162 results on '"Diehl NN"'
Search Results
2. Population-specific frequencies for LRRK2 susceptibility variants in the genetic epidemiology of Parkinson's disease (GEO-PD) consortium
- Author
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Heckman, M, Soto Ortolaza, A, Aasly, J, Abahuni, N, Annesi, G, Bacon, J, Bardien, S, Bozi, M, Brice, A, Brighina, L, Carr, J, Chartier Harlin, M, Dardiotis, E, Dickson, D, Diehl, N, Elbaz, A, Ferrarese, C, Fiske, B, Gibson, J, Gibson, R, Hadjigeorgiou, G, Hattori, N, Ioannidis, J, Boczarska Jedynak, M, Jasinska Myga, B, Jeon, B, Kim, Y, Klein, C, Kruger, R, Kyratzi, E, Lesage, S, Lin, C, Lynch, T, Maraganore, D, Mellick, G, Mutez, E, Nilsson, C, Opala, G, Park, S, Petrucci, S, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Sohn, Y, Stefanis, L, Tadic, V, Theuns, J, Tomiyama, H, Uitti, R, Valente, E, Van Broeckhoven, C, van de Loo, S, Vassilatis, D, Vilariño Güell, C, White, L, Wirdefeldt, K, Wszolek, Z, Wu, R, Hentati, F, Farrer, M, Ross, O, Heckman, MG, Soto Ortolaza, AI, Aasly, JO, Bacon, JA, Dickson, DW, Diehl, NN, Gibson, JM, Hadjigeorgiou, GM, Ioannidis, JPA, Jeon, BS, Kim, YJ, Maraganore, DM, Mellick, GD, Park, SS, Silburn, PA, Sohn, YH, Uitti, RJ, Valente, EM, Vassilatis, DK, White, LR, Wszolek, ZK, Farrer, MJ, Ross, OA, FERRARESE, CARLO, Heckman, M, Soto Ortolaza, A, Aasly, J, Abahuni, N, Annesi, G, Bacon, J, Bardien, S, Bozi, M, Brice, A, Brighina, L, Carr, J, Chartier Harlin, M, Dardiotis, E, Dickson, D, Diehl, N, Elbaz, A, Ferrarese, C, Fiske, B, Gibson, J, Gibson, R, Hadjigeorgiou, G, Hattori, N, Ioannidis, J, Boczarska Jedynak, M, Jasinska Myga, B, Jeon, B, Kim, Y, Klein, C, Kruger, R, Kyratzi, E, Lesage, S, Lin, C, Lynch, T, Maraganore, D, Mellick, G, Mutez, E, Nilsson, C, Opala, G, Park, S, Petrucci, S, Puschmann, A, Quattrone, A, Sharma, M, Silburn, P, Sohn, Y, Stefanis, L, Tadic, V, Theuns, J, Tomiyama, H, Uitti, R, Valente, E, Van Broeckhoven, C, van de Loo, S, Vassilatis, D, Vilariño Güell, C, White, L, Wirdefeldt, K, Wszolek, Z, Wu, R, Hentati, F, Farrer, M, Ross, O, Heckman, MG, Soto Ortolaza, AI, Aasly, JO, Bacon, JA, Dickson, DW, Diehl, NN, Gibson, JM, Hadjigeorgiou, GM, Ioannidis, JPA, Jeon, BS, Kim, YJ, Maraganore, DM, Mellick, GD, Park, SS, Silburn, PA, Sohn, YH, Uitti, RJ, Valente, EM, Vassilatis, DK, White, LR, Wszolek, ZK, Farrer, MJ, Ross, OA, and FERRARESE, CARLO
- Abstract
Variants within the leucine-rich repeat kinase 2 gene are recognized as the most frequent genetic cause of Parkinson's disease. Leucine-rich repeat kinase 2 variation related to disease susceptibility displays many features that reflect the nature of complex, late-onset sporadic disorders like Parkinson's disease.
- Published
- 2013
3. FGF20 and Parkinson's disease: no evidence of association or pathogenicity via alpha-synuclein expression.
- Author
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Wider C, Dachsel JC, Soto AI, Heckman MG, Diehl NN, Yue M, Lincoln S, Aasly JO, Haugarvoll K, Trojanowski JQ, Papapetropoulos S, Mash D, Rajput A, Rajput AH, Gibson JM, Lynch T, Dickson DW, Uitti RJ, Wszolek ZK, and Farrer MJ
- Abstract
Genetic variation in fibroblast growth factor 20 (FGF20) has been associated with risk of Parkinson's disease (PD). Functional evidence suggested the T allele of one SNP, rs12720208 C/T, altered PD risk by increasing FGF20 and alpha-synuclein protein levels. Herein we report our association study of FGF20 and PD risk in four patient-control series (total: 1,262 patients and 1,881 controls), and measurements of FGF20 and alpha-synuclein protein levels in brain samples (nine patients). We found no evidence of association between FGF20 variability and PD risk, and no relationship between the rs12720208 genotype, FGF20 and alpha-synuclein protein levels. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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4. Quality in EUS: an assessment of baseline compliance and performance improvement by using the American Society for Gastrointestinal Endoscopy-American College of Gastroenterology quality indicators.
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Coe SG, Raimondo M, Woodward TA, Gross SA, Gill KR, Jamil LH, Al-Haddad M, Heckman MG, Crook JE, Diehl NN, and Wallace MB
- Abstract
BACKGROUND: An American Society for Gastrointestinal Endoscopy-American College of Gastroenterology (ASGE-ACG) task force recently developed quality indicators for the preprocedure, intraprocedure, and postprocedure phases of each endoscopic procedure. Benchmark rates and clinical significance of compliance have not been determined. OBJECTIVES: To establish baseline compliance rates to the preprocedure and intraprocedure quality indicators in our EUS cases, identify indicators with the lowest compliance rates, and establish change in compliance rates with a targeted performance improvement plan. METHODS: We measured baseline compliance to each of the preprocedure and intraprocedure EUS quality indicators in the EUS procedures performed at Mayo Clinic Jacksonville from March 1996 through August 2006. We developed a performance improvement plan that targeted the 4 indicators with the lowest compliance over the entire time period. Compliance rates in the year after plan implementation were compared with those from January 2004 to August 2006, when adjusting for endoscopist and direct access. RESULTS: We demonstrated areas of high quality as well as areas for improvement in compliance with the ASGE-ACG quality metrics in a large cohort of EUS cases. We achieved improvement in all 4 areas targeted for quality improvement, statistically significant at the 5% level for two of the quality indicators. LIMITATIONS: Limitations included our retrospective design and the use of unstructured procedure dictations that may limit application of our results. It is also unclear whether compliance was truly synonymous with performance. CONCLUSIONS: We established reference levels of compliance rate within our practice and showed that a targeted performance improvement plan that consisted of awareness, individual accountability, and documentation can result in improvement. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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5. Impact of race pace on development of hyponatraemia in full- and half-marathoners
- Author
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Maynard, JR, primary, Taylor III, WC, additional, McNeil, RB, additional, Diehl, NN, additional, Shapiro, SA, additional, Mohseni, MM, additional, Vadeboncoeur, TF, additional, Silvers, SM, additional, Sumrall, SV, additional, and Perez, EA, additional
- Published
- 1970
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6. Salvage radiotherapy for rising prostate-specific antigen levels after radical prostatectomy for prostate cancer: dose-response analysis.
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Bernard JR Jr, Buskirk SJ, Heckman MG, Diehl NN, Ko SJ, Macdonald OK, Schild SE, and Pisansky TM
- Published
- 2010
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7. Dopamine beta-hydroxylase -1021C>T association and Parkinson's disease.
- Author
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Ross OA, Heckman MG, Soto AI, Diehl NN, Haugarvoll K, Vilariño-Güell C, Aasly JO, Sando S, Gibson JM, Lynch T, Krygowska-Wajs A, Opala G, Barcikowska M, Czyzewski K, Uitti RJ, Wszolek ZK, Farrer MJ, Ross, Owen A, Heckman, Michael G, and Soto, Alexandra I
- Abstract
A single nucleotide polymorphism in the promoter region of the dopamine beta-hydroxylase gene (DBH -1021C>T; rs1611115) is reported to regulate plasma enzyme activity levels. This variant has also been the focus of two large association studies in Parkinson's disease yielding conflicting results. We examined this association in four Caucasian patient-control series (n=2696). A modest protective association was observed in the Norwegian series (OR=0.81, p=0.03; n=1676), however, the effect was in the opposite direction in the Polish series (OR=2.01, p=0.01; n=224). No association was observed for DBH -1021C>T with disease susceptibility in the US and Irish series, or combining all four series (OR=0.91, p=0.16, n=2696). We observed a modest association between DBH -1021C>T and AAO in the combined series (p=0.01). Taken together, these findings indicate that DBH -1021C>T does not play a major role in the pathogenesis of Parkinson's disease. [ABSTRACT FROM AUTHOR]
- Published
- 2008
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8. Outcomes in accommodative esotropia with a high AC/A ratio.
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Reynolds MM, Diehl NN, and Mohney BG
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- Accommodation, Ocular, Child, Eyeglasses, Humans, Retrospective Studies, Esotropia therapy, Strabismus
- Abstract
Purpose: The purpose of this retrospective cohort study was to report the outcomes of high AC/A ratio accommodative esotropia (AET) among children., Methods: The medical records of all children <19 years diagnosed with accommodative esotropia and a high AC/A ratio while residing in Olmsted County, Minnesota, from January 1, 1975, through December 31, 2004, were retrospectively reviewed., Results: A total of 512 patients were diagnosed with AET during the 30-year study period, of which 395 (77.1%) had fully accommodative ET, 117 (22.8%) had partially accommodative ET and 106 (20.5%) had a high AC/A ratio. Of the 93 (87.7 %) high AC/A patients managed with bifocals, 50 (53.8 %) discontinued their use after a mean of 58.7 (range: 5.6-229) months. The Kaplan-Meier rate of discontinuing bifocals was 24.5% at 3 years, 36.4% at 5 years, and 61.4% at 10 years. Patients who discontinued bifocals were more likely to have had strabismus surgery (44% vs 18.6%, p = 0.009) than those who did not discontinue bifocals. The high AC/A patients managed with bifocals achieved similar stereoacuity outcomes to those who did not wear bifocals ( p = 0.65) and were no more likely to require surgery ( p = 0.13)., Conclusion: Among this cohort of children with accommodative esotropia and a high AC/A ratio, bifocal use was discontinued in the majority of children within 10 years, and more commonly among those who underwent strabismus surgery. The use of bifocals was not associated with a higher likelihood of undergoing surgery or enhanced stereopsis compared to those who did not use them.
- Published
- 2021
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9. Mitophagy alterations in Alzheimer's disease are associated with granulovacuolar degeneration and early tau pathology.
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Hou X, Watzlawik JO, Cook C, Liu CC, Kang SS, Lin WL, DeTure M, Heckman MG, Diehl NN, Al-Shaikh FSH, Walton RL, Ross OA, Melrose HL, Ertekin-Taner N, Bu G, Petrucelli L, Fryer JD, Murray ME, Dickson DW, Fiesel FC, and Springer W
- Abstract
Introduction: The cytoprotective PTEN-induced kinase 1 (PINK1)-parkin RBR E3 ubiquitin protein ligase (PRKN) pathway selectively labels damaged mitochondria with phosphorylated ubiquitin (pS65-Ub) for their autophagic removal (mitophagy). Because dysfunctions of mitochondria and degradation pathways are early features of Alzheimer's disease (AD), mitophagy impairments may contribute to the pathogenesis., Methods: Morphology, levels, and distribution of the mitophagy tag pS65-Ub were evaluated by biochemical analyses combined with tissue and single cell imaging in AD autopsy brain and in transgenic mouse models., Results: Analyses revealed significant increases of pS65-Ub levels in AD brain, which strongly correlated with granulovacuolar degeneration (GVD) and early phospho-tau deposits, but were independent of amyloid beta pathology. Single cell analyses revealed predominant co-localization of pS65-Ub with mitochondria, GVD bodies, and/or lysosomes depending on the brain region analyzed., Discussion: Our study highlights mitophagy alterations in AD that are associated with early tau pathology, and suggests that distinct mitochondrial, autophagic, and/or lysosomal failure may contribute to the selective vulnerability in disease., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
- Published
- 2020
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10. Ipsilateral gaze deviation as a risk factor for surgical overcorrection in two-muscle surgery for unilateral superior oblique palsy.
- Author
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Nash DL, Diehl NN, and Mohney BG
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- Adolescent, Adult, Aged, Child, Humans, Male, Middle Aged, Oculomotor Muscles surgery, Ophthalmologic Surgical Procedures, Paralysis, Retrospective Studies, Risk Factors, Treatment Outcome, Vision, Binocular, Young Adult, Strabismus surgery, Trochlear Nerve Diseases complications, Trochlear Nerve Diseases surgery
- Abstract
Purpose: To investigate the angle of deviation in various gaze positions as a risk factor for overcorrection of moderate-angle unilateral trochlear nerve palsies treated with two-muscle surgery., Methods: The medical records of consecutive patients with presumed unilateral moderate-angle trochlear nerve palsy who underwent two-muscle surgery were retrospectively reviewed. Patients with overcorrection, defined as reversal of hyperdeviation by prism alternate cover testing at distance (straight ahead) or near measured at 6 weeks, were compared to non-overcorrected patients for their preoperative torsion and ocular alignment at near and distance., Results: A total of 45 patients (age range, 12-77 years; 24 [53%] males) with deviation ranging from 14
Δ to 25Δ in primary position underwent two-muscle surgery, of whom 8 (18%) experienced surgical overcorrection by 6 weeks' follow-up. The preoperative angle of deviation was similar between overcorrected and non-overcorrected patients for eight of nine cardinal distance positions and near gaze; however, patients with smaller deviations in ipsilateral gaze were more likely to be overcorrected with two-muscle surgery (8.5 vs 16.0 [P = 0.029]). Cut point analysis determined that an ipsilateral gaze of ≤9Δ was significantly associated with overcorrection. Greater lateral incomitance also trended toward overcorrection (15.0 vs 9.0 [P = 0.059]). Torsion was not a clinically significant indicator of overcorrection (3.5 vs 6 [P = 0.083])., Conclusions: A preoperative ipsilateral angle of ≤9Δ was associated with overcorrection in patients undergoing two-muscle surgery for moderate angle unilateral trochlear nerve palsies., (Copyright © 2020 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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11. Tau and apolipoprotein E modulate cerebrovascular tight junction integrity independent of cerebral amyloid angiopathy in Alzheimer's disease.
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Liu CC, Yamazaki Y, Heckman MG, Martens YA, Jia L, Yamazaki A, Diehl NN, Zhao J, Zhao N, DeTure M, Davis MD, Felton LM, Qiao W, Li Y, Li H, Fu Y, Wang N, Wren M, Aikawa T, Holm ML, Oue H, Linares C, Allen M, Carrasquillo MM, Murray ME, Petersen RC, Ertekin-Taner N, Dickson DW, Kanekiyo T, and Bu G
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- Aged, Aged, 80 and over, Alzheimer Disease metabolism, Amyloid beta-Peptides metabolism, Apolipoprotein E4 metabolism, Brain metabolism, Female, Humans, Male, Middle Aged, Tight Junction Proteins metabolism, Tight Junctions metabolism, Alzheimer Disease pathology, Brain pathology, Cerebral Amyloid Angiopathy, Tight Junctions pathology, tau Proteins metabolism
- Abstract
Introduction: Cerebrovascular pathologies including cerebral amyloid angiopathy (CAA) and blood-brain barrier (BBB) dysregulation are prominent features in the majority of Alzheimer's disease (AD) cases., Methods: We performed neuropathologic and biochemical studies on a large, neuropathologically confirmed human AD cohort (N = 469). Amounts of endothelial tight junction proteins claudin-5 (CLDN5) and occludin (OCLN), and major AD-related molecules (amyloid beta [Aβ40], Aβ42, tau, p-tau, and apolipoprotein E) in the temporal cortex were assessed by ELISA., Results: Higher levels of soluble tau, insoluble p-tau, and apolipoprotein E (apoE) were independently correlated with lower levels of endothelial tight junction proteins CLDN5 and OCLN in AD brains. Although high Aβ40 levels, APOE ε4, and male sex were predominantly associated with exacerbated CAA severity, those factors did not influence tight junction protein levels., Discussion: Refining the molecular mechanisms connecting tau, Aβ, and apoE with cerebrovascular pathologies is critical for greater understanding of AD pathogenesis and establishing effective therapeutic interventions for the disease., (© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.)
- Published
- 2020
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12. A Randomized, Controlled Pilot Trial Comparing Platelet-Rich Plasma to Topical Minoxidil Foam for Treatment of Androgenic Alopecia in Women.
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Bruce AJ, Pincelli TP, Heckman MG, Desmond CM, Arthurs JR, Diehl NN, Douglass EJ, Bruce CJ, and Shapiro SA
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- Administration, Topical, Adult, Aerosols, Alopecia diagnosis, Alopecia psychology, Cross-Over Studies, Double-Blind Method, Female, Humans, Middle Aged, Patient Satisfaction, Pilot Projects, Treatment Outcome, Alopecia therapy, Minoxidil administration & dosage, Platelet-Rich Plasma, Quality of Life
- Abstract
Background: Androgenic alopecia (AGA) is a common hair loss disorder. Studies have demonstrated successful treatment with platelet-rich plasma (PRP) in men, but studies in women are few., Objective: To evaluate PRP in the treatment of AGA in women, compared with topical minoxidil., Materials and Methods: Twenty women with AGA received topical minoxidil for 12 weeks and injectable PRP for 12 weeks in a randomized crossover design with an 8-week washout between treatments. Standardized TrichoScan analysis and quality-of-life questionnaires were assessed at baseline and 12-week follow-up for each treatment., Results: After PRP, significant increases from baseline to Week 12 in TrichoScan analysis hair count (p = .002) and vellus hair density (p = .009) occurred. However, minoxidil resulted in significant increases in hair count (p < .001), vellus hair density (p = .03), terminal hair density (p = .004), and cumulative thickness (p = .004). Several quality of life responses improved from baseline to Week 12 after PRP treatment, whereas no improvements were noted after minoxidil., Conclusion: Platelet-rich plasma is an effective treatment for hair regrowth in female AGA, although not as effective as minoxidil. However, the improved quality of life responses after PRP, but not minoxidil, suggest a potential overall greater degree of satisfaction with PRP., Levels of Evidence: I., Clinical Trial Registration: NCT03488108.
- Published
- 2020
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13. Association of Tripartite Motif Containing 11 rs564309 With Tau Pathology in Progressive Supranuclear Palsy.
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Valentino RR, Koga S, Heckman MG, Brushaber DE, Diehl NN, Walton RL, Dickson DW, and Ross OA
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- Astrocytes, Humans, Neurofibrillary Tangles, Tripartite Motif Proteins, Ubiquitin-Protein Ligases, tau Proteins genetics, Parkinson Disease, Supranuclear Palsy, Progressive genetics
- Abstract
Background: Intronic variant rs564309 in tripartite motif containing 11 (TRIM11) is associated with clinical phenotypic differences in progressive supranuclear palsy (PSP), whereby the minor allele (A) is more common in atypical PSP than typical PSP (PSP-Richardson's syndrome). However, rs564309 has not been investigated relative to neuropathological outcomes., Objective: Evaluate the association of rs564309 with the neuropathologically assessed severity of tau pathology, as measured by semi-quantitative scores for neurofibrillary tangles, tufted astrocytes, neuropil threads, and oligodendroglial coiled bodies., Methods: 797 neuropathologically confirmed PSP cases were genotyped for TRIM11 rs564309 and assessed for tau pathology across 20 neuroanatomical regions. Tau pathology measures and age at death were examined for association with TRIM11 rs564309-A using multivariable linear regression models., Results: TRIM11 rs564309-A was associated with increased neurofibrillary tangles pathology (P = 0.050), but was not significantly associated with age at death, neuropil threads, coiled bodies, or tufted astrocytes tau pathology scores., Conclusions: TRIM11 rs564309 may influence burden of neurofibrillary tangles tau pathology in PSP; further study is warranted. © 2020 International Parkinson and Movement Disorder Society., (© 2020 International Parkinson and Movement Disorder Society.)
- Published
- 2020
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14. Creation of a score to predict risk of high conscious sedation requirements in patients undergoing endoscopy.
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McCain JD, Stancampiano FF, Bouras EP, DeVault KR, Gilbert EL, Ryan T, Maillis A, Heckman MG, Diehl NN, and Palmer WC
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- Adult, Aged, Analgesics, Opioid adverse effects, Dose-Response Relationship, Drug, Fentanyl administration & dosage, Fentanyl adverse effects, Humans, Hypnotics and Sedatives adverse effects, Meperidine administration & dosage, Meperidine adverse effects, Midazolam administration & dosage, Midazolam adverse effects, Middle Aged, Risk Assessment, Risk Factors, Treatment Outcome, Analgesics, Opioid administration & dosage, Conscious Sedation adverse effects, Conscious Sedation methods, Endoscopy, Digestive System, Hypnotics and Sedatives administration & dosage
- Abstract
Background and Aims: The administration of intravenous conscious sedation to patients undergoing GI endoscopy carries a risk of cardiopulmonary adverse events. Our study aim was to create a score that stratifies the risk of occurrence of either high-dose conscious sedation requirements or a failed procedure., Methods: Patients receiving endoscopy via endoscopist-directed conscious sedation were included. The primary outcome was occurrence of sedation failure, which was defined as one of the following: (1) high-dose sedation, (2) the need for benzodiazepine/narcotic reversal agents, (3) nurse-documented poor patient tolerance to the procedure, or (4) aborted procedure. High-dose sedation was defined as >10 mg of midazolam and/or >200 μg of fentanyl or the meperidine equivalent. Patients with sedation failure (n = 488) were matched to controls (n = 976) without a sedation failure by endoscopist and endoscopy date., Results: Significant associations with sedation failure were identified for age, sex, nonclonazepam benzodiazepine use, opioid use, and procedure type (EGD, colonoscopy, or both). Based on these 5 variables, we created the high conscious sedation requirements (HCSR) score, which predicted the risk of sedation failure with an area under the curve of 0.70. Compared with the patients with a risk score of 0, risk of a sedation failure was highest for patients with a score ≥3.5 (odds ratio, 17.31; P = 2 × 10
-14 ). Estimated area under the curve of the HCSR score was 0.68 (95% confidence interval, 0.63-0.72) in a validation series of 250 cases and 250 controls., Conclusions: The HCSR risk score, based on 5 key patient and procedure characteristics, can function as a useful tool for physicians when discussing sedation options with patients before endoscopy., (Copyright © 2020 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)- Published
- 2020
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15. Association between contact sports participation and chronic traumatic encephalopathy: a retrospective cohort study.
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Bieniek KF, Blessing MM, Heckman MG, Diehl NN, Serie AM, Paolini MA 2nd, Boeve BF, Savica R, Reichard RR, and Dickson DW
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- Adolescent, Adult, Aged, Athletes, Athletic Injuries mortality, Brain pathology, Brain Injuries, Traumatic pathology, Child, Cohort Studies, Dementia pathology, Female, Humans, Male, Middle Aged, Neurodegenerative Diseases pathology, Retrospective Studies, tau Proteins metabolism, Athletic Injuries complications, Chronic Traumatic Encephalopathy mortality
- Abstract
Chronic traumatic encephalopathy is a debilitating neurodegenerative disorder associated with repetitive traumatic brain injuries often sustained through prior contact sport participation. The frequency of this disorder in a diverse population, including amateur athletes, is unknown. Primary historical obituary and yearbook records were queried for 2566 autopsy cases in the Mayo Clinic Tissue Registry resulting in identification of 300 former athletes and 450 non-athletes. In these cases, neocortical tissue was screened for tau pathology with immunohistochemistry, including pathology consistent with chronic traumatic encephalopathy, blinded to exposure or demographic information. Using research infrastructure of the Rochester Epidemiology Project, a comprehensive and established medical records-linkage system of care providers in southern Minnesota and western Wisconsin, medical diagnostic billing codes pertaining to head trauma, dementia, movement disorders, substance abuse disorders and psychiatric disorders were recorded for cases and controls in a blinded manner. A total of 42 individuals had pathology consistent with, or features of, chronic traumatic encephalopathy. It was more frequent in athletes compared to non-athletes (27 cases versus 15 cases) and was largely observed in men (except for one woman). For contact sports, American football had the highest frequency of chronic traumatic encephalopathy pathology (15% of cases) and an odds ratio of 2.62 (P-value = 0.005). Cases with chronic traumatic encephalopathy pathology had higher frequencies of antemortem clinical features of dementia, psychosis, movement disorders and alcohol abuse compared to cases without chronic traumatic encephalopathy pathology. Understanding the frequency of chronic traumatic encephalopathy pathology in a large autopsy cohort with diverse exposure backgrounds provides a baseline for future prospective studies assessing the epidemiology and public health impact of chronic traumatic encephalopathy and sports-related repetitive head trauma., (© 2019 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)
- Published
- 2020
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16. Cost-Utility of Routine Testing in Chronic Urticaria/Angioedema: A Cohort Study.
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Carrillo-Martin I, Dudgeon MG, Chamorro-Pareja N, Haehn DA, Rivera-Valenzuela MG, Spaulding AC, Heckman MG, Diehl NN, Irizarry-Alvarado JM, Helmi H, and Gonzalez-Estrada A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Cohort Studies, Cost-Benefit Analysis, Female, Humans, Male, Middle Aged, Prognosis, Young Adult, Angioedema diagnosis, Angioedema economics, Chronic Urticaria diagnosis, Chronic Urticaria economics
- Abstract
Background: Chronic urticaria/angioedema (CUA) guidelines recommend limiting tests to diagnose and assess prognosis, activity, and severity. Routine testing in CUA might substantially increase cost of disease without benefiting outcome., Objective: To evaluate the utility of tests in CUA and how they influence the cost of disease., Methods: We reviewed 725 electronic medical records of patients who were evaluated for CUA between 2010 and 2018 at a tertiary care center. The sample was gathered through the search of International Classification of Diseases Ninth and Tenth Revision codes pertaining to CUA. Analyses were made to evaluate changes in outcome for patients on whom at least 1 test was performed to evaluate CUA, the costs generated by these tests, and the tendencies to order specific tests from 2010 through 2018., Results: Of 725 patients (age median, 47 years; women, 73.1%), 543 (74.8%) had at least 1 test performed. Tests had an elevated percentage of normal results (>90%). Five patients (0.9%) had a change in outcome and 8 patients were given a different diagnosis (0.1% each). Evaluation, management, and tests accounted for most of the costs. Costs remain similar between 2010-2014 (mean, $569) and 2015-2018 (mean, $569)., Conclusions: In CUA, tests rarely uncover underlying conditions or lead to changes in management and outcome, but they substantially increase the costs generated by the disease. Adherence to current recommendations to limit testing might help in reducing the financial burden of CUA and improve delivery of care., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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17. Quantitative T2 MRI Mapping and 12-Month Follow-up in a Randomized, Blinded, Placebo Controlled Trial of Bone Marrow Aspiration and Concentration for Osteoarthritis of the Knees.
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Shapiro SA, Arthurs JR, Heckman MG, Bestic JM, Kazmerchak SE, Diehl NN, Zubair AC, and O'Connor MI
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- Adult, Aged, Female, Follow-Up Studies, Humans, Injections, Intra-Articular, Knee Joint diagnostic imaging, Magnetic Resonance Imaging methods, Male, Middle Aged, Osteoarthritis, Knee complications, Osteoarthritis, Knee diagnostic imaging, Pain etiology, Pain Management methods, Pain Measurement methods, Pilot Projects, Radiography, Severity of Illness Index, Bone Marrow Transplantation methods, Osteoarthritis, Knee therapy, Tissue and Organ Harvesting methods
- Abstract
Objective: Bone marrow aspiration and concentration (BMAC) is becoming a more common regenerative therapy for musculoskeletal pathology. In our current pilot study, we studied patients with mild-to-moderate bilateral knee osteoarthritis, compared pain at 12-month follow-up between BMAC-injected and saline-injected knees, and examined cartilage appearance measured by magnetic resonance imaging (MRI) T2 quantitative mapping., Design: Twenty-five patients with mild-to-moderate bilateral osteoarthritic knee pain were randomized to receive BMAC into one knee and saline placebo into the other. Bone marrow was aspirated from the iliac crests, concentrated in an automated centrifuge, combined with platelet-poor plasma for knee injection, and compared with saline injection into the contralateral knee. Primary outcome measures were T2 MRI cartilage mapping at 6-month and Visual Analog Scale and Osteoarthritis Research Society International Intermittent and Constant Osteoarthritis Pain scores and radiographs at 12-month follow-up., Results: Constant, intermittent, and overall knee pain remained significantly decreased from baseline at 12-month follow-up (all P ⩽ 0.01), with no apparent difference between BMAC- and saline-treated knees (all P ⩾ 0.54). A similar significant increase from baseline to 12-month follow-up regarding quality of life was observed for both BMAC- and saline-treated knees (all P ⩽ 0.04). T2 quantitative MRI mapping showed no significant changes as a result of treatment., Conclusions: BMAC is safe to perform and relieves pain from knee arthritis but showed no superiority to saline injection at 12-month follow-up. MRI cartilage sequences failed to show regenerative benefit with single BMAC injection. The mechanisms of action that led to pain relief remain unclear and warrant further studies.
- Published
- 2019
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18. Response to Letter to the Editor.
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Shapiro SA, Arthurs JR, Heckman MG, Bestic JM, Diehl NN, Zubair AC, and O'Connor MI
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- Follow-Up Studies, Humans, Magnetic Resonance Imaging, Bone Marrow, Osteoarthritis, Knee
- Published
- 2019
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19. Outcomes of Unilateral Cataracts in Infants and Toddlers 7 to 24 Months of Age: Toddler Aphakia and Pseudophakia Study (TAPS).
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Bothun ED, Wilson ME, Traboulsi EI, Diehl NN, Plager DA, Vanderveen DK, Freedman SF, Yen KG, Weil NC, Loh AR, Morrison D, Anderson JS, and Lambert SR
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- Female, Humans, Incidence, Infant, Intraoperative Complications epidemiology, Male, Postoperative Complications epidemiology, Retrospective Studies, Visual Acuity, Aphakia, Postcataract surgery, Cataract complications, Cataract Extraction adverse effects, Lens Implantation, Intraocular adverse effects, Pseudophakia complications
- Abstract
Purpose: To evaluate outcomes of unilateral cataract surgery in children 7 to 24 months of age., Design: Retrospective case series at 10 Infant Aphakia Treatment Study (IATS) sites., Participants: The Toddler Aphakia and Pseudophakia Study is a registry of children treated by surgeons who participated in the IATS., Methods: Children underwent unilateral cataract surgery with or without intraocular lens (IOL) placement during the IATS enrollment years of 2004 and 2010., Main Outcome Measures: Intraoperative complications, adverse events (AEs), visual acuity, and strabismus., Results: Fifty-six children were included with a mean postoperative follow-up of 47.6 months. Median age at cataract surgery was 13.9 months (range, 7.2-22.9). Ninety-two percent received a primary IOL. Intraoperative complications occurred in 4 patients (7%). At 5 years of age, visual acuity of treated eyes was very good (≥20/40) in 11% and poor (≤20/200) in 44%. Adverse events were identified in 24%, with a 4% incidence of glaucoma suspect. An additional unplanned intraocular surgery occurred in 14% of children. Neither AEs nor intraocular reoperations were more common for children with surgery at 7 to 12 months of age than for those who underwent surgery at 13 to 24 months of age (AE rate, 21% vs. 25% [P = 0.60]; reoperation rate, 13% vs. 16% [P = 1.00])., Conclusions: Although most children underwent IOL implantation concurrent with unilateral cataract removal, the incidence of complications, reoperations, and glaucoma was low when surgery was performed between 7 and 24 months of age and compared favorably with same-site IATS data for infants undergoing surgery before 7 months of age. Our study showed that IOL implantation is relatively safe in children older than 6 months and younger than 2 years., (Copyright © 2019 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
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- 2019
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20. Delay to Colectomy and Survival for Patients Diagnosed with Colon Cancer.
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Bagaria SP, Heckman MG, Diehl NN, Parker A, and Wasif N
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- Humans, Inflammation surgery, Retrospective Studies, Colectomy, Colonic Neoplasms
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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 4,685 patients who underwent a 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 adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality. Results : The number of patients in the wait-time group of 1-21 days was 3,529 (75.3%), 22-42 days was 842 (18.0%), 43-84 days was 253 (5.4%), and >84 days was 61 (1.3%). When compared to patients undergoing surgery in the first week after diagnosis, there was no increased risk of death until wait time >84 days (HR = 1.47; 95% CI, 1.02-2.11; p =.038). Patients in the wait time >84 day group tended to be older, traveled further for colectomy, and had tumors with a lower histologic grade. Conclusions : Colectomy for colon cancer performed up to 3 months following diagnosis is not associated with adverse long-term survival. These data provide a framework to address concerns over prolonged wait-times and direct efforts for timely surgery in patients with colon cancer.
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- 2019
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21. Hepatic iron overload identified by magnetic resonance imaging-based T2* is a predictor of non-diagnostic elastography.
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Ghoz HM, Kröner PT, Stancampiano FF, Bowman AW, Vishnu P, Heckman MG, Diehl NN, McLeod E, Nikpour N, and Palmer WC
- Abstract
Background: Magnetic resonance elastography (MRE) is a non-invasive test used to assess liver stiffness and fibrosis in chronic liver disease, which includes systemic iron overload. However, iron deposition by itself is associated with technical failure of MRE of the liver which necessitates the use of invasive liver biopsy as an alternative monitoring method for these patients. T2*-weighted magnetic resonance imaging (T2*) is a reliable modality to asses for hepatic as well as total body iron overload. Therefore, we aimed to determine a cutoff value on the T2* reading at which MRE would no longer provide accurate stiffness measurements in patients with iron overload., Methods: Ninety-five patients with iron overload who underwent MRE at our institution, between 2010 and 2017 were reviewed retrospectively. We compared T2* values between patients with adequate elastography (N=63) versus those with non-diagnostic elastography (N=32). We additionally examined the ability of T2* to predict the likelihood of non-diagnostic elastography by estimating area under the ROC curve (AUC)., Results: T2* was significantly different between patients with and without an adequate elastography (P<0.0001) and predicted occurrence of non-diagnostic elastography with an AUC of 0.95. All patients with a non-diagnostic elastography had a T2* value below 20 milliseconds (ms), and correspondingly 55% of the patients with a T2* value below 20 ms had a non-diagnostic elastography. The subgroups of patients with a T2* value ≤10, ≤8, and ≤6 ms, had a higher likelihood of non-diagnostic elastography (87%, 92%, and 95%, respectively)., Conclusions: T2* can be used to accurately predict which patients are most likely to have a non-diagnostic elastography reading. T2* of 20 ms or lower reflects a higher likelihood of non-diagnostic elastography., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.
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- 2019
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22. Evaluating the Efficacy, Safety, and Tolerability of the Combination of Tazarotene, Azelaic Acid, Tacrolimus, and Zinc Oxide for the Treatment of Melasma: A Pilot Study.
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Kirsch B, Hoesly PM, Jambusaria A, Heckman MG, Diehl NN, and Sluzevich JC
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Background: Melasma is a common hyperpigmentation disorder of the skin. Combination therapy of topical retinoids, corticosteroids, and hydroquinone has been effective in treating melasma, but long-term use is limited by corticosteroid atrophy and exogenous ochronosis. The aim of this pilot study (NCT02730819) was to determine the efficacy, safety, and tolerability of a novel composition (2013-MCN-333) comprising tazarotene 0.075%, azelaic acid 20%, tacrolimus 0.1%, and (microfine) zinc oxide 10% for the treatment of melasma. Methods: Sixteen patients with moderate-to-severe melasma were treated daily with sunscreen and 2013-MCN-333 for 20 weeks. Primary outcome measure was change in Melasma Area and Severity Index (MASI) score. Results: Twenty-five percent of patients met the primary endpoint of a MASI score of less than eight points at Week 20. MASI score also decreased significantly from baseline (median: 18.9 points) through Week 4 (median: 17.3 points; p =0.006), Week 12 (median: 16.0 points; p =0.001), and Week 20 (median: 13.3 points; p =0.001). Treatment-related adverse events were mild, most of which decreased or resolved over the course of the study. Limitations: The small sample size and nonblinded nature of treatment intervention are potential limitations. Conclusion: Our results suggest daily 2013-MCN-333 could potentially be an effective, safe, and tolerable treatment for moderate-to-severe melasma., Competing Interests: FUNDING:This study was supported in part by the Mayo Foundation for Medical Education and Research. DISCLOSURES:The authors have no conflicts of interest relevant to the content of this article.
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- 2019
23. Incidence and Ocular Features of Pediatric Myasthenias.
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Mansukhani SA, Bothun ED, Diehl NN, and Mohney BG
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- Adolescent, Age of Onset, Autoantibodies blood, Child, Child, Preschool, Disease Progression, Electromyography, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Minnesota epidemiology, Oculomotor Muscles pathology, Receptors, Cholinergic immunology, Retrospective Studies, Myasthenia Gravis diagnosis, Myasthenia Gravis epidemiology
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Purpose: To report the incidence, demographics, and ocular findings of children with myasthenia., Design: Retrospective cohort study., Methods: The medical records of all children (<19 years) examined at Mayo Clinic with any form of myasthenia from January 1 1966, through December 31, 2015, were retrospectively reviewed., Results: A total of 364 children were evaluated during the study period, of which 6 children were residents of the Olmsted County at the time of their diagnosis, yielding an annual age- and sex-adjusted incidence of 0.35 per 100 000 <19 years, or 1 in 285 714 <19 years. The incidence of juvenile myasthenia gravis (JMG) and congenital myasthenic syndrome (CMS) was 0.12 and 0.23 per 100 000, respectively. Of the 364 study children, 217 (59.6%) had JMG, 141 (38.7%) had CMS, and 6 (1.7%) had Lambert-Eaton syndrome, diagnosed at a median age of 13.5, 5.1, and 12.6 years, respectively. A majority of the JMG and CMS patients had ocular involvement (90.3% and 85.1%, respectively), including ptosis and ocular movement deficits. Among children with at least 1 year of follow-up (JMG; median, 7.1 years, CMS; median, 7.0 years), improvement was seen in 88.8% of JMG patients (complete remission in 31.3%) and in 58.3% of CMS patients., Conclusion: Although relatively rare, myasthenia gravis in children has 2 predominant forms, CMS and JMG, both of which commonly have ocular involvement. Improvement is more likely in children with the juvenile form., (Copyright © 2019 Elsevier Inc. All rights reserved.)
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- 2019
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24. Parkinson-Associated SNCA Enhancer Variants Revealed by Open Chromatin in Mouse Dopamine Neurons.
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McClymont SA, Hook PW, Soto AI, Reed X, Law WD, Kerans SJ, Waite EL, Briceno NJ, Thole JF, Heckman MG, Diehl NN, Wszolek ZK, Moore CD, Zhu H, Akiyama JA, Dickel DE, Visel A, Pennacchio LA, Ross OA, Beer MA, and McCallion AS
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- Adult, Aged, Aged, 80 and over, Alleles, Animals, Disease Models, Animal, Female, Genotype, Humans, Introns genetics, Male, Mice, Mice, Transgenic, Middle Aged, Pregnancy, Zebrafish, Chromatin genetics, Dopaminergic Neurons pathology, Enhancer Elements, Genetic genetics, Genetic Predisposition to Disease genetics, Parkinson Disease genetics, alpha-Synuclein genetics
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The progressive loss of midbrain (MB) dopaminergic (DA) neurons defines the motor features of Parkinson disease (PD), and modulation of risk by common variants in PD has been well established through genome-wide association studies (GWASs). We acquired open chromatin signatures of purified embryonic mouse MB DA neurons because we anticipated that a fraction of PD-associated genetic variation might mediate the variants' effects within this neuronal population. Correlation with >2,300 putative enhancers assayed in mice revealed enrichment for MB cis-regulatory elements (CREs), and these data were reinforced by transgenic analyses of six additional sequences in zebrafish and mice. One CRE, within intron 4 of the familial PD gene SNCA, directed reporter expression in catecholaminergic neurons from transgenic mice and zebrafish. Sequencing of this CRE in 986 individuals with PD and 992 controls revealed two common variants associated with elevated PD risk. To assess potential mechanisms of action, we screened >16,000 proteins for DNA binding capacity and identified a subset whose binding is impacted by these enhancer variants. Additional genotyping across the SNCA locus identified a single PD-associated haplotype, containing the minor alleles of both of the aforementioned PD-risk variants. Our work posits a model for how common variation at SNCA might modulate PD risk and highlights the value of cell-context-dependent guided searches for functional non-coding variation., (Copyright © 2018 American Society of Human Genetics. All rights reserved.)
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- 2018
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25. Adult-onset nonparalytic, small-angle hypertropia.
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Shah SM, Martinez-Thompson JM, Diehl NN, and Mohney BG
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- Adult, Age Distribution, Age of Onset, Aged, Aged, 80 and over, Disease Progression, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Minnesota epidemiology, Prevalence, Retrospective Studies, Risk Factors, Sex Distribution, Strabismus diagnosis, Strabismus physiopathology, Time Factors, Eye Movements physiology, Oculomotor Muscles physiopathology, Strabismus epidemiology, Visual Acuity
- Abstract
Purpose: To describe the prevalence and clinical features of a common but underrecognized disorder of adult vertical strabismus., Methods: The medical records of all adult (≥19 years of age) residents of Olmsted County, Minnesota, diagnosed with nonparalytic, small-angle hypertropia (NPSAH) from January 1, 1985, through December 31, 2004, were retrospectively reviewed for demographic and clinical features., Results: Of 753 patients diagnosed with adult-onset strabismus, 99 (13.1%) were found to have NPSAH, yielding an annual incidence of 7.50 per 100,000 patients >18 years of age and a cumulative incidence of 1.28%. The median age at diagnosis was 71 years (range, 27-98 years); 63 (64%) were women. Diplopia was reported at the initial diagnosis in 91 patients (93.8%), with 90 (92.8%) having the diplopia in primary or reading position. The median initial angle of hypertropia was 2
Δ (range, 1Δ -22Δ ) at near and 2Δ (range, 0Δ -12Δ ) at distance. After a median follow-up of 10.8 years (range, 6.2 months to 23.7 years), the final median angle of vertical deviation was 4Δ (range, 0Δ -20Δ ) at near and 4Δ (range, 0Δ -16Δ ) at distance for all 99 patients., Conclusions: NPSAH is a relatively common but infrequently recognized disorder among adults. More prevalent among elderly and female patients in this study cohort, the vast majority presented with diplopia and a hypertropia of ≤10Δ that progressed over time., (Copyright © 2018 American Association for Pediatric Ophthalmology and Strabismus. Published by Elsevier Inc. All rights reserved.)- Published
- 2018
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26. Prevalence of Nephrolithiasis in Patients with Chronic Liver Disease: A Case-Control Study.
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Porter IE 2nd, Palmer WC, Parker AS, Hodge DO, Diehl NN, and Haley WE
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Background and Aims: Nephrolithiasis is known to be associated with several systemic diseases including chronic kidney disease and renal failure, which can also occur as a complication of chronic liver disease (CLD). This study aimed to assess the prevalence of nephrolithiasis in patients with CLD., Methods: A short survey was completed by 198 patients with CLD and 322 controls matched by age, sex, and state of residence. A primary diagnosis of liver disease was confirmed with health record review., Results: The median age of the liver disease group was 63 years and 128 (65%) were male; the median age of the control group was 63 and 199 (63%) were male. Body mass index was higher in the liver disease group (27.8 vs 26.7, P < .01). The most common liver disease diagnosis was hepatitis C (60 [30%]) followed by alcoholic cirrhosis (42 [21.2%]). The self-reported prevalence of nephrolithiasis in the liver disease group was 26%, compared to 14% in the control group ( P < .01). This association remained significant after adjusting for age, sex, body mass index, and family history of kidney stones or liver disease., Conclusions: In this case-control, survey-based study, the prevalence of nephrolithiasis was 2 times higher in patients with CLD.
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- 2018
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27. Stroke in patients with cardiovascular implantable electronic device infection undergoing transvenous lead removal.
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Lee JZ, Agasthi P, Pasha AK, Tarin C, Tseng AS, Diehl NN, Hodge DO, DeSimone CV, Killu AM, Brady PA, Kancharla K, Kusumoto FM, Srivathsan K, Osborn MJ, Espinosa RE, Rea RF, Madhavan M, McLeod CJ, Shen WK, Cha YM, Friedman PA, Asirvatham SJ, and Mulpuru SK
- Subjects
- Aged, Cardiac Resynchronization Therapy Devices microbiology, Echocardiography, Transesophageal, Endocarditis, Bacterial diagnosis, Endocarditis, Bacterial surgery, Female, Follow-Up Studies, Humans, Incidence, Male, Middle Aged, Retrospective Studies, Stroke epidemiology, Stroke surgery, Survival Rate trends, Treatment Outcome, United States epidemiology, Cardiac Resynchronization Therapy Devices adverse effects, Device Removal methods, Endocarditis, Bacterial complications, Stroke etiology
- Abstract
Background: Stroke can be a devastating complication in patients with cardiovascular implantable electronic device (CIED) infection. Paradoxical septic embolism can occur in the presence of device leads and patent foramen ovale (PFO) via embolic dislodgment during transvenous lead removal (TLR)., Objective: The purpose of this study was to examine stroke and its associated factors in patients undergoing TLR for CIED infection., Methods: We performed a retrospective analysis of all patients undergoing TLR for CIED infection from January 1, 2000, to July 30, 2017, from all 3 tertiary referral centers at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). The primary outcome was stroke and was further categorized into preprocedural and postprocedural stroke. Associated risk factors were analyzed., Results: A total of 774 patients (mean age 67.6 ± 14.9 years) underwent TLR for CIED infection. The stroke rate in this cohort was 1.9% (95% confidence interval [CI] 1.1%-3.2%). The preprocedural and postprocedural stroke rate was 0.9% (95% CI 0.4%-1.9%) and 1.0% (95% CI 0.4%-2.0%), respectively. PFOs were identified in 46.7% of patients with stroke and in 12.9% of patients without stroke, and were independently associated with stroke (P = .0002). This was especially in patients with right-sided vegetations with right-to-left shunting (odds ratio 6.4; 95% CI 1.3-31.0; P = .022)., Conclusion: In patients with CIED infection undergoing TLR, the presence of PFO, especially with right-sided vegetation with right-to-left shunting, was associated with an increased risk of stroke. This finding suggests that PFO screening before TLR warrants meticulous attention., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)
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- 2018
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28. APOE ε2 is associated with increased tau pathology in primary tauopathy.
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Zhao N, Liu CC, Van Ingelgom AJ, Linares C, Kurti A, Knight JA, Heckman MG, Diehl NN, Shinohara M, Martens YA, Attrebi ON, Petrucelli L, Fryer JD, Wszolek ZK, Graff-Radford NR, Caselli RJ, Sanchez-Contreras MY, Rademakers R, Murray ME, Koga S, Dickson DW, Ross OA, and Bu G
- Subjects
- Alleles, Alzheimer Disease metabolism, Alzheimer Disease pathology, Animals, Apolipoprotein E4 metabolism, Disease Progression, Humans, Mice, Supranuclear Palsy, Progressive genetics, Supranuclear Palsy, Progressive metabolism, Supranuclear Palsy, Progressive pathology, Apolipoprotein E2 metabolism, Tauopathies metabolism, Tauopathies pathology
- Abstract
Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease mainly by modulating amyloid-β pathology. APOE ε4 is also shown to exacerbate neurodegeneration and neuroinflammation in a tau transgenic mouse model. To further evaluate the association of APOE genotype with the presence and severity of tau pathology, we express human tau via an adeno-associated virus gene delivery approach in human APOE targeted replacement mice. We find increased hyperphosphorylated tau species, tau aggregates, and behavioral abnormalities in mice expressing APOE ε2/ε2. We also show that in humans, the APOE ε2 allele is associated with increased tau pathology in the brains of progressive supranuclear palsy (PSP) cases. Finally, we identify an association between the APOE ε2/ε2 genotype and risk of tauopathies using two series of pathologically-confirmed cases of PSP and corticobasal degeneration. Our data together suggest APOE ε2 status may influence the risk and progression of tauopathy.
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- 2018
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29. Immediate Postoperative Alignment Following Bimedial Rectus Recession for Esotropia in Children Compared to Adults.
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Hassan MB, Diehl NN, and Mohney BG
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Esotropia physiopathology, Female, Follow-Up Studies, Humans, Infant, Male, Middle Aged, Retrospective Studies, Visual Acuity, Esotropia surgery, Oculomotor Muscles surgery, Ophthalmologic Surgical Procedures, Postoperative Period, Vision, Binocular physiology
- Abstract
Purpose: To determine whether the immediate postoperative alignment among patients undergoing successful bilateral weakening surgery for esotropia is different in children compared to adults., Methods: The medical records of all patients undergoing surgery for esotropia by a single surgeon at a major academic referral center between January 1, 2002, and July 1, 2014 (n = 544), were retrospectively reviewed. Exclusion criteria included those with prior strabismus surgery, unilateral surgery, strengthening procedures, vertical or superior oblique surgery, and those wearing hyperopic spectacles for accommodative esotropia. Additionally, all patients had to have a 1- and 6-week postoperative examination and 8 prism diopters (PD) or less of deviation at their 6-week examination., Results: Ninety-five (17.5%) of the 544 patients met the inclusion criteria. Surgery was performed at a median age of 3.7 years (range: 7 months to 86 years) for a median esodeviation of 35 PD (range: 12 to 70 PD). Among the 73 patients younger than 11 years, the immediate mean postoperative alignment was 9 PD of exotropia (range: 14 PD esotropia to 30 PD exotropia) compared to 2 PD of exotropia (range: 9 PD esotropia to 30 PD exotropia) in the 22 patients 11 years or older (P = .001). Seventy-one percent of successfully aligned patients younger than 11 years were exotropic in the immediate postoperative week compared to 23% of those 11 years or older (P < .001). Twenty-four (32.8%) of the younger cohort had an immediate overcorrection of 15 PD or more compared to 1 (4.5%) in the older cohort (P = .006)., Conclusions: Successful bilateral strabismus surgery for children with esotropia results in a significantly greater overcorrection, compared to adults, in the immediate postoperative period. [J Pediatr Ophthalmol Strabismus. 2018;55(5):299-305.]., (Copyright 2018, SLACK Incorporated.)
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- 2018
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30. APOE ε4 is associated with severity of Lewy body pathology independent of Alzheimer pathology.
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Dickson DW, Heckman MG, Murray ME, Soto AI, Walton RL, Diehl NN, van Gerpen JA, Uitti RJ, Wszolek ZK, Ertekin-Taner N, Knopman DS, Petersen RC, Graff-Radford NR, Boeve BF, Bu G, Ferman TJ, and Ross OA
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease complications, Case-Control Studies, Female, Genotype, Humans, Lewy Body Disease complications, Male, Alzheimer Disease pathology, Apolipoproteins E genetics, Brain pathology, Lewy Body Disease pathology
- Abstract
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.)
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- 2018
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31. Serum Electrolyte Levels and Outcomes in Patients Hospitalized with Hepatic Encephalopathy.
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Alsaad AA, Stancampiano FF, Palmer WC, Henry AM, Jackson JK, Heckman MG, Diehl NN, and Keaveny AP
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- Adult, Aged, Aged, 80 and over, Biomarkers blood, Female, Hepatic Encephalopathy diagnosis, Hepatic Encephalopathy etiology, Hepatic Encephalopathy therapy, Hospital Mortality, Humans, Length of Stay, Liver Cirrhosis blood, Liver Cirrhosis diagnosis, Liver Cirrhosis therapy, Male, Middle Aged, Predictive Value of Tests, Respiration, Artificial, Retrospective Studies, Risk Factors, Time Factors, Treatment Outcome, Young Adult, Electrolytes blood, Hepatic Encephalopathy blood, Liver Cirrhosis complications, Patient Admission
- Abstract
Introduction and Aims: Serum electrolyte derangements are common in patients with decompensated cirrhosis hospitalized for hepatic encephalopathy. There are limited data describing the association between electrolyte levels and outcomes in hepatic encephalopathy. We assessed the association between initial serum electrolyte values and outcomes in patients with hepatic encephalopathy., Material and Methods: A total of 385 consecutive patients hospitalized with encephalopathy were included in the study. Baseline electrolyte levels (sodium, potassium, chloride, bicarbonate, calcium and phosphorus) were measured at the time of admission and assessed for association with outcomes, which included survival, admission to the intensive care unit, requirement for mechanical ventilation, and length of hospital stay. P-values ≤ 0.0083 were considered significant after adjustment for multiple testing., Results: In unadjusted analysis, significant associations were identified regarding both bicarbonate and phosphorus (admission to intensive care unit), and calcium (mechanical ventilation); however these findings weakened and no longer approached statistical significance when adjusting for confounding variables. No other significant associations between serum electrolyte measurements and outcomes were observed., Conclusions: Our findings suggest that in patients hospitalized with encephalopathy, serum electrolyte measurements are not strong predictors of patient outcome.
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- 2018
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32. Impact of psychiatric comorbidities on outcomes of elderly liver transplant recipients.
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Niazi SK, Schneekloth TD, Vasquez AR, Keaveny AP, Davis S, Picco M, Heckman MG, Diehl NN, Jowsey-Gregoire SG, Rummans TA, and Burcin Taner C
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- Aged, Aged, 80 and over, Cohort Studies, Comorbidity, Female, Humans, Length of Stay trends, Male, Mental Disorders epidemiology, Middle Aged, Retrospective Studies, Risk Factors, Liver Transplantation psychology, Liver Transplantation trends, Mental Disorders psychology, Transplant Recipients psychology
- Abstract
Objectives: This study evaluated the impact of psychiatric comorbidities in liver transplant (LT) recipients aged ≥65 years (elderly) on length of hospital-stay (LOS), death, and a composite outcome of graft loss or death., Methods: This retrospective study assessed impact of psychiatric comorbidities in 122 elderly LT recipients and a matched group of 122 LT recipients aged <65 years (younger). Associations were assessed using adjusted multivariable regression models., Results: Among elderly, median age at LT was 68 years, most were males (62%), white (85%) and 61.7% had a history of any psychiatric diagnosis. Among younger, median age was 55, most were males (67.2%), white (77.5%) and 61.5% had any psychiatric diagnosis. Median LOS was 8 days for both groups. Among elderly, after a median follow-up of 5 years, 25.4% died and 29.5% experienced graft loss or death. History of adjustment disorder, history of depression, past psychiatric medication use, and pain prior to LT were associated with an increased risk of death or the composite graft loss or death. Perioperative use of SSRIs and lack of sleeping medication use were associated with longer LOS. Among aged <65, after median follow-up of 4.7 years, 21 patients (17%) died and 25 (20%) experienced graft loss or death; history of depression, perioperative SSRIs or sleeping medications use was associated with increased mortality and graft-loss or death., Conclusion: Six out of 10 patients among both elderly and younger cohorts had pre-LT psychiatric comorbidities, some of which adversely affected outcomes after LT., (Copyright © 2018 Elsevier Inc. All rights reserved.)
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- 2018
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33. Association of Total Fluid Intake and Output with Duration of Hospital Stay in Patients with Acute Pancreatitis.
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Koop AH, Stancampiano FF, Jackson J, Henry A, Horsley-Silva J, Pannala R, Heckman MG, Diehl NN, and Palmer WC
- Abstract
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.
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- 2018
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34. Daytime sleepiness in dementia with Lewy bodies is associated with neuronal depletion of the nucleus basalis of Meynert.
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Kasanuki K, Ferman TJ, Murray ME, Heckman MG, Pedraza O, Hanna Al-Shaikh FS, Mishima T, Diehl NN, van Gerpen JA, Uitti RJ, Wszolek ZK, Graff-Radford NR, and Dickson DW
- Subjects
- Aged, Aged, 80 and over, Autopsy, Disorders of Excessive Somnolence etiology, Female, Humans, Lewy Body Disease complications, Longitudinal Studies, Male, Middle Aged, Basal Forebrain pathology, Basal Nucleus of Meynert pathology, Disorders of Excessive Somnolence pathology, Lewy Body Disease pathology
- Abstract
Introduction: Excessive daytime sleepiness is a commonly reported clinical feature of dementia with Lewy bodies (DLB) that can occur early in the disease. Cholinergic depletion is known to be severe in DLB, even when dementia severity is mild. The nucleus basalis of Meynert serves as a primary source of cortical acetylcholine, and has a role in facilitating cortical activation and arousal. We sought to determine whether daytime sleepiness at the initial evaluation of patients with DLB was associated with neuronal loss in the nucleus basalis of Meynert., Methods: Autopsy-confirmed patients who met clinical criteria for probable DLB at their initial evaluation and who were administered the informant-completed Epworth Sleepiness Scale were included in the study (n = 40). Each patient had a dementia at baseline (80% with mild severity) and two or more features of parkinsonism, visual hallucinations, fluctuations, or probable REM sleep behavior disorder. Quantitative digital pathology of the nucleus basalis of Meynert was performed in the DLB group and in 20 non-DLB autopsy controls., Results: DLB had greater neuronal depletion in the nucleus basalis of Meynert (p < 0.0001) than pathologic controls. Sleepiness was present in 58% of the DLB group and those with daytime sleepiness had significantly lower neuron counts in the nucleus basalis of Meynert than their non-sleepy counterparts (p = 0.001). Regression modeling revealed that sleepiness was a stronger predictor of neuronal loss in the nucleus basalis of Meynert than visual hallucinations, fluctuations or dementia severity (p = 0.003)., Conclusions: Excessive daytime sleepiness in early DLB is indicative of a more profound loss of basal forebrain cholinergic integrity., (Copyright © 2018 Elsevier Ltd. All rights reserved.)
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- 2018
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35. Nontuberculous Mycobacterial Infections of the Upper Extremity: 15-Year Experience at a Tertiary Care Medical Center.
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Sotello D, Garner HW, Heckman MG, Diehl NN, Murray PM, and Alvarez S
- Subjects
- Adult, Age Distribution, Aged, Aged, 80 and over, Anti-Bacterial Agents therapeutic use, Arthritis, Infectious epidemiology, Arthritis, Infectious microbiology, Arthritis, Infectious therapy, Debridement, Delayed Diagnosis, Drainage, Female, Florida epidemiology, Granuloma diagnostic imaging, Granuloma microbiology, Humans, Immunocompromised Host, Male, Middle Aged, Mycobacterium Infections, Nontuberculous epidemiology, Osteomyelitis epidemiology, Osteomyelitis microbiology, Osteomyelitis therapy, Retrospective Studies, Risk Factors, Sex Distribution, Synovectomy, Tenosynovitis epidemiology, Tenosynovitis microbiology, Tenosynovitis therapy, Tertiary Care Centers, Upper Extremity surgery, Young Adult, Mycobacterium Infections, Nontuberculous diagnosis, Mycobacterium Infections, Nontuberculous therapy, Upper Extremity microbiology
- Abstract
Purpose: To present our experience with culture-positive, nontuberculous mycobacterial infections (NTMI) of the upper extremity and to compare the clinical features and outcomes of treatment among immunocompetent and immunocompromised patients., Methods: All patients at our medical center diagnosed with NTMI of the upper extremity from December 1, 2000, through December 31, 2015, were included. We performed a retrospective analysis of patient demographic characteristics, delay to diagnosis, risk factors, clinical presentation, specific location, diagnostic testing, treatment regimens, and outcomes. These variables were compared between immunocompetent and immunocompromised patients., Results: Forty-four patients were identified with culture-positive NTMI of the upper extremity. Of the patients, 27 (61%) were men (median age, 59 years [range, 23-83 years]). Twenty (45%) patients were immunocompromised. Immunocompromised patients had fewer known inoculation injuries compared with immunocompetent patients (45% vs 92%). A significant difference existed in the treatment regimens selected for immunocompetent versus immunocompromised patients: immunocompetent patients were more often treated with both antibiotics and surgery (88% vs 50%), whereas immunocompromised patients were more often treated with antibiotics alone (45% vs 4%). Overall, 24% experienced treatment failure and 9% died. Outcomes were relatively similar between immunocompetent and immunocompromised patients. A shorter delay to diagnosis was associated with a lower failure rate., Conclusions: Diagnosis of upper-extremity NTMI is often delayed because of indolent presentation and lack of clinical suspicion. The clinical presentation, diagnostic delay, and diagnostic testing results are similar between immunocompetent and immunocompromised patients. Although treatment varied significantly between patient groups, outcomes were similar. Timely diagnosis has the greatest impact on patient outcome., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2018 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)
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- 2018
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36. Mortality and Cerebrovascular Events After Heart Rhythm Disorder Management Procedures.
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Lee JZ, Ling J, Diehl NN, Hodge DO, Padmanabhan D, Killu AM, Madhavan M, Noseworthy PA, Kapa S, McLeod CJ, Cha YM, Deshmukh AJ, Srivathsan K, Kusumoto FM, Shen WK, Friedman PA, Munger TM, Asirvatham SJ, Packer DL, and Mulpuru SK
- Subjects
- Ablation Techniques mortality, Aged, Aged, 80 and over, Arrhythmias, Cardiac diagnosis, Arrhythmias, Cardiac mortality, Arrhythmias, Cardiac physiopathology, Cardiac Surgical Procedures adverse effects, Cardiac Surgical Procedures instrumentation, Cardiac Surgical Procedures trends, Cardiac Tamponade mortality, Cause of Death, Defibrillators, Implantable, Device Removal mortality, Electrophysiologic Techniques, Cardiac mortality, Female, Humans, Ischemic Attack, Transient diagnosis, Male, Middle Aged, Pacemaker, Artificial, Prosthesis Implantation mortality, Retrospective Studies, Risk Assessment, Risk Factors, Stroke diagnosis, Stroke mortality, Time Factors, Treatment Outcome, United States epidemiology, Arrhythmias, Cardiac therapy, Cardiac Surgical Procedures mortality, Hospital Mortality trends, Ischemic Attack, Transient mortality, Stroke epidemiology
- Abstract
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.)
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- 2018
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37. Age- and disease-dependent increase of the mitophagy marker phospho-ubiquitin in normal aging and Lewy body disease.
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Hou X, Fiesel FC, Truban D, Castanedes Casey M, Lin WL, Soto AI, Tacik P, Rousseau LG, Diehl NN, Heckman MG, Lorenzo-Betancor O, Ferrer I, Arbelo JM, Steele JC, Farrer MJ, Cornejo-Olivas M, Torres L, Mata IF, Graff-Radford NR, Wszolek ZK, Ross OA, Murray ME, Dickson DW, and Springer W
- Subjects
- Aged, Aged, 80 and over, Brain metabolism, Brain ultrastructure, Cohort Studies, Female, HeLa Cells, Humans, Male, Middle Aged, Mutation genetics, Phosphorylation, Phosphoserine metabolism, Protein Binding, alpha-Synuclein metabolism, tau Proteins metabolism, Aging metabolism, Biomarkers metabolism, Lewy Body Disease metabolism, Lewy Body Disease pathology, Mitophagy, Ubiquitin metabolism
- Abstract
Although exact causes of Parkinson disease (PD) remain enigmatic, mitochondrial dysfunction is increasingly appreciated as a key determinant of dopaminergic neuron susceptibility in both familial and sporadic PD. Two genes associated with recessive, early-onset PD encode the ubiquitin (Ub) kinase PINK1 and the E3 Ub ligase PRKN/PARK2/Parkin, which together orchestrate a protective mitochondrial quality control (mitoQC) pathway. Upon stress, both enzymes cooperatively identify and decorate damaged mitochondria with phosphorylated poly-Ub (p-S65-Ub) chains. This specific label is subsequently recognized by autophagy receptors that further facilitate mitochondrial degradation in lysosomes (mitophagy). Here, we analyzed human post-mortem brain specimens and identified distinct pools of p-S65-Ub-positive structures that partially colocalized with markers of mitochondria, autophagy, lysosomes and/or granulovacuolar degeneration bodies. We further quantified levels and distribution of the 'mitophagy tag' in 2 large cohorts of brain samples from normal aging and Lewy body disease (LBD) cases using unbiased digital pathology. Somatic p-S65-Ub structures independently increased with age and disease in distinct brain regions and enhanced levels in LBD brain were age- and Braak tangle stage-dependent. Additionally, we observed significant correlations of p-S65-Ub with LBs and neurofibrillary tangle levels in disease. The degree of co-existing p-S65-Ub signals and pathological PD hallmarks increased in the pre-mature stage, but decreased in the late stage of LB or tangle aggregation. Altogether, our study provides further evidence for a potential pathogenic overlap among different forms of PD and suggests that p-S65-Ub can serve as a biomarker for mitochondrial damage in aging and disease., Abbreviations: BLBD: brainstem predominant Lewy body disease; CCCP: carbonyl cyanide m-chlorophenyl hydrazone; DLB: dementia with Lewy bodies; DLBD: diffuse neocortical Lewy body disease; EOPD: early-onset Parkinson disease; GVB: granulovacuolar degeneration body; LB: Lewy body; LBD: Lewy body disease; mitoQC: mitochondrial quality control; nbM: nucleus basalis of Meynert; PD: Parkinson disease; PDD: Parkinson disease with dementia; p-S65-Ub: PINK1-phosphorylated serine 65 ubiquitin; SN: substantia nigra; TLBD: transitional Lewy body disease; Ub: ubiquitin.
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- 2018
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38. Stereotactic Body Radiotherapy for Medically Inoperable Stage I-II Non-Small Cell Lung Cancer: The Mayo Clinic Experience.
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Hobbs CJ, Ko SJ, Paryani NN, Accurso JM, Olivier KR, Garces YI, Park SS, Hallemeier CL, Schild SE, Vora SA, Ashman JB, Rule WG, Bowers JR, Heckman MG, Diehl NN, and Miller RC
- Abstract
Objective: To examine disease control and survival after stereotactic body radiotherapy (SBRT) for medically inoperable, early-stage non-small cell lung cancer (NSCLC) and determine associations of pretreatment
18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) maximum standardized uptake values (SUVmax), biologically effective dose, and mediastinal staging with disease control and survival outcomes., Patients and Methods: We retrospectively reviewed the cases of consecutive patients with FDG-PET-staged, medically inoperable NSCLC treated with SBRT at our institution between January 1, 2008, and August 4, 2014. Cumulative incidences of recurrence were estimated, accounting for the competing risk of death. Associations of SUVmax, biologically effective dose, and mediastinal staging with outcomes were evaluated using Cox proportional hazards regression models., Results: Among 282 patients, 2-year cumulative incidences of recurrence were 4.9% (95% CI, 2.6%-8.3%) for local, 9.8% (95% CI, 6.3%-14.2%) for nodal, 10.8% (95% CI, 7.0%-15.5%) for ipsilateral lung, 6.0% (3.3%-9.8%) for contralateral lung, 9.7% (95% CI, 6.3%-14.0%) for distant recurrence, and 26.1% (95% CI, 20.4%-32.0%) for any recurrence. The 2-year overall survival was 70.4% (95% CI, 64.5%-76.8%), and the 2-year disease-free survival was 51.2% (95% CI, 44.9%-58.5%). Risk of any recurrence was significantly higher for patients with higher SUVmax (hazard ratio [per each doubling], 1.29 [95% CI, 1.05-1.59]; P =.02). A similar association with SUVmax was observed when considering the composite outcome of any recurrence or death (hazard ratio, 1.23 [95% CI, 1.05-1.44]; P =.01). The SUVmax was not significantly associated with other outcomes ( P ≥0.69). Two-year cumulative incidences of local recurrence for patients receiving 48 Gy in 4 fractions, 54 Gy in 3 fractions, or 50 Gy in 5 fractions were 1.7% (95% CI, 0.3%-5.6%), 3.7% (95% CI, 0.7%-11.4%), and 15.3% (95% CI, 5.9%-28.9%), respectively ( P =.02); this difference was independent of lesion size ( P =.02)., Conclusion: Disease control was excellent for patients who received SBRT for early-stage NSCLC, and this series represents the largest single-institution experience from the United States on SBRT for early-stage inoperable NSCLC. Higher pretreatment FDG-PET SUVmax was associated with increased risk of any recurrence, and the 50 Gy in 5 fractions dose prescription was associated with increased risk of local recurrence.- Published
- 2017
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39. Thromboelastography as a Predictor of Outcomes Following Liver Transplantation.
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Trautman CL, Palmer WC, Taner CB, Canabal JM, Getz T, Goldman A, Heckman MG, Diehl NN, Lee DD, and Stancampiano FF
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- Adult, Aged, Female, Humans, Length of Stay statistics & numerical data, Male, Middle Aged, Postoperative Period, Predictive Value of Tests, Retrospective Studies, Risk Factors, Thrombelastography methods, Treatment Outcome, Hemorrhage etiology, Liver Transplantation adverse effects, Postoperative Complications etiology, Primary Graft Dysfunction etiology, Thrombelastography statistics & numerical data
- Abstract
Background: Thromboelastography (TEG) has been used perioperatively during liver transplantation (LT) to provide a real-time global hemostasis assessment for targeted blood product replacement. We aimed to analyze the relationship between post-LT TEG results and outcomes., Methods: We retrospectively analyzed patients undergoing LT from November 2008 to December 2014 at Mayo Clinic Florida. All 441 single-organ 1st-time LT patients aged ≥18 years requiring post-LT intensive care unit management were included. TEG parameters including r time, k time, α angle, and maximum amplitude were measured regularly during the first 24 hours after LT. Outcomes included return to the operating room secondary to bleeding, length of hospitalization, survival, and early allograft dysfunction., Results: A prolonged and/or lengthening r time, k time, and r+k time were all independently associated with increased length of hospitalization after LT. Increased maximum amplitude on the first post-LT TEG was associated with early allograft dysfunction. No notable associations of TEG parameters with survival or return to operating room were observed., Conclusions: The association of absolute and temporal TEG value changes with increased length of hospitalization and early allograft dysfunction suggests that TEG may have a role in identifying patients at high risk for these outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2017
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40. Parkinson's disease susceptibility variants and severity of Lewy body pathology.
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Heckman MG, Kasanuki K, Diehl NN, Koga S, Soto A, Murray ME, Dickson DW, and Ross OA
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- Aged, Autopsy, Brain pathology, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Lewy Bodies pathology, Parkinson Disease genetics, Parkinson Disease pathology
- Abstract
Introduction: Meta-analyses of genome-wide association studies (GWAS) have established common genetic risk factors for clinical Parkinson's disease (PD); however, associations between these risk factors and quantitative neuropathologic markers of disease severity have not been well-studied. This study evaluated associations of nominated variants from the most recent PD GWAS meta-analysis with Lewy body disease (LBD) subtype (brainstem, transitional, or diffuse) and pathologic burden of LB pathology as measured by LB counts in five cortical regions in a series of LBD cases., Methods: 547 autopsy-confirmed cases of LBD were included and genotyped for 29 different GWAS-nominated PD risk variants. LB counts were measured in middle frontal (MF), superior temporal (ST), inferior parietal (IP), cingulate (CG), and parahippocampal (PH) gyri., Results: None of the variants examined were significantly associated with LB counts in any brain region or with LBD subtype after correcting for multiple testing. Nominally significant (P < 0.05) associations with LB counts where the direction of association was in agreement with that observed in the PD GWAS meta-analysis were observed for variants in BCKDK/STX1B (MF, ST, IP) and SNCA (ST). Additionally, MIR4697 and BCKDK/STX1B variants were nominally associated with LBD subtype., Conclusion: The lack of a significant association between PD GWAS variants and severity of LB pathology is consistent with the generally subtle association odds ratios that have been observed in disease-risk analysis. These results also suggest that genetic factors other than the susceptibility loci may determine quantitative neuropathologic outcomes in patients with LBD., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2017
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41. Regional analysis and genetic association of nigrostriatal degeneration in Lewy body disease.
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Kasanuki K, Heckman MG, Diehl NN, Murray ME, Koga S, Soto A, Ross OA, and Dickson DW
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- Aged, Aged, 80 and over, Dementia classification, Dementia genetics, Endophenotypes, Female, Humans, Lewy Body Disease classification, Lewy Body Disease genetics, Male, Parkinson Disease classification, Parkinson Disease genetics, Tyrosine 3-Monooxygenase immunology, Dementia pathology, Genetic Association Studies, Lewy Body Disease pathology, Parkinson Disease pathology, Putamen pathology, Substantia Nigra pathology
- Abstract
Background: A 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., Objectives: We 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., Methods: The 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., Results: When 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., Conclusions: The 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., (© 2017 International Parkinson and Movement Disorder Society.)
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- 2017
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42. Guiding Patients Toward the Appropriate Surgical Treatment for Obesity: Should Presurgery Psychological Correlates Influence Choice Between Roux-en-Y Gastric Bypass and Vertical Sleeve Gastrectomy?
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Ames GE, Heckman MG, Diehl NN, Shepherd DM, Holgerson AA, Grothe KB, Kellogg TA, Bowers SP, and Clark MM
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- Adult, Affect physiology, Bariatric Surgery adverse effects, Bariatric Surgery psychology, Cohort Studies, Eating psychology, Female, Gastrectomy methods, Gastrectomy psychology, Gastric Bypass methods, Gastric Bypass psychology, Health Behavior physiology, Humans, Male, Middle Aged, Weight Loss physiology, Bariatric Surgery methods, Choice Behavior, Decision Making, Obesity, Morbid psychology, Obesity, Morbid surgery
- Abstract
Background: Helping patients determine which type of bariatric surgery, Roux-en-Y gastric bypass (RYGB) or vertical sleeve gastrectomy (VSG), may be the best treatment can be challenging. This study investigated psychological correlates and their influence on weight loss for patients who underwent RYGB or VSG., Methods: Four hundred twenty-two patients (RYGB = 305; VSG = 117) completed screening questionnaires presurgery and underwent surgery between August 2012 and April 2015. Associations between demographics and questionnaires with percentage weight change were evaluated using multivariable linear regression models., Results: Median age was 48 years and median BMI 45.3 kg/m2 presurgery. Median percentage changes in weight from baseline to years 1 and 2 follow-up were - 31.5% (range - 52.2 to - 9.2%) and - 31.2% (range - 50.0 to - 1.2%) for RYGB and 25.3% (range - 49.8 to - 4.7%) and - 23.3% (range - 58.9 to - 1.6%) for VSG, respectively. Linear regression models revealed that younger patients lost more weight than older patients at years 1 (RYGB p < 0.0001; VSG p = 0.0001) and 2 (RYGB p = 0.005; VSG p = 0.002). No psychological correlates were significantly associated with weight loss outcomes. Post hoc analyses comparing patients who had surgery to those in the same cohort who did not have surgery revealed significantly higher rates of depression (p < 0.001), anxiety (p < 0.001), binge eating (p = 0.003), night eating (p < 0.001), food addiction (p = 0.042), and lower self-efficacy (p < 0.001) among patients who did not have surgery., Discussion: Patients who are psychologically higher functioning are more likely to complete the evaluation process and undergo bariatric surgery. For patients who had surgery, psychological correlates were not associated with weight loss outcome for either RYGB or VSG. Implications for surgical choice are discussed.
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- 2017
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43. Incidence and Types of Pediatric Nystagmus.
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Nash DL, Diehl NN, and Mohney BG
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- Adolescent, Age Distribution, Age of Onset, Child, Child, Preschool, Developmental Disabilities epidemiology, Eye Diseases epidemiology, Female, Humans, Incidence, Infant, Infant, Newborn, Male, Minnesota epidemiology, Nystagmus, Pathologic diagnosis, Retrospective Studies, Sex Distribution, Visual Acuity, Nystagmus, Pathologic classification, Nystagmus, Pathologic epidemiology
- Abstract
Purpose: To report the incidence, prevalent subtypes, and clinical characteristics of pediatric nystagmus diagnosed over a 30-year period., Design: Retrospective, population-based study., Methods: Using the Rochester Epidemiology Project, we reviewed the medical records of all children (<19 years) diagnosed as residents in Olmsted County, Minnesota, with any form of nystagmus from January 1, 1976, through December 31, 2005., Results: Seventy-one children were diagnosed during the 30-year period, yielding an annual incidence of 6.72 per 100,000 younger than 19 years (95% confidence interval [CI], 5.15-8.28) Infantile nystagmus, onset by 6 months, comprised 62 (87.3%) of the study patients, corresponding to a birth prevalence of 1 in 821. The median age at diagnosis for the cohort was 12.7 months (range, 0 days to 18.6 years) and 42 subjects (59.2%) were male. The main types of nystagmus, in declining order, were nystagmus associated with retinal/optic nerve disease in 23 (32.4%), idiopathic or congenital motor nystagmus in 22 (31.0%), manifest latent nystagmus or latent nystagmus in 17 (24.0%), and 2 (2.8%) each associated with Chiari malformation, medication use, tumor of the central nervous system, and no diagnosis. Developmental delay was diagnosed in 31 (43.6%), strabismus in 25 (35.2%), and amblyopia in 10 (14.1%). Eighty percent had 20/40 (or equivalent) or better vision at presentation in at least 1 eye., Conclusions: This study provides population-based data on incidence and clinical characteristics of childhood nystagmus in North America. Idiopathic and nystagmus associated with retinal/optic nerve disease were the most common presentations, with most patients having good vision. Developmental delay, strabismus, and amblyopia were common in this cohort., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
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44. Trends in Sexual Function After Breast Cancer Surgery.
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Cornell LF, Mussallem DM, Gibson TC, Diehl NN, Bagaria SP, and McLaughlin SA
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- Adult, Aged, Female, Humans, Mastectomy, Segmental adverse effects, Middle Aged, Prophylactic Mastectomy adverse effects, Sexual Dysfunction, Physiological physiopathology, Surveys and Questionnaires, Breast Neoplasms surgery, Mastectomy adverse effects, Sexual Dysfunction, Physiological etiology, Sexuality
- Abstract
Purpose: Sexual dysfunction is assumed to be common, but understudied, in breast cancer patients. Herein, we use the validated female sexual functioning index (FSFI) to evaluate changes in female sexual function after breast cancer surgery., Methods: The FSFI assesses sexual function in six domains (desire, arousal, lubrication, orgasm, satisfaction, pain) on a 36-point scale, with scores >26.6 indicating better sexual function. We identified 226 women with unilateral breast cancer undergoing surgery at our institution from June 2010-January 2015. All completed the FSFI preoperatively and at a median of 13 months postoperatively. We quantified declines in FSFI scores and considered p-values <0.05 statistically significant., Results: Overall, 119 women had breast-conserving surgery (BCS), 40 had unilateral mastectomy (UM), and 67 had UM plus contralateral prophylactic mastectomy (CPM). All women had similar baseline FSFI scores (medians: BCS, 26.3; UM, 25.2; UM+CPM, 23.7; p = 0.23). At follow-up, sexual function had declined significantly in BCS (23.5; p < 0.001) and UM (17.4; p = 0.010), but was unchanged in UM+CPM (22.8; p = 0.74) women. Interestingly, all women maintained their desire for sex (p = 0.17). BCS and UM women demonstrated significant declines in all other subscale domains (all p < 0.045). UM+CPM women demonstrated no decline in any subscale domain, yet did not exhibit superior sexual function to those having UM or BCS (medians: BCS, 23.5; UM, 17.4; UM+CPM, 22.8; p = 0.21)., Conclusions: Baseline sexual dysfunction exists in women diagnosed with breast cancer. Surgery negatively impacts sexual function. Patients who choose mastectomy do not exhibit superior sexual function over those having BCS at 13 months following surgery.
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- 2017
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45. Phosphorylated neurofilament heavy chain: A biomarker of survival for C9ORF72-associated amyotrophic lateral sclerosis.
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Gendron TF, Daughrity LM, Heckman MG, Diehl NN, Wuu J, Miller TM, Pastor P, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Benatar M, Silani V, Glass JD, Floeter MK, Jeromin A, Boylan KB, and Petrucelli L
- Subjects
- Adult, Aged, Aged, 80 and over, Amyotrophic Lateral Sclerosis cerebrospinal fluid, Biomarkers cerebrospinal fluid, C9orf72 Protein, Case-Control Studies, Disease Progression, Female, Humans, Male, Middle Aged, Phosphorylation, Survival Analysis, Young Adult, Amyotrophic Lateral Sclerosis genetics, Neurofilament Proteins cerebrospinal fluid, Proteins genetics
- Abstract
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., (© 2017 The Authors Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)
- Published
- 2017
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46. Impact of an Endoscopic Quality Improvement Program Focused on Adenoma Detection on Sessile Serrated Adenoma/Polyp Detection.
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Racho RG, Krishna M, Coe SG, Thomas CS, Crook JE, Diehl NN, and Wallace MB
- Subjects
- Adenoma diagnostic imaging, Colonic Polyps diagnostic imaging, Colorectal Neoplasms diagnostic imaging, Humans, Hyperplasia, Prospective Studies, Retrospective Studies, Tumor Burden, Adenoma pathology, Colonic Polyps pathology, Colonoscopy education, Colonoscopy standards, Colorectal Neoplasms pathology, Quality Improvement
- Abstract
Background: Sessile serrated adenomas/polyps (SSA/P) are an under-recognized disease with a unique malignant pathway. Improved endoscopic recognition and pathological interpretation is needed., Aims: To determine whether an educational intervention that improved adenoma detection rate (ADR) could improve SSA/P detection rate after reclassification of previously termed "hyperplastic" polyps., Methods: We reanalyzed data from a prospective randomized trial of an educational intervention aimed at increasing ADR. All hyperplastic polyps ≥6 mm reported in a previously published study were rereviewed and reclassified using standardized criteria for serrated lesions. Detection rates of sessile serrated adenomas/polyps and other clinically relevant serrated polyps were calculated in the baseline and post-training phases of the original study., Results: Of 263 available for rereview, 33 (12.5%) were reclassified as SSA/P (N = 32) or traditional serrated adenoma (TSA) (N = 1). Reclassification was more common in the right colon (18 vs. 8%, p = 0.02). Baseline SSA/P detection rate was 0.7% in the untrained group and 1.3% in the trained group. Post-training, the SSA/P detection rate increased to 2.1 and 1.5%, respectively. The clinically relevant serrated polyp detection rate at baseline was 14.2% in the untrained group and 11.3% in the trained group. After the educational intervention, the clinically relevant serrated polyp detection rates increased to 16.5 and 14.8% in the untrained and trained groups, respectively. The estimated odds of an endoscopist detecting either a SSA/P or other clinically relevant serrated polyp during colonoscopy increased by only 3% with the educational intervention (OR 1.03, 95% CI 0.61-1.74, p = 0.91)., Conclusions: Pathological re-interpretation of larger serrated polyps resulted in the reclassification of 12.5% of lesions. Quality improvement methods focused on adenoma detection did not impact SSA/P detection, and thus specific methods for serrated polyp detection are needed.
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- 2017
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47. Timing interval from peri-prostatic block to biopsy impacts procedural pain.
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Pathak RA, Thiel DD, Parker A, Heckman MG, Crook JE, Diehl NN, Tavlarides A, Alford SW, and Igel TC
- Subjects
- Adult, Aged, Aged, 80 and over, Humans, Male, Middle Aged, Pain Measurement, Prospective Studies, Time Factors, Anesthesia, Local, Anesthetics, Local administration & dosage, Endoscopic Ultrasound-Guided Fine Needle Aspiration adverse effects, Lidocaine administration & dosage, Pain, Procedural prevention & control, Prostate pathology
- Abstract
Introduction: To compare visual analog scale (VAS) pain scores between patients with a 2-minute versus 10-minute delay of peri-prostatic lidocaine injection prior to transrectal ultrasound-guided prostate biopsies (TRUS-bx)., Materials and Methods: Eighty patients who underwent standard 12-core TRUS-bx by a single surgeon were prospectively randomized into four different treatment arms: bibasilar injection with a 2-minute delay, bibasilar injection plus a single apical injection with a 2-minute delay, bibasilar injection with a 10-minute delay, and bibasilar injection plus a single apical injection with a 10-minute delay. Patients were asked to report their level of pain on the VAS (0-10, with 10 indicating unbearable pain) at the following intervals: probe insertion (baseline), after each core, and post-procedure. The primary outcome measure was mean VAS score across all 12 cores minus baseline VAS score, which we refer to baseline-adjusted mean VAS score., Results: Baseline-adjusted mean VAS score was significantly higher for the 2-minute delay group compared to the 10-minute delay group (mean: -0.7 versus -1.6, p = 0.025). Subset analysis of biopsies 1-3, 4-6, 7-9 and 10-12 also demonstrated higher baseline-adjusted mean VAS scores in the 2-minute delay group (all p ≤ 0.043)., Conclusions: Lower TRUS-bx VAS scores can be achieved by extending the time from lidocaine injection to onset of prostate biopsy from 2 to 10 minutes.
- Published
- 2017
48. Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72 -associated amyotrophic lateral sclerosis.
- Author
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Gendron TF, Chew J, Stankowski JN, Hayes LR, Zhang YJ, Prudencio M, Carlomagno Y, Daughrity LM, Jansen-West K, Perkerson EA, O'Raw A, Cook C, Pregent L, Belzil V, van Blitterswijk M, Tabassian LJ, Lee CW, Yue M, Tong J, Song Y, Castanedes-Casey M, Rousseau L, Phillips V, Dickson DW, Rademakers R, Fryer JD, Rush BK, Pedraza O, Caputo AM, Desaro P, Palmucci C, Robertson A, Heckman MG, Diehl NN, Wiggs E, Tierney M, Braun L, Farren J, Lacomis D, Ladha S, Fournier CN, McCluskey LF, Elman LB, Toledo JB, McBride JD, Tiloca C, Morelli C, Poletti B, Solca F, Prelle A, Wuu J, Jockel-Balsarotti J, Rigo F, Ambrose C, Datta A, Yang W, Raitcheva D, Antognetti G, McCampbell A, Van Swieten JC, Miller BL, Boxer AL, Brown RH, Bowser R, Miller TM, Trojanowski JQ, Grossman M, Berry JD, Hu WT, Ratti A, Traynor BJ, Disney MD, Benatar M, Silani V, Glass JD, Floeter MK, Rothstein JD, Boylan KB, and Petrucelli L
- Subjects
- Adult, Aged, Amyotrophic Lateral Sclerosis cerebrospinal fluid, Amyotrophic Lateral Sclerosis pathology, Animals, Brain metabolism, Brain pathology, Cell Line, Humans, Induced Pluripotent Stem Cells drug effects, Induced Pluripotent Stem Cells metabolism, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear metabolism, Longitudinal Studies, Mice, Middle Aged, Neurons metabolism, Oligonucleotides, Antisense pharmacology, Prognosis, RNA genetics, Amyotrophic Lateral Sclerosis genetics, Biomarkers metabolism, C9orf72 Protein genetics, Dinucleotide Repeats genetics
- Abstract
There is no effective treatment for amyotrophic lateral sclerosis (ALS), a devastating motor neuron disease. However, discovery of a G
4 C2 repeat expansion in the C9ORF72 gene as the most common genetic cause of ALS has opened up new avenues for therapeutic intervention for this form of ALS. G4 C2 repeat expansion RNAs and proteins of repeating dipeptides synthesized from these transcripts are believed to play a key role in C9ORF72 -associated ALS (c9ALS). Therapeutics that target G4 C2 RNA, such as antisense oligonucleotides (ASOs) and small molecules, are thus being actively investigated. A limitation in moving such treatments from bench to bedside is a lack of pharmacodynamic markers for use in clinical trials. We explored whether poly(GP) proteins translated from G4 C2 RNA could serve such a purpose. Poly(GP) proteins were detected in cerebrospinal fluid (CSF) and in peripheral blood mononuclear cells from c9ALS patients and, notably, from asymptomatic C9ORF72 mutation carriers. Moreover, CSF poly(GP) proteins remained relatively constant over time, boding well for their use in gauging biochemical responses to potential treatments. Treating c9ALS patient cells or a mouse model of c9ALS with ASOs that target G4 C2 RNA resulted in decreased intracellular and extracellular poly(GP) proteins. This decrease paralleled reductions in G4 C2 RNA and downstream G4 C2 RNA-mediated events. These findings indicate that tracking poly(GP) proteins in CSF could provide a means to assess target engagement of G4 C2 RNA-based therapies in symptomatic C9ORF72 repeat expansion carriers and presymptomatic individuals who are expected to benefit from early therapeutic intervention., (Copyright © 2017, American Association for the Advancement of Science.)- Published
- 2017
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49. Impact of Minimally Invasive Benign Prostatic Hyperplasia Therapies on 30- and 90-Day Postoperative Office Encounters.
- Author
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Pathak RA, Broderick GA, Igel TC, Petrou SP, Young PR, Wehle MJ, Heckman MG, Diehl NN, Vargas ER, Shah K, and Thiel DD
- Subjects
- Aged, Aged, 80 and over, Follow-Up Studies, Humans, Incidence, Laser Therapy adverse effects, Laser Therapy methods, Male, Middle Aged, Minimally Invasive Surgical Procedures methods, Prognosis, Prostatic Hyperplasia complications, Retrospective Studies, Time Factors, Transurethral Resection of Prostate methods, Treatment Outcome, United States epidemiology, Urinary Bladder Neck Obstruction surgery, Minimally Invasive Surgical Procedures adverse effects, Office Visits trends, Postoperative Complications epidemiology, Prostatic Hyperplasia surgery, Risk Assessment methods, Transurethral Resection of Prostate adverse effects, Urinary Bladder Neck Obstruction etiology
- Abstract
Objective: To compare the frequency of postoperative encounters in the 30-day and 90-day postoperative periods for various bladder outlet obstruction surgical therapies., Materials and Methods: All patients who underwent transurethral resection of the prostate (TURP), GreenLight laser photovaporization of the prostate (GL-PVP) (American Medical Systems Inc.), and holmium laser enucleation of the prostate (HoLEP) from January 1, 2012 to December 31, 2014 were followed for 6 months postoperatively. All postoperative encounters such as patient calls or questions, catheter exchanges or removals, and hospital-based readmissions or emergency department visits were recorded in the electronic medical record., Results: Two hundred and ninety-one consecutive patients underwent outlet procedures during the study period: TURP (N = 199; mean age, 71 years; mean body mass index [BMI], 28.5), HoLEP (N = 60; mean age, 68 years; mean BMI, 28.1), or GL-PVP (N = 32; mean age, 72 years; mean BMI, 29.3). No statistically significant difference was observed for age, BMI, preoperative American Urological Association symptom score, or preoperative maximum flow velocity between the 3 groups. Thirty-day postoperative encounters differed significantly between the 3 surgery types (P < .001). Specifically, there were fewer encounters within 30 days of surgery for TURP compared to both HoLEP (≥1 encounter: TURP = 48.7%, HoLEP = 66.7%; P = .006) and GL-PVP (≥1 encounter: TURP = 48.7%, GL-PVP = 93.7%; P < .001). The number of encounters within 90 days postoperatively was also significantly lower for TURP patients (P < .001)., Conclusion: TURP results in fewer postoperative encounters in both the 30-day and 90-day postoperative periods compared to HoLEP and GL-PVP. Laser prostate therapies may place increased burden on clinic staff during the 30-day and 90-day postoperative periods., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
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50. Endoscopic mucosal resection: learning curve for large nonpolypoid colorectal neoplasia.
- Author
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Bhurwal A, Bartel MJ, Heckman MG, Diehl NN, Raimondo M, Wallace MB, and Woodward TA
- Subjects
- Adenoma pathology, Adult, Aged, Aged, 80 and over, Colonic Polyps pathology, Colonic Polyps surgery, Colonoscopy, Colorectal Neoplasms pathology, Female, Humans, Male, Middle Aged, Neoplasm, Residual, Tumor Burden, Young Adult, Adenoma surgery, Clinical Competence, Colorectal Neoplasms surgery, Endoscopic Mucosal Resection adverse effects, Gastrointestinal Hemorrhage etiology, Learning Curve
- Abstract
Background and Aims: Colorectal EMR for nonpolypoid neoplasia achieves better outcomes when performed by expert endoscopists. The time point at which the endoscopist achieves expert level remains to be defined. The objective of this study was to establish a learning curve of colorectal EMR for nonpolypoid neoplasia based on residual tissue on surveillance colonoscopy and adverse event rate., Methods: Five hundred seventy-eight consecutive patients underwent EMR of colorectal neoplasia by 1 of 3 primary endoscopists between December 2004 and September 2013 in a tertiary academic center. Primary analyses focused on the largest lesion for patients with more than 1 lesion (median age, 69 years; median polyp size, 30 mm; 51% en bloc resection). Data on surveillance colonoscopy were available for 74%. Learning curves were calculated for each of the 3 main outcome measurements: the presence of residual neoplasia on surveillance colonoscopy, endoscopic assessment of incomplete EMR, and the occurrence of an immediate bleeding adverse event., Results: Residual neoplasia on surveillance colonoscopy was present for 23.2% of patients, the rate of endoscopist-assessed incomplete EMR was 27.6%, and immediate bleeding adverse events occurred in 6.9% of patients. Although there was between-endoscopist variability, the overall rates of residual neoplasia and incomplete EMR decreased to below 20% to 25% after 100 EMRs; initial decreases in both rates were observed for earlier EMRs. Immediate bleeding adverse events occurred at a low frequency for each endoscopist across all EMRs. Perforation requiring surgical intervention occurred in 1 patient (0.2%)., Conclusions: This study demonstrated that an unexpectedly high number of 100 colorectal EMR procedures for large nonpolypoid colorectal neoplasia are required to achieve a plateau phase for crucial outcomes., (Copyright © 2016 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF
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