Reducing Cardiac Arrests in the PICU: Initiative to Improve Time to Administration of Prearrest Bolus Epinephrine in Patients With Cardiac Disease.

OBJECTIVES: To evaluate the effectiveness of a quality-improvement initiative in reducing cardiac arrests in infants and children in the cardiac ICU. DESIGN: Prospective observational before-after cohort study. SETTING: Single pediatric cardiac ICU in the United Kingdom. PATIENTS: All patients less than 18 years old admitted to the ICU. INTERVENTION: Initial interdisciplinary training in cardiac arrest prevention followed by clinical practice change whereby patients with high-risk myocardium were identified on daily rounds. High-risk patients had bolus epinephrine preordered and prepared for immediate administration in the event of acute hypotension. MEASUREMENTS AND MAIN RESULTS: Interrupted time series analysis was used to compare the cardiac arrest rate in the 18 months before and 4.5 years after implementation. Mean monthly cardiac arrest rate was 17.2 per 1,000 patient days before and 7.6 per 1,000 patient days after the initiative (56% decrease). Patient characteristics and ICU interventions were similar in the control and intervention periods. In the time series analysis, monthly cardiac arrest rate in the ICU decreased by 12.4 per 1,000 patient days (95% CI, -1.5 to -23.3; p = 0.03) immediately following the intervention, followed by a nonsignificant downward trend of 0.36 per 1,000 patient days per month (95% CI, -1.3 to 0.6; p = 0.44). Bolus epinephrine was administered during 110 hypotension events in 77 patients (eight administrations per 1,000 ICU days); responder rate was 77%. There were no significant changes in ICU and hospital mortality. CONCLUSIONS: Implementation of the initiative led to a significant, sustained reduction in ICU cardiac arrest rate.

Comparative Persistence of Engineered Nanoparticles in a Complex Aquatic Ecosystem.

During nanoparticle environmental exposure, presence in the water column is expected to dominate long distance transport as well as initial aquatic organism exposure. Much work has been done to understand potential ecological and toxicological effects of these particles. However, little has been done to date to understand the comparative persistence of engineered particles in realistic environmental systems. Presented here is a study of the water column lifetimes of 3 different classes of nanoparticles prepared with a combination of surface chemistries in wetland mesocosms. We find that, when introduced as a single pulse, all tested nanoparticles persist in the water column for periods ranging from 36 h to 10 days. Specifically, we found a range of nanoparticle residence times in the order Ag > TiO2 > SWCNT > CeO2. We further explored the hypothesis that heteroaggregation was the primary driving factor for nanoparticle removal from the water column in all but one case, and that values of surface affinity (α) measured in the laboratory appear to predict relative removal rates when heteroaggregation dominates. Though persistence in the water column was relatively short in all cases, differences in persistence may play a role in determining nanoparticle fate and impacts and were poorly predicted by currently prevailing benchmarks such as particle surface preparation.

Atrial arrhythmia after transcatheter closure of secundum atrial septal defects in patients ≥40 years of age.

AIM: Data on arrhythmia outcome following device closure of atrial septal defect (ASD) are lacking. This study provides medium-term follow-up data on atrial arrhythmias in patients who were ≥40 years of age at the time of transcatheter ASD closure. METHODS AND RESULTS: It is a retrospective review. Mean age of the 159 patients was 57 years. Median follow-up was 3.6 years (range 6 months-10.9 years). Patients were classified, according to arrhythmia status prior to ASD closure, into Group I, no history of atrial arrhythmia (n = 119, mean age 55.5 years); Group II, paroxysmal atrial arrhythmia (n = 18, mean age 55.7 years); and Group III, persistent atrial fibrillation (n = 22, mean age 65.7 years). Group III patients were significantly older, had larger left atrial size, and had higher mean pulmonary arterial pressure than Group I and II patients (P < 0.001). Prior to closure, radiofrequency ablation was carried out in 12/18 (66%) of Group II and 3/22 (14%) of Group III. After device closure, 7 patients (6%) of Group I developed new atrial fibrillation. Fifty per cent (9/18) of Group II but only 9% (2/22) of Group III were in sinus rhythm on follow-up. CONCLUSION: Device closure alone in patients with persistent atrial arrhythmia is not likely to restore sinus rhythm in the medium term. New atrial arrhythmia occurred in 6% of patients who were in sinus rhythm prior to device closure. At least 50% of the patients with paroxysmal atrial arrhythmia continue to have significant atrial arrhythmia following device closure, and the role of ablation prior to closure in patients with a history of arrhythmia requires refinement.

Relationship between arterial partial oxygen pressure after resuscitation from cardiac arrest and mortality in children.

BACKGROUND: Observational studies in adults have shown a worse outcome associated with hyperoxia after resuscitation from cardiac arrest. Extrapolating from adult data, current pediatric resuscitation guidelines recommend avoiding hyperoxia. We investigated the relationship between arterial partial oxygen pressure and survival in patients admitted to the pediatric intensive care unit (PICU) after cardiac arrest. METHODS AND RESULTS: We conducted a retrospective cohort study using the Pediatric Intensive Care Audit Network (PICANet) database between 2003 and 2010 (n=122,521). Patients aged <16 years with documented cardiac arrest preceding PICU admission and arterial blood gas analysis taken within 1 hour of PICU admission were included. The primary outcome measure was death within the PICU. The relationship between postarrest oxygen status and outcome was modeled with logistic regression, with nonlinearities explored via multivariable fractional polynomials. Covariates included age, sex, ethnicity, congenital heart disease, out-of-hospital arrest, year, Pediatric Index of Mortality-2 (PIM2) mortality risk, and organ supportive therapies. Of 1875 patients, 735 (39%) died in PICU. Based on the first arterial gas, 207 patients (11%) had hyperoxia (Pa(O)(2) ≥300 mm Hg) and 448 (24%) had hypoxia (Pa(O)(2) <60 mm Hg). We found a significant nonlinear relationship between Pa(O)(2) and PICU mortality. After covariate adjustment, risk of death increased sharply with increasing hypoxia (odds ratio, 1.92; 95% confidence interval, 1.80-2.21 at Pa(O)(2) of 23 mm Hg). There was also an association with increasing hyperoxia, although not as dramatic as that for hypoxia (odds ratio, 1.25; 95% confidence interval, 1.17-1.37 at 600 mm Hg). We observed an increasing mortality risk with advancing age, which was more pronounced in the presence of congenital heart disease. CONCLUSIONS: Both severe hypoxia and, to a lesser extent, hyperoxia are associated with an increased risk of death after PICU admission after cardiac arrest.

Modified protocol for in vivo imaging of wild-type mouse retina with customized miniature spectral domain optical coherence tomography (SD-OCT) device.

This protocol outlines and evaluates a modified scanning procedure for a customized spectral domain optical coherence tomography (SD-OCT) imaging apparatus within the wild-type C57Bl/6 mouse posterior segment. This modified protocol allows for the capture of a 50 degree field of view spanning 3 mm by 3 mm perimeter with the optic disc as the central point. By utilizing this scanning protocol a more reliable measurement of retinal thickness can be achieved outside the fluctuating region of the optic disc. This protocol, when applied to this high resolution device, enables non-invasive in vivo histological imaging and biometric assessment of the various layers of the rodent posterior segment within a 20 - 30 min procedural time-frame. This protocol could establish a standardized method for evaluating morphological changes, with this commercial SDOCT device, when assessing longitudinal disease pathophysiology and treatment response in mouse models for future vision science research.

Toward a Regional Gerontological Agenda: The Use of Empowerment Evaluation.

This article describes the application of an empowerment evaluation approach to nurturing the growth and priority setting of a regional organization. A model is provided of the processes whereby the Southern Gerontological Society (SGS) identified research and service priorities by conducting a survey of stakeholder perceptions of regional needs. The survey goal was to identify important issues faced by older adults in the South as a prelude to refining SGS research and service priorities and developing its contemporary regional gerontological agenda. We trace how the survey findings were translated into actions including shaping the annual meeting program, creating new standing committees, and developing service activities. Underlying the process of developing and refining this agenda are a set of key principles that have come to characterize the operation of SGS. These principles are discussed and provide a model for comparable organizations seeking to develop agendas consistent with their mission and identity.

A spontaneous breathing trial with pressure support overestimates readiness for extubation in children.

OBJECTIVE: To evaluate the performance of an extubation readiness test based on a spontaneous breathing trial using pressure support. DESIGN: Retrospective chart review. SETTING: Pediatric intensive care unit. PATIENTS: All infants and children admitted to the pediatric intensive care unit requiring intubation from July 2007 to December 2008 were eligible for this study. INTERVENTIONS: Routine use of an extubation readiness test using pressure support set according to endotracheal tube size to determine completion of weaning and readiness for extubation. MEASUREMENTS AND MAIN RESULTS: A total of 755 extubation readiness tests were performed in 538 patients with a pass rate of 83%. Of 500 children who passed the extubation readiness test and were extubated without planned noninvasive ventilation use, the extubation failure rate was 11.2% (5.8% required reintubation). Extubation failure was defined as need for noninvasive ventilation or reintubation within 24 hrs of planned extubation. Logistic regression analysis revealed a significant association between duration of mechanical ventilation and extubation failure. Children ventilated for over 48 hrs had an 18.5% failure rate despite passing an extubation readiness test before extubation and the extubation readiness test was not a significant predictor of extubation success. Most extubation failures were the result of inadequate gas exchange attributable to lower respiratory tract dysfunction. CONCLUSIONS: A spontaneous breathing trial using pressure support set at higher levels for smaller endotracheal tubes overestimates readiness for extubation in children and contributes to a higher failed extubation rate. The objective data obtained during an extubation readiness test may help to identify patients who will benefit from extubation to noninvasive ventilation.

Monitoring of Antiplatelet Therapy in Children on Ventricular Assist Device Support: Comparison of Multiplate and Thromboelastography Platelet Mapping.

The optimal method for monitoring antiplatelet therapy in children supported with ventricular assist devices (VADs) is unknown. We conducted a retrospective study to compare Thromboelastography Platelet Mapping (TEG/PM) with multiple electrode platelet aggregometry (MEA) on a Multiplate analyzer (Roche Diagnostics, Mannheim, Germany). We analyzed data from 66 paired blood samples from 9 patients <16 years of age on VAD where platelet function was simultaneously measured with TEG/PM and MEA. Antiplatelet dose-response relationships and intraindividual variability during steady state therapy were determined. Agreement in determination of therapeutic antiplatelet therapy was poor (arachidonic acid, κ 0.23; adenosine diphosphate [ADP], κ 0.13). Rate of aspirin and clopidogrel resistance was much higher when determined using TEG/PM than MEA. In patients receiving ≥5 mg/kg/day aspirin, 72% of TEG/PM measurements showed subtherapeutic response compared with 11% of MEA measurements. There was evidence of a dose-response relationship with clopidogrel and MEA ADP-induced aggregation (R2 = 0.56; p < 0.0001); however, there was no association between dose and TEG/PM% ADP inhibition (p = 0.15). Intraindividual variability in platelet reactivity was far greater when measured by TEG/PM during steady state therapy. Multiple electrode platelet aggregometry appears to be more reliable than TEG/PM for monitoring antiplatelet therapy in children supported with VAD.

The Use of Daptomycin to Treat Methicillin-Resistant Staphylococcus Epidermidis Bacteremia in a Critically Ill Child with Renal Failure.

Daptomycin is excreted primarily unchanged by the kidney. Dosage regimens in children with renal failure remain to be determined. We report the case of an 8-year-old child with multiorgan failure undergoing continuous peritoneal dialysis, successfully treated with intravenous daptomycin for methicillin-resistant Staphylococcus epidermidis bacteremia. A dosage of 8 mg/kg every 48 hour was used. Plasma peak and trough concentrations of daptomycin were 68 mg/L and 14.6 mg/L, respectively, on day 6 of treatment. The dosage regimen achieved daptomycin exposure comparable to that reported in adults undergoing continuous ambulatory peritoneal dialysis and receiving recommended dosages.

Gastrointestinal complications associated with the surgical treatment of heart disease in children.

BACKGROUND/PURPOSE: The gastrointestinal system is prone to complications following heart surgery. We sought to determine the incidence and factors associated with gastrointestinal complication after cardiac surgery in children. METHODS: A retrospective review of patients aged <16years that underwent cardiac surgery between 2009 and 2013. Primary outcome was occurrence of gastrointestinal complication within 30days. Multivariable logistic regression was performed to identify variables related to occurrence of gastrointestinal complication. Patients with gastrointestinal complication were matched with controls and postoperative lengths of stay compared. RESULTS: Eight hundred eighty-one children underwent 1120 cardiac surgical procedures. At time of operation, 18% were neonates and 39% were infants. Cardiopulmonary bypass was used in 79%. Of 1120 procedures, 31 (2.8% [95% CI 2.0-3.9%]) had gastrointestinal complication. Necrotizing enterocolitis accounted for 61% of complications. Of patients with gastrointestinal complication, 87% survived to hospital discharge. Gastrointestinal complication was associated with preoperative co-morbidity (OR 2.2 [95% CI 1.02-4.8]) and univentricular disease (OR 2.5 [95% CI 1.1-5.5]). Neonates had the highest risk of gastrointestinal complication. Patients with gastrointestinal complications had longer hospital stays than controls (median difference, 13days [95% CI 3-43]). CONCLUSIONS: Serious gastrointestinal complications are uncommon but associated with longer hospital stay. Neonates with univentricular disease and preoperative comorbidity are at highest risk. TYPE OF STUDY: Prognosis study. LEVEL OF EVIDENCE: II.

Comparison of paracorporeal and continuous flow ventricular assist devices in children: preliminary results.

Objectives: With the scarcity of organs, a durable, reliable ventricular assist device (VAD) is required. The Berlin Heart EXCOR ® (BH) remains the most established VAD in the paediatric population. Implantable continuous flow (CF) VADs have been introduced to the paediatric field with encouraging early results. In this study, we compared the results of a newly introduced CF VAD (HeartWare VAD [HVAD] ® ) to results in a matched group of BH recipients. Methods: The study included patients aged <16 years who received mechanical left VAD (LVAD) support between December 2005 and January 2016. The preimplant characteristics and postimplant outcomes of patients who received the HVAD were compared with those of a matched group who received the BH. Patients with congenital heart disease were excluded. Results: Thirty patients were included in the study: 13 had received the HVAD and were matched with 17 patients who had received the BH LVAD. The only difference in preimplant characteristics was the need for higher inotropic support in the BH group. There was no difference in the need for right ventricular (RV) support (58.8% for BH vs 53.8% for HVAD, P = 1.00) or in the incidence of cerebrovascular accidents (12.5% vs 7.7%, respectively, P = 1.00), though the BH group showed prolonged mechanical ventilation (31.3% vs 0%, P = 0.047). There were no deaths while on VAD support in either group. Patients with the HVAD showed a bimodal distribution for the primary end point (transplant/explant): All HVAD recipients who also required early RV support reached this end point within 30 days of receiving the implant. Conclusions: Our early experience with the CF intracorporeal LVAD system (HVAD) indicates outcomes comparable to those with the well-established pulsatile flow paracorporeal LVAD (BH). The theoretical durability of the CF device, which might also allow for the possibility of hospital discharge and better quality of life, is yet to be proven.

An Extended Role of Continuous Flow Device in Pediatric Mechanical Circulatory Support.

BACKGROUND: Mechanical circulatory support in the pediatric population is currently limited to pulsatile ventricular assist devices (VAD). In recent years, the use of durable, newer generation, continuous flow devices have increased substantially among adults with end-stage heart failure. We examined the extended role of this device in the pediatric population (aged less than 18 years). METHODS: Between 2010 and 2015, 12 patients (median age 7.1 years; range, 3.7 to 17.0; one third of patients were aged 5 years or less) received a HeartWare ventricular assist device (HVAD; HeartWare, Framingham, MA), 11 for cardiomyopathy and 1 for posttransplant rejection. Right VAD support (n = 5; 42%) was provided by a short-term device (Levitronix, Zurich, Switzerland). RESULTS: Overall, 1 patient died (day 638), 8 patients (67%) underwent transplantation, 1 patient (8.3%) recovered, and 2 patients (17%) remain on HVAD. The mean length of support was 150 days (range, 16 to 638). Four patients (33.3%) were discharged home (all left VAD). In the left VAD group (n = 7), 3 patients subsequently received transplants (days 185, 201, and 234, respectively), 1 recovered (day 149), 1 died (day 638), 1 remained on HVAD (day 198), and 1 needed conversion to biventricular assist device (BIVAD [day 73]). In the BIVAD group (n = 5), right VAD was weaned in 3 (60%), all subsequently received transplants, and 2 remained on BIVAD support until transplant (days 16 and 17, respectively). One BIVAD patient required conversion to central cannulation for longer-term support. Four BIVAD patients (80%) were in Interagency Registry for Mechanically Assisted Circulatory Support level 1 before VAD compared with 2 (29%) in the left VAD group (p = not significant). The actuarial survival rate was 100% at 1 year with no neurologic events. CONCLUSIONS: The third-generation, continuous flow device can provide durable support in the pediatric population. The selection strategy for patients who benefit most from the device continues to evolve. It is anticipated that a smaller design in the future will benefit an even wider pediatric population with heart failure.

Deprivation of bFGF Promotes Spontaneous Differentiation of Human Embryonic Stem Cells into Retinal Pigment Epithelial Cells.

BACKGROUND: The retinal pigment epithelium (RPE), an important tissue monolayer of retina, sustains visual function and retinal homeostasis. In disease conditions such as Retinitis Pigmentosa (RP) and Age related Macular degeneration (AMD), the integrity and functional capacity of RPE monolayer is compromised. Human embryonic stem cells derived RPE (hESC-RPE) is ideal for cell based therapy because of their ability to morphologically and functionally mimic native fetal and adult RPE. However protocols for optimum culture of hESC-RPE are not well established. AIM: To describe a simplified protocol for differentiating human embryonic stem cells (hESC) into retinal pigment epithelial cells. METHODS: hESC (WA09-DL-11) cell lines were grown with standard stem cell culture protocol. After cell colonies were established, basic fibroblast growth factor (bFGF) was deprived (day 0). hESC colonies expressing pigmentation were characterized for expression of RPE65 and Zonular occludens--1 (ZO-1) with immunocytochemistry on days 0, 36, 42, 56 and 70 and western blot analysis on days 0, 40, 48, 53 and 63. In addition, morphological assessment was conducted on transformed cells longitudinally. RESULTS: Pigmented cells were noted 36 days after deprivation of bFGF from growth media. Immunofluorescence demonstrated progressive up regulation of RPE specific proteins (ZO-1 & RPE 65). Immunofluorescence of ZO-1 (in pixels) was (3.08 ± 0.31) on day 42, (5.33 ± 0.89, p = 0.0001) on day 56 and (4.87 ± 0.57, p = 0.0011) on day 70. Similarly expression of RPE 65 was (2.44 ± 0.31) on day 42, which continued to increase (4.23 ± 0.60, p = 0.0011) on day 56 and (5.59 ± 0.36, p < 0.0001) on day 70. Protein expression patterns using western blot confirmed the trends seen in immunofluorescence. Western blot analysis of ZO-1 expression (in optical density unit) was 272.57 ± 31.75 on day 40, 4212.20 ± 911.31 (p = 0.0004) on day 48, 5182.43 ± 1230.38 (p = 0.030) on day 53 and 5848.76 ± 241.04 (p < 0.0001) on day 63. Protein expression of RPE 65 was 1607.64 ± 247.76 on day 40, 2448.07 ± 152.66 on day 48 and (2341.15 ± 52.84) on day 63. hESC-RPE cells displayed a series of specific morphological changes (cytoplasmic, nuclear pigmentary and cell shape) over the course of time frame. By day 70, cells with hexagonal pattern, dark dense nucleus and uniform cytoplasm were noted in densely pigmented RPE colonies. CONCLUSION: bFGF deprivation leads to successful differentiation of hESC into RPE cells. Longitudinal transformative changes were confirmed with measurement of ZO-1 and RPE 65, specific markers of RPE.

Comparison of central corneal thickness: ultrasound pachymetry versus slit-lamp optical coherence tomography, specular microscopy, and Orbscan.

BACKGROUND: Central corneal thickness (CCT) can be measured by using contact and non-contact methods. Ultrasound pachymetry (US pachymetry) is a contact method for measuring CCT and is perhaps the most commonly used method. However, non-contact methods like scanning slit topography (Orbscan II), slit-lamp optical coherence tomography (SL-OCT), and specular microscopy are also used. Not many studies have correlated the measurement of CCT with all four modalities. The purpose of this study was to compare and correlate the CCT measurements obtained by US pachymetry with SL-OCT, specular microscopy, and Orbscan. METHOD: This is a prospective, comparative study done in an institutional setting. Thirty-two eyes of 32 subjects with no known ocular disease and best-corrected visual acuity of 20/20 were enrolled. CCT measurements were obtained using SL-OCT, specular microscopy, scanning slit topography (Orbscan), and US pachymetry. Three measurements were made with each instrument by the same operator. Mean, standard deviation, and coefficient of variation were calculated for CCT measurements acquired by the four measurement devices. Bland-Altman plot was constructed to determine the agreements between the CCT measurements obtained by different equipment. RESULTS: The mean CCT was 548.16±48.68 µm by US pachymetry. In comparison, CCT averaged 546.36±44.17 µm by SL-OCT, 557.61±49.92 µm by specular microscopy, and 551.03±48.96 µm by Orbscan for all subjects. Measurements by the various modalities were strongly correlated. Correlations (r (2)) of CCT, as measured by US pachymetry compared with other modalities, were: SL-OCT (r (2)=0.98, P<0.0001), specular microscopy (r (2)=0.98, P<0.0001), and Orbscan (r (2)=0.96, P<0.0001). All modalities had a linear correlation with US pachymetry measurements. CONCLUSION: In subjects with healthy corneas, SL-OCT, specular microscopy, and Orbscan (with correction factor) can be used interchangeably with US pachymetry in certain clinical settings. The four modalities showed significant linear correlations with one another.

Outcome of mechanical cardiac support in children using more than one modality as a bridge to heart transplantation.

OBJECTIVES: Mechanical cardiac support (MCS) can successfully be applied as a bridging strategy for heart transplantation (OHTx) in children with life-threatening heart failure. Emergent use of MCS is often required before establishing the likelihood of OHTx. This can require bridge-to-bridge strategies to increase survival on the waiting list. We compared the outcome of children with heart failure who underwent single MCS with those who required multiple MCS as a bridge to OHTx. METHODS: A retrospective study of patients aged less than 16 years was conducted. From March 1998 to October 2005, we used either a veno-arterial extracorporeal membrane oxygenator (VA-ECMO), or the Medos® para-corporeal ventricular assist device (VAD). From November 2005 onwards, the Berlin Heart EXCOR® (BHE) device was implanted in the majority of cases. Several combinations of bridge-to-bridge strategies have been used: VA-ECMO and then conversion to BHE; BHE and then conversion to VA-ECMO; left VAD and then upgraded to biventricular support (BIVAD); conversion from pulsatile to continuous-flow pumps. RESULTS: A total of 92 patients received MCS with the intent to bridge to OHTx, including 21 (23%) supported with more than one modality. The mean age and weight at support was similar in both groups, but multimodality MCS was used more often in infancy (P = 0.008) and in children less than 10 kg in weight (P = 0.02). The mean duration of support was longer in the multiple MCS group: 40 ± 48 vs 84 ± 43 days (P = 0.0003). Usage of multimodality MCS in dilated cardiomyopathy (19%) and in other diagnoses (29%) was comparable. Incidence of major morbidity (haematological sequelae, cerebrovascular events and sepsis) was similar in both groups. Survival to OHTx/explantation of the device (recovery) and survival to discharge did not differ between single MCS and multiple MCS groups (78 vs 81% and 72 vs 76%, respectively). CONCLUSION: Bridge to OHTx with multiple MCS does not seem to influence the outcome in our population. Infancy and body weight less than 10 kg do not tend to produce higher mortality in the multiple MCS group. However, children receiving more than one modality are supported for longer durations.

Retinal thickness measurement obtained with spectral domain optical coherence tomography assisted optical biopsy accurately correlates with ex vivo histology.

BACKGROUND: This study determines 'correlation constants' between the gold standard histological measurement of retinal thickness and the newer spectral-domain optical coherence tomography (SD-OCT) technology in adult C57BL/6 mice. METHODS: Forty-eight eyes from adult mice underwent SD-OCT imaging and then were histologically prepared for frozen sectioning with H&E staining. Retinal thickness was measured via 10x light microscopy. SD-OCT images and histological sections were standardized to three anatomical sites relative to the optic nerve head (ONH) location. The ratios between SD-OCT to histological thickness for total retinal thickness (TRT) and six sublayers were defined as 'correlation constants'. RESULTS: Mean (± SE) TRT for SD-OCT and histological sections was 210.95 µm (± 1.09) and 219.58 µm (± 2.67), respectively. The mean 'correlation constant' for TRT between the SD-OCT and histological sections was 0.96. The retinal thickness for all sublayers measured by SD-OCT vs. histology were also similar, the 'correlation constant' values ranged from 0.70 to 1.17. All SD-OCT and histological measurements demonstrated highly significant (p<0.01) strong positive correlations. CONCLUSION: This study establishes conversion factors for the translation of ex vivo data into in vivo information; thus enhancing the applicability of SD-OCT in translational research.

Mechanical cardiac support in children with congenital heart disease with intention to bridge to heart transplantation†.

OBJECTIVES: A significant number of children affected by congenital heart disease (CHD) develop heart failure early or late after surgery, and heart transplantation (OHTx) remains the last treatment option. Due to shortage of donor organs in paediatric group, mechanical circulatory support (MCS) is now routinely applied as bridging strategy to increase survival on the waiting list for OTHx. We sought to assess the impact of MCS as intention to bridge to OHTx in patients with CHD less than 16 years of age. METHODS: From 1998 to 2013, 106 patients received 113 episodes of MCS with paracorporeal devices as intention to bridge to OHTx. Twenty-nine had CHD, 15 (52%) with two-ventricle (Group A) and 14 (48%) with single-ventricle physiology (Group B). In Group A, 5 children had venoarterial extracorporeal membrane oxygenation (VA ECMO), 6 left ventricular assist device (LVAD), 2 biventricular assist device (BIVAD), 1 VA ECMO followed by BIVAD and 1 BIVAD followed by VA ECMO. In Group B, VA ECMO was used in 7 children, univentricular assist device (UVAD) changed to VA ECMO in 4, UVAD in 2 and surgical conversion to two-ventricles physiology with BIVAD support changed to VA ECMO in 1. RESULTS: Twenty-one of 29 (72%) children survived to recovery/OHTx. Seven of 29 (59%) survived to discharge. In Group A, 11/15 (73%) survived to recovery/OHTx and 9/15 (60%) survived to discharge. Four of 15 (27%) died awaiting OHTx. One child had graft failure requiring VA ECMO and was bridged successfully to retransplantation. One child dying after OHTx had acute rejection, was supported with VA ECMO and then BIVAD but did not recover. One patient had an unsuccessful second run on BIVAD 1 year after recovery from VA ECMO. In Group B, 10/14 (71%) survived to recovery/OHTx and 8/14 (57%) survived to discharge. Four of 14 (29%) died awaiting OHTx. Of deaths after OHTx, 1 occurred intraoperatively and 1 was consequent to graft failure and had an unsuccessful second run with VA ECMO. CONCLUSIONS: Children with CHD can be successfully bridged with MCS to heart transplantation. Single-ventricle circulation compared with biventricular physiology does not increase the risk of death before transplant or before hospital discharge.

Recurring extracorporeal circuit clotting during continuous renal replacement therapy in fungal sepsis: successful treatment with argatroban.

The relative effectiveness of anticoagulation strategies during continuous renal replacement therapy (CRRT) may vary according to the clinical circumstances. In this study, the case of a 46-year-old man who developed fungal mediastinitis with the pathogen Scedosporium prolificans after coronary bypass surgery is reported. Numerous debridements and multiple antifungal agents were not effective in this patient. Miltefosine, a non-Food and Drug Administration-approved agent, was started after institutional review board request and approval. CRRT was initiated with regional citrate anticoagulation (RCA) for clinical sepsis with acute kidney injury. Subsequently, crescendo clotting of the extracorporeal circuit (ECC) occurred. Multiple interventions, including escalating RCA, adding increasing heparin to RCA and exchanging the dialysis catheter, were not effective. Argatroban anticoagulation was started without further ECC clotting, and the patient recovered from both acute kidney injury and septic shock, despite continued miltefosine administration. Sepsis may contribute to recurrent ECC clotting. Argatroban, a direct thrombin inhibitor, had a disproportionate effectiveness to maintain ECC patency in this patient.