Identifying Gender and Racial Bias in Pediatric Fellowship Letters of Recommendation: Do Word Choices Influence Interview Decisions?

OBJECTIVES: To describe linguistic differences in letters of recommendation (LORs) for pediatric fellowship candidates based on applicant and letter writer demographics and to examine if these differences influenced the decision to interview a candidate for a fellowship position. STUDY DESIGN: LORs for applicants to 8 pediatric subspecialty fellowships at a single academic center from the 2020 Match were analyzed in this cross-sectional study. Frequency of validated agentic and communal terms in each letter were determined by a language processing web application. Bias was determined as having a >5% surplus of agentic or communal terms. RESULTS: We analyzed 1521 LORs from 409 applicants: 69% were women, 28% were under-represented minorities in medicine (URM), and 50% were invited to interview. Overall, 66% of LORs were agentic biased, 16% communal biased, and 19% neutral. There was no difference in bias in LORs by an applicant's gender (woman 67% agentic vs man 62% agentic; P = .058), race, or ethnicity (non-URM 65% agentic vs URM 67% agentic; P = .660). Despite a lower frequency of agentic terms in LORs for applicants invited for interviews, when accounting for other components of an application and applicant demographics, no significant association was made between language bias in LORs and fellowship interview status. CONCLUSIONS: The frequency of agentic and communal terms in LORs for pediatric subspecialty fellowship candidates were not found to influence the decision to invite a candidate to interview. However, raising awareness of potential areas of bias within the pediatric fellowship selection process might lead to a more equitable and holistic approach to application review.

Unique clinical challenges for the teenager with congenital heart disease.

PURPOSE OF REVIEW: On top of existing rites of passage, adolescents with congenital heart disease (CHD) face additional challenges as related to their underlying medical condition. These include compliance with medications and appointments, establishing heart-healthy behaviors, navigating potential at-risk situations, and transition to adult-oriented care. RECENT FINDINGS: Teenagers with CHD should focus on the importance of exercise as this seems to have important long-term benefits and may help improve weight management. Mental health concerns are a major issue for teens with CHD and awareness and appropriate screening are critical. Discussion regarding sexual health, contraception, pregnancy, and CHD risk in offspring occur rarely in clinical practice, and their absence sets up the CHD adolescent for potential complications. Establishing patterns of trust and communication between physicians and teenage CHD patients are critical to enable the appropriate transition of care to adult congenital care, yet gaps in transition remain common. SUMMARY: The outpatient cardiologist has a critical role to help the teenager with CHD navigate difficult terrain. Returning to the roots of careful history taking, motivational interviewing, and open-ended questions may be of great benefit in warding off complications and helping steer the adolescent with CHD towards a life as a successful adult living with CHD.

Frequency of QTc Interval Prolongation in Children and Adults with Williams Syndrome.

QTc prolongation (≥ 460 ms), according to Bazett formula (QTcB), has been identified to be increased in Williams syndrome (WS) and suggested as a potential cause of increased risk of sudden cardiac death. The Bazett formula tends to overestimate QTc in higher heart rates. We performed a retrospective chart review of WS patients with ≥ 1 electrocardiogram (EKG) with sinus rhythm, no evidence of bundle branch blocks, and measurable intervals. A total of 280 EKGs from 147 patients with WS were analyzed and 123 EKGs from 123 controls. The QTc was calculated using Bazett formula. The average QTcB for individuals with WS and controls was 444 ± 24 ms and 417 ± 26 ms, respectively (p < 0.001). In our WS cohort 34.4% had at least 1 EKG with a QTcB ≥ 460 ms. The mean heart rate (HR) from patients with WS was significantly higher than controls (96 bpm vs 76 bpm, p < 0.001). Linear regression showed that HR contributed 27% to QTcB prolongation in the patients with WS. Patients with WS have a mean QTcB in the normal range but higher than controls, and a higher than expected frequency of QTc ≥ 460 ms compared to the general population. HR is also higher in WS and contributes modestly to the WS QTcB prolongation. Future studies are needed to assess if these findings contribute risk to sudden cardiac death but in the interim we recommend routine EKG testing, especially when starting QTc prolonging medications.

Noonan syndrome and pregnancy outcomes.

BACKGROUND: Noonan syndrome is a genetic disorder with high prevalence of congenital heart defects, such as pulmonary stenosis, atrial septal defect and hypertrophic cardiomyopathy. Scarce data exists regarding the safety of pregnancy in patients with Noonan syndrome, particularly in the context of maternal cardiac disease. STUDY DESIGN: We performed a retrospective chart review of patients at Yale-New Haven Hospital from 2012 to 2020 with diagnoses of Noonan syndrome and pregnancy. We analysed medical records for pregnancy details and cardiac health, including echocardiograms to quantify maternal cardiac dysfunction through measurements of pulmonary valve peak gradient, structural heart defects and interventricular septal thickness. RESULTS: We identified five women with Noonan syndrome (10 pregnancies). Three of five patients had pulmonary valve stenosis at the time of pregnancy, two of which had undergone cardiac procedures. 50% of pregnancies (5/10) resulted in pre-term birth. 80% (8/10) of all deliveries were converted to caesarean section after a trial of labour. One pregnancy resulted in intra-uterine fetal demise while nine pregnancies resulted in the birth of a living infant. 60% (6/10) of livebirths required care in the neonatal intensive care unit. One infant passed away at 5 weeks of age. CONCLUSIONS: The majority of mothers had pre-existing, though mild, heart disease. We found high rates of prematurity, conversion to caesarean section, and elevated level of care. No maternal complications resulted in long-term morbidity. Our study suggests that women with Noonan syndrome and low-risk cardiac lesions can become pregnant and deliver a healthy infant with counselling and risk evaluation.

Hair and skin predict cardiomyopathies: Carvajal and erythrokeratodermia cardiomyopathy syndromes.

Carvajal and erythrokeratodermia cardiomyopathy syndromes (EKC) are rare, inherited cardiocutaneous disorders with potentially fatal consequences in young children. Some patients display features of congestive heart failure and rapidly deteriorate; others exhibit no evident warning signs until sudden death reveals underlying heart disease. We present two patients to illustrate the characteristic hair, skin, teeth, and nail abnormalities, which-especially when distinct from that of other family members-should prompt cardiac evaluation and genetic analysis. In this article, we discuss established treatments as well as a promising, novel therapeutic that has led to nearly complete resolution of the cutaneous and cardiac pathology in EKC syndrome.

T-Cell Receptor Excision Circles in Newborns with Congenital Heart Disease.

OBJECTIVES: To determine if children with congenital heart disease (CHD) have lower newborn T-cell receptor excision circles (TREC) levels than the general population and to evaluate if low TREC levels in newborns with CHD are associated with clinical complications such as hospitalization for infection. STUDY DESIGN: The Connecticut Newborn Screening Program reported TREC levels for newborns with CHD delivered between October 2011 and September 2016 at 2 major Connecticut children's hospitals. TREC levels for children with CHD were compared with the general population. TREC levels and outcome measures, including hospitalization for infection, were compared. RESULTS: We enrolled 575 participants with CHD in the study. The median TREC level for newborns with CHD was lower than the general population (180.1 copies/µL vs 312.5 copies/µL; P < .01). patients with CHD requiring hospitalization for infection had lower median TREC levels than their counterparts (143.0 copies/µL vs 186.7 copies/µL; P < .01). The combination of prematurity and low TREC level had a strong relationship to hospitalization for infection (area under the receiver operative characteristic curve of 0.89). There was no association between TREC level and CHD severity. CONCLUSIONS: Newborns with CHD demonstrated lower TREC levels than the general population. Low TREC levels were associated with hospitalization for infection in preterm children with CHD. Study limitations include that this was a retrospective chart review. These findings may help to identify newborns with CHD at highest risk for infection, allowing for potential opportunities for intervention.

Ventricular arrhythmias immediately following transcatheter pulmonary valve implantation: A cause for concern?

BACKGROUND: Transcatheter pulmonary valve implantation (TPVI) has revolutionized the care of patients with congenital disorders of the right ventricular outflow tract (RVOT) and is increasingly being used in patients with native outflow tracts. This is the first study to specifically report the occurrence of ventricular arrhythmias in the immediate post-TPVI period. METHODS AND RESULTS: Medical records of all adult and pediatric patients who underwent TPVI at our institution between May 1, 2011 and March 1, 2016, were reviewed for the presence of clinically significant ventricular arrhythmias occurring within 30 days of TPVI. We defined a clinically significant arrhythmia as any ventricular arrhythmia that led to hemodynamic instability, resulted in a change of dose or addition of a new anti-arrhythmic medication, caused a delay in discharge, or was the primary reason for readmission. Seventy-five patients, with a median age of 19 years (range 4-65 years), underwent TPVI. In total, 12 (16%) patients had a clinically significant ventricular arrhythmia within 30 days following TPVI. Patients with native outflow tracts were at higher risk of post-TPVI arrhythmias than non-native outflow tract (29% vs. 9%, P = 0.02, adjusted OR 4.8, 95%CI 1.2-20.2). There were no cases of hemodynamic compromise or sudden cardiac death. The arrhythmias were well controlled with beta-blocker therapy. CONCLUSION: In this single center study, ventricular arrhythmias were common following TPVI, particularly in native outflow tract patients. However, the arrhythmias were generally benign and responded well to medical therapy when indicated. Long term therapy was often not needed.

Hypercalcemia in Patients with Williams-Beuren Syndrome.

OBJECTIVE: To evaluate the timing, trajectory, and implications of hypercalcemia in Williams-Beuren syndrome (WBS) through a multicenter retrospective study. STUDY DESIGN: Data on plasma calcium levels from 232 subjects with WBS aged 0-67.1 years were compared with that in controls and also with available normative data. Association testing was used to identify relevant comorbidities. RESULTS: On average, individuals with WBS had higher plasma calcium levels than controls, but 86.7% of values were normal. Nonpediatric laboratories overreport hypercalcemia in small children. When pediatric reference intervals were applied, the occurrence of hypercalcemia dropped by 51% in infants and by 38% in toddlers. Across all ages, 6.1% of the subjects had actionable hypercalcemia. In children, actionable hypercalcemia was seen in those aged 5-25 months. In older individuals, actionable hypercalcemia was often secondary to another disease process. Evidence of dehydration, hypercalciuria, and nephrocalcinosis were common in both groups. Future hypercalcemia could not be reliably predicted by screening calcium levels. A subgroup analysis of 91 subjects found no associations between hypercalcemia and cardiovascular disease, gastrointestinal complaints, or renal anomalies. Analyses of electrogradiography data showed an inverse correlation of calcium concentration with corrected QT interval, but no acute life-threatening events were reported. CONCLUSIONS: Actionable hypercalcemia in patients with WBS occurs infrequently. Although irritability and lethargy were commonly reported, no mortality or acute life-threatening events were associated with hypercalcemia and the only statistically associated morbidities were dehydration, hypercalciuria, and nephrocalcinosis.

Clinical Approaches to the Patient with a Failing Fontan Procedure.

The Fontan operation has been nothing short of revolutionary in its influence on the modern management of patients born with functionally univentricular hearts. The vast majority of these individuals are now surviving well into adulthood. In the 45 years since its introduction, however, there has been increasing recognition of Fontan survivors as a vulnerable population with an altered physiology that has remarkably broad, adverse impact on their long-term health. In this review, the authors discuss the varied manifestations, both cardiac and extracardiac, of the failing Fontan circulation and potential therapeutic options. In addition, a general clinical approach to the patient presenting with Fontan failure is proposed. Ultimately, the key to improving our care and understanding of the Fontan population lies in multi-institutional collaboration and partnership between subspecialty cardiologists and specialists in other organ systems.

Superior Mesenteric Arterial Flow Pattern is Associated with Major Adverse Events in Adults with Fontan Circulation.

Factors contributing to the failure of Fontan circulation in adults are poorly understood. Reduced superior mesenteric arterial (SMA) flow has been identified in pediatric Fontan patients with protein-losing enteropathy. SMA flow has not been profiled in an adult Fontan population and its association with adverse events is unknown. We aimed to examine associations between SMA flow patterns and adverse events in adult Fontan patients. We performed a retrospective review of adult Fontan patients who underwent echocardiograms between 2008 and 2014. SMA Doppler data included peak systolic and end-diastolic velocity and velocity time integral (VTI). Systolic/diastolic (S/D) ratio and resistive index were calculated. The relationship between SMA flow parameters and major adverse events (death or transplantation) was examined using proportional hazard Cox regression analyses. Kaplan-Meyer analysis was conducted to construct survival curve of patients with and without adverse events. 91 post-Fontan adult patients (76 % systemic left ventricle, 20 % atriopulmonary Fontan, mean age 27.9 years) were analyzed. Adverse events occurred in nine patients (death = 4, transplant = 5). When compared with the non-event group, the event group had increased end-diastolic velocity [hazard ratio (HR) 1.5, 95 % confidence interval (CI) 1.1-1.8; p = 0.002], increased systolic VTI (HR 1.5, 95 % CI 1.1-2.2, p = 0.02), increased diastolic VTI (HR 1.7, 95 % CI 1.2-2.4, p = 0.004), decreased S/D velocity ratio (HR 0.32, 95 % CI 0.14-0.71, p = 0.006), decreased S/D VTI ratio (HR 0.76, 95 % CI 0.61-0.97, p = 0.02), and decreased resistive index (HR 0.29, 95 % CI 0.14-0.60, p = 0.0007). Increased end-diastolic velocity and VTI in mesenteric arterial flow, with lower systolic/diastolic ratio and resistive index, were associated with death and need for heart transplant in adult Fontan patients. The mesenteric hyperemic flow was also associated with clinical signs of portal venous outflow obstruction, suggesting the presence of vasodilatory state in end-stage adult Fontan circulation.

Immunologic Aging in Adults with Congenital Heart Disease: Does Infant Sternotomy Matter?

Thymectomy is performed routinely in infants undergoing cardiothoracic surgery. Children post-sternotomy have decreased numbers of T lymphocytes, although the mechanisms involved and long-term consequences of this have not been defined. We hypothesized that lymphopenia in patients with adult congenital heart disease (ACHD) would be reflective of premature T cell maturation and exhaustion. Adults with ACHD who had sternotomy to repair congenital heart disease as infants (<1 year) and age-matched ACHD patients without prior sternotomy were studied using polychromatic flow cytometry interrogating markers of lymphocyte maturation, exhaustion and senescence. Group differences were analyzed using Mann-Whitney U and Fisher's exact tests. Eighteen ACHD patients aged 21-40 years participated: 10 cases and 8 controls. Median age at sternotomy for cases was 52 days. Cases and controls were matched for age (28.9 vs. 29.1 years; p = 0.83), gender (p = 0.15) and race (p = 0.62) and had similar case complexity. Cases had a lower mean percentage of cytotoxic CD8 lymphocytes compared to controls (26.8 vs. 33.9 %; p = 0.016), with fewer naive, undifferentiated CD8 T cells (31.0 vs. 53.6 %; p = 0.027). CD8 cells expressing PD1, a marker of immune exhaustion, trended higher in cases versus controls (25.6 vs. 19.0 %; p = 0.083). Mean percentage of CD4 cells was higher in cases versus controls (65.6 vs. 59.6 %; p = 0.027), without differences in CD4 T cell maturation subtype. In summary, ACHD patients who undergo sternotomy as infants exhibit differences in T lymphocyte composition compared to ACHD controls, suggesting accelerated immunologic exhaustion. Investigation is warranted to assess the progressive nature and clinical impact of this immune phenotypic change.

Beyond a broken heart: circulatory dysfunction in the failing Fontan.

The role of ventricular dysfunction in late morbidity and mortality of univentricular hearts has been described previously. However, a significant proportion of adult Fontan patients who die or require heart transplantation do so with preserved ventricular function. The clinical deterioration in patients who have undergone Fontan palliation requires a broader view of circulatory dysfunction, one that takes into account the complex interaction of regulatory systems affecting hepatic, renal, and pulmonary blood flow, in addition to cardiac function. This review focuses primarily on the pathophysiology of multiple organ involvement in this circulatory dysfunction, with particular focus on the consequences of hepatic dysfunction and portal hypertension. The authors discuss hepatic perfusion, both in health and disease, and review the current understanding of liver histopathology and liver disease in adult Fontan patients and similar clinicopathologic states. They compare and contrast features of postsinusoidal portal hypertension with more typical adult cirrhotic disease. Finally, they delineate the related effects of portal hypertensive physiology on the systemic and pulmonary vasculature, the kidney, and the heart itself and discuss how these changes affect the care of the adult Fontan patient.

How Good Are Cardiologists at Predicting Major Adverse Events in Fontan Patients?

Background: It is unknown how well cardiologists predict which Fontan patients are at risk for major adverse events (MAEs). Objectives: The purpose of this study was to examine the accuracy of cardiologists' ability to identify the "good Fontan" patient, free from MAE within the following year, and compare that predicted risk cohort to patients who experienced MAE. Methods: This prospective, multicenter study included patients ≥10 years with lateral tunnel or extracardiac Fontan. The cardiologist was asked the yes/no "surprise" question: would you be surprised if your patient has a MAE in the next year? After 12 months, the cardiologist was surveyed to assess MAE. Agreement between cardiologist predictions of MAE and observed MAE was determined using the simple kappa coefficient. Multivariable generalized linear mixed effects models were performed to identify factors associated with MAE. Results: Overall, 146 patients were enrolled, and 99/146 (68%) patients w`ere predicted to be a "good Fontan." After 12 months, 17 (12%) experienced a MAE. The simple kappa coefficient of cardiologists' prediction was 0.17 (95% CI: 0.02-0.32), suggesting prediction of MAE was 17% better than random chance. In the multivariable cardiologist-predicted MAE (N = 47) model, diuretic/beta-blocker use (P ≤ 0.001) and systolic dysfunction (P = 0.005) were associated with MAE. In the observed multivariable MAE (N = 17) model, prior unplanned cardiac admission (P = 0.006), diuretic/beta-blocker use (P = 0.028), and ≥moderate atrioventricular valve regurgitation (P = 0.049) were associated with MAE. Conclusions: Cardiologists are marginally able to predict which Fontan patients are at risk for MAE over a year. There was overlap between factors associated with a cardiologist's prediction of risk and observed MAE, namely the use of diuretic/beta-blocker.

"Double whammy": anomalous pulmonary and systemic venous drainage in a patient with scimitar syndrome.

Anomalously draining right pulmonary veins are expected with scimitar syndrome, but systemic venous abnormalities are rare. We present an unusual case of a female patient with scimitar and an interrupted inferior vena cava.

Words Used in Letters of Recommendation for Pediatric Residency Applicants: Demographic Differences and Impact on Interviews.

OBJECTIVE: To describe differences in agentic (achievement) and communal (relationship) terms in letters of recommendation (LORs) for pediatric residency candidates by applicant and letter writer demographics and to examine if LOR language is associated with interview status. METHODS: A random sample of applicant profiles and LORs submitted to one institution were analyzed from the 2020-21 Match. Letters of recommendation text was inputted into a customized natural language processing application which determined the frequency of agentic and communal words in each LOR. Neutral LORs were defined as having< 5% surplus of agentic or communal terms. RESULTS: We analyzed 2094 LORs from 573 applicants: 78% were women, 24% were under-represented in medicine (URiM), and 39% were invited to interview. Most letter writers were women (55%) and of senior academic rank (49%). Overall, 53% of LORs were agency biased, 25% communal biased, and 23% neutral. There was no difference in agency and communally biased LORs by an applicant's gender (men 53% agentic vs women 53% agentic, P = .424), race or ethnicity (non-URiM 53% agentic vs URiM 51% agentic, P = .631). Male letter writers used significantly more agentic terms (8.5%) compared to women (6.7% agentic) or writers of both genders (3.1% communal) (P = .008). Applicants invited to interview were more likely to have a neutral LOR; however, no significant association existed between language and interview status. CONCLUSIONS: No significant differences in language were found by applicant gender or race among pediatric residency candidates. Identifying potential biases within pediatric residency selection processes is important in creating an equitable approach to application review.

Cerebellar metastatic papillary thyroid carcinoma in a pediatric patient with complex congenital heart disease.

This case describes the first pediatric case of metastatic papillary thyroid carcinoma (PTC) to the cerebellum as the presenting sign of cancer in a child with CHARGE syndrome and complex congenital heart disease. Diagnostic radiation exposure as a strong risk factor for PTC is discussed.

Pulmonary venous obstruction in the atrial switch operation: a forgotten complication.

The reported case involved a 7-year-old girl with congenitally corrected transposition of the great arteries (ccTGA) and situs inversus who after surgical management experienced symptoms of dyspnea and left-sided obstructive heart disease. Her symptoms, chest X-ray, and cardiac catheterization demonstrated pulmonary venous obstruction, a known but rare complication associated with intra-atrial baffle obstruction. The incidence of the reported disorder, the follow-up assessment, and the current literature regarding complications of Senning/Mustard surgery are discussed in the context of patients with ccTGA.

T Cell Response to Influenza Vaccination Remains Intact in Adults with Congenital Heart Disease Who Underwent Early Thymectomy.

Introduction: T cells developed in the thymus play a key role in vaccine immunity. Thymectomy occurs during infant congenital heart surgery and results in an altered T cell distribution. We investigated if adults with congenital heart disease (ACHD) who underwent early thymectomy have a diminished response to influenza vaccination. Methods: Blood samples from ACHD with early thymectomy ≤ 1 year of age (ACHD-ET; n = 12), no thymectomy (ACHD-NT; n = 8), and healthy controls (HC; n = 14) were collected prior to and 4 weeks after influenza vaccination. Flow cytometric analysis of T cell subsets and vaccine-specific cytokine expressing CD4+ T cells as well as hemagglutination inhibition (HI) assays were completed. Results: The mean age of the cohort was 34 ± 10.6 years and similar in all groups. The mean frequencies of naïve CD4+ and CD8+ T cells were lower in ACHD-ET than in HC (32.7% vs. 46.5%, p = 0.027 and 37.2% vs. 57.4%, p = 0.032, respectively). There was a rise in the frequency of memory CD4+ and CD8+ T cells in the ACHD-ET group. The ACHD-NT had no statistical difference from either group. The frequencies of influenza-specific memory CD4+ T cells expressing IFN-γ and TNF-α were increased after vaccination across all groups (p < 0.05). Conclusions: ACHD-ET have fewer naïve T cells, suggesting immunosenescence. Despite this, they show an adequate T Cell response to vaccination in young adulthood. Our findings support routine vaccination is effective in this population, but research into older ACHD is necessary.

Unrepaired Maternal Vein of Galen Malformation in Pregnancy: A Case Report.

We present a case of a pregnant patient with an unrepaired vein of Galen malformation (VGAM) and left ventricular (LV) dilation. Patients with VGAM lesions typically present during childhood with cardiac failure or developmental delay prompting embolization. Therefore, it is highly unusual for an adult to present with an unrepaired lesion.1 It poses challenges for obstetric and anesthetic management during pregnancy and delivery to reduce the risk of heart failure, arrhythmia, and intracranial hemorrhage. Our patient safely delivered a term neonate by cesarean delivery with neuraxial analgesia at a Level IV Maternal Care Center.

Familial Recurrence Patterns in Congenitally Corrected Transposition of the Great Arteries: An International Study.

BACKGROUND: Congenitally corrected transposition of the great arteries (ccTGA) is a rare disease of unknown cause. We aimed to better understand familial recurrence patterns. METHODS: An international, multicentre, retrospective cohort study was conducted in 29 tertiary hospitals in 6 countries between 1990 and 2018, entailing investigation of 1043 unrelated ccTGA probands. RESULTS: Laterality defects and atrioventricular block at diagnosis were observed in 29.9% and 9.3%, respectively. ccTGA was associated with primary ciliary dyskinesia in 11 patients. Parental consanguinity was noted in 3.4% cases. A congenital heart defect was diagnosed in 81 relatives from 69 families, 58% of them being first-degree relatives, including 28 siblings. The most prevalent defects in relatives were dextro-transposition of the great arteries (28.4%), laterality defects (13.6%), and ccTGA (11.1%); 36 new familial clusters were described, including 8 pedigrees with concordant familial aggregation of ccTGA, 19 pedigrees with familial co-segregation of ccTGA and dextro-transposition of the great arteries, and 9 familial co-segregation of ccTGA and laterality defects. In one family co-segregation of ccTGA, dextro-transposition of the great arteries and heterotaxy syndrome in 3 distinct relatives was found. In another family, twins both displayed ccTGA and primary ciliary dyskinesia. CONCLUSIONS: ccTGA is not always a sporadic congenital heart defect. Familial clusters as well as evidence of an association between ccTGA, dextro-transposition of the great arteries, laterality defects and in some cases primary ciliary dyskinesia, strongly suggest a common pathogenetic pathway involving laterality genes in the pathophysiology of ccTGA.