Citations

Background and Purpose— Embolic events have long been thought to occur in patients with cardiac tumors secondary to embolization of tumor fragments; however, there are no large studies examining the epidemiology and occurrence of embolism in this group of patients. Methods— From 1957 to 2006, 323 consecutive patients with primary cardiac tumors were treated surgically at our institution. Of these, patients who experienced an embolic event included 80 (cerebrovascular accident 31 [9.7%], transient ischemic attack 30 [9.3%], and other 19 [6%]). Those with no history of an embolic event (n=243 [75%]) were defined as control subjects. Results— Age was similar between the case and control groups (mean 54.5 versus 53.9 years, P =0.8). A multivariate logistic regression model including tumor location, tumor burden, tumor histology, and cerebrovascular risk factors, indicated that left atrial tumors (OR, 1.95; P =0.04), aortic valve tumors (OR, 4.17; P =0.002), and smaller tumor burden (OR, 2.20; P =0.01) were the most significant factors in the occurrence of embolism ( P <0.001). The presence of mitral regurgitation (OR, 0.12; P =0.006) and decreased functional status (New York Heart Association III/IV; OR, 0.31; P <0.001) were protective against the occurrence of embolism. Follow-up was obtained in 82% at a mean follow-up time of 6.17±6.9 years. There were no recurrent embolic events at follow-up. A Kaplan-Meier survival curve demonstrated no difference in survival between both groups ( P =0.78). Conclusion— Aortic valve and left atrial tumors have the greatest anatomic risk for embolism. Furthermore, patients with smaller tumors, minimal symptomatology, and no evidence of mitral regurgitation have a high risk of embolism. Cardiac tumors can be resected with low early mortality, and late survival after operation in the context of an embolic event is similar to patients with cardiac tumors who undergo resection for other indications.

Background and Purpose— Risk for both intracranial aneurysms (IAs) and aortic aneurysms (AAs) is thought to be heritable with mounting evidence for genetic predisposition. The concept of shared risk for these conditions is challenged by differences in age of diagnosis and demographic characteristics. We performed a genomewide linkage analysis in multiplex families with both IA and AA from the Familial Intracranial Aneurysm study. Methods— Available medical records of subjects who reported IA or abdominal/thoracic AA were reviewed with adjudication as definite/probable, possible, or not a case. To identify genes contributing to the susceptibility for IA and AA, genomewide linkage analysis was performed in the 26 multiplex IA families who had members who also had thoracic or abdominal AA. Individuals (n=91) were defined as affected if they had an IA (definite/probable) or an aortic or thoracic AA (definite/probable). Results— Maximum logarithm of odds (LOD) scores were found on chromosomes 11 (144 cM; LOD=3.0) and 6 (33 cM; LOD=2.3). In both chromosomal regions, analyses of these same 26 families considering only IA as the disease phenotype produced LOD scores of 1.8 and 1.6, respectively. Conclusions— Our linkage analysis in these 26 families using the broadest disease phenotype, including IA, abdominal AA, and thoracic AA, supports the concept of shared genetic risk. The chromosome 11 locus appears to confirm earlier independent associations in IA and AA. The chromosome 6 finding is novel. Both warrant further investigation.

A number of inherited disorders result in renal cyst development. The most common form, autosomal dominant polycystic kidney disease (ADPKD), is a disorder most often diagnosed in adults and caused by mutation in PKD1 or PKD2. The PKD1 protein, polycystin-1, is a large receptor-like protein, whereas polycystin-2 is a transient receptor potential channel. The polycystin complex localizes to primary cilia and may act as a mechanosensor essential for maintaining the differentiated state of epithelia lining tubules in the kidney and biliary tract. Elucidation of defective cellular processes has highlighted potential therapies, some of which are now being tested in clinical trials. ARPKD is the neonatal form of PKD and is associated with enlarged kidneys and biliary dysgenesis. The disease phenotype is highly variable, ranging from neonatal death to later presentation with minimal kidney disease. ARPKD is caused by mutation in PKHD1, and two truncating mutations are associated with neonatal lethality. The ARPKD protein, fibrocystin, is localized to cilia/basal body and complexes with polycystin-2. Rare, syndromic forms of PKD also include defects of the eye, central nervous system, digits, and/or neural tube and highlight the role of cilia and pathways such as Wnt and Hh in their pathogenesis.

Background: Laparoscopic ventral hernia repair (LVHR) has gained wide acceptance by both surgeons and patients, but hernias that approach a bony prominence are more complex due to the difficulty of proper fixation. This study was conducted to evaluate the use of bone anchor mesh fixation for complex LVHR. Methods: A prospective study of patients having complex LVHR with bone anchors was conducted using patients from 2 academic institutions between July 2003 and December 2007. Patient demographic data, characteristics of the hernia, operative details, and postoperative outcomes were recorded. Results: A total of 30 patients who had LVHR using bone anchors were evaluated (20 women, 10 men; mean age 60.9 years, range 41-83 years). In all, 17 suprapubic and 13 lateral hernias were included, requiring a mean of 2.8 and 3.2 bone anchors, respectively. The average hernia defect was 263 cm 2 (range 35-690 cm 2 ), and the average mesh size was 663 cm 2 (range 255-1360 cm 2 ). Mean operative time was 218 minutes (range 98-420 minutes), with an estimated blood loss of 46 mL (range 10-100 mL). The average length of stay was 5.2 days (range 1-26 days). Seven patients (23.3%) developed postoperative complications, and 1 patient in this study died (mortality 3.3%). During follow-up of 13.2 months (range 1-26 months), 2 patients (6.7%) developed a recurrent hernia. Conclusions: Bone anchors can be used successfully in the laparoscopic repair of complex ventral hernias, particularly with suprapubic and lateral hernias that approach a bony prominence. The complication rate is acceptable, with a short hospital stay and low recurrence rate.

Abstract Motivation: Specific non-covalent binding of metal ions and ligands, such as nucleotides and cofactors, is essential for the function of many proteins. Computational methods are useful for predicting the location of such binding sites when experimental information is lacking. Methods that use structural information, when available, are particularly promising since they can potentially identify non-contiguous binding motifs that cannot be found using only the amino acid sequence. Furthermore, a prediction method that can utilize low-resolution models is advantageous because high-resolution structures are available for only a relatively small fraction of proteins. Results: SitePredict is a machine learning-based method for predicting binding sites in protein structures for specific metal ions or small molecules. The method uses Random Forest classifiers trained on diverse residue-based site properties including spatial clustering of residue types and evolutionary conservation. SitePredict was tested by cross-validation on a set of known binding sites for six different metal ions and five different small molecules in a non-redundant set of protein–ligand complex structures. The prediction performance was good for all ligands considered, as reflected by AUC values of at least 0.8. Furthermore, a more realistic test on unbound structures showed only a slight decrease in the accuracy. The properties that contribute the most to the prediction accuracy of each ligand were also examined. Finally, examples of predicted binding sites in homology models and uncharacterized proteins are discussed. Availability: Binding site prediction results for all PDB protein structures and human protein homology models are available at http://sitepredict.org/. Contact: bordner.andrew@mayo.edu Supplementary information: Supplementary data are available at Bioinformatics online.

Pulmonary edema is a rare, potentially fatal complica tion associated with major resection of the lung, usually pneumonectomy. Although pulmonary edema in this setting can often be attributed to a variety of causes such as cardiac failure, bacterial pneumonia, and fluid overload, the specific syndrome of postpneumonec tomy pulmonary edema (PPE) occurs in the absence of these factors. PPE remains a diagnosis of exclusion, and its pathophysiology is poorly understood. Overzealous perioperative fluid administration has traditionally been implicated in clinical cases of postpneumonectomy pulmonary edema, but there is a body of evidence suggesting several other potential mechanisms. These include increases in cardiac output secondary to cat echolamine release, interruption of mediastinal lym phatic drainage, endothelial injury secondary to release of humoral factors or stretching of intercellular junc tions, hyperinflation, and other unknown factors.

Provision of anesthesia care to patients undergoing thoracoscopic procedures, especially video-assisted thoracoscopy, requires thorough knowledge of the sur gical procedure and the physiology of one-lung ventila tion, as well as meticulous attention to detail by the anesthesia personnel caring for these patients. Thoracos copy is used increasingly to perform almost the entire range of thoracic surgical procedures in a minimally invasive fashion. Excellent quality anesthetic care is necessary to assure the benefits of minimally invasive surgery to the maximum number of patients undergo ing thoracic surgery. This article will provide anesthesi ologists caring for patients undergoing thoracoscopy with the necessary working knowledge of the technical aspects of the procedure and understanding of the relevant anesthetic implications. Preoperative, intraop erative, and postoperative concerns will be addressed. The scope of this article will be limited to noncardiac uses of thoracoscopy.

Paraplegia is a major complication associated with repair of thoracoabdominal aortic aneurysms (TAAA). A number of therapies have been tried over the years, none of which has been successful. Recently, regional lumbar epidural cooling has been tried in an attempt to prolong the safe ischemic time during aortic cross- clamping. In approximately 90 patients in whom the authors have tried this technique, there was no de crease in the incidence of paraplegia in patients with type II TAAAs. This is perhaps not unanticipated be cause the paraplegia is related to a number of factors including the duration of the aortic cross-clamping, the adequacy of collateral circulation, embolization during the procedure, and perhaps thrombosis in situ. Given the multimodal cause of paraplegia, perhaps it is naive to think that a single therapy would be of benefit. Additional studies are necessary to explore the mecha nisms and to prove efficacy or lack of benefit of any techniques designed to decrease the incidence of paraplegia in patients undergoing TAAA repair.