Relationship between molecular properties and degradation mechanisms of organic solar cells based on bis-adducts of phenyl-C61 butyric acid methyl ester.

Environmental stability remains a major challenge for the commercialisation of organic solar cells and degradation pathways remain poorly understood. Designing materials for improved device stability requires an understanding of the relationship between the properties of the donor or acceptor molecule and different degradation mechanisms. Here we study the correlations between various molecular parameters of the fullerene derivative bis-PCBM and the degradation rate of polymer:bis-PCBM organic solar cells, based on the same carbazole-alt-benzothiadiazole polymer, in aerobic and anaerobic conditions. We compare eight high purity bis-PCBM isomers with different electronic, chemical and packing properties along with PCBM and the mixture of bis isomers. In the case of aerobic photodegradation, we find that device degradation rate is positively correlated to the LUMO energy of the bis-PCBM isomer and to the degree of crystallinity of the isomer, while the correlation of degradation with driving force for epoxide formation is unclear. These results support the idea that in these samples, aerobic photodegradation proceeds via superoxide formation by the photogenerated polaron on the fullerene, followed by further chemical reaction. In the absence of air, photodegradation rate is correlated with molecular structure, supporting the mechanism of microstructural degradation via fullerene dimerization. The approach and findings presented here show how control of specific molecular parameters through chemical design can serve as a strategy to enhance stability of organic solar cells.

Toward Improved Environmental Stability of Polymer:Fullerene and Polymer:Nonfullerene Organic Solar Cells: A Common Energetic Origin of Light- and Oxygen-Induced Degradation.

With the emergence of nonfullerene electron acceptors resulting in further breakthroughs in the performance of organic solar cells, there is now an urgent need to understand their degradation mechanisms in order to improve their intrinsic stability through better material design. In this study, we present quantitative evidence for a common root cause of light-induced degradation of polymer:nonfullerene and polymer:fullerene organic solar cells in air, namely, a fast photo-oxidation process of the photoactive materials mediated by the formation of superoxide radical ions, whose yield is found to be strongly controlled by the lowest unoccupied molecular orbital (LUMO) levels of the electron acceptors used. Our results elucidate the general relevance of this degradation mechanism to both polymer:fullerene and polymer:nonfullerene blends and highlight the necessity of designing electron acceptor materials with sufficient electron affinities to overcome this challenge, thereby paving the way toward achieving long-term solar cell stability with minimal device encapsulation.

Anterior lumbar discectomy and fusion for acute cauda equina syndrome caused by recurrent disc prolapse: report of 3 cases.

There is a lack of information and consensus regarding the optimal treatment for recurrent disc herniation previously treated by posterior discectomy, and no reports have described an anterior approach for recurrent disc herniation causing cauda equina syndrome (CES). Revision posterior decompression, irrespective of the presence of CES, has been reported to be associated with significantly higher rates of dural tears, hematomas, and iatrogenic nerve root damage. The authors describe treatment and outcomes in 3 consecutive cases of patients who underwent anterior lumbar discectomy and fusion (ALDF) for CES caused by recurrent disc herniations that had been previously treated with posterior discectomy. All 3 patients were operated on within 12 hours of presentation and were treated with an anterior retroperitoneal lumbar approach. Follow-up ranged from 12 to 24 months. Complete retrieval of herniated disc material was achieved without encountering significant epidural scar tissue in all 3 cases. No perioperative infection or neurological injury occurred, and all 3 patients had neurological recovery with restoration of bladder and bowel function and improvement in back and leg pain. ALDF is one option to treat CES caused by recurrent lumbar disc prolapse previously treated with posterior discectomy. The main advantage is that it avoids dissection around epidural scar tissue, but the procedure is associated with other risks and further evaluation of its safety in larger series is required.

The current state of the evidence for the use of drains in spinal surgery: systematic review.

PURPOSE: Search for evidence pertaining to the effectiveness of drains used in spinal surgeries. METHOD: PubMed and EMBASE databases were searched for articles pertaining to the use of drains in all types of spinal surgery. The bibliographies of relevant studies were searched for additional papers that met the initial inclusion criteria. Level I and II studies were scored according to guidelines in the Cochrane Collaboration Back Review Group. We utilised the Population, Intervention, Comparison, Outcomes and Study design (PICOS) method to define our study eligibility criteria. RESULTS: Nineteen papers were identified: four level I studies, eight level III studies and seven level IV studies. The four level I, involving the randomization of patients into 'drain' and 'non-drain' groups, identified a total of 363 patients. Seven of the eight level III retrospective studies concluded that the use of drains did not reduce complications. Two of the seven level IV studies agreed with this conclusion. The remaining five level IV studies reported the benefits of lumbar drainage following dural tears. CONCLUSIONS: There is a paucity of published literature on the use of drains following spinal surgery. This is the first study to assess the evidence for the benefits of drains post-operatively in spinal surgery. The identified studies have shown that drains do not reduce the incidence of complications in anterior cervical discectomy and fusion, one and two level posterior cervical fusions, lumbar laminectomies, lumbar decompressions or discectomies and posterior spinal fusion for adolescent scoliosis. Further level I and II studies are needed.

Recommendations for Lengthening of Magnetically Controlled Growing Rods in Children With Pacemakers.

PURPOSE OF THE STUDY: Pacemakers are currently identified as a contraindication for the use of magnetic growth rods (MGRs). This arises from concern that magnetic fields generated by the MGR external remote controller (ERC) during lengthening procedures may induce pacemaker dysfunction. We investigated (1) whether MGR lengthening affects pacemaker function, and (2) if the magnetic field of a pacemaker affects MGR lengthening. METHODS: MGRs were tested in conjunction with an magnetic resonance imaging-compatible pacemaker, which was connected to a virtual patient under continuous cardiac monitoring. To determine whether pacemaker function was affected during MGR lengthening, the electrocardiogram trace was monitored for arrhythmias, whereas an ERC was applied to lengthen the MGRs at varying distances from the pacemaker. To investigate if MGR lengthening was affected by the presence of a pacemaker, at the start and end of the experiment, the ability of the rods to fully elongate and shorten was tested to check for conservation of function. RESULTS: When the pacemaker was in normal mode, <16 cm away from the activated ERC during MGR lengthening, pacemaker function was affected by the ERC's magnetic forces. At this distance, prophylactically switching the pacemaker to tonic mode before lengthening prevented occurrence of inappropriate pacing discharges. No deleterious effect of the pacemaker's magnetic field on the MGR lengthening mechanism was identified. CONCLUSIONS: Magnetic resonance imaging-compatible pacemakers appear safe for concomitant use with MGRs, provided a pacemaker technician prophylactically switches the pacemaker to tonic function before outpatient lengthening procedures. CLINICAL RELEVANCE: This experiment was designed to provide the first safety information on MGR lengthening in children with pacemakers. Although currently a rare clinical scenario, with increasing use of MGRs, this clinical scenario may arise more frequently in the future.

Neurological Injury in Intermediate-Risk Transcatheter Aortic Valve Implantation.

BACKGROUND: The application of transcatheter aortic valve implantation (TAVI) to intermediate-risk patients is a controversial issue. Of concern, neurological injury in this group remains poorly defined. Among high-risk and inoperable patients, subclinical injury is reported on average in 75% undergoing the procedure. Although this attendant risk may be acceptable in higher-risk patients, it may not be so in those of lower risk. METHODS AND RESULTS: Forty patients undergoing TAVI with the Edwards SAPIEN-XT™ prosthesis were prospectively studied. Patients were of intermediate surgical risk, with a mean±standard deviation Society of Thoracic Surgeons score of 5.1±2.5% and a EuroSCORE II of 4.8±2.4%; participant age was 82±7 years. Clinically apparent injury was assessed by serial National Institutes of Health Stroke Scale assessments, Montreal Cognitive Assessments (MoCA), and with the Confusion Assessment Method. These identified 1 (2.5%) minor stroke, 1 (2.5%) episode of postoperative delirium, and 2 patients (5%) with significant postoperative cognitive dysfunction. Subclinical neurological injury was assessed using brain magnetic resonance imaging, including diffusion-weighted imaging (DWI) sequences preprocedure and at 3±1 days postprocedure. This identified 68 new DWI lesions present in 60% of participants, with a median±interquartile range of 1±3 lesions/patient and volumes of infarction of 24±19 µL/lesion and 89±218 µL/patient. DWI lesions were associated with a statistically significant reduction in early cognition (mean ΔMoCA -3.5±1.7) without effect on cognition, quality of life, or functional capacity at 6 months. CONCLUSIONS: Objectively measured subclinical neurological injuries remain a concern in intermediate-risk patients undergoing TAVI and are likely to manifest with early neurocognitive changes. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Australian & New Zealand Clinical Trials Registry: ACTRN12613000083796.

Alternative technique in atypical spinal decompression: the use of the ultrasonic scalpel in paediatric achondroplasia.

Spinal stenosis can be a very disabling condition. Surgical decompression carries a risk of dural tear and neural injury, which is increased in patients with severe stenosis or an atypical anatomy. We present an unusual case of symptomatic stenosis secondary to achondroplasia presenting in a paediatric patient, and highlight a new surgical technique used to minimise the risk of dural and neural injury during decompression.

Effects of milk containing only A2 beta casein versus milk containing both A1 and A2 beta casein proteins on gastrointestinal physiology, symptoms of discomfort, and cognitive behavior of people with self-reported intolerance to traditional cows' milk.

BACKGROUND: Cows' milk generally contains two types of ß-casein, A1 and A2 types. Digestion of A1 type can yield the peptide ß-casomorphin-7, which is implicated in adverse gastrointestinal effects of milk consumption, some of which resemble those in lactose intolerance. This study aimed to compare the effects of milk containing A1 ß-casein with those of milk containing only A2 ß-casein on inflammation, symptoms of post-dairy digestive discomfort (PD3), and cognitive processing in subjects with self-reported lactose intolerance. METHODS: Forty-five Han Chinese subjects participated in this double-blind, randomized, 2 × 2 crossover trial and consumed milk containing both ß-casein types or milk containing only A2 ß-casein. Each treatment period was 14 days with a 14-day washout period at baseline and between treatment periods. Outcomes included PD3, gastrointestinal function (measured by smart pill), Subtle Cognitive Impairment Test (SCIT), serum/fecal laboratory biomarkers, and adverse events. RESULTS: Compared with milk containing only A2 ß-casein, the consumption of milk containing both ß-casein types was associated with significantly greater PD3 symptoms; higher concentrations of inflammation-related biomarkers and ß-casomorphin-7; longer gastrointestinal transit times and lower levels of short-chain fatty acids; and increased response time and error rate on the SCIT. Consumption of milk containing both ß-casein types was associated with worsening of PD3 symptoms relative to baseline in lactose tolerant and lactose intolerant subjects. Consumption of milk containing only A2 ß-casein did not aggravate PD3 symptoms relative to baseline (i.e., after washout of dairy products) in lactose tolerant and intolerant subjects. CONCLUSIONS: Consumption of milk containing A1 ß-casein was associated with increased gastrointestinal inflammation, worsening of PD3 symptoms, delayed transit, and decreased cognitive processing speed and accuracy. Because elimination of A1 ß-casein attenuated these effects, some symptoms of lactose intolerance may stem from inflammation it triggers, and can be avoided by consuming milk containing only the A2 type of beta casein. TRIAL REGISTRATION: ClinicalTrials.gov/NCT02406469.

Actuator pin fracture in magnetically controlled growing rods: two cases.

BACKGROUND CONTEXT: Magnetically controlled growing rods (MCGRs) are used in the management of early-onset scoliosis (EOS). Each MCGR contains a telescopic actuator that serves as the distraction element when stimulated by an external remote controller (ERC), permitting non-invasive lengthening in the outpatient clinic. PURPOSE: This report highlights a subtle cause of MCGR failure. We present the first two reported cases of lengthening pin fracture in patients with dual-MCGR constructs. STUDY DESIGN: We present two cases of patients with EOS treated with dual-construct MAGEC (MAGnetic Expansion Control, Ellipse Technologies Inc, Aliso Viejo, CA, USA) MCGRs. METHODS: A 12-year-old boy presented describing a "popping" sensation in his thoracic spine and resultant grating 36 months following MCGR insertion. RESULTS: A plain radiograph revealed a subtle fracture of the lengthening pin within the actuator of the right MCGR. Following identification of this case of implant failure, we reviewed the most recent radiographs of all nine of our patients treated with this MCGR in our institution, resulting in the discovery of bilateral MCGR lengthening pin fractures in an otherwise asymptomatic 11-year-old girl. CONCLUSIONS: Clinicians should have a high index of suspicion of structural implant failure when presented with histories similar to those reported in our first case, or following unsuccessful distraction of MCGRs. In such cases new radiographs should be taken, and all previous images should be reviewed for evidence of this phenomenon. Centers that document MCGR lengthening with ultrasound should obtain plain radiographs every 6 months to evaluate the structural integrity of the implant.

The silent and apparent neurological injury in transcatheter aortic valve implantation study (SANITY): concept, design and rationale.

BACKGROUND: The incidence of clinically apparent stroke in transcatheter aortic valve implantation (TAVI) exceeds that of any other procedure performed by interventional cardiologists and, in the index admission, occurs more than twice as frequently with TAVI than with surgical aortic valve replacement (SAVR). However, this represents only a small component of the vast burden of neurological injury that occurs during TAVI, with recent evidence suggesting that many strokes are clinically silent or only subtly apparent. Additionally, insult may manifest as slight neurocognitive dysfunction rather than overt neurological deficits. Characterisation of the incidence and underlying aetiology of these neurological events may lead to identification of currently unrecognised neuroprotective strategies. METHODS: The Silent and Apparent Neurological Injury in TAVI (SANITY) Study is a prospective, multicentre, observational study comparing the incidence of neurological injury after TAVI versus SAVR. It introduces an intensive, standardised, formal neurologic and neurocognitive disease assessment for all aortic valve recipients, regardless of intervention (SAVR, TAVI), valve-type (bioprosthetic, Edwards SAPIEN-XT) or access route (sternotomy, transfemoral, transapical or transaortic). Comprehensive monitoring of neurological insult will also be recorded to more fully define and compare the neurological burden of the procedures and identify targets for harm minimisation strategies. DISCUSSION: The SANITY study undertakes the most rigorous assessment of neurological injury reported in the literature to date. It attempts to accurately characterise the insult and sustained injury associated with both TAVI and SAVR in an attempt to advance understanding of this complication and associations thus allowing for improved patient selection and procedural modification.

Dietary A1 ß-casein affects gastrointestinal transit time, dipeptidyl peptidase-4 activity, and inflammatory status relative to A2 ß-casein in Wistar rats.

We compared the gastrointestinal effects of milk-based diets in which the ß-casein component was either the A1 or A2 type in male Wistar rats fed the experimental diets for 36 or 84 h. Gastrointestinal transit time was significantly greater in the A1 group, as measured by titanium dioxide recovery in the last 24 h of feeding. Co-administration of naloxone decreased gastrointestinal transit time in the A1 diet group but not in the A2 diet group. Colonic myeloperoxidase and jejunal dipeptidyl peptidase (DPP)-4 activities were greater in the A1 group than in the A2 group. Naloxone attenuated the increase in myeloperoxidase activity but not that in DPP-4 activity in the A1 group. Naloxone did not affect myeloperoxidase activity or DPP-4 activity in the A2 group. These results confirm that A1 ß-casein consumption has direct effects on gastrointestinal function via opioid-dependent (gastrointestinal transit and myeloperoxidase activity) and opioid-independent (DPP-4 activity) pathways.

Recognition of CD1d-sulfatide mediated by a type II natural killer T cell antigen receptor.

Natural killer T cells (NKT cells) are divided into type I and type II subsets on the basis of differences in their T cell antigen receptor (TCR) repertoire and CD1d-antigen specificity. Although the mode by which type I NKT cell TCRs recognize CD1d-antigen has been established, how type II NKT cell TCRs engage CD1d-antigen is unknown. Here we provide a basis for how a type II NKT cell TCR, XV19, recognized CD1d-sulfatide. The XV19 TCR bound orthogonally above the A' pocket of CD1d, in contrast to the parallel docking of type I NKT cell TCRs over the F' pocket of CD1d. At the XV19 TCR-CD1d-sulfatide interface, the TCRα and TCRß chains sat centrally on CD1d, where the malleable CDR3 loops dominated interactions with CD1d-sulfatide. Accordingly, we highlight the diverse mechanisms by which NKT cell TCRs can bind CD1d and account for the distinct antigen specificity of type II NKT cells.

Recognition of ß-linked self glycolipids mediated by natural killer T cell antigen receptors.

The most potent foreign antigens for natural killer T cells (NKT cells) are α-linked glycolipids, whereas NKT cell self-reactivity involves weaker recognition of structurally distinct ß-linked glycolipid antigens. Here we provide the mechanism for the autoreactivity of T cell antigen receptors (TCRs) on NKT cells to the mono- and tri-glycosylated ß-linked agonists ß-galactosylceramide (ß-GalCer) and isoglobotrihexosylceramide (iGb3), respectively. In binding these disparate antigens, the NKT cell TCRs docked onto CD1d similarly, achieving this by flattening the conformation of the ß-linked ligands regardless of the size of the glycosyl head group. Unexpectedly, the antigenicity of iGb3 was attributable to its terminal sugar group making compensatory interactions with CD1d. Thus, the NKT cell TCR molds the ß-linked self ligands to resemble the conformation of foreign α-linked ligands, which shows that induced-fit molecular mimicry can underpin the self-reactivity of NKT cell TCRs to ß-linked antigens.

A molecular basis for NKT cell recognition of CD1d-self-antigen.

The antigen receptor for natural killer T cells (NKT TCR) binds CD1d-restricted microbial and self-lipid antigens, although the molecular basis of self-CD1d recognition is unclear. Here, we have characterized NKT TCR recognition of CD1d molecules loaded with natural self-antigens (Ags) and report the 2.3 Å resolution structure of an autoreactive NKT TCR-phosphatidylinositol-CD1d complex. NKT TCR recognition of self- and foreign antigens was underpinned by a similar mode of germline-encoded recognition of CD1d. However, NKT TCR autoreactivity is mediated by unique sequences within the non-germline-encoded CDR3ß loop encoding for a hydrophobic motif that promotes self-association with CD1d. Accordingly, NKT cell autoreactivity may arise from the inherent affinity of the interaction between CD1d and the NKT TCR, resulting in the recognition of a broad range of CD1d-restricted self-antigens. This demonstrates that multiple self-antigens can be recognized in a similar manner by autoreactive NKT TCRs.

An application of outcomes monitoring for coronary artery bypass surgery 2005-2008 at TPCH.

OBJECTIVE: To describe monitoring of four years' isolated coronary artery bypass surgery outcomes and complications at The Prince Charles Hospital, Brisbane, Australia. METHODS: Analysis of Cardiac Surgical Register database using tabulations, funnel plots and random-effects (Bayesian shrinkage) analysis for aggregated data. Combined CUSUM and cumulative observed minus expected (modified VLAD) charts and combined CUSUM and cumulative funnel plots used for individual observation sequential data and binomial control charts and generalised additive models (GAMs) for quarterly sequential data. Risk adjustment employed re-calibrated EuroSCORE. RESULTS: There were 2575 procedures with an unadjusted in-hospital mortality rate of 1.17%. Mean age was 65 years and 21% of patients were female; 43.6% were elective procedures. Median ventilation time was 10 hours and median length of stay in intensive care (ICU) was 23 hours. Return to theatre for bleeding occurred in 3% of cases. Return to theatre for surgical site infection occurred in 0.4% of cases; 4% were re-do procedures. Permanent stroke or neurological deficit occurred in 1%, perioperative myocardial infarction in 0.8%, arrest in 1.2%, renal failure in 1.6% and ICU return in 2.3% of cases. CONCLUSIONS: Complication rates and mortality were comparable with similar units. Use of random-effects (Bayesian shrinkage) analysis for aggregated data is encouraged together with generalised additive models (GAMs) and combined CUSUM and cumulative observed minus expected (modified VLAD) charts for sequential data.

Determinants of in-hospital and long-term surgical outcomes after repair of postinfarction ventricular septal rupture.

OBJECTIVES: Surgical repair of post-myocardial infarction ventricular septal rupture is challenging with reported early mortality being substantial. In addition, congestive cardiac failure and ventricular tachyarrhythmia frequently occur long term after the operation, although frequency and predictive factors of these events have been poorly identified. METHODS: A consecutive series of 68 patients who underwent repair of postinfarction ventricular septal rupture by 14 surgeons between 1988 and 2007 was studied. Fifty-eight (85%) patients underwent repair in an urgent setting (<48 hours after diagnosis). Coronary artery bypass grafting was concomitantly performed in 48 (71%) patients. Mean follow-up period was 9.2 +/- 4.9 years. RESULTS: Thirty-day mortality was 35%, with previous myocardial infarction, previous cardiac surgery, preoperative left ventricular ejection fraction less than 40%, and urgent surgery being independent risk factors. Actuarial survival of 30-day survivors was 88% at 5 years, 73% at 10 years, and 51% at 15 years. Actuarial freedom from congestive cardiac failure and ventricular tachyarrhythmia was 70% and 85% at 5 years, 54% and 71% at 10 years, and 28% and 61% at 15 years, respectively. Independent predictors for congestive cardiac failure included hypertension, posterior septal rupture, residual interventricular communication, and preoperative left ventricular ejection fraction less than 40%, whereas concomitant ventricular aneurysmectomy and preoperative occlusion of the left anterior descending artery were independent predictors of ventricular tachyarrhythmia. CONCLUSIONS: Long-term outcomes after surgical repair of postinfarction ventricular septal rupture was favorable, despite infrequent exposure by individual surgeons to the pathologic features, indicating that an aggressive surgical approach is warranted. Predictors of congestive cardiac failure and ventricular arrhythmia long term varied.

Structural insights into mechanism and specificity of O-GlcNAc transferase.

Post-translational modification of protein serines/threonines with N-acetylglucosamine (O-GlcNAc) is dynamic, inducible and abundant, regulating many cellular processes by interfering with protein phosphorylation. O-GlcNAcylation is regulated by O-GlcNAc transferase (OGT) and O-GlcNAcase, both encoded by single, essential, genes in metazoan genomes. It is not understood how OGT recognises its sugar nucleotide donor and performs O-GlcNAc transfer onto proteins/peptides, and how the enzyme recognises specific cellular protein substrates. Here, we show, by X-ray crystallography and mutagenesis, that OGT adopts the (metal-independent) GT-B fold and binds a UDP-GlcNAc analogue at the bottom of a highly conserved putative peptide-binding groove, covered by a mobile loop. Strikingly, the tetratricopeptide repeats (TPRs) tightly interact with the active site to form a continuous 120 A putative interaction surface, whereas the previously predicted phosphatidylinositide-binding site locates to the opposite end of the catalytic domain. On the basis of the structure, we identify truncation/point mutants of the TPRs that have differential effects on activity towards proteins/peptides, giving first insights into how OGT may recognise its substrates.

Arterial switch operation in patients with Taussig-Bing anomaly--influence of staged repair and coronary anatomy on outcome.

OBJECTIVE: This study evaluated the results of arterial switch operation and closure of ventricular defects (ASO+VSDc) for double outlet right ventricle with sub-pulmonary ventricular septal defect (Taussig-Bing anomaly). METHODS: Between 1988 and 2003, 33 patients (25 male, 76%) with Taussig-Bing anomaly underwent ASO+VSDc (median age 39 days, 1 day-2.1 years). The relationship of the great arteries was antero-posterior (Group I, n=19) or side-by-side (Group II, n=14). Coronary anatomy (Yacoub's classification) was exclusively type A or D in Group I and predominantly type D or E in Group II (64%). Incidence of sub-aortic obstruction and aortic arch obstruction was similar in Group I and II (37% vs 57%, p=0.25 and 84% vs 79%, p=0.98, respectively). Twenty-five patients (76%) had one-stage total correction. Risk factors were analysed using multivariable analysis. Follow-up was complete (median interval of 6.2 years; range, 0.6-15.2 years). RESULTS: There were three early (9%) and one late death. Actuarial survival was 88+/-6% at 1 and 10 years. There were two early and four late re-operations. Freedom from re-operation was 90+/-5% and 75+/-9% at 1 and 10 years. Four patients required cardiological re-interventions. Freedom from re-intervention at 5 and 10 years was 79+/-9%. On multivariable analysis, complex coronary anatomy (type B and C) was a risk for early mortality (p<0.001) but all other anatomical variables and staged strategy did not influence early or actuarial survival. CONCLUSIONS: The ASO+VSDc approach can be applied to Taussig-Bing anomaly with acceptable mortality and morbidity and it is the procedure of choice at our institution. Anatomical variables did not influence outcomes with this strategy. A staged strategy is still appropriate in complex cases.

Factors influencing early and late outcome following the Fontan procedure in the current era. The 'Two Commandments'?

OBJECTIVE: This study was undertaken to identify the factors affecting early and late outcome following the Fontan procedure in the current era. We have examined whether conventional selection criteria, the 'Ten Commandments', are still applicable in the current era. MATERIALS AND METHODS: Between January 1988 and July 2004, 406 patients underwent a modified Fontan procedure at a median age of 4.7 years (IQR, 3.8-7.1 years). The single functional ventricle was of left (n=241, 59%) or right ventricular morphology (n=163, 40%). The modified Fontan procedure was performed using an atriopulmonary connection (n=162, 40%) or total cavopulmonary connection (TCPC) involving a lateral atrial tunnel (n=50, 12%) or extracardiac conduit (n=194, 48%). They were fenestrated in 216 patients (53%). RESULTS: The early mortality was 4.4% (n=18) and four other patients required takedown of the Fontan circulation. On multivariable analysis, early outcome was adversely influenced by two factors (p<0.05): preoperative impaired ventricular function and elevated pulmonary artery pressures. Two risk models were constructed for early outcome based on preoperative and predictable operative variables (Model 1) and all preoperative and operative data (Model 2). Both models were calibrated across all deciles (p=0.83, p=0.25) and discriminated well. The area under the ROC curve was 0.85 and 0.89, respectively. There were 21 late deaths, 1 patient required late takedown of the Fontan circulation and 3 required orthotopic cardiac transplantation. Actuarial survival was 90+/-2%, 86+/-2% and 82+/-3% at 5, 10 and 15 years, respectively. Multivariable analysis identified that outcome was influenced by preoperatively impaired ventricular function, elevated preoperative pulmonary artery pressures and an earlier year of operation. The freedom from reintervention was 83+/-4%, 76+/-4% and 74+/-8% at 5, 10 and 15 years, respectively. Additional risk factors for reintervention were right atrial isomerism and preoperative small pulmonary artery size. CONCLUSIONS: Late outcome of the Fontan circulation is encouraging. Ventricular morphology, surgical technique and fenestration do not appear to influence early or late outcome. Preoperatively impaired ventricular function and elevated pulmonary artery pressures have an adverse influence on both early and late outcome. Reintervention is common, with small preoperative pulmonary artery size being an additional risk factor.

Levosimendan for low cardiac output: a pediatric experience.

This was a retrospective observational study in a pediatric intensive care unit, in which 19 patients received levosimendan. There were no adverse events attributable to levosimendan and no instances where the clinical condition worsened after administration. Arterial lactate levels decreased significantly following levosimendan administration during cardiopulmonary bypass for anticipated low cardiac output. In those with established low cardiac output, trends toward improved hemodynamics were seen, with heart rate reduction, an increase in mean blood pressure, a reduction in arterial lactate, and reduced conventional inotrope use. Levosimendan was safely used in a small number of pediatric patients with established low cardiac output state who demonstrated improved hemodynamics and tissue perfusion, with a tendency to reduced conventional inotrope usage, and this warrants its evaluation as an inotrope in the pediatric population.