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Bilateral native nephrectomy reduces systemic oxalate level after combined liver-kidney transplant: A case report

Tue, 06/20/2017 - 2:36pm

Primary hyperoxaluria type 1 (PH1) is a rare liver enzymatic defect that causes overproduction of plasma oxalate. Accumulation of oxalate in the kidney and subsequent renal failure are fatal to PH1 patients often in pediatric age. Combined liver and kidney transplantation is the therapy of choice for end-stage renal disease due to PH1. Levels of plasma oxalate remain elevated for several months after liver transplantation, as the residual body oxalate is slowly excreted. Patients with persistent hyperoxaluria after transplant often require hemodialysis, and accumulation of residual oxalate in the kidney can induce graft dysfunction. As the native kidneys are the main target of calcium oxalate accumulation, we postulated that removal of native kidneys could drastically decrease total body oxalate levels after transplantation. Here, we report a case of bilateral nephrectomy at the time of combined liver-kidney transplantation in a pediatric PH1 patient. Bilateral nephrectomy induced a rapid decrease in plasma oxalate to normal levels in less than 20 days, compared to the several months reported in the literature. Our results suggest that removal of native kidneys could be an effective strategy to decrease the need for hemodialysis and the risk of renal dysfunction after combined liver-kidney transplantation in patients with PH1.

Outcomes From Pediatric Gastroenterology Maintenance of Certification Using Web-based Modules

Tue, 06/20/2017 - 2:36pm

OBJECTIVES: Beginning in 2013, the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) sponsored and developed subspecialty field-specific quality improvement (QI) activities to provide Part 4 Maintenance of Certification (MOC) credit for ongoing certification of pediatric gastroenterologists by the American Board of Pediatrics. Each activity was a Web-based module that measured clinical practice data repeatedly over at least 3 months as participants implemented rapid cycle change. Here, we examine existing variations in clinical practice among participating pediatric gastroenterologists and determine whether completion of Web-based MOC activities improves patient care processes and outcomes.

METHODS: We performed a cross-sectional and prospective analysis of physician and parent-reported clinical practice data abstracted from Web-based MOC modules on the topics of upper endoscopy, colonoscopy, and informed consent collected from pediatric gastroenterologists from North America from 2013 to 2016.

RESULTS: Among 134 participating pediatric gastroenterologists, 56% practitioners practiced at an academic institution and most (94%) were NASPGHAN members. Participating physicians reported data from 6300 procedures. At baseline, notable practice variation across measured activities was demonstrated. Much of the rapid cycle changes implemented by participants involved individual behaviors, rather than system/team-based improvement activities. Participants demonstrated significant improvements on most targeted process and quality care outcomes.

CONCLUSIONS: Pediatric gastroenterologists and parents reported baseline practice variation, and improvement in care processes and outcomes measured during NASPGHAN-sponsored Web-based MOC QI activities. Subspecialty-oriented Web-based MOC QI activities can reveal targets for reducing unwarranted variation in clinical pediatric practice, and can effectively improve care and patient outcomes.

Wide Variation Found in Care of Opioid-Exposed Newborns

Tue, 06/20/2017 - 2:36pm

OBJECTIVE: Standardized practices for the management of neonatal abstinence syndrome (NAS) are associated with shorter lengths of stay, but optimal protocols are not established. We sought to identify practice variations for newborns with in utero chronic opioid exposure among hospitals in the Better Outcomes Through Research for Newborns (BORN) network.

METHODS: Nursery site leaders completed a survey about hospitals' policies and practices regarding care for infants with chronic opioid exposure (>/=3 weeks).

RESULTS: The 76 (80%) of 95 respondent hospitals were in 34 states, varied in size (8000 births and 200 opioid-exposed infants per year), with most affiliated with academic centers (89%). Most (80%) had protocols for newborn drug exposure screening; 90% used risk-based approaches. Specimens included urine (85%), meconium (76%), and umbilical cords (10%). Of sites (88%) with NAS management protocols, 77% addressed medical management, 72% nursing care, 72% pharmacologic treatment, and 58% supportive care. Morphine was the most common first-line pharmacotherapy followed by methadone. Observation periods for opioid-exposed newborns varied; 57% observed short-acting opioid exposure for 2 to 3 days, while 30% observed for >/=5 days. For long-acting opioids, 71% observed for 4 to 5 days, 19% for 2 to 3 days, and 8% for >/=7 days. Observation for NAS occurred mostly in level 1 nurseries (86%); however, most (87%) transferred to NICUs when pharmacologic treatment was indicated.

CONCLUSIONS: Most BORN hospitals had protocols for the care of opioid-exposed infants, but policies varied widely and characterized areas of needed research. Identification of variation is the first step toward establishing best practice standards to improve care for this rapidly growing population.

Infant Nutritional Status and Markers of Environmental Enteric Dysfunction are Associated with Midchildhood Anthropometry and Blood Pressure in Tanzania

Tue, 06/20/2017 - 2:36pm

OBJECTIVE: To assess whether growth and biomarkers of environmental enteric dysfunction in infancy are related to health outcomes in midchildhood in Tanzania.

STUDY DESIGN: Children who participated in 2 randomized trials of micronutrient supplements in infancy were followed up in midchildhood (4.6-9.8 years of age). Anthropometry was measured at age 6 and 52 weeks in both trials, and blood samples were available from children at 6 weeks and 6 months from 1 trial. Linear regression was used for height-for-age z-score, body mass index-for-age z-score, and weight for age z-score, and blood pressure analyses; log-binomial models were used to estimate risk of overweight, obesity, and stunting in midchildhood.

RESULTS: One hundred thirteen children were followed-up. Length-for-age z-score at 6 weeks and delta length-for-age z-score from 6 to 52 weeks were associated independently and positively with height-for-age z-score and inversely associated with stunting in midchildhood. Delta weight-for-length and weight-for-age z-score were also positively associated with midchildhood height-for-age z-score. The 6-week and delta weight-for-length z-scores were associated independently and positively with midchildhood body mass index-for-age z-score and overweight, as was the 6-week and delta weight-for-age z-score. Delta length-for-age z-score was also associated with an increased risk of overweight in midchildhood. Body mass index-for-age z-score in midchildhood was associated positively with systolic blood pressure. Serum anti-flagellin IgA concentration at 6 weeks was also associated with increased blood pressure in midchildhood.

CONCLUSIONS: Anthropometry at 6 weeks and growth in infancy independently predict size in midchildhood, while anti-flagellin IgA, a biomarker of environmental enteric dysfunction, in early infancy is associated with increased blood pressure in midchildhood. Interventions in early life should focus on optimizing linear growth while minimizing excess weight gain and environmental enteric dysfunction.

TRIAL REGISTRATION: NCT00197730 and NCT00421668.

Laurence A. Boxer, MD, 1940-2017

Tue, 06/20/2017 - 2:36pm

Obituary for Laurence A. Boxer, MD, retired professor from the University of Michigan Medical School, where he held the Henry and Mala Dorfman Family Chair in Pediatric Hematology/Oncology.

Diverse stimuli engage different neutrophil extracellular trap pathways

Mon, 06/19/2017 - 5:12pm

Neutrophils release neutrophil extracellular traps (NETs) which ensnare pathogens and have pathogenic functions in diverse diseases. We examined the NETosis pathways induced by five stimuli; PMA, the calcium ionophore A23187, nigericin, Candida albicans and Group B Streptococcus. We studied NET production in neutrophils from healthy donors with inhibitors of molecules crucial to PMA induced NETs including protein kinase C, calcium, reactive oxygen species, the enzymes myeloperoxidase (MPO) and neutrophil elastase. Additionally, neutrophils from chronic granulomatous disease patients, carrying mutations in the NADPH oxidase complex or a MPO-deficient patient were examined. We show that PMA, C. albicans and GBS use a related pathway for NET induction whereas ionophores require an alternative pathway but that NETs produced by all stimuli are proteolytically active, kill bacteria and composed mainly of chromosomal DNA. Thus, we demonstrate that NETosis occurs through several signalling mechanisms, suggesting that extrusion of NETs is important in host defence.

Closed-cell stent for coil embolization of intracranial aneurysms: clinical and angiographic results

Mon, 06/19/2017 - 10:55am

BACKGROUND AND PURPOSE: Recanalization is observed in 20-40% of endovascularly treated intracranial aneurysms. To further reduce the recanalization and expand endovascular treatment, we evaluated the safety and efficacy of closed-cell SACE.

MATERIALS AND METHODS: Between 2007 and 2010, 147 consecutive patients (110 women; mean age, 54 years) presenting at 2 centers with 161 wide-neck ruptured and unruptured aneurysms were treated by using SACE. Inclusion criteria were wide-neck aneurysms ( > 4 mm or a dome/neck ratio

RESULTS: Eighteen aneurysms (11%) were treated following rupture. Procedure-related mortality and permanent neurologic deficits occurred in 2 (1.4%) and 5 patients (3.4%), respectively. In total, 7 patients (4.8%) died, including 2 with reruptures. Of the 140 surviving patients, 113 (80.7%) patients with 120 aneurysms were available for follow-up neurologic examination at a mean of 11.8 months. An increase in mRS score from admission to follow-up by 1, 2, or 3 points was seen in 7 (6.9%), 1 (1%), and 2 (2%) patients, respectively. Follow-up angiography was performed in 120 aneurysms at a mean of 11.9 months. Recanalization occurred in 12 aneurysms (10%), requiring retreatment in 7 (5.8%). Moderate in-stent stenosis was seen in 1 (0.8%), which remained asymptomatic.

CONCLUSIONS: This series adds to the evidence demonstrating the safety and effectiveness of SACE in the treatment of intracranial aneurysms. However, SACE of ruptured aneurysms and premature termination of antiplatelet treatment are associated with increased morbidity and mortality.

The effect of intracranial stent implantation on the curvature of the cerebrovasculature

Mon, 06/19/2017 - 10:55am

BACKGROUND AND PURPOSE: Recently, the use of stents to assist in the coiling and repair of wide-neck aneurysms has been shown to be highly effective; however, the effect of these stents on the RC of the parent vessel has not been quantified. The purpose of this study was to quantify the effect of intracranial stenting on the RC of the implanted artery using 3D datasets.

MATERIALS AND METHODS: Twenty-four patients receiving FDA-approved neurovascular stents to support coil embolization of brain aneurysms were chosen for this study. The stents were located in the ICA, ACA, or MCA. We analyzed C-arm rotational angiography and contrast-enhanced cone beam CT datasets before and after stent implantation, respectively, to ascertain changes in vessel curvature. The images were reconstructed, and the vessel centerline was extracted. From the centerline, the RC was calculated.

RESULTS: The average implanted stent length was 25.4 +/- 5.8 mm, with a pre-implantation RC of 7.1 +/- 2.1 mm and a postimplantation RC of 10.7 +/- 3.5 mm. This resulted in a 3.6 +/- 2.7 mm change in the RC due to implantation (P < .0001), more than a 50% increase from the pre-implantation value. There was no difference in the change of RC for the different locations studied. The change in RC was not impacted by the extent of coil packing within the aneurysm.

CONCLUSIONS: The implantation of neurovascular stents can be shown to have a large impact on the RC of the vessel. This will lead to a change in the local hemodynamics and flow pattern within the aneurysm.

Effectiveness of mechanical endovascular thrombectomy in a model system of cerebrovascular occlusion

Mon, 06/19/2017 - 10:55am

BACKGROUND AND PURPOSE: A number of thrombectomy devices are currently undergoing clinical evaluation; meanwhile, various novel devices are under investigation. The aims of this study were to quantify flow restoration and the particle size distribution of the effluent pursuant to MET in an in vitro occlusion model.

MATERIALS AND METHODS: The model system was composed of 3 elements: an ICA/MCA replica, a clot model with mechanical properties similar to those of thrombi found in patients at risk of stroke, and a pulsatile flow loop. Different thrombectomy mechanisms including mechanical retrieval, aspiration, and waveguide induced cavitation were used. The efficacy end points were recanalization rate and amount of flow restoration. The risk of the embolic shower was assessed to evaluate device safety.

RESULTS: The recanalization rates were the following: Merci, 67%; Solitaire, 100%; Penumbra, 83%; Enterprise, 17%; and the waveguide, 0%. In experiments in which recanalization was achieved, the amount of flow restoration for the Merci, Solitaire, and Enterprise devices was 100%, 92%, and 86%, respectively. The mean sizes of generated small and large clot fragments were between 23 and 37 and 215 and 285 mum, respectively, depending on the device used. The Merci device generated the fewest number of large fragments compared with the Penumbra system (P < .05) and Solitaire (not significant).

CONCLUSIONS: The risk of embolic shower was influenced by the mechanism of action for the thrombectomy device. Clinically reported recanalization rates for the Solitaire, Penumbra, and Merci devices were nearly identical in this model system, suggesting that this model may provide a predictive tool for preclinical evaluation of MET.

Pneumothorax following ultrasound-guided jugular vein puncture for central venous access in interventional radiology: 4 years of experience

Mon, 06/19/2017 - 10:55am

PURPOSE: The purpose of our study was to review the rate of pneumothorax following central venous access, using real-time ultrasound guidance.

MATERIALS AND METHODS: Data related to ultrasound-guided venous puncture, for central venous access, performed between July 1, 2004 and June 30, 2008 was retrospectively and prospectively collected. Access route, needle gauge, catheter type, and diagnosis of pneumothorax on the intraprocedure spot radiographs and or the postprocedure chest radiographs, were recorded.

RESULTS: A total of 1262 ultrasound-guided jugular venous puncture for central venous access were performed on a total of 1066 patients between July 1, 2004 and June 30, 2008. Access vessels included 983 right internal jugular veins, 275 left internal jugular veins, and 4 right external jugular veins. No pneumothorax (0%) was identified.

CONCLUSION: Due to an extremely low rate of pneumothorax following ultrasound-guided central venous access, 0% in our study and other published studies, we suggest that routine postprocedure chest radiograph to exclude pneumothorax may be dispensed unless it is suspected by the operator or if the patient becomes symptomatic.

A review of partial volume correction techniques for emission tomography and their applications in neurology, cardiology and oncology

Mon, 06/19/2017 - 10:55am

Accurate quantification in PET and SPECT requires correction for a number of physical factors, such as photon attenuation, Compton scattering and random coincidences (in PET). Another factor affecting quantification is the limited spatial resolution. While considerable effort has gone into development of routine correction techniques for the former factors, less attention has been paid to the latter. Spatial resolution-related effects, referred to as 'partial volume effects' (PVEs), depend not only on the characteristics of the imaging system but also on the object and activity distribution. Spatial and/or temporal variations in PVE can often be confounding factors. Partial volume correction (PVC) could in theory be achieved by some kind of inverse filtering technique, reversing the effect of the system PSF. However, these methods are limited, and usually lead to noise-amplification or image artefacts. Some form of regularization is therefore needed, and this can be achieved using information from co-registered anatomical images, such as CT or MRI. The purpose of this paper is to enhance understanding of PVEs and to review possible approaches for PVC. We also present a review of clinical applications of PVC within the fields of neurology, cardiology and oncology, including specific examples.

Incidental genitourinary findings on obstetrics/gynecology ultrasound

Mon, 06/19/2017 - 10:55am

Ultrasound is the standard-of-care imaging modality for initial imaging in obstetrics and gynecology. Given the close proximity of the genitourinary system to the uterus and adnexa, it is not surprising that these studies can result in the discovery of incidental genitourinary findings such as ureterocele, ectopic ureter, bladder mass, ureteral stones, cystitis, bladder diverticulum, and pelvic kidney. Recognition of the etiology of these findings is important for appropriate diagnosis and, at times, patient care. Many of these findings are truly incidental and clinically unimportant but other times can be related to the patient's chief complaint.

ACR appropriateness criteria jaundice

Mon, 06/19/2017 - 10:55am

A fundamental consideration in the workup of a jaundiced patient is the pretest probability of mechanical obstruction. Ultrasound is the first-line modality to exclude biliary tract obstruction. When mechanical obstruction is present, additional imaging with CT or MRI can clarify etiology, define level of obstruction, stage disease, and guide intervention. When mechanical obstruction is absent, additional imaging can evaluate liver parenchyma for fat and iron deposition and help direct biopsy in cases where underlying parenchymal disease or mass is found. Imaging techniques are reviewed for the following clinical scenarios: (1) the patient with painful jaundice, (2) the patient with painless jaundice, and (3) the patient with a nonmechanical cause for jaundice. The ACR Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 2 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. rights reserved.

Finding the striatum in sheep: use of a multi-modal guided approach for convection enhanced delivery

Mon, 06/19/2017 - 10:55am

Our goal is delivery of a long-term treatment for Huntington's disease. We administer intracerebrally in sheep adeno-associated virus (AAV) to establish optimal safety, spread and neuronal uptake of AAV based therapeutics. Sheep have large gyrencephalic brains and offer the opportunity to study a transgenic Huntington's disease model. However, lack of a relevant brain stereotactic atlas and the difficulty of skull fixation make conventional stereotaxy unreliable. We describe a multi-modal image-guidance technique to achieve accurate placement of therapeutics into the sheep striatum.

A next-generation, flow-diverting implant used to treat brain aneurysms: in vitro evaluation of magnetic field interactions, heating and artifacts at 3-T

Mon, 06/19/2017 - 10:55am

BACKGROUND AND PURPOSE: Fine-mesh braided, stent-like structures (flow diverters) have been proposed for treatment of brain aneurysms. To date, the safety of performing magnetic resonance imaging (MRI) in patients with these implants is unknown. Therefore, the purpose of this study was to evaluate MRI issues at 3-T for a new flow-diverting implant used to treat brain aneurysms.

METHODS: The Surpass NeuroEndoGraft (Surpass Medical, Ltd., Tel Aviv, Israel) underwent evaluation for magnetic field interactions, MRI-related heating and artifacts using standardized techniques. Magnetic field interactions were assessed for this implant with regard to translational attraction (i.e., using the deflection angle technique) and torque (qualitative assessment method). MRI-related heating was evaluated by placing the implant in a gelled-saline-filled, head/torso phantom and performing MRI using a transmit/receive radiofrequency body coil at a whole-body-averaged specific absorption rate of 2.9 W/kg for 15 min. Artifacts were characterized using T1-weighted, spin echo (SE) and gradient echo (GRE) pulse sequences.

RESULTS: The Surpass NeuroEndoGraft exhibited minor magnetic field interactions (21 degrees deflection angle and no torque), which were acceptable from a safety consideration. Heating was not substantial, with the highest temperature change being 2.3 degrees C (background temperature rise without the implant was 1.5 degrees C). Artifacts may create issues if the area of interest is in the same area or close to this implant.

CONCLUSIONS: The findings demonstrated that it would be acceptable for patients with this next-generation, flow-diverting implant to undergo MRI at 3-T or less.

Yield of radiographic skeletal surveys for detection of hand, foot, and spine fractures in suspected child abuse

Mon, 06/19/2017 - 10:54am

OBJECTIVE: Previous studies have found that fractures involving the spine, hands, and feet are rare on skeletal surveys in cases of suspected child abuse, leading some authors to suggest eliminating these regions from the initial skeletal survey protocol. We assessed this recommendation by performing a historical review of these injuries in a pediatric population undergoing film screen-based radiographic skeletal surveys for suspected child abuse.

MATERIALS AND METHODS: This cross-sectional retrospective study reviewed reports of initial skeletal surveys of all children younger than 2 years with suspected abuse imaged between April 1988 and December 2001. Radiographic skeletal survey imaging was performed according to American College of Radiology standards. Sixty-two percent (225/365) of all skeletal surveys had positive findings, and 44% (98/225) showed more than one fracture. Surveys with fractures involving the spine, hands, or feet were identified, and the data were tabulated and analyzed.

RESULTS: Twenty of 365 studies (5.5%) yielded fractures involving the spine, hands, or feet. Of all positive skeletal surveys, 8.9% (20/225) had fractures involving the spine, hands, or feet. Of all patients with more than one fracture on skeletal survey, 20.4% (20/98) had fractures involving these regions.

CONCLUSION: These data, acquired during the film-screen era, suggest that fractures of the spine, hands, and feet may not be rare in infants and toddlers in cases of suspected child abuse. The benefits of eliminating views of these regions from the initial skeletal survey should be carefully weighed against the cost of missing these potentially important injuries in at-risk pediatric populations.

Porcine brachial artery tortuosity for in vivo evaluation of neuroendovascular devices

Mon, 06/19/2017 - 10:54am

We report a novel model of arterial tortuosity in the porcine brachial artery for testing of endovascular devices in the flexed forelimb position. This provides an ideal vascular territory for an in vivo assessment of guidewires, microcatheters, and endovascular implants because it closely mimics the challenging curvature at the carotid siphon.

Reduction in distal emboli with proximal flow control during mechanical thrombectomy: a quantitative in vitro study

Mon, 06/19/2017 - 10:54am

BACKGROUND AND PURPOSE: To evaluate the impact of proximal flow control on efficacy and safety of mechanical thrombectomy in an in vitro middle cerebral artery occlusion. METHODS: Three independent variables, including clot type, device (Merci Retriever, Solitaire FR, and Trevo devices), and use of a balloon guide catheter, were used to ascertain the impact of proximal flow control on the size and number of distal emboli generated during thrombectomy. Secondary end points were the recanalization rate and amount of flow restored. RESULTS: Use of the balloon guide catheter during thrombectomy of the fragile, hard clot significantly reduced the formation of large distal emboli with a diameter > 1 mm, regardless of the device used (P<0.01). Applying aspiration via the balloon guide catheter in place of the conventional guide catheter resulted in a significant increase of flow reversal (P<0.0001). Prior to thrombectomy, deployment of the stent-trievers produced immediate flow restoration through the soft and hard clot occlusions, 69.2 +/- 27.3 and 45.5 +/- 22.8 mL/min, respectively, that was preserved after the balloon inflation because of collateral flow via the posterior communication artery. After deployment but before thrombectomy, no flow was restored when using the Merci Retriever. After thrombectomy, complete flow restoration was achieved in a majority of cases. The Merci Retriever required more thrombectomy attempts to achieve hard clot removal compared with the stent-trievers when the conventional guide catheter was used (1.5 versus 1.1). CONCLUSIONS: The risk of distal embolization was significantly reduced with the use of the balloon guide catheter.