Hemidiaphragmatic paralysis increases postoperative morbidity after a modified Fontan operation

AbstractObjectives: After a Fontan procedure, forward pulmonary blood flow is augmented during inspiration because of negative intrathoracic pressure. Total pulmonary blood flow is higher during inspiration. With hemidiaphragmatic paralysis, inspiratory augmentation of pulmonary flow is lost or diminished. The objective of this study was to compare early postoperative morbidity after the modified Fontan operation in patients with and without hemidiaphragmatic paralysis. Methods: A case-control analysis was performed comparing 10 patients with documented hemidiaphragmatic paralysis against 30 patients without paralysis who were matched for diagnosis, fenestration, and age. The following early postoperative outcomes were assessed: duration of ventilator support, duration of hospital stay, incidence of ascites, prolonged effusions, and readmission. Results: Preoperatively, there were no significant differences between the 2 groups. However, among the postoperative outcomes, the duration of hospital stay (25.4 ± 16.6 days vs 10.8 ± 6.3 days; P =.03), incidence of ascites (70% vs 3%; P ||.001), prolonged pleural effusions (60% vs 13%; P =.007), and readmission (50% vs 7%; P =.007) were significantly greater in patients with hemidiaphragmatic paralysis than in those without hemidiaphragmatic paralysis. Conclusions: Hemidiaphragmatic paralysis after the modified Fontan operation is associated with an increase in early morbidity. Care should be taken to avoid injury to the phrenic nerve. Patients with prolonged effusions should be evaluated for hemidiaphragmatic paralysis.J Thorac Cardiovasc Surg 2001;122:856-6

Early results of the extracardiac conduit Fontan operation

AbstractBackground: Among the modifications of the Fontan operation, the extracardiac approach may offer the greatest potential for optimizing early postoperative ventricular and pulmonary vascular function, insofar as it can be performed with short periods of normothermic partial cardiopulmonary bypass and without cardioplegic arrest in most cases. In this study, we reviewed our experience with the extracardiac conduit Fontan operation, with a focus on early postoperative outcomes. Methods and results: Between July 1992 and April 1997, 51 patients (median age 4.9 years) underwent an extracardiac conduit Fontan operation. Median cardiopulmonary bypass time was 92 minutes and has decreased significantly over the course of our experience. Intracardiac procedures were performed in only 5 patients (10%), and the aorta was crossclamped in only 11 (22%). Intraoperative fenestration was performed in 24 patients (47%). There were no early deaths. Fontan failure occurred in 1 patient who was a poor candidate for the Fontan procedure. Transient supraventricular tachyarrhythmias occurred in 5 patients (10%). Median duration of chest tube drainage was 8 days. Factors significantly associated with prolonged resource use (mechanical ventilation, inotropic support, intensive care unit stay, and hospital stay) included longer bypass time and higher Fontan pressure. At a median follow-up of 1.9 years, there was 1 death from bleeding at reoperation. Conclusions: The extracardiac conduit Fontan procedure can be performed with minimal mortality and morbidity. Improved results may be related to advantages of the extracardiac approach and improved preservation of ventricular and pulmonary vascular function. (J Thorac Cardiovasc Surg 1999;117:688-96

Condiciones óptimas para el tratamiento, con vapor, del hormigón

Not availableEl fraguado acelerado se obtiene la mayor parte de las veces en hormigones de cemento mediante elevadas temperaturas y con una humedad relativa del aire del 100%. Si se aplica el tratamiento hidrotérmico, sin tener en cuenta los procesos físicos y físicoquímicos que se desarrollan durante el fraguado, hay que contar con un consumo elevado de cemento y un largo tratamiento térmico. Además, las consecuencias son: reducidas resistencias mecánicas y una insuficiente resistencia a la helada

Revision of previous Fontan connections to total extracardiac cavopulmonary anastomosis: A multicenter experience

AbstractBackground: Conversion to total extracardiac cavopulmonary anastomosis is an option for managing patients with dysfunction of a prior Fontan connection. Methods: Thirty-one patients (19.9 ± 8.8 years) underwent revision of a previous Fontan connection to total extracardiac cavopulmonary anastomosis at four institutions. Complications of the previous Fontan connection included atrial tachyarrhythmias (n = 20), progressive heart failure (n = 17), Fontan pathway obstruction (n = 10), effusions (n = 10), pulmonary venous obstruction by an enlarged right atrium (n = 6), protein-losing enteropathy (n = 3), right atrial thrombus (n = 2), subaortic stenosis (n = 1), atrioventricular valve regurgitation (n = 3), and Fontan baffle leak (n = 5). Conversion to an extracardiac cavopulmonary connection was performed with a nonvalved conduit from the inferior vena cava to the right pulmonary artery, with additional procedures as necessary. Results: There have been 3 deaths. Two patients died in the perioperative period of heart failure and massive effusions. The third patient died suddenly 8 months after the operation. All surviving patients were in New York Heart Association class I (n = 20) or II (n = 7), except for 1 patient who underwent heart transplantation. Early postoperative arrhythmias occurred in 10 patients: 4 required pacemakers, and medical therapy was sufficient in 6. In 15 patients, pre-revision arrhythmias were improved. Effusions resolved in all but 1 of the patients in whom they were present before revision. The condition of 2 patients with protein-losing enteropathy improved within 30 days. Conclusions: Conversion of a failing Fontan connection to extracardiac cavopulmonary connection can be achieved with low morbidity and mortality. Optimally, revision should be undertaken early in symptomatic patients before irreversible ventricular failure ensues. (J Thorac Cardiovasc Surg 2000;119:340-6

Topological Data Analysis for Discovery in Preclinical Spinal Cord Injury and Traumatic Brain Injury

Data-driven discovery in complex neurological disorders has potential to extract meaningful syndromic knowledge from large, heterogeneous data sets to enhance potential for precision medicine. Here we describe the application of topological data analysis (TDA) for data-driven discovery in preclinical traumatic brain injury (TBI) and spinal cord injury (SCI) data sets mined from the Visualized Syndromic Information and Outcomes for Neurotrauma-SCI (VISION-SCI) repository. Through direct visualization of inter-related histopathological, functional and health outcomes, TDA detected novel patterns across the syndromic network, uncovering interactions between SCI and co-occurring TBI, as well as detrimental drug effects in unpublished multicentre preclinical drug trial data in SCI. TDA also revealed that perioperative hypertension predicted long-term recovery better than any tested drug after thoracic SCI in rats. TDA-based data-driven discovery has great potential application for decision-support for basic research and clinical problems such as outcome assessment, neurocritical care, treatment planning and rapid, precision-diagnosis

Uncovering precision phenotype-biomarker associations in traumatic brain injury using topological data analysis

Background: Traumatic brain injury (TBI) is a complex disorder that is traditionally stratified based on clinical signs and symptoms. Recent imaging and molecular biomarker innovations provide unprecedented opportunities for improved TBI precision medicine, incorporating patho-anatomical and molecular mechanisms. Complete integration of these diverse data for TBI diagnosis and patient stratification remains an unmet challenge. Methods and findings: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot multicenter study enrolled 586 acute TBI patients and collected diverse common data elements (TBI-CDEs) across the study population, including imaging, genetics, and clinical outcomes. We then applied topology-based data-driven discovery to identify natural subgroups of patients, based on the TBI-CDEs collected. Our hypothesis was two-fold: 1) A machine learning tool known as topological data analysis (TDA) would reveal data-driven patterns in patient outcomes to identify candidate biomarkers of recovery, and 2) TDA-identified biomarkers would significantly predict patient outcome recovery after TBI using more traditional methods of univariate statistical tests. TDA algorithms organized and mapped the data of TBI patients in multidimensional space, identifying a subset of mild TBI patients with a specific multivariate phenotype associated with unfavorable outcome at 3 and 6 months after injury. Further analyses revealed that this patient subset had high rates of post-traumatic stress disorder (PTSD), and enrichment in several distinct genetic polymorphisms associated with cellular responses to stress and DNA damage (PARP1), and in striatal dopamine processing (ANKK1, COMT, DRD2). Conclusions: TDA identified a unique diagnostic subgroup of patients with unfavorable outcome after mild TBI that were significantly predicted by the presence of specific genetic polymorphisms. Machine learning methods such as TDA may provide a robust method for patient stratification and treatment planning targeting identified biomarkers in future clinical trials in TBI patients

Prospective Home-use Study on Non-invasive Neuromodulation Therapy for Essential Tremor.

Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (p≪0.0001), with 62% (TETRAS) and 68% (BF-ADL) of \u27severe\u27 or \u27moderate\u27 patients improving to \u27mild\u27 or \u27slight\u27. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients

Comprehensive Structural and Substrate Specificity Classification of the Saccharomyces cerevisiae Methyltransferome

Methylation is one of the most common chemical modifications of biologically active molecules and it occurs in all life forms. Its functional role is very diverse and involves many essential cellular processes, such as signal transduction, transcriptional control, biosynthesis, and metabolism. Here, we provide further insight into the enzymatic methylation in S. cerevisiae by conducting a comprehensive structural and functional survey of all the methyltransferases encoded in its genome. Using distant homology detection and fold recognition, we found that the S. cerevisiae methyltransferome comprises 86 MTases (53 well-known and 33 putative with unknown substrate specificity). Structural classification of their catalytic domains shows that these enzymes may adopt nine different folds, the most common being the Rossmann-like. We also analyzed the domain architecture of these proteins and identified several new domain contexts. Interestingly, we found that the majority of MTase genes are periodically expressed during yeast metabolic cycle. This finding, together with calculated isoelectric point, fold assignment and cellular localization, was used to develop a novel approach for predicting substrate specificity. Using this approach, we predicted the general substrates for 24 of 33 putative MTases and confirmed these predictions experimentally in both cases tested. Finally, we show that, in S. cerevisiae, methylation is carried out by 34 RNA MTases, 32 protein MTases, eight small molecule MTases, three lipid MTases, and nine MTases with still unknown substrate specificity