A pilot study evaluating the use of sirolimus in children and young adults with desmoid-type fibromatosis.

Deregulation of the mTOR pathway may play an important role in tumor biology when the APC/ß-catenin pathway is disrupted in desmoid-type fibromatosis (DT). A pilot study was conducted to determine whether sirolimus can block the mTOR pathway (primary aim) as well as determine whether it can safely be given in the preoperative setting, decrease tumor size/recurrence, and decrease tumor-associated pain in children and young adults (secondary aims) with DT. Nine subjects ages 5-28 years were enrolled from 2014 to 2017 across four centers. Sirolimus was feasible and was associated with a nonstatistically significant decrease in pS706K activation.

Prostaglandin E2 resistance in granulocytes from patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is an inflammatory condition of the respiratory tract and is characterized by overproduction of leukotrienes (LT) and large numbers of circulating granulocyte-platelet complexes. LT production can be suppressed by prostaglandin E(2) (PGE(2)) and the cyclic AMP-dependent protein kinase A (PKA). OBJECTIVE: To determine if PGE(2)-dependent control of LT production by granulocytes is dysregulated in AERD. METHODS: Granulocytes from well-characterized patients with and without AERD were activated ex vivo and subjected to a range of functional and biochemical analyses. RESULTS: Granulocytes from subjects with AERD generated more LTB4 and cysteinyl LTs than did granulocytes from controls with aspirin-tolerant asthma and controls without asthma. When compared with controls, granulocytes from subjects with AERD had comparable levels of EP(2) protein expression and PGE(2)-mediated cAMP accumulation, yet were resistant to PGE(2)-mediated suppression of LT generation. Percentages of platelet-adherent neutrophils correlated positively with LTB4 generation and inversely with responsiveness to PGE(2)-mediated suppression of LTB(4). The PKA inhibitor H89 potentiated LTB4 generation by control granulocytes but was inactive in granulocytes from individuals with AERD and had no effect on platelet P-selectin induction. Both tonic PKA activity and levels of PKA catalytic gamma subunit protein were significantly lower in granulocytes from individuals with AERD relative to those from controls. CONCLUSIONS: Impaired granulocyte PKA function in AERD may lead to dysregulated control of 5-lipoxygenase activity by PGE(2), whereas adherent platelets lead to increased production of LTs, which contributes to the features of persistent respiratory tract inflammation and LT overproduction.

Morbidity Associated with Deviation from Pediatric Status Epilepticus Guidelines.

Treatment guidelines for the management of pediatric status epilepticus (PSE) are often institution-specific. We aim to characterize deviation from our hospital-based PSE treatment guidelines, the total dosage of benzodiazepines administered, and the need for intubation. The study population included all patients with an ICD -10 code for PSE who required admission to the Pediatric Intensive Care Unit (PICU) from April 2019 to April 2022. There were 66 PICU admissions. All patients with concern for PSE and altered mental status are admitted to the PICU. The cohort was divided between those treated according to the PSE protocol (benzodiazepine dose (0.05 mg/kg- 0.2 mg/kg) versus those who had low dose (≤0.05 mg/kg) and high-dose benzodiazepine (> 0.2 mg/kg) totals. The dosage was calculated as the total dose of benzodiazepines received pre-hospital and in the ED before intubation or transport. Forty-one (62 %) of patients received high-dose benzodiazepines (median 0.34 mg/kg [IQR 0.29-0.56], 19 (29 %) received recommended-dose benzodiazepines (median 0.13 mg/kg [IQR 0.09,0.15] and 6 (9 %) received low-dose (median 0.05 mg/kg [IQR 0.03,0.05]. The high-dose group was 15.9 (95 % CI = 3.7, 99.9) times more likely to be intubated controlling for the location of care (tertiary versus community hospital), and the age of the patient. The recommended-dose and low-dose groups required intubation with much less frequency.

Racial differences in triage assessment at rural vs urban Maine emergency departments.

Data continue to accumulate demonstrating that those belonging to racialized groups face implicit bias in the emergency care delivery system across many indices, including triage assessment. The Emergency Severity Index (ESI) was developed and widely implemented across the US to improve the objectivity of triage assessment and prioritization of care delivery; however, research continues to support the presence of subjective bias in triage assessment. We sought to assess the relationship between perceived race and/or need for translator and assigned ESI score and whether this was impacted by hospital geography. We performed retrospective EMR-based review of patients presenting to urban and rural emergency departments of a health system in Maine with one of the top ten most common chief complaints (CC) across a 5-year period, excluding psychiatric CCs. We used multivariable regression to analyze the relationships between perceived race, need for translator, and gender with ESI score, wait time, and hallway bed assignments. We found that patients perceived as non-white were more likely to receive lower acuity ESI scores and have longer wait times as compared to patients perceived as white. Patients perceived as female were more likely to receive lower acuity scores and wait longer to be seen than patients perceived as male. The need for an interpreter was associated with increased wait times but not significantly associated with ESI score. After stratification by hospital geography, evidence of subjective bias was limited to urban emergency departments and was not evident in rural emergency departments. Further investigation of subjective bias in emergency departments in Maine, particularly in urban settings, is warranted.

Telemedicine Improves Rate of Successful First Visit to NICU Follow-up Clinic.

OBJECTIVES: NICU graduates require ongoing surveillance in follow-up clinics because of the risk of lower cognitive, motor, and academic performance. We hypothesized that multiple programmatic changes, including availability of telemedicine consultation before hospital discharge, would improve NICU follow-up clinic attendance rates. METHODS: In this retrospective study, we included infants who survived and were premature (≤29 6/7 weeks/<1500 g) or had brain injury (grade III/IV intraventricular hemorrhage, stroke or seizure, hypoxic ischemic encephalopathy). We compared rates of follow-up for the early cohort (January 2018-June 2019; no telemedicine) with the late cohort (May 2020-May 2021; telemedicine available); and performed a mediation analysis to assess other programmatic changes for the late cohort including improved documentation to parents and primary care provider regarding NICU follow-up. RESULTS: The rate of successful 12-month follow-up improved from 26% (early cohort) to 61% (late cohort) (P < .001). After controlling for maternal insurance, the odds of attending a 12-month follow-up visit were 3.7 times higher for infants in the late cohort, for whom telemedicine was available (confidence interval, 1.8-7.9). Approximately 37% of this effect was mediated by including information for NICU follow-up in the discharge documentation for parents (P < .001). CONCLUSIONS: Telemedicine consultation before NICU discharge, in addition to improving communication regarding the timing and importance of NICU follow-up, was effective at improving the rate of attendance to NICU follow-up clinics.

Association of medication-assisted treatment and short acting opioids with newborn head circumference and birth weight.

OBJECTIVE: We compared the association of methadone, buprenorphine, and short-acting opioid exposure with newborn head circumference (HC) and birth weight (BW), and evaluated gestational age (GA) as a mediator. STUDY DESIGN: We included newborns born 2013-2018 identified by neonatal abstinence syndrome diagnosis code (N = 572) and birthday-matched unexposed controls (N = 571). Linear regressions of opioid exposure with HC and BW controlled for tobacco, marijuana, cocaine, gabapentin, cesarean section, Medicaid, and newborn sex, with mediation analysis by GA. RESULT: Methadone was associated with 0.81 cm lower HC (95% CI = -1.22, -0.40) and 0.23 kg lower BW (95% CI = -0.35, -0.10) with approximately 24% and 41% mediated by GA, respectively. Buprenorphine and short acting opioids were not associated with HC or BW. CONCLUSION: Methadone exposed newborns have smaller HC and lower BW not fully attributable to younger GA, suggesting a direct effect of methadone on intrauterine growth. Exploration of potential developmental consequences of this is urgently needed.

Telemedicine Consultation to Assess Neonatal Encephalopathy in Rural Community Hospitals and Tertiary Care Centers.

Introduction: Teleconsultation is used in tertiary care hospitals to evaluate neonatal encephalopathy. Neonates born in community hospitals, however, often experience delayed evaluation due to transport to the tertiary care center. We studied teleconsultations in community hospitals to decrease this disparity. Methods: Prospective observational study in 9 community hospitals and 1 neonatal intensive care unit. Inclusion criteria: gestational age greater than or equal to 35 weeks and one of the following: umbilical cord pH less than or equal to 7.2, 5-minute Apgar less than 7, prolonged respiratory support, perinatal event, or abnormal neurological exam. We performed synchronized, unscheduled telemedicine consults with the main outcome of time to teleconsultation. Results: From April 2018 to September 2020, we performed 53 teleconsultations: 34 (64%) in community hospitals and 19 (36%) in the tertiary care center. Teleconsultations occurred at a median of 98 minutes (IQR, 76-127) in community hospitals versus 68 minutes (IQR, 43-91) in the tertiary care center (p = .004). Nine (26%) neonates born in a community hospital remained with their parents and were not transferred to the tertiary care center for further assessment. Discussion: Neonates born in rural community hospitals have slightly later teleconsultations than neonates born in the tertiary care center. Telemedicine use reduced this disparity from nearly 5 hours in our prior study to 98 minutes in this study by permitting evaluation of neonates in community hospitals without transporting them to the tertiary care center. Conclusions: Teleconsultations to evaluate neonatal encephalopathy are a feasible, accessible, and reliable way to bring expert-level care into rural community hospitals.

Simulation-Based Outreach Program Improves Rural Hospitals' Team Confidence in Neonatal Resuscitation.

INTRODUCTION: Neonatal resuscitation is a high acuity, low occurrence event (HALO), and in rural community hospitals, low birth rates prevent providers from regular opportunities to maintain essential resuscitation skills. Simulation is an effective training modality for medical education, although resources for simulation are often limited in rural hospitals. Our primary objective was to test the hypothesis that in situ neonatal resuscitation simulation training improves rural hospitals' delivery room team confidence in performing key Neonatal Resuscitation Program® (NRP®) skills. Our secondary objective was to compare confidence to performance as measured by adherence to NRP® guidelines. METHODS: We conducted a quasi-experimental pre-training survey and post-training survey of delivery room team confidence in NRP® skills at five level one delivery hospitals before and after an in situ simulation training program. Participants included rural hospitals' usual delivery room team members. Participants rated their confidence on a five-point Likert scale. Simulations were analyzed using an adapted version of a validated scoring tool for NRP® adherence and presented as overall percentage scores. RESULTS: Our data demonstrate a significant improvement in self-assessed confidence levels pre- and post-simulation training in key areas of neonatal resuscitation. Participants reported higher confidence in airway management (4 vs. 3, p=0.003), emergency intravenous access (3 vs. 2, p=0.007), and the ability to manage a code in the delivery room (4 vs. 3, p=0.013) and the operating room (4 vs. 3, p=0.028). Improvements were also noted in their team member's knowledge and skills to perform neonatal resuscitation. While improvements were appreciated in confidence, the performance of skills (NRP® adherence scores) was often in the sub-optimal performance range. CONCLUSIONS: An in situ-based neonatal resuscitation outreach simulation program improves self-confidence among rural delivery room teams. Additional research is needed to understand how to translate improved confidence into actual improved performance.

Comparing whole-genome shotgun sequencing and DNA metabarcoding approaches for species identification and quantification of pollen species mixtures.

Molecular identification of mixed-species pollen samples has a range of applications in various fields of research. To date, such molecular identification has primarily been carried out via amplicon sequencing, but whole-genome shotgun (WGS) sequencing of pollen DNA has potential advantages, including (1) more genetic information per sample and (2) the potential for better quantitative matching. In this study, we tested the performance of WGS sequencing methodology and publicly available reference sequences in identifying species and quantifying their relative abundance in pollen mock communities. Using mock communities previously analyzed with DNA metabarcoding, we sequenced approximately 200Mbp for each sample using Illumina HiSeq and MiSeq. Taxonomic identifications were based on the Kraken k-mer identification method with reference libraries constructed from full-genome and short read archive data from the NCBI database. We found WGS to be a reliable method for taxonomic identification of pollen with near 100% identification of species in mixtures but generating higher rates of false positives (reads not identified to the correct taxon at the required taxonomic level) relative to rbcL and ITS2 amplicon sequencing. For quantification of relative species abundance, WGS data provided a stronger correlation between pollen grain proportion and sequence read proportion, but diverged more from a 1:1 relationship, likely due to the higher rate of false positives. Currently, a limitation of WGS-based pollen identification is the lack of representation of plant diversity in publicly available genome databases. As databases improve and costs drop, we expect that eventually genomics methods will become the methods of choice for species identification and quantification of mixed-species pollen samples.

A Comparison of the Bacterial Nasal Microbiome in Allergic Rhinitis Patients Before and After Immunotherapy.

OBJECTIVES/HYPOTHESIS: Recent research has examined the nasal microbiome in rhinosinusitis and nondiseased states. Given immunologic alterations in allergic rhinitis (AR) and after allergen immunotherapy (IT), we evaluated the nasal microbiome in these conditions. STUDY DESIGN: Cross-sectional comparison. METHODS: In this cross-sectional study, nasal swabs for microbiome analysis were collected from three patient groups: IT-naïve AR patients, AR patients undergoing IT for greater than 12 months, and a control group without sinonasal inflammatory disease. RESULTS: Nasal swabs were successfully collected for 14 IT-naïve AR patients, 20 post-IT patients, and 17 controls. The α diversity showed a statistical difference in evenness but not in richness amongst samples, whereas the ß-diversity was significantly different between groups. Corynebacterium and Staphylococcus were the most prevalent bacteria across all groups. CONCLUSIONS: ß-diversity was found to be significantly different across the three groups, but the AR groups were found to be more similar to each other than to the controls. Although there is symptomatic improvement in the AR group undergoing IT, the microbiome does not appear to transition to a healthy microbiome composition. LEVEL OF EVIDENCE: 4 Laryngoscope, 2020.

Maternal serum concentrations of perfluoroalkyl substances and birth size in British boys.

Per- and polyfluoroalkyl substances (PFAS) have been widely used in commercial and industrial manufacturing processes since the 1950s. Inverse associations between prenatal exposure to PFAS and birth size have been found in populations around the globe. This study examined the association of prenatal maternal serum concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA) and birth size in British boys. The study included 457 mother-son dyads participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Birth weight (g), crown to heel length (cm), and head circumference (cm) were collected at delivery. PFAS were detected in all maternal serum samples during pregnancy (median: 30 weeks gestation (interquartile range: 12-33)). Median concentrations (interquartile range) were 13.8 ng/mL (11.0, 17.7), 3.0 ng/mL (2.3, 3.8), 1.9 ng/mL (1.4, 2.5), and 0.4 ng/mL (0.3, 0.5) for PFOS, PFOA, PFHxS, and PFNA, respectively. In multivariable linear regression models, inverse associations were detected between PFOS (continuous) and birth weight (ß = -8.50 g, 95% CI = -15.93, -1.07 g), crown to heel length (ß = -0.04 cm, 95% CI = -0.08, -0.01 cm), and head circumference (ß = -0.02 cm, 95% CI = -0.04, -0.002 cm). In conclusion, prenatal exposure to high levels of PFOS may be associated with reduced birth size in male infants.

Stability of the vaginal, oral, and gut microbiota across pregnancy among African American women: the effect of socioeconomic status and antibiotic exposure.

OBJECTIVE: A growing body of research has investigated the human microbiota and pregnancy outcomes, especially preterm birth. Most studies of the prenatal microbiota have focused on the vagina, with fewer investigating other body sites during pregnancy. Although pregnancy involves profound hormonal, immunological and metabolic changes, few studies have investigated either shifts in microbiota composition across pregnancy at different body sites or variation in composition at any site that may be explained by maternal characteristics. The purpose of this study was to investigate: (1) the stability of the vaginal, oral, and gut microbiota from early (8-14 weeks) through later (24-30 weeks) pregnancy among African American women according to measures of socioeconomic status, accounting for prenatal antibiotic use; (2) whether measures of socioeconomic status are associated with changes in microbiota composition over pregnancy; and (3) whether exposure to prenatal antibiotics mediate any observed associations between measures of socioeconomic status and stability of the vaginal, oral, and gut microbiota across pregnancy. METHODS: We used paired vaginal, oral, or gut samples available for 16S rRNA gene sequencing from two time points in pregnancy (8-14 and 24-30 weeks) to compare within-woman changes in measures of alpha diversity (Shannon and Chao1) and beta-diversity (Bray-Curtis dissimilarity) among pregnant African American women (n = 110). Multivariable linear regression was used to examine the effect of level of education and prenatal health insurance as explanatory variables for changes in diversity, considering antibiotic exposure as a mediator, adjusting for age, obstetrical history, and weeks between sampling. RESULTS: For the oral and gut microbiota, there were no significant associations between measures of socioeconomic status or prenatal antibiotic use and change in Shannon or Chao1 diversity. For the vaginal microbiota, low level of education (high school or less) was associated with an increase in Shannon and Chao1 diversity over pregnancy, with minimal attenuation when controlling for prenatal antibiotic use. Conversely, for within-woman Bray-Curtis dissimilarity for early compared to later pregnancy, low level of education and prenatal antibiotics were associated with greater dissimilarity for the oral and gut sites, with minimal attenuation when controlling for prenatal antibiotics, and no difference in dissimilarity for the vaginal site. CONCLUSIONS: Measures of maternal socioeconomic status are variably associated with changes in diversity across pregnancy for the vaginal, oral, and gut microbiota, with minimal attenuation by prenatal antibiotic exposure. Studies that evaluate stability of the microbiota across pregnancy in association with health outcomes themselves associated with socioeconomic status (such as preterm birth) should incorporate measures of socioeconomic status to avoid finding spurious relationships.

Complication Rates and Short-Term Outcomes After Operative Hammertoe Correction in Older Patients.

BACKGROUND: Hammertoe deformities are the most common lesser toe deformity. To date, no studies have looked at outcomes of operative management in the geriatric population, which may be at greater risk for complications or functional compromise because of comorbidities. METHODS: Data on 58 patients undergoing operative correction of hammertoe deformities were prospectively collected. Clinical outcomes were assessed using preoperative and postoperative visual analogue scale (VAS) and Short Form Health Survey (SF-36) scores with a minimum of 6-month follow-up. Patients were divided into 2 groups on the basis of age at the time of surgery: younger than 65 and 65 and older. Complication rates and mean VAS and SF-36 improvement were compared. Forty-seven patients met inclusion criteria (7 men, 40 women), with 26 patients (37 toes) in the younger cohort and 21 patients (39 toes) in the older cohort. RESULTS: Overall, patients demonstrated significant improvement from baseline to 6 and 12 months postoperatively in VAS ( P < .001 and P < .001) and SF-36 ( P < .001 and P < .001) scores. Mean improvement in VAS and SF-36 scores was not significantly different between the groups at 6 and 12 months postoperatively. Complications occurred in 13.5% and 10.3% of patients in the younger and older cohorts, respectively. CONCLUSIONS: Outcomes of operative correction of hammertoe deformities in older patients were similar to outcomes in younger patients after greater than 6 months of follow-up. Overall improvement in VAS and SF-36 was statistically significant for both cohorts. There was no associated increase in complications for older patients. LEVEL OF EVIDENCE: Level, III comparative series.