Currently, there are about 10,000 pediatric patients in the United States who rely on dialysis for renal replacement therapy. Dialysis allows children with chronic kidney disease a means of support ...until renal transplant is feasible. All forms of renal replacement therapy require a surgical intervention, whether the modality is hemodialysis or peritoneal dialysis. Despite peritoneal dialysis being the most common modality of dialysis in children, there is not prospectively collected much evidence in the literature which can guide the pediatric surgeon about best practices on access placement, management of complications, and timing of removal. Most available studies are small, single-center retrospective reviews. This limits the power of the data collected to help guide decision-making in the management of peritoneal dialysis catheters.
The purpose of this review is to provide a consolidated source of best available evidence and identify important areas for future study. Furthermore, this is an area of pediatric surgical care that lacks up to date outcomes research with robust surgeon participation. Lack of coordinated, evidence-based best practices likely results in heterogenous surgical practices and uneven strategies for managing complications. Furthermore, with improvements in neonatal critical care and fetal interventions available for obstructive uropathies and other congenital kidney disorders, there is increased likelihood of the need for dialysis access in more infants, who represent a particularly vulnerable patient population. Importantly, peritoneal dialysis access should be instituted into the national PEDScore curriculum for pediatric surgical fellows, as this procedure is common enough that any pediatric surgeon could be consulted for catheter placement and management. Surgeon awareness of, and participation in the formulation, of guidelines and prospective studies is of paramount importance to ensure optimal care of this vulnerable population of children.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND:Unconventional natural gas development has expanded rapidly. In Pennsylvania, the number of producing wells increased from 0 in 2005 to 3,689 in 2013. Few publications have focused on ...unconventional natural gas development and birth outcomes.
METHODS:We performed a retrospective cohort study using electronic health record data on 9,384 mothers linked to 10,946 neonates in the Geisinger Health System from January 2009 to January 2013. We estimated cumulative exposure to unconventional natural gas development activity with an inverse-distance squared model that incorporated distance to the mother’s home; dates and durations of well pad development, drilling, and hydraulic fracturing; and production volume during the pregnancy. We used multilevel linear and logistic regression models to examine associations between activity index quartile and term birth weight, preterm birth, low 5-minute Apgar score and small size for gestational age birth, while controlling for potential confounding variables.
RESULTS:In adjusted models, there was an association between unconventional natural gas development activity and preterm birth that increased across quartiles, with a fourth quartile odds ratio of 1.4 (95% confidence interval = 1.0, 1.9). There were no associations of activity with Apgar score, small for gestational age birth, or term birth weight (after adjustment for year). In a posthoc analysis, there was an association with physician-recorded high-risk pregnancy identified from the problem list (fourth vs. first quartile, 1.3 95% confidence interval = 1.1, 1.7).
CONCLUSION:Prenatal residential exposure to unconventional natural gas development activity was associated with two pregnancy outcomes, adding to evidence that unconventional natural gas development may impact health.See Video Abstract at http://links.lww.com/EDE/B14.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
IMPORTANCE: Asthma is common and can be exacerbated by air pollution and stress. Unconventional natural gas development (UNGD) has community and environmental impacts. In Pennsylvania, UNGD began in ...2005, and by 2012, 6253 wells had been drilled. There are no prior studies of UNGD and objective respiratory outcomes. OBJECTIVE: To evaluate associations between UNGD and asthma exacerbations. DESIGN: A nested case-control study comparing patients with asthma with and without exacerbations from 2005 through 2012 treated at the Geisinger Clinic, which provides primary care services to over 400 000 patients in Pennsylvania. Patients with asthma aged 5 to 90 years (n = 35 508) were identified in electronic health records; those with exacerbations were frequency matched on age, sex, and year of event to those without. EXPOSURES: On the day before each patient’s index date (cases, date of event or medication order; controls, contact date), we estimated activity metrics for 4 UNGD phases (pad preparation, drilling, stimulation hydraulic fracturing, or “fracking”, and production) using distance from the patient’s home to the well, well characteristics, and the dates and durations of phases. MAIN OUTCOMES AND MEASURES: We identified and defined asthma exacerbations as mild (new oral corticosteroid medication order), moderate (emergency department encounter), or severe (hospitalization). RESULTS: We identified 20 749 mild, 1870 moderate, and 4782 severe asthma exacerbations, and frequency matched these to 18 693, 9350, and 14 104 control index dates, respectively. In 3-level adjusted models, there was an association between the highest group of the activity metric for each UNGD phase compared with the lowest group for 11 of 12 UNGD-outcome pairs: odds ratios (ORs) ranged from 1.5 (95% CI, 1.2-1.7) for the association of the pad metric with severe exacerbations to 4.4 (95% CI, 3.8-5.2) for the association of the production metric with mild exacerbations. Six of the 12 UNGD-outcome associations had increasing ORs across quartiles. Our findings were robust to increasing levels of covariate control and in sensitivity analyses that included evaluation of some possible sources of unmeasured confounding. CONCLUSIONS AND RELEVANCE: Residential UNGD activity metrics were statistically associated with increased risk of mild, moderate, and severe asthma exacerbations. Whether these associations are causal awaits further investigation, including more detailed exposure assessment.
We conducted a systematic review and meta‐analysis of observational studies investigating the association between antibiotic exposure in infancy and risk of childhood overweight and obesity. Thirteen ...studies, including a total of 527 504 children, were included in the systematic review and 8 were included in meta‐analyses. Exposure to antibiotics in infancy was associated with an increased odds ratio (OR) of childhood overweight and obesity (OR 1.11, 95% confidence interval CI 1.02‐1.20). Whereas exposure to 1 treatment only and exposure between 6 and 24 months were not associated with increased risk of childhood overweight and obesity, exposure to >1 treatment was associated with an OR of 1.24 (95% CI 1.09‐1.43) and exposure within the first 6 months of life was associated with an OR of 1.20 (95% CI 1.04‐1.37). In conclusion, antibiotic exposure in infancy was associated with a slightly increased risk of childhood overweight and obesity, mainly if children were exposed to repeated treatments or treatment within the first 6 months of life. It is unclear whether this association is mediated via direct effects of antibiotics on the gut microbiota.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Human endogenous retroviruses (HERVs) are genetic elements in the human genome, which resulted from ancient retroviral germline infections. HERVs have strong transcriptional promoters and enhancers ...that affect a cell's transcriptome. They also encode proteins that can exert effects in human cells. This review examines how our increased understanding of HERVs have led to their potential use as biomarkers and immunologic targets.
PubMed/Medline, Embase, Web of Science, and Cochrane databases were used in a systematic search to identify all articles studying the potential impact of HERVs on surgical diseases. The search included studies that involved clinical patient samples in diseases including cancer, inflammatory conditions, and autoimmune disease. Articles focused on conditions not routinely managed by surgeons were excluded.
Eighty six articles met inclusion and quality criteria for this review and were included. Breast cancer and melanoma have robust evidence regarding the use of HERVs as potential tumor markers and immunologic targets. Reported evidence of the activity of HERVs in colorectal cancer, pancreatic cancer, hepatocellular cancer, prostate and ovarian cancer, germ cell tumors as well as idiopathic pulmonary hypertension, and the inflammatory response in burns was also reviewed.
Increasingly convincing evidence indicates that HERVs may play a role in solid organ malignancy and present important biomarkers or immunologic targets in multiple cancers. Innovative investigation of HERVs is a valuable focus of translational research and can deepen our understanding of cellular physiology and the effects of endogenous retroviruses on human biology. As strategies for treatment continue to focus on genome-based interventions, understanding the impact of endogenous retroviruses on human disease will be critical.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Given that diseases associated with anti-SSA/Ro autoantibodies, such as systemic lupus erythematosus and Sjögren syndrome, are linked with an upregulation of IFN and type I IFN-stimulated genes, ...including sialic acid-binding Ig-like lectin 1 (Siglec-1), a receptor on monocytes/macrophages, recent attention has focused on a potential role for IFN and IFN-stimulated genes in the pathogenesis of congenital heart block (CHB). Accordingly, three approaches were leveraged to address the association of IFN, IFN-stimulated genes, and the phenotype of macrophages in affected fetal cardiac tissue: 1) cultured healthy human macrophages transfected with hY3, an anti-SSA/Ro-associated ssRNA, 2) RNA isolated from freshly sorted human leukocytes/macrophages after Langendorff perfusion of three fetal hearts dying with CHB and three healthy gestational age-matched hearts, and 3) autopsy tissue from three additional human CHB hearts and one healthy heart. TLR ligation of macrophages with hY3 led to the upregulation of a panel of IFN transcripts, including SIGLEC1, a result corroborated using quantitative PCR. Using independent and agnostic bioinformatics approaches, CD45
CD11c
and CD45
CD11c
human leukocytes flow sorted from the CHB hearts highly expressed type I IFN response genes inclusive of SIGLEC1. Furthermore, Siglec-1 expression was identified in the septal region of several affected fetal hearts. These data now provide a link between IFN, IFN-stimulated genes, and the inflammatory and possibly fibrosing components of CHB, positioning Siglec-1-positive macrophages as integral to the process.
Unconventional natural gas development (UNGD) produces environmental contaminants and psychosocial stressors. Despite these concerns, few studies have evaluated the health effects of UNGD.
We ...investigated associations between UNGD activity and symptoms in a cross-sectional study in Pennsylvania.
We mailed a self-administered questionnaire to 23,700 adult patients of the Geisinger Clinic. Using standardized and validated questionnaire items, we identified respondents with chronic rhinosinusitis (CRS), migraine headache, and fatigue symptoms. We created a summary UNGD activity metric that incorporated well phase, location, total depth, daily gas production and inverse distance-squared to patient residences. We used logistic regression, weighted for sampling and response rates, to assess associations between quartiles of UNGD activity and outcomes, both alone and in combination.
The response rate was 33%. Of 7,785 study participants, 1,850 (24%) had current CRS symptoms, 1,765 (23%) had migraine headache, and 1,930 (25%) had higher levels of fatigue. Among individuals who met criteria for two or more outcomes, adjusted odds ratios for the highest quartile of UNGD activity compared with the lowest were OR (95% CI) 1.49 (0.78, 2.85) for CRS plus migraine, 1.88 (1.08, 3.25) for CRS plus fatigue, 1.95 (1.18, 3.21) for migraine plus fatigue, and 1.84 (1.08, 3.14) for all three outcomes together. Significant associations were also present in some models of single outcomes.
This study provides evidence that UNGD is associated with nasal and sinus, migraine headache, and fatigue symptoms in a general population representative sample. Citation: Tustin AW, Hirsch AG, Rasmussen SG, Casey JA, Bandeen-Roche K, Schwartz BS. 2017. Associations between unconventional natural gas development and nasal and sinus, migraine headache, and fatigue symptoms in Pennsylvania. Environ Health Perspect 125:189-197; http://dx.doi.org/10.1289/EHP281.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Opiate use in neonates can affect clinical outcomes after surgery and may alter future neurodevelopment. We implemented a multimodal opioid reduction strategy in our NICU for infants undergoing ...nonemergent gastrointestinal surgery.
After multiple stakeholder's meetings, our opioid reduction intervention included giving neonates postoperative standing intravenous acetaminophen every 6 hours for 48 hours, a standardized postsurgical sign-out with the NICU team in which pain control was directly addressed, and a series of postsurgical pain education seminars with NICU providers. To assess the impact of our quality improvement project, we used process control charts to investigate trends in postoperative opioid use in our preintervention (January 2012 to April 2016) and postintervention (May 2016 to September 2019) cohorts.
A total of 77 infants were included in the study (40 in the preintervention cohort and 37 in the postintervention cohort). Patient characteristics were equivalent. The intervention significantly reduced the trend in postoperative morphine equivalents (median: 7.96 mg/kg in preintervention cohort versus 0.095 mg/kg in postintervention cohort;
< .0001). The Neonatal Pain, Agitation, and Sedation Scale pain scores and safety profiles were equivalent in both groups. The intervention was also associated with a 24-hour reduction in postoperative ventilation time (
< .048) and a 7-day reduction in the use of total parenteral nutrition (
< .017).
Standing intravenous acetaminophen coupled with provider education can successfully reduce opioid use in postsurgical neonates. Given the concern for opioid exposure in neonatal neurodevelopment as well as clinical benefits of reduced opioids, similar strategies for opioid reduction may prove useful at other institutions.
Hepatoblastoma is the most common liver malignancy in children. In order to advance therapy against hepatoblastoma, novel immunologic targets and biomarkers are needed. Our purpose in this ...investigation is to examine hepatoblastoma transcriptomes for the expression of a class of genomic elements known as Human Endogenous Retrovirus (HERVs). HERVs are abundant in the human genome and are biologically active elements that have been associated with multiple malignancies and proposed as immunologic targets in a subset of tumors. A sub-family of HERVs, HERV-K(HML-2) (HERV-K), have been shown to be tightly regulated in fetal development, making investigation of these elements in pediatric tumors paramount.
We first created a HERVK-FASTA file utilizing 91 previously described HML-2 proviruses. We then concatenated the file onto the GRCh38.95 cDNA library from Ensembl. We used this reference database to evaluate existing RNA-seq data from 10 hepatoblastoma tumors and 3 normal liver controls (GEO accession ID: GSE8977575). Quantification and differential proviral expression analysis between hepatoblastoma and normal liver controls was performed using the pseudo-alignment program Salmon and DESeq2, respectively.
HERV-K mRNA was expressed in hepatoblastoma from multiple proviral loci. All expressed HERV-K proviral loci were upregulated in hepatoblastoma compared to normal liver controls. Five HERV-K proviruses (1q21.3, 3q27.2, 7q22.2, 12q24.33 and 17p13.1) were significantly differentially expressed (p-adjusted value <0.05, |log2 fold change| > 1.5) across conditions. The provirus at 17p13.1 had an approximately 300-fold increased expression in hepatoblastoma as compared to normal liver. This was in part due to the near absence of HERV-K mRNA at the 17p13.1 locus in fully differentiated liver samples.
Our investigation demonstrates that HERV-K is expressed from multiple loci in hepatoblastoma and that the expression is increased for several proviruses compared to normal liver controls. Our results suggest that HERV-K mRNA expression may be useful as a biomarker in hepatoblastoma, given the large differential expression profiles in hepatoblastoma, with very low mRNA levels in liver control samples.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Radon is the second-leading cause of lung cancer worldwide. Most indoor exposure occurs by diffusion of soil gas. Radon is also found in well water, natural gas, and ambient air. Pennsylvania has ...high indoor radon concentrations; buildings are often tested during real estate transactions, with results reported to the Department of Environmental Protection (PADEP).
We evaluated predictors of indoor radon concentrations.
Using first-floor and basement indoor radon results reported to the PADEP between 1987 and 2013, we evaluated associations of radon concentrations (natural log transformed) with geology, water source, building characteristics, season, weather, community socioeconomic status, community type, and unconventional natural gas development measures based on drilled and producing wells.
Primary analysis included 866,735 first measurements by building, with the large majority from homes. The geologic rock layer on which the building sat was strongly associated with radon concentration (e.g., Axemann Formation, median = 365 Bq/m3, IQR = 167-679 vs. Stockton Formation, median = 93 Bq/m3, IQR = 52-178). In adjusted analysis, buildings using well water had 21% higher concentrations (β = 0.191, 95% CI: 0.184, 0.198). Buildings in cities (vs. townships) had lower concentrations (β = -0.323, 95% CI: -0.333, -0.314). When we included multiple tests per building, concentrations declined with repeated measurements over time. Between 2005 and 2013, 7,469 unconventional wells were drilled in Pennsylvania. Basement radon concentrations fluctuated between 1987 and 2003, but began an upward trend from 2004 to 2012 in all county categories (p < 0.001), with higher levels in counties having ≥ 100 drilled wells versus counties with none, and with highest levels in the Reading Prong.
Geologic unit, well water, community, weather, and unconventional natural gas development were associated with indoor radon concentrations. Future studies should include direct environmental measurement of radon, as well as building features unavailable for this analysis.
Casey JA, Ogburn EL, Rasmussen SG, Irving JK, Pollak J, Locke PA, Schwartz BS. 2015. Predictors of indoor radon concentrations in Pennsylvania, 1989-2013. Environ Health Perspect 123:1130-1137; http://dx.doi.org/10.1289/ehp.1409014.
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CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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