Diehl, Nancy N.

Background/Aims. The aim of this study was to evaluate the association of fluid balance with outcomes in patients hospitalized with acute pancreatitis (AP).Methods. This was a retrospective study of patients hospitalized between May 2008 and June 2016 with AP and a clinical order for strict recording of intake and output. Data collected included various types of fluid intake and output at 24 and 48 hours after admission. The primary outcome was length of stay (LOS). Analysis was performed using single-variable and multivariable negative binomial regression models.Results. Of 1256 patients hospitalized for AP during the study period, only 71 patients (5.6%) had a clinical order for strict recording of intake and output. Increased urine output was associated with a decreased LOS at 24 and 48 hours in univariable analysis. An increasingly positive fluid balance (total intake minus urine output) at 24 hours was associated with a longer LOS in multivariable analysis.Conclusions. Few patients hospitalized for AP had a documented order for strict monitoring of fluid intake and output, despite the importance of monitoring fluid balance in these patients. Our study suggests an association between urine output and fluid balance with LOS in AP.

Background: Recognition of rates and causes of hard, patient-centered outcomes of death and cerebrovascular events (CVEs) after heart rhythm disorder management (HRDM) procedures is an essential step for the development of quality improvement programs in electrophysiology laboratories. Our primary aim was to assess and characterize death and CVEs (stroke or transient ischemic attack) after HRDM procedures over a 17-year period. Methods: We performed a retrospective cohort study of all patients undergoing HRDM procedures between January 2000 and November 2016 at the Mayo Clinic. Patients from all 3 tertiary academic centers (Rochester, Phoenix, and Jacksonville) were included in the study. All in-hospital deaths and CVEs after HRDM procedures were identified and were further characterized as directly or indirectly related to the HRDM procedure. Subgroup analysis of death and CVE rates was performed for ablation, device implantation, electrophysiology study, lead extraction, and defibrillation threshold testing procedures. Results: A total of 48 913 patients (age, 65.7±6.6 years; 64% male) who underwent a total of 62 065 HRDM procedures were included in the study. The overall mortality and CVE rates in the cohort were 0.36% (95% confidence interval [CI], 0.31–0.42) and 0.12% (95% CI, 0.09–0.16), respectively. Patients undergoing lead extraction had the highest overall mortality rate at 1.9% (95% CI, 1.34–2.61) and CVE rate at 0.62% (95% CI, 0.32–1.07). Among patients undergoing HRDM procedures, 48% of deaths directly related to the HDRM procedure were among patients undergoing device implantation procedures. Overall, cardiac tamponade was the most frequent direct cause of death (40%), and infection was the most common indirect cause of death (29%). The overall 30-day mortality rate was 0.76%, with the highest being in lead extraction procedures (3.08%), followed by device implantation procedures (0.94%). Conclusions: Half of the deaths directly related to an HRDM procedure were among the patients undergoing device implantation procedures, with cardiac tamponade being the most common cause of death. This highlights the importance of the development of protocols for the quick identification and management of cardiac tamponade even in procedures typically believed to be lower risk such as device implantation.

ABSTRACTBackgroundA number of genetic loci are associated with risk for Parkinson's disease (PD) based on genome‐wide association studies; however, the relationship between genetic variants and nigrostriatal degeneration, which is the structural correlate of parkinsonism, has not been reported.ObjectivesWe quantified nigrostriatal dopaminergic integrity with image analysis of putaminal tyrosine hydroxylase immunoreactivity in 492 brains with Lewy body disease and used this pathologic endophenotype to explore possible association with PD genetic variants.MethodsThe study cases had Lewy‐related pathology and variable degrees of nigrostriatal degeneration. They were assigned to one of the following clinical subgroups according to their predominant clinical syndrome: parkinsonism‐predominant, parkinsonism+dementia, and dementia‐predominant. In addition to putaminal tyrosine hydroxylase immunoreactivity, semiquantitative scoring was used to assess substantia nigra neuronal loss. A total of 29 PD genetic risk variants were genotyped on each case.ResultsWhen compared with controls, tyrosine hydroxylase immunoreactivity was reduced in Lewy body cases in the dorsolateral (79%) and ventromedial (57%) putamen. The dorsolateral region was better preserved in dementia‐predominant cases than in cases with parkinsonism. Dorsolateral putaminal tyrosine hydroxylase immunoreactivity correlated with neuronal loss in the ventrolateral substantia nigra. Genetic analyses showed no significant association of PD risk variants with putaminal tyrosine hydroxylase immunoreactivity.ConclusionsThe results confirm regional differences in putaminal dopaminergic degeneration and vulnerability of nigrostriatal pathway in Lewy body disorders with parkinsonism. The lack of association with PD genetic risk variants suggests that they may not be associated with quantitative endophenotypes of nigrostriatal degeneration, but more likely related to the risk of disease per se. © 2017 International Parkinson and Movement Disorder Society

As potential treatments for C9ORF72‐associated amyotrophic lateral sclerosis (c9ALS) approach clinical trials, the identification of prognostic biomarkers for c9ALS becomes a priority. We show that levels of phosphorylated neurofilament heavy chain (pNFH) in cerebrospinal fluid (CSF) predict disease status and survival in c9ALS patients, and are largely stable over time. Moreover, c9ALS patients exhibit higher pNFH levels, more rapid disease progression, and shorter survival after disease onset than ALS patients without C9ORF72 expansions. These data support the use of CSF pNFH as a prognostic biomarker for clinical trials, which will increase the likelihood of successfully developing a treatment for c9ALS. Ann Neurol 2017;82:139–146

Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics for treating C9ORF72 -associated amyotrophic lateral sclerosis.

94 Background: Octogenarian breast cancer (BrCa) patients accept less aggressive BrCa treatment due to decreased life expectancy, increased comorbidities, and high likelihood of death from other causes. Unfortunately little data exist stratifying octogenarian outcomes by disease risk. We sought to characterize treatment and recurrence patterns in patients >80yo. Methods: Retrospective review identified 432 women >80yo treated surgically for stage 0-3 BrCa between 11/99-8/11. We gathered clinicopathologic data and classified patients by disease risk as DCIS only, low risk (<2cm and ER positive and node negative), or high risk (>2cm or ER negative or node positive). We compared recurrence rates and estimated survival by Kaplan-Meier curves. Results: Among the 432 women, disease was found by mammogram in 86%, treated with BCT in 64%, and predominantly ER-positive (87%). We classified patients as having DCIS only (N=61), low risk (N=205), or high risk (N=166) disease. We identified the following deviations from standard treatment guidelines: 68% DCIS BCT and 38% high risk BCT patients did not have radiation therapy, 25% low risk BCT patients had surgery only, 51% low risk patients did not take adjuvant hormonal therapy, and 40% high risk patients had no adjuvant chemo/hormonal therapy. At 5 and 10 years the overall estimated survival was 63% and 31%, respectively. Overall, 19/432 (5%) patients developed recurrence (table 1). Patients needing mastectomy for high risk disease had significantly higher risk of recurrence than high or low risk BCT patients (p=0.02). Of the 19 recurrence patients, 7/19 (37%; 1 DCIS, 1 low risk, 5 high risk) occurred despite standard multimodality treatment, while12 (63%; 3 low risk, 9 high risk) had the initial tumor treated less aggressively due to patient choice (n=9) or medical co-morbidities (n=3). Conclusions: Significant deviations from treatment guidelines occur in women >80yo. Those with high risk disease should be counseled accordingly and encouraged to receive adjuvant treatment as two thirds of women >80yo will live at least 5 years. [Table: see text]

541 Background: A long wait-time for colectomy for colon cancer should theoretically affect survival but, to date, the association between delay to colectomy and survival remains unresolved. Methods: We studied 4,692 patients who underwent colectomy for colon cancer between 1990 and 2012. Wait-time was defined as the number of days between diagnosis and colectomy. Cox regression models were used to estimate all-cause mortality across wait-time categories. Multivariable analyses were controlled for clinicopathologic variables and Charlson comorbidity index. Results: The number of patients in the wait-time group of 1-28 days was 3,950 (84.2%), 29-84 days was 681 (22.7%), and >84 days was 61 (1.3%). A wait-time of 29-84 days was not associated with an increased risk of death (HR=1.13; p=0.056) when compared to a wait-time of 1-28 days. Though a wait-time >84 days represented a small group, it was associated with an increased risk of death (HR=1.60; p=0.013). For patients with stage I and II disease, wait-times of 29-84 days (HR =1.44; p=0.0001) and >84 days (adjusted HR=2.24; p=0.0007) were associated with an increased risk of mortality. Conclusions: A wait-time for colon cancer surgery of up to 12 weeks is likely safe for most patients. However, those suspected to have early-stage colon cancer may benefit from less of delay. These data provide a framework to address concerns over prolonged wait-times and can direct efforts for timely surgical intervention in patients with colon cancer. [Table: see text]

ABSTRACTBackgroundMutations in the leucine‐rich repeat kinase 2 gene (LRRK2) are the most common genetic cause of Parkinson's disease (PD). Unexpectedly, tau pathology has been reported in a subset of LRRK2 mutation carriers.MethodsTo estimate the frequency of pathogenic LRRK2 mutations and to evaluate the association of common LRRK2 variants with risk of primary tauopathies, we studied 1039 progressive supranuclear palsy (PSP) and 145 corticobasal degeneration patients from the Mayo Clinic Florida brain bank and 1790 controls ascertained at Mayo Clinic. Sanger sequencing of LRRK2 exons 30, 31, 35, and 41 was performed in all patients, and genotyping of all 17 known exonic variants with minor allele frequency >0.5% was performed in patients and controls.ResultsLRRK2 mutational screening identified 2 known pathogenic mutations (p.G2019S and p.R1441C), each in 1 PSP patient, the novel p.A1413T mutation in a PSP patient and the rare p.R1707K mutation in a corticobasal degeneration patient. Both p.A1413T and p.R1707K mutations were predicted damaging by at least 2 of 3 prediction programs and affect evolutionary conserved sites of LRRK2. Association analysis using common LRRK2 variants only showed nominal association of the p.L153L variant with PSP.ConclusionsOur study confirms the presence of pathogenic and potentially pathogenic LRRK2 mutations in pathologically confirmed primary tauopathies, albeit with low frequency. In contrast to PD, common LRRK2 variants do not appear to play a major role in determining PSP and corticobasal degeneration risk. © 2016 International Parkinson and Movement Disorder Society.