Cardiac tamponade on ECPELLA: a case report of a unique hemodynamic picture

Extracorporeal membrane oxygenation is rapidly becoming a preferred therapy for short-term hemodynamic support in cardiogenic shock, along with the use of devices such as Impella (Abiomed, Andover, MA). The two together can create unique hemodynamics resulting in altered presentation of common hemodynamic conditions such as tamponade. We present a case of a patient with fulminant myocarditis requiring veno-arterial extracorporeal membrane oxygenation and Impella support. The patient later developed a pericardial effusion with atypical tamponade physiology which masked the left ventricular systolic function recovery. We further highlight the complex hemodynamics of cardiac tamponade in patients with such mechanical circulatory support and its implications on echocardiography

Interaction Between the AAA+ ATPase p97 and Its Cofactor Ataxin3 in Health and Disease

p97 is an essential ATPase associated with various cellular activities (AAA+) that functions as a segregase in diverse cellular processes, including the maintenance of proteostasis. p97 interacts with different cofactors that target it to distinct pathways; an important example is the deubiquitinase ataxin3, which collaborates with p97 in endoplasmic reticulum associated degradation. However, the molecular details of this interaction have been unclear. We have characterized the binding of ataxin3 to p97, showing that ataxin3 binds with low-micromolar affinity to both wild-type p97 and mutants linked to degenerative disorders known as multisystem proteinopathy 1 (MSP1); we further showed that the stoichiometry of binding is one ataxin3 molecule per p97 hexamer. We have mapped the binding determinants on each protein, demonstrating that ataxin3’s p97/VCP-binding motif (VBM) interacts with the inter-lobe cleft in the N-domain of p97. We also probed the nucleotide dependence of this interaction, confirming that ataxin3 and p97 associate in the presence of ATP and in the absence of nucleotide, but not in the presence of ADP. Our experiments suggest that an ADP-driven downward movement of the p97 N-terminal domain dislodges ataxin3 by inducing a steric clash between the D1-domain and ataxin3’s C-terminus. In contrast, MSP1 mutants of p97 bind ataxin3 irrespective of their nucleotide state, indicating a failure by these mutants to translate ADP binding into a movement of the N-terminal domain. Our model provides a mechanistic explanation for how nucleotides regulate the p97-ataxin3 interaction and why atypical cofactor binding is observed with MSP1 mutants.Ph.D., Biochemistry -- Drexel University, 201

A Unique Case of Inflow Cannula Obstruction by a Tissue Membrane

The use of a left ventricular assist device has increased and is a primary surgical treatment for heart failure. However, one major complication of left ventricular assist device support is an obstruction in the blood flow pathway. Pump thrombosis and outflow graft occlusion are some of the common causes of such obstructions. Here, we describe a unique case of HeartMate II (Abbott Laboratories) inflow cannula obstruction from a membranous structure without evidence of thrombus. The histology showed evidence of fibrous tissue and heart muscle tissue in the membrane. The patient underwent a successful device exchange with a HeartMate 3 (Abbott Laboratories) and is doing well

Cangrelor: Safe and Effective for Left Ventricular Assist Device Thrombosis

Pump thrombosis is a devastating complication of left ventricular assist device implantation as it increases the risk of mortality and morbidity. Early and effective treatment is important to prevent the progression of the clot and to avoid the surgical need for pump exchange or heart transplant. The current strategies of intensifying anticoagulation therapy are not consistently effective and carry significant bleeding risks. Cangrelor is a new pharmacological agent that has been utilized as an antiplatelet agent in several cardiac procedures. In this case series, we describe the use of cangrelor for left ventricular assist device thrombosis in five patients. Cangrelor appears to be a potentially safe and effective alternative strategy

Seeing into the Future: HeartMate 3 to the Systemic Right Ventricle in a Completely Blind Patient with Congenitally-corrected Transposition of the Great Arteries

A 24-year-old, blind male with congenitally-corrected transposition of the great arteries and systemic right ventricular failure presented with New York Heart Association class IV heart failure despite home inotropic therapy. He was not a transplant candidate due to psychosocial issues. He underwent a successful HeartMate 3 (Abbott Laboratories) placement with the implementation of techniques to guide home ventricular assist device care despite blindness

Link and subgraph likelihoods in random undirected networks with fixed and partially fixed degree sequence

The simplest null models for networks, used to distinguish significant features of a particular network from {\it a priori} expected features, are random ensembles with the degree sequence fixed by the specific network of interest. These "fixed degree sequence" (FDS) ensembles are, however, famously resistant to analytic attack. In this paper we introduce ensembles with partially-fixed degree sequences (PFDS) and compare analytic results obtained for them with Monte Carlo results for the FDS ensemble. These results include link likelihoods, subgraph likelihoods, and degree correlations. We find that local structural features in the FDS ensemble can be reasonably well estimated by simultaneously fixing only the degrees of few nodes, in addition to the total number of nodes and links. As test cases we use a food web, two protein interaction networks (\textit{E. coli, S. cerevisiae}), the internet on the autonomous system (AS) level, and the World Wide Web. Fixing just the degrees of two nodes gives the mean neighbor degree as a function of node degree, $_k$, in agreement with results explicitly obtained from rewiring. For power law degree distributions, we derive the disassortativity analytically. In the PFDS ensemble the partition function can be expanded diagrammatically. We obtain an explicit expression for the link likelihood to lowest order, which reduces in the limit of large, sparse undirected networks with $L$ links and with $k_{\rm max} \ll L$ to the simple formula $P(k,k') = kk'/(2L + kk')$. In a similar limit, the probability for three nodes to be linked into a triangle reduces to the factorized expression $P_{\Delta}(k_1,k_2,k_3) = P(k_1,k_2)P(k_1,k_3)P(k_2,k_3)$.Comment: 17 pages, includes 11 figures; first revision: shortened to 14 pages (7 figures), added discussion of subgraph counts, deleted discussion of directed network

A Unique Case of Systemic Lupus Erythematosus Myocarditis Complicated by Plasmapheresis-Responsive Cardiogenic Shock

A 25-year-old woman with systemic lupus erythematosus complicated by biventricular failure with a history of multiple admissions presented with cardiogenic shock unresponsive to steroids, intravenous immunoglobulin, cyclophosphamide, and required extra-corporeal membrane oxygenation. Left ventricular function eventually recovered after plasmapheresis

Presence of early CKD-related metabolic complications predict progression of stage 3 CKD: a case-controlled study

Only a subset of patients who enter stage 3 chronic kidney disease (CKD) progress to stage 4. Identifying which patients entering stage 3 are most likely to progress could improve outcomes, by allowing more appropriate referrals for specialist care, and spare those unlikely to progress the adverse effects and costliness of an unnecessarily aggressive approach. We hypothesized that compared to non-progressors, patients who enter stage 3 CKD and ultimately progress have experienced greater loss of renal function, manifested by impairment of metabolic function (anemia, worsening acidosis and mineral abnormalities), than is reflected in the eGFR at entry to stage 3. The purpose of this case-controlled study was to design a prediction model for CKD progression using laboratory values reflecting metabolic status. Using data extracted from the electronic health record (EHR), two cohorts of patients in stage 3 were identified: progressors (eGFR declined >3 ml/min/1.73m2/year; n = 117) and non-progressors (eGFR declined <1 ml/min/1.73m2; n = 364). Initial laboratory values recorded a year before to a year after the time of entry to stage 3, reflecting metabolic complications (hemoglobin, bicarbonate, calcium, phosphorous, and albumin) were obtained. Average values in progressors and non-progressors were compared. Classification algorithms (Naïve Bayes and Logistic Regression) were used to develop prediction models of progression based on the initial lab data. At the entry to stage 3 CKD, hemoglobin, bicarbonate, calcium, and albumin values were significantly lower and phosphate values significantly higher in progressors compared to non-progressors even though initial eGFR values were similar. The differences were sufficiently large that a prediction model of progression could be developed based on these values. Post-test probability of progression in patients classified as progressors or non-progressors were 81% (73% − 86%) and 17% (13% − 23%), respectively. Our studies demonstrate that patients who enter stage 3 and ultimately progress to stage 4 manifest a greater degree of metabolic complications than those who remain stable at the onset of stage 3 when eGFR values are equivalent. Lab values (hemoglobin, bicarbonate, phosphorous, calcium and albumin) are sufficiently different between the two cohorts that a reasonably accurate predictive model can be developed