Survival does not differ by annual center transplant volume-A Pediatric Heart Transplant Society Registry study.

BACKGROUND: There are conflicting data regarding the relationship between center volume and outcomes in pediatric heart transplantation. Previous studies have not fully accounted for differences in case mix, particularly in high-risk congenital heart disease (CHD) groups. We aimed to evaluate the relationship between center volume and outcomes using the Pediatric Heart Transplant Society (PHTS) Registry and explore how case mix may affect outcomes. METHODS: A retrospective cohort study of all pediatric patients in the PHTS Registry who received a heart transplant from 2009 to 2018 was performed. Centers were divided into 5 groups based on average yearly transplant volume. The primary outcome was time to death or graft loss and outcomes were compared using Kaplan-Meier analysis. RESULTS: There were 4583 cases among 55 centers included. There was no difference in time to death or graft loss by center volume in the entire cohort (p = .75), in patients with CHD (p = .79) or in patients with cardiomyopathy (p = .23). There was also no difference in time to death or graft loss by center size in patients undergoing transplant after Norwood, Glenn or Fontan (log rank p = .17, p = .31, and p = .10 respectively). There was a statistically significant difference in outcomes by center size in the positive crossmatch group (p < .0001), though no discernible pattern related to high or low center volume. CONCLUSIONS: Outcomes are similar among transplant centers of all sizes, including for high-risk patient groups with CHD. Future work is needed to understand how patient-specific risk factors may vary among centers of various sizes and whether this influences patient outcomes.

Diffusion basis spectrum imaging detects subclinical traumatic optic neuropathy in a closed-head impact mouse model of traumatic brain injury.

Introduction: Traumatic optic neuropathy (TON) is the optic nerve injury secondary to brain trauma leading to visual impairment and vision loss. Current clinical visual function assessments often fail to detect TON due to slow disease progression and clinically silent lesions resulting in potentially delayed or missed treatment in patients with traumatic brain injury (TBI). Methods: Diffusion basis spectrum imaging (DBSI) is a novel imaging modality that can potentially fill this diagnostic gap. Twenty-two, 16-week-old, male mice were equally divided into a sham or TBI (induced by moderate Closed-Head Impact Model of Engineered Rotational Acceleration device) group. Briefly, mice were anesthetized with isoflurane (5% for 2.5 min followed by 2.5% maintenance during injury induction), had a helmet placed over the head, and were placed in a holder prior to a 2.1-joule impact. Serial visual acuity (VA) assessments, using the Virtual Optometry System, and DBSI scans were performed in both groups of mice. Immunohistochemistry (IHC) and histological analysis of optic nerves was also performed after in vivo MRI. Results: VA of the TBI mice showed unilateral or bilateral impairment. DBSI of the optic nerves exhibited bilateral involvement. IHC results of the optic nerves revealed axonal loss, myelin injury, axonal injury, and increased cellularity in the optic nerves of the TBI mice. Increased DBSI axon volume, decreased DBSI λ||, and elevated DBSI restricted fraction correlated with decreased SMI-312, decreased SMI-31, and increased DAPI density, respectively, suggesting that DBSI can detect coexisting pathologies in the optic nerves of TBI mice. Conclusion: DBSI provides an imaging modality capable of detecting subclinical changes of indirect TON in TBI mice.

Dorsal striatal response to taste is modified by obesity and insulin resistance.

OBJECTIVE: In preclinical models, insulin resistance in the dorsal striatum (DS) contributes to overeating. Although human studies support the concept of central insulin resistance, they have not investigated its effect on consummatory reward-induced brain activity. METHODS: Taste-induced activation was assessed in the caudate and putamen of the DS with blood oxygen level-dependent (BOLD) functional magnetic resonance imaging. Three phenotypically distinct groups were studied: metabolically healthy lean, metabolically healthy obesity, and metabolically unhealthy obesity (MUO; presumed to have central insulin resistance). Participants with MUO also completed a weight loss intervention followed by a second functional magnetic resonance imaging session. RESULTS: The three groups were significantly different at baseline consistent with the design. The metabolically healthy lean group had a primarily positive BOLD response, the MUO group had a primarily negative BOLD response, and the metabolically healthy obesity group had a response in between the two other groups. Food craving was predicted by taste-induced activation. After weight loss in the MUO group, taste-induced activation increased in the DS. CONCLUSIONS: These data support the hypothesis that insulin resistance and obesity contribute to aberrant responses to taste in the DS, which is only partially attenuated by weight loss. Aberrant responses to food exposure may be a barrier to weight loss.

Family-Based Behavioral Treatment for Childhood Obesity Implemented in Pediatric Primary Care: A Randomized Clinical Trial.

Importance: Intensive behavioral interventions for childhood overweight and obesity are recommended by national guidelines, but are currently offered primarily in specialty clinics. Evidence is lacking on their effectiveness in pediatric primary care settings. Objective: To evaluate the effects of family-based treatment for overweight or obesity implemented in pediatric primary care on children and their parents and siblings. Design, Setting, and Participants: This randomized clinical trial in 4 US settings enrolled 452 children aged 6 to 12 years with overweight or obesity, their parents, and 106 siblings. Participants were assigned to undergo family-based treatment or usual care and were followed up for 24 months. The trial was conducted from November 2017 through August 2021. Interventions: Family-based treatment used a variety of behavioral techniques to develop healthy eating, physical activity, and parenting behaviors within families. The treatment goal was 26 sessions over a 24-month period with a coach trained in behavior change methods; the number of sessions was individualized based on family progress. Main Outcomes and Measures: The primary outcome was the child's change from baseline to 24 months in the percentage above the median body mass index (BMI) in the general US population normalized for age and sex. Secondary outcomes were the changes in this measure for siblings and in BMI for parents. Results: Among 452 enrolled child-parent dyads, 226 were randomized to undergo family-based treatment and 226 to undergo usual care (child mean [SD] age, 9.8 [1.9] years; 53% female; mean percentage above median BMI, 59.4% [n = 27.0]; 153 [27.2%] were Black and 258 [57.1%] were White); 106 siblings were included. At 24 months, children receiving family-based treatment had better weight outcomes than those receiving usual care based on the difference in change in percentage above median BMI (-6.21% [95% CI, -10.14% to -2.29%]). Longitudinal growth models found that children, parents, and siblings undergoing family-based treatment all had outcomes superior to usual care that were evident at 6 months and maintained through 24 months (0- to 24-month changes in percentage above median BMI for family-based treatment and usual care were 0.00% [95% CI, -2.20% to 2.20%] vs 6.48% [95% CI, 4.35%-8.61%] for children; -1.05% [95% CI, -3.79% to 1.69%] vs 2.92% [95% CI, 0.58%-5.26%] for parents; and 0.03% [95% CI, -3.03% to 3.10%] vs 5.35% [95% CI, 2.70%-8.00%] for siblings). Conclusions and Relevance: Family-based treatment for childhood overweight and obesity was successfully implemented in pediatric primary care settings and led to improved weight outcomes over 24 months for children and parents. Siblings who were not directly treated also had improved weight outcomes, suggesting that this treatment may offer a novel approach for families with multiple children. Trial Registration: ClinicalTrials.gov Identifier: NCT02873715.

Peak Serum Cortisol Cutoffs to Diagnose Adrenal Insufficiency Across Different Cortisol Assays in Children

Objective: Current peak serum cortisol cutoffs for the diagnosis of adrenal insufficiency (AI) after Cosyntropin stimulation have been established using polyclonal antibody (pAb) immunoassays. However, new and highly specific cortisol monoclonal antibody (mAb) immunoassays are being used more widely, which can potentially yield higher false positive rates. Thus, this study aimed to redefine the biochemical diagnostic cutoff points for AI in children when using a highly specific cortisol mAb immunoassay and liquid chromatography tandem mass spectrometry (LC/MS) to avoid unnecessary steroid use. Methods: Cortisol levels from 36 children undergoing 1 mcg Cosyntropin stimulation tests to rule out AI were measured using pAb immunoassay (Roche Elecsys Cortisol I), mAB immunoassay (Roche Elecsys Cortisol II), and LC/MS. Logistic regression was used to predict AI using the pAB as the reference standard. A receiver operator characteristic curve, area under the curve (AUC), sensitivity, specificity, and kappa agreement were also calculated. Results: Using a peak serum cortisol cutoff value of 12.5 µg/dL for the mAb immunoassay provided 99% sensitivity and 94% specificity for diagnosing AI, when compared to the historical pAb immunoassay cutoff of 18 µg/dL (AUC=0.997). Likewise, a cutoff of value of 14 µg/dL using the LC/MS, provided 99% sensitivity and 88% specificity when compared to the pAb immunoassay (AUC=0.995). Conclusion: To prevent overdiagnosis of AI in children undergoing 1 mcg Cosyntropin stimulation test, our data support using a new peak serum cortisol cutoff of 12.5 µg/dL and 14 µg/dL to diagnose AI when using mAb immunoassays and LC/MS in children, respectively.

Median Nerve Stimulation for Treatment of Tics: Randomized, Controlled, Crossover Trial.

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained the sensorimotor cortex EEG signal and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested, and stimulation blocks lasted only 1 min. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Preregistration was completed at ClinicalTrials.gov, under number NCT04731714. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to the order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity, and urges, but the two treatments did not differ significantly. Participant masking was effective, and there was no carryover effect. Several participants described a dramatic benefit. Discomfort was minimal. There was no evidence that the MNS benefit persisted after stimulation ended. These results replicate the tic benefit from MNS but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain the benefit; alternatively, these data do not exclude a placebo effect.

Anticoagulation-Free Pediatric Extracorporeal Membrane Oxygenation: Single-Center Retrospective Study.

OBJECTIVES: To analyze hemorrhage and thrombosis data related to anticoagulation-free pediatric extracorporeal membrane oxygenation (ECMO). DESIGN: Retrospective cohort study. SETTINGS: High-volume ECMO single institution data. PATIENTS: Children (0-18 yr) supported with ECMO (>24 hr) with initial anticoagulation-free period of greater than or equal to 6 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Utilizing consensus American Thoracic Society definitions for hemorrhage and thrombosis on ECMO, we evaluated thrombosis and associated patient and ECMO characteristics during anticoagulation-free period. Thirty-five patients met inclusion criteria from 2018 to 2021 having a median age (interquartile range [IQR]) of 13.5 months (IQR, 3-91 mo), median ECMO duration of 135 hours (IQR, 64-217 hr), and 964 anticoagulation-free hours. Increased RBC transfusion needs were associated with longer anticoagulation-free periods ( p = 0.03). We identified 20 thrombotic events: only four during the anticoagulation-free period and occurring in three of 35 (8%) patients. Compared with those without thrombotic events, anticoagulation-free clotting events were associated with younger age (i.e., 0.3 mo [IQR, 0.2-0.3 mo] vs 22.9 mo [IQR, 3.6-112.9 mo]; p = 0.02), lower weight (2.7 kg [IQR, 2.7-3.25 kg] vs 13.2 kg [5.9-36.4 kg]; p = 0.006), support with lower median ECMO flow rate (0.5 kg [IQR, 0.45-0.55 kg] vs 1.25 kg [IQR, 0.65-2.5 kg]; p = 0.04), and longer anticoagulation-free ECMO duration (44.5 hr [IQR, 40-85 hr] vs 17.6 hr [IQR, 13-24.1]; p = 0.008). CONCLUSIONS: In selected high-risk-for-bleeding patients, our experience is that we can use ECMO in our center for limited periods without systemic anticoagulation, with lower frequency of patient or circuit thrombosis. Larger multicentered studies are required to assess weight, age, ECMO flow, and anticoagulation-free time limitations that are likely to pose risk for thrombotic events.

Peripheral nerve induction of inhibitory brain circuits to treat Tourette syndrome: A randomized crossover trial.

A prior study showed that rhythmic, but not arrhythmic, 12 Hz stimulation of the median nerve (MNS) entrained sensorimotor cortex EEG signal, and found that 10 Hz MNS improved tics in Tourette syndrome (TS). However, no control condition was tested and stimulation blocks lasted only 1 minute. We set out to replicate the TS results and to test whether tic improvement occurs by the proposed cortical entrainment mechanism. Thirty-two people with TS, age 15-64, completed two study visits with repeated MNS on and off blocks in random order, one visit for rhythmic and one for arrhythmic MNS. Subjects and staff were blind to order; a video rater was additionally blind to stimulation and to order of visits and blocks. Rhythmic MNS at 10 Hz improved tics. Both rhythmic and arrhythmic 12 Hz MNS improved tic frequency, intensity and urges without significant difference. Participant masking was effective and there was no carryover effect. Several participants described dramatic benefit. Discomfort was minimal. MNS benefit did not persist after the end of stimulation. These results replicate the tic benefit from MNS, but show that the EEG entrainment hypothesis cannot explain that benefit. Another electrophysiological mechanism may explain benefit; alternatively, these data do not exclude a placebo effect. Registration: ClinicalTrials.gov , NCT04731714 .

A pilot randomized controlled trial of a cognitive-behavioral therapy guided self-help mobile app for the post-acute treatment of anorexia nervosa: A registered report.

INTRODUCTION: Relapse following acute treatment for anorexia nervosa (AN) is common. Evidence suggests cognitive-behavioral therapy (CBT) may be useful in the post-acute period, but few patients have access to trained providers. mHealth technologies have potential to increase access to high-quality care for AN, including in the post-acute period. The aim of this study is to estimate the preliminary feasibility and effectiveness of a CBT-based mobile intervention plus treatment as usual (TAU), offered with and without an accompanying social networking feature. METHOD: In the current pilot randomized controlled trial, women with AN who have been discharged from acute treatment in the past 2 months (N = 90) will be randomly assigned to a CBT-based mobile intervention plus treatment as usual (TAU), a CBT-based mobile intervention including social networking plus TAU, or TAU alone. We will examine feasibility, acceptability, and preliminary effectiveness of the three conditions in terms of reducing eating disorder psychopathology, reducing frequency of eating disorder behaviors, achieving weight maintenance, reducing depression and suicidal ideation, and reducing clinical impairment. We will examine rehospitalization and full recovery rates in an exploratory fashion. We will also examine whether the mobile intervention and social networking feature change the proposed targets and whether changes in targets are associated with benefit, as well as conduct exploratory analyses to identify within-mobile intervention predictors and moderators of outcome. DISCUSSION: Ultimately, this research may lead to increased access to evidence-based treatment for individuals with AN and prevention of the extreme negative consequences that can result from this serious disorder. PUBLIC SIGNIFICANCE: Relapse after acute treatment for anorexia nervosa is common, and few patients have access to trained providers to support them following acute care. This study will pilot a coached mobile app, including a social networking component, for this population. If ultimately successful, our approach could greatly increase access to evidence-based treatment for individuals with anorexia nervosa and ultimately prevent the extreme negative consequences that can result from this serious disorder.

Quantitative and Qualitative Changes in Peripheral Chemoreceptor Activity in Preterm Infants.

Rationale: Preterm infants are at risk for ventilatory control instability that may be due to aberrant peripheral chemoreceptor activity. Although term infants have increasing peripheral chemoreceptor contribution to overall ventilatory drive with increasing postnatal age, how peripheral chemoreceptor contribution changes in preterm infants with increasing postmenstrual age is not known. Objectives: To evaluate peripheral chemoreceptor activity between 32 and 52 weeks postmenstrual age in preterm infants, using both quantitative and qualitative measures. Methods: Fifty-five infants born between 24 weeks, 0 days gestation and 28 weeks, 6 days gestation underwent hyperoxic testing at one to four time points between 32 and 52 weeks postmenstrual age. Quantitative [Formula: see text] decreases were calculated, and qualitative responses were categorized as apnea, continued breathing with a clear reduction in [Formula: see text], sigh breaths, and no response. Measurements and Main Results: A total of 280 hyperoxic tests were analyzed (2.2 ± 0.3 tests per infant at each time point). Mean peripheral chemoreceptor contribution to ventilatory drive was 85.2 ± 20.0% at 32 weeks and 64.1 ± 22.0% at 52 weeks. Apneic responses were more frequent at earlier postmenstrual ages. Conclusions: Among preterm infants, the peripheral chemoreceptor contribution to ventilatory drive was greater at earlier postmenstrual ages. Apnea was a frequent response to hyperoxic testing at earlier postmenstrual ages, suggesting high peripheral chemoreceptor activity. A clearer description of how peripheral chemoreceptor activity changes over time in preterm infants may help explain how ventilatory control instability contributes to apnea and sleep-disordered breathing later in childhood. Clinical trial registered with www.clinicaltrials.gov (NCT03464396).

An Assessment of Pediatric Residency Applicant Perceptions of "Fit" During the Virtual Interview Era.

PURPOSE: Residency recruitment events and interviews are widely considered an integral component of the residency match experience. Due to the COVID-19 pandemic, residency recruitment and interviewing throughout the 2020-2021 academic year were performed virtually, which created challenges for applicants' ability to discern "fit" to a program. Given this change, it is reasonable to suspect that applicants would be less able to discern program fit. Therefore, this study evaluated how virtual interviews impacted pediatric residency applicants' ability to assess factors contributing to fit and subsequently how applicants assessed their self-perceived fit to their top-ranked programs. METHODS: An online, anonymous survey was distributed to all residency applicants who applied to any specialty at our large academic institution. The survey utilized a 5-point Likert-type scale to evaluate qualities of fit as well as the applicants' self-perceived ability to assess these qualities through a virtual platform. RESULTS: 1,840 surveys were distributed, of which 473 residency applicants responded (25.7% response rate). Among these responses, 81 were pediatric applicants (27.6%). Factors deemed most important in determining fit included how well the residents get along with one another (98.8%), how much the program appeared to care about its trainees (97.5%), and how satisfied residents were with their program (97.5%). Qualities deemed most difficult for applicants to discern included the quality of facilities (18.6%), patient diversity (29.4%), and how well the residents got along with one another (30.2%). When compared to all other residency applicants, pediatric applicants placed more value on whether a program was family-friendly (p = 0.015), the quality of the facilities (p = 0.009), and the on-call system (p = 0.038). CONCLUSION: This study highlights factors that influence pediatric applicants' perception of fit into a program. Unfortunately, many factors deemed most important for pediatric applicants were also among the most difficult to assess virtually. These include resident camaraderie, whether a program cares about its residents, and overall resident satisfaction. Taken together, these findings and the recommendations presented should be considered by all residency program leaders to ensure the successful recruitment of a pediatric residency class.

National Trends in Pediatric Metabolic and Bariatric Surgery: 2010-2017.

BACKGROUND: The childhood obesity epidemic has grown exponentially and is known to disproportionately affect minority groups. Successful treatment of this complex health issue requires a multidisciplinary approach including metabolic and bariatric surgery (MBS) for qualifying pediatric patients. This study examines current national trends in pediatric bariatric surgery from 2010 to 2017 using the National Inpatient Sample. METHODS: This study analyzed MBS among pediatric patients <19 years old using weighted discharge data from 2010 to 2017. The primary outcome was national procedure rates. Secondary analyses included procedure type, demographics, BMI, comorbidities, length of stay, and complication rates. RESULTS: From 2010 to 2017, annual bariatric procedure rates increased from 2.29 to 4.62 per 100 000 (P < .001). Laparoscopic sleeve gastrectomy outpaced Roux-en-Y gastric bypass and laparoscopic adjustable gastric band over time (0.31-3.99 per 100 000, P < .0001). The mean age was stable over time 18.10-17.96 (P = .78). The cohort was primarily female (76.5% to 75.4%), white (54.0% to 45.0%), and privately-insured (59.9% to 53.4%). Preoperative BMI increased from 2010 to 2017 (P < .001), whereas number of obesity-related comorbidities was stable (P > .05). Length of stay was <2 days (2.02-1.75, P = .04) and in-hospital complication rates were low (7.2% to 6.45%, P = .88). CONCLUSIONS: Pediatric MBS is underutilized nationally with disproportionately lower rates among minority groups. Despite incremental progress, further investigation into the racial and social determinants that limit access to pediatric weight loss surgery is critical.

Uncertainty analysis of chest X-ray lung height measurements and size matching for lung transplantation.

Background: Errors in measuring chest X-ray (CXR) lung heights could contribute to the occurrence of size-mismatched lung transplant procedures. Methods: We first used Bland-Altman analysis for repeated measures to evaluate contributors to measurement error of chest X-ray lung height. We then applied error propagation theory to assess the impact of measurement error on size matching for lung transplantation. Results: A total 387 chest X-rays from twenty-five donors and twenty-five recipients were measured by two raters. Individual standard deviation for lung height differences were independent of age, sex, donor vs. recipient, diagnostic group and race/ethnicity and all were pooled for analysis. Bias between raters was 0.27 cm (±0.03) and 0.22 cm (±0.06) for the right and left lung respectively. Within subject variability was the biggest contributor to error in measurement, 2.76 cm (±0.06) and 2.78 cm (±0.2) for the right and left lung height. A height difference of 4.4 cm or more (95% CI: ±4.2, ±4.6 cm) between the donor and the recipient right lung height has to be accepted to ensure matching for at least 95% of patients with the same true lung height. This difference decreases to ±1.1 cm (95% CI: ±0.9, ±1.3 cm) when the average from all available chest X-rays is used. The probability of matching a donor and a recipient decreases with increasing true lung height difference. Conclusions: Individual chest X-ray lung heights are imprecise for the purpose of size matching in lung transplantation. Averaging chest X-rays lung heights reduced uncertainty.

SARS-CoV-2 mRNA Vaccination Causes Prolonged Increased Cortical Thickening and Vascularity in Ipsilateral Axillary Lymph Nodes.

OBJECTIVES: To describe the serial grey-scale and color Doppler appearance of ipsilateral axillary lymphadenopathy in response to the Pfizer-BioNTech Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) messenger RNA (mRNA) vaccine over 24 to 28 weeks. METHODS: The data for this study were collected during an observational study to determine whether mRNA vaccination induced a germinal center B cell reaction in blood and draining axillary lymph nodes. The current study evaluated the serial color Doppler and grey-scale sonographic appearance of these lymph nodes. Ten participants who each underwent 6 sonograms and FNAs over 24 to 28 weeks were included in the study. A total of 11 lateral lymph nodes were identified. Cortical thickness was measured and absence or presence of color Doppler flow in the hilum and lymph node cortex was graded (scale: 0-2). RESULTS: Eleven lateral axillary lymph nodes were biopsied over 24 to 28 weeks. Mean thickness varied through time (P < .001) and was greater weeks 2 to 7 compared to weeks 24 to 28 (mean differences of 2.6 to 1.3; P < .006), but weeks 14 to 17 mean thickness was not different from weeks 24 to 28 (0.57; P = .15). Cortical vascularity was increased in all 11 lymph nodes by week 5. Mean vascularity varied through time (P < .001) and was greater weeks 2 to 14 compared to weeks 24 to 28; mean differences ranged from 1.7 to 0.83 (P < .001). CONCLUSIONS: Serial grey-scale and color Doppler appearance of ipsilateral axillary lymph nodes after mRNA vaccination manifest as increased and prolonged cortical thickening and vascularity that diminishes and approaches normal by 24 to 28 weeks.

Poor Reliability of Common Measures of Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation.

Anticoagulation management in pediatric extracorporeal membrane oxygenation (ECMO) is challenging with multiple laboratory measures utilized across institutions without consensus guidelines. These include partial thromboplastin time (PTT), thromboelastography (TEG), and antifactor Xa (aXa). We aimed to evaluate the consistency of TEG R-time, PTT, and aXa correlation to bivalirudin and heparin dosing. We conducted a single-center restrospective review of pediatric ECMO cases from 2018 to 2020 anticoagulated with bivalirudin or heparin. We collected up to 14 serial simultaneous TEG R-time, PTT, and aXa measurements over a 7 day ECMO course with corresponding bivalirudin or heparin dosing. We analyzed the correlation between bivalirudin, heparin, and the three measurements of anticoagulation. A total of 67 ECMO runs, 32 bivalirudin, and 35 heparin, and more than 1,500 laboratory values, of which >80% simultaneous, were analyzed. When assessing correlations at the individual patient level, there was no consistent correlation between dosing and at least one laboratory parameter in the majority of patients. Furthermore, 44% of the bivalirudin cohort and 37% of the heparin cohort exhibited no correlation with any parameters. There were statistically significant correlations only between bivalirudin and heparin dosing and the sum total of the different laboratory tests. These inconsistencies highlight the importance of multimodality testing of anticoagulation in the management of pediatric ECMO anticoagulation and cannot be relied on in isolation from bedside clinical judgment.

Effect of elexacaftor-tezacaftor-ivacaftor on body weight and metabolic parameters in adults with cystic fibrosis.

BACKGROUND: Though weight gain has been reported in some clinical trials of CFTR modulators, the effect of elexacaftor-tezacaftor-ivacaftor on body weight, body mass index (BMI), blood pressure, lipids and glycemic control in the real-world setting remains incompletely described. METHODS: We performed a single-center, retrospective, observational analysis of the effect of elexacaftor-tezacaftor-ivacaftor on body weight and cardiometabolic parameters in 134 adult CF patients of the Washington University Adult Cystic Fibrosis Center. Body weight, BMI, and blood pressure were extracted from outpatient clinic visits for the year preceding and the period following the initiation of elexacaftor-tezacaftor-ivacaftor. Other metabolic parameters were extracted at baseline and at latest available follow-up. RESULTS: A mean of 12.2 months of follow-up data was available for analysis. The mean rate of change in BMI was 1.47 kg/m2/yr (95% CI, 1.08 to 1.87) greater after initiation of elexacaftor-tezacaftor-ivacaftor. Significant increases in blood pressure were observed. In those without CFRD, random blood glucose and hemoglobin A1c were decreased after elexacaftor-tezacaftor-ivacaftor initiation. In those with CFRD, elexacaftor-tezacaftor-ivacaftor increased serum total cholesterol, HDL-cholesterol, and LDL-cholesterol. CONCLUSIONS: In this single-center, retrospective, observational study of 134 adults with CF, initiation of elexacaftor-tezacaftor-ivacaftor was associated with increases in BMI at a mean follow up of 12.2 months. Changes in other cardiometabolic risk factors were also observed. Widespread use of elexacaftor-tezacaftor-ivacaftor may be expected to increase the incidence of overnutrition in the CF population.

Management and Microbiology of Perforated Appendicitis in Pediatric Patients: A 5-Year Retrospective Study.

INTRODUCTION: This study aims to assess the current epidemiology and microbiology of perforated appendicitis, how antibiotic choice and duration correlate with meaningful clinical outcomes, and whether serial white blood cell (WBC) counts provide clinical value. METHODS: Five-year retrospective cohort study, 2015-2019, among 333 consecutive children, ages 0-18 years, treated at St. Louis Children's Hospital for perforated appendicitis. Main outcomes included length of stay (LOS), postoperative abscess formation, and readmission. Statistical analysis was performed with uni- and multi-variate analyses. RESULTS: Intra-abdominal cultures most commonly grew Bacteroides fragilis (52%) and Escherichia coli (50%). Patients who initially received broad-spectrum antibiotics (meropenem, piperacillin-tazobactam, fourth-generation cephalosporins) for perforated appendicitis had greater rates of postoperative abscess formation (25% vs. 12%, p < 0.01) and LOS (7.0 vs. 5.7 days, p < 0.01). Similarly, antibiotics at time of discharge were associated with greater postoperative abscess formation (22% vs. 9%, p < 0.01) and LOS (6.4 vs. 5.6 days, p = 0.02). However, discharge with strictly oral antibiotics was not correlated with greater LOS, postoperative abscess formation, or readmission rates compared to discharge without antibiotics. Serial WBC counts had no predictive value for LOS, postoperative abscess formation, or readmission. CONCLUSIONS: Bacteroides fragilis and E. coli were the most common intra-abdominal microbes for perforated appendicitis among our cohort. In non-critically ill children, the routine use of broad-spectrum antibiotics or continuation of antibiotics beyond discharge was not correlated with improved clinical outcomes. Additionally, WBC counts were not correlated with meaningful clinical outcomes.

Context-Responsive Anticoagulation Reduces Complications in Pediatric Extracorporeal Membrane Oxygenation.

Purpose: We sought to determine the impact of a comprehensive, context-responsive anticoagulation and transfusion guideline on bleeding and thrombotic complication rates and blood product utilization during extracorporeal membrane oxygenation (ECMO). Design: Single-center, observational pre- and post-implementation cohort study. Setting: Academic pediatric hospital. Patients: Patients in the PICU, CICU, and NICU receiving ECMO support. Interventions: Program-wide implementation of a context-responsive anticoagulation and transfusion guideline. Measurements: Pre-implementation subjects consisted of all patients receiving ECMO between January 1 and December 31, 2012, and underwent retrospective chart review. Post-implementation subjects consisted of all ECMO patients between September 1, 2013, and December 31, 2014, and underwent prospective data collection. Data collection included standard demographic and admission data, ECMO technical specifications, non-ECMO therapies, coagulation parameters, and blood product administration. A novel grading scale was used to define hemorrhagic complications (major, intermediate, and minor) and major thromboembolic complications. Main Results: Seventy-six ECMO patients were identified: 31 during the pre-implementation period and 45 in the post-implementation period. The overall observed mortality was 33% with no difference between groups. Compared to pre-implementation, the post-implementation group experienced fewer major hemorrhagic and major thrombotic complications and less severe hemorrhagic complications and received less RBC transfusion volume per kg. Conclusions: Use of a context-responsive anticoagulation and transfusion guideline was associated with a reduction in hemorrhagic and thrombotic complications and reduced RBC transfusion requirements. Further evaluation of guideline content, compliance, performance, and sustainability is needed.

The association between body composition, leptin levels and glucose dysregulation in youth with cystic fibrosis.

BACKGROUND: Optimization of nutritional status is recommended in patients with cystic fibrosis (CF) given the association between lower body mass index (BMI) and poor clinical outcomes. However, higher BMI and body fat correlate with glucose impairment and higher leptin levels in the general population. Differences in body composition and leptin levels between the categories of glucose tolerance were assessed in youth with CF and healthy controls. METHODS: In a cross-sectional study, 59 adolescents and young adults with CF and 15 healthy controls matched by age and gender, underwent body composition analysis using dual energy X-ray absorptiometry (DXA) and a 2-hour oral glucose tolerance test (OGTT). Measures of insulin sensitivity, ß-cell insulin secretion and fasting leptin levels were obtained. RESULTS: Of the participants with CF, 62% were classified as abnormal glucose tolerant and 22% with cystic fibrosis related diabetes (CFRD). Patients with CFRD had a lower fat mass index (FMI) z-score, wt z-score and leptin levels compared to the control group (-1.86 vs. - 0.59, p=0.01; -1.86 vs 0.44, p=<0.001 and 7.9 vs vs. 27.7 µg/L, p=0.01). Leptin correlated positively with FMI z-score, BMI, weight z-score and indices of insulin secretion. FMI z-score correlated positively with higher insulin resistance (HOMA-IR), and lower insulin sensitivity (Matsuda index) (r=0.31; p =0.01 and r=-0.29; p=0.02, respectively) in the CF group. CONCLUSIONS: This study shows that despite new therapeutic strategies, youth with CF have lower body fat, weight z-score and leptin levels, particularly in subjects with early onset CFRD.