Assessing the impact of aging and blood pressure on dermal microvasculature by reactive hyperemia optical coherence tomography angiography.

Visualization and quantification of the skin microvasculature are important for studying the health of the human microcirculation. We correlated structural and pathophysiological changes of the dermal capillary-level microvasculature with age and blood pressure by using the reactive hyperemia optical coherence tomography angiography (RH-OCT-A) technique and evaluated both conventional OCT-A and the RH-OCT-A method as non-invasive imaging alternatives to histopathology. This observational pilot study acquired OCT-A and RH-OCT-A images of the dermal microvasculature of 13 young and 12 old healthy Caucasian female subjects. Two skin biopsies were collected per subject for histological analysis. The dermal microvasculature in OCT-A, RH-OCT-A, and histological images were automatically quantified and significant indications of vessel rarefaction in both old subjects and subjects with high blood pressure were observed by RH-OCT-A and histopathology. We showed that an increase in dermal microvasculature perfusion in response to reactive hyperemia was significantly lower in high blood pressure subjects compared to normal blood pressure subjects (117% vs. 229%). These results demonstrate that RH-OCT-A imaging holds functional information of the microvasculature with respect to physiological factors such as age and blood pressure that may help to monitor early disease progression and assess overall vascular health. Additionally, our results suggest that RH-OCT-A images may serve as a non-invasive alternative to histopathology for vascular analysis.

Improvement of Reliability of Diffusion Tensor Metrics in Thigh Skeletal Muscles.

OBJECTIVE: Quantitative diffusion tensor imaging (DTI) of skeletal muscles is challenging due to the bias in DTI metrics, such as fractional anisotropy (FA) and mean diffusivity (MD), related to insufficient signal-to-noise ratio (SNR). This study compares the bias of DTI metrics in skeletal muscles via pixel-based and region-of-interest (ROI)-based analysis. METHODS: DTI of the thigh muscles was conducted on a 3.0-T system in N = 11 volunteers using a fat-suppressed single-shot spin-echo echo planar imaging (SS SE-EPI) sequence with eight repetitions (number of signal averages (NSA) = 4 or 8 for each repeat). The SNR was calculated for different NSAs and estimated for the composite images combining all data (effective NSA = 48) as standard reference. The bias of MD and FA derived by pixel-based and ROI-based quantification were compared at different NSAs. An "intra-ROI diffusion direction dispersion angle (IRDDDA)" was calculated to assess the uniformity of diffusion within the ROI. RESULTS: Using our standard reference image with NSA = 48, the ROI-based and pixel-based measurements agreed for FA and MD. Larger disagreements were observed for the pixel-based quantification at NSA = 4. MD was less sensitive than FA to the noise level. The IRDDDA decreased with higher NSA. At NSA = 4, ROI-based FA showed a lower average bias (0.9% vs. 37.4%) and narrower 95% limits of agreement compared to the pixel-based method. CONCLUSION: The ROI-based estimation of FA is less prone to bias than the pixel-based estimations when SNR is low. The IRDDDA can be applied as a quantitative quality measure to assess reliability of ROI-based DTI metrics.

Association of gadolinium-enhanced magnetic resonance imaging with hepatic fibrosis and inflammation in primary sclerosing cholangitis.

OBJECTIVE: To evaluate magnetic resonance imaging (MRI) parameters T2 signal, contrast enhancement (CE), and relative liver enhancement (RLE) of extracellular gadolinium-based contrast agent (GBCA)-enhanced MRI as a marker for hepatic fibrosis and inflammation in patients with primary sclerosing cholangitis (PSC). METHODS: 3.0-Tesla MRI scans and liver biopsies of 40 patients (41.2 ± 17.1 years) were retrospectively reviewed. Biopsies were obtained within a mean time of 54 ± 55 days to MRI scans and specimens were categorized according to Ishak modified hepatic activity index (mHAI) and Scheuer staging of fibrosis. T2 signal (N = 40), CE alterations (N = 29), and RLE (N = 29) were assessed by two raters. Mixed-effects regression models were applied to estimate the association between histopathology and MRI parameters. RESULTS: No significant association was observed between T2 signal or CE alterations with stages of fibrosis or mHAI grading. Regression models revealed significant positive associations of portal venous phase RLE with mHAI grade ≥ 7 points [ß = 25.5; 95% CI (2.53; 48.62); p = 0.04] and delayed phase RLE with stages of fibrosis [stage 2: ß = 35.13; 95% CI (11.35; 58.87); p = 0.007; stage 3/4: ß = 69.24; 95% CI (45.77; 92.75); p < 0.001]. The optimal cut-off value of 66.6% delayed phase RLE distinguished fibrosis stages 0-2 from 3-4 with a sensitivity of 0.833 and specificity of 0.972. Inter-rater reliability (IRR) for quantification of RLE was 'excellent' (r = 0.90-0.98). IRR was 'substantial' for detection of T2 signal in the right liver lobe (RL) (Kappa = 0.77) and 'almost perfect' for T2 signal of the left liver lobe (LL) and CE of both lobes (Kappa = 0.87-1.0). CONCLUSION: The simple and reproducible method of RLE quantification on standard extracellular GBCA-enhanced MRI may provide a correlate measure of advanced stages of hepatic fibrosis and potentially also inflammation in PSC patients, if validated in larger cohorts.

Novel Telestroke Program Improves Thrombolysis for Acute Stroke Across 21 Hospitals of an Integrated Healthcare System.

BACKGROUND AND PURPOSE: Faster treatment with intravenous alteplase in acute ischemic stroke is associated with better outcomes. Starting in 2015, Kaiser Permanente Northern California redesigned its acute stroke workflow across all 21 Kaiser Permanente Northern California stroke centers to (1) follow a single standardized version of a modified Helsinki model and (2) have all emergency stroke cases managed by a dedicated telestroke neurologist. We examined the effect of Kaiser Permanente Northern California's Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke program on door-to-needle (DTN) time, alteplase use, and symptomatic intracranial hemorrhage rates. METHODS: The program was introduced in a staggered fashion from September 2015 to January 2016. We compared DTN times for a seasonally adjusted 9-month period at each center before implementation to the corresponding 9-month calendar period from the start of implementation. The primary outcome was the DTN time for alteplase administration. Secondary outcomes included rate of alteplase administrations per month, symptomatic intracranial hemorrhage, and disposition at time of discharge. RESULTS: This study included 310 patients treated with alteplase in the pre-EXpediting the PRrocess of Evaluating and Stopping Stroke period and 557 patients treated with alteplase in the EXpediting the PRrocess of Evaluating and Stopping Stroke period. After implementation, alteplase administrations increased to 62/mo from 34/mo at baseline (P<0.001). Median DTN time decreased to 34 minutes after implementation from 53.5 minutes prior (P<0.001), and DTN time of <60 minutes was achieved in 87.1% versus 61.0% (P<0.001) of patients. DTN times <30 minutes were much more common in the Stroke EXpediting the PRrocess of Evaluating and Stopping Stroke period (40.8% versus 4.2% before implementation). There was no significant difference in symptomatic intracranial hemorrhage rates in the 2 periods (3.8% versus 2.2% before implementation; P=0.29). CONCLUSIONS: Introduction of a standardized modified Helsinki protocol across 21 hospitals using telestroke management was associated with increased alteplase administrations, significantly shorter DTN times, and no increase in adverse outcomes.

Pushing the boundaries of ECLS: Outcomes in <34 week EGA neonates.

PURPOSE: Extracorporeal life support (ECLS) is usually reserved for infants ≥34weeks estimated gestational age (EGA) owing to concerns about increased mortality and incidence of intracranial hemorrhage (ICH). We sought to characterize survival, rates of ICH, and complications in <34week EGA neonates placed on ECLS. METHODS: 752 neonates of EGA 29-34weeks were identified in the Extracorporeal Life Support Organization (ELSO) Registry (1976-2008). Data analyzed included birthweight, survival, pre-ECLS conditions, ventilatory parameters and complications (including ICH and other neurological outcomes). Data were compared using t-test, Chi-square and logistic regression analyses. RESULTS: When compared to survival rates of 34week EGA neonates (58%), survival was statistically different for 29-33week EGA (48%, p=0.05). No significant difference in ICH incidence was seen between the 29-33week and 34week groups (21% vs. 17%, respectively), but a significant difference was seen in the incidence of cerebral infarct between groups (22% for 29-33weeks vs. 16% for 34weeks; p=0.03). ICH and survival did not correlate with EGA during logistic regression analysis. CONCLUSIONS: Though rates of survival and cerebral infarction were worse at 29-33weeks EGA compared with 34weeks, these differences were modest and may be clinically acceptable. This suggests that EGA<34weeks may not be an absolute contraindication to use of ECLS. LEVEL OF EVIDENCE: III.

Direct insertion of Amplatzer plugs to control lumbar arteries during open repair of type II endoleaks.

Type II endoleak after endovascular repair of an infrarenal aortic aneurysm (EVAR) may be difficult to diagnose and treat in the best of circumstances. Management is more difficult in the patient with significant renal insufficiency. We report an 81-year-old man with stage IV chronic kidney disease and a rapidly expanding, asymmetric aortic aneurysm sac, 31 months after EVAR. A type II lumbar endoleak was diagnosed by duplex ultrasound imaging and managed successfully with open aortic exposure and direct insertion of Amplatzer plugs into two bleeding lumbar arteries due to complex anatomic factors.

Development of an artificial placenta IV: 24 hour venovenous extracorporeal life support in premature lambs.

An extracorporeal artificial placenta would change the paradigm of treating extremely premature infants. We hypothesized that a venovenous extracorporeal life support (VV-ECLS) artificial placenta would maintain fetal circulation, hemodynamic stability, and adequate gas exchange for 24 hours. A near-term neonatal lamb model (130 days; term = 145 days) was used (n = 9). The right jugular vein was cannulated for VV-ECLS outflow, and an umbilical vein was used for inflow. The circuit included a peristaltic roller pump and a 0.5 m(2) hollow fiber oxygenator. Lambs were maintained on VV-ECLS in an "amniotic bath" for up to 24 hours. Five of nine fetuses survived for 24 hours. In the survivors, average mean arterial pressure was 69 ± 10 mm Hg for the first 4 hours and 36 ± 8 mm Hg for the remaining 20 hours. The mean fetal heart rate was 202 ± 30. Mean VV-ECLS flow was 94 ± 20 ml/kg/min. Using a gas mixture of 50% O(2)/3% CO(2) and sweep flow of 1-2 L/min, the mean pH was 7.27 ± 0.09, with Po(2) of 35 ± 12 mm Hg and Pco(2) of 48 ± 12 mm Hg. Necropsy revealed a patent ductus arteriosus in all cases, and there was no gross or microscopic intracranial hemorrhage. Complications in failed attempts included technically difficult cannulation and multisystem organ failure. Future studies will enhance stability and address the factors necessary for long-term support.

Total liquid ventilation provides superior respiratory support to conventional mechanical ventilation in a large animal model of severe respiratory failure.

Total liquid ventilation (TLV) has the potential to provide respiratory support superior to conventional mechanical ventilation (CMV) in the acute respiratory distress syndrome (ARDS). However, laboratory studies are limited to trials in small animals for no longer than 4 hours. The objective of this study was to compare TLV and CMV in a large animal model of ARDS for 24 hours. Ten sheep weighing 53 ± 4 (SD) kg were anesthetized and ventilated with 100% oxygen. Oleic acid was injected into the pulmonary circulation until PaO2:FiO2 ≤ 60 mm Hg, followed by transition to a protective CMV protocol (n = 5) or TLV (n = 5) for 24 hours. Pathophysiology was recorded, and the lungs were harvested for histological analysis. Animals treated with CMV became progressively hypoxic and hypercarbic despite maximum ventilatory support. Sheep treated with TLV maintained normal blood gases with statistically greater PO2 (p < 10(-9)) and lower PCO2 (p < 10(-3)) than the CMV group. Survival at 24 hours in the TLV and CMV groups were 100% and 40%, respectively (p < 0.05). Thus, TLV provided gas exchange superior to CMV in this laboratory model of severe ARDS.

Endorectal pull-through for Hirschsprung's disease-a multicenter, long-term comparison of results: transanal vs transabdominal approach.

PURPOSE: Previous studies have reported decreased continence in patients undergoing transanal endorectal pull-through (TERP) for Hirschsprung's disease compared to the older transabdominal approach (TAA). To address this, we examined long-term stooling outcomes in a large, multicenter cohort of patients undergoing either TERP or TAA. METHODS: Data were collected from 5 large pediatric institutions. Patient families were surveyed using a stooling score system (0-40, best to worst total score). Inclusion criteria included patients older than 3 years and those who had more than 6 months of recovery after pull-through. Those with total colonic aganglionosis were excluded. Statistical analysis included univariate and multivariate linear regression (significance, P < .05). RESULTS: Two hundred eighty-one patients underwent TERP (192) or TAA (89). Interviews were completed in 149 (104 [52%] TERP vs 45 [52%] TAA). The TAA group had a significantly greater number of daily bowel movements for each respective postoperative year and experienced more early complications (3% vs 1% with >1 complication; P = .061) and late complications (19% vs 4% with >1 complication; P < .001). Although the TAA group had a higher mean enterocolitis score (3.3 +/- 0.4 vs 1.8 +/- 0.2; P < .001), this was not borne out by multivariate regression analysis (P = .276). Parental survey showed that there were no significant differences between procedures in mean total, continence, or stooling pattern scores. CONCLUSION: Transanal endorectal pull-through was associated with fewer complications and fewer episodes of enterocolitis. In contrast to prior studies, TERP patients did not have a higher rate of incontinence. These results support use of TERP as an excellent surgical approach for children with Hirschsprung's disease.

No free ride? The hidden costs of delayed operative management using a spring-loaded silo for gastroschisis.

PURPOSE: The ideal management of gastroschisis (primary vs staged closure) has not yet been established. Despite the ease of silo placement, anecdotal experience shows that silos do not always offer benefit. The aim of this study was to highlight concerns regarding use of spring loaded silos and compare outcomes to primary closure. METHODS: Thirty-seven neonates with gastroschisis treated with either primary (n = 10) or staged closure with a spring-loaded silo (n = 27) were reviewed (1998-2007). Variables included ventilator days, daily intravenous fluid, hospital days, and complication rates. SPSS (SPSS Inc, Chicago, Ill) was used to perform t test and chi(2) analyses (significance P < .05). RESULTS: Survival for primary closure was 100% (10/10) compared to 89% (24/27) for staged closure (P = .548). Patients managed with silos required prolonged ventilation (16.1 +/- 4 days vs 3.6 +/- 1 days; P < or = .05) and greater intravenous fluids on days 3, 4, and 5 of life (132 +/- 25 mL/kg per day vs 104 +/- 18 mL/kg per day; P < or = .01). Although there was no difference in the complication rates between the groups, several problems were evident in the silo group: 15% (4/27) required silo replacement, 44% (12/27) required fascial defect enlargement for silo placement, and 19% (5/27) required mesh at closure. No significant differences in recovery of intestinal function were observed. Three silo patients developed ischemic complications because of vascular insufficiency at the level of the abdominal wall, leading to significant intestinal loss, ventilator and total parenteral nutrition dependence, and increased hospital stay. CONCLUSIONS: Patients managed with a silo had longer ventilator requirements and greater fluid needs. This Specific technical complications leading to bowel ischemia were notable in the silo group. The silo should be carefully placed to avoid bowel twisting and the funnel effect. Larger prospective studies should be performed to provide decision-making criteria for the use of a silo vs primary closure.

Two-stage basilic vein transposition-a new approach for pediatric dialysis access.

PURPOSE: The fistula first initiative has led to increased efforts to create arteriovenous fistulas (AVFs) as primary dialysis access. Two-stage basilic vein transposition (BVT) allows maturation of smaller veins, often a limiting factor in the pediatric population, before elevation and use. We sought to determine whether using 2-stage BVT improves maturation, use, and patency compared with other AVFs, including arteriovenous (AV) grafts. METHODS: Thirty-one patients underwent AV access creation between 1997 and 2008. Data were collected on types of access, maturation, complications, and patency. RESULTS: Forty-two AV access procedures were performed: 15 (36%) 2-stage BVT, 13 (31%) 1-stage BVT, 6 (14%) radiocephalic, 3 (7%) brachiocephalic, 1 (2%) brachiobrachial, and 4 (10%) AV grafts. Follow-up averaged 20.4 +/- 3.2 months for 2-stage BVT and 47.9+/-4.1 months for other AVFs (P < .001). All 2-stage BVT matured compared with 52% (14/27) of other AVFs (P = .001). More 2-stage BVTs (87%) were used for dialysis than other AVFs (48%, P = .024). Fistula failure occurred in 7% 2-stage BVT compared with 59% other AVFs (P = .001). One-year patency rates were 91% for 2-stage BVT vs 47% for other AVFs (P = .003). CONCLUSIONS: Rates of fistula maturation, use, and patency are higher for 2-stage BVT with lower rates of failure. Two-stage BVT shows great promise as the preferred approach to creation of AVF in pediatric patients, especially those with smaller veins.

Thoracoscopic repair of congenital diaphragmatic hernia in neonates: lessons learned.

PURPOSE: We sought to characterize our recent experience with thoracoscopic congenital diaphragmatic hernia (CDH) repair and identify patient selection factors. METHODS: We reviewed the medical records of full-term neonatal (<1 month of age) patients who underwent thoracoscopic CDH repair between 2004 and 2008 (n = 15). We obtained data on prenatal diagnosis, characteristics of the CDH and repair, complications, and outcome. RESULTS: All patients were stabilized preoperatively and underwent repair at an average of 5.7 +/- 1.3 days. Six patients were prenatally diagnosed, including the 5 inborn. Thirteen defects were left-sided. All were intubated shortly after birth and 2 required extracorporeal membrane oxygenation (ECMO). Twelve of 15 (80%) patients underwent successful thoracoscopic primary repair, including 1 of the patients who required ECMO prior to repair. Conversion to open repair occurred in 3 of 15 (20%) patients because of the need for patch closure or intraoperative instability. Among those converted to open, all had left-sided CDH defects and 3 had stomach herniation (of 5 such patients). Patients spent an average of 6.9 +/- 1.0 days on the ventilator following repair. The average time until full-enteral feeding was 16.7 +/- 2.25 days, and average length of hospital stay was 23.8 +/- 2.73 days. All patients survived to discharge, and average length of follow-up was 15.3 +/- 3.6 months. CONCLUSIONS: Thoracoscopic repair of CDH is a safe, effective strategy in patients who have undergone prior stabilization. Stomach herniation is associated with, but does not categorically predict, conversion to open repair. ECMO use prior to repair should not be an absolute contraindication to thoracoscopic repair.

Right-sided congenital diaphragmatic hernia: high utilization of extracorporeal membrane oxygenation and high survival.

PURPOSE: The purpose of the study was to assess the treatment strategies and outcome of right-sided congenital diaphragmatic hernia (R-CDH), particularly extracorporeal membrane oxygenation (ECMO). METHODS: We reviewed the cases of 42 patients treated for R-CDH at our institution from 1991 to 2006. We gathered demographic information, documented ECMO use and the type of surgical repair, and compared outcomes with predicted survival as calculated by the CDH Study Group's equation. RESULTS: Of the 35 patients included in our statistical analysis (7 were excluded), 12 (34%) were born at our institution, all of whom were prenatally diagnosed with R-CDH. Nineteen patients (54%) required ECMO therapy. Extracorporeal membrane oxygenation was initiated after repair of the R-CDH in 2 patients (11%). Of those patients who went on ECMO before repair, 4 patients (21%) were repaired on ECMO, 9 patients (47%) underwent repair after ECMO, and 4 patients (21%) underwent ECMO but died before their R-CDH could be repaired. Primary repair of the diaphragm was possible in 15 cases (56%), and primary closure of the abdominal incision was possible in 15 of the 23 open repairs (65%). The mean predicted survival for all 35 patients was 63%, whereas 28 (80%) actually survived. Logistic regression showed a significant association between the presence of cardiac defects and mortality (odds ratio = 0.008, P = .014). CONCLUSIONS: Our data suggest that patients with R-CDH have high ECMO utilization and may experience greater relative benefit from ECMO as evidenced by their higher-than-expected overall survival. Extracorporeal membrane oxygenation may be found to have a distinctive role in managing R-CDH. More high-powered series are needed to elucidate differences between R-CDH and left-sided CDH that may dictate alternate forms of management.

Development of an artificial placenta I: pumpless arterio-venous extracorporeal life support in a neonatal sheep model.

PURPOSE: Effective treatment of respiratory failure in premature infants remains an unsolved problem. The development of an artificial placenta, in the form of a pumpless arteriovenous extracorporeal life support (AV-ECLS) circuit that maintains fetal circulation, is an appealing alternative. METHODS: A near-term (140 d/term = 145 days) neonatal lamb model was used (n = 7). Fetuses were exposed by hysterotomy, and flow probes were placed on the ductus arteriosus, aorta, and carotid artery. Catheters were placed into the umbilical vessels, and pumpless AV-ECLS was initiated. Fetuses were submerged in a warm saline bath, and support was maintained for up to 4 hours. RESULTS: Mean initial device flow was 383 mL/min but steadily declined to 177 mL/min at 4 hours. Mean initial pO(2) was 24 mm Hg and 18 mm Hg at 4 hours. Initial mean pCO(2) was 60 mm Hg and declined to 42 mm Hg at 4 hours. Mean arterial pressure was initially 43 mm Hg and decreased to 34 mm Hg at 4 hours. Flow in the ductus arteriosus was maintained for 4 hours. Of 7 fetuses, 5 survived 4 hours of support. CONCLUSIONS: Pumpless AV-ECLS can support gas exchange and maintain fetal circulation in a neonatal lamb model for a 4-hour period. Prolonged support (>4 hours) is hampered by high cannula resistance and declining device flow.

Clinical outcomes of intraoperative radiation therapy for extremity sarcomas.

Purpose. Radiation of extremity lesions, a key component of limb-sparing therapy, presents particular challenges, with significant risks of toxicities. We sought to explore the efficacy of intraoperative radiation therapy (IORT) in the treatment of soft tissue sarcomas of the extremities. Patients. Between 1995 and 2001, 17 patients received IORT for soft tissue sarcomas of the extremities. Indications for IORT included recurrent tumors in a previously radiated field or tumors adjacent to critical structures. Results. Gross total resections were achieved in all 17 patients. Two patients experienced locoregional relapses, six patients recurred at metastatic sites, and one patient died without recurrence. Thirty-six month estimates for locoregional control, disease free survival, and overall survival were 86%, 50%, and 78%, respectively. IORT was extremely well tolerated, with no toxicities referable to IORT. Conclusions. For patients with soft tissue sarcomas of the extremities, IORT used as a boost to EBRT provides excellent local control, with limited acute toxicities.