Mitral Valve Surgery for Severe Mitral Regurgitation and Dilated Cardiomyopathy—A Bridge to Transplant: Case Report and a Review of Literature

We report a child with myocardial necrosis, dilated cardiomyopathy, and severe mitral valve (MV) regurgitation following neonatal enteroviral myocarditis. He underwent MV annuloplasty at 18 months and MV replacement at 3 years of age. He remains asymptomatic on medical therapy at 8 years of age. Mitral valve surgery may stabilize the evolution of dilated cardiomyopathy and delay the ultimate need for heart transplant.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93665/1/chd626.pd

Predictors of Left Ventricular Remodeling after Aortic Valve Replacement in Pediatric Patients with Isolated Aortic Regurgitation

Objective. To identify the risk factors that could predict postoperative outcome after aortic valve replacement in pediatric patients with isolated aortic regurgitation ( AR ). Background. There is controversy regarding the appropriate timing of surgery in asymptomatic or minimally symptomatic patients with isolated AR . In the pediatric age group, there are limited studies in this regard and most of them are on combined aortic valve stenosis and regurgitation. Methods. All patients with biventricular physiology and morphologic left ventricle ( LV ) who underwent aortic valve surgery for AR from J anuary 1988 to J uly 2010 were included in the study. Demographic, clinical, and echocardiographic data were collected at presurgical visit, early postoperative, 1 year, and most recent follow‐up. Results. Among 53 patients (36 males), 18 had LV end‐diastolic diameter ( LVEDD ) z ‐score >4 standard deviation ( SD ) (group I ) and 35 had LVEDD 4 SD predicted persistent LV dilation (>2 SD ) at early post‐op ( P  4 SD ) are significant predictors of incomplete LV remodeling or persistent LV dysfunction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97538/1/chd703.pd

Forcing Spring Bulbs in High Tunnels for Profitability

High tunnels are a relatively new concept primarily used by vegetable growers for season extension (both spring and fall, but mainly for early spring production). There also are a few Iowa growers raising strawberries and cut flowers. Almost any annual outdoor vegetable crop can be raised successfully in a high tunnel, but the key is profitability. A common structure is 30 × 96 ft and typically costs about $1.60 to$2.35/sq ft (with automatic side rollup). Some crops can be double cropped in a high tunnel (peppers, pole beans, and specialty cucumbers)

Prevalence and Risk Factors for Upper Airway Obstruction after Pediatric Cardiac Surgery

Objective To determine the prevalence of and risk factors for extrathoracic upper-airway obstruction after pediatric cardiac surgery. Study design A retrospective chart review was performed on 213 patients younger than 18 years of age who recovered from cardiac surgery in our multidisciplinary intensive care unit in 2012. Clinically significant upper-airway obstruction was defined as postextubation stridor with at least one of the following: receiving more than 2 corticosteroid doses, receiving helium-oxygen therapy, or reintubation. Multivariate logistic regression analysis was performed to determine independent risk factors for this complication. Results Thirty-five patients (16%) with extrathoracic upper-airway obstruction were identified. On bivariate analysis, patients with upper-airway obstruction had greater surgical complexity, greater vasoactive medication requirements, and longer postoperative durations of endotracheal intubation. They also were more difficult to calm while on mechanical ventilation, as indicated by greater infusion doses of narcotics and greater likelihood to receive dexmedetomidine or vecuronium. On multivariable analysis, adjunctive use of dexmedetomedine or vecuronium (OR 3.4, 95% CI 1.4-8) remained independently associated with upper-airway obstruction. Conclusion Extrathoracic upper-airway obstruction is relatively common after pediatric cardiac surgery, especially in children who are difficult to calm during endotracheal intubation. Postoperative upper-airway obstruction could be an important outcome measure in future studies of sedation practices in this patient population

Risk Factors for Extubation Failure following Neonatal Cardiac Surgery

Objective: Extubation failure after neonatal cardiac surgery has been associated with considerable postoperative morbidity, although data identifying risk factors for its occurrence are sparse. We aimed to determine risk factors for extubation failure in our neonatal cardiac surgical population. Design: Retrospective chart review. Setting: Urban tertiary care free-standing children’s hospital. Patients: Neonates (0–30 d) who underwent cardiac surgery at our institution between January 2009 and December 2012 was performed. Interventions: Extubation failure was defined as reintubation within 72 hours after extubation from mechanical ventilation. Multivariate logistic regression analysis was performed to determine independent risk factors for extubation failure. Measurements and Main Results: We included 120 neonates, of whom 21 (17.5%) experienced extubation failure. On univariate analysis, patients who failed extubation were more likely to have genetic abnormalities (24% vs 6%; p = 0.023), hypoplastic left heart (43% vs 17%; p = 0.009), delayed sternal closure (38% vs 12%; p = 0.004), postoperative infection prior to extubation (38% vs 11%; p = 0.002), and longer duration of mechanical ventilation (median, 142 vs 58 hr; p = 0.009]. On multivariate analysis, genetic abnormalities, hypoplastic left heart, and postoperative infection remained independently associated with extubation failure. Furthermore, patients with infection who failed extubation tended to receive fewer days of antibiotics prior to their first extubation attempt when compared with patients with infection who did not fail extubation (4.9 ± 2.6 vs 7.3 ± 3; p = 0.073). Conclusions: Neonates with underlying genetic abnormalities, hypoplastic left heart, or postoperative infection were at increased risk for extubation failure. A more conservative approach in these patients, including longer pre-extubation duration of antibiotic therapy for postoperative infections, may be warranted

Passive Peritoneal Drainage versus Pleural Drainage after Pediatric Cardiac Surgery

Background: We aimed to determine whether infants undergoing cardiac surgery would more efficiently attain negative fluid balance postoperatively with passive peritoneal drainage as compared to traditional pleural drainage. Methods: A prospective, randomized study including children undergoing repair of tetralogy of Fallot (TOF) or atrioventricular septal defect (AVSD) was completed between September 2011 and June 2013. Patients were randomized to intraoperative placement of peritoneal catheter or right pleural tube in addition to the requisite mediastinal tube. The primary outcome measure was fluid balance at 48 hours postoperatively. Variables were compared using t tests or Fisher exact tests as appropriate. Results: A total of 24 patients were enrolled (14 TOF and 10 AVSD), with 12 patients in each study group. Mean fluid balance at 48 hours was not significantly different between study groups, −41 ± 53 mL/kg in patients with periteonal drainage and −9 ± 40 mL/kg in patients with pleural drainage (P = .10). At 72 hours however, postoperative fluid balance was significantly more negative with peritoneal drainage, −52.4 ± 71.6 versus +2.0 ± 50.6 (P = .04). On subset analysis, fluid balance at 48 hours in patients with AVSD was more negative with peritoneal drainage as compared to pleural, −82 ± 51 versus −1 ± 38 mL/kg, respectively (P = .02). Fluid balance at 48 hours in patients with TOF was not significantly different between study groups. Conclusion: Passive peritoneal drainage may more effectively facilitate negative fluid balance when compared to pleural drainage after pediatric cardiac surgery, although this benefit is not likely universal but rather dependent on the patient’s underlying physiology

Specific Inhibition of p97/VCP ATPase and Kinetic Analysis Demonstrate Interaction between D1 and D2 ATPase domains

The p97 AAA (ATPase associated with diverse cellular activities), also called VCP (valosin-containing protein), is an important therapeutic target for cancer and neurodegenerative diseases. p97 forms a hexamer composed of two AAA domains (D1 and D2) that form two stacked rings, and an N-terminal domain that binds numerous cofactor proteins. The interplay between the three domains in p97 is complex, and a deeper biochemical understanding is needed in order to design selective p97 inhibitors as therapeutic agents. It is clear that the D2 ATPase domain hydrolyzes ATP in vitro, but whether D1 contributes to ATPase activity is controversial. Here, we use Walker A and B mutants to demonstrate that D1 is capable of hydrolyzing ATP, and show for the first time that nucleotide binding in the D2 domain increases the catalytic efficiency (kcat/Km) of D1 ATP hydrolysis 280-fold, by increasing kcat 7-fold and decreasing Km about 40-fold. We further show that an ND1 construct lacking D2 but including the linker between D1 and D2 is catalytically active, resolving a conflict in the literature. Applying enzymatic observations to small-molecule inhibitors, we show that four p97 inhibitors (DBeQ, ML240, ML241, and NMS-873) have differential responses to Walker A and B mutations, to disease-causing IBMPFD mutations, and to the presence of the N-domain binding cofactor protein p47. These differential effects provide the first evidence that p97 cofactors and disease mutations can alter p97 inhibitor potency and suggest the possibility of developing context-dependent inhibitors of p97

Specific Inhibition of p97/VCP ATPase and Kinetic Analysis Demonstrate Interaction between D1 and D2 ATPase domains

The p97 AAA (ATPase associated with diverse cellular activities), also called VCP (valosin-containing protein), is an important therapeutic target for cancer and neurodegenerative diseases. p97 forms a hexamer composed of two AAA domains (D1 and D2) that form two stacked rings, and an N-terminal domain that binds numerous cofactor proteins. The interplay between the three domains in p97 is complex, and a deeper biochemical understanding is needed in order to design selective p97 inhibitors as therapeutic agents. It is clear that the D2 ATPase domain hydrolyzes ATP in vitro, but whether D1 contributes to ATPase activity is controversial. Here, we use Walker A and B mutants to demonstrate that D1 is capable of hydrolyzing ATP, and show for the first time that nucleotide binding in the D2 domain increases the catalytic efficiency (k_(cat)/K_m) of D1 ATP hydrolysis 280-fold, by increasing k_(cat) 7-fold and decreasing K_m about 40-fold. We further show that an ND1 construct lacking D2 but including the linker between D1 and D2 is catalytically active, resolving a conflict in the literature. Applying enzymatic observations to small-molecule inhibitors, we show that four p97 inhibitors (DBeQ, ML240, ML241, and NMS-873) have differential responses to Walker A and B mutations, to disease-causing IBMPFD mutations, and to the presence of the N-domain binding cofactor protein p47. These differential effects provide the first evidence that p97 cofactors and disease mutations can alter p97 inhibitor potency and suggest the possibility of developing context-dependent inhibitors of p97

Protein crystals in adenovirus type 5-infected cells: requirements for intranuclear crystallogenesis, structural and functional analysis

Intranuclear crystalline inclusions have been observed in the nucleus of epithelial cells infected with Adenovirus serotype 5 (Ad5) at late steps of the virus life cycle. Using immuno-electron microscopy and confocal microscopy of cells infected with various Ad5 recombinants modified in their penton base or fiber domains, we found that these inclusions represented crystals of penton capsomers, the heteromeric capsid protein formed of penton base and fiber subunits. The occurrence of protein crystals within the nucleus of infected cells required the integrity of the fiber knob and part of the shaft domain. In the knob domain, the region overlapping residues 489–492 in the FG loop was found to be essential for crystal formation. In the shaft, a large deletion of repeats 4 to 16 had no detrimental effect on crystal inclusions, whereas deletion of repeats 8 to 21 abolished crystal formation without altering the level of fiber protein expression. This suggested a crucial role of the five penultimate repeats in the crystallisation process. Chimeric pentons made of Ad5 penton base and fiber domains from different serotypes were analyzed with respect to crystal formation. No crystal was found when fiber consisted of shaft (S) from Ad5 and knob (K) from Ad3 (heterotypic S5-K3 fiber), but occurred with homotypic S3K3 fiber. However, less regular crystals were observed with homotypic S35-K35 fiber. TB5, a monoclonal antibody directed against the Ad5 fiber knob was found by immunofluorescence microscopy to react with high efficiency with the intranuclear protein crystals in situ. Data obtained with Ad fiber mutants indicated that the absence of crystalline inclusions correlated with a lower infectivity and/or lower yields of virus progeny, suggesting that the protein crystals might be involved in virion assembly. Thus, we propose that TB5 staining of Ad-infected 293 cells can be used as a prognostic assay for the viability and productivity of fiber-modified Ad5 vectors

The nomenclature, definition and classification of cardiac structures in the setting of heterotaxy

AbstractIn 2000, The International Nomenclature Committee for Pediatric and Congenital Heart Disease was established. This committee eventually evolved into the International Society for Nomenclature of Paediatric and Congenital Heart Disease. The working component of this international nomenclature society has been The International Working Group for Mapping and Coding of Nomenclatures for Paediatric and Congenital Heart Disease, also known as the Nomenclature Working Group. The Nomenclature Working Group created the International Paediatric and Congenital Cardiac Code, which is available for free download from the internet at [http://www.IPCCC.NET].In previous publications from the Nomenclature Working Group, unity has been produced by cross-mapping separate systems for coding, as for example in the treatment of the functionally univentricular heart, hypoplastic left heart syndrome, or congenitally corrected transposition. In this manuscript, we review the nomenclature, definition, and classification of heterotaxy, also known as the heterotaxy syndrome, placing special emphasis on the philosophical approach taken by both the Bostonian school of segmental notation developed from the teachings of Van Praagh, and the European school of sequential segmental analysis. The Nomenclature Working Group offers the following definition for the term "heterotaxy": "Heterotaxy is synonymous with 'visceral heterotaxy' and 'heterotaxy syndrome'. Heterotaxy is defined as an abnormality where the internal thoraco-abdominal organs demonstrate abnormal arrangement across the left-right axis of the body. By convention, heterotaxy does not include patients with either the expected usual or normal arrangement of the internal organs along the left-right axis, also known as 'situs solitus', nor patients with complete mirror-imaged arrangement of the internal organs along the left-right axis also known as 'situs inversus'." "Situs ambiguus is defined as an abnormality in which there are components of situs solitus and situs inversus in the same person. Situs ambiguus, therefore, can be considered to be present when the thoracic and abdominal organs are positioned in such a way with respect to each other as to be not clearly lateralised and thus have neither the usual, or normal, nor the mirror-imaged arrangements."The heterotaxy syndrome as thus defined is typically associated with complex cardiovascular malformations. Proper description of the heart in patients with this syndrome requires complete description of both the cardiac relations and the junctional connections of the cardiac segments, with documentation of the arrangement of the atrial appendages, the ventricular topology, the nature of the unions of the segments across the atrioventricular and the ventriculoarterial junctions, the infundibular morphologies, and the relationships of the arterial trunks in space. The position of the heart in the chest, and the orientation of the cardiac apex, must also be described separately. Particular attention is required for the venoatrial connections, since these are so often abnormal. The malformations within the heart are then analysed and described separately as for any patient with suspected congenital cardiac disease. The relationship and arrangement of the remaining thoraco-abdominal organs, including the spleen, the lungs, and the intestines, also must be described separately, because, although common patterns of association have been identified, there are frequent exceptions to these common patterns. One of the clinically important implications of heterotaxy syndrome is that splenic abnormalities are common. Investigation of any patient with the cardiac findings associated with heterotaxy, therefore, should include analysis of splenic morphology. The less than perfect association between the state of the spleen and the form of heart disease implies that splenic morphology should be investigated in all forms of heterotaxy, regardless of the type of cardiac disease. The splenic morphology should not be used to stratify the form of disease within the heart, and the form of cardiac disease should not be used to stratify the state of the spleen. Intestinal malrotation is another frequently associated lesion that must be considered. Some advocate that all patients with heterotaxy, especially those with isomerism of the right atrial appendages or asplenia syndrome, should have a barium study to evaluate for intestinal malrotation, given the associated potential morbidity. The cardiac anatomy and associated cardiac malformations, as well as the relationship and arrangement of the remaining thoraco-abdominal organs, must be described separately. It is only by utilizing this stepwise and logical progression of analysis that it becomes possible to describe correctly, and to classify properly, patients with heterotaxy