Assessment of rare bleeding disorders in adolescents with heavy menstrual bleeding.

INTRODUCTION: There are a significant number of patients with mucocutaneous bleeding, specifically heavy menstrual bleeding (HMB), who do not have a diagnosed bleeding disorder. These patients receive nontargeted interventions and may have suboptimal treatments. Functional assays, particularly for fibrinolytic and rare platelet function defects, are not robust and not readily available. AIM: We aimed to prospectively evaluate the prevalence of genetic defects associated with rare bleeding disorders and describe alterations of coagulation and fibrinolysis in a cohort of adolescents with HMB. METHODS: We performed a prospective observational cohort study of patients with HMB and unexplained bleeding. The study utilized a next generation sequencing panel and investigational global assays of coagulation and fibrinolysis. Additionally, specific functional assays were performed to help characterize novel variants that were identified. RESULTS: In 10 of the 17 patients (∼59%), genetic variants were identified on molecular testing. Thrombin generation by calibrated thromboelastography was not significantly altered in this patient population. The clot formation and lysis assay showed a trend towards increased fibrinolysis with rapid phase of decline in 23% of the patients. Further corresponding functional assays and study population are described. CONCLUSION: Our study describes a unique correlative model in a homogenous cohort of patients with HMB and unexplained bleeding which may inform future diagnostic algorithms, genotype-phenotype correlations as well as aid in specific targeted treatment approaches. Larger future studies may inform risk stratification of patients and improve health related outcomes in patients with HMB.

Intramedullary spinal cord tumors in pediatric patients presenting later with brain lesions: case series and systematic review of the literature.

PURPOSE: Intramedullary spinal cord tumors are an uncommon pathology in adults and children. Most descriptive studies of intramedullary spinal cord tumors have not focused on a possible association with future brain lesions. To the best of our knowledge, few reports describe this potential relationship. This is one of the most extensive case series of secondary brain lesions of intramedullary spinal cord tumors in the pediatric population. METHODS: Retrospective chart review was performed on pediatric patients (21 years old and younger) who underwent resection of an intramedullary spinal cord tumor at two tertiary care hospitals from 2001 to 2020. Patients previously treated or diagnosed with spinal cord tumor, and subsequent development of intracranial manifestation of the same or different tumor, were included. Data regarding epidemiology, surgical intervention, and clinical and follow-up course were gathered. Data analysis was performed according to a standardized clinical protocol with a literature review. RESULT: More than 500 patients underwent intradural spinal tumor resection surgeries at participating hospitals from 2001 to 2020. After excluding adult patients (older than 21 years old) and those with extramedullary lesions, 103 pediatric patients were identified who underwent resection of an intramedullary spinal cord tumor. Four underwent resection of an intermedullary tumor and later in their follow-up course developed a secondary intracranial neoplasm. In every case, the secondary neoplasm had the same pathology as the intramedullary tumor. Three of the patients had tumors at the cervico-thoracic junction, and one patient had a high cervical tumor. These patients had a negative primary workup for any metastatic disease at the time of the presentation or diagnosis. Complete and near complete resection was performed in three patients and subtotal in one patient. CONCLUSION: Secondary brain tumors disseminated after initial spinal cord tumor are extremely rare. This study aims to allow specialists to better understand these pathologies and treat these rare tumors with more certainty and better expectations of unusual associated lesions and conditions.

Interaction of hydrocortisone and illness severity on head growth in cohort of ELBW infants.

BACKGROUND: Extremely low birth weight (ELBW) infants comprise a fragile population at risk for neurodevelopmental disabilities (NDD). Systemic steroids were previously associated with NDD, but more recent studies suggest hydrocortisone (HCT) may improve survival without increasing NDD. However, the effects of HCT on head growth adjusted for illness severity during NICU hospitalization are unknown. Thus, we hypothesize that HCT will protect head growth, accounting for illness severity using a modified neonatal Sequential Organ Failure Assessment (M-nSOFA) score. METHODS: We conducted a retrospective study that included infants born at 23-29 weeks gestational age (GA) and < 1000 g. Our study included 73 infants, 41% of whom received HCT. RESULTS: We found negative correlations between growth parameters and age, similar between HCT and control patients. HCT-exposed infants had lower GA but similar normalized birth weights; HCT-exposed infants also had higher illness severity and longer lengths of hospital stay. We found an interaction between HCT exposure and illness severity on head growth, such that infants exposed to HCT had better head growth compared to those not exposed to HCT when adjusted for illness severity. CONCLUSION: These findings emphasize the importance of considering patient illness severity and suggest that HCT use may offer additional benefits not previously considered. IMPACT: This is the first study to assess the relationship between head growth and illness severity in extremely preterm infants with extremely low birth weights during their initial NICU hospitalization. Infants exposed to hydrocortisone (HCT) were overall more ill than those not exposed, yet HCT exposed infants had better preserved head growth relative to illness severity. Better understanding of the effects of HCT exposure on this vulnerable population will help guide more informed decisions on the relative risks and benefits for HCT use.

Dexamethasone for Pediatric Critical Asthma: A Multicenter Descriptive Study.

BACKGROUND: Systemic corticosteroids are vital to critical asthma management. While intravenous methylprednisolone is routinely used in the pediatric intensive care unit (PICU) setting, recent data supports dexamethasone as an alternative. Using the Pediatric Health Information System (PHIS) registry, we assessed trends and variation in corticosteroid prescribing among children hospitalized for critical asthma. METHODS: We performed a multicenter retrospective cohort study using PHIS data among children 3-17 years of age admitted for critical asthma from 2011 through 2019. Primary outcomes were corticosteroid prescribing rates by year and participating sites. Exploratory outcomes were corticosteroid-related adverse effects, rates of adjunctive pharmaceutical and respiratory interventions, mortality and length of stay. RESULTS: Of the 49 children's hospitals assessed, 26 907 encounters were included for study. Mean dexamethasone exposure rates were 18.1 ± 2.4% where 2.4 ± 1.2% represented dexamethasone-alone prescribing. Dexamethasone alone prescribing exhibited a linear trend (annual increase of 0.5 ± 0.1% annually R2 = 0.845) without correlation to cumulative site critical asthma admission rates. Compared to encounters prescribed solely methylprednisolone or a combination of dexamethasone and methylprednisolone, subjects provided dexamethasone alone had reduced asthma severity indices, length of stay, and exposure rates to adjunctive asthma interventions. Adverse events were rare and the dexamethasone-alone group less frequently experienced gastritis and hyperglycemia. CONCLUSIONS: In this multicenter retrospective study from 49 children's hospitals, dexamethasone prescribing rates appear increasing for pediatric critical asthma. Observed variability in corticosteroid prescribing implies a continued need for controlled prospective comparative analyses to define ideal corticosteroid regimens for pediatric critical asthma.

Suicide, Stimulants, and Selective Serotonin Reuptake Inhibitors: A Retrospective Chart Review.

Background: Previous studies suggest that selective serotonin reuptake inhibitors (SSRIs) may increase the risk of suicide among children and youth, although the association between suicide risk and the combination of SSRIs with other medication such as stimulants in this population remains unclear. This study explored whether the combination of SSRIs with stimulants influenced suicide risk. Methods: A retrospective cohort study was conducted at a single children's hospital campus-based ambulatory psychiatric clinic between September 1, 2017, and September 30, 2020. Subjects were 6-21 years of age and prescribed either stimulants or stimulants and SSRIs only. The primary outcome was suicidal thoughts and behaviors (STB), defined by documented suicidal thoughts, plans, or behaviors. Firth logistic regression evaluated associations between medication class and STB. Results: Among 349 patients, the prevalence of STB was 5.7% (n = 20). In unadjusted model, patients prescribed SSRIs and stimulants had a 2.9-fold increase of STB compared to patients prescribed stimulants only, along with increasing age, male sex, and the diagnoses of anxiety and/or depression. In the final model adjusted for each of these factors, the observed association of medication regiment with STB was attenuated (odds ratio [OR]: 1.3, confidence interval [CI]: 0.3-4.9, p = 0.7). The magnitude of the adjusted association between depressive diagnosis and STB was notable (OR: 3.6, CI: 1.0-12.6, p = 0.049). Conclusions: Among patients followed in a children's hospital-based ambulatory psychiatric clinic, a combination medication regimen of SSRIs and stimulants after adjusting for genetic sex, age, anxiety diagnosis, and depression diagnosis, the observed association between STB and combination stimulant and SSRI treatment was attenuated. This finding suggests that other factors, including depression, may have contributed to the association between SSRI treatment and STB. Larger, prospective studies of the relationship between combination pharmacotherapy and suicide risk are warranted to guide clinical/pharmacological decision making and to better clarify these relationships.

Hemorrhagic Disease of the Newborn: A Case Series Illustrating Preventable Harm.

Newborns are susceptible to postnatal Vitamin K deficiencies from limited placental transfer, gastrointestinal absorption, and bioavailability in breast milk and formula preparations. For over 50 years, the American Academy of Pediatrics has recommended prophylactic vitamin K to prevent hemorrhagic disease in newborns. Yet, public skepticism contributes to increasing refusal rates. We present three cases of vitamin K-dependent bleeding following parental refusal of postnatal prophylaxis. Two patients experienced intracranial hemorrhage with resultant neurological devastation and mortality, respectively. The third child presented with symptomatic hematuria. Perinatal providers must partner with families and advocate vitamin K prophylaxis to limit unnecessary morbidity and mortality.

Dexamethasone versus methylprednisolone for critical asthma: A single center, open-label, parallel-group clinical trial.

BACKGROUND: Evidence for the use of dexamethasone for pediatric critical asthma is limited. We sought to compare the clinical efficacy and safety of dexamethasone versus methylprednisolone among children hospitalized in the pediatric intensive care unit (PICU) for critical asthma. METHODS: A prospective, single center, open-label, two-arm, parallel-group, nonrandomized trial among children ages 5-17 years hospitalized within the PICU from April 2019 to December 2021 for critical asthma consented to receive methylprednisolone (standard care) or dexamethasone (intervention) at a 2:1 allocation ratio, respectively. The intervention arm received intravenous dexamethasone 0.25 mg/kg/dose (max: 15 mg/dose) every 6 h for 48 h and the standard care arm intravenous methylprednisolone 1 mg/kg/dose every 6 h (max dose: 60 mg/dose) for 5 days. Study endpoints were clinical efficacy (i.e., length of stay [LOS], continuous albuterol duration, and a composite of adjunctive asthma interventions) and safety (i.e., corticosteroid-related adverse events). RESULTS: Ninety-two participants were analyzed of whom 31 were allocated to the intervention arm and 61 the standard care arm. No differences in demographics, clinical characteristics, or acute/chronic asthma severity indices were observed. Regarding efficacy and safety endpoints, no differences in hospital LOS, continuous albuterol duration, adjunctive asthma intervention rates, or corticosteroid-related adverse events were noted. Compared to the intervention arm, participants in the standard care arm more frequently were prescribed corticosteroids at discharge (72% vs. 13%, p < 0.001). CONCLUSIONS: Among children hospitalized for critical asthma, dexamethasone appears safe and warrants further investigation to fully assess clinical efficacy and potential advantages over commonly applied agents such as methylprednisolone.

Tiny Bodies, Big Needs: Prospective Biobanking of Neonatal Clinical Remnant Samples.

Repurposing biological samples collected for required diagnostic purposes into suitable biobanking projects is a particularly useful method for enabling research in vulnerable populations. This approach is especially appropriate for the neonate in the neonatal intensive care unit (NICU), where blood volume reductions can quickly increase beyond minimal risk for adverse events, such as iatrogenic anemia, and proxy consent provided by parents or guardians is required. The method described in this study provides a framework to prospectively collect and store blood-derived clinical samples after all clinical and regulatory requirements are fulfilled. The consent approach incorporated a 30-day window to allow parents and guardians ample consideration time with follow-up involvement with NICU embedded study team members. The study enrolled 875 participants over a 3-year period. This established a critically needed biobank to support investigator-initiated research with explicit study aims requiring samples at defined day of life frequencies within the NICU and created a normative control reference bank for case comparisons for premature and full-term neonates with brain injury.

Postoperative Feeding Guidelines Improve Outcomes in Surgical Infants.

BACKGROUND: Early introduction of enteral nutrition (EN) in postoperative infants improves intestinal adaptation, reducing the risk of intestinal failure-associated liver disease (IFALD). Our objective was to determine whether guideline use reduces feeding variability and improves outcomes in the neonatal intensive care unit (NICU). METHODS: In a cohort study, surgical infants at risk for IFALD were evaluated pre and post implementation of feeding guidelines at 2 NICUs. A total of 167 guideline infants (2013-2018) were compared with 242 historical controls (2007-2013). Adherence was measured with timing and volume of initial postoperative feed. Primary outcomes were IFALD incidence and time to reach 50% and 100% of energy from EN. Secondary outcomes were parenteral nutrition (PN) days, postoperative necrotizing enterocolitis (NEC), central line-associated bloodstream infection (CLABSI), and length of stay (LOS). RESULTS: Moderate IFALD decreased from 32% to 20% (P = .005) in the guideline group. Time to achieve 50% and 100% energy from EN was decreased from medians of 8 to 5 and 28 to 21 days, respectively (P < .001). There was an overall decrease in PN use from 41 to 29 days (P = .002), CLABSI incidence from 25% to 5% (P < .001), and LOS from 70 to 53 days (P = .030). Once stratified by diagnosis, infants with NEC showed greatest improvement and reduction in IFALD from 67% to 42% (P = .045). With no difference in postoperative NEC (P = .464). CONCLUSION: Early standardized postoperative EN guidelines in intestinal-surgery infants was associated with improved outcomes, including faster achievement of feeding goals and reduced IFALD severity, especially in infants with NEC.

Risk factors for pediatric cerebral sinovenous thrombosis: A case-control study with case validation.

INTRODUCTION: Cerebral sinovenous thrombosis (CSVT) represents the second most common type of venous thromboembolism (VTE) in children. Current literature includes limited evidence on risk factors for CSVT, particularly in the pediatric population. We sought to determine risk factors for CSVT in pediatric patients through a single-institutional case-control study. In addition, we evaluated thrombophilias, treatments and outcomes in CSVT among cases. METHODS: A case-control study was performed at Johns Hopkins All Children's Hospital on patients admitted from March 31, 2006 through April 1, 2018. Cases were identified using diagnostic codes and confirmed based on electronic health record (EHR) and neuroimaging review. Controls were matched in a 2:1 fashion accounting for the month and year of admission. RESULTS: A total of 60 CSVT cases and 120 controls were identified. Median (range) age was 4.8 years (0-21.3 years) for cases and 5.6 years (0-20.0 years) for controls. Factors putatively associated with CSVT in unadjusted analyses were: corticosteroid use, presence of a central venous catheter, mechanical ventilation, systemic infection, head/neck infection, head/neck trauma, and chronic inflammatory disease. In the multivariable model, head/neck infection (OR: 13.8, 95% CI: 4.87-38.7; P < 0.01), head/neck trauma (OR: 12.7, 95% CI: 2.88-56.2; P < 0.01), and mechanical ventilation (OR: 9.32, 95% CI: 2.35-36.9; P = 0.01) remained independent, statistically-significant risk factors. 61% of patients were subacutely treated with anticoagulants and of those, only two developed relevant bleeding after initiation of therapy. CONCLUSIONS: This single-institutional case-control study reveals that head/neck infection, head/neck trauma, and mechanical ventilation are independent risk factors for pediatric CSVT. These findings will be further investigated via a cooperative registry of pediatric hospital-acquired VTE, by which a risk model for pediatric CSVT will be developed and validated, in order to inform future preventive strategies in at-risk pediatric patients.

Benefits of Thoracic Epidural Analgesia in Patients Undergoing an Open Posterior Component Separation for Abdominal Herniorrhaphy.

An open posterior component separation (PCS) is a commonly utilized surgical approach for repair of complex abdominal wall defects and hernias. Although this approach may improve surgical outcomes, significant postoperative pain can be expected given the required laparotomy and extensive abdominal wall manipulation. Both systemic opioids and thoracic epidural analgesia (TEA) are viable postoperative analgesic options, and both are commonly utilized. Although the benefits of TEA have been investigated following a variety of surgeries, there is a paucity of literature related to its efficacy for this particular surgery. The aim of this study was to evaluate the benefits of TEA following open PCS under the hypothesis that the incorporation of TEA into the postoperative analgesic regimen would hasten bowel recovery. Patients who previously underwent an open PCS were identified through an electronic medical record query. A retrospective chart review was then performed, and patients who had TEA, either alone or combined with systemic opioids, were compared with patients who had only systemic opioids. The primary end point was a comparison of the postoperative day (POD) on which a full diet was started. Secondarily, time to liquid diet, postsurgical length of stay (LOS), intensive care unit (ICU) admission rate, ICU LOS, and the rates of several postoperative adverse events were compared. A post hoc analysis was also performed, using the same end points, to compare the subgroup of TEA patients who avoided systemic opioids with all patients who received systemic opioids, whether alone or combined with TEA. One hundred and one patients were ultimately included for analysis. Time to full diet was not significantly different between patients who had TEA, either with or without systemic opioids, and those who received only systemic opioids (TEA 2.6 ± 1.7 vs. systemic opioids 3.1 ± 2.1 [mean POD ± SD], P = .21). Additionally, no statistically significant differences were found for any secondary outcome. In the post hoc analysis, the subgroup of TEA patients who avoided systemic opioids had a significantly faster time to bowel recovery when compared with all patients who received systemic opioids (2.2 ± 1.0 vs. 3.2 ± 2.2, P = .0033). This subgroup also had a significantly shorter time to liquid diet and a decreased postoperative LOS. In conclusion, for patients undergoing an open PCS, the inclusion of TEA in the postoperative analgesic regimen did not by itself hasten the return of bowel function. However, when TEA was utilized and systemic opioids were avoided, bowel recovery occurred significantly sooner and resulted in a shortened hospital LOS.