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Objectives In this study, the authors hypothesized that intraprocedural improvement of pulmonary venous (PV) waveforms are predictive of improved outcomes. In this report, they analyzed intraprocedural invasive and echocardiographic changes with respect to rehospitalization and mortality. Background The effects of hemodynamic changes during percutaneous mitral valve repair (PMVR) with MitraClip (Abbott Vascular, Santa Clara, California) are incompletely characterized. Methods The authors retrospectively reviewed records and intraprocedural transesophageal echocardiograms of 115 consecutive patients (age 76 ± 12 years) who underwent PMVR for mitral regurgitation (MR) from May 2013 to January 2017 at Emory University Hospital. They assessed intraprocedural PV waveforms for improvement in morphology, measured change in MR grade by semiquantitative methods, evaluated invasive changes in left atrial pressure (LAP) and V-wave, and compared with 30-day and 1-year rehospitalization and all-cause mortality. Results Ninety-three cases (80%) had PV waveforms before and after clip placement sufficient for analysis, of which 67 (73%) demonstrated intraprocedural improvement in PV morphology and 25 (27%) did not. At 24 months, 57 (85%) of those with PV improvement were living, compared with only 10 (40%) of those without improvement. Proportional hazards models demonstrated a significant survival advantage in those with PV improvement (hazard ratio [HR]: 0.28, 95% confidence interval [CI]: 0.08 to 0.93, p = 0.038). By multivariable analysis, PV improvement predicted reduced 1-year cardiac rehospitalization (odds ratio [OR]: 0.18, p = 0.044). Intraprocedural assessment of MR grade and invasive hemodynamics did not consistently predict mortality and rehospitalization. Conclusions PV waveforms are important markers of procedural success after PMVR. Our data show intraprocedural PV waveforms may predict rehospitalization and mortality after PMVR. A larger, multicenter cohort will be important to clarify this relationship.

Transcatheter mitral valve replacement (TMVR) is a promising strategy for patients with mitral valve disease and no surgical options. Left ventricular outflow tract (LVOT) obstruction is a life-threatening complication of TMVR. Although there are no commercially available devices to prevent LVOT obstruction, the risk of it can be reduced by careful preprocedure planning and the use of novel modifications to commercially available devices. This article summarizes current techniques to prevent LVOT obstruction with an emphasis on electrosurgical strategies.

The retinoblastoma protein (Rb) and its homologs p107 and p130 are critical regulators of gene expression during the cell cycle. Functional inactivation of Rb family proteins leads to loss of cell-cycle control and promotes genome instability and proliferation, which are hallmarks of cancer. Rb proteins share a structural domain, known as the “pocket domain”, which mediates association with a large number of cellular proteins. A cleft in the pocket domain binds an LxCxE sequence motif in these proteins, many of which function with Rb proteins to co-regulate transcription during quiescence and G1. Proteins from oncogenic DNA viruses also bind this cleft to inactivate Rb family proteins, and the E7 protein from the human papillomavirus has been used as the primary model for understanding LxCxE motif interactions. Evidence presented previously and here demonstrates that the E7 sequence binds tighter and competes with cellular proteins for the LxCxE site, but the molecular basis for the relatively weak affinities of the cellular proteins has been poorly understood. Here, we present binding data and a series of crystal structures of the p107 pocket domain in complex with LxCxE peptides derived from the transcriptional co-repressor proteins HDAC1, ARI4DA, and EID1. The structures reveal determinants of protein binding beyond the L-C-E core that include the N and C-terminal sides of the LxCxE motif and the x (wild card) residues. Our results explain how differences in these interactions outside the L-C-E core result in weaker affinities of pocket protein for cellular LxCxE proteins compared to E7 and result in differences in Rb and p107 affinities for some LxCxE-containing sequences. Our study provides new insights into how Rb proteins bind their myriad of cell partners and lays the foundation for structure-based design of peptides that inhibit oncogenic viral protein interactions.

Resumen Introduccion y objetivo La disociacion albuminocitologica en el liquido cefalorraquideo (LCR) apoya el diagnostico de sindrome de Guillain-Barre (SGB) pero no ayuda en el pronostico, por lo que el objetivo de este estudio es determinar la utilidad de las cifras de proteinas en el LCR para predecir la evolucion en pacientes pediatricos. Pacientes y metodos Se realizo un estudio de prueba diagnostica, en pacientes pediatricos con SGB, analizando variables sociodemograficas, clinicas y proteinas en LCR, asi como electromiografia; tambien se documento la presencia de disautonomias. Resultados Se analizaron datos de 23 pacientes, predominando el sexo masculino (87%), la edad escolar (43,5%) y el antecedente de infeccion digestiva (73,9%). Mediante la curva COR se encontro, para la presencia de disautonomias, un area bajo la curva de 0,966 con mejor punto de corte de proteinas en LCR de 87-92 proteinas/mm, y para evaluar la pobre respuesta al tratamiento con inmunoglobulina intravenosa, de 0,969, con mejor punto de corte en 157 proteinas/mm. Conclusion La cantidad de proteinas en el LCR puede utilizarse como un indicador pronostico y de gravedad, de tal manera que unas proteinas mayores de 100 en el LCR se traducen en una evolucion torpida y con mayores complicaciones.

Introduction and objective The albumin-cytologic dissociation in cerebrospinal fluid (CSF) supports the diagnosis of Guillain–Barre syndrome (GBS) but does not support the prognosis, so the aim of this study is to determine the usefulness of protein numbers in the CSF to predict progression in pediatric patients. Patients and methods A diagnostic test was performed in pediatric patients with GBS, analysing sociodemographic, clinical and protein variables in CSF as well as electromyography. The presence of dysautonomia was also documented. Results Data were analyzed from 23 patients, predominantly males (87%), school age (43.5%) and history of digestive infection (73.9%). Using the ROC curve, an area under the curve of 0.966 with best CSF protein cut-off point of 87–92 proteins/mm was found for the presence of dysautonomias and to evaluate the poor response to treatment with 0.969 intravenous immunoglobulin with better cut-off point in 157 proteins/mm. Conclusion The amount of proteins in the CSF can be used as a prognostic indicator and severity, such that proteins greater than 100 in CSF translate into a torpid evolution and with greater complications.

Left ventricular outflow tract (LVOT) obstruction following transcatheter mitral valve replacement (TMVR) portends significant morbidity and mortality and is an exclusion criterion in approximately 50% of patients screened for TMVR clinical trials. Pre-emptive alcohol septal ablation is a feasible

Transcatheter aortic valve replacement (TAVR) demonstrates similar clinical outcomes in patients with tricuspid and bicuspid aortic valves. To date, patients undergoing TAVR for bicuspid aortic stenosis have not been compared with patients undergoing surgical aortic valve replacement (SAVR). This

LAMPOON (intentional laceration of the anterior mitral leaflet to prevent left ventricular outflow tract [LVOT] obstruction) has been shown to reduce the risk of LVOT obstruction. With experience, a simplified antegrade modification of this technique was developed. This is a single-center

Cardiogenic shock in the setting of decompensated aortic stenosis is associated with high mortality and poor surgical outcomes. TAVR may be a viable alternative to open cardiac surgery. This is a retrospective cohort study of patients at Emory Healthcare from January 2012 to December 2018. The

Patients with severe mitral regurgitation (MR) despite MitraClip (MC) placement present a challenging clinical scenario as they lack traditional surgical or transcatheter options. Transcatheter electrosurgery may allow for the selective laceration of failed MC and subsequent placement of a dedicated

Coronary obstruction is a rare (

Higher body mass index is reported to be related to early degeneration of bioprostheses. However, there are minimal data regarding the relationship between overweight/obese compared to normal weight patients and their outcomes after transcatheter aortic valve replacement (TAVR) with a current

End stage renal disease (ESRD) portends worse outcomes including early bioprosthetic degeneration after either surgical or transcatheter aortic valve replacement (TAVR). There are minimal data about THE impact of hemodialysis (HD) on early valve degeneration and clinical outcomes after TAVR. We

The optimal valve sizing strategy for patients undergoing TAVR for an acquired bicuspid aortic valve remains unknown. As leaflet fusion may inhibit the transcatheter heart valve's ability to fully circularize, a supra-annular measurement of valve area may account for the anatomical point of maximal

Current limitations of transcatheter aortic valve replacement include paravalvular aortic regurgitation (PAR). We hypothesized that there are varying propensities for location of PAR in the Medtronic CoreValve and the Edwards Sapien Valve. The secondary goal was to longitudinally evaluate PAR

Duchenne Muscular Dystrophy (DMD) presents a series of significant challenges to the development of gene therapy approaches, including the frequency of new mutations, the size of the gene and mRNA and the complexity of the mutations involved. Animal models can significantly accelerate the process for development of novel therapies if they accurately mimic the human disease. To date, the only animal that develops disease with a course and severity similar to humans, without requiring additional mutations or manipulations, is the dog. Several canine models have been identified and their mutations characterized, confirming that this disease occurs at a relatively high frequency, can have variable effects, and is the result of many different mutations. Unlike other canine inherited diseases, Duchenne-like Muscular Dystrophy occurs spontaneously in multiple families within in a breed, leading to more than one mutation in a given breed of dog. Using a rapid PCR based screen, we have identified the putative mutations in two canine models of DMD. Data from a Labrador Retriever family and a Welsh Corgi family indicate that the mutations in both families consist of the precise insertion of repetitive DNA elements in the mRNA between exon pairs. The mutations involve different repetitive sequences and different exon pairs in each family. In addition, affected animals from another distinct Labrador Retriever family and a West Highland White family have been identified. Preliminary data supporting the independent nature of these mutations as well as their localization within the gene will be presented. The relatively large size, intact immune system, and potential to measure beneficial effects combined with the assortment of different mutations available provide an excellent resource in which gene therapy approaches for DMD can be tested.