Audiological Outcomes of Weekly vs. Triweekly Cisplatin in Head and Neck Cancer with Cochlear-Sparing Intensity-Modulated Radiation Therapy.

Cisplatin, one of the most ototoxic anti-neoplastic agents, causes permanent hearing loss in up to 90% of patients. We assessed ototoxicity rates and prospectively collected audiologic outcomes of patients receiving low-dose or high-dose cisplatin with concurrent cochlear-sparing intensity-modulated radiation therapy (IMRT). Patients with head and neck squamous cell carcinoma (HNSCC) receiving definitive or adjuvant cisplatin-based chemoradiotherapy (CRT) were analyzed. Cisplatin was administered either in low doses weekly (40 mg/m2) for up to seven doses or in high doses triweekly (100 mg/m2) for up to three doses. Cochlear-sparing IMRT was delivered in all cases. Audiologic data were prospectively collected before, during, and after treatment completion. The primary endpoint was a hearing change grade of ≥3 after CRT completion. Of the 96 HNSCC patients evaluated, 69 received weekly cisplatin and 58 received definitive CRT. Of patients receiving weekly cisplatin, 13% developed ≥G3 ototoxicity vs. 56% of patients who received triweekly cisplatin (p < 0.001). In multivariable modeling, the cisplatin dose schedule remained significant (OR: 8.4, 95%CI: 2.8-27.8, p < 0.001) for risk of severe irreversible ototoxicity. Triweekly cisplatin CRT significantly increased the ≥G3 severe irreversible ototoxicity risk compared to low-dose weekly cisplatin, irrespective of the cumulative cisplatin dose, even with the use of cochlear-sparing IMRT. No significant difference in oncologic outcomes was observed between the two schedules.

The First 100 Seconds of Sleep of rEEGs Can Be a Reliable Scoring Method for D/EE-SWAS.

PURPOSE: Developmental/epileptic encephalopathy with spike wave activation with sleep, formerly known as electrical status epilepticus in sleep, is an electrographic pattern in which the interictal epileptiform activity is augmented by transition to sleep. Recent studies demonstrate the utility of the first 100 seconds of sleep of long-term monitoring (LTM) as a scoring method for electrical status epilepticus in sleep. Our aim was to measure the reliability of the spike-wave index (SWI) of the first 100 seconds of sleep of routine EEG (rEEG) as a tool for diagnosis of developmental/epileptic encephalopathy with spike wave activation with sleep. METHODS: Approximately three hundred forty LTMs were reviewed, and 25 studies from 25 unique patients had comparable rEEGs. Two neurophysiologists calculated the SWI of the first 100 seconds of spontaneous stage II non-random eye movement sleep, the first 5-minute bin of sleep, and three separate 5-minute bins throughout sleep in LTM. This was compared to the SWI of the first 100 seconds of sleep in rEEG. Agreement was analyzed using Lin's concordance correlation coefficient (CCC). RESULTS: Using 50% as a diagnostic cut-off, we observed moderate agreement between the SWI of the first 100 seconds of sleep of rEEG and three bin LTM (CCC = 0.94, 95% CI: 0.88-0.97). Agreement was slightly higher for the comparison to first bin LTM SWI (CCC = 0.96, 95% CI: 0.92-0.98) and first 100 seconds LTM SWI (CCC = 0.96, 95% CI: 0.92-0.98). CONCLUSIONS: This study demonstrates the first 100 seconds of sleep of rEEG technique as a time efficient diagnostic tool for patients with concern for developmental/epileptic encephalopathy with spike wave activation with sleep.

Disease Control and Toxicity Outcomes after Stereotactic Ablative Radiation Therapy for Recurrent and/or Metastatic Cancers in Young-Adult and Pediatric Patients.

BACKGROUND: Pediatric patients with metastatic and/or recurrent solid tumors have poor survival outcomes despite standard-of-care systemic therapy. Stereotactic ablative radiation therapy (SABR) may improve tumor control. We report the outcomes with the use of SABR in our pediatric solid tumor population. METHODS: This was a single-institutional study in patients < 30 years treated with SABR. The primary endpoint was local control (LC), while the secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. The survival analysis was performed using Kaplan-Meier estimates in R v4.2.3. RESULTS: In total, 48 patients receiving 135 SABR courses were included. The median age was 15.6 years (interquartile range, IQR 14-23 y) and the median follow-up was 18.1 months (IQR: 7.7-29.1). The median SABR dose was 30 Gy (IQR 25-35 Gy). The most common primary histologies were Ewing sarcoma (25%), rhabdomyosarcoma (17%), osteosarcoma (13%), and central nervous system (CNS) gliomas (13%). Furthermore, 57% of patients had oligometastatic disease (≤5 lesions) at the time of SABR. The one-year LC, PFS, and OS rates were 94%, 22%, and 70%, respectively. No grade 4 or higher toxicities were observed, while the rates of any grade 1, 2, and 3 toxicities were 11.8%, 3.7%, and 4.4%, respectively. Patients with oligometastatic disease, lung, or brain metastases and those who underwent surgery for a metastatic site had a significantly longer PFS. LC at 1-year was significantly higher for patients with a sarcoma histology (95.7% vs. 86.5%, p = 0.01) and for those who received a biological equivalent dose (BED10) > 48 Gy (100% vs. 91.2%, p = 0.001). CONCLUSIONS: SABR is well tolerated in pediatric patients with 1-year local failure and OS rates of <10% and 70%, respectively. Future studies evaluating SABR in combination with systemic therapy are needed to address progression outside of the irradiated field.

Safety and Feasibility of Stereotactic Radiosurgery for Patients with 15 or more Brain Metastases.

Background: Current standard of care treatment for patients with ≥15 brain metastases (BM) is whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery (SRS), with the aim of evaluating safety, cognitive outcomes, and survival metrics. Methods: Patients who received SRS for ≥15 BMs in 1 to 5 fractions from 2014 to 2022 were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System (PROMIS) scores. The Kaplan-Meier method was used for survival analysis and log-rank test for intergroup comparisons. Results: Overall, 118 patients underwent 124 courses of LINAC-based SRS. The median number of lesions treated per course was 20 (range, 15-94). Most patients received fractionated SRS to a dose of 24 Gy in 3 fractions (81.5%). At the time of SRS, 19.4% patients had received prior WBRT, and 24.2% had received prior SRS. The rate of any grade radiation necrosis (RN) and grade ≥3 RN were 15.3% and 3.2%, respectively. When evaluating longitudinal PROMIS score trends, 25 of 31 patients had a stable/improved PROMIS score. Patients who did not receive prior brain RT had a longer median survival (7.4 months vs 4.6 months, P = .034). The 12m local control was 97.6%, and the cumulative incidence of distant intracranial failure, with death as a competing event, was 46% (95% CI, 36%, 55%). One year freedom from neurologic death, leptomeningeal disease, and salvage WBRT were 89%, 94.6%, and 84%, respectively. Conclusion: We present here one of the largest studies evaluating SRS for patients with ≥15 BMs. SRS was safe, had favorable cognitive outcomes, and had comparable survival outcomes to contemporary studies evaluating WBRT in this population. Treatment-naïve patients had a median survival of >6 months, long enough to benefit from cognitive sparing with SRS. Our study supports randomized studies comparing SRS and hippocampal avoidance WBRT approaches for these patients.

Comparing Outcomes Between Direct and ED Admissions for Neonatal Hyperbilirubinemia.

OBJECTIVES: Pediatric direct admissions (DA) have multiple benefits including reduced emergency department (ED) volumes, greater patient and provider satisfaction, and decreased costs without compromising patient safety. We sought to compare resource utilization and outcomes between patients with a primary diagnosis of neonatal hyperbilirubinemia directly admitted with those admitted from the ED. METHODS: Single-center, retrospective study at a large, academic, free-standing children's hospital (2017-2021). Patients were between 24 hours and 14 days old with a gestational age of ≥35 weeks, admitted with a primary diagnosis of neonatal hyperbilirubinemia. Outcomes included length of stay (LOS), time to clinical care, resource utilization, NICU transfer, and 7-day readmission for phototherapy. RESULTS: A total of 1098 patients were included, with 276 (25.1%) ED admissions and 822 (74.9%) DAs. DAs experienced a shorter median time to bilirubin level collection (1.9 vs 2.1 hours, P = .003), received less intravenous fluids (8.9% vs 51.4%, P < .001), had less bilirubin levels collected (median of 3.0 vs 4.0, P < .001), received phototherapy sooner (median of 0.8 vs 4.2 hours, P < .001), and had a shorter LOS (median of 21 vs 23 hours, P = .002). One patient who was directly admitted required transfer to the NICU. No differences were observed in the 7-day readmission rates for phototherapy. CONCLUSIONS: Directly admitting patients for the management of neonatal hyperbilirubinemia is a preferred alternative to ED admission as our study demonstrated that DAs had a shorter time to clinical care, shorter LOS, and less unnecessary resource utilization with no difference in 7-day readmissions for phototherapy.

Nucleus pulposus structure and function assessed in shear using magnetic resonance elastography, quantitative MRI, and rheometry.

Background: In vivo quantification of the structure-function relationship of the intervertebral disc (IVD) via quantitative MRI has the potential to aid objective stratification of disease and evaluation of restorative therapies. Magnetic resonance elastography (MRE) is an imaging technique that assesses tissue shear properties and combined with quantitative MRI metrics reflective of composition can inform structure-function of the IVD. The objectives of this study were to (1) compare MRE- and rheometry-derived shear modulus in agarose gels and nucleus pulposus (NP) tissue and (2) correlate MRE and rheological measures of NP tissue with composition and quantitative MRI. Method: MRE and MRI assessment (i.e., T1ρ and T2 mapping) of agarose samples (2%, 3%, and 4% (w/v); n = 3-4/%) and of bovine caudal IVDs after equilibrium dialysis in 5% or 25% PEG (n = 13/PEG%) was conducted. Subsequently, agarose and NP tissue underwent torsional mechanical testing consisting of a frequency sweep from 1 to 100 Hz at a rotational strain of 0.05%. NP tissue was additionally evaluated under creep and stress relaxation conditions. Linear mixed-effects models and univariate regression analyses evaluated the effects of testing method, %agarose or %PEG, and frequency, as well as correlations between parameters. Results: MRE- and rheometry-derived shear moduli were greater at 100 Hz than at 80 Hz in all agarose and NP tissue samples. Additionally, all samples with lower water content had higher complex shear moduli. There was a significant correlation between MRE- and rheometry-derived modulus values for homogenous agarose samples. T1ρ and T2 relaxation times for agarose and tissue were negatively correlated with complex shear modulus derived from both techniques. For NP tissue, shear modulus was positively correlated with GAG/wet-weight and negatively correlated with %water content. Conclusion: This work demonstrates that MRE can assess hydration-induced changes in IVD shear properties and further highlights the structure-function relationship between composition and shear mechanical behaviors of NP tissue.

Characterization and modulation of the pro-inflammatory effects of immune cells in the canine intervertebral disk.

Background: Intervertebral disk (IVD) degeneration affects both humans and canines and is a major cause of low back pain (LBP). Mast cell (MC) and macrophage (MØ) infiltration has been identified in the pathogenesis of IVD degeneration (IVDD) in the human and rodent model but remains understudied in the canine. MC degranulation in the IVD leads to a pro-inflammatory cascade and activates protease activated receptor 2 (PAR2) on IVD cells. The objectives of the present study are to: (1) highlight the pathophysiological changes observed in the degenerate canine IVD, (2) further characterize the inflammatory effect of MCs co-cultured with canine nucleus pulposus (NP) cells, (3) evaluate the effect of construct stiffness on NP and MCs, and (4) identify potential therapeutics to mitigate pathologic changes in the IVD microenvironment. Methods: Canine IVD tissue was isolated from healthy autopsy research dogs (beagle) and pet dogs undergoing laminectomy for IVD herniation. Morphology, protein content, and inflammatory markers were assessed. NP cells isolated from healthy autopsy (Mongrel hounds) tissue were co-cultured with canine MCs within agarose constructs and treated with cromolyn sodium (CS) and PAR2 antagonist (PAR2A). Gene expression, sulfated glycosaminoglycan content, and stiffness of constructs were assessed. Results: CD 31+ blood vessels, mast cell tryptase, and macrophage CD 163+ were increased in the degenerate surgical canine tissue compared to healthy autopsy. Pro-inflammatory genes were upregulated when canine NP cells were co-cultured with MCs and the stiffer microenvironment enhanced these effects. Treatment with CS and PAR2 inhibitors mediated key pro-inflammatory markers in canine NP cells. Conclusion: There is increased MC, MØs, and vascular ingrowth in the degenerate canine IVD tissue, similar to observations in the clinical population with IVDD and LBP. MCs co-cultured with canine NP cells drive inflammation, and CS and PAR2A are potential therapeutics that may mitigate the pathophysiology of IVDD in vitro.

Beyond the bias! Sex distribution in paediatric growth hormone deficiency reexamined.

OBJECTIVES: Various biases pertaining to stature account for a male sex predominance in growth hormone deficiency (GHD) cases diagnosed by endocrinology clinics. This manuscript will assess the sex distribution when biases are minimised. METHODS: Retrospective chart review was conducted on patients diagnosed with GHD between 3 and 16 years of age. The sex distribution of cases was ascertained according to: (1) peak GH (pGH) by groups; based on growth hormone provocative testing, (2) pituitary gland imaging results, and (3) isolated GHD (IGHD) versus multiple pituitary hormone deficiencies (MPHD). The relative frequency of each sex was compared according to these subgroups with significance evaluated at α = .05 level. RESULTS: Of the 5880 clinic referrals for short stature, there were 3709 boys (63%) and 2171 girls (37%). Of these, 20% of boys (n = 745) and 15.3% of girls (n = 332) underwent provocative testing for GHD. Of those tested, 39.2% of boys (n = 292) and 32.2% of girls (n = 107) were diagnosed with GHD, all p < .001. There was a male predominance in GHD cases based on pGH or GHD severity. Though not significant, girls were more likely than boys to have MPHD (p = .056), even across pGH groups (p = .06). Both boys and girls had a similar distribution of imaging abnormalities. CONCLUSION: Stratifying by sex, we found similar percentages of pituitary imaging abnormalities (including tumours) and the number of pituitary hormone deficiencies in boys and girls as the cause of GHD. For these classifications, we did not find the historically reported male sex predominance.

Consideration of Metastasis-Directed Therapy for Patients With Metastatic Colorectal Cancer: Expert Survey and Systematic Review.

BACKGROUND: A survey of medical oncologists (MOs), radiation oncologists (ROs), and surgical oncologists (SOs) who are experts in the management of patients with metastatic colorectal cancer (mCRC) was conducted to identify factors used to consider metastasis-directed therapy (MDT). MATERIALS AND METHODS: An online survey to assess clinical factors when weighing MDT in patients with mCRC was developed based on systematic review of the literature and integrated with clinical vignettes. Supporting evidence from the systematic review was included to aid in answering questions. RESULTS: Among 75 experts on mCRC invited, 47 (response rate 62.7%) chose to participate including 16 MOs, 16 ROs, and 15 SOs. Most experts would not consider MDT in patients with 3 lesions in both the liver and lung regardless of distribution or timing of metastatic disease diagnosis (6 vs. 36 months after definitive treatment). Similarly, for patients with retroperitoneal lymph node and lung and liver involvement, most experts would not offer MDT regardless of timing of metastatic disease diagnosis. In general, SOs were willing to consider MDT in patients with more advanced disease, ROs were more willing to offer treatment regardless of metastatic site location, and MOs were the least likely to consider MDT. CONCLUSIONS: Among experts caring for patients with mCRC, significant variation was noted among MOs, ROs, and SOs in the distribution and volume of metastatic disease for which MDT would be considered. This variability highlights differing opinions on management of these patients and underscores the need for well-designed prospective randomized trials to characterize the risks and potential benefits of MDT.

Concentration of novel urinary tract infection biomarkers in neonates.

Urinary tract infections (UTIs) are a common comorbidity in hospitalized neonates. The current UTI diagnostics have several limitations including invasive collection of urinary samples to ensure sterility, risk of contamination and lack of consensus definitions of UTI based on urine culture. Antimicrobial peptides (AMPs) have been recently utilized as novel biomarkers that can efficiently and accurately diagnose pediatric UTI. However, the concentration of AMPs in neonatal urine is not well-defined. Urine from neonates admitted to a single level IV neonatal intensive care unit was obtained to determine baseline concentration of two AMPs, Ribonuclease 7 (RNase 7) and Beta Defensin-1 (BD-1) and to define the relationship between AMP concentration and gestational age (GA). AMP levels were normalized to urine creatinine. RNase 7 and BD-1 were expressed in neonatal urine (n = 66) regardless of GA and as early as 22 weeks gestation. Urinary concentrations of both AMPs decreased as GA and birthweight increased. The overall median urinary RNase 7/UCr and BD-1/UCr values were 271 ng/mg, and 116 ng/mg, respectively. Median urinary concentrations of RNase 7/UCr for infants born at < 27, 27-32, 33-35 and ≥ 36 weeks were 569, 308, 254, and 124 ng/mg respectively. Similarly, the concentrations of BD-1/UCr at these GA were 166, 115, 108, and 14 ng/mg, respectively. Baseline neonatal urinary concentration of two AMPs (RNase 7 and BD-1) and the variation by GA were identified. This is an essential first step toward the potential utilization of AMPs in improving neonatal UTI diagnostics.

Urinary biomarkers associated with acute kidney injury in pediatric mechanical circulatory support patients.

BACKGROUND: In patients requiring mechanical circulatory support (MCS), the incidence of acute kidney injury (AKI) is between 37 and 63%. In this study, we performed an exploratory analysis evaluating the relationship of multiple urine biomarkers with AKI development in pediatric MCS patients. METHODS: This is a single center retrospective study in a pediatric cohort receiving MCS from August 2014 to November 2020. We measured 14 urine biomarkers of kidney injury on day 1 following MCS initiation and analyzed their association with development of AKI in the first 7 days of MCS initiation. RESULTS: Sixty patients met inclusion criteria. Patients with AKI were more likely to be supported by venoarterial extracorporeal membrane oxygenation (65% vs. 8.3%, p < 0.001), compared to the no AKI group and less likely to have ventricular assist devices (10% vs. 50%, p < 0.001). There was a significant increase in the median urine albumin and urine osteoactivin in the AKI group, compared to the no AKI group (p = 0.020 and p = 0.018, respectively). When normalized to urine creatinine (UCr), an increased log osteoactivin/UCr was associated with higher odds of AKI development (OR: 2.05; 95% CI: 1.07, 4.44; p = 0.028), and higher log epidermal growth factor (EGF)/UCr (OR: 0.41; 95% CI: 0.15, 0.96) was associated with decreased odds of AKI. CONCLUSIONS: Early increase in urine osteoactivin is associated with AKI development within 7 days of MCS initiation in pediatric patients. Contrary, an increased urine EGF is associated with kidney protection. A higher resolution version of the Graphical abstract is available as Supplementary information.

Vertebral Compression Fracture After Spine Stereotactic Body Radiotherapy: The Role of Vertebral Endplate Disruption.

BACKGROUND AND OBJECTIVES: Vertebral compression fracture (VCF) is a common, but serious toxicity of spinal stereotactic body radiotherapy (SBRT). Several variables that place patients at high risk of VCF have previously been identified, including advanced Spinal Instability Neoplastic Score (SINS), a widely adopted clinical decision criterion to assess spinal instability. We examine the role of tumoral endplate (EP) disruption in the risk of VCF and attempt to incorporate it into a simple risk stratification system. METHODS: This study was a retrospective cohort study from a single institution. Demographic and treatment information was collected for patients who received spinal SBRT between 2013 and 2019. EP disruption was noted on pre-SBRT computed tomography scan. The primary end point of 1-year cumulative incidence of VCF was assessed on follow-up MRI and computed tomography scans at 3-month intervals after treatment. RESULTS: A total of 111 patients were included. The median follow-up was 18 months. Approximately 48 patients (43%) had at least one EP disruption. Twenty patients (18%) experienced a VCF at a median of 5.2 months from SBRT. Patients with at least one EP disruption were more likely to experience VCF than those with no EP disruption (29% vs 6%, P < .001). A nomogram was created using the variables of EP disruption, a SINS of ≥7, and adverse histology. Patients were stratified into groups at low and high risk of VCF, which were associated with 2% and 38% risk of VCF ( P < .001). CONCLUSION: EP disruption is a novel risk factor for VCF in patients who will undergo spinal SBRT. A simple nomogram incorporating EP disruption, adverse histology, and SINS score is effective for quickly assessing risk of VCF. These data require validation in prospective studies and could be helpful in counseling patients regarding VCF risk and referring for prophylactic interventions in high-risk populations.

The Rosetta Phenotype Harmonization Method Facilitates Finding a Relationship Quantitative Trait Locus for a Complex Cognitive Trait.

Genetics researchers increasingly combine data across many sources to increase power and to conduct analyses that cross multiple individual studies. However, there is often a lack of alignment on outcome measures when the same constructs are examined across studies. This inhibits comparison across individual studies and may impact the findings from meta-analysis. Using a well-characterized genotypic (brain-derived neurotrophic factor: BDNF) and phenotypic constructs (working memory and reading comprehension), we employ an approach called Rosetta, which allows for the simultaneous examination of primary studies that employ related but incompletely overlapping data. We examined four studies of BDNF, working memory, and reading comprehension with a combined sample size of 1711 participants. Although the correlation between working memory and reading comprehension over all participants was high, as expected (ρ = 0.45), the correlation between working memory and reading comprehension was attenuated in the BDNF Met/Met genotype group (ρ = 0.18, n.s.) but not in the Val/Val (ρ = 0.44) or Val/Met (ρ = 0.41) groups. These findings indicate that Met/Met carriers may be a unique and robustly defined subgroup in terms of memory and reading comprehension. This study demonstrates the utility of the Rosetta method when examining complex phenotypes across multiple studies, including psychiatric genetic studies, as shown here, and also for the mega-analysis of cohorts generally.

Long term outcome after surgical treatment for hypothalamic hamartoma.

PURPOSE: To determine long-term outcome for seizure control and clinical predictors for seizure freedom in patients undergoing surgical treatment for epilepsy associated with hypothalamic hamartoma (HH). METHODS: 155 patients underwent surgical treatment for HHs and treatment-resistant epilepsy at one center (Barrow Neurological Institute at St. Joseph's Hospital and Medical Center, Phoenix, Arizona, USA) between February 2003 and June 2010. Data collection included medical record review and direct follow-up interviews to determine seizure outcome. Statistical analysis included descriptive summaries of patient characteristics and time-to-event analysis for seizure freedom. RESULTS: Long-term survival with follow-up of at least five years since first surgical treatment was available for 108 patients (69.7% of the treatment cohort). The surgical approach for first HH intervention consisted of transventricular endoscopic resection (n = 57; 52.8%), transcallosal interforniceal resection (n = 35; 32.4%), pterional resection (n = 7; 6.5%), and gamma knife radiosurgery (n = 9; 8.3%). Multiple surgical procedures were required for 39 patients (36.1%). There were 10 known deaths from all causes in the treatment cohort (6.5%). Of these, one (0.6%) was related to immediate complications of HH surgery, three (1.9%) were attributed to Sudden Unexpected Death in Epileptic Persons (SUDEP), and one (0.6%) to complications of status epilepticus. For surviving patients with long-term follow-up, 55 (50.9%) were seizure-free for all seizure types. Univariable analysis showed that seizure-freedom was related to 1) absence of a pre-operative history for central precocious puberty (p = 0.01), and 2) higher percentage of HH lesion disconnection after surgery (p = 0.047). Kaplan-Meier survival analysis shows that long-term seizure outcome following HH surgery is comparable to short-term results. SUMMARY: These uncontrolled observational results show that long-term seizure control following HH surgical treatment is comparable to other forms of epilepsy surgery. Late relapse (at least one year after surgery) and SUDEP do occur, but in a relatively small number of treated patients. These results inform clinical practice and serve as a comparable benchmark for newer technologies for HH surgery, such as magnetic resonance imaging-guided laser interstitial thermal therapy, where long-term outcome results are not yet available.

Emerging Resistance Trends in Viridans Group Streptococci Bloodstream Infections Among Immunocompromised Children Receiving Levofloxacin Prophylaxis.

BACKGROUND: Levofloxacin prophylaxis (LVXp) is often used for patients with underlying leukemia and severe neutropenia to reduce the risk of fever and bacteremia. This study evaluated trends in viridans group streptococci (VGS) antibiotic susceptibilities over time and clinical outcomes of children with VGS bloodstream infections (BSIs) during institutional adoption of LVXp. METHODS: VGS blood culture isolates between 1/1/2010 and 12/31/2021 with susceptibility testing reported were included. Available isolates were re-identified to the species level and additional susceptibility testing was performed. Demographic and clinical data were abstracted from medical records. RESULTS: A total of 264 VGS BSI isolates were identified in immunocompromised (IC, n = 125) and non-immunocompromised subjects, (non-IC, n = 139). IC subjects had lower rates of VGS isolates susceptible (S) to LVX and higher minimum inhibitory concentration (MICs) to LVX (p = 0.004) and ciprofloxacin (p = 0.0005) compared with non-IC subjects. No other evaluated antibiotic had increased MICs in either group. Fifteen of 19 (74%) LVX not susceptible (NS) isolates occurred in IC subjects, 13 represented breakthrough infections. IC subjects had higher rates of VGS-related shock (p = 0.012), need for pressor support (p = 0.039), and longer duration of hospitalization than non-IC subjects (p < 0.001). Clinical outcomes were comparable between subjects with LVX S and NS VGS BSI isolates. CONCLUSIONS: VGS with reduced susceptibility to LVX emerged during institutional adoption of LVXp in high-risk children with immunocompromising conditions, but did not result in significant differences in clinical outcomes. Ongoing surveillance and susceptibility testing are critical in weighing the utility of LVXp against emerging antimicrobial resistance in this high-risk population.

Preterm and Term Infants Evaluated for Sepsis: Differences in Management and Clinical Outcomes.

BACKGROUND AND OBJECTIVES: To describe differences in practice patterns and outcomes of young preterm versus age-matched term infants evaluated for sepsis, because evaluation and management of this group are not well defined. METHODS: We conducted a retrospective single-center study at an academic, freestanding children's hospital of previously healthy preterm and term infants aged 0 to 60 days, who presented for initial evaluation of fever and/or hypothermia from 2014 to 2019. We classified infants by gestational age as preterm (32-36 6/7 weeks) and term (37-42 weeks) and compared diagnostic evaluation, management, and clinical outcomes. RESULTS: Out of 363 preterm infants evaluated for sepsis, 336 met inclusion criteria; within the same study period, 2331 term infants were evaluated for sepsis, of which 600 were randomly selected and 554 were included. Clinicians performed inflammatory marker testing and chest x-rays more frequently in preterm infants 31% vs 25% (P = .034) and 50% vs 32% (P < .001), respectively. Preterm infants had a higher rate of bacteremia 5.9% vs 2.5% (P = .035), were hospitalized more frequently 72% vs 63% (P = .006), and required ICU level of care more often 32% vs 5% (P < .001) than term infants. They had lower rates of viral infections 33% vs 42% (P = .015) and no significant increased return visits. Febrile preterm and term infants, and older hypothermic preterm infants had relatively higher rates of serious bacterial infections. Hypothermic preterm infants had the longest hospitalizations. CONCLUSIONS: Preterm infants had increased rates of bacteremia and required higher level of care compared with age-matched term infants, likely reflecting their increased risk for sepsis and other concomitant morbidities associated with preterm birth.

The Impact of the COVID-19 Pandemic on Pediatric Bicycle Injury.

Bicycling is a common childhood activity that is associated with significant injury risk. This study's aim was to assess pediatric bicycle injury epidemiology and impacts of the COVID-19 pandemic. We conducted a cross-sectional evaluation of patients age < 18 years presenting with bicycle injury to a pediatric trauma center. A pre-pandemic period (1 March 2015-29 February 2020) was compared to the pandemic period (1 March 2020-28 February 2021). A total of 611 injury events for children < 18 years were included (471 pre-pandemic events and 140 pandemic events). The relative frequency of pandemic injuries was greater than pre-pandemic injuries (p < 0.001), resulting in a 48% increase in pandemic period injuries versus the pre-pandemic average (141 pandemic vs. 94.4/year pre-pandemic). Individuals of female sex represented a larger proportion of injuries in the pandemic period compared to the pre-pandemic period (37% pandemic vs. 28% pre-pandemic, p = 0.035). Injuries were more common on weekends versus weekdays (p = 0.01). Time series analysis showed a summer seasonality trend. Localizing injury events to ZIP codes showed regional injury density patterns. During COVID-19, there was an increase in bicycle injury frequency and proportional shift toward more injuries involving individuals of female sex. Otherwise, injury patterns were largely unchanged. These results demonstrate the necessity of safety interventions tailored to community needs.

Institutional Evaluation of Fetal Neurology Consults and Postnatal Outcomes: A 10-Year Retrospective Cohort Review.

Background and Objectives: An increasing number of centers are offering fetal neurology consultation services; however, there is limited information available in overall institutional experiences. Data are lacking on the fetal characteristics, pregnancy course, and the influence of fetal consultation on perinatal outcomes. The aim of this study is to provide insight on the institutional fetal neurology consult process and areas of strengths and weaknesses. Methods: We performed a retrospective electronic chart review of fetal consults from April 2, 2009, to August 8, 2019, at Nationwide Children's Hospital. The objectives were to summarize clinical characteristics, agreement of prenatal and postnatal diagnoses based on best available imaging, and postnatal outcomes. Results: Of the 174 maternal-fetal neurology consults placed, 130 qualified for inclusion based on data available for review. Of the 131 anticipated fetuses, 5 experienced fetal demise, 7 underwent elective termination, and 10 died in the postnatal period. The majority were admitted to the neonatal intensive care unit; 34 (31%) required supportive intervention for feeding, breathing, or hydrocephalus, and 10 (8%) experienced seizures during their neonatal intensive care unit (NICU) stay. Imaging results from 113 babies who had prenatal and postnatal imaging of the brain were analyzed based on the primary diagnosis. The most common malformations were as follows (prenatal % vs postnatal %): midline anomalies (37% vs 29%), posterior fossa abnormalities (26% vs 18%), and ventriculomegaly (14% vs 8%). Additional disorders of neuronal migration were not seen on fetal imaging but were present in 9% of the postnatal studies. Analysis of agreement between prenatal and postnatal diagnostic imaging for the 95 babies who had MRIs at both time points found moderate concordance (Cohen kappa: 0.62, 95% CI 0.5-0.73; percent agreement: 69%, 95% CI 60%-78%). Consult recommendations for neonatal blood tests affected postnatal care in 64 of 73 cases in which the infant survived and data were available. Discussion: Establishing a multidisciplinary fetal clinic can provide timely counseling and create rapport with families to have continuity of care for birth planning and postnatal management. Prognosis based on radiographic prenatal diagnosis requires caution as some neonatal outcomes may vary considerably.

Caregiver disclosure of common early childhood pediatric urologic surgeries.

BACKGROUND: Certain pediatric urologic diagnoses can have serious long-term adverse health outcomes. As a result, it is important for a child to be aware of their diagnosis and a prior surgery. When children have surgery prior to the age of memory formation, it is incumbent upon their caregiver to disclose this surgery. When and how to disclose this information and even if this occurs, is not clear. OBJECTIVE: We developed a survey to assess caregiver plans to disclose early childhood pediatric urologic surgery and evaluate for predictors of disclosure and resources needed. METHODS: A questionnaire was distributed to caregivers of male children ≤4 years old undergoing single stage repair of hypospadias, inguinal hernia, chordee, or cryptorchidism as part of an IRB approved research study. These surgeries were chosen due to being outpatient surgeries with potential long-term complications and impact. The age criteria was chosen due to likely being before patient memory formation and thus reliance on caregiver disclosure of prior surgery. Surveys were collected the day of surgery and contained information on caregiver demographics, validated health literacy screening, and plans to disclose surgery. RESULTS: 120 survey responses were collected (Summary Table). The majority of caregivers responded affirmatively to planning to disclose their child's surgery (108; 90%). There was no impact of caregiver age, gender, race, marital status, education level, health literacy, or personal surgical history on plans to disclose surgery (p ≥ 0.05). Plan to disclose was also not different across urologic surgery type. Race was significantly associated with being "concerned or nervous about disclosing the surgery to the patient". The median patient age for planned disclosure was 10 years (IQR: 7-13). Only 17 respondents (14%) stated they received any information about how to discuss this surgery with the patient, however 83 (69%) felt this information would be helpful. CONCLUSIONS: Our study suggests that most caregivers plan to discuss early childhood urologic surgeries with children, however want further guidance in how to talk to their child. While no specific surgery or demographic factor was found to be significantly associated with plans to disclose surgery, it is concerning that one in ten patients will potentially never learn about impactful surgery they had as a child. There is an opportunity for us to better counsel our patients' families about surgical disclosure and fill this gap with quality improvement efforts.