The predictors of post-transplant coronary events among liver transplant recipients

Background/purpose

Cardiac morbidities can occur during the peri- and post-liver transplant (LT) period, affecting the long-term survival. The purpose of this study was to identify the potential factors that predict a coronary event post-transplantation.

Methods

Medical records of patients who underwent liver transplantation at Johns Hopkins Hospital between 2009 and 2013 were retrospectively reviewed. We looked at pre-liver transplant cardiac risk factors and the diagnostic tests utilized for coronary artery disease screening. Patients with and without post-liver transplant coronary events were compared.

Results

There were a total of 146 patients with a mean age at LT of 55.3 years. The prevalence of hypertension, tobacco use and diabetes within the patient population was 61.6 % (n = 90), 39 % (n = 57) and 37.6 % (n = 55), respectively. There were 29 deaths and 30 coronary events over a median follow-up period of 1.75 years. Age at the time of liver transplant was predictive of coronary event (OR 1.11, CI 1.01–1.20). The 1-year survival in patients with a coronary event was 47 versus 94 % in patients without a coronary event. The combined use of a dobutamine stress echocardiogram and coronary artery calcium score predicted a coronary event with a sensitivity of 62.5 % and specificity of 66.7 %.

Conclusion

In conclusion, LT recipients with cardiac events had limited survival as compared to the cohort without coronary events. Identification of such patients with noninvasive screening may provide a practical alternative to an invasive cardiac workup. Further improvement in screening strategies may minimize the liver transplant cardiac morbidity.

     

Chlorogenic Acid Protects against Advanced Alcoholic Steatohepatitis in Rats via Modulation of Redox Homeostasis,Inflammation, and Lipogenesis

The aim of this study was to evaluate the therapeutic effects of chlorogenic acid (CGA) in rats with advanced alcoholic steatohepatitis. The rats were fed on a high-fat diet and gavaged with ethanol (4 g/kg) for 8 weeks. The livers of ethanol-treated rats showed steatosis; necrosis and mononuclear infiltration; and significant upregulation of the mRNA expression of the prooxidant (Cyp2e1, iNos), lipogenic (Srebp1, Acc), proinflammatory (Tlr4, Nf-κb, TnfA, Il-1B, and Il-6), and profibrogenic (TgfB, Col1, VegfA) genes. Simultaneously, a downregulation of level of Sod and Nrf2 was observed, which was accompanied by increased serum transaminase, TnfA, and serum and liver triglycerides levels. CGA administration (40 and 80 mg/kg, 8 weeks) to ethanol-fed group reduced the liver expression levels of Cyp2e1 and iNos, whereas it markedly enhanced the expression of Sod, Nrf2, and Ho-1. CGA at both doses downregulated the expressions of lipogenic, proinflammatory, and profibrogenic genes, while the expression of Tlr4 was lowered only after the higher dose of CGA. The higher dose of CGA efficiently prevented the progression of alcohol-induced steatosis and reduced inflammation through regulation of the expression of genes encoding the proteins involved in the Tlr4/Nf-κB signaling pathway and fibrosis. The study revealed hepatoprotective and anti-inflammatory effects of CGA through the regulation of expression of genes encoding Cyp2e1/Nrf2 involved in oxidative stress modulation. These results demonstrate CGA as a therapeutic candidate for the prevention and treatment of alcoholic steatohepatitis.     

Multi-colour FISH on preoperative renal tumour biopsies to confirm the diagnosis of uncertain renal masses

Purpose  

In some cases with uncertain renal tumour lesions, it would be helpful to perform biopsies for the preoperative differential diagnosis. In our study, we evaluated the benefit of multi-colour interphase fluorescence in situ hybridization (M-FISH) on fine-needle core biopsies in uncertain renal masses.     

Electrochemical detection of a single cytomegalovirus at an ultramicroelectrode and its antibody anchoring

We report observations of stochastic collisions of murine cytomegalovirus (MCMV) on ultramicroelectrodes (UMEs), extending the observation of discrete collision events on UMEs to biologically relevant analytes. Adsorption of an antibody specific for a virion surface glycoprotein allowed differentiation of MCMV from MCMV bound by antibody from the collision frequency decrease and current magnitudes in the electrochemical collision experiments, which shows the efficacy of the method to size viral samples. To add selectivity to the technique, interactions between MCMV, a glycoprotein-specific primary antibody to MCMV, and polystyrene bead “anchors,” which were functionalized with a secondary antibody specific to the Fc region of the primary antibody, were used to affect virus mobility. Bead aggregation was observed, and the extent of aggregation was measured using the electrochemical collision technique. Scanning electron microscopy and optical microscopy further supported aggregate shape and extent of aggregation with and without MCMV. This work extends the field of collisions to biologically relevant antigens and provides a novel foundation upon which qualitative sensor technology might be built for selective detection of viruses and other biologically relevant analytes.Over the past decade, the study of discrete collision events on ultramicroelectrodes (UMEs) has gained attention due to the interest in understanding stochastic phenomena by electrochemistry. By observing the collisions of small particles, there is the possibility that information can be deduced that is not available in ensemble measurements. The electrochemical study of single collision events has been applied to a wide range of hard nanoparticles (NPs), which include metal, metal oxide, and organic NPs [platinum (1), silver (2), gold (3), nickel (4), copper (5), iridium oxide (6), cerium oxide (7), titanium oxide (8), silicon oxide (9), indigo (10), polystyrene (11), and relatively large aggregates of fullerene (12)]. Recently, collisions of soft particles have been investigated, such as toluene droplets (13) and liposomes (14). Also, collisions of toluene and tri-n-propylamine droplets were observed simultaneously by both electrochemical and electrogenerated chemiluminescent (ECL) measurements (15).Similarly, a variety of techniques have been developed to observe these collision events. The interested reader can consult the references for a discussion on each of the techniques used to observe stochastic events electrochemically: blocking (9, 13), electrocatalytic amplification (1), open circuit potential (16), droplet blocking/reactor (13, 14), and ECL (15, 17,18). The simplest and most reproducible method of observing collisions is a technique termed blocking, which is so named because particles, which are brought to the electrode by a diffusion-limited flux and/or electrophoretic migration, irreversibly adsorb (1) to the electrode surface, blocking the flux of redox active species. In this experiment, an appropriate concentration of redox active species is dissolved into the aqueous continuous phase such that individual adsorption events can be distinguished from the background. Potassium ferrocyanide [K₄Fe(CN)₆, KFCN, E^o = ∼0.24 V vs. Ag/AgCl], was chosen as the redox active species in this study because KFCN incompletely dissociates during dissolution (19–21) due to ion pairing (22). This incomplete dissociation is advantageous in solutions of colloidal suspensions because high ionic strength media will cause suspensions to aggregate. This means that solutions of 100–400 mM KFCN are achievable without noticeable aggregation of particles over the time scale of the experiments, which has been observed for less stable (zeta, ζ-potential = −15 mV) toluene droplets in 200 mM KFCN (13). When an insulating particle, suspended in the aqueous solution of KFCN, stochastically collides with the UME surface, it blocks the flux of redox active species, which manifests itself as a current step in amperometry. The cause of this step shape is an almost instantaneous decrease in steady-state current upon collision of the particle with the electrode surface followed by a leveling off at a new steady-state current value.Because of the success in studying many systems using collisions, such as early work using electrocatalytic amplification as a sensitive means of detecting DNA (23), it was our hope to extend the field of collisions to more biologically relevant species, such as viruses. Cytomegaloviruses (CMVs) are the prototypic members of the β-herpesvirus family. These large (100–200-nm) dsDNA viruses establish lifelong latent infections after primary infection and do not cause significant disease in healthy individuals. However, immunocompromised individuals infected with human cytomegalovirus (HCMV) are at a significantly greater risk of morbidity and mortality (24), including patients receiving chemotherapeutics, AIDS patients, and organ transplant recipients. Moreover, HCMV congenital infection is a leading cause of birth defects and developmental disabilities including hearing and vision loss, microcephaly, and cognitive disabilities (25). Thus, highly sensitive and rapid detection of CMV infection in patients is an important part of mitigating transmission and disease. Like most herpesviruses, HCMV is highly species specific, and murine cytomegalovirus (MCMV) serves as an important model system for HCMV pathogenesis, sharing significant genetic and biological characteristics. MCMV provides a powerful, genetically tractable infection system in a natural mouse host and has yielded significant insights into CMV biology. Relatively arduous techniques, with varying degrees of sensitivity, exist for the detection of pathogens, including ELISA methods, sensitive PCR techniques, culturing, ECL, and microscopy. A comparison of these techniques with the proposed electrochemical technique is given in SI Appendix.In this article, the electrochemical study of discrete collision events is extended to the detection of biological species. Due to the widespread interest in rapid diagnostics for infectious diseases, quick and sensitive techniques to detect ultralow concentrations of biologically relevant species are actively being investigated across many fields of research. Detection of dilute concentrations of pathogens is an especially important goal. The utilization of electrochemical collisions has been demonstrated to be sensitive enough to differentiate nanoparticle aggregates, such as aggregates of silver nanoparticles from monomers and dimers to higher order aggregates (26). Here, we present a technique to selectively detect viruses based on blocking and specific interactions between MCMV, an MCMV-specific antibody, and polystyrene beads (PSBs). The viruses act as a type of “bond” between the PSBs and cause aggregation, which manifests itself in two ways during a collision experiment: a decrease in frequency of collision, due to an overall decrease in diffusion coefficient of the aggregates versus single beads, and larger current step heights, due to rare collisions of larger aggregates.     

Mechanisms of neurologic failure in critical illness

Critical illness frequently is associated with neurologic failure that may involve the central and peripheral nervous systems. Central nervous system failure is associated with a spectrum of neurobehavioral changes including delirium, coma, and long-term cognitive dysfunction. Peripheral neurologic failure, or critical illness neuromuscular abnormalities, is suggested by diffuse arreflexic weakness and protracted respiratory insufficiency, and may also persist long after the acute hospitalization. While the burden of neurological disease complicating critical illness is considerable, preventive or therapeutic options are limited. This article provides an overview of research evaluating the relationship between critical illness and neurologic function, with a special emphasis on underlying mechanisms.     

Point-of-care ultrasound in pediatric anesthesiology and critical care medicine

Ultrasound has increasingly become a clinical asset in the hands of the anesthesiologist and intensivist who cares for children. Though many applications for ultrasound parallel adult modalities, children as always are not simply small adults and benefit from the application of ultrasound to their management in various ways. Body composition and size are important factors that affect ultrasound performance in the child, as are the pathologies that may uniquely afflict children and aspects of procedures unique to this patient population. Ultrasound simplifies vascular access and other procedures by visualizing structures smaller than those in adults. Maturation of the thoracic cage presents challenges for the clinician performing pulmonary ultrasound though a greater proportion of the thorax can be seen. Moreover, ultrasound may provide unique solutions to sizing the airway and assessing it for cricothyroidotomy. Though cardiac ultrasound and neurosonology have historically been performed by well-developed diagnostic imaging services, emerging literature stresses the utility of clinician ultrasound in screening for pathology and providing serial observations for monitoring clinical status. Use of ultrasound is growing in clinical areas where time and diagnostic accuracy are crucial. Implementation of ultrasound at the bedside will require institutional support of education and credentialing. It is only natural that the pediatric anesthesiologist and intensivist will lead the incorporation of ultrasound in the future practice of these specialties.     

Radiological correlation of mechanism of intravascular migration of the ventriculoperitoneal shunt and technical considerations for endovascular retrieval

Migration of ventriculoperitoneal shunt into the pulmonary artery is a rare complication that can lead to shunt malfunction and cardiopulmonary complications. This case illustrates the significance of accidental transvenous placement of the shunt. Identification of the transvenous course of the catheter on cross sectional imaging can predict future catheter migration and also aid at surgical extraction. Formation of knot within the distal portion of the shunt catheter during migration or endovascular retrieval can occur, therefore measures to retrieve with knot and adhesions should be factored in before.     

Nanostructured Luminescent Gratings for Sensorics

Two-dimensional holographic structures based on photopolymer compositions with luminescent nanoparticles, such as quantum dots, are promising candidates for multiresponsive luminescence sensors. However, their applicability may suffer from the incompatibility of the components, and hence aggregation of the nanoparticles. We showed that the replacement of an organic shell at the CdSe/ZnS quantum dots’ surface with monomer molecules of the photopolymerizable medium achieved full compatibility with the surrounding medium. The effect was demonstrated by luminescence spectroscopy, and steady-state and time-resolved luminescent laser scanning microscopy. We observed the complete spectral independence of local photoluminescence decay, thus proving the absence of even nanoscale aggregation, either in the liquid composition or in the nodes and antinodes of the grating. Therefore, nanostructured luminescent photopolymer gratings with monomer-covered quantum dots can act as hybrid diffractive–luminescent sensor elements.     

[In Press] Effect of open ultraviolet germicidal irradiation lamps on functionality of excimer lasers used in cornea surgery

We report on the impact of direct ultraviolet germicidal irradiation (UVGI) on reflective optics, used in the excimer laser system Allegretto Eye-Q. The aim of our work was to confirm our hypothesis based on long-rate observations of obtained anomalies in post-operative results that are attributed to degradation of reflective optics upon ultraviolet radiation. The presence of direct ultraviolet germicidal irradiation (UV-C) coupled with humidity in the operating environment caused merging anomalies and unwanted post-operative correction values. UV-A radiation caused a similar effect on the reflective cover of the mirrors.     

Continuous Cerebral Blood Flow Autoregulation Monitoring in Patients Undergoing Liver Transplantation

Background

Clinical monitoring of cerebral blood flow (CBF) autoregulation in patients undergoing liver transplantation may provide a means for optimizing blood pressure to reduce the risk of brain injury. The purpose of this pilot project is to test the feasibility of autoregulation monitoring with transcranial Doppler (TCD) and near-infrared spectroscopy (NIRS) in patients undergoing liver transplantation and to assess changes that may occur perioperatively.

Methods

We performed a prospective observational study in 9 consecutive patients undergoing orthotopic liver transplantation. Patients were monitored with TCD and NIRS. A continuous Pearson??s correlation coefficient was calculated between mean arterial pressure (MAP) and CBF velocity and between MAP and NIRS data, rendering the variables mean velocity index (Mx) and cerebral oximetry index (COx), respectively. Both Mx and COx were averaged and compared during the dissection phase, anhepatic phase, first 30?min of reperfusion, and remaining reperfusion phase. Impaired autoregulation was defined as Mx????0.4.

Results

Autoregulation was impaired in one patient during all phases of surgery, in two patients during the anhepatic phase, and in one patient during reperfusion. Impaired autoregulation was associated with a MELD score?>15 (p?=?0.015) and postoperative seizures or stroke (p?p?=?0.0029). The relationship between COx and Mx remained when only patients with bilirubin?>1.2?mg/dL were evaluated (p?=?0.0419). There was no correlation between COx and baseline bilirubin (p?=?0.2562) but MELD score and COx were correlated (p?=?0.0458). Average COx was higher for patients with a MELD score?>15 (p?=?0.073) and for patients with a neurologic complication than for patients without neurologic complications (p?=?0.0245).

Conclusions

These results suggest that autoregulation is impaired in patients undergoing liver transplantation, even in the absence of acute, fulminant liver failure. Identification of patients at risk for neurologic complications after surgery may allow for prompt neuroprotective interventions, including directed pressure management.