Perioperative Management of a Patient with Hemophilia C and Allergy to Fresh Frozen Plasma.

Hemophilia C is a rare bleeding disorder characterized by a deficiency in clotting factor XI (fXI) and has no standard of care for preoperative optimization before cardiac surgery. Normalization of fXI levels in patients with hemophilia C can be achieved with fresh frozen plasma (FFP), which sometimes results in allergic reactions. We present a case of a patient with hemophilia C requiring coronary artery bypass grafting surgery who developed an allergic reaction to FFP. Our report underscores the balance between thrombosis and bleeding risks when devising a perioperative plan for patients with hemophilia C.

Anesthetic Management of a Large Right Ventricular Mass due to Idiopathic Hypereosinophilic Syndrome in a Patient Undergoing Cardiac Surgery, a Case Report.

Cardiovascular complications of hypereosinophilic syndrome (HES) constitute a significant source of morbidity and mortality, with heart involvement found in approximately 40%-80% of patients. In patients with right heart failure due to an intracardiac mass, induction of general anesthesia poses numerous challenges. The effects of positive pressure ventilation on right ventricular (RV) physiology can quickly lead to precipitous cardiovascular collapse, which increases the importance of maintaining adequate negative pressure ventilation strategies. Current strategies involve awake femoro-femoral cannulation with partial vs full flow femoro-femoral cardiopulmonary bypass (CPB), but both methods increase the risk of intraoperative blood loss due to systemic heparinization prior to sternotomy. In this case report, the authors describe an approach to anesthetizing a patient with severe right ventricular heart failure due to an intracardiac mass due to idiopathic HES. This approach involves femoral cannulation prior to induction of general anesthesia, airway topicalization, inhalational induction with fiberoptic intubation, and sternotomy with aortic/bicaval cannulation before paralysis.

Diagnosis and Management of a Unique Iatrogenic Biatrial Gerbode Defect.

The Gerbode defect was first described in the late 1950s as a congenital peri-membranous ventricular septal defect (VSD), resulting in a left to right ventriculoatrial shunt. We present a case of a patient with restenosis of a prior bioprosthetic aortic valve (AV) who underwent reoperative AV replacement (AVR), which was complicated by a unique iatrogenic Gerbode defect with concurrent LV-LA communication. Our case highlights the unique complications resulting from ventriculoatrial shunts, with consideration paid to the management of ventriculoatrial defects described.

Predictors and Impact of Low Diastolic Blood Pressure and Widened Pulse Pressure Following Transcatheter Aortic Valve Replacement.

BACKGROUND: The association between post-operative diastolic blood pressure (DBP) and pulse pressure (PP) with outcomes following transcatheter aortic valve replacement (TAVR) remains unclear. We sought to assess the prevalence, predictors, and impact of post-operative DBP and PP on presence of post-procedural aortic insufficiency (AI) and mortality in adults undergoing TAVR. METHODS: The study population included 194 patients who underwent TAVR from 2016 to 2017 at an academic tertiary medical center, of which 176 had invasive arterial pressures available postoperatively. Low DBP and widened PP were defined as ≤40 mmHg and ≥80 mmHg respectively on invasive arterial line on post-operative day 1. Clinical outcomes of interest included post-procedural AI and 1-year all-cause mortality. RESULTS: Post-operative low DBP and widened PP were noted in 32.4% and 58.5% of the study population. No significant association between post-operative AI and low DBP (p = 0.82) or widened PP (p = 0.32) was noted. There was a trend toward higher rates of mortality in patients with low DBP (19.3% vs 9.2%, p = 0.06) but no difference in mortality in patients with widened PP (10.7% vs 15.1%, p = 0.39) or those with ≥1+ post-procedural AI (16.7% vs 10.7%, p = 0.32). In multivariable analysis, low DBP was associated with a trend toward higher rates of 1-year mortality [odds ratio (OR) 2.43, 95% confidence interval (CI) 0.97-6.11, p = 0.06]. When excluding patients with a post-operative invasive systolic blood pressure < 80 mmHg, low DBP was associated with significantly higher risk-adjusted mortality at 1 year [OR 2.75, 95% CI (1.07-7.07), p = 0.04]. CONCLUSIONS: In this contemporary study of adults undergoing TAVR, low DBP and widened PP were widely prevalent post TAVR. Low DBP was associated with a trend toward higher rates of 1-year mortality but not with post-procedural AI.

Comprehensive Quality Improvement Program for Intraoperative Transesophageal Echocardiography: Development, Implementation, and Initial Experience.

OBJECTIVE: To develop and implement a comprehensive transesophageal echocardiography (TEE) quality improvement (QI) program and assess for potential improvements in TEE performed by cardiac anesthesiologists. DESIGN: Prospective institutionally approved QI program. SETTING: Academic tertiary care center. PARTICIPANTS: The study comprised cardiac anesthesiologists. INTERVENTIONS: An instrument comprising 15 quality measures to assess TEE examinations pre- and post-cardiopulmonary bypass (CPB) was developed for the present study. TEE examinations before the introduction of the QI program were assessed retrospectively, and examinations performed after its introduction were reviewed prospectively over a 2-year period. MEASUREMENTS AND MAIN RESULTS: A total of 118 TEE studies were analyzed, 48 and 70 studies before and after introduction of the TEE QI program, respectively. Half of the studies were performed pre-CPB, and half of them were performed post-CPB. Multivariate linear mixed regression models were used to assess the effect of the QI program. Interrater variability was assessed among internal reviewers by means of the Shrout-Fleiss reliability intraclass correlation coefficient. Five quality measures demonstrated a significant improvement in studies after CPB after implementation, including 3 imaging criteria (left ventricle, tricuspid valve, and pulmonary artery) and 2 documentation criteria (completeness of demographic/clinical data and timely reporting of documentation). The inter-rater variability analysis yielded an average intraclass correlation coefficient of 0.90 before and 0.78 after the QI program initiation, consistent with excellent agreement among the 4 reviewers. CONCLUSIONS: The present study demonstrated the ability to create and implement a formal QI program for intraoperative TEE in an academic tertiary care cardiac surgical group. The initial data showed significant improvement in several quality measures related to TEE performance.

Methylene Blue for Vasoplegia When on Cardiopulmonary Bypass During Double-Lung Transplantation.

Vasoplegia syndrome, characterized by hypotension refractory to fluid resuscitation or high-dose vasopressors, low systemic vascular resistance, and normal-to-increased cardiac index, is associated with increased morbidity and mortality after cardiothoracic surgery. Methylene blue inhibits inducible nitric oxide synthase and guanylyl cyclase, and has been used to treat vasoplegia during cardiopulmonary bypass. However, because methylene blue is associated with increased pulmonary vascular resistance, its use in patients undergoing lung transplantion has been limited. Herein, we report the use of methylene blue to treat refractory vasoplegia during cardiopulmonary bypass in a patient undergoing double-lung transplantation.

Regulation of eIF2alpha phosphorylation by different functions that act during discrete phases in the herpes simplex virus type 1 life cycle.

Multiple herpes simplex virus type 1 functions control translation by regulating phosphorylation of the initiation factor eIF2 on its alpha subunit. Both of the two known regulators, the gamma(1)34.5 and Us11 gene products, are produced late in the viral life cycle, although the gamma(1)34.5 gene is expressed prior to the gamma(2) Us11 gene, as gamma(2) genes require viral DNA replication for their expression while gamma(1) genes do not. The gamma(1)34.5 protein, through a GADD34-related domain, binds a cellular phosphatase (PP1alpha), maintaining pools of active, unphosphorylated eIF2. Infection of a variety of cultured cells with a gamma(1)34.5 mutant virus results in the accumulation of phosphorylated eIF2alpha and the inhibition of translation prior to the completion of the viral lytic program. Ectopic, immediate-early Us11 expression prevents eIF2alpha phosphorylation and the inhibition of translation observed in cells infected with a gamma(1)34.5 mutant by inhibiting activation of the cellular kinase PKR and the subsequent phosphorylation of eIF2alpha; however, a requirement for the Us11 protein, produced in its natural context as a gamma(2) polypeptide, remains to be demonstrated. To determine if Us11 regulates late translation, we generated two Us11 null viruses. In cells infected with a Us11 mutant, elevated levels of activated PKR and phosphorylated eIF2alpha were detected, viral translation rates were reduced 6- to 7-fold, and viral replication was reduced 13-fold compared to replication in cells infected with either wild-type virus or a virus in which the Us11 mutation was repaired. This establishes that the Us11 protein is critical for proper late translation rates. Moreover, it demonstrates that the shutoff of protein synthesis observed in cells infected with a gamma(1)34.5 mutant virus, previously ascribed solely to the gamma(1)34.5 mutation, actually results from the combined loss of gamma(1)34.5 and Us11 functions, as the gamma(2) Us11 mRNA is not translated in cells infected with a gamma(1)34.5 mutant.

In vivo replication of an ICP34.5 second-site suppressor mutant following corneal infection correlates with in vitro regulation of eIF2 alpha phosphorylation.

In animal models of herpes simplex virus type 1 (HSV-1) infection, ICP34.5-null viruses are avirulent and also fail to grow in a variety of cultured cells due to their inability to prevent RNA-dependent protein kinase (PKR)-mediated inhibition of protein synthesis. We show here that the inability of ICP34.5 mutants to grow in vitro is due specifically to the accumulation of phosphorylated eIF2 alpha. Mutations suppressing the in vitro phenotype of ICP34.5-null mutants have been described which map to the unique short region of the HSV-1 genome, resulting in dysregulated expression of the US11 gene. Despite the inability of the suppressor mutation to suppress the avirulent phenotype of the ICP34.5-null parental virus following intracranial inoculation, the suppressor mutation enhanced virus growth in the cornea, trigeminal ganglia, and periocular skin following corneal infection compared to that with the ICP34.5-null virus. The phosphorylation state of eIF2 alpha following in vitro infection with the suppressor virus was examined to determine if in vivo differences could be attributed to differential regulation of eIF2 alpha phosphorylation. The suppressor virus prevented accumulation of phosphorylated eIF2 alpha, while the wild-type virus substantially reduced eIF2 alpha phosphorylation levels. These data suggest that US11 functions as a PKR antagonist in vivo, although its activity may be modulated by tissue-specific differences in translation regulation.

Identification of a lytic-cycle Epstein-Barr virus gene product that can regulate PKR activation.

The Epstein-Barr virus (EBV) SM protein is a posttranscriptional regulator of viral gene expression. Like many transactivators encoded by herpesviruses, SM transports predominantly unspliced viral mRNA cargo from the nucleus to the cytosol, where it is subsequently translated. This activity likely involves a region of the protein that has homology to the herpes simplex virus type 1 (HSV-1) ICP27 gene product, the first member of this class of regulators to be discovered. However, SM also contains a repetitive segment rich in arginine and proline residues that is dispensable for its effects on RNA transport and splicing. This portion of SM, comprised of RXP triplet repeats, shows homology to the carboxyl-terminal domain of Us11, a double-stranded RNA (dsRNA) binding protein encoded by HSV-1 that inhibits activation of the cellular PKR kinase. To evaluate the intrinsic ability of SM to regulate PKR, we expressed and purified several SM protein derivatives and examined their activity in a variety of biochemical assays. The full-length SM protein bound dsRNA, associated physically with PKR, and prevented PKR activation. Removal of the 37-residue RXP domain significantly compromised all of these activities. Furthermore, the SM RXP domain was itself sufficient to inhibit PKR activation and interact with the kinase. Relative to its Us11 counterpart, the SM RXP segment bound dsRNA with reduced affinity and responded differently to single-stranded competitor polynucleotides. Thus, SM represents the first EBV gene product expressed during the lytic cycle that can prevent PKR activation. In addition, the RXP repeat segment appears to be a conserved herpesvirus motif capable of associating with dsRNA and modulating activation of the PKR kinase, a molecule important for the control of translation and the cellular antiviral response.