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Article ; Online: Alzheimer's Targeted Treatments: Focus on Amyloid and Inflammation.

Iwatsubo, Takeshi / Irizarry, Michael C / Lewcock, Joseph W / Carrillo, Maria C

The Journal of neuroscience : the official journal of the Society for Neuroscience

2023 Volume 43, Issue 47, Page(s) 7894–7898

Abstract: Alzheimer's disease (AD) is the major cause of dementia that is now threatening the lives of billions of elderly people on the globe, and recent progress in the elucidation of the pathomechanism of AD is now opening venue to tackle the disease by ... ...

Abstract	Alzheimer's disease (AD) is the major cause of dementia that is now threatening the lives of billions of elderly people on the globe, and recent progress in the elucidation of the pathomechanism of AD is now opening venue to tackle the disease by developing and implementing "disease-modifying therapies" that directly act on the pathophysiology and slow down the progression of neurodegeneration. A recent example is the success of clinical trials of anti-amyloid b antibody drugs, whereas other therapeutic targets, e.g., inflammation and tau, are being actively investigated. In this dual perspective session, we plan to have speakers from leading pharmas in the field representing distinct investments in the AD space, which will be followed by the comment from scientific leadership of the Alzheimer's Association who will speak on behalf of all stakeholders. Neuroscientists participating in the Society for Neuroscience may be able to gain insights into the cutting edge of the therapeutic approaches to AD and neurodegenerative disorders, and discuss future contribution of neuroscience to this field.
MeSH term(s)	Humans ; Aged ; Alzheimer Disease/drug therapy ; Amyloid beta-Peptides ; Inflammation/drug therapy ; tau Proteins
Chemical Substances	Amyloid beta-Peptides ; tau Proteins
Language	English
Publishing date	2023-11-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	604637-x
ISSN	1529-2401 ; 0270-6474
ISSN (online)	1529-2401
ISSN	0270-6474
DOI	10.1523/JNEUROSCI.1576-23.2023
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Zs.A 1668: Show issues

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Article ; Online: Traumatic Degloving Wounds Treated With Low Continuous Wall Suction Drainage: A Novel and Effective Technique to Prevent Recurrence.

Fraser, Helyn G / Hernandez-Irizarry, Roberto C / Bundschuh, Kyle E / Maceroli, Michael A

Orthopedics

2023 Volume 46, Issue 4, Page(s) e257–e263

Abstract: Soft tissue degloving wounds overlying fractures present a technical surgical challenge and have a high rate of recurrence. Despite several current treatment methods, there remains a need for improved therapies to address this complex issue. The purpose ... ...

Abstract	Soft tissue degloving wounds overlying fractures present a technical surgical challenge and have a high rate of recurrence. Despite several current treatment methods, there remains a need for improved therapies to address this complex issue. The purpose of this study was to introduce a novel technique for managing soft tissue degloving wounds in the setting of fractures requiring operative fixation. Eleven consecutive patients with soft tissue degloving wounds overlying operatively managed fractures were treated with our novel technique for "dead space" elimination in the peri-operative period. The technique entails placing Jackson Pratt drain(s) within the degloving wound during operative debridement and placing them to low continuous wall suction postoperatively. This patient series shows that the application of 40 to 60 mm Hg of negative pressure allows for thorough drainage of the hemolymphatic fluid collection and elimination of dead space, allowing the delaminated tissue layers to heal together and preventing recurrence. [
MeSH term(s)	Humans ; Suction ; Degloving Injuries/surgery ; Drainage/methods ; Wound Healing ; Fractures, Bone/surgery ; Debridement ; Treatment Outcome
Language	English
Publishing date	2023-06-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	424447-3
ISSN	1938-2367 ; 0147-7447
ISSN (online)	1938-2367
ISSN	0147-7447
DOI	10.3928/01477447-20230531-03
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Zs.A 1487: Show issues

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Article ; Online: Stacked fibula flap for unilateral total maxillectomy reconstruction with orbital preservation.

Chan, Tyler G / Nickel, Chris / Solares, Clementino / Irizarry, Rachel / Pipkorn, Patrik / Baddour, Harry Michael / Gross, Jennifer H

Head & neck

2023 Volume 46, Issue 1, Page(s) 218–227

Abstract: Unilateral total maxillectomy is indicated for locally advanced maxillary tumors that require complete removal of the midface bony structure and inferior orbital rim. Reconstruction of this defect is challenging due to aesthetic and functional concerns. ... ...

Abstract	Unilateral total maxillectomy is indicated for locally advanced maxillary tumors that require complete removal of the midface bony structure and inferior orbital rim. Reconstruction of this defect is challenging due to aesthetic and functional concerns. A retrospective review of patients at two tertiary-care institutions undergoing unilateral total maxillectomy reconstruction with a stacked fibula flap from 2018 to 2022 was performed. Each patient's clinical course was reviewed, and attention was focused on the demonstration of surgical steps with photos. Twenty patients underwent stacked fibula flap reconstruction for unilateral total maxillectomy orbital preservation defects. Surgical extirpation was performed for malignancy (80%, 16/20) and for osteoradionecrosis or benign tumor in 20% (4/20). The complication rate was 30% (6/20). Most flaps survived (95%, 19/20). We present a modified, reproducible method of fibula flap reconstruction for unilateral total maxillectomy with orbital preservation that only requires two segments and maintains positive aesthetic and functional results.
MeSH term(s)	Humans ; Plastic Surgery Procedures ; Maxilla/surgery ; Fibula/surgery ; Surgical Flaps/surgery ; Maxillary Neoplasms/surgery
Language	English
Publishing date	2023-11-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	645165-2
ISSN	1097-0347 ; 0148-6403 ; 1043-3074
ISSN (online)	1097-0347
ISSN	0148-6403 ; 1043-3074
DOI	10.1002/hed.27567
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Zs.A 1493: Show issues

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Article ; Online: Commentary on: Adipose Stem Cell Function Maintained with Age: An Intra-Subject Study of Long-Term Cryopreserved Cells.

Irizarry, Dre / Longaker, Michael T / Wan, Derrick C

Aesthetic surgery journal

2017 Volume 37, Issue 4, Page(s) 464–465

MeSH term(s)	Adipocytes ; Adipose Tissue ; Cryopreservation ; Humans ; Stem Cells
Language	English
Publishing date	2017--01
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2087022-X
ISSN	1527-330X ; 1090-820X ; 1084-0761
ISSN (online)	1527-330X
ISSN	1090-820X ; 1084-0761
DOI	10.1093/asj/sjw224
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Zs.A 5721: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A west African ancestry-associated SNP on 8q24 predicts a positive biopsy in African American men with suspected prostate cancer following PSA screening.

Gu, Jian / Chery, Lisly / González, Graciela M Nogueras / Huff, Chad / Strom, Sara / Jones, Jeffrey A / Griffith, Donald P / Canfield, Steven E / Wang, Xuemei / Huang, Xuelin / Roberson, Pamela / Meng, Qing H / Troncoso, Patricia / Ittmann, Michael / Covinsky, Michael / Scheurer, Michael / Irizarry Ramirez, Margarita / Pettaway, Curtis A

The Prostate

2024 Volume 84, Issue 7, Page(s) 694–705

Abstract: Background: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of ... ...

Abstract	Background: African American (AA) men have the highest incidence and mortality rates of prostate cancer (PCa) among all racial groups in the United States. While race is a social construct, for AA men, this overlaps with west African ancestry. Many of the PCa susceptibility variants exhibit distinct allele frequencies and risk estimates across different races and contribute substantially to the large disparities of PCa incidence among races. We previously reported that a single-nucleotide polymorphism (SNP) in 8q24, rs7824364, was strongly associated with west African ancestry and increased risks of PCa in both AA and Puerto Rican men. In this study, we determined whether this SNP can predict biopsy positivity and detection of clinically significant disease (Gleason score [GS] ≥ 7) in a cohort of AA men with suspected PCa. Methods: SNP rs7824364 was genotyped in 199 AA men with elevated total prostate-specific antigen (PSA) (>2.5 ng/mL) or abnormal digital rectal exam (DRE) and the associations of different genotypes with biopsy positivity and clinically significant disease were analyzed. Results: The variant allele carriers were significantly over-represented in the biopsy-positive group compared to the biopsy-negative group (44% vs. 25.7%, p = 0.011). In the multivariate logistic regression analyses, variant allele carriers were at a more than a twofold increased risk of a positive biopsy (odds ratio [OR] = 2.14, 95% confidence interval [CI] = 1.06-4.32). Moreover, the variant allele was a predictor (OR = 2.26, 95% CI = 1.06-4.84) of a positive biopsy in the subgroup of patients with PSA < 10 ng/mL and normal DRE. The variant allele carriers were also more prevalent in cases with GS ≥ 7 compared to cases with GS < 7 and benign biopsy. Conclusions: This study demonstrated that the west African ancestry-specific SNP rs7824364 on 8q24 independently predicted a positive prostate biopsy in AA men who were candidates for prostate biopsy subsequent to PCa screening.
MeSH term(s)	Male ; Humans ; United States ; Prostate-Specific Antigen ; Black or African American/genetics ; Polymorphism, Single Nucleotide ; Early Detection of Cancer ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/genetics ; Prostatic Neoplasms/pathology ; Biopsy
Chemical Substances	Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2024-03-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	604707-5
ISSN	1097-0045 ; 0270-4137
ISSN (online)	1097-0045
ISSN	0270-4137
DOI	10.1002/pros.24686
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Zs.A 1608: Show issues

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Article ; Online: The AHEAD 3-45 Study: Design of a prevention trial for Alzheimer's disease.

Rafii, Michael S / Sperling, Reisa A / Donohue, Michael C / Zhou, Jin / Roberts, Claire / Irizarry, Michael C / Dhadda, Shobha / Sethuraman, Gopalan / Kramer, Lynn D / Swanson, Chad J / Li, David / Krause, Stephen / Rissman, Robert A / Walter, Sarah / Raman, Rema / Johnson, Keith A / Aisen, Paul S

Alzheimer's & dementia : the journal of the Alzheimer's Association

2022 Volume 19, Issue 4, Page(s) 1227–1233

Abstract: Introduction: The Alzheimer's disease (AD) continuum begins with a long asymptomatic or preclinical stage, during which amyloid beta (Aβ) is accumulating for more than a decade prior to widespread cortical tauopathy, neurodegeneration, and manifestation ...

Abstract	Introduction: The Alzheimer's disease (AD) continuum begins with a long asymptomatic or preclinical stage, during which amyloid beta (Aβ) is accumulating for more than a decade prior to widespread cortical tauopathy, neurodegeneration, and manifestation of clinical symptoms. The AHEAD 3-45 Study (BAN2401-G000-303) is testing whether intervention with lecanemab (BAN2401), a humanized immunoglobulin 1 (IgG1) monoclonal antibody that preferentially targets soluble aggregated Aβ, initiated during this asymptomatic stage can slow biomarker changes and/or cognitive decline. The AHEAD 3-45 Study is conducted as a Public-Private Partnership of the Alzheimer's Clinical Trial Consortium (ACTC), funded by the National Institute on Aging, National Institutes of Health (NIH), and Eisai Inc. Methods: The AHEAD 3-45 Study was launched on July 14, 2020, and consists of two sister trials (A3 and A45) in cognitively unimpaired (CU) individuals ages 55 to 80 with specific dosing regimens tailored to baseline brain amyloid levels on screening positron emission tomography (PET) scans: intermediate amyloid (≈20 to 40 Centiloids) for A3 and elevated amyloid (>40 Centiloids) for A45. Both trials are being conducted under a single protocol, with a shared screening process and common schedule of assessments. A3 is a Phase 2 trial with PET-imaging end points, whereas A45 is a Phase 3 trial with a cognitive composite primary end point. The treatment period is 4 years. The study utilizes innovative approaches to enriching the sample with individuals who have elevated brain amyloid. These include recruiting from the Trial-Ready Cohort for Preclinical and Prodromal Alzheimer's disease (TRC-PAD), the Australian Dementia Network (ADNeT) Registry, and the Japanese Trial Ready Cohort (J-TRC), as well as incorporation of plasma screening with the C2N mass spectrometry platform to quantitate the Aβ 42/40 ratio (Aβ 42/40), which has been shown previously to reliably identify cognitively normal participants not likely to have elevated brain amyloid levels. A blood sample collected at a brief first visit is utilized to "screen out" individuals who are less likely to have elevated brain amyloid, and to determine the participant's eligibility to proceed to PET imaging. Eligibility to randomize into the A3 Trial or A45 Trial is based on the screening PET imaging results. Result: The focus of this article is on the innovative design of the study. Discussion: The AHEAD 3-45 Study will test whether with lecanemab (BAN2401) can slow the accumulation of tau and prevent the cognitive decline associated with AD during its preclinical stage. It is specifically targeting both the preclinical and the early preclinical (intermediate amyloid) stages of AD and is the first secondary prevention trial to employ plasma-based biomarkers to accelerate the screening process and potentially substantially reduce the number of screening PET scans.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides/metabolism ; Australia ; Tauopathies/metabolism ; Brain/diagnostic imaging ; Brain/metabolism ; Positron-Emission Tomography ; Cognitive Dysfunction/metabolism ; Biomarkers/metabolism ; tau Proteins/metabolism
Chemical Substances	Amyloid beta-Peptides ; Biomarkers ; tau Proteins
Language	English
Publishing date	2022-08-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12748
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Zs.A 6316: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 540: Show issues

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Article ; Online: Plasma Aβ42/Aβ40 and phospho-tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease.

Alzheimer's & dementia : the journal of the Alzheimer's Association

2023 Volume 20, Issue 2, Page(s) 1214–1224

Abstract: Introduction: Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency.: Methods: Plasma Aβ, phosphorylated tau (p-tau)181, and p-tau217 concentration levels ...

Abstract	Introduction: Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency. Methods: Plasma Aβ, phosphorylated tau (p-tau)181, and p-tau217 concentration levels from AHEAD 3-45 study participants were measured using mass spectrometry. Tau concentration ratios for each proteoform were calculated to normalize for inter-individual differences. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by > 20 Centiloids. Mixture of experts analysis assessed the value of including tau concentration ratios into the existing predictive algorithm for amyloid positron emission tomography status. Results: The area under the receiver operating curve (AUC) was 0.87 for Aβ42/Aβ40, 0.74 for phosphorylated variant p-tau181 ratio (p-tau181/np-tau181), and 0.92 for phosphorylated variant p-tau217 ratio (p-tau217/np-tau217). The Plasma Predicted Centiloid (PPC), a predictive model including p-tau217/np-tau217, Aβ42/Aβ40, age, and apolipoprotein E improved AUC to 0.95. Discussion: Including plasma p-tau217/np-tau217 along with Aβ42/Aβ40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials. Clinicaltrials: gov Identifier: NCT04468659 HIGHLIGHTS: The addition of plasma phosphorylated variant p-tau217 ratio (p-tau217/np-tau217) significantly improved plasma biomarker algorithms for identifying preclinical amyloid positron emission tomography positivity. Prediction performance at higher NAV Centiloid levels was improved with p-tau217/np-tau217. All models generated for this study are incorporated into the Plasma Predicted Centiloid (PPC) app for public use.
MeSH term(s)	Humans ; Alzheimer Disease/diagnosis ; Amyloid beta-Peptides ; Peptide Fragments ; Amyloid ; tau Proteins ; Positron-Emission Tomography ; Biomarkers
Chemical Substances	Amyloid beta-Peptides ; Peptide Fragments ; Amyloid ; tau Proteins ; Biomarkers
Language	English
Publishing date	2023-11-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13542
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Zs.MO 540: Show issues

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Article ; Online: Lewy body dementia: Overcoming barriers and identifying solutions.

Agarwal, Kanishka / Backler, Wendi / Bayram, Ece / Bloom, Leah / Boeve, Bradley F / Cha, Jang-Ho / Denslow, Maria / Ferman, Tanis J / Galasko, Douglas / Galvin, James E / Gomperts, Stephen N / Irizarry, Michael C / Kantarci, Kejal / Kaushik, Harsh / Kietlinski, Matt / Koenig, Aaron / Leverenz, James B / McKeith, Ian / McLean, Pamela J /

Montine, Thomas J / Moose, Sandra O / O'Brien, John T / Panier, Valery / Ramanathan, Sharad / Ringel, Michael S / Scholz, Sonja W / Small, Jonnell / Sperling, Reisa A / Taylor, Angela / Taylor, John-Paul / Ward, Rebecca A / Witten, Lisa / Hyman, Bradley T

Alzheimer's & dementia : the journal of the Alzheimer's Association

2024 Volume 20, Issue 3, Page(s) 2298–2308

Abstract: Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to ... ...

Abstract	Despite its high prevalence among dementias, Lewy body dementia (LBD) remains poorly understood with a limited, albeit growing, evidence base. The public-health burden that LBD imposes is worsened by overlapping pathologies, which contribute to misdiagnosis, and lack of treatments. For this report, we gathered and analyzed public-domain information on advocacy, funding, research outputs, and the therapeutic pipeline to identify gaps in each of these key elements. To further understand the current gaps, we also conducted interviews with leading experts in regulatory/governmental agencies, LBD advocacy, academic research, and biopharmaceutical research, as well as with funding sources. We identified wide gaps across the entire landscape, the most critical being in research. Many of the experts participated in a workshop to discuss the prioritization of research areas with a view to accelerating therapeutic development and improving patient care. This white paper outlines the opportunities for bridging the major LBD gaps and creates the framework for collaboration in that endeavor. HIGHLIGHTS: A group representing academia, government, industry, and consulting expertise was convened to discuss current progress in Dementia with Lewy Body care and research. Consideration of expert opinion,natural language processing of the literature as well as publicly available data bases, and Delphi inspired discussion led to a proposed consensus document of priorities for the field.
MeSH term(s)	Humans ; Lewy Body Disease/diagnosis ; Lewy Body Disease/therapy
Language	English
Publishing date	2024-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.13674
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Article: Biomarkers of Alzheimer disease in plasma.

Irizarry, Michael C

NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics

2005 Volume 1, Issue 2, Page(s) 226–234

Abstract: Plasma and serum biochemical markers proposed for Alzheimer disease (AD) are based on pathophysiologic processes such as amyloid plaque formation [amyloid beta-protein (A beta), A beta autoantibodies, platelet amyloid precursor protein (APP) isoforms], ... ...

Abstract	Plasma and serum biochemical markers proposed for Alzheimer disease (AD) are based on pathophysiologic processes such as amyloid plaque formation [amyloid beta-protein (A beta), A beta autoantibodies, platelet amyloid precursor protein (APP) isoforms], inflammation (cytokines), oxidative stress (vitamin E, isoprostanes), lipid metabolism (apolipoprotein E, 24S-hydroxycholesterol), and vascular disease [homocysteine, lipoprotein (a)]. Most proteins or metabolites evaluated in plasma or serum thus far are, at best, biological correlates of AD: levels are statistically different in AD versus controls in some cohorts, but they lack sensitivity or specificity for diagnosis or for tracking response to therapy. Approaches combining panels of existing biomarkers or surveying the range of proteins in plasma (proteomics) show promise for discovering biomarker profiles that are characteristic of AD, yet distinct from nondemented patients or patients with other forms of dementia.
MeSH term(s)	Alzheimer Disease/blood ; Alzheimer Disease/diagnosis ; Biomarkers/blood ; Humans ; Plasma
Chemical Substances	Biomarkers
Language	English
Publishing date	2005-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	2205033-4
ISSN	1545-5351 ; 1545-5343
ISSN (online)	1545-5351
ISSN	1545-5343
DOI	10.1602/neurorx.1.2.226
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Zs.A 6156: Show issues

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Article ; Online: Improving Value of Care: Cessation of Screening Urine Culture Prior to Orthopedic and Spinal Surgery.

Hellinger, Walter C / Haehn, Daniela A / Heckman, Michael G / Irizarry Alvarado, Joan M / Bosch, Wendelyn / Pai, Sher-Lu

Mayo Clinic proceedings. Innovations, quality & outcomes

2020 Volume 4, Issue 2, Page(s) 126–131

Abstract: Objective: To assess the impact of cessation of screening urine cultures on surgical site infection (SSI) incidence in clinical practice.: Patients and methods: Our study included patients undergoing hip replacement, knee replacement, spinal fusion, ... ...

Abstract	Objective: To assess the impact of cessation of screening urine cultures on surgical site infection (SSI) incidence in clinical practice. Patients and methods: Our study included patients undergoing hip replacement, knee replacement, spinal fusion, and laminectomy 12 months before (preintervention) and after (postintervention) cessation of preoperative screening urine cultures on June 1, 2017, at our institution. Urine cultures and urinalyses performed within 30 days before surgery during the 12 months before and after cessation were reviewed. SSI surveillance was performed in accordance with the methods of the National Healthcare Safety Network. Results: A total of 2754 patients were included (1286 preintervention and 1468 postintervention). In the preintervention period, 1141 urine cultures were performed, compared to 153 in the postintervention period; 35 and 6 episodes of asymptomatic bacteriuria were treated, respectively. The occurrence of SSI did not differ noticeably between time periods (1.2% vs 0.7%, Conclusion: An 86.6% (153 vs 1141) reduction in screening urine cultures over a 12-month period was associated with a reduction of 988 unnecessary urine cultures, an 82.8% (6 vs 35) decline in inappropriate antibiotic treatment of asymptomatic bacteriuria, and no increase in SSI incidence after hip replacement, knee replacement, spinal fusion, or laminectomy procedures. No value of screening urine cultures before clean surgery was identified.
Language	English
Publishing date	2020-04-06
Publishing country	Netherlands
Document type	Journal Article
ISSN	2542-4548
ISSN (online)	2542-4548
DOI	10.1016/j.mayocpiqo.2019.12.007
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