Use of central venous access devices outside of the pediatric intensive care units.

BACKGROUND: Central venous access devices (CVAD) are associated with central line associated bloodstream infection (CLABSI) and venous thromboembolism (VTE). We identified trends in non-intensive care unit (ICU) CVAD utilization, described complication rates, and compared resources between low and high CVAD sites. METHODS: We combined data from the Pediatric Health Information System (PHIS) database and surveys from included hospitals. We analyzed 10-year trends in CVAD encounters for non-ICU children between 01/2012-12/2021 and described variation and complication rates between 01/2017-12/2021. Using Fisher's exact test, we compared resources between low and high CVAD users. RESULTS: CVAD use decreased from 6.3% to 3.8% of hospitalizations over 10 years. From 2017-2021, 67,830 encounters with CVAD were identified. Median age was 7 (IQR 2-13) years; 46% were female. Significant variation in CVAD utilization exists (range 1.4-16.9%). Rates of CLABSI and VTE were 4.0% and 3.4%, respectively. Survey responses from 33/41 (80%) hospitals showed 91% had vascular access teams, 30% used vascular access selection guides, and 70% used midline/long peripheral catheters. Low CVAD users were more likely to have a team guiding device selection (100% vs 43%, p = 0.026). CONCLUSIONS: CVAD utilization decreased over time. Significant variation in CVAD use remains and may be associated with hospital resources. IMPACT: Central venous access device (CVAD) use outside of the ICU is trending down; however, significant variation exists between institutions. Children with CVADs hospitalized on the acute care units had a CLABSI rate of 4% and VTE rate of 3.4%. 91% of surveyed institutions have a vascular access team; however, the services provided vary between institutions. Even though 70% of the surveyed institutions have the ability to place midline/long peripheral catheters, the majority use these catheters less than a few times per month. Institutions with low CVAD use are more likely to have a vascular access team that guides device selection.

Differences in intestinal bacteria in traumatic injury survivors with and without probable posttraumatic stress disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is a common consequence of traumatic injury, yet certain biological factors contributing to PTSD are poorly understood. The gut microbiome may influence mental health outcomes, but its role in heterogeneous PTSD presentations requires elucidation. METHODS: Bacterial composition was examined in adults 2-4 years post-trauma with probable PTSD (n = 24) versus trauma-exposed controls without probable PTSD (n = 24). 16S rRNA sequencing and bioinformatic tools assessed microbial diversity and abundance. Relationships between taxa and PTSD symptom clusters were evaluated. RESULTS: No differences were found in overall microbial community structure between groups. The probable PTSD group exhibited significantly reduced Actinobacteriota and increased Verrucomicrobiota phylum abundance compared to controls. Specific taxa showed notable inverse associations with negative mood/cognition versus hyperarousal symptoms. Prevotella and Ruminococcaceae were negatively associated with negative mood but positively associated with hyperarousal. CONCLUSIONS: Results demonstrate microbial signatures of probable PTSD subtypes, highlighting the microbiome as a potential mediator of heterogeneous trauma psychopathology. Definition of PTSD microbial correlates provides a foundation for personalized psychobiotic interventions targeting predominant symptom profiles.

Multimodal Assessment and Intramodal Comparison of Imaging Techniques for Pediatric Pulmonary Vein Stenosis with Pulmonary Hypertension.

Pulmonary vein stenosis (PVS) is a rare, serious, and progressive disease in the pediatric population. Evaluation is complex and involves multimodality imaging. Diagnosis is important as early treatment to prevent progressive pulmonary hypertension and right ventricular dysfunction is essential. Adult studies have shown good correlation between various imaging modalities; however, there are limited data in children. This is a single-center retrospective pilot study to determine the reliability of measurement of pulmonary vein stenosis and pulmonary hypertension across different imaging modalities-computed tomography angiography (CTA), echocardiography (echo), lung perfusion scan (LPS), and cardiac catheterization (cath). PVS was defined as > 2 mmHg by echo and cath and/or 50% reduction in diameter by CTA. Patients had to have an echo, CTA and cath performed within a 1-month timeframe of one another to be included in the study, with LPS data included if testing was completed at initial evaluation. Fifteen total patients were enrolled; 87% were categorized as primary PVS; a condition not directly related to direct injury or prior surgical intervention. Twenty-seven total stenotic pulmonary veins were identified (mean 1.8, range 1-4). CTA had a slightly better agreement with cath than echo in identifying PVS in different vein locations except in the LLPV. Additionally, echo and CTA had excellent sensitivity (91%) and specificity (100%) compared to cath for diagnosis of PH. We conclude that non-invasive imaging of echo and CTA has an acceptable correlation to cardiac catheterization for screening and initial evaluation of PVS and PH, as directly related to PVS, in pediatrics.

Operative Complications, Vaginal Bleeding, and Practice Considerations for Patients on Testosterone Undergoing Gender-Affirming Hysterectomy.

STUDY OBJECTIVE: To evaluate operative complications and healthcare utilization in transgender patients on testosterone undergoing minimally invasive gender-affirming hysterectomy compared to control patients. DESIGN: We performed a retrospective cohort study. Operative reports were used to gather information on intraoperative complications. We collected information on postoperative complications, electronic medical record (EMR) messages, phone calls, emergency department utilization, and clinic visits through a 90-day postoperative period. Healthcare utilization reasons were categorized as vaginal bleeding, pain, vaginal discharge, dysuria, urinary retention, bowel concern, incision concern, or other. SETTING: Tertiary care academic medical center. PATIENTS: Patients aged 18 to 55 who underwent a benign minimally invasive hysterectomy with or without oophorectomy performed between January 2014 and December 2022. The testosterone-using cohort consisted of patients who had a gender identity of male, transgender male, genderqueer, or nonbinary with documented testosterone use prior to surgery (n = 88). The control cohort consisted of patients who identified as female, genderqueer, or nonbinary with no documented testosterone use (n = 242). INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: Patients using testosterone were younger, had a lower body mass index, lower American Society of Anesthesiologists class, and were more likely to be nulliparous. The median time patients used testosterone was 2.5 years (1.5-5.0). Patients on testosterone are at increased risk of intraoperative perineal lacerations requiring repair (RR 3.3, CI 95% [1.03-10.5]). A higher number of patients on testosterone reported vaginal bleeding via EMR message or phone call (RR 1.74 CI 95% [1.1-2.7]) compared to controls. No difference in reasons for emergency department visits was noted. The use of postoperative vaginal estrogen started at the postoperative visit was more frequent in the testosterone-using patients (7 [8.0%] vs 4 [1.7%], p = .01). CONCLUSION: This study demonstrates that testosterone use preoperatively may increase risk of intraoperative vaginal laceration requiring repair. Testosterone use also correlates with increased reports of vaginal bleeding through EMR message, phone call, and clinic visit. These results contribute new evidence to include in preoperative counseling and support existing evidence surrounding the safety of gender-affirming hysterectomy.

Objective Quantification of Bilateral Bubble Contrast Echocardiography Correlates with Systemic Oxygenation in Patients with Single Ventricle Circulation.

Bubble contrast echocardiography is commonly used to diagnose pulmonary arteriovenous malformations (PAVMs) in single ventricle congenital heart disease (CHD), yet previous studies inconsistently report a correlation between bubble echoes and oxygenation. In this study, we sought to re-evaluate the correlation between bubble echoes and oxygenation by assessing total bilateral shunting and unilateral shunting. We conducted a single-center, retrospective study of patients with single ventricle CHD and previous Glenn palliation who underwent a cardiac catheterization and bubble echocardiogram during the same procedure from 2011 to 2020. Spearman's rank correlation was performed to examine the relationship between total bilateral shunting and measures of systemic oxygenation, as well as unilateral shunting and ipsilateral pulmonary vein oxygenation. For all patients (n = 72), total bilateral shunting moderately correlated with peripheral oxygen saturation (SpO2) (rs = -0.44, p < 0.0001). For patients with Glenn/Kawashima circulation (n = 49), total bilateral shunting was moderately correlated (SpO2: rs = -0.38, p < 0.01). In contrast, unilateral shunting did not correlate with ipsilateral pulmonary vein oxygenation for any vein measured (p = 0.16-p > 0.99). In conclusion, the total burden of bilateral bubble shunting correlated with systemic oxygenation and may better reflect the total PAVM burden from all lung segments. Unilateral correlation may be adversely influenced by non-standardized approaches to pulmonary vein sampling.

Respiratory culture growth and 3-years lung health outcomes in children with bronchopulmonary dysplasia and tracheostomies.

BACKGROUND: While bacteria identification on respiratory cultures is associated with poor short-term outcomes in children with bronchopulmonary dysplasia (BPD) and tracheostomies, the influence on longer-term respiratory support needs remains unknown. OBJECTIVE: To determine if respiratory culture growth of pathogenic organisms is associated with ongoing need for respiratory support, decannulation, and death at 3 years posttracheostomy placement in children with BPD and tracheostomies. METHODS: This single center, retrospective cohort study included infants and children with BPD and tracheostomies placed 2010-2018 and ≥1 respiratory culture obtained in 36 months posttracheostomy. Primary predictor was any pathogen identified on respiratory culture. Additional predictors were any Pseudomonas aeruginosa and chronic P. aeruginosa identification. Outcomes included continued use of respiratory support (e.g., oxygen, positive pressure), decannulation, and death at 3 years posttracheostomy. We used Poisson regression models to examine the relationship between respiratory organisms and outcomes, controlling for patient-level covariates and within-patient clustering. RESULTS: Among 170 children, 59.4% had a pathogen identified, 28.8% ever had P. aeruginosa, and 3.5% had chronic P. aeruginosa. At 3 years, 33.1% of alive children required ongoing respiratory support and 24.8% achieved decannulation; 18.9% were deceased. In adjusted analysis, any pathogen and P. aeruginosa were not associated with ongoing respiratory support or mortality. However, P. aeruginosa was associated with decreased decannulation probability (adjusted risk ratio 0.48, 95% CI 0.23-0.98). Chronic P. aeruginosa was associated with lower survival probability. CONCLUSION: Our findings suggest that respiratory pathogens including P. aeruginosa may not promote long-term respiratory dysfunction, but identification of P. aeruginosa may delay decannulation.

Use of Low-Dose Computed Tomography in Children With Nephrolithiasis: An Analysis From 2 Tertiary Pediatric Centers.

INTRODUCTION: Although ultrasound (US) is the preferred first-line imaging for pediatric nephrolithiasis, CT may be necessary in cases of a nondiagnostic US or when US in not available. Utilization of dose reduction strategies in children undergoing CT for nephrolithiasis is not well described. We compared use of low-dose CT (LDCT) in children presenting to 2 pediatric centers. METHODS: We performed a retrospective chart review of children ≤ 17 years of age presenting with suspected nephrolithiasis to 2 tertiary children's hospitals, inclusive of those referred to these centers from nonpediatric facilities between 2013 and 2019. Children were included with an index CT scan from either the pediatric or referring center while those who had prior documented CT for nephrolithiasis within the study period or missing radiation dose assessment were excluded. The primary outcome was LDCT as defined as radiation dose < 3 mGy. The primary comparator was pediatric vs outside referral center. Exploratory analysis evaluated other factors associated with LDCT, including radiation dosage as a continuous variable. RESULTS: A total of 155 individuals met inclusion criteria, with 126 (81.3%) receiving standard dose and 29 (18.7%) receiving LDCT. Pediatric facilities were more likely to utilize LDCT as compared to referral centers (P < .05). Older age and higher BMI were also found to be associated with increased radiation dose exposure. CONCLUSIONS: Pediatric facilities utilized LDCT more frequently, although age and BMI may also influence imaging choices. An understanding of the factors associated with dose reduction in CT will impact future efforts to explore optimum imaging stewardship in pediatric nephrolithiasis.

Effects of physical activity on placental analytes in nulliparous persons.

INTRODUCTION: Physical activity during pregnancy has long been investigated for its role in preeclampsia prevention. The mechanism of this relationship is unknown, although some studies suggest physical activity may affect placental analytes throughout pregnancy. The objective of this study was to determine the effect of physical activity on preeclampsia-associated placental analytes using a prospective cohort of pregnant nulliparous patients. METHODS: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be. Frequency and duration of up to three leisure activities was reported in the first and second trimesters and was analyzed, with participants either meeting or not meeting the recommended exercise of 150 min per week. Levels of the following placental analytes, placental growth factor, soluble endoglin, and soluble fms-like tyrosine kinase-1 (sFLT1), were analyzed stratified by the physical activity level. RESULTS: A total of 1,956 participants were included in the analysis. The level of sFLT1 in the first trimester was lower in the group that had ≥ 150 min per week of physical activity, compared to the group that had < 150 min (846.3 [821.6, 871,8] versus 893.0 [864.5,922.5], p = 0.017). There were no significant sFLT1 changes in the second trimester based on physical activity. After controlling for maternal demographic and clinical factors, sFLT1 levels in the second trimester were significantly lower (p = 0.049) in participants that had ≥ 150 min of physical activity per week. DISCUSSION: Our findings of decreased sFLT1 levels suggest this could be the mechanism explaining the association between PA in pregnancy and lower risk of preeclampsia.

Brain microvascular endothelial cells possess a second cilium that arises from the daughter centriole.

Primary cilia from the brain microvascular endothelial cells (ECs) are specialized cell-surface organelles involved in mediating sensory perception, cell signaling, and vascular stability. Immunofluorescence (IF) analysis of human primary brain microvascular ECs reveals two cilia per cell. To confirm the in vitro observation of the two-cilia phenotype in human primary brain ECs, ECs isolated from mouse brain were cultured and stained for cilium. Indeed, brain ECs from a ciliopathic mouse (polycystic kidney disease or Pkd2 -/-) also possess more than one cilium. Primary cilium emerges from the mother centriole. Centriole analysis by IF suggests that in brain ECs, markers for the mother and daughter centrioles stain both cilia, suggesting that the second cilium in brain ECs arises from the daughter centriole. Further quantification of cilia size in brain ECs revealed that cilia arising from the mother centriole are bigger in size compared with cilia from the daughter centriole. Cell cycle analyses using immunoblotting and flow cytometry suggest that the ciliary proteins ARL13B and IFT88 involved in brain EC ciliogenesis are highly expressed only in the G0/G1 and S phases of the cell cycle. The IF analyses of cells arrested at different cell cycle stages indicate that the two-cilia phenotype is highly specific to the G0/G1 phase. Our findings suggest that in addition to the mother centriole, the daughter centriole also plays a role in ciliogenesis in primary cultured ECs.

Profibrotic COVID-19 subphenotype exhibits enhanced localized ER-dependent HSP47+ expression in cardiac myofibroblasts in situ.

We recently described a subgroup of autopsied COVID-19 subjects (∼40%), termed 'profibrotic phenotype,' who exhibited clusters of myofibroblasts (Mfbs), which were positive for the collagen-specific chaperone heat shock protein 47 (HSP47+) in situ. This report identifies increased, localized (hot spot restricted) expression of αSMA, COLα1, POSTN and FAP supporting the identity of HSP47+ cells as myofibroblasts and characterizing a profibrotic extracellular matrix (ECM) phenotype. Coupled with increased GRP78 in COVID-19 subjects, these data could reflect induction of the unfolded protein response for mitigation of proteostasis (i.e., protein homeostasis) dysfunction in discrete clusters of cells. ECM shifts in selected COVID-19 subjects occur without significant increases in either global trichrome positive staining or myocardial injury based quantitively on standard H&E scoring. Our findings also suggest distinct mechanism(s) for ECM remodeling in the setting of SARS-CoV-2 infection. The ratio of CD163+/CD68+ cells is increased in hot spots of profibrotic hearts compared with either controls or outside of hot spots in COVID-19 subjects. In sum, matrix remodeling of human COVID-19 hearts in situ is characterized by site-restricted profibrotic mediated (e.g., HSP47+ Mfbs, CD163+ Mφs) modifications in ECM (i.e., COLα1, POSTN, FAP), with a strong correlation between COLα1 and HSP47+cells within hot spots. Given the established associations of viral infection (e.g., human immunodeficiency virus; HIV), myocardial fibrosis and sudden cardiac death, early screening tools (e.g., plasma biomarkers, noninvasive cardiac magnetic resonance imaging) for diagnosis, monitoring and treatment of fibrotic ECM remodeling are warranted for COVID-19 high-risk populations.

A Cross-Sectional Study of Pediatric Feeding Disorder in Children with Cystic Fibrosis.

BACKGROUND: The exact prevalence of feeding problems in children with cystic fibrosis (CF) is unknown. Pediatric feeding disorder (PFD) encompasses poor oral intake with associated medical, nutrition, psychosocial, or feeding skill dysfunction. We hypothesized that PFD is common in CF and aimed to categorize feeding dysfunction across various domains in children with CF. METHODS: An observational cross-sectional study was conducted in children with CF. Data collected included anthropometrics, nutrition data (including need for tube feeding/enteral nutrition [EN] or high-energy beverages, dietary diversity), feeding skills (Pediatric version of the Eating Assessment tool [pEAT]), and psychosocial function (About Your Child's Eating questionnaire [AYCE] in children 2-17 years of age/Behavioral Pediatric Feeding Assessment Scale [BPFAS] in children 12-23 months of age). PFD was defined as poor oral intake with: (a) pEAT score > 5; and/or (b) AYCE or BPFAS score > 2 standard deviation of normative controls; and/or (c) nutrition dysfunction (body mass index/weight-for-length z score < -1 and/or preference of oral high energy beverages or dependence on EN and/or decreased dietary diversity). RESULTS: Of 103 children in the study, 62 (60.1%) had PFD, 7 children (6.8%) were malnourished, 10 needed EN (9.7%), and 30 (29.1%) needed oral high-energy beverages. Dietary diversity was decreased in 42 children (41.5%), 1 child had feeding skill dysfunction, and 11 (10.8%) met criteria for psychosocial dysfunction. CONCLUSION: Almost 2/3rd of children with CF have PFD and many have poor dietary diversity. A significant percentage of children rely on EN and oral supplements, but psychosocial dysfunction is less prevalent.

Implementation of a Bleeding Risk Screening Tool and Hematology Referral Process Prior to Pediatric Endoscopy.

OBJECTIVES: Gastrointestinal (GI) endoscopic procedures are considered low risk with an overall bleeding risk for upper and lower endoscopies of 0.11%. However, a certain population of patients may have a higher risk for bleeding, and there is not a standardized process for screening patients to determine who these patients are. METHODS: At Children's Wisconsin, our gastroenterology and hematology divisions adapted an abbreviated version of a validated, history-based bleeding risk screening tool and implemented a hematology referral process to identify those at risk for bleeding prior to their first endoscopy. Provider compliance with the bleeding screen, referral to hematology, time to be seen in hematology clinic, new diagnoses of bleeding disorders, and bleeding complications were assessed from 2019 to 2021 across 3 phases. RESULTS: Provider compliance with the bleeding screen improved throughout our study from 48% (120/251) to 75% (189/253). For those who screened positive, compliance with referral to hematology ranged from 38% to 74% across our phases. The overall time to be seen by hematology decreased from 30 days to 7.5 days. Eighteen patients ultimately screened positive and were seen in hematology clinic, of whom 22% (4/18) were diagnosed with a new bleeding disorder. No bleeding complications were seen in our study population. CONCLUSIONS: Our quality improvement project provided a standardized screening tool to assess preoperative bleeding risk and reinforced the value of a history-based screening tool. This modified screening tool identified those with an undiagnosed bleeding disorder and preventative measures were undertaken to prevent procedural bleeding complications.

Intralesional measles, mumps, and rubella vaccine after failure of intralesional Candida antigen for the treatment of recalcitrant pediatric warts.

Numerous studies have investigated the efficacy of intralesional immunotherapy for warts, but there are a lack of studies investigating the efficacy of alternative intralesional immunotherapies following failure of initial intralesional immunotherapy. In this retrospective study, we aimed to investigate the efficacy of intralesional measles, mumps, and rubella vaccine for the treatment of pediatric warts following failure of intralesional therapy with Candida antigen. Following intralesional measles, mumps, and rubella vaccine administration, 8/51 (15.5%) patients had complete resolution of their warts, 6/51 (12%) had near complete resolution, 19/51 (37%) had partial improvement, 12/51 (23.5%) had no change, and 6/51 (12%) had worsening. Although limited by retrospective nature and low sample size, our results demonstrate that intralesional immunotherapy with measles, mumps, and rubella vaccine provides an alternative therapeutic option for the treatment of recalcitrant pediatric warts in patients who fail to respond to intralesional Candida antigen.

Considerations for pharmacologic thromboprophylaxis following inpatient brachytherapy for gynecologic malignancies.

PURPOSE: Brachytherapy irradiation carries risks of both bleeding and venous thromboembolism (VTE). No screening or management recommendations for VTE in this setting have been developed. Our study aims to understand the incidence of VTE, compile published anticoagulation guidelines, and call for future guidelines to address thromboprophylaxis in this population. METHODS AND MATERIALS: A retrospective, single institution study of patients undergoing brachytherapy irradiation between 2012 and 2022 was undertaken. We analyzed 2 cohorts: 87 patients undergoing brachytherapy with an inpatient admission, and 66 patients assessed for risk of VTE or bleeding after discharge from an inpatient admission for brachytherapy. Caprini risk scores were calculated for each patient, and statistical analyses were performed. RESULTS: Eighty-seven patients were included, and 25% had a VTE diagnosis. Forty-seven (54%) of patients included underwent brachytherapy as definitive treatment of cervical cancer, and 16 (18%) received brachytherapy irradiation to treat recurrent endometrial cancer. In the cohort of 66 patients assessed for risk of VTE or bleeding after brachytherapy discharge, 23 (34.8%) were discharged with thromboprophylaxis, and 43 (65.2%) were discharged without thromboprophylaxis. None of the patients discharged on thromboprophylaxis were diagnosed with a VTE within 90 days of discharge after brachytherapy, whereas 3 of 43 (7%) discharged without thromboprophylaxis were diagnosed with a VTE, OR and 95% CI: 0.25 (0.01-5.29), p = 0.37. Of the 23 patients discharged on thromboprophylaxis, 1 was readmitted for bleeding OR and 95% CI: 5.8 (0.22-155.18), p = 0.29. The median Caprini score was 11. CONCLUSIONS: VTE is a common occurrence in patients undergoing brachytherapy. Patients undergoing brachytherapy irradiation who require inpatient admission represent a unique population, and specialty organizations should develop consensus recommendations to address these clinical challenges.

Vaccines and use of immunosuppressive and immunomodulatory therapy in a pediatric dermatology clinic-A single institution experience.

Vaccine type and timing are critical issues to prevent unintended infections in those on immunosuppressive therapies. We retrospectively chart reviewed patients at Children's Wisconsin Pediatric Dermatology Clinic on immunosuppressives and immunomodulators between 11/1/2012 and 6/1/2020 and found that approximately 76% of patient encounters do not have documented vaccine counseling in the medical chart before initiation of immunosuppressives and immunomodulators. As age increased, vaccine counseling was less likely to be documented (odds ratio: 0.89; 95% confidence interval: 0.84-0.95, p = .001). In addition, 13 patient encounters (4%) were not up to date with live vaccines before immunosuppressive or immunomodulating therapy. There is an opportunity to improve clinical processes to ensure documentation of vaccination status and vaccine counseling before starting immunosuppressive and immunomodulator medications in a pediatric dermatology clinic.

GAP (gestational diabetes and pharmacotherapy) - study protocol for a randomized controlled, two-arm, single-site trial.

BACKGROUND: Gestational diabetes (GDM) complicates 10% of pregnancies in the US. First-line treatment is medical nutrition therapy (MNT) and exercise. Second line is pharmacotherapy. The definition of what constitutes an unsuccessful trial of MNT and exercise has not been established. Tight glycemic control has been demonstrated to reduce GDM-related neonatal and maternal clinical complications. However, it could also increase rates of small-for-gestational age and carry negative effects on patient-reported outcomes such as anxiety and stress. We will study the effect of earlier and stricter pharmacotherapy in GDM on clinical and patient-reported outcomes. METHODS: GDM and pharmacotherapy (GAP) study is a two-arm parallel, pragmatic randomized controlled trial, where 416 participants with GDM are randomized 1:1 to: 1) Intervention group - insulin initiation at 20% elevated glucose values on a weekly glucose log following MNT and exercise trial and insulin titration to keep elevated glucose values <20%; or 2) Active control group - insulin initiation at 40% elevated glucose values on a weekly log following MNT and exercise and insulin titration to keep elevated glucose values <40%. The primary outcome is a composite neonatal outcome of large-for-gestational-age, macrosomia, birth trauma, preterm birth, hypoglycemia, and hyperbilirubinemia. Secondary outcomes include preeclampsia, cesarean birth, small-for-gestational-age, maternal hypoglycemia, and patient-reported outcomes of anxiety, depression, perceived stress, and diabetes self-efficacy. CONCLUSIONS: The GAP study will investigate the optimal glycemic threshold for pharmacotherapy addition to MNT and exercise in GDM. The GAP study will promote standardization in GDM management and will have direct relevance for clinical practice.

Collagen-Specific HSP47+ Myofibroblasts and CD163+ Macrophages Identify Profibrotic Phenotypes in Deceased Hearts With SARS-CoV-2 Infections.

Background Cardiac fibrosis complicates SARS-CoV-2 infections and has been linked to arrhythmic complications in survivors. Accordingly, we sought evidence of increased HSP47 (heat shock protein 47), a stress-inducible chaperone protein that regulates biosynthesis and secretion of procollagen in heart tissue, with the goal of elucidating molecular mechanisms underlying cardiac fibrosis in subjects with this viral infection. Methods and Results Using human autopsy tissue, immunofluorescence, and immunohistochemistry, we quantified Hsp47+ cells and collagen α 1(l) in hearts from people with SARS-CoV-2 infections. Because macrophages are also linked to inflammation, we measured CD163+ cells in the same tissues. We observed irregular groups of spindle-shaped HSP47+ and CD163+ cells as well as increased collagen α 1(I) deposition, each proximate to one another in "hot spots" of ≈40% of hearts after SARS-CoV-2 infection (HSP47+ P<0.05 versus nonfibrotics and P<0.001 versus controls). Because HSP47+ cells are consistent with myofibroblasts, subjects with hot spots are termed "profibrotic." The remaining 60% of subjects dying with COVID-19 without hot spots are referred to as "nonfibrotic." No control subject exhibited hot spots. Conclusions Colocalization of myofibroblasts, M2(CD163+) macrophages, and collagen α 1(l) may be the first evidence of a COVID-19-related "profibrotic phenotype" in human hearts in situ. The potential public health and diagnostic implications of these observations require follow-up to further define mechanisms of viral-mediated cardiac fibrosis.

Respiratory viral infections are prevalent but uncomplicated in single ventricle CHD.

BACKGROUND: Patients with single ventricle CHD have significant morbidity and healthcare utilisation throughout their lifetime, including non-cardiac hospital admissions. Respiratory viral infections are the main cause of hospitalisation in children, but few data exist for single ventricle patients. We sought to identify how respiratory viral infections impact patients with single ventricle CHD and potential differences between Glenn and Fontan circulation. METHODS: We conducted a retrospective study of patients seen from 01/01/2011-12/31/2020. We identified patients with a history of single ventricle CHD and Glenn palliation, and a normoxic control group with isolated atrial septal defect requiring surgical closure. We compared viral-related clinical presentations, admissions, and admission characteristics. RESULTS: A total of 312 patients were included (182 single ventricle, 130 atrial septal defect). Single ventricle patients were more likely than children with isolated atrial septal defect to be admitted with a respiratory virus (odds ratio 4.15 [2.30-7.46]), but there was no difference in mechanical ventilation or hospital length of stay (p = 0.4709). Single ventricle patients with Glenn circulation were more likely than those with Fontan circulation to present and be admitted (odds ratio 3.25 [1.62-6.52]), but there was no difference in ICU admission, mechanical ventilation, or hospital length of stay (p = 0.1516). CONCLUSIONS: Respiratory viral infections are prevalent but uncomplicated in patients with single ventricle CHD. Viral-related presentations and admissions are more prevalent during the period of Glenn circulation compared to Fontan circulation; however, rate of mechanical ventilation and hospital length of stay are similar.

Clinical Variables Associated with Pre-Fontan Aortopulmonary Collateral Burden.

Aortopulmonary collaterals (APCs) develop universally, but to varying degrees, in patients with single ventricle congenital heart disease (CHD). Despite their ubiquitous presence, APCs remain poorly understood. We sought to evaluate the association between APC burden and common non-invasive clinical variables. We conducted a single center, retrospective study of patients with single ventricle CHD and previous Glenn palliation who underwent pre-Fontan cardiac magnetic resonance (CMR) imaging from 3/2018 to 3/2021. CMR was used to quantify APC flow, which was normalized to aortic (APC/QAo) and pulmonary vein (APC/QPV) blood flow. Univariate, multivariable, and classification and regression tree (CART) analyses were done to investigate the potential relationship between CMR-quantified APC burden and clinical variables. A total of 29 patients were included, all of whom had increased APC flow (APC/QAo: 26.9, [22.0, 39.1]%; APC/QPV: 39.4 [33.3, 46.9]%), but to varying degrees (APC/QAo: range 11.9-44.4%; APC/QPV: range 17.7-60.0%). Pulmonary artery size (Nakata index, at pre-Fontan CMR) was the only variable associated with APC flow on multivariable analysis (APC/QAo: p = 0.020, R2 = 0.19; APC/QPV: p = 0.0006, R2 = 0.36) and was the most important variable associated with APC burden identified by CART analysis (size inversely related to APC flow). APC flow is universally increased but highly variable in patients with single ventricle CHD and Glenn circulation. Small branch pulmonary artery size is a key factor associated with increased APC burden; however, the pathogenesis of APCs is likely multifactorial. Further research is needed to better understand APC pathogenesis, including predisposing and mitigating factors.

A Trying Time: Problematic Internet Use (PIU) and its association with depression and anxiety during the COVID-19 Pandemic.

BACKGROUND: The prevalence of problematic Internet use (PIU) among adolescents and young adults (AYA) was approximately 9-11% before the COVID-19 pandemic. The purpose of this study was to determine the prevalence of PIU among AYAs (especially younger adolescents) during the COVID-19 pandemic using the Problematic and Risky Internet Use Screening Scale (PRIUSS). Additionally, we examined the relationship between PIU, depression and anxiety among AYAs during the same period. METHODS: A descriptive-analysis survey study was completed over a 6-month period from January 4, 2021, to June 30, 2021. It was conducted at a tertiary care Adolescent Medicine Clinic with AYAs age 12-21. The PRIUSS screened for PIU, the PHQ-9A [Patient Health Questionnaire-9A] screened for depression, and the GAD-7 [General Anxiety Disorder-7] screened for generalized anxiety. Fisher's exact test, the Mann-Whitney test and Spearman correlations were performed. RESULTS: A positive PRIUSS score was observed in 18% of the 447 participants. Of these participants, 44% had a pre-existing diagnosis of depression, 39% had a pre-existing diagnosis of anxiety and 29% had a pre-existing diagnosis of depression and anxiety. There was a positive correlation between PRIUSS, PHQ-9A and GAD-7 total scores. A higher PRIUSS score was associated with a higher PHQ-9A and GAD-7 score (p < 0.001). There was also a positive correlation between a positive PRIUSS score and a pre-existing diagnosis of depression (p < 0.001). CONCLUSIONS: This study showed a higher prevalence of PIU during the COVID-19 pandemic using the PRIUSS. In addition, a positive correlation between PRIUSS scores and pre-existing diagnosis of depression, positive GAD-7 and PHQ-9A scores was noted. In conclusion, medical providers should consider screening for PIU in AYAs with positive mental health screens.