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Southern Regional Meeting 2019 New Orleans, LA February 21–23, 2019
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Cardiovascular II

10:30 AM

Saturday February 23, 2019

671 Eosinophilic endocardial fibrosis causing heart failure

E Sherman

A Penmetsa

A Nat

K Galbraith

SUNY Upstate, Syracuse, NY

Case report

Endomyocardial fibrosis is an idiopathic etiology which progressively weakens the cardiac muscle causing restrictive physiology. Loffler’s disease, first described in the 1930s, includes peripheral eosinophilia, endocardial fibrosis and small vessel vasculitis. Echocardiogram, cardiac MRI and occasionally cardiac muscle biopsy are used to yield the diagnosis. Patients suffer from heart failure and treatment includes diuretics or surgical resection of the fibrosis. We present a 63-year-old male, working as an airplane mechanic, with hypertension and stage 3 kidney disease who suddenly developed shortness of breath and pleuritic chest pain. He was found to have bilateral pleural effusions, mild peripheral eosinophilia, marked neutrophilia and lymphocytopenia. The effusions were tapped and were transudative with two negative cytology samples. Other causes of dyspnea were ruled out so acute heart failure exacerbation was diagnosed. Echocardiogram showed a restrictive physiology and work up was subsequently negative for autoimmune pathology. Heavy metal toxicity screen was unremarkable. Given his degree of hypoxia and diuretic resistant effusions, he had a right heart catheterization which revealed severe pulmonary hypertension with PCWP of 19/20/18 mmHg and normal cardiac output. He also necessitated bilateral pleural catheters and bleomycin pleurodesis. Cardiac MRI showed asymmetric basal septal and inferior hypertrophy, chronic RV strain, mild diffuse pericardial thickening due to possible mild pericarditis, dilated pulmonary artery and mild mediastinal lymphadenopathy. This prompted a left cardiac catheterization which showed stenosis in the distal LAD for which he received a DES and a cardiac biopsy demonstrated eosinophils and dense fibrosis in the endocardium. Stains were negative for amyloid. He became unstable, went into ARDS, required intubation and hemodialysis. Repeat cardiac catheterizations disclosed normal PA and heart filling pressures. Despite paralysis and proning, he deteriorated and expired shortly after. Our patient likely had a subtype of Loeffler’s disease with mild peripheral eosinophilia but without vasculitis. Our goal is to emphasize that heart failure treatment is not identical for every patient, and an underlying etiology may change management significantly.

672 A case of angioedema leading to left atrial collapse

M Heckle1

L Julio1

Romero Legro I2

N Garg1

1University of Tennessee Health Science Center, Memphis, TN

2University of Tennessee, Memphis, TN

Background

Angioedema secondary to angiotensin-converting-enzyme (ACE) inhibitors is a rare but well known life threatening complication, with an overall incidence of 0.1%–0.2%. This rapid vasodilation and accumulation of interstitial fluid classically involves the mucus membranes of the tongue, lips and face, but has the potential to affect all areas of the body. We present a case of angioedema of the tongue, lips and esophagus causing hemodynamic collapse due to ACE inhibitor.

Case report

An 83-year-old African American male with a past medical history of hypertension, diabetes mellitus, coronary artery disease and chronic kidney disease presents to the emergency department with a chief complaint of tongue swelling. On presentation, he was in respiratory distress requiring intubation with severe swelling of his lips and tongue. He was admitted to the intensive care unit due to respiratory failure and refractory hypotension despite volume resuscitation. A bedside echocardiogram was performed by the intensivist team, which showed left atrial compression with concerns of focal tamponade. A formal transthoracic echocardiogram revealed a trivial pericardial effusion and evidence of left atrial collapse from an extracardiac mass. A non-contrast computed tomography scan of the chest showed severe esophageal swelling resulting in compression of the left atrium. After cessation of his ACE inhibitor and supportive care his clinical status improved.

Conclusions

Angioedema secondary to ACE inhibitor classically involves the lips, tongue and orpharynx. However, a visceral form exists that can affect the mucus membranes anywhere along the gastrointestinal tract. The presentation of this form of angioedema can be variable with non-specific abdominal complaints, which makes the diagnosis challenging. Our case is unique in that the severe degree of esophageal angioedema lead to left atrial compression and hemodynamic compromise of the patient.

674 Noncompaction or overreaction?

B Lennep

WF Campbell

MR McMullan

ME Hall

University of Mississippi Medical Center, Madison, MS

Case report

A 22 year old man presented via ambulance after a syncopal episode witnessed by his mother. She could not feel a pulse and began chest compressions. On ambulance arrival he was in sinus rhythm and hemodynamically stable. Echocardiography demonstrated mildly reduced left ventricular (LV) systolic function. Because his LV ejection fraction was >35% and there was no documented arrhythmia, he did not meet criteria for a secondary prevention defibrillator (ICD). Still, our team was concerned about his syncope with reported pulselessness. A cardiac MRI was performed which demonstrated biventricular hypertrabeculation. Late gadolinium enhancement (LGE) imaging (figure 1) showed extensive midmyocardial and subepicardial enhancement suggestive of fibrosis. This fibrosis, along with the hypertrabeculation and physical exam finding of dysmorphic facies, suggested a diagnosis of noncompaction cardiomyopathy. After some debate, we elected to implant an ICD based on the high-risk LGE finding of diffuse fibrosis. A few months later, he had a long run of ventricular tachycardia with syncope.

Noncompaction cardiomyopathy is associated with heart failure, arrhythmias, and sudden cardiac death. There are many proposed diagnostic criteria, but cardiac MRI provides important additional information such as fibrosis burden which has significant prognostic implications. In this case, it helped us make the decision to implant an ICD.

Endocrinology and Metabolism

Concurrent Session

1:00 PM

Saturday February 23, 2019
675 Vitamin d supplementation adherence among mobile gulf coast area pediatricians

D Chen

N Bilbao

University of South Alabama, Mobile, AL

Purpose of study

Vitamin D toxicity is on the rise in the Mobile Gulf Coast area in young, breastfed infants from age 2–4 months. They present with poor oral intake, lethargy, and dehydration. Long-term complications include hypercalciuria, nephrocalcinosis, and consequently chronic hypertension. The cause is usually inadvertent use of highly concentrated formulations of vitamin D which are not intended for breastfed infants. We hypothesized that adherence to guidelines for vitamin D supplementation in breastfed infants can be improved by educational intervention.

Methods used

We distributed 2 surveys in person regarding Vitamin D supplementation to various Pediatric clinics in the Mobile Gulf Coast Area. Between surveys we handed out latest appropriate recommendations on vitamin D supplementation from the AAP and the Pediatric Endocrine Society. The surveys included 8 questions regarding age, dosing, medication reconciliation, and testing for vitamin D levels for breastfed infants.

Summary of results

30 pediatricians filled out the pre-survey and 17 filled out the post-survey. For the 1st survey, 19/30 pediatricians always recommend or prescribe vitamin D, 22/30 prescribed at 1–2 months of age, 25/30 prescribed 400 IU daily. 25/30 never test for vitamin D levels in breastfed infants. 19/30 do not send for laboratory tests for vitamin D level. On 2nd survey 14/17 pediatricians prescribe vitamin D supplementation, 17/17 prescribed at 1–2 months, 17/17 prescribed 400 IU per day. 6/17 pediatricians never test for vitamin D levels in breastfed infants, and 10/17 tested only when there were concerns for high or low vitamin D. 7/17 order 25-OH hydroxy vitamin D while 9/17 do not send for any laboratory tests.

Conclusions

Pediatricians in the Mobile Gulf Coast Area prescribe appropriate amounts of vitamin D to breastfed infants (400 IU daily) and at the right age (1–2 months). With education, improvement is seen in the percentage prescribing vitamin D supplementation (63% to 82%) and prescribing at 1–2 months (83% to 100%). Survey weaknesses include low power and high number lost to follow-up with 2nd survey. The surveys were also not directed at other professionals who prescribe Vitamin D, including Family Practice physicians, Nurse Practitioners, Physician Assistants, and Naturopathic providers.

676 Temporal relationship between inflammation and insulin resistance and their joint effect on hyperglycemia: the bogalusa heart study

Y Yan1

S Li1

Y Liu1

L Bazzano1

J He1

J Mi2

W Chen1

1Tulane University, New Orleans, LA

2Beijing Children’s Hospital, Beijing, China

Purpose of study

To examine the temporal relationship between C-reactive protein (CRP) and insulin resistance and their joint effect on hyperglycemia in middle-aged adults.

Methods used

The longitudinal cohort consisted of 509 non-diabetic adults (360 whites and 149 blacks, mean age=42.8 years at follow-up) who had CRP, fasting glucose and insulin measured twice at baseline and follow-up over 6.8 years. Cross-lagged panel model was used to examine the temporal relationship between CRP and insulin resistance measured by homeostasis model assessment (HOMA). Incident type 2 diabetes (T2DM) information was collected in a survey in 6.1 years after the follow-up survey.

Summary of results

After adjusting for race, sex, age, body mass index, smoking, alcohol drinking and follow-up years, the path coefficient from baseline CRP to follow-up HOMA (β2=0.105, p=0.009) was significant and greater than the path from baseline HOMA to follow-up CRP (β1=0.005, p=0.903), with p=0.011 for the difference between β1 and β2. This one-directional path from baseline CRP to follow-up HOMA was significant in the hyperglycemia group but not in the normoglycemia group. In addition, participants with high levels of baseline CRP and follow-up HOMA had greater risks of T2DM (odds ratio, OR=2.38, p=0.035), pre-T2DM (OR=2.27, p=0.006) and hyperglycemia (OR=2.18, p=0.003) than those with low-low levels.

Conclusions

These findings provide strong evidence that elevated CRP precedes insulin resistance in non-diabetic middle-aged adults, and their joint effect plays a crucial role in the development of T2DM. Interventional studies regarding anti-inflammatory therapy for prevention of insulin resistance and T2DM are warranted.

677 Gene expression patterns in single islets from organ donors with or without diabetes

L Gunnels1

N Lenchik1

E Butterworth2

M Campbell-Thompson2

C Mathews2

M Atkinson2

I Gerling1

1University of Tennessee Health Science Center, Memphis, TN

2University of Florida, Gainesville, Gainesville, FL

Purpose of study

Type 1 diabetes (T1D) is the result of immune cell mediated destruction of insulin producing pancreatic islet beta cells. Preclinical disease progression is usually characterized by the appearance of autoantibodies in a patient’s serum. Single autoantibody positive individuals (sAb+) have a lower chance of progression to overt disease, compared to multiple autoantibody positive individuals (mAb+). Changes in gene expression patterns of the islet cells at different preclinical stages may help gain a better understanding of the pathogenesis and its progression.

Methods used

We collected individual pancreatic islets by laser-capture microscopy from multiple sAb+, mAb+, and T1D organ donors. We obtained comprehensive gene expression information by microarray analyses from each islet and compared expression data from all insulitic islets (those staining positive for insulin and CD3 T-cells) within the three donor cohorts. We then obtained lists of differentially expressed genes between each donor cohort using a Student’s t-test and performed data mining techniques using an online modern bioinformatics toolset.

Summary of results

Insulitic islets from sAb +donors, when compared to T1D donors, were found to express higher levels of transcripts relating to mitochondrial structure and oxidative phosphorylation as well as genes involved in immune activity and activation. Interestingly, however, mAb +donors, when compared to T1D donors, did not express significantly higher levels of mitochondrial genes and instead, showed a difference in expression of genes from pathways involved with immune activity and activation. When comparing sAb +and mAb +donors, we found the former expressed higher levels of mitochondrial genes, many of which overlapped with those differentially expressed in sAb +versus T1D. sAb +and mAb +donors did not exhibit significant differences in expression of immune activity genes.

Conclusions

This data suggests that, in a timeline for insulitic islets, mitochondrial genes change expression between progression from sAb +to mAb +status, while mAb +to T1D progression is marked by altered expression of immune activity and activation markers in insulitic T1D islets.

678 Activation of toll like receptor pathways in insulitic islets of type 1 diabetes

GB Nelson1

N Lenchik1

E Butterworth2

M Campbell-Thompson2

C Matthews2

M Atkinson2

I Gerling1

1University of Tennessee Health Science Center, Memphis, TN

2University of Florida, Gainesville, FL

Purpose of study

Type 1 diabetes (T1D) is an autoimmune condition, long hypothesized to be enhanced or triggered by certain viral infections. Islet pathology of T1D is characterized by destruction of insulin producing pancreatic beta cells. The purpose of this study was to identify specific pathways with differential expression of host genes in islets to identify evidence suggesting responses to a viral infection.

Methods used

Pancreatic tissue samples were obtained from non-diabetic donors (controls), autoantibody positive donors, and donors with T1D through the Network for Pancreatic Organ donors with Diabetes program. Laser microdissection was used to manually isolate individual islets based on presence or absence of insulin, with T-lymphocyte RNA isolated and microarray used to assess transcriptomes. Using Student’s t-tests, we analyzed expression levels of genes known to be involved in host response to viral infection. After finding increased expression of TLR2 in T1D islets versus controls, we used anchored analysis to identify other genes with similar expression patterns. These were then cross-referenced to confirm relationships with TLR pathways.

Summary of results

TLR2 showed higher expression in TID vs. controls (p=8.46E-5) and insulitic (Insulin +CD3+) islets vs. controls (p=3.8E-3). Using TLR2, an anchored analysis yielded ∼100 genes with an R≥0.65. Among these were several involved in the TLR signaling pathways. Increased expression in INS+CD3+vs INS+CD3 INS- islets was seen in a variety of genes including TLR pathway inhibitors: LAIR1 (p=2.77E-8), SIGLEC7 (p=8.33E-6), SIGLEC9 (p=1.59E-4), and C1q (p=6.11E-16); as well as genes downstream of the TLR pathway: CD163 (p=2.34E-11), CTSS (p=9.89E-7) and IFNγ (p=5.9E-8).

Conclusions

TLRs are very important for host response to viral infection. Much of the TLR pathway is regulated by phosphorylation or ubiquination and may not be upregulated at the RNA level. However, we demonstrate here that specific genes involved in TLR2 signaling are up-regulated in T1D islets, specifically in those with signs of immune activation and residual insulin positivity (INS+CD3+). This suggests the potential involvement of host viral response pathways in the development of T1D.

679 Evaluation of metabolic bone disease in preterm infants with intrauterine growth restriction

O Ginnard

Y Khairandish

M Aly

S Bhatia

M Abraham

S Jain

UTMB, Friendswood, TX

Purpose of study

Metabolic bone disease (MBD) remains an insidious comorbidity in premature infants. MBD is associated with numerous risk factors such as degree of prematurity, low birth weight, postnatal factors, medications that alter bone metabolism and mineralization, prolonged parenteral nutrition, and inability to tolerate enteral feeds. However, there is limited literature regarding the effect of intrauterine growth restriction (IUGR) on the development of MBD. Our goal was to compare the incidence of MBD in premature infants with and without IUGR.

Methods used

An 18 month retrospective study of very low birth weight (VLBW) infants and infants born at less than 34 weeks gestation without major anomalies was conducted to compare the incidence of MBD in infants with and without IUGR. Bone minerals and markers obtained at 4–6 weeks of age included: serum alkaline phosphatase (APA), calcium (Ca), phosphorus (P), magnesium (Mg), parathyroid hormone (PTH), and 25-OHVitamin D (25-OH-D).

Summary of results

306 neonates were included. Mean gestational age was 30±2 weeks with a birth weight of 1491±561 grams. 111 (36%) neonates had risk factors that warranted screening for MBD per American Academy of Pediatric recommendations. Thirty (27%) of the screened neonates were found to have MBD and started on treatment. Overall prevalence of MBD was 9.8%. Sixty-one (20%) of the total cohort of neonates included in the study were identified as IUGR via prenatal ultrasound, defined by estimated fetal weight <10% tile. 17% of the IUGR infants were found to have MBD. All of the IUGR neonates with MBD were found to have other concomitant risk factors, including bronchopulmonary dysplasia, exogenous corticosteroid use, and prolonged parenteral nutrition.

Conclusions

These preliminary findings suggest that IUGR is not a sole risk factor in the development of MBD in VLBW neonates or infants born less than 34 weeks. However, it may be possible that IUGR has a synergistic effect in developing MBD in infants with prolonged oxygen need, corticosteroid use, or parenteral nutrition need. Limitations include single-institution study and confounding effect of other comorbidities.

680 Diabetes alters ischemia-induced gene expression

FI Ariganjoye1

R Peravali1

L Gunnels1

I Gerling1,2

A Dokun1

1University of Tennessee Health Science Center, Memphis, TN

2Veterans Affairs Medical Center, Memphis, TN

Purpose of study

Peripheral Arterial Disease (PAD) is the result of atherosclerosis that impairs blood flow to the lower extremities and constitutes a major complication of diabetes. Individuals with Diabetes are more likely to develop PAD and when they have PAD, they have poorer outcomes. We hypothesized that Diabetes may alter normal adaptive gene expression in PAD.

Methods used

Type 2 diabetic (T2D) mice were generated by placing C57Bl/6 mice on high fat diet (HFD) starting at 6 weeks. 14–16 week old HFD fed C57BL/6 (B6) mice were used. Experimental PAD was achieved by unilateral femoral artery ligation and excision. Controls were strain, age, and sex matched. Total RNA was extracted from the ischemic gastrocnemius muscle on day 3 post-op. RNA was processed and hybridized onto Affymetrix Mouse430 expression arrays according to the manufacturer’s protocols. Expression values were normalized and provided expression analysis data on a total of 45 101 probe sets.

Summary of results

We identified 1261 probe set with highly significant expression differences between controls and experimental mice (p<0.005, no multiple test correction). ), 496 had lower expression in T2D compared to non-diabetic mice, while 765 genes had higher expression in T2D. To better understand the molecular pathways and biological processes associated with the genes altered in T2D we performed the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses on the top 500 differentially expressed genes. Our analysis identified important biologic pathways such as ‘metabolic pathways’, ‘phagosomes’, ‘lysosomes’ and ‘regulation of actin cytoskeleton’. In addition to KEGG pathways, we performed Gene ontology analyses (p<0.005, no multiple test correction) to better categorize genes found to be differentially expressed between non-diabetic and T2D mice. Gene ontology categories most strongly represented are ‘cellular processes’, ‘metabolic processes,’ localization and ‘binding’.

Conclusions

Our results confirmed that T2D alters post ischemic gene expression and advanced our knowledge about the specific genes and pathways that may modulate PAD severity and outcomes in T2D.

681 Differences in treatment of peripheral arterial disease procedures in hospitalized patients with type 1 or 2 diabetes

N Jain1

M Agarwal2

A Dokun1

1University of Tennessee, Memphis, Memphis, TN

2University of Tennessee Health Science Center, Memphis, TN

Purpose of study

Since Limited literature exists describing differences in treatment and outcomes, we sought to study procedural admissions among individuals with peripheral arterial occlusive disease (PAD) based upon type of diabetes.

Methods used

Using the Nationwide Inpatient Sample (NIS) database 2005 to 2014, we identified adult (age ≥18 years) diabetics with PAD along with critical limb ischemia or intermittent claudication who underwent treatment procedures: open revascularization, endovascular revascularization or amputation. This unselected national cohort was then studied to analyze the differences in clinical characteristics, treatment procedures and outcomes based on presence of type of DM (Type 1, T1DM vs. Type 2, T2DM).

Summary of results

Among 1,082,665 PAD procedural admissions in diabetics, 5.0% (n=53,831) had T1DM. Overall, T1DM were younger, more likely to be white, males, have private insurance and less likely to have concurrent diagnoses of hypertension, smoking, dyslipidemia, coronary artery disease, congestive heart failure, atrial fibrillation, cerebrovascular disease and chronic pulmonary disease (all p<0.001). T1DM group had significantly higher concurrent diagnoses of chronic renal failure. T1DM patients were more likely to undergo amputation (60.7% vs. 47.9%, adjusted odds ratio=1.39, 95% CI 1.35 to 1.42) and less likely to undergo endovascular (15.6% vs. 22.7%, adjusted odds ratio=0.86, 95% CI 0.84 to 0.88) and open revascularization procedures (10.7% vs. 15.5%, adjusted odds ratio=0.82, 95% CI 0.80 to 0.84). Overall in-hospital mortality was 1.8%; 1.9% in T1DM and 1.8% in T2DM. The overall median (IQR) length of stay (in days) was 7 (4 to 12); 8 (5 to 14) for T1DM and 7 (4 to 12) for T2DM. Overall median hospitalization cost was 38,108 (20,110 to 72,328); 52, 659 (28,871 to 97, 209) for T1DM and 52, 172 (30, 027 to 92, 824) for T2DM.

Conclusions

This is the first study to examine the differences in lower extremity PAD related procedural hospitalization based on type of diabetes. We observed that T1DM patients undergoing procedural hospitalizations were younger, preferentially were treated with amputations, and had higher length of stay when compared to those with T2DM.

682 Establishment of a novel placental barrier model of preeclampsia complicated by diabetes

R McLeese1,2

J Yu1

D Fu2

D Brazil2

T Lyons1

1MUSC, Charleston, SC

2Queen’s University Belfast, Belfast, UK

Purpose of study

Women with diabetes (DM) have a 4-fold increased risk of developing preeclampsia (PE) compared to the general population. Mechanisms for PE development are not well understood; however, abnormal placentation has been implicated. Trophoblast cells form the placental barrier that separates the maternal and fetal circulations. We hypothesize that in pregnancy complicated by DM, placental barriers may be compromised, leading to maternal systemic endothelial dysfunction. In this study, we sought to establish a model of placental barrier injury by exposing a monolayer of cultured trophoblasts to modified lipoproteins (which accumulate in vascular tissues of patients with DM) and/or high glucose.

Methods used

Human trophoblasts were cultured on semi-permeable transwell inserts (0.4 µm pores). Transepithelial electrical resistance (TEER) was measured every two days to assess barrier integrity. TEER levels reached a plateau 12–14 days after initial seeding. Cells were subsequently exposed to ‘highly-oxidized, glycated’ low-density lipoprotein (HOG-LDL) vs native-LDL (N-LDL) (200 µg/ml protein, 0–24 hours) on either apical or basolateral surfaces, in each case in the presence of normal vs high glucose. Zona occludens-1 (ZO-1) immunostaining was performed. Soluble endoglin (sEng) levels in cell supernatant and infranatant were determined by ELISA.

Summary of results

Following treatment with HOG-LDL (200 µg/ml, 24 hours) on either the apical or basolateral surface, TEER was significantly decreased by 22.8%±3.8% and 32.8%±3.0% respectively vs. untreated control (n=6, mean ±SEM, p≤0.05). High glucose alone did not elicit significant effects, nor did it amplify the effect of HOG-LDL. HOG-LDL appeared to disrupt barrier function, assessed by ZO-1 immunostaining. Following treatment with HOG-LDL vs N-LDL (200 µg/ml, 24 hours) on the apical side of the monolayer, sEng levels (mediator of PE) increased on the apical surface (3.1±1.5 vs. 1.7±0.8 ng/ml, n=6, mean ±SEM, p≤0.01), but not on the basolateral surface.

Conclusions

Extravasated, modified LDL may be involved in placental barrier injury, contributing to the high risk of PE in women with DM. This cell model has potential to be a valuable tool for the evaluation of novel therapeutics aiming to preserve placental barrier dysfunction in PE.

683 Effect of rosuvastatin on lipoprotein sphingolipids in patients with type 2 diabetes

CB Kelly1

MJ Leyva1

S Hammad1

R Klein1,2

M Lopes-Virella1,2

A Gosmanova3

P Alaupovic4

C Aston3

T Lyons1

1Medical University of South Carolina, Charleston, SC

2Veterans Affairs Medical Center, Charleston, SC

3University of Oklahoma Health Sciences Center, Oklahoma City, OK

4Oklahoma Medical Research Foundation, Oklahoma City, OK

Purpose of study

Statin therapy is indicated to reduce cardiovascular risk in Type 2 diabetes (T2D), acting in part by improving dyslipidemia, and in part through ‘pleiotrophic’ effects. Sphingolipids, including ceramides, are amphiphilic components that, with phospholipids, form lipoprotein surface monolayers and function as key signalling molecules. Sphingolipids regulate lipoprotein surface fluidity; ceramides are specifically associated with apoptosis and increased risk for premature coronary heart disease. Effects of statins on the sphingolipid content of lipoproteins are poorly defined.

Methods used

We determined, by liquid chromatography electrospray ionization–tandem mass spectrometry, whole plasma concentrations of individual ceramides, sphingoid bases, sphingomyelins, and glycosphingolipids (hexosyl- and lactosyl-ceramides) in plasma from 19 men and 21 women, with T2D, before and after rosuvastatin, 10 mg/day. Using earlier compositional data, we calculated effects on non-HDL sphingolipid content.

Summary of results

Rosuvastatin reduced total cholesterol (−33%), triglycerides (−20%) and LDL-cholesterol (−49%); HDL-cholesterol was unaffected. It decreased total sphingomyelin (−15%), ceramides (−29%), hexosyl- (−30%) and lactosylceramides (−34%), independent of gender. Assuming that sphingolipids in HDL were unaffected, rosuvastatin reduced non-HDL sphingomyelin by 42% (p<0.001) and ceramide by 61% (p<0.001). These reductions remained significant after correction for non-HDL cholesterol and/or lipoprotein surface area.

Conclusions

Rosuvastatin lowers not only the number of non-HDL particles, but also the sphingolipid and especially the ceramide content of each particle. This effect is independent of gender, and is potentially anti-atherogenic. Further studies are needed to determine mechanism(s).

684 Effect of ivacaftor on cystic fibrosis related diabetes in adults

RH Scofield1,2,3

HL Gaines1

KR Jones1,3

N Mehdi4

D Berry4

1University of Oklahoma Health Sciences Center, Oklahoma City, OK

2Oklahoam Medical REsearch Foundation, Oklahoma City, OK

3Department of Veterans Affairs Medical Center, Oklahoam City, OK

4University of Oklahoma Health Sciences Center, Oklahoma City, OK

Purpose of study

Cystic fibrosis (CF) is a common autosomal recessive disease for which life expectancy has increased greatly with almost all patients living to adulthood. About of adults with CF acquire cystic fibrosis related diabetes (CFRD) in which there is a severe decrement in insulin secretion after meals. Recently several new classes of drugs have been introduced that modulate the function of the cystic fibrosis transmembrane regulator (CFTR), which is expressed in pancreatic beta cells. We undertook this study to determine the effect of one of these drugs, ivacaftor, on CRFD.

Methods used

We reviewed the medical records of all adult CF patients followed in the comprehensive CF clinic at Oklahoma University Medical Center. Data were collected for age at diagnosis of CF and CFRD, use of CFTR modulators, use of insulin and hypoglycemia.

Summary of results

There were 66 adult CF patients with 30 (46%) of these having CFRD. Fourteen patients were taking ivacaftor of whom 13 (92%) had CFRD, compared to 17 of 52 (33%) of those not taking ivacaftor (p=0.05 by Fisher’s exact test). Among the 13 CFRD patients taking ivacaftor, 4 (31%) stopped insulin completely. A fifth patient went from three times a day short acting insulin with meals to using insulin once a week. No patient not taking ivacaftor markedly changed the insulin regimen (5 of 13 versus 0 of 17, p=0.009 by Fisher’s exact test).

Conclusions

Use of ivacaftor was associated with resolution of CFRD in a substantial fraction of patients. The CFTR is expressed in the beta cell and involved in insulin release. Ivacaftor potentiates the function of the CFTR protein in an ATP-independent manner. This effect likely occurs in the beta cell and improves insulin secretion resulting in improvement in CFRD.

685 Metformin increases survival in T2DM patients with pancreatic cancer and lymphoma

A Vacheron1,2

A Wynn1,2

J Zuber1,2

S Solomon1,2

1University of Tennesee Health Science Center, Memphis, TN

2VA Medical Center Memphis, Memphis, TN

Purpose of study

The biguanide drug metformin is one of the most commonly used drugs for treatment of T2DM. Diabetics are at an increased risk for cancer and metformin has been shown to possess anti-cancer properties. Previous studies using patient records have demonstrated improved outcomes in patients taking metformin suffering from prostate, colon, lung, thyroid, and esophageal cancers. Metformin’s main anti-neoplastic mechanism of action is widely believed to be mediated through AMPK resulting in inhibition of mTOR, inhibition of HIF-1 alpha, and activation of p53. We investigated the overall survival of T2DM patients on metformin with pancreatic cancer and lymphoma using the Computerized Patient Record System (CPRS) at the VA Medical Center, Memphis.

Methods used

Lymphoma and pancreatic cancer patients with DM2 were sorted into an experimental (metformin) group and a control (non-metformin) group. Patients were matched on baseline characteristics such as race, BMI, treatment, etc. Cancer outcomes, i.e. overall survival, metastasis, recurrences, incidence of new malignancies were recorded. Hemoglobin A1C and creatinine values were recorded and compared. Statistical analyses used included unpaired t-test and Chi-squared test.

Summary of results

There was significantly greater overall long-term survival in the metformin group compared to the non-metformin group for lymphoma (5.89 vs 1.29 years, p<0.001) and for pancreatic cancer (0.68 vs 0.22 years, p=0.016). Treatment modalities in both groups, i.e. surgery, radiation, and chemotherapy were comparable.

Conclusions

Metformin has a significant, positive therapeutic effect in T2DM patients with pancreatic cancer and lymphoma by increasing overall survival. The HbA1c values in both groups were comparable so greater mortality in the non-metformin group was not due to a lack of diabetic control. These results are very encouraging, and we would like to see a prospective study with metformin to confirm these results.

Health Care Research, Quality Improvement and Patient Safety

Concurrent Session

1:00 PM

Saturday February 23, 2019
686 Targeting errors of omission improves nutrition in the NICU: a quality improvement study

KE Chetta1

E Lombard2

J Davis2

C Domonoske2

C Arnold1

1University of Texas at Houston, Houston, TX

2Memorial Hermann Hospital, Houston, TX

Purpose of study

We conducted a quality improvement project in our level IV academic neonatal intensive care unit (NICU) designed to reduce the energy and protein deficits that typically accumulate over the first weeks after birth in very low birth weight (VLBW) newborns.

Methods used

Practice changes were implemented in 3 phases: (1) we created and distributed tables of energy (cals/kg) and protein (g/kg) goals by day of age to the NICU staff (2) we asked prescribing clinicians to record the total (enteral +parenteral) energy and protein prescribed in daily progress notes, and to report these data to supervising faculty on daily rounds; (3) we disseminated feedback reports showing compliance with new guidelines. Nutrition orders on days 7, 14, 21, and 28 were abstracted for all inborn infants and those transferred in <24 hours,<33 gestational age (GA) and <1500 g birth weight (BW), from September 2016-July 2018, excluding infants with major congenital anomalies and deaths before 28 days. Amounts of energy and protein prescribed were compared by phase and we adjusted for differences in GA and BW Z-score.

Summary of results

The average GA and BW were 27.7±2.9 wk and 1.02±0.3 kg for 288 VLBW newborns. GA and BW were similar from baseline through all phases. The adjusted mean increase in energy prescribed per phase was 3.7 cal/kg/day (108 cal/kg/d at baseline and 112, 116, and 120 cal/kg/d in phases 1–3). The increase from baseline vs phase 3 was 10.1 cal/kg/d, (95% CI 4.7 to 15.5, p<0.001). At baseline, 33% of orders met energy goals vs 55% in phase 3, p=0.002. For prescribed protein, the adjusted mean increase in per phase was 0.1 g/kg/d (3.5 at baseline and 3.6, 3.7, and 3.8 g/kg/d in phases 1–3). The increase from baseline vs phase 3 was 0.3 g/kg/d, (95% CI 0.13 to 0.45, p<0.001). At baseline, 47% of orders met protein goals vs 66% in phase 3, p<0.001.

Conclusions

Establishing nutritional goals by day of age, integrating enteral and parenteral nutrition orders, and daily attention to amounts prescribed resulted in improved nutrition prescribing practices. Nutritional deficits may be in part due to ordering oversight or errors of omission. These practices could improve nutrition for VLBW newborns in other NICUs.

687 Impact of a statewide computed tomography (CT) scan educational campaign on effective radiation dose for injured children transferred to a level I pediatric trauma center

R Nabaweesi1,2

C Akmyradov2

R Ramakrishnaiah1

C Cox4

C Rodgers3

R Maxson1

1University of Arkansas, Little Rock, AR

2Arkansas Children’s Research Institute, Little Rock, AR

3Arkansas Foundation for Medical Care, Little Rock, AR

4University of Central Arkansas, Conway, AR

Purpose of study

To determine the impact of a statewide Computed Tomography (CT) scan educational campaign on radiation dose among injured children transferred to a level I pediatric trauma center.

Methods used

All injured children who underwent CT imaging and were transferred to a Level I pediatric trauma center during 2010 to 2013 (pre campaign) and 2015 (post-campaign) were reviewed. Patient demographics, mode of transportation and emergency department length of stay at receiving hospital, scanned body region, injury severity score and trauma center level were analyzed. Median effective radiation dose controlled for each variable, pre-campaign and post-campaign, were compared using Wilcoxon rank sum test.

Summary of results

Three hundred eighty seven children younger than 17 years, were transferred to a Level I pediatric trauma center from 46 and 49 hospitals during the pre and post-campaign, respectively. In 2015, most (39%) transferring hospitals were centrally located in urban areas, closely followed by critical area hospitals (35%). Large and small hospitals accounted for 41% each. While patient demographics were similar, ground transportation increased from 60% to 80%. We analyzed 396 and 222 CT scans for the pre and post-campaign period respectively. Emergency Department disposition to Intensive Care or Operating Room decreased from 30.6% to 22.2%. Overall, median effective radiation dose significantly decreased from 3.80 to 2.84. Effective radiation dose for abdominal CT scans declined significantly from 7.2 to 4.13 p value 0.02, and radiation dose for head CT scans 3.28 to 2.50 p value <0.0001.

Conclusions

The statewide educational campaign contributed to the decline in effective radiation dose, acknowledging externalities that could affect the campaign’s impact. Our state potentially affords an ideal opportunity to implement standard dosing across trauma centers through audit and feedback, education, or policy change.

688 Long term sustainability of team based intervention to reduce impact of nonactionable alarms

J Yeh1

R Wilson2

L Young3

L Pahl4

S Whitney3

K Dellsperger5

P Schafer5

1Medical College of Georgia, Augusta University, Bogart, GA

2Children’s Hospital of Georgia, Augusta Medical Center, Augusta, GA

3Augusta University, Augusta, GA

4Philips Healthcare, Augusta, GA

5Medical College of Georgia at Augusta University, Augusta, GA

Purpose of study

Nonactionable alarms comprise over 70% of alarms and have been identified by the National Joint Safety Commission as a threat to patient safety due to clinician alarm fatigue and desensitization. A variety of interventions were reported to be efficacious to reduce alarm overload: however, few studies have reported results from sustained implementation. The objective of this study is to examine short and long-term effectiveness of an interdisciplinary team based alarm reduction intervention.

Methods used

This is a pre- and post-, longitudinal cohort study performed in the adult cardiology intermediate care unit at a 480-bed academic medical center in Georgia. The data were collected at baseline (pre-intervention), two weeks, and across an 18–30 month span post-intervention. Interventions included adjusting alarm thresholds, turning off premature ventricular contraction alarms, and others. The primary outcome is the change in number of total alarm signals before and after intervention.

Summary of results

The number of total alarms was reduced by 39% over a 14 day period post-intervention. The total number of alarms per patient bed per day decreased by 47%. The most prevalent nonactionable respiratory parameter alarms decreased by 58%, and the nonactionable arrhythmia alarms were lowered by 51%. Two-year follow up demonstrated a sustained 19% reduction in the total number of alarms per patient bed per day.

Conclusions

It is feasible to translate and maintain system-level interventions addressing alarm fatigue using an interdisciplinary team based approach. This is the first study reporting the translation and sustainability of a system-level alarm reduction program into the practice setting. Additional research studies are needed to test the feasibility, sustainability, and effects of system-level approaches in real-world settings.

689 Improving sedation levels: a quality improvement project

S Lavigne-Sims1

K Iheagwara1

R Mathews2

G Walker3

P McMahon1

1Our Lady of the Lake, Baton Rouge, LA

2Our Lady of the Lake Hospital, Baton Rouge, LA

3PCA, Baton Rouge, LA

Purpose of study

There is little guidance on sedation protocols and a lack of standardized care for intubated and mechanically ventilated children in many pediatric intensive care units (PICUs). We aimed to implement a quality improvement (QI) project to increase the percent of assessments in the PICU indicating approriate sedation levels of mechanically ventilated children.

Methods used

Our institution did not have a standardized approach to sedation. After studying the literature, we decided to use the State Behavior Scale (SBS), a valid and reliable tool that describes sedation levels in young,mechanically ventilated patients. We also implemented a sedation protocol modified from Children’s Hospital of Philadelphia’s protocol.

We tracked the adequacy of sedation over several ‘Plan, Do, Study, Act’ cycles. Interventions involved education delivered by unit champions that included teaching PICU nurses how to use the SBS to measure sedation levels. This was supplemented with checks to ensure the instrument was being used properly. The SBS was then included as a required task in the electronic medical record. A second series of training sessions focused on implementation of the sedation protocol. Booster sessions reviewing the SBS and protocol and posters displaying the protocol supplemented the original education sessions. Lastly, we provided a second booster session in which the SBS and sedation protocol were reviewed with nursing staff on the day shift.

Summary of results

At baseline, 62.5% of all SBS measurements indicated that patients were adequately sedated. After the final intervention, 85% of all SBS measurements indicated adequate sedation levels. See SBS Run Chart (figure 1).

Abstract 689 Figure 1

SBS run chart

Conclusions

Our series of interventions resulted in a substantial improvement in the percent of time PICU patients met standards for adequate sedation.

690 Developing an assessment of sub-intern communication skills involving transitions of patient care

AV Kusnoor

MM Rocha

Baylor College of Medicine, Houston, TX

Purpose of study

In response to a curricular gap and patient safety, we developed a Sub-Internship Communication Skills Curriculum (SI-CSC) for students focused on transitions of patient care. SI-CSC was delivered as 3 workshops using active role play: patient handoffs, requesting consults and discharging patients. Self-assessment data demonstrates students are achieving the learning objectives, but performance data is lacking. The objectives of this study are to design a multi-station observed structured clinical encounter (OSCE) to measure the sub-interns’ communication skills and perform a feasibility and effectiveness study.

Methods used

A multidisciplinary team of medical clinician educators developed cases and grading rubrics to assess the following skills:

  1. deliver a handoff,

  2. write a sign–out report,

  3. call a consult, and

  4. write a discharge summary.

‘Standardized residents’ (SRs) and faculty were trained to score student performance using reference norms. The SRs completed verbal communication checklists and delivered feedback. The faculty scored the written sigh-out report and discharge summary. Simple desriptive statistics were used to analyze student OSCE performance data and post-OSCE survey data. The rater’s global assessment of competence suggested competency cut-points.

Summary of results

27 sub-interns completed the exam. Surveyed sub-interns (88%) found the OSCE to be a fair test of their skills. For the written communication skills stations, the students scored a mean of 79%±14% (written sign-out) and 82%±11% (discharge summary). For both the handoff and consult stations, where mean scores were 80%±14% and 76%±13% respectively, a score of 70% or greater correlated with the rater’s global assessment of competence, suggesting a cut-point of 70%.

Conclusions

This feasibility study confirms that sub-intern communication skills for transitions of patient care can be objectively evaluated. The OSCE is poised to complement the SI-CSC and improve the communication skills of sub-interns to positively impact patient safety.

691 Hepatitis c testing in primary care patients with abnormal liver tests

A Schreiner

J Bian

J Zhang

W Moran

P Mauldin

D Rockey

Medical University of South Carolina, Charleston, SC

Purpose of study

Despite the attention paid to hepatitis C virus (HCV) birth cohort screening, HCV testing patterns in response to abnormal liver tests are less well known. We sought to assess factors associated with HCV testing in primary care patients with persistently abnormal liver tests.

Methods used

This retrospective cohort study used primary care patients with two consecutive abnormal liver tests. Patients were categorized by clinical pattern of abnormality: cholestatic, hepatocellular, and mixed patterns. The primary outcome was HCV antibody (Ab) testing. A second analysis evaluated those patients with HCV testing and a positive result. Different variables were evaluated for association with outcomes using multivariate logistic regression.

Summary of results

Of the 4586 patients included, only 739 (16.1%) patients had HCV testing. Variables associated with testing included hepatocellular or cholestatic liver test patterns, being older, and having a history of alcohol consumption (table 1). A total of 81 (11.0% of those tested) patients were HCV Ab positive. Multivariate logistic regression demonstrated that a positive HCV Ab test was associated with a hepatocellular (OR, 10.96) or mixed patterns (OR, 8.53) of liver test abnormality (table 1). Male gender, Medicaid enrollment, and drug or tobacco use were also associated with higher odds of HCV Ab positivity.

Abstract 691 Table 1

Multivariable logistic regression: odds ratios

Conclusions

Persistently abnormal liver tests, particularly with hepatocellular patterns of abnormality and in conjunction with male gender, alcohol, drug or tobacco use, should prompt HCV testing.

692 Electrocardiogram utility in tricyclic antidepressant therapy for functional gastrointestinal disorders

K Bonello

L Klein

A Milazzo

R Noel

Duke University Health, Durham, NC

Purpose of study

Tricyclic antidepressants (TCAs) are often prescribed at low dose for treatment of functional gastrointestinal disorders (FGIDs). Information on effects of low dose TCAs on cardiac conduction is sparse. We aim to investigate the utility of screening electrocardiograms (ECGs) for FGIDs in pediatric patients. Our goal is to reduce the number of unnecessary ECGs ordered. In addition, we aim to determine whether screening ECG helps identify clinically significant cardiovascular abnormalities and whether ECG data impacts the use of amitriptyline in a meaningful way.

Methods used

We conducted a single center retrospective chart review of all pediatric patients with an ECG ordered by a pediatric gastroenterologist when considering starting TCA therapy between 1/1/11–2/1/18. For all subjects, we collected demographic data, previous cardiovascular testing results, and TCA dosing. The ECGs were reviewed and compared to subsequent ECGs when available. We reviewed all subsequent cardiovascular testing and collected data on all subsequent cardiac diagnoses.

Summary of results

There were 233 subjects who met the aforementioned criteria. Most (55.6%) were treated for irritable bowel syndrome and the average dose of the TCA was 0.4 mg/kg/day. Nine patients (3.8%) were referred to cardiology. One underwent cardiac MRI, which was normal. One had prolonged QTc, The other seven were cleared from a cardiac standpoint. Of those who had a repeat ECG (n=18) while on a TCA, the average increase of the QTc was 6.5 milliseconds, which did not translate to a clinically significant change. Of note, there were 25 ECGs ordered when the subject had a normal ECG previously.

Conclusions

Our data support that repeat ECGs are not needed once starting amitriptyline therapy. In addition, providers should determine whether a patient already has a normal ECG prior to ordering a screening ECG. Only one patient was found to have prolonged QTc on ECG, resulting in an incidence of 0.4% in our study population; this is similar to published incidence of 0.4%. The broader goal of reducing the total number of ECGs ordered requires a cost/benefit discussion among providers in both pediatric cardiology and gastroenterology. However, our data supports the low incidence of prolonged QTc and clinically insignificant change in QTc while on low dose TCA.

693 Impact of an electronic medical record (EMR) intervention on clostridioides difficile testing

J Howard-Anderson

C Robichaux

M Sexton

J Varkey

B Albrecht

KA Jones

Z Wiley

J Jacob

Emory University, Atlanta, GA

Purpose of study

Testing patients with laxative-induced loose stools can detect asymptomatic colonization of C. difficile, leading to inappropriate treatment and financial penalties. We sought to assess the effect of an EMR intervention on the rates of C. difficile orders.

Methods used

In 2017, 4 hospitals implemented an EMR intervention to cancel inappropriate C. difficile orders when a laxative had been administered within 24 hours, unless overridden by the provider. We analyzed monthly rates of total C. difficile orders, first orders that were inappropriate and percent test positivity for 2 years pre- and 1 year post-intervention. We used χ2 and t-tests, and interrupted time series (ITS) in SAS 9.4 to assess the intervention effect.

Summary of results

13 934 unique patients had 17 902 admissions with at least one C. difficile order. 53% were female with a mean age of 61±17 years and a median Charlson Comorbidity Index of 4±4. The mean C. difficile order rate per 1000 patient-days was 21.5±1.4 pre- and 16.5±0.7 post-intervention (p<0.001). Using ITS, the intervention significantly decreased the monthly rate of C. difficile orders (p<0.01, figure 1). 14.7% of initial C. difficile orders were inappropriate (15.5% pre- v. 12.9% post-intervention, p<0.001). However, ITS analysis did not show a change in the monthly proportion of inappropriate orders (p=0.15). The C. difficile positivity rate remained stable (17.0% v 16.0%, p=0.10).

Abstract 693 Figure 1

C. difficile orders per month

Conclusions

A simple EMR intervention significantly decreased the C. difficile order rate. Since the proportion of positive tests was unchanged, the intervention may have improved diagnostic efficiency, but it did not reduce the proportion of inappropriate orders.

694 Analysis of recent pediatric firearm-related fatalities in a southern urban county

SE Richard

D Atherton

K Monroe

University of Alabama, Birmingham, AL

Purpose of study

In recent years, increased gun violence has focused national attention on communities’ attitudes toward guns and gun-related legislation, particularly in the wake of mass shootings and school shootings. These shootings, however, comprise only a small proportion of pediatric firearm-related injuries and deaths in most communities.The primary objective of this study was to analyze various forensic data surrounding cases of pediatric gun-related deaths observed in Jefferson County, Alabama since 2014 to both elucidate how local children have died in shootings and investigate potential avenues for community-based firearms interventions.

Methods used

This was a retrospective study in which the authors reviewed all pediatric firearm-related deaths that occurred in Jefferson County, Alabama from January 2014 through May 2018. Case files containing police reports, investigative reports, and autopsy reports were reviewed for information including cause and manner of death, type of gun used, and relationship of the owner and shooter of the gun.

Summary of results

From 2014 to May 2018, the JCCMEO assumed jurisdiction of 38 pediatric deaths related to firearm injuries. These comprised 20% of all pediatric deaths examined by the JCCMEO in that same period. Four (11%) of cases were accidental, 3 (8%) of cases were suicides, and the remaining 31 (81%) were homicides. Handguns were most often the kind of gun causing death. In the majority of cases which were ruled suicides and accidents, the owner of the gun was a relative of the decedent. In only one case was a fatality due to an injury received at a school, and in that case, there was evidence that the shooting was unintentional.

Conclusions

Firearm-related violence is an important public health concern and accounts for a significant proportion of pediatric injury and fatality. There are a wide variety of circumstances surrounding how these injuries occur. While mass?and school shootings understandably receive significant national attention, in most jurisdictions other circumstances of violence account for most pediatric gun-related deaths. This study emphasizes the need for continually evolving interventional community strategies that reduce the potential for firearm-related pediatric violence and fatalities.

695 Evaluating the impact of a student-run hospital consult service for patients experiencing homelessness on health care utilization

F Gill

G Green

Tulane University School of Medicine, New Orleans, LA

Purpose of study

Patients experiencing homelessness face substantial barriers to accessing high quality, coordinated care. These barriers include a highly fragmented social safety net, as well as poor access to transporation and financial resources. Inpatient hospital stays are unique opportunities to bridge gaps in care in this highly vulnerable population. To provide additional support to these patients during their hospital stay, the Homeless Hospital Liaison (HHL) program was developed. HHL is a student-run hospital consult service for patients experiencing homelessness. HHL is operated by medical and social work students, who work collaboratively to provide interdiscliplinary care that meets the unique health and social needs of this population. The purpose of this study is to assess the impact of the HHL program on health care utilization in this population.

Methods used

To assess the impact of the HHL program, we compared several metrics of health care utilization, including emergency department visits, hospital days, hospital admissions, and follow-up appointment attendance rates between the nine months before and after our intervention. We used a paired t-test to compare these metrics. In addition to performing a pre-/post- intervention comparison, we also compared the health care utilization of participants in our program to that of patients eligible for our program but not enrolled. To further elucidate the impact of our intervention, we will stratify results by patient characteristics and specific arms of our intervention, and we will perform a cost-analysis to assess whether or not our intervention has resulted in any cost savings for the hospital.

Summary of results

Preliminary results indicate that participants in our program have a statistically significant decrease in hospital admissions of 49.4% (p<0.01) and hospital days of 47.7% (p<0.01). However, emergency department visits increased by 2%, although this value was not statistically significant.

Conclusions

Although preliminary results are encouraging, our sample size is still quite small (n=60). Still, the significant decrease in hospital days and hospital admissions strongly suggests that our intervention has resulted in altered health care utilization patterns in this population.

696 Characterizing failure to establish hepatitis c care among patients diagnosed in an urban academic emergency department

J Blackwell

J Rodgers

E Hess

UAB School of Medicine, Birmingham, AL

Purpose of study

We implemented an opt-out hepatitis C virus (HCV) screening program in 2013 targeting baby boomers presenting to the emergency department (ED). A linkage-to-care (LTC) program was initiated to link confirmed HCV-positive cases to care, and screening was expanded to all ED patients in 2015. The purpose of the current study is to determine predictors of linkage failure among all confirmed HCV-positive cases. By characterizing patients at highest risk for LTC failure, we hope to develop targeted interventions to optimize LTC efforts.

Methods used

All patients presenting to the ED (an academic ED with 73 000 annual visits) between 2015 and 2018 were offered an HCV antibody screening test. Patients screening positive were contacted (when possible) by a linkage coordinator, who sought to facilitate linkage to outpatient care. Linkage outcomes (linked vs. not linked) were analyzed based on known LTC barriers, demographics, and factors influencing HCV treatment eligibility. Successful linkage was defined as a patient attending a scheduled HCV clinic visit. Logistic regression was used to measure the univariate association between each predictor and successful LTC.

Summary of results

Between August 2015 and June 2018, 48 947 patients were screened for HCV, yielding 4026 positive results. HCV infection was confirmed in 1798 patients, 1496 of whom were eligible for the current study. By July 2018, 819 eligible patients (54.7%) had been successfully linked to care. Variables associated with LTC failure included treatment ineligibility at the time of screening (OR 19.5, 95% CI 6.0 to 63.0), specifically ineligibility due to a medical comorbidity (OR 15.3, 95% CI 5.5 to 42.7). In addition, belonging to the baby boomer cohort was associated with a decreased risk of LTC failure (OR 0.78, 95% CI 0.63 to 0.97). Factors such as insurance status, homelessness, mental health disorder, and substance abuse were not found to be associated with LTC failure.

Conclusions

Various factors have been associated with failure to establish care for patients with HCV. While further analysis needs to be conducted, our preliminary results indicate that birth cohort and medical ineligibility for HCV treatment may predict linkage outcomes.

Medical Education/Medical Ethics/Advocacy

Concurrent Session

1:00 PM

Saturday February 23, 2019
697 New view for otitis media

C Smola

A Fowler

NP Shah

K Monroe

UAB, Birmingham, AL

Purpose of study

Acute otitis media (AOM) is one of the most common diagnoses in childhood and one of the most frequent patient encounters in the emergency department or pediatric office. However, teaching of ear exams in real time is difficult due to limitation of visibility of the tympanic membrane (TM) by both teacher and student at the same time. A device, Oto, has been developed that turns an iPhone into an otoscope and allows for visualization of TM by more than one person at a time and possibility for recording pictures. The purpose of this study was to evaluate the utility of this device in teaching ear exams to residents in real time.

Methods used

Pediatric and Medicine-Pediatric residents used the Oto device with an iPhone in our Pediatric Emergency Department from March to June of 2018. Residents completed a survey to obtain their level of training, if they had used Oto or similar device, and comfort level with ear exams. Residents then used Oto for patient encounters and took a video of the TM. We included all possible patient encounters with and without diagnoses of AOM. After the exam, residents recorded their diagnosis and basic demographics of the patient. Two attending pediatricians reviewed the images to see if their diagnoses matched the resident diagnosis. The reviewers classified the photos as TM visualized or not.

Summary of results

18 residents completed our survey and used Oto with 154 patient encounters recorded. Comfort level was most commonly recorded as 5. Chief complaint was varied with about half of encounters presenting for an acute illness. AOM was diagnosed 6 times out of the 154 encounters with 2 indeterminate exams by residents. There was substantial agreement between our two attending pediatricians on video ear exams conducted by pediatric residents (Cohen’s kappa=0.737; p<0.0001). There was 66.7% agreement between the reviewers and the diagnosis recorded by the residents.

Conclusions

Residents give positive feedback regarding the device in sharing findings; however, there was a learning curve to obtaining clear videos with the device. Overall, there was significant agreement for videos that were clear. Disagreement between reviewers and residents resulted more from a style of practice disagreement than from the videos themselves. This leads us to believe that continued use of the Oto device will continue to improve education regarding diagnosis AOM.

698 Improving safety and injury prevention training in early education settings

K Morgan

C Garbe

M Dunlap

University of Oklahoma Health Sciences Center, Oklahoma City, OK

Purpose of study

The purpose was to improve safety and injury prevention in children by educating early education providers through training with AAP safety and injury prevention modules. We sought to establish whether AAP safety and injury prevention training increased community educators’ knowledge of common early childhood injuries and prevention strategies for implementation at sites.

Methods used

Standardized Safety and Injury Prevention training presentation developed through AAP was delivered to early childhood educators at 2018 Oklahoma Head Start conference. Surveys were administered to participants prior to and immediately following the training. Chi-square tests were used to test the equality of proportions, investigating whether the proportion of individuals answering correctly changed significantly from the pre to the post training tests.

Summary of results

12 pre and post surveys were collected from early childhood educators who completed training at the conference. Participants from regions across Oklahoma had a mean of 25.5 years experience in early education settings. The following had the largest improvement in pre vs post-test knowledge. For identifying falls as the most common preventable cause of death for children ages 1–4, 25.0% correct pre and 83.3% post-test (p value 0.004). For identifying latex balloons’ association with the highest rate of death from choking, 8.3% correct pre and 100% post-test (p value<0.0001). For identifying cooking as the leading cause of home fires and home fire injuries, 8.3% correct pre and 83.3% post-test (p value 0.0002). Participants gave feedback on a scale of 1 to 10 with 1 as not valuable and 10 as extremely valuable. On how well the training informed them of updated child safety and injury prevention guidelines, 58.3% rated a 10, 16.7% a 9, 16.7% an 8% and 8.3% a 7. On how likely they are to recommend this training to colleagues, 58.3% rated a 10, 33.3% a 9, and 8.3% an 8. On how likely they were to implement any guidelines at their facility, 58.3% rated a 10, 16.7% a 9, 16.7% an 8, and 8.3% a 7.

Conclusions

Safety and injury prevention knowledge gaps exist in early childhood educators, even those with decades of experience. Participants enjoyed the AAP training and their knowledge increased with a significant improvement in correct answers to questions following the training.

699 The effect of lumbar puncture simulations on pediatric residents

R Parlar-Chun

MGovern Medical School, Houston, TX

Purpose of study

Lumbar punctures (LPs) are an ACGME requirement, and one of the most important procedures that a pediatrician performs. There are variable rates of success particularly among learners in academic hospitals. Simulation based medical education may be useful in improving success and providing experience, education, and confidence in performing LPs.

Methods used

Pediatric residents were surveyed at the end of each month regarding their confidence, success, need for multiple attempts, use of local anesthetic, and use of stylet out technique. Pre-intervention period was from July 2017 to December 2017. From January 2018 to June 2018, pediatric residents received monthly LP simulation sessions at the beginning of the month that included a review of a LP procedural checklist, viewing of POISE Pediatric Lumbar Puncture instructional video, and hands on practice on LP simulation modules. Chi square and Fisher Exact Test were used as appropriate to compare the pre and post intervention groups.

Summary of results

105 resident responses and 150 LP attempts were recorded. Overall, no significant difference was found in overall success rate of LPs, need for multiple attempts, or use of local anesthesia in the pre and post simulation group. There was a significant increase in knowledge of stylet out technique (52% vs. 95%), and use of the technique (30% vs. 72%). Increasing PGY 1–3 status (22%, 40%, 61%) and experience 0–5 v.>5 LPs (28%, 61%) showed a significant increase in success. Increasing confidence also showed similar increase in success, with a significant increase in confidence in the post-simulation group.

Abstract 699 Table 1

Pre and post simulation outcomes

Abstract 699 Table 2

Increasing confidence post-simulation

Conclusions

Monthly lumbar puncture simulations are not enough to increase LP success rates. However simulation may be useful in increasing knowledge, experience, and confidence in the procedure.

700 Shifting approach to resuscitation in the ‘gray zone’ of gestational viability

K Arbour

A Dunbar

EB Lindsay

Tulane University School of Medicine, New Orleans, LA

Purpose of study

In 2007 published data indicated a ‘gray zone’ of viability at 23 to 24 weeks gestational age (GA).1 We reassessed neonatologists’ approach to resuscitation of neonates born at the limit of gestational viability.

Methods used

A Qualtrics survey was developed and emailed to practicing neonatologists across the country. The survey assessed delivery room care for infants born at 22 to 26 weeks GA, factors affecting decision-making for these infants, and resources utilized for resuscitation. Only completed surveys were examined. Descriptive statistics were used for analysis.

Summary of results

162 completed responses were analyzed. There was consensus supporting full resuscitation at 25 to 26 weeks. Below 25 weeks, the percentage of neonatologists endorsing full resuscitation decreased with decreasing GA and deference to parental wishes regarding resuscitative efforts increased with decreasing GA, except for resuscitation at 22 weeks. Provision of comfort care only was endorsed at 23 and 22 weeks (figure 1). Outcomes based on population data (72%) most impacted decision-making regarding resuscitation at 26 weeks, while parental wishes (35%), outcomes based on population data (31%), and futility (20%) were most influential at 22 weeks gestation.

Conclusions

Our survey indicates a shift in the ‘gray zone’ of viability to 22 to 23 weeks over the past decade.1 This shift may reflect increased use of population data to guide resuscitative efforts and revised resuscitation guidelines. Resources and management of resuscitation in the ‘gray zone’ vary.

Reference

  1. Singh J, Fanaroff J, Andrews B, Caldarelli L, Lagatta J, Plesha-Troyke S, Lantos J, Meadow W. Resuscitation in the ‘gray zone’ of viability: determining physician preferences and predicting infant outcomes. Pediatrics2007September;120(3):519–26.

701 Exploring third-year medical students’ professional identity formation after clinical simulation

L Tien

T Wyatt

M Tews

A Kleinheksel

Augusta University, Augusta, GA

Purpose of study

Simulation is a valuable tool in medical education by standardizing clinical experiences in order to train and assess medical students without the risk of patient harm. Beyond the scope of training and assessment, simulation may also be a valuable tool in promoting students’ professional identity formation (PIF) and sense of patient ownership. There is currently no known research on PIF and patient ownership within a simulated clinical environment. The purpose of this study was to explore how simulation affects students’ PIF and sense of patient ownership.

Methods used

A mixed-methods study was conducted with third-year medical students who experienced a simulated in-patient case of acute chest pain. A post-simulation survey asked students’ about their simulation experience, clerkship rotation (in-patient vs. out-patient), prior clinical experience, and included open-ended prompts on PIF and patient ownership. Textual data were coded as part of the latent content analysis and included individual element codes (thinking like a doctor, acting like a doctor, feeling like a doctor, metacognition) and contextual element codes (people in the simulation, material environment, time, place, language). Code frequencies were recorded for each students’ responses as their Individual Element Score (IES) and Contextual Element Score (CES). A two-way MANOVA was performed to explore relationships between the independent variables (clerkship block and prior clinical experience) and the dependent variables (IES and CES). Post-hoc analysis was conducted using two independent samples t-tests.

Summary of results

Students who had an in-patient clerkship block had significantly higher IES (2.65+0.897) compared to students who had an out-patient clerkship block (2.18+0.727), p=0.017. Students who did not have prior clinical experience before their clerkships had significantly higher IES (2.63+0.761) compared to students who did have prior clinical experience (2.14+0.932), p=0.017.

Conclusions

This study showed that simulation can promote students’ PIF and patient ownership, particularly in students who completed an in-patient clerkship block or lacked prior clinical experience. Simulation can be intentionally designed to promote PIF and patient ownership and should be used more often and earlier in medical education.

702 Medical-legal partnership in an urban medicaid population

M Michalopulos1,2

K Ramsey2,3

E Dobish1,2

1University of Tennessee Health Science Center, Memphis, TN

2Le Bonheur Children’s Hospital, Memphis, TN

3University of Memphis School of Law, Memphis, TN

Purpose of study

Patients who suffer from chronic illness often have environmental factors that exacerbate disease burden and hinder development. Access to legal services can help ensure these environmental factors are addressed. Le Bonheur Children’s Hospital has partnered with the University of Memphis School of Law and Memphis Area Legal Services to form the Memphis Children’s Health Law Directive (CHiLD), comprised of a pediatrician, attorneys, and licensed medical social worker. Memphis CHiLD provides legal support to assist with the management of medical conditions. Our aim was to review the clients served by Memphis CHiLD and look for trends in medical diagnoses with legal needs.

Methods used

Retrospective medical chart review of clients served by Memphis CHiLD was performed. Demographics including race, age, and gender were collected. Charts were screened for medical diagnoses prompting the referral for legal services. IHELP (income, housing, education, legal status, personal/family stability) category indicating legal need was also included for analysis.

Summary of results

79 records had all pertinent demographic information. Median client age was 12.08 years with a range of 23.8 years. The oldest was 25.25 years and the youngest 1.42 years. 39 clients were male and 40 were female. 13 identified as white, 58 as black, 4 Hispanic/Latino, and 3 other. Common diagnoses necessitating referral for services included epilepsy (n=23), developmental delay (n=13), asthma (n=9), genetic anomaly (n=9), trauma (n=8), autism (n=7), and other behavior problems (n=5). Legal aid was provided for income (n=9), housing (n=15), education (n=12), legal status (n=1), personal stability (n=33).

Conclusions

Memphis CHiLD serves a diverse group of clients ranging from toddlers to adults. The primary underlying condition of patients prompting referrals were related to neurologic and developmental conditions, but various medical conditions were represented. This preliminary data highlights the importance of collaboration between the medical and legal fields and the diverse medical conditions that often have legal components as a part of the treatment plan. Further analysis is needed into health related quality of life outcomes after legal aid is provided.

703 Longitudinal wellness curriculum: normalizing resident wellness

C Park1,2

C Abrams1,2

J Wilson1,2

M Bugnitz1,2

B Bagga1,2

1University of Tennessee Health Science Center, Memphis, TN

2LeBonheur Children’s Hospital, Memphis, TN

Purpose of study

Design a longitudinal curriculum to improve resident wellness in the pediatric residency program. We hypothesized that a longitudinal wellness curriculum implemented during work hours would ensure resident participation and improve resident wellness.

Methods used

A needs assessment was done to evaluate the need for a longitudinal wellness curriculum. Subsequently, we initiated monthly wellness morning reports (WMRs) on ward teams (Sept 2016) facilitated by Chief Resident(s) and an Associate Program Director (APD) identified as ‘wellness champions’. This was done during usual work hours after night team sign-out to ensure participation of both day and night teams and the Attending Physician. The content of WMRs was semi-structured addressing multiple topics around burnout and wellness, including but not limited to team building, reflection, debriefing, self-care, and healthy coping mechanisms. A post-survey was done to evaluate the curriculum.

Summary of results

1. Needs Assessment: 98% of residents agreed that a longitudinal wellness curriculum would be valuable (n=42/43). Majority (88%) of the residents felt that resident wellness was ‘very important’. All residents expressed that the likelihood of participation would increase if the curriculum was implemented during protected time at work. 26% said they would NEVER participate in activities outside of work hours. 2) Curriculum Evaluation: When asked ‘how beneficial the WMRs were’, the average rating was 4/5 (n=32). Majority (>90%) of the residents reported an increase in knowledge about resident wellness after participation. Also, residents reflected positively on WMRs, with common themes being around the ‘comfort of hearing that everyone struggles’, ‘learning from each others’ and the attendings’ coping mechanisms’, and the ‘importance of being able to express their emotions and struggles in a safe space’.

Conclusions

Most residents in our program felt that it is important to address wellness and preferred a longitudinal curriculum within work hours. Residents felt a longitudinal curriculum comprising of WMRs led by APD/Chief Resident(s) for the ward teams addressing resident wellness/coping skills is beneficial. Ongoing input from residents continues to help modify our curriculum to better target their needs.

704 Self-directed video vs. instructor-based neonatal resuscitation training of novice providers: a randomized. controlled, blinded, non-inferiority, international study

D Dannaway

EG Szyld

University of Oklahoma Health Sciences Center, Oklahoma City, OK

Purpose of study

Despite practice changes, neonatal mortality remains high, notably in underserved areas. Too few neonatal resuscitation trainers are available to provide adequate training, widening this gap. The use of video-based self-directed instructional programs has expanded, though without systematic efficacy research. We compared two such programs: one self-directed and one instructor-led.

Methods used

This multicenter, randomized, blinded, non-inferiority trial compared neonatal resuscitation skills of novice healthcare trainees on a standardized Objective Structured Clinical Examination (OSCE). All trainees watched the same self-directed video developed for this study and based on Neonatal Resuscitation Program guidelines for positive pressure ventilation via mask. In two-hour training sessions, both groups practiced with T-piece resuscitators and neonatal mannequins; the self-video group did so independently, the ins-video group with an instructor present. We hypothesized that OSCE performance would be the same for both training methods. OSCE performance was assessed before and after training via video recording and scored by a blinded evaluator. Trainees also completed a resuscitation knowledge survey after training. Three international centers (Chile, Argentina and US) participated with IRB approval from each site.

Summary of results

116 trainees were enrolled: 59 randomized to Self-Video, and 57 to Ins-Video instruction. There were no differences in age, gender or profession. Groups did not differ on pre- or post-training OSCE scores or on post-training resuscitation knowledge. A non-inferiority analysis found that the self-video group was not inferior on any outcome measure.

Abstract 704 Table 1

OSCE and knowledge test scores

Conclusions

Training with a self-directed video does not differ from and is as effective as standard instructor-based training.

705 Medical student evaluation of novel feedback sessions

A Caldwell

AG Darden

University of Oklahoma Health Sciences Center, Oklahoma City, OK

Purpose of study

The Mini Positive Feedback Session was created to improve the frequency and effectiveness of feedback to third year medical students during their outpatient pediatric rotation and used during four hour clinic sessions. The objective of this study was to evaluate the use of the sessions on medical student experiences.

Methods used

Learners were asked to participate in an optional positive feedback session. Each learner identified one strength exhibited during the session and one strength their colleague exhibited. The faculty member facilitated the discussion, which lasted around 5 min. This is a retrospective survey study using anonymous faculty evaluations from medical students 2017-present. In a range from 1 to 7 students were asked to respond to the statement: ‘Seeks feedback from and gives feedback to students, questions students to probe their knowledge and judgement,’ mean and standard deviation of responses was determined. Qualitative responses from medical student comments were coded and analyzed.

Summary of results

There were 77 anonymous medical student evaluations. During the 2017–2018 academic year, students responded an average of 6.84 (Stdev 0.5) in response to the question regarding feedback. During 2018–2019, responses were an average of 7.00 (Stdev 0). Themes from responses included that students thought favorably of the sessions, ‘Excellent feedback sessions,’ and ‘I loved the positive feedback sessions that she implemented at the end of the day.’ Also, the sessions helped students identify strengths, ‘Not only did it help me identify my strengths, but it also helped create a positive atmosphere between students,’ and ‘The incorporation of a positive feedback session is amazing, as a lot of feedback 3rd years receive aren’t typically that positive.’ The third theme was that the positive feedback could be used constructively by medical students to improve clinical interaction with patients.

Conclusions

This novel feedback approach was appreciated by medical students. Utilizing this technique for providing feedback could facilitate student learning during clerkship. Faculty could implement this technique to improve feedback for medical students and other learners, particularly in busy clinics when there is limited time for feedback.

706 A novel sub-internship communication skills curriculum for transitions of patient care

MM Rocha

AV Kusnoor

Baylor College of Medicine, Houston, TX

Purpose of study

Effective communication between physicians is critical for safe patient transitions, yet these skills are taught in fewer than half of sub-internships. Finding this gap, we developed and implemented a Sub-Internship Communication Skills Curriculum (SI-CSC): workshops (WSs) on patient handoffs, requesting consults, and patient discharges. The study objectives were to assess the effects of participating in SI-CSC and to develop a blueprint to improve the SI-CSC.

Methods used

SI-CSC objectives were mapped to AAMC core-EPAs for Entering Residency. SI-CSC was delivered as 3 WSs using active role play. Following day 1 WSs each month (1/2017 – 6/2018), students self-assessed changes in knowledge/skill using 5-point scaled items; and described attitudinal changes and feedback via free-text responses. On end-of-course evaluations, students self-assessed skills and provided WS comments. Data were analyzed using descriptive statistics, and significance tests and effect-sizes from Wilcoxon Signed-Rank Tests were tabulated (SPSS 25). Thematic analysis was used to analyze free-text data.

Summary of results

Response rates for the SI-CSC and end-of-course evaluations were 96% (856/889), and 88% (227/258), respectively. For all paired-items asking about pre-/post changes in knowledge/skill, median responses increased from 2 to 5 (p<0.001), and all demonstrated moderate to large effects sizes (r-values 0.51 to 0.59). Median confidence in performing key skills increased from before to after WS, and from before WS to end-of-course ‘I can apply’ and ‘I can perform’ items all showed statistically significant increases in median responses (p<0.001). A large majority of students agreed/strongly agreed that WSs were ‘beneficial preparation for my role as a sub-intern.’ Students reported a rise in confidence performing key skills in all 3 domains. An improvment blueprint for the SI-CSC was generated.

Conclusions

Gains in communication skills for patient care transitions following the SI-CSC were statistically significant with moderate-to-large effect sizes. Gains were sustained over the month. Sub-interns described the SI-CSC as confidence-building and provided feedback to improve WSs. Next, we will develop and evaluate an OSCE assessing the SI-CSC skills and revise the SI-CSC WSs.

707 Reach out and read training in residency continuity clinics

A Caldwell1

E Erickson2

N Shearman3

C Garbe1

R Needlman4

M Dunlap1

1University of Oklahoma Health Sciences Center, Oklahoma City, OK

2Duke, Durham, NC

3Reach Out and Read, Boston, MA

4Case Western Reserve University School of Medicine, Cleveland, OH

Purpose of study

Improvements in early childhood literacy as a result of the Reach Out and Read (ROR) intervention have been well described. However, it remains unclear to what extent physicians are trained through residency in regards to early childhood literacy. The purpose of this study is to describe ROR training that pediatric and internal medicine/pediatrics residents receive nationally and their use of ROR.

Methods used

This study was a part of a collaboration between ROR and Continuity Research Network (CORNET). Faculty and residents at participating CORNET sites completed an anonymous online survey. Descriptive statistics were determined. Chi square testing was performed.

Summary of results

There were 1695 total responses from 42 institutions. Faculty were more likely than residents to report receiving online ROR training: 61.9% of faculty and 42.6% of residents (p<0.0001). There was no difference between the proportion of faculty and residents who reported any of the other training modalities. In regards to formal training in continuity clinic, 62.4% of faculty and 65.0% of residents (p=0.39) reported receiving this training, 53.3% of faculty and 51.9% of residents (p=0.47) reported formal in person training, while 88.2% of faculty and 90.3% of residents (p=0.17) reported learning in clinic from other residents or faculty. In regards to grand rounds, 39.4% of faculty and 34.9% of residents (p=0.06) reported receiving this, while 45.0% of faculty and 44.6% of residents (p=0.84) reported receiving ROR training from a conference. More faculty than residents reported giving out a book in clinic, 97.3% vs 94.7% of residents (p=0.02), providing literacy based anticipatory guidance, 87.3% vs 72.5% (p<0.0001), modeling shared reading, 69.1% vs 41.4% (p<0.0001), and using a book as a tool for developmental assessment, 79.7% of faculty and 56.0% of residents (p<0.0001).

Conclusions

Most residents and faculty are trained in use of ROR from others in clinic. Many residents have not received the online ROR training. Improvements in formal training modalities could improve use of the ROR program.

Perinatal Medicine II

Concurrent Session

1:00 PM

Saturday February 23, 2019
708 Prolonged antibiotic therapy alters intestinal development and increase permeability in neonatal mice

H Chaaban1

J Eckert1

K Burge1

M Patel2

F Lupu2

1Oklahoma University Health Sciences Center, Oklahoma, OK

2OMRF, Oklahoma, OK

Purpose of study

Evidence suggest that prolonged antibiotics in premature infants is associated with increased mortality and morbidities such as late onset sepsis (LOS) and necrotizing enterocolitis (NEC). These effects are likely due to microbial alteration; however, the exact mechanism is still unclear.

Methods used

Mice pups were randomized after birth to receive I.P. injection of ampicillin and gentamicin (antibiotics group, ATB) for 5 and 10 days, or placebo (Sham). To examine the effect of ATB on intestinal permeability, pups in both groups received oral FITC dextran on the day of euthanization. Effect of ATB on intestinal development, epithelial cell proliferation (Ki67 staining) and differentiation (MUC2 for goblet cells, lyzosyme for Paneth cells) was determined using standard histology and immunohistochemical staining techniques. Comparison between intestinal villi length, crypt depth, goblet and paneth cell was done by blinded investigator using ImageJ. Intestinal differentiation and tight junction (TJ) formation were also assessed by qPCR analysis of MUC1-4, and TJ array from ileal tissue. Finally effect on intestinal immune modulation was assessed by measuring anti/proinflammatory cytokine expression in ileal tissue using multiplex assay.

Summary of results

There was no difference in daily weight or small intestinal length between pups in the ATB group and Sham. Histological analysis of ileal tissue demonstrated >10% difference in villus height in the ATB group vs Sham (Mean ± SEM of 199±4.6 um, versus 237±6.9 um respectively, p<0.0001), crypt depth (Mean ± SEM of 39.9±0.9 um, 55.9±2.1 um respectively, p<0.0001), and a decreased Ki67 staining/crypts. In addition, compared to sham, ATB for 5 and 10 days was associated with >3 fold increase in intestinal permeability (p<0.001), 2-fold reduction in goblet cells/field (p<0.05), and altered MUC1-4 gene expression. Lastly, intestinal cytokine expression of TNF-α, Gro-α, and IL-1β was statistically elevated in ATB treated pups compared to sham, whereas IL-10 levels was significantly reduced.

Conclusions

ATB in neonatal pups affects intestinal maturation, differentiation, and promote increased intestinal permeability and inflammation.This could partly explain the increased risk of LOS and NEC with prolonged ATB therapy in premature infants.

709 Chondroitin sulfate protective against bacterial infection through tight junction-independent mechanism

K Burge

J Eckert

A Gunasekaran

L Hannah

H Chaaban

University of Oklahoma Health Sciences Center, Oklahoma City, OK

Purpose of study

Necrotizing enterocolitis (NEC), an inflammatory disease of the intestine, is a leading cause of morbidity and mortality in preterm infants. Dysfunction of the intestinal barrier, premature immune status, and bacterial invasion and translocation have been suggested to play major roles in the disease. Breast milk (BM) is known to be protective against NEC, but the mechanism is unclear. The presence of glycosaminoglycans (GAGs) in milk has been emphasized in the literature, and chondroitin sulfate (CS) constitutes the highest GAG by percentage [55%] in human BM. The effects of CS on bacterial invasion and translocation, intestinal macromolecule permeability, IL-8 production, and changes in tight junction protein localization and gene expression potentially related to intestinal barrier integrity and function were explored in an intestinal in vitro model.

Methods used

T84 cell monolayers were treated with CS and then challenged with E. coli invasion and translocation. Tight junction barrier function was assessed by both transepithelial electrical resistance (TER) and FITC-dextran flux measurements. Cytokine levels were determined by ELISA. Tight junction protein localization and gene expression after inoculation with bacteria and/or treatment with CS were measured by immunofluorescence and RT-PCR, respectively.

Summary of results

CS at 750 µg/ml was associated with a 75% decrease in both bacterial invasion and translocation compared to control. In addition, gene expression and immunofluorescence data in CS-treated cells show changes in claudins and ZO-1 compared to control, but likely do not explain the mechanism of protection by CS.

Conclusions

Further studies are needed to identify the ways in which CS protects against bacterial invasion and translocation. However, these results suggest that CS may play a protective role in human BM.

710 Alterations in gut microbiota influence lung development after hyperoxia exposure in a neonatal murine model

MH Althouse

W Jiang

C Stewart

B Moorthy

K Lingappan

Baylor College of Medicine, Houston, TX

Purpose of study

Cross-talk between the intestinal microbiome and the lung and its role in lung health is of growing interest. In preterm neonates, bronchopulmonary dysplasia (BPD) is a debilitating lung disease with significant morbidity. Perinatal exposure to antibiotics disrupts the neonatal microbiome and may have long-term impacts on the developing preterm lung. The purpose of this study is to determine the additive effect of perinatal antibiotics and hyperoxia exposure on BPD severity and the microbiome in a neonatal murine model.

Methods used

Pregnant C57BL/6 wild type mice were treated with perinatal antibiotics (ampicillin, gentamicin, vancomycin) from E17 to PND 5 via oral gavage. Control dams received phosphate-buffered saline (PBS). Neonatal pups were exposed to hyperoxia (95% oxygen) for 4 days or room air. Intestinal tissue was collected on PND 8 and 21 and subjected to 16S rRNA gene sequencing. Lung tissue collected on PND 21 was analyzed for alveolarization and pulmonary vascularization.

Summary of results

Intestinal microbiome beta diversity was statistically different between antibiotic and PBS treated pups at PND 21 in hyperoxia and room air groups. In antibiotic treated groups, beta diversity was statistically different at PND 21 between pups exposed to hyperoxia compared to room air controls. Alpha diversity was decreased in antibiotic groups at PND 21. Hyperoxia exposure adversely impacted alveolarization and pulmonary vascularization across all groups, however, pups also exposed to perinatal antibiotics had statistically higher mean linear intercept and decreased microvessel number and radial alveolar count when compared to controls.

Conclusions

Our data suggests that alterations in the intestinal microbiome with perinatal antibiotics may influence lung development and repair after injury in a murine model. In our study, pups exposed to perinatal antibiotics and hyperoxia developed a worse phenotype of BPD including both impaired vascularization and alveolar simplification when compared to pups exposed to hyperoxia alone. This study has great implications for the important role of the intestinal microbiome in the development of bronchopulmonary dysplasia in preterm neonates.

711 Inhibition of lipopolysaccharide-induced nuclear factor-κB activation and subsequent oligodendrocyte progenitor cell injury by azithromycin

S Ramarao

Y Pang

K Carter

AJ Bhatt

University of Mississippi Medical Center, Madison, MS

Purpose of study

Oligodendrocyte progenitor cell (OPC) is the major cellular target of brain damage in very low birth weight (VLBW) infants. We hypothesize that Azithromycin (AZ), protects OPC’s against lipopolysaccaride (LPS) activated microglia.

To investigate if AZ:

  1. Suppresses inflammatory cytokines release by LPS activated microglia

  2. Protects OPCs against damage by LPS activated microglia

  3. Rescues OPC differentiation arrest by LPS activated microglia.

Methods used

Microglia and OPCs were cultured from cortices of P1 rat brain. Microglia were activated by LPS treatment. There were 4 groups: 1: Control; 2: LPS; 3: AZ only; and 4: AZ+LPS (OPCs pretreated with AZ for 30 min before LPS exposure). Following treatment, MCM was collected to treat OPCs or to determine levels of cytokines by ELISA. OPC survival and death were measured by XTT and Caspase-3 immunocytochemistry (ICC), respectively. Oligodendrocyte (OL) differentiation was assessed by ICC using immature OL cell marker NG2 and mature OL marker APC. Expression of myelin basic protein (MBP) in OLs and nuclei translocation of NF-κB in microglia was determined by Western blot. Statistical analysis was done using two-way ANOVA, followed by post hoc Holm-Sidak test.

Summary of results

AZ significantly suppressed cytokines in MCM from LPS treatment a (p≤0.01, n=4), consistent with its ability to block NFkb p65 translocation into microglia nuclei (figure 1). AZ inhibited OPC death shown by decreased caspase-3 immunostaining and conversely also promoted OPC survival measured by XTT assay following LPS activated MCM (p≤0.01, n=3). OPCs treated with MCM from LPS group showed a significantly higher percentage of NG2 positive cells but a lower percentage of APC positive cells after 5 d, which were prevented by AZ treatment (p≤0.01, n=3). Similarly, AZ ameliorated LPS-MCM-induced suppression on MBP expression in OLs at 72 hour (p<0.05, n=3).

Conclusions

AZ ameliorates NFkb activation and subsequent OPC injury mediated by activated microglia and thus holds therapeutic potentials for inflammatory brain injury in VLBW infants.

712 High cerebral resistive index is associated with development of intraventricular hemorrhage in preterm infants

A Pal

D Stewart

H Fischer

University of Louisville, Louisville, KY

Purpose of study

Preterm infants are vulnerable to alterations in cerebral blood flow (CBF) due to impaired autoregulation which correlates with development of intra-ventricular hemorrhage (IVH).

Our primary hypothesis was that an altered CBF in the first 36 hours of life would result in altered Doppler indices, specifically resistive index (RI), which in turn could be predictive for IVH in preterm infants<29 weeks gestation.

Secondary aim was to study the relationship between RI and various maternal and infant variables such as presence of hemodynamically significant patent ductus arteriosus (hs-PDA), antenatal steroid use, delayed cord clamping and score for neonatal acute physiology with perinatal extension (SNAPPE-II).

Methods used

Prospective cohort study in which a single operator performed cranial doppler in preterm infants<29 weeks gestational age at two time points;<36 hours of age and between 5–7 days of age after obtaining written informed consent. Doppler indices evaluated included CBF velocities and resistive index (RI) measured from the middle cerebral artery (MCA). Images were reviewed by a pediatric radiologist. Statistical tests used included Pearson’s chi-square, exact test and regression analysis.

Summary of results

Thirty preterm infants were enrolled in the study with a mean gestational age of 26±1.5 weeks and birthweight of 899 g (±242 g). Twenty-seven percent developed an IVH. RI at <36 hours of life for the IVH group was significantly higher than that for the non-IVH group (p=0.02), odd’s ratio=1.46 (95% CI, 1.05–2.13). This difference was not seen in the RI at 5–7 days of age (see table 1). Linear regression showed positive correlation between systolic/diastolic velocity ratio and development of IVH (r=0.49, p=0.01). Babies with high RI were also noted to have higher SNAPPE-II scores (p=0.03).

RI had no significant correlation with antenatal steroid use, delayed cord clamping or presence of hs-PDA.

Absatrct 712 Table 1

Resistive index and IVH

Conclusions

Doppler indices specifically, Resistive Index, measured early (<36 hours) can be predictive of IVH in preterm infants<29 weeks.

713 Application of nanoparticle drug delivery systems for lutein and colistin in invitro cell culture models

D Sambalingam

X Gong

Texas Tech University Health Sciences Center, El Paso, TX

Purpose of study

Targeted drug delivery by nanoparticle technology is thought to help to decrease drug related toxicity, increase patient compliance and less frequent dosing. These smart nanospheres if biodegradable sometimes are not detected by reticulo-endothelial system (PEG). The aims of the study are to show that the intra-cytoplasmic bioavailability of lutein (carotenoid) and colistin (antibiotic) is better with PEG coated nanoparticles than regular forms.

Methods used

Lutein was experimented with 2 neuroblastoma cell line cultures (SH-SY5Y, SK-N-BE2 – ATCC) and Colistin nanoparticles was tested with corneal epithelial cell line cultures. Each of the neuroblastoma cell cultures were exposed to 3 forms of lutein preparations – 10% lutein (kemin), PEG coated nanoparticles and PEG-FOLATE coated nanoparticles. Similarly corneal cell cultures were exposed to 2 forms of colistin – Regular and PEGylated forms. After 24 hours of exposure the plasma is isolated. The cytoplasm is extracted from cells and lutein measured with HPLC. Similar experiments were done with colistin on corneal epithelial cell cultures.

Summary of results

Lutein and colistin nanoparticles with biological coats helped achieve higher intra-cellular concentrations and lutein concentrations in the neural cells were further boosted with folate addition to the coat of the nanoparticles.

Conclusions

This targeted delivery approach has widespread implications in various newborn and pediatric conditions. Creating the ideal nano-particle drug delivery system (DDS) is challenging especially in newborn.

714 Early introduction of enteral feeds after necrotizing enterocolitis decreases recurrence or stricture: a new meta-analysis

E Patel

RM Ryan

D Wilson

A Lesher

Medical University of South Carolina, Charleston, SC

Purpose of study

There is no recommendation for when to re-initiate enteral feedings after non-surgical necrotizing enterocolitis (NEC). Two prior studies (Bohnhorst 2003, Brotschi 2009) reported experiences with earlier feeding (<5 days or median 4 days) and found little harm and perhaps some benefits to earlier refeeding after NEC. While our recent retrospective study (Arbra 2018) was under review, a meta-analysis of the 2 prior studies was published (Hock 2018). Our meta-analysis increases the cohort of patients by 40 patients in the earlier feeding group (<7 days) and 98 patients in the later feeding group (≥7 days).

Methods used

A search of Cochrane, Pubmed, Scopus, Google Scholar and clinical trials’ database was performed. The same 2 publications were found as well as our publication and the recent meta-analysis. No randomized control trials (RCT) were found. An aggregate data meta-analysis was performed of the 3 studies available to examine the occurrence of intestinal stricture, NEC recurrence or both (STATA, Stata Corporation).

Summary of results

A total of 229 patients were available: 96 in the earlier feeding group and 133 in the later feeding group. NEC recurrence (pooled OR=0.56; 95% CI=0.19–1.60) or post-NEC stricture (pooled OR=0.28; 95% CI=0.08–1.02) did not differ between between earlier and later groups. The composite negative outcome (recurrence or stricture) showed a significant benefit (pooled OR=0.32; 95% CI=0.13–0.78) to earlier refeeding (figure 1). The weighted mean time to full feeds after re-initiation was significantly lower in the earlier group compared to the late group (12.9±3.5 vs. 11.0±2.1 days, p<0.001).

Abstract 714 Figure 1

Reprted odds ratios for either NEC recurrence or stricture

Conclusions

There was no increase in negative outcome with earlier refeeding after NEC. In fact, earlier refeeding resulted in a significantly lower risk for the combined outcome of NEC recurrence or stricture. However, the evidence is based on 3 single institution studies; a RCT should be performed to confirm these results.

715 Higher or usual volume feeds in very preterm infants: a randomized controlled trial

C Travers1

T Wang2

AA Salas1

E Schofield3

MM Dills4

D Laney1

A Yee5

AB Attawala1

L Winter1

N Ambalavanan1

WA Carlo1

1University of Alabama at Birmingham, Birmingham, AL

2Cincinnati Children’s Hospital, Cincinnati, OH

3University of Maryland, Baltimore, MD

4University of Alabama School of Medicine, Birmingham, AL

5Nemours A.I. DuPont, Wilmington, DE

Purpose of study

To determine if higher volume (HV) feeds (180–200 mL/kg/day) compared with usual volume (UV) feeds (140–160 mL/kg/day) improve postnatal growth among infants≤32 weeks’ gestation.

Methods used

This was a single-center randomized controlled trial with a 1:1 parallel allocation to either HV or UV feeds after establishment of full enteral feeding (≥120 mL/kg/day). The study intervention continued until discharge or 36 weeks postmenstrual age. The primary outcome was growth velocity in g/kg/day from randomization to 36 weeks PMA or hospital discharge. Measurements including weight, head circumference, mid-arm circumference, and length were recorded at study entry and study completion. A sample size of 224 infants achieved 80% power to detect a 3 g/kg/day difference in growth velocity with a standard deviation of 8 g/kg/day and a 0.05 significance level.

Summary of results

224 infants with a mean gestational age of 30 3/7±1 week and a birth weight of 1445±256 g were enrolled. Growth velocity rates were higher in the HV group compared with the LV group [mean ±SD, 20.4±4.6 vs 18.0±4.4 g/kg/day; p<0.001]. The mean weight at study completion was also higher among infants in the HV group compared with infants in the UV group [2365±324 g (Z?score −0.62) vs 2200±308 g (Z score −0.90); p<0.001]. Similarly, head circumference [31.9±1.2 cm (Z score −0.51) vs 31.4±1.3 cm (Z score −0.75); p<0.01] and mid-arm circumference [8.8±0.8 cm vs. 8.4±0.8 cm; p<0.01] at study completion were higher among infants in the HV group compared to infants in the UV group. Infant length at study completion, weight <10 centile at study completion, and length of stay after randomization did not differ between groups. Rates of BPD, hemodynamically significant PDA, NEC≥stage 2, or other adverse outcomes did not differ between groups.

Conclusions

Higher volume feeds increased growth velocity and head growth compared with usual volume feeds in very preterm infants.

716 Differences in the salivary proteome between gastroschis and term infants

EJ Sager

E Steen

H Li

S Keswani

AB Hair

Baylor College of Medicine, Houston, TX

Purpose of study

Gastroschisis (GS) is an abdominal wall defect. Though survival rates are high, there are significant morbidities including feeding intolerance, infection and prolonged hospitalization. Past studies have demonstrated the importance of specific salivary proteins and their effect on gastrointestinal (GI) health. There are no current studies evaluating the salivary proteome in infants with GS compared to healthy term infants. Differences in the protein composition may implicate disease pathology and may be an important biomarker for outcome. The purpose of this study is to compare saliva from infants with GS to term controls using proteomic profiling.

Methods used

Saliva samples were collected from infants with gastroschisis (n=4) and from term control (n=2) on day of life 1–2. Sample collection is still ongoing. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was performed to determine the salivary proteome. Scaffold was used to validate MS/MS-based peptide identifications.

Summary of results

435 proteins were identified. 146 were unique to infants with GS and 27 were unique to term controls. Proteins exclusive to infants with GS included poly(rC)-binding protein, endoplasmin, protein S100-P, histone H1.3, and keratin type II cytoskeletal 7. Proteins found in significantly higher concentrations in infants with GS included arachidonate 12-lipoxygenase12-S type, heat shock protein 90-alpha, cluster of tublin beta-4-beta chain, cluster of keratin type I cytoskeletal 18, prelamin A/C, plastin-3, transitional endoplasmic reticulum ATPase, and galectin-3. The functions/biological activities these proteins were related to inflammatory and innate immune responses (59%), programmed cell death (35%), unfolded protein responses (41%), cytoskeleton-mediated cell migration/proliferation and transport (29%) and the maintenance of GI and skin epithelium (41%).

Conclusions

This is the first study to evaluate the salivary proteome of infants with GS. Preliminary data show several differences in the salivary proteome between GS and healthy term infants. Further studies are underway to correlate the proteome with outcomes of gastroschisis patients as a potential biomarker of GI health and readiness for enteral nutrition.

717 Very low birth weight (VLBW) infant reaching full enterall feeds within two postnatal weeks—implementation and outcome of an enteral nutrition protocol

A Fenin1

JC Newman1

S Taylor2

1Medical University of South Carolina, Charleston, SC

2Yale School of Medicine, New Haven, CT

Purpose of study

Identify whether new enteral nutrition (EN) goals (reach full EN by 7 postnatal days for infants 1–1.5 kg and by 14 postnatal days for infants<1 kg) were achieved, tolerated, and associated with positive or negative outcomes.

Methods used

After IRB waiver, VLBW infants admitted in first postnatal day data was abstracted from a clinical nutrition database and categorized as either 6 months prior to revised EN protocol (Epoch 1) or after (Epoch 2). The implemented protocol included feed initiation 6–24 hours post-birth, decrease in trophic feed days, discontinuation of gastric residual monitoring with a schedule to 1) reach full EN by postnatal day 7 with CVL removal by postnatal day 5 for infants born 1–1.5 kg and 2) reach full EN by day 14 with central venous lines (CVL) removal on day 12 for infants born <1 kg.

Summary of results

One hundred-thirty infants were studied [50 (31 1–1.5 kg and 19<1 kg) in Epoch 1 and 80 in Epoch 2 (56 1–1.5 kg and 24<1 kg)]. Infants 1–15 kg reaching full EN by 7 days were 36% In Epoch 1% and 80% in Epoch 2 (p<0.0001). Infant <1 kg reaching full EN by 14 days were 32% in Epoch 1% and 79% in Epoch 2 (p=0.0017).Median (interquartile range) CVL days from Epoch 1 to Epoch 2 decreased, for infants 1–1.5 kg, from 9 (8,11) to 6 (5,7) and, for infants<1 kg, decreased from 17 (14,32) to 9 (7.5,9.5) (p<0.0001 for both). Median (interquartile range) parenteral nutrition (PN) days from Epoch 1 to Epoch 2 decreased, for infants 1–1.5 kg, from 8 (6,10) to 6 (5,6) and, for infants<1 kg, decreased from 17 (14,16) to 9 (8,9.5) (p<0.0001 for both). Mean (standard deviation) growth velocity (g/kg/day) in Epoch 1 for infants 1–1.5 kg was 11.7 (2.7) compared to 12 (2.5) in Epoch 2 (p=0.69). For infants<1 kg, the mean GV for Epoch 1 and Epoch 2 were 12.2 (5) and 12.6 (3) respectively (p=0.78).

Conclusions

In this study, with the implemented protocol,∼80% of infants born 1–1.5 kg/ and <1 kg reached full EN by 7 and 14 postnatal days, respectively, with a significant decrease in CVL and PN days. Further study to ensure safety and sustain these improvements is warranted, but the observed decreased risk has potential for a significant improvement in neonatal care.

718 Microcytic anemia is associated with increased kidney injury marker levels in premature infants

JM Davidson

M Elabiad

University of Tennessee Health Science Center, Memphis, TN

Purpose of study

There remains a wide range of practice on hematocrit indices that would trigger a blood transfusion in premature infants. Increase levels of Kidney injury molecule 1 (KIM) have been used as markers of kidney injury. We hypothesized that in premature infants, there is an inverse relationship between hematocrit and KIM levels.

Methods used

Prospectively, infants in the NICU had urine collected to measure KIM levels when blood was being collected for hematocrit. Basic demographic and clinical data were collected. Mean corpuscular volume (MCV) and reticulocyte count were also recorded.

Summary of results

62 infants were enrolled with mean gestational 28.2±3.8 weeks, mean birth weight 1170±611 g. There were a total of 275 hematocrit levels. In univariate analysis, hematocrit, gender, exposure to antibiotics in the preceding 72 hours, level of respiratory support, number of transfusions to date, and birth weight all had a trend towards an association with KIM levels with 0.05<p<0.20. MCV was available on 71 collections. It was significantly associated with KIM levels, p=0.009, R-Square=0.1. As MCV was also associated with hematocrit and with the number of transfusions to date, adjusting was done but did not affect the result of the model, p=0.03, R-Square=0.14.

Conclusions

In premature infants, an increase in kidney injury markers was not fully explained by low hematocrit levels. Lower MCV levels were significantly associated with higher KIM levels even after adjusting for other important factors like degree of anemia and history of blood transfusions. As lower MCV is associated with iron deficiency anemia, future research should explore the role that MCV may have in defining critical threshold of anemia that may warrant initiation of iron therapy before initiating a blood transfusion.

Renal, Electrolyte and Hypertension II

Concurrent Session

1:00 PM

Saturday February 23, 2019
719 The mevalonate/cholesterol biosynthesis pathway in nephron progenitor cell renewal

JB Hughes

T LI

I Brumfield

SS El-Dahr

Z Saifudeen

Tulane University, New Orleans, LA

Purpose of study

Nephron endowment is established during embryonic development and is a critical determinant of renal and cardiovascular health in adults. Hence, a keen understanding of pathways regulating efficient nephron progenitor cell (NPC) self-renewal is critical to maintain a robust progenitor pool for nephrogenesis during embryonic life. We have demonstrated that renewing NPC are dependent on glycolysis, and inhibition of glycolysis potentiates NPC differentiation and nephrogenesis. Glycolysis–generated cytosolic acetyl CoA is utilized in the mevalonate-cholesterol biosynthesis pathway, protein/histone acetylation and fatty acid synthesis. Here we analyze the contribution of the mevalonate pathway to NPC renewal/differentiation decisions.

Methods used

Embryonic age 12.5 (E12.5) mouse kidneys were cultured ex vivo in complete DMEM/F12 media without or with the HMG-CoA reductase inhibitor Pravastatin (10 uM), or pathway intermediate Mevalonic acid (0.5 mM MVA) for 24 hour. Kidneys were fixed for whole mount immunofluorescence staining for markers of NPC (Six2), collecting duct (dolichos biflorus lectin) and nascent nephrons (Lhx1). FACS-isolated E13.5 NPC were similarly treated and metabolic profiles measured. Both glycolysis (extracellular acidification rate, ECAR) and mitochondrial respiration (oxygen consumption rate, OCR) were measured.

Summary of results

Pravastatin-treated kidneys showed a significant 30% (p<0.05, n=7 kidney pairs) increase in number of Lhx1 +nascent nephrons factored per UB tip, and an apparently smaller Six2 +NPC domain. Moreover, statin-treated NPC demonstrate a 25% decrease in glycolytic capacity and a 40% decline in glycolytic reserve. MVA-treated kidneys did not demonstrate alteration in either Six2 +cap size or number of Lhx1 +nascent nephrons. Neither statin nor MVA-treated NPC exhibit altered basal respiration or glycolysis rates.

Conclusions

Whereas pathway inhibition (statin) adversely impacts NPC glycolytic capacity and reserve, pathway supplementation (MVA) does not. As NPC renewal is glycolysis-dependent (JASN 2017), our current data suggests that the mevalonate/cholesterol biosynthesis pathway is a key downstream effector of glycolysis-mediated NPC renewal.

720 COX2 and prostaglandin E2 receptors are down regulated in a porcine model of acute kidney rejection

A Harner1

Y Wang1

X Fang1

T Merchen1

S Nahman1,2

1Augusta University, Augusta, GA

2Charlie Norwood VAMC, Augusta, GA

Purpose of study

Prostaglandin E2 (PGE2) is generated from arachidonic acid via cyclooxygenase-2 (COX2), and is known to modulate the immune response via its receptors: EP1, EP2, EP3, and EP4. Receptors EP2 and EP4 are G-protein coupled and inhibit T-cell function through downregulation of inflammatory cytokines and increased expression of the anti-inflammatory cytokine IL-10. Consequently, their activation may play a role in minimizing cellular injury during rejection. Thus, we set out to determine whether there was a correlation between COX2, EP2, and EP4 expression in various degrees of kidney rejection using a porcine model.

Methods used

29 pig kidney transplants were performed including allotransplants (n=17), autotransplants (n=5) and control right kidneys (n=7). Left kidneys were transplanted and right nephrectomy was performed at the time of the transplant. Pigs were sacrificed 72 hours post-transplant and nephrectomy was performed. Rejection was assessed by Banff criteria. Renal function (serum creatinine, BUN) were assessed pre and postoperatively. Protein expression for COX2 and EP receptors was assessed using western blotting and immunohistochemical staining (COX2).

Summary of results

Rejection ranged from mild ATN to frank necrosis. Serum creatinine was significantly increased in allotransplants compared to autotransplants (5.36±5.09 mean +SD, vs 1.64±0.91 mg/dL, respectively). COX2 expression decreased significantly with increased rejection and showed a strong negative correlation (p<0.05; R2=0.6943). EP2 and EP4 receptor expression was significantly reduced as the level of rejection increased (p<0.05). Similar negative correlations were observed in EP2 (R2=0.6141) and EP4 (R2=0.7414) expression.

Conclusions

COX2, EP2, and EP4 expression is downregulated in acute kidney rejection. Mild rejection was associated with greater expression of COX2, EP2, and EP4 compared to severe rejection. Our results suggest that the COX2/PGE2/EP2-EP4 pathway may play an important role in immune suppression during solid organ transplant, and suppression of these components may promote rejection.

721 Dominance of purinergic P2X1 and P2X7 receptors mitigates angiotensin at1 receptors influence on renal microvascular resistance in angiotensin ii dependent hypertension

S Kulthinee1,2

W Shao1

G Brand1

M Franco3

L Navar1

1Tulane University, New Orleans, LA

2Thammasat University, Pathum Thani, Thailand

3Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, Mexico

Purpose of study

In angiotensin II (ANG II) hypertension, ANG II activates AT1 receptors (AT1R) which influence renal microvascular resistance and blood pressure. Interestingly, the increased arterial pressure augments interstitial ATP levels which activate purinergic P2XR receptors (P2XR). The interactions between the respective receptors remain unclear, but P2XR blockade reduces renal vascular resistance. Accordingly, experiments were performed in ANG II infused hypertensive rats to determine the AT1R and P2XR interactions.

Methods used

Using the juxtamedullary nephron technique, afferent arteriolar inside diameters (AAD) were measured in response to increases in renal perfusion pressure (RPP) from 100 mmHg to 140 mmHg followed by superfusion with the following inhibitors (i); P2 × 1 Ri (NF-449) 1 µM, P2 × 7 Ri (A-438079) 1 µM and AT1Ri (SML-1394) 1 µM.

Summary of results

Increases in RPP to 140 mmHg decreased AAD from 14.82±0.13 µm to 12±0.17 µm (n=25, p<0.05) demonstrating autoregulation. Treatment with AT1Ri slightly increased AAD by 8%±1% (13.42±0.2 µm vs. 12.46±0.17 µm, n=10, p<0.05). P2 × 1R inhibition increased AAD further 13±3% to values similar to those at 100 mmHg (14.77±0.29 µm, n=5). Treatment with the P2 × 7 Ri also vasodilated AAD by 6%±2% (14.56±0.27 µm n=5). Initial treatment with P2 × 1 Ri significantly increased AAD by 21%±5% (14.33±0.15 µm vs. 11.94±0.54 µm, n=5, p<0.05), and treatment with the P2 × 7 Ri also vasodilated AAD by 20%±9% (13.13±0.16 µm vs. 10.94±0.21 µm, n=5, p<0.05). Superimposed AT1Ri further increased AAD slightly (7%±2%) reaching values similar to baseline values at 100 mmHg. Similarly, treatment with P2 × 1 Ri plus P2 × 7 Ri increased AAD by 21%±2% (14.76±0.12 µm vs. 12.2±0.13 µm, n=5, p<0.05). Further treatment with AT1Ri significantly increased AAD to values higher than the value observed with P2 × 1 Ri plus P2 × 7 Ri by 5%±1% (15.43±0.23 µm).

Conclusions

The results indicate that while P2XR exert dominant effects, AT1R and P2XR may share post receptor signaling convergent pathways in the regulation of AAD in ANG II dependent hypertension.

722 Long-term outcomes of induction therapies with alemtuzumab, basiliximab or methylprednisolone in kidney transplant patients with delayed graft function

A Zhang

F Teran

R Zhang

Tulane University, New Orleans, LA

Purpose of study

Delayed graft function (DGF) after kidney transplant is associated with high risk of acute rejection (AR) and graft failure. The optimal immunosuppressive strategy for patients with DGF remains unknown.

Methods used

We compare the 5 year outcomes of induction therapies with methylprednisolone (n=58), basiliximab (n=56) or alemtuzumab (n=98) in patients with DGF. Maintenance was tacrolimus and mycophenolate with prednisone in methylprednisolone and basiliximab groups or without prednisone in alemtuzumab group.

Summary of results

Protocol biopsies were performed, and 5 year biopsy-confirmed acute rejection (AR) rates were significantly different among the 3 groups (39.7%, 28.6% and 20.4% in methylprednisolone, basiliximab and alemtuzumab group, respectively; p=0.034). There was a trend of difference in Kaplan-Meier estimated 5 year graft survivals among the 3 groups (65.5%, 71.4% and 80.6%, respectively; log rank p=0.07). Alemtuzumab group had a lowest incidence of AR and highest graft survival. The 5 year patient survivals were not statistically different in the 3 groups (75.9%, 82.1% and 84.7%, log rank p=0.4). Multivariable analysis using methylprednisolone induction as control indicated that alemtuzumab (HR 0.36, 95% CI 0.13 to 0.85; p=0.036) and basiliximab (HR 0.67, 95% CI 0.20 to 0.97; p=0.023) were associated with lower risk of AR.

Conclusions

Despite of steroid-withdrawal maintenance, alemtuzumab induction can decrease the risk of AR and may provide a long-term graft survival benefit in patients with DGF.

723 previously unreported KLHL3 variant in an infant with gordon syndrome

C Chu1

SE Yancovich2

D Doan2

SS El-Dahr3

R Baliga2

1Willis-Knighton, Shreveport, LA

2Louisiana State University Health Sciences Center Shreveport, Shreveport, LA

3Tulane Medical Center, New Orleans, LA

Purpose of study

Gordon syndrome (GS) is a rare genetic disorder characterized by hypertension (HTN), hyperkalemia, normal anion gap metabolic acidosis (NAGMA), normal renal function, low renin and variable aldosterone levels. It affects the regulation of the sodium chloride cotransporter (NCC) in the distal renal tubule. Mutation in the protein Kelch3, encoded by KLHL3, is one of the causes of GS because it results in the upregulation of NCC and thus excess sodium and chloride reabsorption. Thiazides, which inhibit NCC, characteristically correct the electrolyte disturbances seen in GS. We report an infant with a novel KLHL3 variant who presented with typical findings of GS in the absence of HTN.

Methods used

A normotensive 2-month-old female presented with history of irritability and poor feeding. Initial laboratory studies revealed serum potassium of 6.6 mmol/L with EKG changes. Serum bicarbonate was 18 with chloride of 108 mmol/L and normal anion gap. Plasma renin activity was 2.8 (1.4 to 7.8) ng/dl/hr and serum aldosterone level 10 (6.5 to 16) ng/dl. Kidney function was normal with serum creatinine and BUN at 0.27 and 11 mg/dl respectively. Urine sodium was <7, potassium 12.3 and chloride <15 mmol/L. Kidney ultrasound showed no evidence of obstruction or abnormality. Genetic testing revealed a heterozygous variant in the KLHL3 gene NM_017415.2;c.1421 C>T(p.Ala474Val). Administration of chlorothiazide resulted in normalization of serum potassium and correction of acidosis.

Summary of results

To our knowledge this is the youngest patient reported with GS, and this genetic variant has not been previously described in individuals with KLHL3 related conditions. We believe the absence of HTN in this patient is probably related to the early detection of this syndrome.

Conclusions

GS should be considered in any infant who presents with persistent hyperkalemia as early diagnosis may prevent the adverse effects of hyperkalemia and development of hypertension.

724 Persistent hyperparathyroidism after successful kidney transplant: a single center pilot study

S Ong

KM Wille

F Saad

C Kew

UAB, Birmingham, AL

Purpose of study

Patients with chronic kidney disease or end stage kidney disease often have secondary hyperparathyroidism, which improves after kidney transplantation. However, persistent hyperparathyroidism requiring continued treatment with a calcimimetic agent or parathyroidectomy is common. We performed a retrospective cohort study to examine persistent hyperparathyroidism in our patients after renal transplant. We hypothesized that the intact parathyroid hormone (iPTH) level at time of transplant would predict subsequent parathyroidectomy or cinacalcet use.

Methods used

We reviewed records of all kidney transplant recipients between 1/1/2016 and 12/31/2016. Data collected included various demographic, clinical, and biochemical variables. Patients with persistent hyperparathyroidism and/or who needed a calcimimetic (cinacalcet) or parathyroidectomy were compared with those who did not.

Summary of results

184 patients were identified. Of these recipients, 39.9% were female, and 60% were black. Mean age was 50.0 (SD 11.6) years. Deceased donor organs were used in 63%; 82% had been on chronic dialysis, with a mean duration of 50.2 (SD 46.4) months. Pre-transplant, 95.2% of patients had hyperparathyroidism, with a mean iPTH of 656.73 (SD 973.4) pg/ml. Before transplant, 6 (4.9%) patients had a parathyroidectomy, and 114 (61.9%) used cinacalcet. At 1 year post-transplant, parathyroidectomy occurred in 12 (6.5%) patients, and 37 (20%) remained on cinacalcet. Only 15.7% of patients had a 1 year iPTH result within the normal range (<88 pg/ml), mean iPTH was 220.1 (SD 167.1) pg/ml and mean 25-hydroxy vitamin D level was 29.19 (SD 12.6) ng/ml. Multi-variable logistic regression analysis identified the following as associated with cinacalcet use and/or parathyroidectomy at 1 year post transplant: pre-transplant cinacalcet use (OR 12.3 [95% CI: 3.78 to 39.79], p<0.0001), adjusted Ca2+ at transplant (OR 3.47 [95% CI 1.71 to 7.97] p=0.001), and duration of dialysis (OR 1.02 [95% CI 1.01 to 1.03], p=0.008). iPTH level at transplant was not associated with cinacalcet use or parathyroidectomy at 1 year post-transplant.

Conclusions

Persistent hyperparathyroidism requiring intervention was prevalent in our patient cohort. Surprisingly, the iPTH level at the time of transplant did not predict need for cinacalcet or parathyroidectomy at 1 year post-transplant.

725 Treatment of psoriasis reduces infections and mortality in end-stage renal disease patients

M Schwade1

L Tien1

J Waller1

S Nahman1,2

L Davis1

SL Baer1,2

A Mohammed1,2

L Young1

M Kheda1

W Bollag1,2

1Augusta University, Augusta, GA

2Charlie Norwood VA Medical Center, Augusta, GA

Purpose of study

Psoriasis (Ps) is an immune-mediated skin disease characterized by epidermal dysfunction, which includes disrupted barrier function. Patients with end-stage renal disease (ESRD) also suffer from a loss of normal skin barrier function due to the need for chronic vascular or peritoneal access and are at increased risk for infection and mortality. Treatment of Ps has proven to be effective in restoring skin barrier function. We theorized that ESRD patients with Ps may benefit from anti-psoriatic therapy, with a decrease in co-morbidities related to infection as well as in overall mortality.

Methods used

We queried the United States Renal Data System for Ps patients and therapies. The association between treatment (systemic, local, light therapy, or no treatment) and clinical risk factors with infectious outcomes or survival was determined using generalized linear and Cox Proportional Hazards models with propensity scores.

Summary of results

From 2004–2011 9537 patients had a diagnosis of Ps and 11% received treatment. The adjusted relative risk [aRR, 95% Confidence Interval] of infectious complications was significantly reduced for all forms of therapy, with systemic treatment offering the greatest reduction of risk for bacteremia (0.64, 0.49–0.85), septicemia (0.73, 0.57–0.92), systemic inflammatory response syndrome (0.66, 0.52–0.83), onychomycosis (0.70, 0.54–0.90), and cellulitis (0.74, 0.60–0.91). Local and light therapies showed similar reductions for several, but not all infectious outcomes. However, systemic (1.56, 1.04–2.33) and local therapy (1.96, 1.36–2.82) had a significantly increased aRR for Herpes Zoster. For survival, all forms of therapy significantly reduced mortality when compared to untreated patients, with systemic therapy showing the greatest reduction in the adjusted hazard ratio, (0.51, 0.30–0.87).

Conclusions

Treatment of Ps in ESRD patients may significantly reduce the risk of infectious complications and mortality, possibly by strengthening the epidermal barrier with a consequent reduction in comorbidities. These data suggest that systemic treatment of Ps in ESRD patients is warranted.

726 Rhabdomyolysis without a predisposing risk factor in the adulthood

LO Gerena Montano

San Juan City Hospital, San Juan, PR

Case report

Rhabdomyolysis is a syndrome characterized by muscle necrosis and the release of intracellular muscle constituents into the circulation. Creatine phosphokinase (CPK) levels are typically markedly elevated, muscle pain and myoglobinuria may be present. The severity of illness ranges from asymptomatic elevations in serum muscle enzymes to life-threatening disease characterized by extreme enzyme elevations, electrolyte imbalances, and acute kidney injury (AKI).

We present the case of a 29 year old man with no past medical history that came to our urgency room complaining of muscle pain, malaise and gross hematuria. Pain is more prominent in proximal muscle of upper and lower extremities, cramping, 7/10 in intensity, not radiating, aggravated by movement and affects ambulation due to pain, of 3 days of evolution. Denied any recent medications, toxic habits, fever, nausea, vomiting, diarrhea, chills, seizures, shortness of breath, cough, chest pain, recent travel, sick contacts, sore throat, rhinorrhea, animal contact, exercise or similar episode on the past. At younger age he used to be very active and play different sports including track and field, basketball and baseball without any symptoms. Initial pertinent laboratory work-up results showed CPK levels of 72,132 IU/L, myoglobinuria and Glomerular Filtration Rate of 40 mL/minutes. After history, physical examination and studies a metabolic myopathy was very high in the differential diagnosis. After muscle biopsy and genetic testing were done the diagnosis of McArdle’s disease was confirmed.

McArdle’s disease is a glycogen storage disease affecting the muscle due to muscle phosphorylase deficiency affecting 1:1 67 000 of the population. It is a type of metabolic myopathy that may cause rhabdomyolysis. Metabolic myopathies represent a very small percentage of cases of rhabdomyolysis and it is more common among patients with recurrent episodes of rhabdomyolysis after exertion. Symptoms commonly are present in the first decade of life. He had an unusual presentation of the disease which was a challenge to get the correct diagnosis. We as physicians have to be aware about these uncommon conditions that may cause recurrent rhabdomyolysis with consequent myoglobinuria, in which AKI among other complications may develop.

727 Pregnancy outcomes in end stage renal disease

K Martin1

AA Mohammed1,2

J Waller1

S Nahman1,2

SL Baer1,2

L Young1

WB Bollag1,2

M Kheda1

S Faiyaz1

1Augusta University, Augusta, Georgia

2Charlie Norwood VA Medical Center, Augusta, GA

Purpose of study

When compared to the general population, rates of conception and uncomplicated term delivery are lower in end stage renal disease (ESRD) patients. As a result, spontaneous abortion (SAB) and pre-term labor (PTL) are higher in the ESRD cohort. Information however, is limited by small numbers of patients studied. To address this question in a larger population, we queried the United States Renal Data System for the incidence of SAB and PTL in pregnant ESRD patients over a 7 year period.

Methods used

Female ESRD patients aged 14–50 starting dialysis between 2004–2011 were included in this study. ICD-9 codes from hospital claims identified patients with SAB and PTL. Form 2728 was used to identify demographics and etiology of ESRD. Generalized linear models assuming a binomial distribution were used to estimate the adjusted relative risk (aRR) of an outcome.

Summary of results

There were 1393 pregnancies in this study, with mean maternal age 33.9±8.9, 39.9% white race and 90.7% on hemodialysis. The etiology of ESRD was: 43% diabetes, 7.4% hypertension (HTN), 28.6% lupus and 17.8% glomerulonephritis (GN). From this group, the incidence of SAB and PTL were 7% and 10% respectively. There were no differences in the prevalence of SAB between ESRD etiologies, however the prevalence of PTL was increased among those with an ESRD etiology of HTN, lupus and GN. The aRR [95% confidence interval (CI)] of SAB was increased in non-white, non-black race (2.30, 1.10–4.78) and decreased with every 1 year increase in maternal age (0.96, 0.93–0.98). For PTL the aRR increased with pre-eclampsia (1.66, 1.01–2.74), eclampsia (2.00, 1.35–2.96) and intrauterine growth retardation (3.56, 2.33–5.44).

Conclusions

SAB and PTL are common outcomes in pregnant ESRD patients. PTL was higher in patients with ESRD from HTN, lupus and GN. The risk of SAB was decreased in older patients. It is unknown why older age results in better pregnancy outcomes amongst the ESRD population, contrary to what is seen in the general population. Understanding the high-risk groups for complications may improve pre-term care and outcomes.

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