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Article ; Online: A living donor kidney transplant recipient with mycobacterium senegalense bacteremia: A case report.

Bugeja, Ann / Hae, Richard / Rajda, Ewa / Clark, Edward G / Akbari, Ayub / Fairhead, Todd / Arianne Buchan, C

Transplant infectious disease : an official journal of the Transplantation Society

2021 Volume 23, Issue 4, Page(s) e13596

Abstract: Mycobacterium senegalense is primarily known in sub-Saharan Africa to cause bovine farcy, a chronic granulomatous inflammation of the skin and lymphatics in cows. Reports of M. senegalense are rare among humans. We report a unique case of M. senegalense ... ...

Abstract	Mycobacterium senegalense is primarily known in sub-Saharan Africa to cause bovine farcy, a chronic granulomatous inflammation of the skin and lymphatics in cows. Reports of M. senegalense are rare among humans. We report a unique case of M. senegalense bloodstream infection in a living donor kidney transplant recipient with multiple possible sources of infection.
MeSH term(s)	Animals ; Bacteremia/diagnosis ; Bacteremia/drug therapy ; Cattle ; Female ; Humans ; Kidney Transplantation/adverse effects ; Living Donors ; Mycobacteriaceae ; Mycobacterium
Language	English
Publishing date	2021-03-11
Publishing country	Denmark
Document type	Case Reports
ZDB-ID	1476094-0
ISSN	1399-3062 ; 1398-2273
ISSN (online)	1399-3062
ISSN	1398-2273
DOI	10.1111/tid.13596
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Zs.A 5100: Show issues

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Article ; Online: Early Outcomes of Bivalirudin Therapy for Thrombotic Thrombocytopenia and Cerebral Venous Sinus Thrombosis After Ad26.COV2.S Vaccination.

Clark, Richard Todd / Johnson, Lee / Billotti, Jamie / Foulds, Georgia / Ketels, Taryn / Heard, Kennon / Calvello Hynes, Emilie

Annals of emergency medicine

2021 Volume 78, Issue 4, Page(s) 511–514

Abstract: Vaccine-induced thrombotic thrombocytopenia is a newly described disease process in the setting of expanding access to COVID-19 vaccination. The United States Centers for Disease Control and Prevention recommends treatment with an alternative to heparin ... ...

Abstract	Vaccine-induced thrombotic thrombocytopenia is a newly described disease process in the setting of expanding access to COVID-19 vaccination. The United States Centers for Disease Control and Prevention recommends treatment with an alternative to heparin in patients suspected of having vaccine-induced thrombotic thrombocytopenia. At this time there have been no reported outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. We describe the early outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. A 40-year-old Caucasian woman was found to have thrombocytopenia, cerebral venous sinus thrombosis, and pulmonary embolism following vaccination for COVID-19 with Ad26.COV2.S. She exhibited a steady rise in platelet count: 20×10
MeSH term(s)	Ad26COVS1 ; Adult ; Blood Chemical Analysis ; Blood Physiological Phenomena ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Female ; Fibrinolytic Agents/therapeutic use ; Hirudins ; Humans ; Peptide Fragments/therapeutic use ; Pulmonary Embolism/drug therapy ; Pulmonary Embolism/etiology ; Recombinant Proteins/therapeutic use ; Sinus Thrombosis, Intracranial/drug therapy ; Sinus Thrombosis, Intracranial/etiology ; Thrombocytopenia/drug therapy ; Thrombocytopenia/etiology
Chemical Substances	Ad26COVS1 (JT2NS6183B) ; COVID-19 Vaccines ; Fibrinolytic Agents ; Hirudins ; Peptide Fragments ; Recombinant Proteins ; bivalirudin (TN9BEX005G)
Language	English
Publishing date	2021-07-03
Publishing country	United States
Document type	Case Reports
ZDB-ID	603080-4
ISSN	1097-6760 ; 0196-0644
ISSN (online)	1097-6760
ISSN	0196-0644
DOI	10.1016/j.annemergmed.2021.04.035
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Zs.A 1344: Show issues

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Article ; Online: LIGHTSITE III: 13-Month Efficacy and Safety Evaluation of Multiwavelength Photobiomodulation in Nonexudative (Dry) Age-Related Macular Degeneration Using the Lumithera Valeda Light Delivery System.

Boyer, David / Hu, Allen / Warrow, David / Xavier, Samantha / Gonzalez, Victor / Lad, Eleonora / Rosen, Richard B / Do, Diana / Schneiderman, Todd / Ho, Allen / Munk, Marion R / Jaffe, Glenn / Tedford, Stephanie E / Croissant, Cindy L / Walker, Michael / Rückert, Rene / Tedford, Clark E

Retina (Philadelphia, Pa.)

2023 Volume 44, Issue 3, Page(s) 487–497

Abstract: Purpose: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System.: Methods: LIGHTSITE III is a randomized, ... ...

Abstract	Purpose: The LIGHTSITE III study evaluated multiwavelength photobiomodulation (PBM) therapy in nonexudative (dry) age-related macular degeneration (AMD) using the LumiThera Valeda Light Delivery System. Methods: LIGHTSITE III is a randomized, controlled trial to assess the safety and effectiveness of PBM in dry AMD. Subjects were given multiwavelength PBM (590, 660, and 850 nm) or Sham treatment delivered in a series of nine sessions over 3 to 5 weeks every four months over 24 months. Subjects were assessed for efficacy and safety outcomes. Data from the 13-month analysis are presented in this report. Results: A total of 100 subjects (148 eyes) with dry AMD were randomized. LIGHTSITE III met the primary efficacy best-corrected visual acuity endpoint with a significant difference between PBM (n = 91 eyes) and Sham (n = 54 eyes) groups (Between group difference: 2.4 letters (SE 1.15), CI: -4.7 to -0.1, P = 0.02) (PBM alone: 5.4 letters (SE 0.96), CI: 3.5 to 7.3, P < 0.0001; Sham alone: 3.0 letters (SE 1.13), CI: 0.7-5.2, P < 0.0001). The PBM group showed a significant decrease in new onset geographic atrophy ( P = 0.024, Fisher exact test, odds ratio 9.4). A favorable safety profile was observed. Conclusion: LIGHTSITE III provides a prospective, randomized, controlled trial showing improved clinical and anatomical outcomes in intermediate dry AMD following PBM therapy.
MeSH term(s)	Humans ; Low-Level Light Therapy ; Prospective Studies ; Visual Acuity ; Macular Degeneration/diagnosis ; Macular Degeneration/radiotherapy ; Macular Degeneration/drug therapy ; Eye ; Geographic Atrophy/diagnosis ; Geographic Atrophy/radiotherapy
Language	English
Publishing date	2023-11-14
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	603192-4
ISSN	1539-2864 ; 0275-004X
ISSN (online)	1539-2864
ISSN	0275-004X
DOI	10.1097/IAE.0000000000003980
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Zs.A 1724: Show issues

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Article ; Online: Validation of a Novel, Rapid Sepsis Diagnostic for Emergency Department Use.

O'Neal, Hollis R / Sheybani, Roya / Janz, David R / Scoggins, Robert / Jagneaux, Tonya / Walker, James E / Henning, Daniel J / Rosenman, Elizabeth / Mahler, Simon A / Regunath, Hariharan / Sampson, Christopher S / Files, D Clark / Fremont, Richard D / Noto, Michael J / Schneider, Erica E / Shealey, Wesley R / Berlinger, Matthew S / Carver, Thomas C / Walker, Morgan K /

Ledeboer, Nathan A / Shah, Ajay M / Tse, Henry T K / DiCarlo, Dino / Rice, Todd W / Thomas, Christopher B

Critical care explorations

2024 Volume 6, Issue 2, Page(s) e1026

Abstract: Objectives: To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis.: Design: Prospective cohort study.: ... ...

Abstract	Objectives: To assess the in vitro IntelliSep test, a microfluidic assay that quantifies the state of immune activation by evaluating the biophysical properties of leukocytes, as a rapid diagnostic for sepsis. Design: Prospective cohort study. Setting: Five emergency departments (EDs) in Louisiana, Missouri, North Carolina, and Washington. Patients: Adult patients presenting to the ED with signs (two of four Systemic Inflammatory Response Syndrome criteria, where one must be temperature or WBC count) or suspicion (provider-ordered culture) of infection. Interventions: All patients underwent testing with the IntelliSep using ethylene diamine tetraacetic acid-anticoagulated whole blood followed by retrospective adjudication for sepsis by sepsis-3 criteria by a blinded panel of physicians. Measurements and main results: Of 599 patients enrolled, 572 patients were included in the final analysis. The result of the IntelliSep test is reported as the IntelliSep Index (ISI), ranging from 0.1 to 10.0, divided into three interpretation bands for the risk of sepsis: band 1 (low) to band 3 (high). The median turnaround time for ISI results was 7.2 minutes. The ISI resulted band 1 in 252 (44.1%), band 2 in 160 (28.0%), and band 3 in 160 (28.0%). Sepsis occurred in 26.6% (152 of 572 patients). Sepsis prevalence was 11.1% (95% CI, 7.5-15.7%) in band 1, 28.1% (95% CI, 21.3-35.8%) in band 2, and 49.4% (95% CI, 41.4-57.4%) in band 3. The Positive Percent Agreement of band 1 was 81.6% and the Negative Percent Agreement of band 3 was 80.7%, with an area under the receiver operating characteristic curve of 0.74. Compared with band 1, band 3 correlated with adverse clinical outcomes, including mortality, and resource utilization. Conclusions: Increasing ISI interpretation band is associated with increasing probability of sepsis in patients presenting to the ED with suspected infection.
Language	English
Publishing date	2024-02-07
Publishing country	United States
Document type	Journal Article
ISSN	2639-8028
ISSN (online)	2639-8028
DOI	10.1097/CCE.0000000000001026
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Article ; Online: Risk factors for service use and trends in coverage of different HIV testing and counselling models in northwest Tanzania between 2003 and 2010.

Cawley, Caoimhe / Wringe, Alison / Todd, Jim / Gourlay, Annabelle / Clark, Benjamin / Masesa, Clemens / Machemba, Richard / Reniers, Georges / Urassa, Mark / Zaba, Basia

Tropical medicine & international health : TM & IH

2015 Volume 20, Issue 11, Page(s) 1473–1487

Abstract: Objectives: To investigate the relative effectiveness of different HIV testing and counselling (HTC) services in improving HIV diagnosis rates and increasing HTC coverage in African settings.: Methods: Patient records from three HTC services [ ... ...

Abstract	Objectives: To investigate the relative effectiveness of different HIV testing and counselling (HTC) services in improving HIV diagnosis rates and increasing HTC coverage in African settings. Methods: Patient records from three HTC services [community outreach HTC during cohort study rounds (CO-HTC), walk-in HTC at the local health centre (WI-HTC) and antenatal HIV testing (ANC-HTC)] were linked to records from a community cohort study using a probabilistic record linkage algorithm. Characteristics of linked users of each HTC service were compared to those of cohort participants who did not use the HTC service using logistic regression. Data from three cohort study rounds between 2003 and 2010 were used to assess trends in the proportion of persons testing at different service types. Results: The adjusted odds ratios for HTC use among men with increasing numbers of sexual partners in the past year, and among HIV-positive men and women compared to HIV-negative men and women, were higher at WI-HTC than at CO-HTC and ANC-HTC. Among sero-survey participants, the largest numbers of HIV-positive men and women learned their status via CO-HTC. However, we are likely to have underestimated the numbers diagnosed at WI-HTC and ANC-HTC, due to low sensitivity of the probabilistic record linkage algorithm. Conclusions: Compared to CO-HTC or ANC-HTC, WI-HTC was most likely to attract HIV-positive men and women, and to attract men with greater numbers of sexual partners. Further research should aim to optimise probabilistic record linkage techniques, and to investigate which types of HTC services most effectively link HIV-positive people to treatment services relative to the total cost per diagnosis made.
Language	English
Publishing date	2015-08-25
Publishing country	England
Document type	Journal Article
ZDB-ID	1314080-2
ISSN	1365-3156 ; 1360-2276
ISSN (online)	1365-3156
ISSN	1360-2276
DOI	10.1111/tmi.12578
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Zs.A 4415: Show issues

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Article ; Online: The safety of oral anticoagulants registry (SOAR): A national, ED-based study of the evaluation and management of bleeding and bleeding concerns due to the use of oral anticoagulants.

Pollack, Charles V / Peacock, W Frank / Bernstein, Richard A / Clark, Carol L / Douketis, James / Fermann, Gregory J / Fiore, Gregory J / Frost, Alex / Jahromi, Babak / Johnson, Charles / Merli, Geno / Silber, Steven / Villines, Todd C / Fanikos, John

The American journal of emergency medicine

2019 Volume 38, Issue 6, Page(s) 1163–1170

Abstract: Objective: The Safety of Oral Anticoagulants Registry (SOAR) was designed to describe the evaluation and management of patients with oral anticoagulant (OAC)-related major bleeding or bleeding concerns who present to the emergency department (ED) with ... ...

Abstract	Objective: The Safety of Oral Anticoagulants Registry (SOAR) was designed to describe the evaluation and management of patients with oral anticoagulant (OAC)-related major bleeding or bleeding concerns who present to the emergency department (ED) with acute illness or injury. Patients in the ED are increasingly taking anticoagulants, which can cause bleeding-related complications as well as impact the acute management of related or unrelated clinical issues that prompt presentation. Modifications of emergency evaluation and management due to anticoagulation have not previously been studied. Methods: This was a multicenter observational in-hospital study of patients who were judged to be experiencing an active OAC effect and had (a) an obvious bleeding event or (b) were deemed at risk for serious bleeding spontaneously, after injury, or during an indicated invasive procedure. Diagnostic testing, therapies employed, and clinical outcomes were collected. Results: Thirty-one US hospitals contributed data to SOAR. Of 1513 subjects, acute hemorrhage (AH) qualified 78%, while 22% had a bleeding concern (BC). Warfarin was the index OAC in 37.3%, dabigatran in 13.3%, and an anti-Factor X Conclusion: Care of anticoagulated patients in the acute care setting is inconsistent, reflecting the diversity of presentation. As the prevalence of OAC use increases with the aging of the US population, further study and targeted educational efforts are needed to drive more evidence-based care of these patients.
MeSH term(s)	Aged ; Aged, 80 and over ; Dabigatran/adverse effects ; Dabigatran/therapeutic use ; Emergency Service, Hospital/organization & administration ; Emergency Service, Hospital/statistics & numerical data ; Factor Xa Inhibitors/adverse effects ; Factor Xa Inhibitors/therapeutic use ; Female ; Gastrointestinal Hemorrhage/epidemiology ; Gastrointestinal Hemorrhage/etiology ; Hemorrhage/epidemiology ; Hemorrhage/etiology ; Humans ; Intracranial Hemorrhages/epidemiology ; Intracranial Hemorrhages/etiology ; Male ; Middle Aged ; Registries/standards ; Registries/statistics & numerical data ; Warfarin/adverse effects ; Warfarin/therapeutic use
Chemical Substances	Factor Xa Inhibitors ; Warfarin (5Q7ZVV76EI) ; Dabigatran (I0VM4M70GC)
Language	English
Publishing date	2019-12-28
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	605890-5
ISSN	1532-8171 ; 0735-6757
ISSN (online)	1532-8171
ISSN	0735-6757
DOI	10.1016/j.ajem.2019.12.023
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Zs.A 2005: Show issues

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Article: Reducing crude protein in beef cattle diet reduces ammonia emissions from artificial feedyard surfaces.

Todd, Richard W / Cole, N Andy / Clark, R Nolan

Journal of environmental quality

2006 Volume 35, Issue 2, Page(s) 404–411

Abstract: Concentrated animal feeding operations are major sources of ammonia to the atmosphere. Control methods to reduce emissions include acidifying amendments, urease inhibitors, and absorbents. For beef cattle, decreasing crude protein (CP) in diets may be ... ...

Abstract	Concentrated animal feeding operations are major sources of ammonia to the atmosphere. Control methods to reduce emissions include acidifying amendments, urease inhibitors, and absorbents. For beef cattle, decreasing crude protein (CP) in diets may be the most practical and cost-effective method to reduce ammonia emissions. Our objective was to quantify the effect of reducing CP in beef cattle diet on ammonia emissions. Two groups of steers were fed diets with either 11.5 or 13.0% CP and all urine and feces were collected. Manures from the two diet treatments were applied in a replicated laboratory chamber experiment, and ammonia emission was quantified using acid gas washing. In four seasonal field trials, manures from the two diet treatments were applied to two 10-m-diameter, circular, artificial feedyard surfaces, and ammonia emission was quantified using the integrated horizontal flux method. Manure from steers fed 11.5% CP diet had less urine, less urinary N, and a lesser fraction of total N in urine, compared with the 13.0% CP diet. Decreasing crude protein in beef cattle diets from 13 to 11.5% significantly decreased ammonia emission by 44% (p < 0.01) in the closed chamber laboratory experiment, and decreased mean daily ammonia flux by 30% (p = 0.10), 52% (p = 0.08), and 29% (p < 0.01) in summer, autumn, and spring field trials, respectively. No difference was observed in winter. On an annual basis, decreasing crude protein reduced daily ammonia flux by 28%. Reducing crude protein in beef cattle diets may provide the most practical and cost-effective way to reduce ammonia emissions from feedyards.
MeSH term(s)	Air Pollutants/analysis ; Air Pollution/analysis ; Air Pollution/prevention & control ; Ammonia/analysis ; Animal Feed ; Animals ; Cattle ; Diet ; Dietary Proteins ; Manure/analysis ; Nitrogen/analysis ; Nitrogen/urine
Chemical Substances	Air Pollutants ; Dietary Proteins ; Manure ; Ammonia (7664-41-7) ; Nitrogen (N762921K75)
Language	English
Publishing date	2006-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	120525-0
ISSN	1537-2537 ; 0047-2425
ISSN (online)	1537-2537
ISSN	0047-2425
DOI	10.2134/jeq2005.0045
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Zs.A 2958: Show issues

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Article ; Online: Corrigendum to "Priorities to inform research on marine plastic pollution in Southeast Asia" [Sci. Total Environ. volume 841 (2022) Article 156704].

Omeyer, Lucy C M / Duncan, Emily M / Aiemsomboon, Kornrawee / Beaumont, Nicola / Bureekul, Sujaree / Cao, Bin / Carrasco, Luis R / Chavanich, Suchana / Clark, James R / Cordova, Muhammad R / Couceiro, Fay / Cragg, Simon M / Dickson, Neil / Failler, Pierre / Ferraro, Gianluca / Fletcher, Stephen / Fong, Jenny / Ford, Alex T / Gutierrez, Tony /

Hamid, Fauziah Shahul / Hiddink, Jan G / Hoa, Pham T / Holland, Sophie I / Jones, Lowenna / Jones, Nia H / Koldewey, Heather / Lauro, Federico M / Lee, Charlotte / Lewis, Matt / Marks, Danny / Matallana-Surget, Sabine / Mayorga-Adame, Claudia G / McGeehan, John / Messer, Lauren F / Michie, Laura / Miller, Michelle A / Mohamad, Zeeda F / Nor, Nur Hazimah Mohamed / Müller, Moritz / Neill, Simon P / Nelms, Sarah E / Onda, Deo Florence L / Ong, Joyce J L / Pariatamby, Agamuthu / Phang, Sui C / Quilliam, Richard / Robins, Peter E / Salta, Maria / Sartimbul, Aida / Shakuto, Shiori / Skov, Martin W / Taboada, Evelyn B / Todd, Peter A / Toh, Tai Chong / Valiyaveettil, Suresh / Viyakarn, Voranop / Wonnapinij, Passorn / Wood, Louisa E / Yong, Clara L X / Godley, Brendan J

The Science of the total environment

2022 Volume 857, Issue Pt 3, Page(s) 159595

Language	English
Publishing date	2022-10-26
Publishing country	Netherlands
Document type	Published Erratum
ZDB-ID	121506-1
ISSN	1879-1026 ; 0048-9697
ISSN (online)	1879-1026
ISSN	0048-9697
DOI	10.1016/j.scitotenv.2022.159595
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Zs.A 949: Show issues

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Article ; Online: Uptake of services for prevention of mother-to-child transmission of HIV in a community cohort in rural Tanzania from 2005 to 2012.

Gourlay, Annabelle / Wringe, Alison / Todd, Jim / Cawley, Caoimhe / Michael, Denna / Machemba, Richard / Clark, Benjamin / Masesa, Clemens / Marston, Milly / Urassa, Mark / Zaba, Basia

BMC health services research

2016 Volume 16, Page(s) 4

Abstract: Background: Estimates of population-level coverage with prevention of mother-to-child transmission (PMTCT) services are vital for monitoring programmes but are rarely undertaken. This study describes uptake of PMTCT services among HIV-positive pregnant ... ...

Abstract	Background: Estimates of population-level coverage with prevention of mother-to-child transmission (PMTCT) services are vital for monitoring programmes but are rarely undertaken. This study describes uptake of PMTCT services among HIV-positive pregnant women in a community cohort in rural Tanzania. Methods: Kisesa cohort incorporates demographic and HIV sero-surveillance rounds since 1994. Cohort data were linked retrospectively to records from four Kisesa clinics with PMTCT services from 2009 (HIV care and treatment clinic (CTC) available in one facility from 2008; referrals to city hospitals for PMTCT and antiretroviral treatment (ART) from 2005). The proportion of HIV-positive pregnant women residing in Kisesa in 2005-2012 who accessed PMTCT service components (based on linkage to facility records) was calculated per HIV-positive pregnancy and by year, with adjustments made to account for the sensitivity of the linkage algorithm. Results: Out of 1497 HIV-positive pregnancies overall (to 849 women), 26% (n = 387/1497) were not linked to any facility records, 35% (n = 519/1497) registered for ANC but not HIV services (29% (n = 434/1497) were not tested at ANC or diagnosed previously), 8% (n = 119/1497) enrolled in PMTCT but not CTC services (6 % (n = 95/1497) received antiretroviral prophylaxis), and 32% (n = 472/1497) registered for CTC (14% (n = 204/1497) received ART or prophylaxis) (raw estimates). Adjusted estimates for coverage with ANC were 92%, 57% with HIV care, and 29 % with antiretroviral drugs in 2005-2012, trending upwards over time. Conclusions: Population-level coverage with PMTCT services was low overall, with weaknesses throughout the service continuum, but increased over time. Option B+ should improve coverage with antiretrovirals for PMTCT through simplified decisions for initiating ART, but will rely on strengthening access to CTC services.
MeSH term(s)	Adult ; Child ; Community Health Services/statistics & numerical data ; Female ; HIV Infections/drug therapy ; HIV Infections/prevention & control ; HIV Infections/transmission ; Health Knowledge, Attitudes, Practice ; Humans ; Infectious Disease Transmission, Vertical/prevention & control ; Patient Acceptance of Health Care/psychology ; Patient Acceptance of Health Care/statistics & numerical data ; Pregnancy ; Pregnant Women/psychology ; Referral and Consultation ; Retrospective Studies ; Rural Population/statistics & numerical data ; Tanzania/epidemiology ; Young Adult
Language	English
Publishing date	2016-01-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2050434-2
ISSN	1472-6963 ; 1472-6963
ISSN (online)	1472-6963
ISSN	1472-6963
DOI	10.1186/s12913-015-1249-6
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Article ; Online: Integrated molecular and multiparametric MRI mapping of high-grade glioma identifies regional biologic signatures.

Hu, Leland S / D'Angelo, Fulvio / Weiskittel, Taylor M / Caruso, Francesca P / Fortin Ensign, Shannon P / Blomquist, Mylan R / Flick, Matthew J / Wang, Lujia / Sereduk, Christopher P / Meng-Lin, Kevin / De Leon, Gustavo / Nespodzany, Ashley / Urcuyo, Javier C / Gonzales, Ashlyn C / Curtin, Lee / Lewis, Erika M / Singleton, Kyle W / Dondlinger, Timothy / Anil, Aliya /

Semmineh, Natenael B / Noviello, Teresa / Patel, Reyna A / Wang, Panwen / Wang, Junwen / Eschbacher, Jennifer M / Hawkins-Daarud, Andrea / Jackson, Pamela R / Grunfeld, Itamar S / Elrod, Christian / Mazza, Gina L / McGee, Sam C / Paulson, Lisa / Clark-Swanson, Kamala / Lassiter-Morris, Yvette / Smith, Kris A / Nakaji, Peter / Bendok, Bernard R / Zimmerman, Richard S / Krishna, Chandan / Patra, Devi P / Patel, Naresh P / Lyons, Mark / Neal, Matthew / Donev, Kliment / Mrugala, Maciej M / Porter, Alyx B / Beeman, Scott C / Jensen, Todd R / Schmainda, Kathleen M / Zhou, Yuxiang / Baxter, Leslie C / Plaisier, Christopher L / Li, Jing / Li, Hu / Lasorella, Anna / Quarles, C Chad / Swanson, Kristin R / Ceccarelli, Michele / Iavarone, Antonio / Tran, Nhan L

Nature communications

2023 Volume 14, Issue 1, Page(s) 6066

Abstract: Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi- ... ...

Abstract	Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution. Infiltrative NE tumor is alternatively enriched with tumor cells exhibiting neuronal or glycolytic/plurimetabolic cellular states, two principal transcriptomic pathway-based glioma subtypes, which respectively demonstrate abundant private mutations or enrichment in immune cell signatures. These NE phenotypes are non-invasively identified through normalized K2 imaging signatures, which discern cell size heterogeneity on dynamic susceptibility contrast (DSC)-MRI. NE tumor populations predicted to display increased cellular proliferation by mean diffusivity (MD) MRI metrics are uniquely associated with EGFR amplification and CDKN2A homozygous deletion. The biophysical mapping of infiltrative HGG potentially enables the clinical recognition of tumor subpopulations with aggressive molecular signatures driving tumor progression, thereby informing precision medicine targeting.
MeSH term(s)	Humans ; Brain Neoplasms/diagnostic imaging ; Brain Neoplasms/genetics ; Brain Neoplasms/pathology ; Multiparametric Magnetic Resonance Imaging ; Homozygote ; Sequence Deletion ; Glioma/diagnostic imaging ; Glioma/genetics ; Glioma/pathology ; Magnetic Resonance Imaging/methods ; Biological Products
Chemical Substances	Biological Products
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-41559-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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