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Objective: To evaluate whether APOE ε4 is associated with severity of Lewy body (LB) pathology, independently of Alzheimer disease (AD) pathology., Methods: Six hundred fifty-two autopsy-confirmed LB disease (LBD) cases and 660 clinical controls were genotyped for APOE . In case-control analysis, LBD cases were classified into 9 different groups according to severity of both LB pathology (brainstem, transitional, diffuse) and AD pathology (low, moderate, high) to assess associations between APOE ε4 and risk of different neuropathologically defined LBD subgroups in comparison to controls. In LBD cases only, we also measured LB counts from 5 cortical regions and evaluated associations with ε4 according to severity of AD pathology., Results: As expected, APOE ε4 was associated with an increased risk of transitional and diffuse LBD in cases with moderate or high AD pathology (all odds ratios ≥3.42, all p ≤ 0.004). Of note, ε4 was also associated with an increased risk of diffuse LBD with low AD pathology (odds ratio = 3.46, p = 0.001). In the low AD pathology LBD subgroup, ε4 was associated with significantly more LB counts in the 5 cortical regions, independently of Braak stage and Thal phase (all p ≤ 0.002)., Conclusions: Our results indicate that APOE ε4 is independently associated with a greater severity of LB pathology. These findings increase our understanding of the mechanism behind reported associations of ε4 with risk of dementia with Lewy bodies and Parkinson disease with dementia, and suggest that ε4 may function as a modifier of processes that favor LB spread rather than acting directly to initiate LB pathology., (© 2018 American Academy of Neurology.)

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., (© 2017 American Heart Association, Inc.)

Objective: The aim of this study was to evaluate the association between common exonic variants in the leucine-rich repeat kinase 2 (LRRK2) gene and risk of multiple system atrophy (MSA)., Methods: One series from the United States (92 patients with pathologically confirmed MSA, 416 controls) and a second series from the United Kingdom (85 patients with pathologically confirmed MSA, 352 controls) were included in this case-control study. We supplemented these data with those of 53 patients from the United States with clinically probable or possible MSA. Seventeen common LRRK2 exonic variants were genotyped and assessed for association with MSA., Results: In the combined series of 177 patients with pathologically confirmed MSA and 768 controls, there was a significant association between LRRK2 p.M2397T and MSA (odds ratio [OR] = 0.60, p = 0.002). This protective effect was observed more strongly in the US series (OR = 0.46, p = 0.0008) than the UK series (OR = 0.82, p = 0.41). We observed other noteworthy associations with MSA for p.G1624G (OR = 0.63, p = 0.006) and p.N2081D (OR = 0.15, p = 0.010). The p.G1624G-M2397T haplotype was significantly associated with MSA in the US series (p < 0.0001) and combined series (p = 0.003) but not the UK series (p = 0.67). Results were consistent when additionally including the US patients with clinical MSA, where the strongest single-variant association was again observed for p.M2397T (OR = 0.59, p = 0.0005)., Conclusions: These findings provide evidence that LRRK2 exonic variants may contribute to susceptibility to MSA. Validation in other series and meta-analytic studies will be important., (© 2014 American Academy of Neurology.)

Background: Preanesthesia medical examination is a common procedure performed before ophthalmic surgery. The frequency and characteristics of new medical issues and unstable medical conditions revealed by ophthalmic preanesthesia medical examination are unknown. We conducted a prospective observational study to estimate the proportion of patients with new medical issues and unstable medical conditions discovered during ophthalmic preanesthesia medical examination. Secondary aims were to characterize abnormal findings and assess surgical delay and adverse perioperative events, in relation to findings., Methods: Patients having preanesthesia medical examination, before ophthalmic surgery, were enrolled over a period of 2 years. A review was conducted of historical, physical examination, and test findings from the preanesthesia medical examination., Results: From review of medical records of 530 patients, 100 patients (19%; 95% CI, 16-23%) were reported by providers to have abnormal conditions requiring further medical evaluation. Of these, 12 (12%) had surgery delayed. Retrospective review of examination results identified an additional 114 patients with abnormal findings for a total of 214 (40%; 95% CI, 36-45%) patients. Among the 214 patients, primary findings were cardiovascular (139, 26%), endocrine (26, 5%), and renal (24, 5%). Complications occurred in 49 (9%; 95% CI, 7-12%) patients within 1 month of surgery., Conclusions: Ophthalmic preanesthesia medical examination frequently detects new medical issues or unstable existing conditions, which do not typically alter conduct of perioperative procedures or outcomes. However, these conditions are relevant to long-term patient health and should be conveyed to primary care physicians for further evaluation.

Background: Cytomegalovirus (CMV) has been inconsistently associated with recurrent hepatitis C virus (HCV) after liver transplant (LT)., Methods: A retrospective study of 347, donor or recipient CMV seropositive, first LT recipients transplanted for HCV was performed to evaluate the associations of CMV infection and disease occurring within 1-year of LT with the primary endpoints of allograft inflammation grade ≥2 and fibrosis stage ≥2. Associations were evaluated using multivariable Cox regression models., Results: CMV infection and disease occurred in 111 (32%) and 24 (7%) patients, respectively. Hepatic allograft inflammation grade ≥2 and fibrosis stage ≥2 occurred in 221 (64%) and 140 (40%) patients, respectively. CMV infection was associated with increased risk of fibrosis stage ≥2 (relative risk [RR], 1.52; P=0.033). CMV disease was associated with increased risk of inflammation grade ≥2 (RR, 3.40; P<0.001), and although not significant, with fibrosis stage ≥2 (RR, 2.03; P=0.052). These associations did not differ significantly according to recipient CMV seropositivity., Conclusions: Our results support an association between CMV infection and disease with recurrence of HCV after LT. Investigation of prevention of CMV infection and disease as a strategy to mitigate recurrent HCV in LT recipients is warranted.

Background: Extremely few objective estimates of traumatic brain injury incidence include all ages, both sexes, all injury mechanisms, and the full spectrum from very mild to fatal events., Methods: We used unique Rochester Epidemiology Project medical records-linkage resources, including highly sensitive and specific diagnostic coding, to identify all Olmsted County, MN, residents with diagnoses suggestive of traumatic brain injury regardless of age, setting, insurance, or injury mechanism. Provider-linked medical records for a 16% random sample were reviewed for confirmation as definite, probable, possible (symptomatic), or no traumatic brain injury. We estimated incidence per 100,000 person-years for 1987-2000 and compared these record-review rates with rates obtained using Centers for Disease Control and Prevention (CDC) data-systems approach. For the latter, we identified all Olmsted County residents with any CDC-specified diagnosis codes recorded on hospital/emergency department administrative claims or death certificates during 1987-2000., Results: Of sampled individuals, 1257 met record-review criteria for incident traumatic brain injury; 56% were ages 16-64 years, 56% were male, and 53% were symptomatic. Mechanism, sex, and diagnostic certainty differed by age. The incidence rate per 100,000 person-years was 558 (95% confidence interval = 528-590) versus 341 (331-350) using the CDC data-system approach. The CDC approach captured only 40% of record-review cases. Seventy-four percent of missing cases presented to the hospital/emergency department; none had CDC-specified codes assigned on hospital/emergency department administrative claims or death certificates; and 66% were symptomatic., Conclusions: Capture of symptomatic traumatic brain injuries requires a wider range of diagnosis codes, plus sampling strategies to avoid high rates of false-positive events.

Background: Risk factors for surgical site infection (SSI) after liver transplantation and outcomes associated with these infections have not been assessed using consensus surveillance and optimal analytic methods., Methods: A cohort study was performed of patients undergoing first liver transplantation at Mayo Clinic, Jacksonville, Florida, in 2003 and 2004. SSIs were identified by definitions and methods of the National Nosocomial Infections Surveillance System. Measures of known or suspected risk factors for SSI, graft loss, or death were collected on all patients. Associations of SSI with these factors and also with the primary composite endpoint of graft loss or death within 1 year of liver transplantation were examined using Cox proportional hazards models; relative risks (RRs) were estimated along with 95% confidence intervals (CIs)., Results: Of 370 patients, 66 (18%) had SSI and 57 (15%) died or sustained graft loss within 1 year after liver transplantation. Donor liver mass-to-recipient body mass ratio of less than 0.01 (RR 2.56; 95% CI 1.17-5.62; P=0.019) and increased operative time (RR 1.19 [1-hr increase]; 95% CI 1.03-1.37; P=0.018) were associated with increased SSI risk. SSI was associated with increased risk of death or graft loss within the first year after liver transplantation (RR 3.06; 95% CI 1.66-5.64; P<0.001)., Conclusion: SSI is associated with increased risk of death or graft loss during the first year after liver transplantation. Increased operative time and decreased donor liver-to-recipient body mass ratio showed evidence of association with SSI.