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Article ; Online: Pathologically based criteria to distinguish essential tremor from controls: analyses of the human cerebellum.

Faust, Phyllis L / McCreary, Morgan / Musacchio, Jessica B / Kuo, Sheng-Han / Vonsattel, Jean-Paul G / Louis, Elan D

Annals of clinical and translational neurology

2024

Abstract: Objective: Essential tremor is among the most prevalent neurological diseases. Diagnosis is based entirely on neurological evaluation. Historically, there were few postmortem brain studies, hindering attempts to develop pathologically based criteria to ... ...

Abstract	Objective: Essential tremor is among the most prevalent neurological diseases. Diagnosis is based entirely on neurological evaluation. Historically, there were few postmortem brain studies, hindering attempts to develop pathologically based criteria to distinguish essential tremor from control brains. However, an intensive effort to bank essential tremor brains over recent years has resulted in postmortem studies involving >200 brains, which have identified numerous degenerative changes in the essential tremor cerebellar cortex. Although essential tremor and controls have been compared with respect to individual metrics of pathology, there has been no overarching analysis to derive a combination of metrics to distinguish essential tremor from controls. We asked whether there is a constellation of pathological findings that separates essential tremor from controls, and how well that constellation performs. Methods: Analyses included 100 essential tremor brains from the essential tremor centralized brain repository and 50 control brains. A standard tissue block from the cerebellar cortex was used to quantify 11 metrics of pathological change. Three supervised classification algorithms were investigated, with data divided into training and validation samples. Results: Using three different algorithms, we illustrate the ability to correctly predict a diagnosis of essential tremor, with sensitivity and specificity >87%, and in the majority of situations, >90%. We also provide a web-based application that uses these metric values, and based on specified cutoffs, determines the likely diagnosis. Interpretation: These analyses set the stage for use of pathologically based criteria to distinguish clinically diagnosed essential tremor cases from controls, at the time of postmortem.
Language	English
Publishing date	2024-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2740696-9
ISSN	2328-9503 ; 2328-9503
ISSN (online)	2328-9503
ISSN	2328-9503
DOI	10.1002/acn3.52068
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Article: Quasi-Two-Dimensional Magnon Identification in Antiferromagnetic FePS

McCreary, Amber / Simpson, Jeffrey R / Mai, Thuc T / McMichael, Robert D / Douglas, Jason E / Butch, Nicholas / Dennis, Cindi / Aguilar, Rolando Valdes / Walker, Angela R Hight

Physical review. B

2024 Volume 101

Abstract: Recently it was discovered that van der Waals-bonded magnetic materials retain long range magnetic ordering down to a single layer, opening many avenues in fundamental physics and potential applications of these fascinating materials. One such material ... ...

Abstract	Recently it was discovered that van der Waals-bonded magnetic materials retain long range magnetic ordering down to a single layer, opening many avenues in fundamental physics and potential applications of these fascinating materials. One such material is FePS
Language	English
Publishing date	2024-03-25
Publishing country	United States
Document type	Journal Article
ZDB-ID	209770-9
ISSN	1095-3795 ; 1550-235X ; 2469-9950 ; 1098-0121 ; 0163-1829 ; 0556-2805
ISSN (online)	1095-3795 ; 1550-235X
ISSN	2469-9950 ; 1098-0121 ; 0163-1829 ; 0556-2805
DOI	10.1103/PhysRevB.101.064416
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Article ; Online: Histopathology of the cerebellar cortex in essential tremor and other neurodegenerative motor disorders: comparative analysis of 320 brains.

Louis, Elan D / Martuscello, Regina T / Gionco, John T / Hartstone, Whitney G / Musacchio, Jessica B / Portenti, Marisa / McCreary, Morgan / Kuo, Sheng-Han / Vonsattel, Jean-Paul G / Faust, Phyllis L

Acta neuropathologica

2023 Volume 145, Issue 3, Page(s) 265–283

Abstract: In recent years, numerous morphologic changes have been identified in the essential tremor (ET) cerebellar cortex, distinguishing ET from control brains. These findings have not been fully contextualized within a broader degenerative disease spectrum, ... ...

Abstract	In recent years, numerous morphologic changes have been identified in the essential tremor (ET) cerebellar cortex, distinguishing ET from control brains. These findings have not been fully contextualized within a broader degenerative disease spectrum, thus limiting their interpretability. Building off our prior study and now doubling the sample size, we conducted comparative analyses in a postmortem series of 320 brains on the severity and patterning of cerebellar cortex degenerative changes in ET (n = 100), other neurodegenerative disorders of the cerebellum [spinocerebellar ataxias (SCAs, n = 47, including 13 SCA3 and 34 SCA1, 2, 6, 7, 8, 14); Friedreich's ataxia (FA, n = 13); multiple system atrophy (MSA), n = 29], and other disorders that may involve the cerebellum [Parkinson's disease (PD), n = 62; dystonia, n = 19] versus controls (n = 50). We generated data on 37 quantitative morphologic metrics, grouped into 8 broad categories: Purkinje cell (PC) loss, heterotopic PCs, PC dendritic changes, PC axonal changes (torpedoes), PC axonal changes (other than torpedoes), PC axonal changes (torpedo-associated), basket cell axonal hypertrophy, and climbing fiber-PC synaptic changes. Principal component analysis of z scored raw data across all diagnoses (11,651 data items) revealed that diagnostic groups were not uniform with respect to pathology. Dystonia and PD each differed from controls in only 4/37 and 5/37 metrics, respectively, whereas ET differed in 21, FA in 10, SCA3 in 10, MSA in 21, and SCA1/2/6/7/8/14 in 27. Pathological changes were generally on the milder end of the degenerative spectrum in ET, FA and SCA3, and on the more severe end of that spectrum in SCA1/2/6/7/8/14. Comparative analyses across morphologic categories demonstrated differences in relative expression, defining distinctive patterns of changes in these groups. In summary, we present a robust and reproducible method that identifies somewhat distinctive signatures of degenerative changes in the cerebellar cortex that mark each of these disorders.
MeSH term(s)	Humans ; Cerebellar Cortex/pathology ; Cerebellum/pathology ; Dystonia/pathology ; Dystonic Disorders/pathology ; Essential Tremor/metabolism ; Motor Disorders ; Multiple System Atrophy/pathology ; Parkinson Disease/pathology ; Purkinje Cells/pathology ; Spinocerebellar Ataxias/pathology
Language	English
Publishing date	2023-01-06
Publishing country	Germany
Document type	Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1079-0
ISSN	1432-0533 ; 0001-6322
ISSN (online)	1432-0533
ISSN	0001-6322
DOI	10.1007/s00401-022-02535-z
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Article ; Online: A rapid turnaround gene panel for severe autoinflammation: Genetic results within 48 hours.

McCreary, Dara / Omoyinmi, Ebun / Hong, Ying / Jensen, Barbara / Burleigh, Alice / Price-Kuehne, Fiona / Gilmour, Kimberly / Eleftheriou, Despina / Brogan, Paul

Frontiers in immunology

2022 Volume 13, Page(s) 998967

Abstract: There is an important unmet clinical need for fast turnaround next generation sequencing (NGS) to aid genetic diagnosis of patients with acute and sometimes catastrophic inflammatory presentations. This is imperative for patients who require precise and ... ...

Abstract	There is an important unmet clinical need for fast turnaround next generation sequencing (NGS) to aid genetic diagnosis of patients with acute and sometimes catastrophic inflammatory presentations. This is imperative for patients who require precise and targeted treatment to prevent irreparable organ damage or even death. Acute and severe hyper- inflammation may be caused by primary immunodeficiency (PID) with immune dysregulation, or more typical autoinflammatory diseases in the absence of obvious immunodeficiency. Infectious triggers may be present in either immunodeficiency or autoinflammation. We compiled a list of 25 genes causing monogenetic immunological diseases that are notorious for their acute first presentation with fulminant inflammation and which may be amenable to specific treatment, including hemophagocytic lymphohistiocytosis (HLH); and autoinflammatory diseases that can present with early-onset stroke or other irreversible neurological inflammatory complications. We designed and validated a pipeline that enabled return of clinically actionable results in hours rather than weeks: the Rapid Autoinflammation Panel (RAP). We demonstrated accuracy of this new pipeline, with 100% sensitivity and 100% specificity. Return of results to clinicians was achieved within 48-hours from receiving the patient's blood or saliva sample. This approach demonstrates the potential significant diagnostic impact of NGS in acute medicine to facilitate precision medicine and save "life or limb" in these critical situations.
MeSH term(s)	Hereditary Autoinflammatory Diseases/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Immune System Diseases ; Immunologic Deficiency Syndromes/genetics ; Inflammation/genetics
Language	English
Publishing date	2022-09-20
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.998967
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Article ; Online: Haemodynamics as a determinant of need for pre-hospital application of a pelvic circumferential compression device in adult trauma patients.

McCreary, D / Cheng, C / Lin, Z C / Nehme, Z / Fitzgerald, M / Mitra, B

Injury

2019 Volume 51, Issue 1, Page(s) 4–9

Abstract: Introduction: Pelvic ring fractures are common following high-energy blunt trauma and can lead to substantial haemorrhage, morbidity and mortality. Pelvic circumferential compression devices (PCCDs) improve position and stability of open-book type ... ...

Abstract	Introduction: Pelvic ring fractures are common following high-energy blunt trauma and can lead to substantial haemorrhage, morbidity and mortality. Pelvic circumferential compression devices (PCCDs) improve position and stability of open-book type pelvic fracture, and can improve haemodynamics in patients with hypovolaemic shock. However, PCCDs may cause adverse outcomes including worsening of lateral compression fracture patterns and routine use is associated with high costs. Controversy regarding indication of PCCDs exists with some centres recommending PCCD in the setting of hypovolaemic shock compared to placement for any suspected pelvic injury. Objective: To assess the need for PCCD application based on pre-hospital vital signs and mechanism of injury. Methods: A retrospective cohort study was conducted in a single adult major trauma centre examining a 2-year period. Patients were sub-grouped based on initial pre-hospital and emergency department observations as haemodynamically normal (heart rate <100 bpm, systolic blood pressure ≥100 mmHg and Glasgow Coma Scale ≥13) or abnormal. Diagnostic accuracy of pre-hospital haemodynamics as a predictor of pelvic fracture requiring intervention within 24 h was assessed. Results: There were 376 patients with PCCD in-situ on hospital arrival. Pelvic fractures were diagnosed in 137 patients (36.4%). Of these, 39 (28.5%) were haemodynamically normal and 98 (71.5%) were haemodynamically abnormal. The most common mechanisms of injury were motor vehicle collision (57.7%) and motorcycle collision (13.8%). Of those with fractures, 40 patients (29.2%) required pelvic intervention within 24 h of admission; of these, 8 (20%) were haemodynamically normal and 32 (80%) were haemodynamically abnormal. As a test for pelvic fracture requiring intervention within 24 h, abnormal pre-hospital haemodynamics had a sensitivity of 0.80 (95% CI 0.64-0.91), specificity of 0.32 (95% CI 0.27-0.38) and negative predictive value (NPV) of 0.93 (95% CI 0.88-0.96). Combined with absence of a major mechanism of injury, normal haemodynamics had a sensitivity 1.00, specificity 0.51 (95% CI 0.36-0.66) and NPV of 1.00 for pelvic intervention within 24 h. Conclusion: Normal haemodynamic status, combined with absence of major mechanism of injury can rule out requirement for urgent pelvic intervention. Ongoing surveillance is recommended to monitor for any adverse effects of this change in practice.
MeSH term(s)	Adult ; Bandages ; Emergency Service, Hospital ; Equipment Design ; Female ; Fracture Fixation/instrumentation ; Fractures, Bone/therapy ; Humans ; Male ; Middle Aged ; Pelvic Bones/injuries ; Retrospective Studies
Language	English
Publishing date	2019-08-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	218778-4
ISSN	1879-0267 ; 0020-1383
ISSN (online)	1879-0267
ISSN	0020-1383
DOI	10.1016/j.injury.2019.08.001
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Zs.A 778: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A Multicenter Weighted Lottery to Equitably Allocate Scarce COVID-19 Therapeutics.

White, Douglas B / McCreary, Erin K / Chang, Chung-Chou H / Schmidhofer, Mark / Bariola, J Ryan / Jonassaint, Naudia N / Persad, Govind / Truog, Robert D / Pathak, Parag / Sonmez, Tayfun / Unver, M Utku

American journal of respiratory and critical care medicine

2022 Volume 206, Issue 4, Page(s) 503–506

MeSH term(s)	COVID-19 ; Health Care Rationing ; Humans
Language	English
Publishing date	2022-05-12
Publishing country	United States
Document type	Letter ; Multicenter Study ; Research Support, N.I.H., Extramural
ZDB-ID	1180953-x
ISSN	1535-4970 ; 0003-0805 ; 1073-449X
ISSN (online)	1535-4970
ISSN	0003-0805 ; 1073-449X
DOI	10.1164/rccm.202201-0133LE
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Article: APDM gait and balance measures fail to predict symptom progression rate in Parkinson's disease.

Dewey, D Campbell / Chitnis, Shilpa / McCreary, Morgan C / Gerald, Ashley / Dewey, Chadrick H / Pantelyat, Alexander / Dawson, Ted M / Rosenthal, Liana S / Dewey, Richard B

Frontiers in neurology

2022 Volume 13, Page(s) 1041014

Abstract: Parkinson's disease (PD) results in progressively worsening gait and balance dysfunction that can be measured using computerized devices. We utilized the longitudinal database of the Parkinson's Disease Biomarker Program to determine if baseline gait and ...

Abstract	Parkinson's disease (PD) results in progressively worsening gait and balance dysfunction that can be measured using computerized devices. We utilized the longitudinal database of the Parkinson's Disease Biomarker Program to determine if baseline gait and balance measures predict future rates of symptom progression. We included 230, 222, 164, and 177 PD subjects with 6, 12, 18, and 24 months of follow-up, respectively, and we defined progression as worsening of the following clinical parameters: MDS-UPDRS total score, Montreal Cognitive Assessment, PDQ-39 mobility subscale, levodopa equivalent daily dose, Schwab and England score, and global composite outcome. We developed ridge regression models to independently estimate how each gait or balance measure, or combination of measures, predicted progression. The accuracy of each ridge regression model was calculated by cross-validation in which 90% of the data were used to estimate the ridge regression model which was then tested on the 10% of data left out. While the models modestly predicted change in outcomes at the 6-month follow-up visit (accuracy in the range of 66-71%) there was no change in the outcome variables during this short follow-up (median change in MDS-UPDRS total score = 0 and change in LEDD = 0). At follow-up periods of 12, 18, and 24 months, the models failed to predict change (accuracy in the held-out sets ranged from 42 to 60%). We conclude that this set of computerized gait and balance measures performed at baseline is unlikely to help predict future disease progression in PD. Research scientists must continue to search for progression predictors to enhance the performance of disease modifying clinical trials.
Language	English
Publishing date	2022-11-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.1041014
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Article ; Online: Community Members’ Perceptions of Tuberculosis (TB) Stigmatization in Rural Maharashtra, India

S. Tilekar / D. Rajaput / B. Varghese / L.L. McCreary

Annals of Global Health, Vol 83, Iss

2017 Volume 1

Keywords	Infectious and parasitic diseases ; RC109-216 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2017-04-01T00:00:00Z
Publisher	Ubiquity Press
Document type	Article ; Online
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Article ; Online: Factors Impacting Discharge Destination Following Head and Neck Microvascular Reconstruction.

Sweeny, Larissa / Slijepcevic, Allison / Curry, Joseph M / Philips, Ramez / Bonaventure, Caroline A / DiLeo, Michael / Luginbuhl, Adam J / Crawley, Meghan B / Guice, Kelsie M / McCreary, Eleanor / Buncke, Michelle / Petrisor, Daniel / Wax, Mark K

The Laryngoscope

2022 Volume 133, Issue 1, Page(s) 95–104

Abstract: Objective: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction.: Study design: Retrospective review of prospectively collected databases.: Methods: Consecutive ... ...

Abstract	Objective: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction. Study design: Retrospective review of prospectively collected databases. Methods: Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death). Results: The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty-day readmission rates were similar when stratified by discharge destination. Conclusion: There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination. Level of evidence: 4 Laryngoscope, 133:95-104, 2023.
MeSH term(s)	Humans ; Alcoholism/complications ; Risk Factors ; Substance Withdrawal Syndrome/complications ; Free Tissue Flaps/blood supply ; Patient Discharge ; Retrospective Studies ; Head and Neck Neoplasms/surgery ; Head and Neck Neoplasms/complications ; Postoperative Complications/epidemiology ; Postoperative Complications/etiology
Language	English
Publishing date	2022-05-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	80180-x
ISSN	1531-4995 ; 0023-852X
ISSN (online)	1531-4995
ISSN	0023-852X
DOI	10.1002/lary.30149
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Article ; Online: Impact of COVID-19 vaccinations on emergency department presentations.

Brichko, Lisa / Van Breugel, Lila / Underhill, Andrew / Tran, Huyen / Mitra, Biswadev / Cameron, Peter A / Smit, De Villiers / Giles, Michelle L / McCreary, David / Paton, Andrew / O'Reilly, Gerard M

Emergency medicine Australasia : EMA

2022 Volume 34, Issue 6, Page(s) 913–919

Abstract: Objective: The aim of the present study was to describe the burden of patients presenting to the ED with symptoms occurring after receiving a COVID-19 vaccination.: Methods: This was a retrospective cohort study performed over a 4-month period across ...

Abstract	Objective: The aim of the present study was to describe the burden of patients presenting to the ED with symptoms occurring after receiving a COVID-19 vaccination. Methods: This was a retrospective cohort study performed over a 4-month period across two EDs. Participants were eligible for inclusion if it was documented in the ED triage record that their ED attendance was associated with the receipt of a COVID-19 vaccination. Data regarding the type of vaccine (Comirnaty or ChAdOx1) were subsequently extracted from their electronic medical record. Primary outcome was ED length of stay (LOS) and secondary outcomes included requests for imaging and ED disposition destination. Results: During the study period of 22 February 2021 to 21 June 2021, 632 patients were identified for inclusion in the present study, of which 543 (85.9%) had received the ChAdOx1 vaccination. The highest proportion of COVID-19 vaccine-related attendances occurred in June 2021 and accounted for 21 (8%) of 262 total daily ED attendances. Patients who had an ED presentation related to ChAdOx1 had a longer median ED LOS (253 vs 180 min, P < 0.001) compared to Comirnaty and a higher proportion had haematology tests and imaging requested in the ED. Most patients (n = 588, 88.8%) were discharged home from the ED. Conclusion: There was a notable proportion of ED attendances related to recent COVID-19 vaccination administration, many of which were associated with lengthy ED stays and had multiple investigations. In the majority of cases, the patients were able to be discharged home from the ED.
MeSH term(s)	Humans ; COVID-19 Vaccines/adverse effects ; Retrospective Studies ; COVID-19/epidemiology ; COVID-19/prevention & control ; Emergency Service, Hospital ; Length of Stay ; Vaccination
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2022-06-24
Publishing country	Australia
Document type	Journal Article
ZDB-ID	2161824-0
ISSN	1742-6723 ; 1742-6731 ; 1035-6851
ISSN (online)	1742-6723
ISSN	1742-6731 ; 1035-6851
DOI	10.1111/1742-6723.14012
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