Early Functional Status Change After Cardiopulmonary Resuscitation in a Pediatric Heart Center: A Single-Center Retrospective Study.

Children with cardiac disease are at significantly higher risk for in-hospital cardiac arrest (CA) compared with those admitted without cardiac disease. CA occurs in 2-6% of patients admitted to a pediatric intensive care unit (ICU) and 4-6% of children admitted to the pediatric cardiac-ICU. Treatment of in-hospital CA with cardiopulmonary resuscitation (CPR) results in return of spontaneous circulation in 43-64% of patients and survival rate that varies from 20 to 51%. We aimed to investigate the change in functional status of survivors who experienced an in-hospital CA using the functional status scale (FSS) in our heart center by conducting a retrospective study of all patients 0-18 years who experienced CA between June 2015 and December 2020 in a free-standing university-affiliated quaternary children's hospital. Of the 165 CA patients, 61% (n = 100) survived to hospital discharge. The non-survivors had longer length from admission to CA, higher serum lactate levels peri-CA, and received higher number of epinephrine doses. Using FSS, of the survivors, 26% developed new morbidity, and 9% developed unfavorable outcomes. There was an association of unfavorable outcomes with longer CICU-LOS and number of epinephrine doses given. Sixty-one-percent of CA patients survived to hospital discharge. Of the survivors, 26% developed new morbidity and 91% had favorable outcomes. Future multicenter studies are needed to help better identify modifiable risk factors for development of poor outcomes and help improve outcomes of this fragile patient population.

Outcomes after intrauterine insemination are independent of provider type.

OBJECTIVE: We sought to determine whether the success of intrauterine insemination (IUI) varies based on the type of health care provider performing the procedure. STUDY DESIGN: This was a retrospective cohort study set at an infertility clinic at an academic institution. The patients who comprised this study were 1575 women who underwent 3475 IUI cycles from late 2003 through early 2012. Cycles were stratified into 3 groups according to the type of provider who performed the procedure: attending physician, fellow physician, or registered nurse (RN). The primary outcome was live birth. Additional outcomes of interest included positive pregnancy test and clinical pregnancy. Repeated measures log binomial regression was used to estimate the risk ratios (RR) and 95% confidence intervals (CI) for the outcomes and to evaluate the effect of potential confounders. All tests were 2-sided, and P values < .05 were considered statistically significant. RESULTS: Of the 3475 IUI cycles, 2030 (58.4%) were gonadotropin stimulated, 929 (26.7%) were clomiphene citrate stimulated, and 516 (14.9%) were natural. The incidences of clinical pregnancy and live birth among all cycles were 11.8% and 8.8%, respectively. After adjusting for female age, male partner age, and cycle type, the incidence of live birth was similar for RNs compared with attending physicians (RR, 0.80; 95% CI, 0.58-1.1) and fellow physicians compared with attending physicians (RR, 0.84; 95% CI, 0.58-1.2). Similar results were seen for positive pregnancy test and clinical pregnancy. CONCLUSION: There was no significant difference in live birth following IUI cycles in which the procedure was performed by a fellow physician or RN compared with an attending physician.

Velocity encoded mitral valve inflow cine: A novel and more reproducible method to determine cardiac rest periods during coronary magnetic resonance angiography.

A high temporal resolution, 4-chamber (4CH) cine is the standard method for determining cardiac rest periods during whole heart coronary magnetic resonance angiography (CMRA). We evaluated the image quality and reproducibility between the 4CH cine method and a novel approach using a velocity encoded mitral valve inflow cine (MVI). The goal of this study was to compare the quality of CMRAs utilizing MVI versus 4CH methods. Sharpness and vessel length for the LCA and RCA using each method were determined using Soap Bubble and two blinded observers independently assessed coronary image quality. Offline analysis on a separate, retrospective cohort (n = 25) was used to compare MVI and 4CH reproducibility. In the prospectively evaluated cohort there was no difference in overall vessel sharpness (4CH vs MVI mean ± SD) (31.0 ± 5.5% vs 30.5 ± 5.7%, p = .63), LCA vessel sharpness (30.0 ± 5.4% vs 31.1 ± 8.2%, p = .44), LCA length (4.7 ± 1.4 cm vs 4.6 ± 1.6 cm, p = .66), RCA vessel sharpness (32.1 ± 6.9% vs 31.1 ± 7.7%, p = .55), RCA length (5.51 ± 2.6 cm vs 5.95 ± 2.4 cm, p = .38), or image quality rating (2.66 vs 2.62, p = .80) between methods. In the retrospective cohort, the MVI method had 5.4% lower inter-observer variability (95% CI 3.7,7.2%, p < .0001) and 3.9% lower intra-observer variability (95% CI 2.4,5.4%, p < .0001) than the 4CH method. MVI is a technically feasible and more reproducible method to determine cardiac rest periods compared to 4CH while preserving vessel sharpness, vessel length & image quality.

Association of Digoxin With Preserved Echocardiographic Indices in the Interstage Period: A Possible Mechanism to Explain Improved Survival?

Background For patients with hypoplastic left heart syndrome, digoxin has been associated with reduced interstage mortality after the Norwood operation, but the mechanism of this benefit remains unclear. Preservation of right ventricular (RV) echocardiographic indices has been associated with better outcomes in hypoplastic left heart syndrome. Therefore, we sought to determine whether digoxin use is associated with preservation of the RV indices in the interstage period. Methods and Results We conducted a retrospective cohort study of prospectively collected data using the public use data set from the Pediatric Heart Network Single Ventricle Reconstruction trial, conducted in 15 North American centers between 2005 and 2008. We included all patients who survived the interstage period and had echocardiographic data post-Norwood and pre-Glenn operations. We used multivariable linear regression to compare changes in RV parameters, adjusting for relevant covariates. Of 289 patients, 94 received digoxin at discharge post-Norwood. There were no significant differences in baseline clinical characteristics or post-Norwood echocardiographic RV indices (RV end-diastolic volume indexed, RV end-systolic volume indexed, ejection fraction) in the digoxin versus no-digoxin groups. At the end of the interstage period and after adjustment for relevant covariates, patients on digoxin had better preserved RV indices compared with those not on digoxin for the ΔRV end-diastolic volume (11 versus 15 mL, P=0.026) and the ΔRV end-systolic volume (6 versus 9 mL, P=0.009) with the indexed ΔRV end-systolic volume (11 versus 20 mL/BSA1.3, P=0.034). The change in the RV ejection fraction during the interstage period between the 2 groups did not meet statistical significance (-2 versus -5, P=0.056); however, the trend continued to be favorable for the digoxin group. Conclusions Digoxin use during the interstage period is associated with better preservation of the RV volume and tricuspid valve measurements leading to less adverse remodeling of the single ventricle. These findings suggest a possible mechanism of action explaining digoxin's survival benefit during the interstage period.

Racial Disparities in Fertility Care: an Analysis of 4537 Intrauterine Insemination Cycles.

BACKGROUND: Studies suggest that race may affect access to fertility treatments and their outcomes. We examined whether race affects the following: duration of infertility prior to seeking evaluation, diagnosis, treatment cycle characteristics, and outcomes. MATERIALS AND METHODS: Design: Retrospective cohort. SETTINGS: Academic fertility center. PATIENTS: 4537 intrauterine insemination ± ovulation induction (IUI ± OI) cycles/1495 patients. INTERVENTIONS: IUI following: (i) OI with either clomiphene citrate or gonadotropins and (ii) ultrasound-monitored natural cycles. OUTCOME MEASURES: Duration of infertility prior to seeking treatment, SART diagnosis, treatment cycle characteristics and outcomes (spontaneous abortion (SABR), clinical (CPR) and multiple pregnancy rates (MPR)). RESULTS: Asians and Hispanics compared to Caucasians waited significantly longer prior to seeking fertility evaluation (p < 0.01). The mean age of patients seeking infertility evaluation did not differ between groups nor did the type of treatment initially chosen by the patients. Idiopathic infertility was more common among Caucasians (p < 0.05, compared to all others) while PCOS and tubal factor infertility were more frequent among Hispanics (p < 0.05, compared to Caucasian, Asian, and mixed ancestry women) and decreased ovarian reserve was more common among African-Americans (p < 0.01, compared to Caucasians, Asians, and Hispanics). Gonadotropin cycle characteristics including dosing and duration of treatment, follicular recruitment, peak estradiol levels, and endometrial lining thickness differed between certain groups. However, no difference was found in CPR, MPR, and SABR between groups. CONCLUSION: Race affects timely access to infertility care, diagnosis, and treatment cycle characteristics but not outcomes. Considering the nation's growing multiracial population, understanding the effect of race on fertility care becomes increasingly important.

Screening for GPR101 defects in pediatric pituitary corticotropinomas.

Cushing disease (CD) in children is caused by adrenocorticotropic hormone (ACTH)-secreting pituitary adenomas. Germline or somatic mutations in genes such as MEN1, CDKIs, AIP, and USP8 have been identified in pediatric CD, but the genetic defects in a significant percentage of cases are still unknown. We investigated the orphan G protein-coupled receptor GPR101, a gene known to be involved in somatotropinomas, for its possible involvement in corticotropinomas. We performed GPR101 sequencing, expression analyses by RT-qPCR and immunostaining, and functional studies (cell proliferation, pituitary hormones secretion, and cAMP measurement) in a series of patients with sporadic CD secondary to ACTH-secreting adenomas in whom we had peripheral and tumor DNA (N=36). No increased GPR101 expression was observed in tumors compared to normal pituitary (NP) tissues, nor did we find a correlation between GPR101 and ACTH expression levels. Sequence analysis revealed a very rare germline heterozygous GPR101 variant (p.G31S) in one patient with CD. Overexpression of the p.G31S variant did not lead to increased growth and proliferation, although modest effects on cAMP signaling were seen. GPR101 is not overexpressed in ACTH-secreting tumors compared to NPs. A rare germline GPR101 variant was found in one patient with CD but in vitro studies did not support a consistent pathogenic effect. GPR101 is unlikely to be involved in the pathogenesis of CD.

Preconceptional thyroid-stimulating hormone levels and outcomes of intrauterine insemination among euthyroid infertile women.

OBJECTIVE: To evaluate differences in intrauterine insemination (IUI) outcomes among euthyroid women with preconceptional thyroid-stimulating hormone (TSH) values in the normal (0.4-2.4 mIU/L) and high-normal (2.5-4.9 mIU/L) ranges. DESIGN: Cohort study. SETTING: A single fertility center. PATIENT(S): A total of 1,477 women who underwent 4,064 IUI cycles between the years 2004 and 2012. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Live birth, clinical pregnancy, spontaneous abortion (SAB), and IUI cycle parameters. RESULT(S): Cycles were categorized into 4 groups based on preconceptional TSH values: 0.40-1.36 mIU/L; 1.37-1.86 mIU/L; 1.87-2.49 mIU/L; and 2.50-4.99 mIU/L. No statistically significant differences were found in IUI cycle parameters, clinical pregnancy rates, or live births per initiated cycle among the 4 TSH groups. However, preconceptional TSH was inversely related to SAB and positively related to live birth among women who achieved a clinical pregnancy. In this group of women, cycles with TSH values between 2.5 and 4.9 mIU/L were related to lower odds of SAB (odds ratio: 0.32; 95% confidence interval: 0.16-0.65) and higher odds of live birth (odds ratio: 2.80; 95% confidence interval: 1.43-5.48) compared with cycles among women in the lowest TSH group. CONCLUSION(S): Among euthyroid patients, preconceptional TSH values in the high-normal range (between 2.5 and 4.9 mIU/L) are not associated with adverse IUI outcomes.

Hair mercury concentrations and in vitro fertilization (IVF) outcomes among women from a fertility clinic.

Total hair mercury (Hg) was measured among 205 women undergoing in vitro fertilization (IVF) treatment and the association with prospectively collected IVF outcomes (229 IVF cycles) was evaluated. Hair Hg levels (median=0.62ppm, range: 0.03-5.66ppm) correlated with fish intake (r=0.59), and exceeded the recommended EPA reference of 1ppm in 33% of women. Generalized linear mixed models with random intercepts accounting for within-woman correlations across treatment cycles were used to evaluate the association of hair Hg with IVF outcomes adjusted for age, body mass index, race, smoking status, infertility diagnosis, and protocol type. Hair Hg levels were not related to ovarian stimulation outcomes (peak estradiol levels, total and mature oocyte yields) or to fertilization rate, embryo quality, clinical pregnancy rate or live birth rate.

The ARMC5 gene shows extensive genetic variance in primary macronodular adrenocortical hyperplasia.

OBJECTIVE: Primary macronodular adrenal hyperplasia (PMAH) is a rare type of Cushing's syndrome (CS) that results in increased cortisol production and bilateral enlargement of the adrenal glands. Recent work showed that the disease may be caused by germline and somatic mutations in the ARMC5 gene, a likely tumor suppressor gene (TSG). We investigated 20 different adrenal nodules from one patient with PMAH for ARMC5 somatic sequence changes. DESIGN: All of the nodules were obtained from a single patient who underwent bilateral adrenalectomy. DNA was extracted by standard protocol and the ARMC5 sequence was determined by the Sanger method. RESULTS: Sixteen of 20 adrenocortical nodules harbored, in addition to what appeared to be the germline mutation, a second somatic variant. The p.Trp476* sequence change was present in all 20 nodules, as well as in normal tissue from the adrenal capsule, identifying it as the germline defect; each of the 16 other variants were found in different nodules: six were frame shift, four were missense, three were nonsense, and one was a splice site variation. Allelic losses were confirmed in two of the nodules. CONCLUSION: This is the most genetic variance of the ARMC5 gene ever described in a single patient with PMAH: each of 16 adrenocortical nodules had a second new, 'private,' and--in most cases--completely inactivating ARMC5 defect, in addition to the germline mutation. The data support the notion that ARMC5 is a TSG that needs a second, somatic hit, to mediate tumorigenesis leading to polyclonal nodularity; however, the driver of this extensive genetic variance of the second ARMC5 allele in adrenocortical tissue in the context of a germline defect and PMAH remains a mystery.

Primary Aldosteronism and ARMC5 Variants.

CONTEXT: Primary aldosteronism is one of the leading causes of secondary hypertension, causing significant morbidity and mortality. A number of genetic defects have recently been identified in primary aldosteronism, whereas we identified mutations in ARMC5, a tumor-suppressor gene, in cortisol-producing primary macronodular adrenal hyperplasia. OBJECTIVE: We investigated a cohort of 56 patients who were referred to the National Institutes of Health for evaluation of primary aldosteronism for ARMC5 defects. METHODS: Patients underwent step-wise diagnosis, with measurement of serum aldosterone and plasma renin activity followed by imaging, saline suppression and/or oral salt loading tests, plus adrenal venous sampling. Cortisol secretion was also evaluated; unilateral or bilateral adrenalectomy was performed, if indicated. DNA, protein, and transfection studies in H295R cells were conducted by standard methods. RESULTS: We identified 12 germline ARMC5 genetic alterations in 20 unrelated and two related individuals in our cohort (39.3%). ARMC5 sequence changes in 6 patients (10.7%) were predicted to be damaging by in silico analysis. All affected patients carrying a variant predicted to be damaging were African Americans (P = .0023). CONCLUSIONS: Germline ARMC5 variants may be associated with primary aldosteronism. Additional cohorts of patients with primary aldosteronism and metabolic syndrome, particularly African Americans, should be screened for ARMC5 sequence variants because these may underlie part of the known increased predisposition of African Americans to low renin hypertension.

Patient-specific predictions of outcome after gonadotropin ovulation induction/intrauterine insemination.

OBJECTIVE: To use patient-specific and cycle-specific characteristics to predict clinical pregnancy, multiple pregnancy, and spontaneous abortion rates after gonadotropin ovulation induction (OI)/IUI. DESIGN: Retrospective chart review. SETTING: Academic fertility center. PATIENT(S): A total of 1,438 women who underwent 3,375 gonadotropin OI/IUI cycles. INTERVENTION(S): Individual and cycle-specific characteristics were evaluated to determine predictors of the rates of clinical pregnancy, multiple pregnancy, and spontaneous abortion. Logistic regression using individual parameters was used to create predictive models. MAIN OUTCOME MEASURE(S): Clinical pregnancy (CPR), multiple pregnancy (MPR), and spontaneous abortion rates (SABR). RESULT(S): Multiple predictors were identified for CPR, MPR, and SABR. The presence of at least two follicles ≥ 13 mm at ovulation trigger significantly increased CPR (odds ratio [OR], 95% confidence interval [CI] = 1.45, 1.18-1.78) and MPR (OR, 95% CI = 5.17, 2.16-12.41). An E2 level >400 pg/mL significantly increased MPR (OR, 95% CI = 9.54, 2.31-39.42). Logistic regression models were developed for individualized predictions of outcome. CONCLUSION(S): Regression analysis reveals the patient and cycle-specific characteristics that are significant predictors of CPR, MPR, and SABR after OI/IUI. Logistic models using significant or nearly significant predictors for CPR, MPR, and SABR offer improved predictive power relative to simpler models, and allow for the development of a risk calculator for personalized patient counseling.