Influencing functional outcomes: a look at role performance and satisfaction with life following liver transplant

Abstract 572 The success of orthotopic liver transplantation (OLT), originally measured as survival, now extends to quality of the life saved. Return to work (RTW) is also a desired outcome. Our AIM was to explore the relationship between 5 pre-OLT factors & 5 post-OLT quality of life (QOL) domains with life satisfaction and primary productive role to better understand how to improve both. METHODS: Patients (pts)1-3 yrs post-OLT filled QOL form during follow-up clinic visits between 7/04 to 6/05. The Liver transplantation Database-Quality of life (LTD-QOL) form yielded data on 5 domains: measure of disease (MOD), psychological distress/well-being (PDW), personal function (PF), social/role function (SRF) & general health perception (GHP). Results: 229 pts were first categorized as satisfied overall with life (79%), or dissatisfied, and then assigned to groups based on primary productive role (51%), no primary productive role, or retired. Pre-OLT variables were age, gender, marital status, education, & etiology of liver disease; HCV (33%), alcohol liver disease (ALD)(11%), HCV+ALD (10%), & others (46%). Marital status & age were not significantly related to the outcome variables. Etiology of liver disease, education, and time since OLT and 5 post-OLT QOL domains were significantly associated with both outcome variables; satisfaction and primary productive role (p<.0001).To understand the differences, the 5 physical & men-tal QOL domains were regressed on primary productive role and satisfaction. Pts (mean age 54 yrs (19-74 yrs), males, 70%) fell into the category of primary productive role rates (51%). Pts transplanted for ALD were significantly (p<.05) more likely to be satisfied with life, whereas individuals with HCV±ALD, had lowest satisfaction and were most likely to be unable/uninterested in work. Stepwise logistical regression analysis of satisfaction demonstrated that GHP and SRF correlated most highly. Although satisfaction was significant in bivariate analysis, regression analysis of the influence of domains of QOL, as well as employment, demonstrated that SRF & GHP correlated most highly with life satisfaction. CONCLUSIONS: SRF and GHP correlate with good QOL post OLT. HCV patients have low levels of satisfaction whereas the highest level of satisfaction is in the ALD group. Further studies should address methods to improve satisfaction in those with HCV

Postoperative Atrial Fibrillation and Flutter in Liver Transplantation: An Important Predictor of Early and Late Morbidity and Mortality

Postoperative atrial fibrillation/flutter (POAF) is the most common perioperative arrhythmia and may be particularly problematic after liver transplantation (LT). This study is a single‐center retrospective analysis of POAF to determine its incidence following LT, to identify risk factors, to assess its impact on clinical outcomes, and to summarize management strategies. The records of all patients who underwent LT between 2010 and 2018 were reviewed. Extracted data included pre‐LT demographics and cardiac evaluation, in‐hospital post‐LT cardiac events, early and late complications, and survival. Among 1011 patients, the incidence of post‐LT POAF was 10%. Using binary logistic regression, pre‐LT history of atrial fibrillation was the strongest predictor of POAF (odds ratio [OR], 6.72; 95% confidence interval [CI], 2.00‐22.57; P < 0.001), followed by history of coronary artery disease (CAD; OR, 2.52; 95% CI, 1.10‐5.81; P = 0.03). Cardiac stress testing abnormality and CAD on cardiac catheterization were also associated with higher risk. Median time to POAF onset after LT was 3 days with 72% of cases resolving within 48 hours. POAF patients had greater hospital length of stay, death during the LT admission, and 90‐day and 1‐year mortality. POAF was an independent risk factor for post‐LT mortality (OR, 2.0; 95% CI, 1.3‐3.0; P < 0.01). Amiodarone was administered to 73% of POAF patients with no evidence of increased serum alanine aminotransferase levels. POAF occurred in 10% of post‐LT patients with early onset and rapid resolution in most affected patients. POAF patients, however, had significant morbidity and mortality, suggesting that POAF is an important marker for worse early and late post‐LT outcomes

Expanding the Donor Pool with Utilization of Extended Criteria DCD Livers

Utilization of donation after circulatory death donor (DCD) livers for transplantation has remained cautious in the U.S. The aim of this study was to demonstrate the expansion of DCD liver transplant (LT) program with the use of extended criteria DCD livers. After institutional review board approval, 135 consecutive DCD LTs were retrospectively studied. ECD DCD livers were defined as those with one of the followings: 1) donor age >50 years, 2) donor BMI >35 kg/m2, 3) donor functional warm ischemia time (fWIT) >30 minutes, and 4) donor liver macrosteatosis >30%. An optimization protocol was introduced in July 2011 to improve outcomes of DCD LT, which included thrombolytic donor flush, and efforts to minimize ischemic times. The impact of this protocol on outcomes was evaluated in terms of graft loss, ischemic cholangiopathy (IC) and change in DCD LT volume. Of 135 consecutive DCD LT, 62 were ECD DCDs. 24 ECD DCD LT were performed before (Era I) and 38 after the institution of optimization protocol (Era II), accounting for an increase in the use of ECD DCD livers from 39% to 52%. Overall outcomes of ECD DCD LT improved in Era II, with a significantly lower incidence of IC (5% vs. 17% in Era I; P = 0.03) and better 1‐year graft survival (93% vs. 75% in Era I, P = 0.07). Survival outcomes for ECD DCD LT in Era II were comparable to matched deceased donor (DBD) LT. With the expansion of the DCD donor pool, the number of DCD LT performed at our center gradually increased in Era II to account for > 20% of the center's LT volume. In conclusion, with the optimization of perioperative conditions, ECD DCD livers can be successfully transplanted to expand the donor pool for LT

Vocal repertoire of Scinax v-signatus (Lutz 1968) (Anura, Hylidae) and comments on bioacoustical synapomorphies for Scinax perpusillus species group

Herein we describe the vocal repertoire of Scinax v-signatus, compare it to the other species belonging to the S. perpusillus species group and discuss the bioacoustical synapomorphies proposed for the group. We recorded an advertisement call and an aggressive call of S. v-signatus. The advertisement call is similar to the one described for others species of the Scinax perpusillus group. Similarly to Scinax cosenzai, the first note in the advertisement call of S. v-signatus is the longest. The aggressive call was preceded by a series of advertisement calls. We suggest that bioacoustical parameters proposed as synapomorphies for the Scinax perpusillus group are not valid, as they are also observed in species belonging to other groups within the genus

Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice

<p>Abstract</p> <p>Background</p> <p>Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I.</p> <p>Methods</p> <p>C57BL/6 mice received 4 × 10³PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue.</p> <p>Results</p> <p>All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4⁺and CD8⁺T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain.</p> <p>Conclusion</p> <p>Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.</p

Case–control study of HLA-G promoter methylation status, HPV infection and cervical neoplasia in Curitiba, Brazil: a pilot analysis

BACKGROUND: The causal association between persistent human papillomavirus (HPV) infection and cervical cancer has been established, but the mechanisms that favor HPV persistence in cervical cells are still unknown. The diminished capability of the immune system to control and resolve HPV infection is one of several hypotheses. The tolerogenic protein HLA-G has shown aberrant expression in a variety of cancers, which has been suggested as a mechanism for tumor escape from immunosurveillance. In the present study we evaluate the role of epigenetic modification (promoter de-methylation) of the HLA-G gene on susceptibility to HPV infection and development of high-grade cervical lesions. METHODS: A case–control study was carried out in Curitiba, Brazil, between February and June 2010. A total of 789 women aged 15–47 years were recruited: 510 controls with normal cervical cytology, and 279 cases with histologically confirmed cervical intraepithelial neoplasia grade 2 (CIN2, N = 150) or grade 3 (CIN3, N = 129). All women were administered a questionnaire by interview, which collected information on demographic and lifestyle factors, and a cervical sample was collected. HPV DNA detection was performed by GP5+/GP6+ primer-mediated PCR. HPV-positive samples were genotyped by multiplex PCR. A pilot analysis of HLA-G promoter methylation was carried out in a subset of the study population (96 cases and 76 controls) by pyrosequencing. HLA-G methylation and HPV infection status of cases and controls were compared, and confounding factors were computed by t Student and non-parametric Wilcoxon tests. Comparison of HLA-G methylation between cases and controls was assessed by the Bonferroni correction. The association of HLA-G methylation with CIN2/3 was evaluated by logistic regression. RESULTS: HPV prevalence was 19.6% in controls and 94.3% in CIN2/3 cases. HPV16, 31, 33, 35 and 18 were the most prevalent types. Methylation analysis of seven CpGs in the HLA-G promoter did not reveal any spontaneous de-methylation events in CIN2/3 cases (mean proportion of methylation: 75.8%) with respect to controls (mean 73.7%; odds ratio 1.01, 95% confidence interval 0.96, 1.07). CONCLUSIONS: This study did not support the hypothesis that spontaneous de-methylation events in the HLA-G promoter play a primary role in promoting escape from immunosurveillance in the development of precancerous cervical lesions

Pre‐Liver Transplant Cardiac Catheterization is Associated with Low Rate of Myocardial Infarction and Cardiac Mortality

Background A previous study at Indiana University demonstrated a reduction in myocardial infarction (MI) incidence with increased frequency of cardiac catheterization (CATH) in liver transplant (LT) candidates. A strict protocol for performing CATH based upon predefined risk factors, rather than non‐invasive testing alone, was applied to a subgroup (2009‐2010) from that study. CATH was followed by percutaneous coronary intervention (PCI) in cases of significant coronary artery disease (CAD; ≥50% stenosis). The current study applies this screening protocol to a larger cohort (2010‐2016) to assess post‐LT clinical outcomes. Results Among 811 LT patients, 766 underwent stress testing (94%), and 559 underwent CATH (69%) of whom 10% had CAD requiring PCI. The sensitivity of stress echocardiography in detecting significant CAD was 37%. Predictors of PCI included increasing age, male gender and personal history of CAD (p<0.05 for all). Compared to patients who had no CATH, patients who underwent CATH had higher mortality (p=0.07), and the hazard rates (HR) for mortality increased with CAD severity [normal CATH (HR: 1.35 [95% CI: 0.79, 2.33], p=0.298); non‐obstructive CAD (HR: 1.53 [95% CI: 0.84, 2.77], p=0.161); and significant CAD (HR: 1.96 [95% CI: 0.93, 4.15], p=0.080)]. Post‐LT outcomes were compared to the 2009‐2010 subgroup from the previous study and showed similar 1‐year overall mortality (8% and 6%, p=0.48); 1‐year MI incidence (<1% and <1%, p=0.8); and MI deaths as portion of all deaths (3% and 9%, p=0.35). Conclusion Stress echocardiography alone is not reliable in screening LT patients for CAD. Aggressive CAD screening with CATH is associated with low rate of MI and cardiac mortality and validates the previously published protocol when extrapolated over a larger sample and longer follow‐up period

Observational and Dynamical Characterization of Main-Belt Comet P/2010 R2 (La Sagra)

We present observations of comet-like main-belt object P/2010 R2 (La Sagra) obtained by Pan-STARRS 1 and the Faulkes Telescope-North on Haleakala in Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on Mauna Kea, the Danish 1.54 m telescope at La Silla, and the Isaac Newton Telescope on La Palma. An antisolar dust tail is observed from August 2010 through February 2011, while a dust trail aligned with the object's orbit plane is also observed from December 2010 through August 2011. Assuming typical phase darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag between August 2010 and December 2010, suggesting that dust production is ongoing over this period. These results strongly suggest that the observed activity is cometary in nature (i.e., driven by the sublimation of volatile material), and that P/La Sagra is therefore the most recent main-belt comet to be discovered. We find an approximate absolute magnitude for the nucleus of H_R=17.9+/-0.2 mag, corresponding to a nucleus radius of ~0.7 km, assuming an albedo of p=0.05. Using optical spectroscopy, we find no evidence of sublimation products (i.e., gas emission), finding an upper limit CN production rate of Q_CN<6x10^23 mol/s, from which we infer an H2O production rate of Q_H2O<10^26 mol/s. Numerical simulations indicate that P/La Sagra is dynamically stable for >100 Myr, suggesting that it is likely native to its current location and that its composition is likely representative of other objects in the same region of the main belt, though the relatively close proximity of the 13:6 mean-motion resonance with Jupiter and the (3,-2,-1) three-body mean-motion resonance with Jupiter and Saturn mean that dynamical instability on larger timescales cannot be ruled out.Comment: 23 pages, 13 figures, accepted for publication in A

Impact of Recipient Age in Combined Liver-Kidney Transplantation: Caution Is Needed for Patients ≥70 Years

Background. Elderly recipients (≥70 y) account for 2.6% of all liver transplants (LTs) in the United States and have similar outcomes as younger recipients. Although the rate of elderly recipients in combined liver-kidney transplant (CLKT) is similar, limited data are available on how elderly recipients perform after CLKT. Methods. We have previously shown excellent outcomes in CLKT using delayed kidney transplant (Indiana) Approach (mean kidney cold ischemia time = 53 ± 14 h). Between 2007 and 2018, 98 CLKTs were performed using the Indiana Approach at Indiana University (IU) and the data were retrospectively analyzed. Recipients were subgrouped based on their age: 18–45 (n = 16), 46–59 (n = 34), 60–69 (n = 40), and ≥70 years (n = 8). Results. Overall, more elderly patients received LT at IU (5.2%) when compared nationally (2.6%). The rate of elderly recipients in CLKT at IU was 8.2% (versus 2% Scientific Registry of Transplant Recipient). Recipient and donor characteristics were comparable between all age groups except recipient age and duration of dialysis. Patient survival at 1 and 3 years was similar among younger age groups, whereas patient survival was significantly lower in elderly recipients at 1 (60%) and 3 years (40%) (P = 0.0077). Control analyses (replicating Scientific Registry of Transplant Recipient’s survival stratification: 18–45, 46–64, ≥65 y) showed similar patient survival in all age groups. Conclusions. Although LT can be safely performed in elderly recipients, extreme caution is needed in CLKT due to the magnitude of operation