen was maculopapular rash (25%) among these patients. In the causality assessment using WHO guidelines, there were 66 (9.1%) certain, 224 (30.83%) probable, and 436 (60%) possible cases. Naranjo score showed 73 (10%) definite cases, 255 (35%) probable cases, and 400 (55%) possible cases, while Hartwigs score showed level 2 in 122 (16.7%) cases and level 3 in 412 (56.7%) cases. Conclusion: Wide spectrum of drug reactions were observed in this study. Antimicrobials were the most common causative agents of ACDR.

Exercise testing in patients with multisystem inflammatory syndrome in children-related myocarditis versus idiopathic or viral myocarditis.

BACKGROUND: While most children with multisystem inflammatory syndrome in children have rapid recovery of cardiac dysfunction, little is known about the long-term outcomes regarding exercise capacity. We aimed to compare the exercise capacity among patients with multisystem inflammatory syndrome in children versus viral/idiopathic myocarditis at 3-6 months after initial diagnosis. METHODS: We performed a retrospective cohort study among patients with multisystem inflammatory syndrome in children in June 2020 to May 2021 and patients with viral/idiopathic myocarditis in August 2014 to January 2020. Data from cardiopulmonary exercise test as well as echocardiographic and laboratory data were obtained. Inclusion criteria included diagnosis of multisystem inflammatory syndrome in children or viral/idiopathic myocarditis, exercise test performed within 3-6 months of hospital discharge, and maximal effort on cardiopulmonary exercise test as determined by respiratory exchange ratio >1.10. RESULTS: Thirty-one patients with multisystem inflammatory syndrome in children and 25 with viral/idiopathic myocarditis were included. The mean percent predicted peak VO2 was 90.84% for multisystem inflammatory syndrome in children patients and 91.08% for those with viral/idiopathic myocarditis (p-value 0.955). There were no statistically significant differences between the groups with regard to percent predicted maximal heart rate, metabolic equivalents, percent predicted peak VO2, percent predicted anerobic threshold, or percent predicted O2 pulse. There was a statistically significant correlation between lowest ejection fraction during hospitalisation and peak VO2 among viral/idiopathic myocarditis patients (r: 0.62, p-value 0.01) but not multisystem inflammatory syndrome in children patients (r: 0.1, p-value 0.6). CONCLUSIONS: Patients with multisystem inflammatory syndrome in children and viral myocarditis appear to, on average, have normal exercise capacity around 3-6 months following hospital discharge. For patients with viral/idiopathic myocarditis, those with worse ejection fraction during hospitalisation had lower peak VO2 on cardiopulmonary exercise test.

Diagnosis of adrenal insufficiency in children: a survey among pediatric endocrinologists in North America.

OBJECTIVES: Adrenal insufficiency (AI) is a life-threatening condition where an accurate diagnosis is critical. While the ACTH stimulation test is the diagnostic test of choice, there remains uncertainty around its protocols and interpretation of results. In this context, the objective of this study was to understand practices of North American pediatric endocrinology providers on the diagnosis of AI in children. METHODS: An anonymous electronic survey was sent to members of the Pediatric Endocrine Society. RESULTS: A total of 221 participants were included. The majority practiced in academic centers (78%). All respondents ordered ACTH stimulation tests. While 85% used high-dose ACTH stimulation tests (HDST) to diagnose primary AI, there was less consistency in the choice of tests (HDST vs. low-dose ACTH stimulation test; LDST) when diagnosing secondary AI. When interpreting results, 95% used peak cortisol levels, 70% considered the clinical picture, and 49% used relative increase in cortisol levels. Median (IQR) cortisol cutoff level after ACTH stimulation test that was considered sufficient was 18 (15.5-18) µg/L [496 (428-496) nmol/L]; 17% used different cutoffs for LDST, and 18% used different cutoffs for newborns. Finally, 47% were unaware of the assay that was used in their institution for cortisol measurements. CONCLUSIONS: Pediatric endocrinology providers use ACTH stimulation tests variably, including in the choice between HDST vs. LDST, test protocols, and interpretation of results.

Influence of Critical Parameters on Cytotoxicity Induced by Mesoporous Silica Nanoparticles.

Mesoporous Silica Nanoparticles (MSNs) have received increasing attention in biomedical applications due to their tuneable pore size, surface area, size, surface chemistry, and thermal stability. The biocompatibility of MSNs, although generally believed to be satisfactory, is unclear. Physicochemical properties of MSNs, such as diameter size, morphology, and surface charge, control their biological interactions and toxicity. Experimental conditions also play an essential role in influencing toxicological results. Therefore, the present study includes studies from the last five years to statistically analyse the effect of various physicochemical features on MSN-induced in-vitro cytotoxicity profiles. Due to non-normally distributed data and the presence of outliers, a Kruskal-Wallis H test was conducted on different physicochemical characteristics, including diameter sizes, zeta-potential measurements, and functionalisation of MSNs, based on the viability results, and statistical differences were obtained. Subsequently, pairwise comparisons were performed using Dunn's procedure with a Bonferroni correction for multiple comparisons. Other experimental parameters, such as type of cell line used, cell viability measurement assay, and incubation time, were also explored and analysed for statistically significant results.

Implementation of Appropriate Use Criteria for Transthoracic Echocardiography in Follow-Up Care of Pediatric Patients with Congenital Heart Disease.

BACKGROUND: Indications for transthoracic echocardiography (TTE) from the 2020 Appropriate Use Criteria (AUC) for congenital heart disease (CHD) were incorporated into the institutional electronic ordering system as a clinical decision support tool. The purpose of this study was to evaluate the utilization of TTE and factors affecting the appropriateness of orders for TTE during follow-up care of patients with CHD. METHODS: All transthoracic echocardiographic studies performed during follow-up clinic visits from May 1, 2020, to November 30, 2020, were included. Indications for TTE were rated appropriate, may be appropriate, or rarely appropriate on the basis of the AUC and unclassifiable if the indication was not in the document but related to included lesions. CHD was graded as simple, moderate, or complex on the basis of the Bethesda classification. Logistic regression was used to determine the association of ratings with patient age, insurance status, CHD complexity, and clinician experience and specialty. RESULTS: Of the 5,158 studies, 3,979 (77.2%) were for CHD included in the AUC document, 322 (8%) were unclassifiable, 37 (0.7%) were for CHD not in the document, and 1,142 (22.1%) were for non-CHD indications. Of the 3,657 transthoracic echocardiographic examinations to which AUC ratings could be applied, 95.6% were rated appropriate, 2.4% may be appropriate, and 2.0% rarely appropriate. The highest utilization of TTE was for follow-up of ventricular septal defects, left ventricular outflow tract obstruction, and single ventricles; 46% for unrepaired CHD; 78% for routine surveillance; and the remaining for changes in clinical status. On multivariable analysis, the only significant factor associated with may be appropriate and rarely appropriate ratings was simple CHD (odds ratio, 11.58; 95% CI, 5.36 - 24.98; P < .001). CONCLUSIONS: Three quarters of transthoracic echocardiographic studies ordered during follow-up care in pediatric cardiology clinics are for indications related to CHD. Most examinations for follow-up of CHD were for routine surveillance and indications rated appropriate. Orders for TTE for may be appropriate and rarely appropriate ratings were associated with simple CHD. Although the 2020 AUC document successfully stratifies the majority of indications related to CHD, future documents should consider the unclassifiable CHD indications and the non-CHD indications.

Comparison of Multisystem Inflammatory Syndrome in Children-Related Myocarditis, Classic Viral Myocarditis, and COVID-19 Vaccine-Related Myocarditis in Children.

Background Although rare, classic viral myocarditis in the pediatric population is a disease that carries significant morbidity and mortality. Since 2020, myocarditis has been a common component of multisystem inflammatory syndrome in children (MIS-C) following SARS-CoV-2 infection. In 2021, myocarditis related to mRNA COVID-19 vaccines was recognized as a rare adverse event. This study aims to compare classic, MIS-C, and COVID-19 vaccine-related myocarditis with regard to clinical presentation, course, and outcomes. Methods and Results In this retrospective cohort study, we compared patients aged <21 years hospitalized at our institution with classic viral myocarditis from 2015 to 2019, MIS-C myocarditis from March 2020 to February 2021, and vaccine-related myocarditis from May 2021 to June 2021. Of 201 total participants, 43 patients had classic myocarditis, 149 had MIS-C myocarditis, and 9 had vaccine-related myocarditis. At presentation, ejection fraction was lowest for those with classic myocarditis, with ejection fraction <55% present in 58% of patients. Nearly all patients with MIS-C myocarditis (n=139, 93%) and all patients with vaccine-related myocarditis (n=9, 100%) had normal left ventricular ejection fraction at the time of discharge compared with 70% (n=30) of the classic myocarditis group (P<0.001). At 3 months after discharge, of the 21 children discharged with depressed ejection fraction, none of the 10 children with MIS-C myocarditis had residual dysfunction compared with 3 of the 11 (27%) patients in the classic myocarditis group. Conclusions Compared with classic myocarditis, those with MIS-C myocarditis had better clinical outcomes, including rapid recovery of cardiac function. Patients with vaccine-related myocarditis had prompt resolution of symptoms and improvement of cardiac function.

Update and review of contrast-associated acute kidney injury.

Contrast associated acute kidney injury (CA-AKI) is a controversial subject in the field of nephrology, cardiology, radiology and hospital medicine. Much has been written and published concerning the causes, risk factors, outcomes, and potential treatments to avoid the ultimate outcome of complete kidney failure requiring dialysis. Over the decades many proposed preventative strategies and treatments have failed to produce a reliable outcome. Additionally, there is now a growing discussion of the severity and sincerity of CA-AKI being a major entity to worry about for patients. We discuss the present state of CA-AKI and highlight potential risk factors and possible therapeutic interventions to minimize any impact a contrast procedure may have on a patient in order to maximize the medical care.

Prioritization in visual attention does not work the way you think it does.

A common assumption in attention theories is that attention prioritizes search items based on their similarity to the target. Here, we tested this assumption and found it wanting. Observers searched through displays containing candidates (distractors that cannot be confidently differentiated from the target by peripheral vision) and lures (distractors that can be). Candidates had high or low similarity to the target. Search displays were either candidate-homogeneous (all items of same similarity) or candidate-heterogeneous (equal numbers of each similarity). Response times to candidate-heterogeneous displays were equivalent to the average of high- and low-similarity displays, suggesting that attention was allocated randomly, rather than toward the high-similarity candidates first. Lures added a response time cost that was independent of the candidates, suggesting they were rejected prior to candidates being inspected. These results suggest a "reverse" prioritization process: Distributed attention discards least target-similar items first, while focused spatial attention is randomly directed to target-similar items. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Treadmill exercise testing improves diagnostic accuracy in children with concealed congenital long QT syndrome.

BACKGROUND: Resting electrocardiogram (ECG) identification of long QT syndrome (LQTS) has limitations. Uncertainty exists on how to classify patients with borderline prolonged QT intervals. We tested if exercise testing could help serve to guide which children with borderline prolonged QT intervals may be gene positive for LQTS. METHODS: Pediatric patients (n = 139) were divided into three groups: Controls (n = 76), gene positive LQTS with borderline QTc (n = 21), and gene negative patients with borderline QTc (n = 42). Borderline QTc was defined between 440-470 (male) and 440-480 (female) ms. ECGs were recorded supine, sitting, and standing. Patients then underwent treadmill stress testing with Bruce protocol followed by a 9-minute recovery phase. RESULTS: Supine resting QTc, age, and Schwartz score for the three groups were: (a) gene positive: 446 ± 23 ms, 12.4 ± 3.4 years old, 3.2 ± 1.8; (b) gene negative: 445 ± 20 ms, 12.1 ± 2 years old, 2.0 ± 1.2; and (c) control: 400 ± 24 ms, 15.0 ± 3 years old. The three groups could be differentiated by their QTc response at two time points: standing and recovery phase at 6 minutes. Standing QTc ≥460 ms differentiated borderline prolonged QTc patients (gene positive and gene negative) from controls. Late recovery QTc ≥480 ms distinguished gene positive from gene negative patients. CONCLUSION: Exercise stress testing can be useful to identify children who are gene positive borderline LQTS from a normal population and gene negative borderline QTc children, allowing for selective gene testing in a higher risk group of patients with borderline QTc intervals and intermediate Schwartz scores.