A heart transplant center experience with basiliximab induction strategies: A double edged sword?

BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.

Reduced Hospitalizations, Emergency Room Visits, and Costs Associated with a Web-Based Health Literacy, Aligned-Incentive Intervention: Mixed Methods Study.

BACKGROUND: The association between health literacy and health care costs, particularly for hospitalizations and emergency room services, has been previously observed. Health information interventions aimed at addressing the negative impacts of inadequate health literacy are needed. The MedEncentive Mutual Accountability and Information Therapy (MAIT) Program is a Web-based system designed to improve health and lower costs by aligning patient-doctor incentives. OBJECTIVE: In this mixed methods study of a Web-based patient-doctor aligned-incentive, information therapy program conducted in an 1800-member employee health plan, we aimed to (1) determine the program's quantitative impact on hospitalization and emergency room utilization and costs, and (2) assess survey responses about the program's perceived value. METHODS: We used a mixed methods, single within-group, pre-post, descriptive study design. We analyzed quantitative data using pre-post mean utilization and cost differences and summarized the data using descriptive statistics. We used open-ended electronic survey items to collect descriptive data and analyzed them using thematic content analysis. RESULTS: Hospitalizations and emergency room visits per 1000 decreased 32% (26.5/82.4) and 14% (31.3/219.9), respectively, after we implemented the program in 2015-2017, relative to 2013-2014. Correspondingly, the plan's annual per capita expenditures declined US $675 (95% CI US $470-865), or 10.8% ($675/$6260), after program implementation in 2015-2017 (US $5585 in 2013-2014 dollars), relative to the baseline years of 2013-2014 (US $6260; P<.05). Qualitative findings suggested that respondents valued the program, benefiting from its educational and motivational aspects to better self-manage their health. CONCLUSIONS: Analyses suggested that the reported reductions in hospitalizations, emergency room visits, and costs were associated with the program. Qualitative findings indicated that targeted users perceived value in participating in the MAIT Program. Further research with controls is needed to confirm these outcomes and more completely understand the health improvement and cost-containment capabilities of this Web-based health information, patient-doctor, aligned-incentive program.

The acceptability of high resolution anoscopy examination in patients attending a tertiary referral centre.

BACKGROUND: High resolution anoscopy (HRA) examination is regarded as the best method for the management of anal high grade squamous intraepithelial lesions to prevent anal squamous carcinoma. However, little is known about the acceptability of this procedure. This analysis looks at patient experience of HRA examination and ablative treatment under local anaesthetic. METHODS: Patients took part in anonymised feedback of their experience immediately after their HRA examinations and/or treatments. A standard questionnaire was used that included assessment of pain and overall satisfaction scores as well as willingness to undergo future HRA examinations. RESULTS: Four hundred four (89.4%) responses were received and all responses were analysed. The group consisted of 119 females (29.4%) and 261 males (64.6%) with median age of 45 years (IQR = 19) and 45 years (IQR = 21) respectively, and included 58 new cases, 53 treatment cases and 202 surveillance cases. 158 patients (39.1%) had at least one biopsy during their visits. The median pain score was 2 [Inter Quartile Range (IQR) 3] on a visual analogue scale of 0 to 10, where 0 indicated no pain / discomfort and 10 indicated severe pain. The median pain score was 2 (IQR 2) in men and 4 (IQR = 3) in women [Dunn's Test = 4.3, p < 0.0001] and 3 (IQR 4.5) in treatment cases. Problematic pain defined as a pain score of ≥7 occurred more frequently in women (14%) than in men (6%), [Chi square test (chi2) = 5.6, p = 0.02]. Patient satisfaction with the care they received, measured on a scale of 0 (not happy) to 10 (very happy) found the median score to be 10 with 76% reporting a score of 10. Out of 360 responses, 98% of women and 99% of men said that they would be willing to have a future HRA examination. CONCLUSIONS: In this cohort, the overall pain scores were low and similar across appointment types. However, women had a higher pain score, including troublesome pain levels. Despite this, both women and men were equally satisfied with their care and were willing to have a future examination. The results of the analysis show that the procedure is acceptable to patient groups. A small number of women may need general anaesthesia for their examinations/treatment.

A novel monoclonal antibody to characterize pathogenic polymers in liver disease associated with alpha1-antitrypsin deficiency.

UNLABELLED: Alpha(1)-antitrypsin is the most abundant circulating protease inhibitor. The severe Z deficiency allele (Glu342Lys) causes the protein to undergo a conformational transition and form ordered polymers that are retained within hepatocytes. This causes neonatal hepatitis, cirrhosis, and hepatocellular carcinoma. We have developed a conformation-specific monoclonal antibody (2C1) that recognizes the pathological polymers formed by alpha(1)-antitrypsin. This antibody was used to characterize the Z variant and a novel shutter domain mutant (His334Asp; alpha(1)-antitrypsin King's) identified in a 6-week-old boy who presented with prolonged jaundice. His334Asp alpha(1)-antitrypsin rapidly forms polymers that accumulate within the endoplasmic reticulum and show delayed secretion when compared to the wild-type M alpha(1)-antitrypsin. The 2C1 antibody recognizes polymers formed by Z and His334Asp alpha(1)-antitrypsin despite the mutations directing their effects on different parts of the protein. This antibody also recognized polymers formed by the Siiyama (Ser53Phe) and Brescia (Gly225Arg) mutants, which also mediate their effects on the shutter region of alpha(1)-antitrypsin. CONCLUSION: Z and shutter domain mutants of alpha(1)-antitrypsin form polymers with a shared epitope and so are likely to have a similar structure.

Genetic population structure of the ectomycorrhizal fungus Pisolithus microcarpus suggests high gene flow in south-eastern Australia.

Pisolithus are ectomycorrhizal fungi that associate with roots of numerous plant species in natural and plantation forests worldwide. Despite the fact that Pisolithus spp. are present in plantation forests in many countries, knowledge of the genetic population structure of Pisolithus spp. remains limited. In this study, we have tested the hypothesis that a propensity for long-distance spore dispersal in Pisolithus microcarpus, along with the widespread distribution of potential eucalypt and acacia plant hosts in south-eastern Australia facilitates gene flow that limits population differentiation. Five polymorphic simple sequence repeat markers were used to investigate the population structure of P. microcarpus. Isolates were grouped according to geographical origin and isolate genotypes were analysed among the geographical populations. Pairwise F (ST) estimates indicated limited genetic differentiation among the geographical populations. Analysis of molecular variance revealed that most of the genetic variation present was within geographical populations, with only 1.3% of the genetic variation among P. microcarpus geographical populations. This was particularly pronounced for four geographical populations within a ca 7,000 km(2) area New South Wales, which were each separated by < 100 km and appeared to be genetically homogeneous. The lack of population structure is suggested to be due to a high degree of gene flow, via basidiospores, between the New South Wales geographical populations.

Coronavirus disease 2019 in heart transplant recipients: Risk factors, immunosuppression, and outcomes.

BACKGROUND: COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear. METHODS: We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression, adjusting for age and time since transplant. RESULTS: The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea, oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor, antimetabolite, and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy. CONCLUSIONS: We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.

Characteristics and Outcomes of COVID-19 in Patients on Left Ventricular Assist Device Support.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic continues to afflict millions of people worldwide. Patients with end-stage heart failure and left ventricular assist devices (LVADs) may be at risk for severe COVID-19 given a high prevalence of complex comorbidities and functional impaired immunity. The objective of this study is to describe the clinical characteristics and outcomes of COVID-19 in patients with end-stage heart failure and durable LVADs. METHODS: The Trans-CoV-VAD registry is a multi-center registry of LVAD and cardiac transplant patients in the United States with confirmed COVID-19. Patient characteristics, exposure history, presentation, laboratory data, course, and clinical outcomes were collected by participating institutions and reviewed by a central data repository. This report represents the participation of the first 9 centers to report LVAD data into the registry. RESULTS: A total of 40 patients were included in this cohort. The median age was 56 years (interquartile range, 46-68), 14 (35%) were women, and 21 (52%) were Black. Among the most common presenting symptoms were cough (41%), fever, and fatigue (both 38%). A total of 18% were asymptomatic at diagnosis. Only 43% of the patients reported either subjective or measured fever during the entire course of illness. Over half (60%) required hospitalization, and 8 patients (20%) died, often after lengthy hospitalizations. CONCLUSIONS: We present the largest case series of LVAD patients with COVID-19 to date. Understanding these characteristics is essential in an effort to improve the outcome of this complex patient population.

Ericoid mycorrhizal fungi are common root inhabitants of non-Ericaceae plants in a south-eastern Australian sclerophyll forest.

Fungi were isolated from the roots of 17 plant species from the families Apiaceae, Cunoniaceae, Cyperaceae, Droseraceae, Fabaceae-Mimosoideae, Lomandraceae, Myrtaceae, Pittosporaceae, Proteaceae and Stylidiaceae at a sclerophyll forest site in New South Wales, Australia. Internal transcribed spacer (ITS) restriction fragment length polymorphism (RFLP) and sequence comparisons indicated that the isolated fungi had affinities to a range of ascomycetes, basidiomycetes and zygomycetes. Four RFLP types had closest affinities to previously identified Helotiales ericoid mycorrhizal (ERM) or Oidiodendron spp. Isolates representing six RFLP types, which were variously isolated from all 17 plant species, formed ERM coils in hair root epidermal cells of Woollsia pungens (Ericaceae) under gnotobiotic conditions. Three of these isolates formed intercellular hyphae, intracellular hyphae and/or microsclerotia, which are typical of dark septate endophyte infection, in roots of Stylidium productum (Stylidiaceae), indicating an ability to form different types of association with roots of different hosts. Overall the data indicate that a broad range of plant taxa may act as repositories for ERM fungi in sclerophyll forest soil.

Parent management training as a treatment for children with oppositional defiant disorder referred to a mental health clinic.

Parent Management Training (PMT) has been shown to be an empirically supported intervention in ameliorating antisocial behaviour problems. Less evidence is available to demonstrate the effectiveness of PMT in routine public-health-oriented community-based settings where the presence of comorbid disorders complicates the picture. The current study was undertaken to investigate the effectiveness of PMT as a treatment for primary school-age children with Oppositional Defiant Disorder (ODD) and comorbid disorders offered by clinical staff as part of clinical practice. An Australian sample of 94 parents of children diagnosed with ODD by structured interview was provided with eight sessions of PMT. Measures used to assess changes in child behaviour symptoms were the Eyberg Child Behavior Inventory, the Parent Stress Index Child Domain, and the Child Behavior Checklist. Clinically relevant and statistically significant outcome results were found at posttreatment and at 5 months follow-up. There was a reduction in child symptomatology but no evidence of any effect of comorbidity on outcome. These findings are important for the clinical field as they show that PMT is a robust intervention suitable for routine clinical practice even when comorbid disorders are present in addition to ODD.

Cholesterol efflux capacity of high-density lipoprotein correlates with survival and allograft vasculopathy in cardiac transplant recipients.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major cause of mortality after cardiac transplantation. High-density lipoprotein (HDL) cholesterol efflux capacity (CEC) is inversely associated with coronary artery disease. In 2 independent studies, we tested the hypothesis that reduced CEC is associated with mortality and disease progression in CAV. METHODS: We tested the relationship between CEC and survival in a cohort of patients with CAV (n = 35). To determine whether reduced CEC is associated with CAV progression, we utilized samples from the Clinical Trials in Organ Transplantation 05 (CTOT05) study to determine the association between CEC and CAV progression and status at 1 year (n = 81), as assessed by average change in maximal intimal thickness (MIT) on intravascular ultrasound. RESULTS: Multivariable Cox proportional hazard models demonstrated that higher levels of CEC were associated with improved survival (hazard ratio 0.26, 95% confidence interval 0.11 to 0.63) per standard deviation CEC, p = 0.002). Patients who developed CAV had reduced CEC at baseline and 1-year post-transplant. We observed a significant association between pre-transplant CEC and the average change in MIT, particularly among patients who developed CAV at 1 year (ß = -0.59, p = 0.02, R2 = 0.35). CONCLUSION: Reduced CEC is associated with disease progression and mortality in CAV patients. These findings suggest the hypothesis that interventions to increase CEC may be useful in cardiac transplant patients for prevention or treatment of CAV.

Successful explantation of a ventricular assist device following fulminant influenza type A-associated myocarditis.

We report a case of fulminant myocarditis associated with refractory ventricular fibrillation following influenza A infection. Histologic examination was consistent with myocarditis and serology confirmed the viral etiology. The patient was supported with biventricular assist devices for 20 days during which her refractory ventricular fibrillation resolved spontaneously. This is the first documented case of resolution of prolonged ventricular fibrillation while on a ventricular assist device. This case suggests those patients with fulminant viral myocarditis and refractory ventricular arrhythmias may be supported successfully with ventricular assist devices until myocardial recovery takes place.

Impact of liquid-based gynecologic cytology on an HIV-positive population.

OBJECTIVE: To examine the imprint of liquid-based technologies for cervicovaginal cytology on HIV-positive women, who are at high risk for cervical intraepithelial neoplasia. STUDY DESIGN: We performed a retrospective search of the cytopathology files of Johns Hopkins Hospital for the cervicovaginal cytology of HIV-positive women to examine the effect of liquid-based technology on this population. RESULTS: Significant intraepithelial lesions (SILs) (low grade SIL or greater) were identified in 24% of the conventional smears and 23% of the liquid-based cytology. Atypical squamous cells of undetermined significance (ASCUS)/atypical glandular cells of undetermined significance was diagnosed in 15% of the conventional smears and 9% of the liquid-based preparations (P = .02). In patients with ASCUS diagnoses and tissue follow-up within 7 months, significant SILs were identified in 29% with conventional smears and in 65% with liquid-based cytology. CONCLUSION: There was no statistically significant difference in the rate of SILs between conventional smears and liquid-based cervicovaginal preparations in HIV-positive women. The diagnosis of ASCUS on liquid-based cytology may have an increased likelihood of representing a significant SIL in comparison to conventional smears. For the high-risk, HIV-positive population, immediate colposcopy and biopsy may be warranted following ASCUS diagnoses on liquid-based cytology.

Interactive effects of preindustrial, current and future atmospheric CO2 concentrations and temperature on soil fungi associated with two Eucalyptus species.

Soil microbial processes have a central role in global fluxes of the key biogenic greenhouse gases and are likely to respond rapidly to climate change. Whether climate change effects on microbial processes lead to a positive or negative feedback for terrestrial ecosystem resilience is unclear. In this study, we investigated the interactive effects of [CO(2)] and temperature on soil fungi associated with faster-growing Eucalyptus saligna and slower-growing Eucalyptus sideroxylon, and fungi that colonised hyphal in-growth bags. Plants were grown in native soil under controlled soil moisture conditions, while subjecting the above-ground compartment to defined atmospheric conditions differing in CO(2) concentrations (290, 400, 650 µL L(-1)) and temperature (26 and 30 °C). Terminal restriction fragment length polymorphism and sequencing methods were used to examine effects on the structure of the soil fungal communities. There was no significant effect of host plant or [CO(2)]/temperature treatment on fungal species richness (α diversity); however, there was a significant effect on soil fungal community composition (ß diversity) which was strongly influenced by eucalypt species. Interestingly, ß diversity of soil fungi associated with both eucalypt species was significantly influenced by the elevated [CO(2) ]/high temperature treatment, suggesting that the combination of future predicted levels of atmospheric [CO(2)] and projected increases in global temperature will significantly alter soil fungal community composition in eucalypt forest ecosystems, independent of eucalypt species composition. These changes may arise through direct effects of changes in [CO(2)] and temperature on soil fungi or through indirect effects, which is likely the case in this study given the plant-dependent nature of our observations. This study highlights the role of plant species in moderating below-ground responses to future predicted changes to [CO(2)] and temperature and the importance of considering integrated plant-soil system responses.

Epidemiology of viral respiratory tract infections in a prospective cohort of infants and toddlers attending daycare.

BACKGROUND: The epidemiology of respiratory tract infections (RTIs) in a daycare cohort has not been explored using molecular techniques. OBJECTIVES: (1) Determine the overall incidence of RTIs in a daycare cohort using real-time reverse transcriptase polymerase chain reaction (RT-PCR). (2) Determine the relative incidence and impact of specific respiratory viruses, and characterize and compare clinical features associated with these pathogens. STUDY DESIGN: In this prospective cohort study conducted from February 2006 to April 2008, nasal swabs were obtained from symptomatic children ages 0-30 months enrolled in fulltime daycare. RT-PCR was performed to detect respiratory syncytial virus (RSV), human metapneumovirus (MPV), influenza (Flu) viruses A and B, parainfluenza (PIV), adenovirus (AdV), human coronaviruses (CoV) and rhinovirus (RhV). Symptom diaries were completed for each illness. RESULTS: We followed 119 children (mean age 10 months; range 2-24 months) for 115 child years. The mean annual incidence of RTI per child was 4.2 the first year and 1.2 the second year of the study. At least 1 virus was identified in 67% RTIs. Co-infections were common (27% RTIs), with RhV, CoV, and AdV the most common co-pathogens. PIV was identified in 12% of RTIs with a high incidence of PIV4. The viruses with the greatest impact on our population were RSV, RhV and AdV. CONCLUSIONS: Using molecular techniques, viruses were identified in approximately twice as many RTIs as previously reported in a daycare cohort. Infections with newly identified viruses, such as HMPV and CoV subtypes were less frequent and severe than infections with RSV, AdV and RhV.

Identical genotypes of an ericoid mycorrhiza-forming fungus occur in roots of Epacris pulchella (Ericaceae) and Leptospermum polygalifolium (Myrtaceae) in an Australian sclerophyll forest.

Assemblages of fungi associated with roots of cooccurring Epacris pulchella (Ericaceae) and Leptospermum polygalifolium (Myrtaceae) seedlings at a sclerophyll forest site in New South Wales, Australia, were investigated by direct DNA extraction and analysis of rRNA gene internal transcribed spacer (ITS) products by denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism (T-RFLP) analyses. While ordination of the DGGE data suggested that the assemblages did not differ significantly between the two plant taxa, T-RFLP data provided marginal statistical support for the presence of different assemblages. Fungi isolated from roots of both plants were identified by ITS sequence comparisons largely as ascomycetes, several of which had close sequence identity to Helotiales ericoid mycorrhizal (ERM) fungi. One isolate morphotype from E. pulchella had close sequence similarity to ectomycorrhizal fungi in the Cenococcum geophilum complex, and neighbour-joining analysis grouped this strongly with other Australian C. geophilum-like sequences. Distribution of genotypes of an ERM Helotiales ascomycete in root systems of the two plant taxa was also investigated using inter-simple sequence repeat (ISSR)-PCR. Nineteen ISSR genotypes were identified, two of which were present in roots of both plant taxa. The results are discussed in the context of potential mycelial connections between Ericaceae and non-Ericaceae plants.

Status of bone mineral density in patients selected for cardiac transplantation.

OBJECTIVE: To determine the prevalence and correlates of low bone mineral density (BMD) in ambulatory outpatients with end-stage heart failure who were awaiting cardiac transplantation. METHODS: Fifty-five cardiac transplant candidates with end-stage heart failure were enrolled in this study. Bone mineral density at the lumbar spine and proximal femur was determined by dual-energy x-ray absorptiometry. Laboratory studies included serum alkaline phosphatase, calcium, intact parathyroid hormone, and 25-hydroxyvitamin D. RESULTS: The mean proximal femur and lumbar spine Z scores were 0.3 +/- 1.1 and 0.3 +/- 1.5, respectively. The mean BMD was not lower than that of the age-and sex-matched reference population. Z scores were less than -1 in 23% at the lumbar spine and 15% at the proximal femoral neck. On the basis of T scores, osteopenia (T scores between -1 and -2.5) was present in 24% (confidence interval, 13% to 35%) of patients at the lumbar spine and in 20% (confidence interval, 10% to 30%) at the proximal femur; osteoporosis (T scores of less than -2.5) was present in 4% of the study population. Half of the patients in this study sample had elevated intact parathyroid hormone levels, and a third of the patients had low 25-hydroxyvitamin D levels. CONCLUSION: Lumbar spine and hip BMD measurements were not significantly low relative to age and sex in ambulatory patients with heart failure awaiting cardiac transplantation.

Ectomycorrhizal mycobionts of Pisonia grandis on coral cays in the Capricorn-Bunker group, Great Barrier Reef, Australia.

The diversity of ectomycorrhizal mycobionts of Pisonia grandis (Nyctaginaceae) from coral cays in the Capricorn-Bunker group, Great Barrier Reef, Australia, was examined. Only two ectomycorrhiza morphotypes (brown and black) were identified in soil from seven cays and DNA from both morphotypes was subjected to ITS-RFLP and sequence analysis. The brown morphotype was present in soil from all cays but the black morphotype was only observed in soil from three cays. ITS-RFLP analysis showed that the brown and black morphotypes were formed by different fungal taxa, with the RFLP pattern for the black morphotype being consistent with that of the culture previously obtained from black ectomycorrhizal roots on Heron Island. Comparison with the GenBank database revealed that closest matches to both morphotypes were sequences for various Thelephoraceae (Basidiomycota), but the brown and black morphotypes had only 80% sequence similarity to each other. Neighbour-joining analysis of these sequences with sequences for other Thelephoraceae grouped the brown and black morphotypes in a well-supported clade with several Tomentella species, suggesting that both belong to this genus. The data are discussed in relation to ectomycorrhizal fungal diversity and the coral cay habitat.

Prolonged repolarization after ventricular assist device support is associated with arrhythmias in humans with congestive heart failure.

BACKGROUND: Recent observations indicate that the QTc interval often increases in the early postoperative period (<1 week) after mechanical unloading of severely failing hearts with a left ventricular assist device (LVAD). The present study examined whether early changes in ventricular repolarization after LVAD placement are associated with ventricular arrhythmias. METHODS AND RESULTS: An electrocardiogram was obtained within 4 days before LVAD placement, <12 hours after LVAD placement, and weekly thereafter. Patient records were reviewed for documented ventricular tachycardia (VT) or ventricular fibrillation (VF) for 1 week preoperatively and the first 2 weeks postoperatively. Differences in QTc interval between patients with and without VT were evaluated. Ten of 17 patients enrolled (59%) had VT or VF after LVAD placement. Of these, 4 required therapeutic intervention because of clinical instability or symptoms. The change in the QTc (DeltaQTc) between the preoperative and immediate postoperative period was significantly different among patients with VT/VF compared with patients without VT/VF (+23 ms vs. -68 ms, P < .001). CONCLUSION: The early period after initiation of LVAD support of the failing human heart is associated with a relatively high incidence of significant ventricular arrhythmias after LVAD placement. Beyond the impact of myocardial inflammation and wound healing occurring after all LVAD implants, early postoperative increases in the QTc interval after cardiac unloading appear to predispose to ventricular arrhythmias.

Aurora-A over-expression in high-grade PIN lesions and prostate cancer.

BACKGROUND: Over-expression of Aurora-A (Aurora 2 kinase, STK-15), a protein found in centrosomes thought to be associated with genetic instability, has been previously documented in prostate cancer [Pihan et al.: Cancer Res 61(5):2212-2219, 2001]. It is unknown if this protein is also over-expressed in high-grade prostatic intraepithelial neoplasia (PIN) lesions. METHODS: PIN lesions were examined for increased Aurora-A using immunohistochemical staining on archival paraffin embedded prostatectomy tissue. Aurora-A expression was scored using size, number, and staining intensity. Protein expression was examined and compared between stromal cells, normal glands, high-grade PIN lesions, and invasive cancer. RESULTS: Immunohistochemistry shows an increased expression of Aurora-A in 96% of high-grade PIN cases, and 98% in cancer lesions. Twenty-nine percent of cases of normal glands from cancerous prostates also showed increased Aurora-A expression. CONCLUSIONS: Over-expression of Aurora-A is present in some normal and the majority of high-grade PIN lesions indicating that this may be an early event that leads to the genetic instability seen in prostate carcinogenesis.