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Article ; Online: Mucormycosis.

Steinbrink, Julie M / Miceli, Marisa H

Infectious disease clinics of North America

2021 Volume 35, Issue 2, Page(s) 435–452

Abstract: Mucormycosis is a rare but aggressive fungal disease that mainly affects patients with poorly controlled diabetes mellitus and those who are severely immunocompromised, including patients with hematological malignancies and solid organ transplant ... ...

Abstract	Mucormycosis is a rare but aggressive fungal disease that mainly affects patients with poorly controlled diabetes mellitus and those who are severely immunocompromised, including patients with hematological malignancies and solid organ transplant recipients. Early recognition of infection is critical for treatment success, followed by prompt initiation of antifungal therapy with lipid formulation amphotericin B. Posaconazole and isavuconazole should be used for stepdown and salvage therapy. Surgical debridement is key for tissue diagnosis and treatment and should be pursued urgently whenever possible. In addition to surgery and antifungal therapy, reverting the underlying risk factor for infection is important for treatment response.
MeSH term(s)	Antifungal Agents/therapeutic use ; Diabetes Mellitus, Type 2/complications ; Humans ; Immunocompromised Host ; Mucorales/isolation & purification ; Mucorales/pathogenicity ; Mucormycosis/diagnosis ; Mucormycosis/drug therapy ; Mucormycosis/epidemiology
Chemical Substances	Antifungal Agents
Language	English
Publishing date	2021-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1077676-x
ISSN	1557-9824 ; 0891-5520
ISSN (online)	1557-9824
ISSN	0891-5520
DOI	10.1016/j.idc.2021.03.009
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Article ; Online: Infectious complications of vascularized composite allograft transplantation.

Steinbrink, Julie M / Wolfe, Cameron R

Current opinion in organ transplantation

2020 Volume 25, Issue 4, Page(s) 377–382

Abstract: Purpose of review: Vascularized composite allograft (VCA) transplants constitute multiple tissues transplanted together as one functional unit. These procedures are increasing in frequency and complexity, yet data about graft survival, quality of life, ... ...

Abstract	Purpose of review: Vascularized composite allograft (VCA) transplants constitute multiple tissues transplanted together as one functional unit. These procedures are increasing in frequency and complexity, yet data about graft survival, quality of life, and infection risk remain limited. Recent findings: Informative guidance for this patient population is often inferred from the solid organ transplantation literature. Yet, it is important to understand that VCA transplantation additionally carries its own significant and distinctive risk factors for infection. Summary: In this review, we give an overview of previously described infectious complications of VCA transplantation in the literature, discuss risk factors for future infection in these patients, and discuss how to manage such obstacles.
MeSH term(s)	Composite Tissue Allografts/microbiology ; Composite Tissue Allografts/transplantation ; Graft Survival ; Humans ; Infections/epidemiology ; Infections/etiology ; Infections/microbiology ; Organ Transplantation/methods ; Organ Transplantation/statistics & numerical data ; Quality of Life ; Vascularized Composite Allotransplantation/methods ; Vascularized Composite Allotransplantation/statistics & numerical data
Language	English
Publishing date	2020-06-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	1390429-2
ISSN	1531-7013 ; 1087-2418
ISSN (online)	1531-7013
ISSN	1087-2418
DOI	10.1097/MOT.0000000000000780
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Article ; Online: Misinformation and Disinformation: The Potential Disadvantages of Social Media in Infectious Disease and How to Combat Them.

Desai, Angel N / Ruidera, Diandra / Steinbrink, Julie M / Granwehr, Bruno / Lee, Dong Heun

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2022 Volume 74, Issue Suppl_3, Page(s) e34–e39

Abstract: Although the use of social media to spread misinformation and disinformation is not a new concept, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has further highlighted the dangers that misinformation can pose to public health. ...

Abstract	Although the use of social media to spread misinformation and disinformation is not a new concept, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has further highlighted the dangers that misinformation can pose to public health. More than two-thirds of Americans receive their news from at least 1 social media outlet, most of which do not undergo the same review process as academic journals and some professional news organizations. Unfortunately, this can lead to inaccurate health information being conveyed as truth. The purpose of this article is to inform the infectious diseases community of the history and dangers of health misinformation and disinformation in social media, present tools for identifying and responding to misinformation, and propose other ethical considerations for social media.
MeSH term(s)	COVID-19 ; Communicable Diseases ; Communication ; Disinformation ; Humans ; SARS-CoV-2 ; Social Media ; United States
Language	English
Publishing date	2022-05-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciac109
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Article ; Online: Antiviral Treatment Failures After Transplantation of Organs From Donors With Hepatitis C Infection: A Report of 4 Cases.

Steinbrink, Julie M / Narayanasamy, Shanti / Wolfe, Cameron R / Maziarz, Eileen / Byrns, Jennifer / Kiser, Jennifer J / Naggie, Susanna

American journal of kidney diseases : the official journal of the National Kidney Foundation

2023 Volume 82, Issue 3, Page(s) 368–372

Abstract: The transplantation of organs from donors with hepatitis C virus (HCV) infection into uninfected recipients has expanded the available organ donor pool. With the advancement of direct-acting antivirals (DAAs), high rates of cure among transplant ... ...

Abstract	The transplantation of organs from donors with hepatitis C virus (HCV) infection into uninfected recipients has expanded the available organ donor pool. With the advancement of direct-acting antivirals (DAAs), high rates of cure among transplant recipients are possible. Although DAAs are highly effective, treatment failure can occur following an appropriate 12-week course of a pan-genotypic regimen. Here we describe 4 kidney transplant recipients of organs from donors with HCV infection (3 with genotype 3, 1 genotype 1a) in whom first-line DAA treatment with either glecaprevir-pibrentasvir or sofosbuvir-velpatasvir was unsuccessful, started 22-35 days after the day of transplantation. All ultimately achieved sustained virologic response with second- or third-line therapy. Post-treatment resistance-associated substitutions were tested and noted to be present in 2 cases. Additionally, antiviral levels were assessed in 2 cases and found to be therapeutic in each. This article explores possible reasons for treatment failure, including medication interactions, bariatric surgery, viral dynamics, and drug resistance.
MeSH term(s)	Humans ; Antiviral Agents/therapeutic use ; Antiviral Agents/pharmacology ; Hepatitis C, Chronic/drug therapy ; Sofosbuvir/therapeutic use ; Sofosbuvir/pharmacology ; Hepatitis C/drug therapy ; Hepacivirus/genetics ; Treatment Failure ; Tissue Donors ; Sustained Virologic Response ; Genotype
Chemical Substances	Antiviral Agents ; Sofosbuvir (WJ6CA3ZU8B)
Language	English
Publishing date	2023-02-04
Publishing country	United States
Document type	Case Reports ; Research Support, N.I.H., Extramural
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2022.12.006
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Article ; Online: Transcriptional responses define dysregulated immune activation in Hepatitis C (HCV)-naïve recipients of HCV-infected donor kidneys.

Steinbrink, Julie M / Miller, Cameron / Myers, Rachel A / Sanoff, Scott / Mazur, Anna / Burke, Thomas W / Byrns, Jennifer / Jackson, Annette M / Luo, Xunrong / McClain, Micah T

PloS one

2023 Volume 18, Issue 1, Page(s) e0280602

Abstract: Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to ...

Abstract	Renal transplantation from hepatitis C (HCV) nucleic acid amplification test-positive (NAAT-positive) donors to uninfected recipients has greatly increased the organ donation pool. However, there is concern for adverse outcomes in these recipients due to dysregulated immunologic activation secondary to active inflammation from acute viremia at the time of transplantation. This includes increased rates of cytomegalovirus (CMV) DNAemia and allograft rejection. In this study, we evaluate transcriptional responses in circulating leukocytes to define the character, timing, and resolution of this immune dysregulation and assess for biomarkers of adverse outcomes in transplant patients. We enrolled 67 renal transplant recipients (30 controls, 37 HCV recipients) and performed RNA sequencing on serial samples from one, 3-, and 6-months post-transplant. CMV DNAemia and allograft rejection outcomes were measured. Least absolute shrinkage and selection operator was utilized to develop gene expression classifiers predictive of clinical outcomes. Acute HCV incited a marked transcriptomic response in circulating leukocytes of renal transplant recipients in the acute post-transplant setting, despite the presence of immunosuppression, with 109 genes significantly differentially expressed compared to controls. These HCV infection-associated genes were reflective of antiviral immune pathways and generally resolved by the 3-month timepoint after sustained viral response (SVR) for HCV. Differential gene expression was also noted from patients who developed CMV DNAemia or allograft rejection compared to those who did not, although transcriptomic classifiers could not accurately predict these outcomes, likely due to sample size and variable time-to-event. Acute HCV infection incites evidence of immune activation and canonical antiviral responses in the human host even in the presence of systemic immunosuppression. After treatment of HCV with antiviral therapy and subsequent aviremia, this immune activation resolves. Changes in gene expression patterns in circulating leukocytes are associated with some clinical outcomes, although larger studies are needed to develop accurate predictive classifiers of these events.
MeSH term(s)	Humans ; Hepatitis C ; Hepacivirus/genetics ; Tissue Donors ; Antiviral Agents/therapeutic use ; Kidney ; Cytomegalovirus Infections/drug therapy ; Transplant Recipients
Chemical Substances	Antiviral Agents
Language	English
Publishing date	2023-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0280602
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Real-world Experiences in the Transplantation of Hepatitis C-NAAT-positive Organs.

Steinbrink, Julie M / Byrns, Jennifer / Berg, Carl / Kappus, Matthew / King, Lindsay / Ellis, Matthew J / Sanoff, Scott / Agarwal, Richa / DeVore, Adam D / Reynolds, John M / Hartwig, Matthew G / Milano, Carmelo / Sudan, Debra / Maziarz, Eileen K / Saullo, Jennifer / Alexander, Barbara D / Wolfe, Cameron R

Transplantation direct

2023 Volume 9, Issue 11, Page(s) e1539

Abstract: Background: Hepatitis C virus (HCV) nucleic acid amplification test (NAAT)-positive donors have increased the organ pool. Direct-acting antivirals (DAAs) have led to high rates of treatment success and sustained virologic response (SVR) in recipients ... ...

Abstract	Background: Hepatitis C virus (HCV) nucleic acid amplification test (NAAT)-positive donors have increased the organ pool. Direct-acting antivirals (DAAs) have led to high rates of treatment success and sustained virologic response (SVR) in recipients with donor-derived HCV infection without significant adverse effects, although variability remains in the timing and duration of antivirals. Methods: This retrospective study analyzed all adult HCV-NAAT-negative transplant recipients who received an organ from HCV-NAAT-positive donors from November 24, 2018, to March 31, 2022, at Duke University Medical Center with protocolized delay of DAA initiation until after hospital discharge, with at least 180-d follow-up on all patients. Transplant and HCV-related outcomes were analyzed. Results: Two hundred eleven transplants (111 kidneys, 41 livers, 34 hearts, and 25 lungs) were performed from HCV-NAAT-positive donors to HCV-NAAT-negative recipients. Ninety percent of recipients became viremic within 7 d posttransplant. Ninety-nine percent of recipients were initiated on pangenotypic DAAs in the outpatient setting a median of 52 d posttransplant, most commonly with 12-wk courses of sofosbuvir-velpatasvir (lungs) and glecaprevir-pibrentasvir (heart, kidney, and liver). Ninety-seven percent of recipients had SVR after a first-line DAA; all ultimately achieved SVR at 12 wk after subsequent treatment courses. The median peak HCV RNA for all organ systems was 2 436 512 IU/mL; the median time from antiviral to undetectable RNA was 48 d, although differences were noted between organ groups. No patient deaths or graft losses were directly attributable to HCV infection. Conclusions: One hundred percent of transplant recipients of HCV-NAAT-positive organs ultimately developed SVR without significant adverse effects when HCV antivirals were initiated in the outpatient setting after transplant hospitalization, suggesting that this real-world treatment pathway is a viable option.
Language	English
Publishing date	2023-10-10
Publishing country	United States
Document type	Journal Article
ISSN	2373-8731
ISSN	2373-8731
DOI	10.1097/TXD.0000000000001539
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Article ; Online: Transcriptional Profiles Elucidate Differential Host Responses to Infection with

Holcomb, Zachary E / Steinbrink, Julie M / Zaas, Aimee K / Betancourt, Marisol / Tenor, Jennifer L / Toffaletti, Dena L / Alspaugh, J Andrew / Perfect, John R / McClain, Micah T

Journal of fungi (Basel, Switzerland)

2022 Volume 8, Issue 5

Abstract: Many aspects of the host response to invasive cryptococcal infections remain poorly understood. In order to explore the pathobiology of infection with common clinical strains, we infected BALB/cJ mice ... ...

Abstract	Many aspects of the host response to invasive cryptococcal infections remain poorly understood. In order to explore the pathobiology of infection with common clinical strains, we infected BALB/cJ mice with
Language	English
Publishing date	2022-04-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2784229-0
ISSN	2309-608X ; 2309-608X
ISSN (online)	2309-608X
ISSN	2309-608X
DOI	10.3390/jof8050430
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Article: The robust and rapid role of molecular testing in precision fungal diagnostics: A case report.

Steinbrink, Julie M / Hong, David K / Bergin, Stephen P / Al-Rohil, Rami N / Perfect, John R / Maziarz, Eileen K

Medical mycology case reports

2020 Volume 27, Page(s) 77–80

Abstract: Diagnosis of invasive fungal disease remains an ongoing challenge for clinicians, while continuously evolving treatment regimens increase patient risk for invasive infection. This case highlights how molecular testing led to the diagnosis of co-infection ...

Abstract	Diagnosis of invasive fungal disease remains an ongoing challenge for clinicians, while continuously evolving treatment regimens increase patient risk for invasive infection. This case highlights how molecular testing led to the diagnosis of co-infection with two fungal pathogens producing invasive disease in a hematopoietic stem cell transplant recipient with graft-versus-host disease (GVHD).
Language	English
Publishing date	2020-02-13
Publishing country	Netherlands
Document type	Case Reports
ISSN	2211-7539
ISSN	2211-7539
DOI	10.1016/j.mmcr.2020.02.003
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Article ; Online: A transcriptional signature accurately identifies Aspergillus Infection across healthy and immunosuppressed states.

Steinbrink, Julie M / Zaas, Aimee K / Betancourt, Marisol / Modliszewski, Jennifer L / Corcoran, David L / McClain, Micah T

Translational research : the journal of laboratory and clinical medicine

2020 Volume 219, Page(s) 1–12

Abstract: Invasive aspergillosis (IA) is a major cause of critical illness in immunocompromised (IC) patients. However, current fungal tests are limited. Disease-specific gene expression patterns in circulating host cells show promise as novel diagnostics, however ...

Abstract	Invasive aspergillosis (IA) is a major cause of critical illness in immunocompromised (IC) patients. However, current fungal tests are limited. Disease-specific gene expression patterns in circulating host cells show promise as novel diagnostics, however it is unknown whether such a 'signature' exists for IA and the effect of iatrogenic immunosuppression on any such biomarkers. Male BALB/c mice were separated into 6 experimental groups based on Aspergillus fumigatus inhalational exposure and IC status (no immunosuppression, cyclophosphamide, and corticosteroids). Mice were sacrificed 4 days postinfection. Whole blood was assayed for transcriptomic responses in peripheral white blood cells via microarray. An elastic net regularized logistic regression was employed to develop classifiers of IA based on gene expression. Aspergillus infection triggers a powerful response in non-IC hosts with 2718 genes differentially expressed between IA and controls. We generated a 146-gene classifier able to discriminate between non-IC infected and uninfected mice with an AUC of 1. However, immunosuppressive medications exhibited a confounding effect on this transcriptomic classifier. After controlling for the genomic effects of immunosuppression, we were able to generate a 187-gene classifier with an AUC of 0.92 in the absence of immunosuppression, 1 with cyclophosphamide, and 0.9 with steroids. The host transcriptomic response to IA is robust and conserved. Pharmacologic perturbation of the host immune response has powerful effects on classifier performance and must be considered when developing such novel diagnostics. When appropriately designed, host-derived peripheral blood transcriptomic responses demonstrate the ability to accurately diagnose Aspergillus infection, even in the presence of immunosuppression.
MeSH term(s)	Animals ; Aspergillosis/diagnosis ; Aspergillosis/genetics ; Aspergillosis/microbiology ; Aspergillus fumigatus/genetics ; Aspergillus fumigatus/isolation & purification ; Aspergillus fumigatus/pathogenicity ; Case-Control Studies ; Colony Count, Microbial ; Genes, Fungal ; Immunocompromised Host ; Lung/microbiology ; Male ; Mice ; Mice, Inbred BALB C ; Reproducibility of Results ; Transcription, Genetic
Language	English
Publishing date	2020-02-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2246684-8
ISSN	1878-1810 ; 1532-6543 ; 1931-5244
ISSN (online)	1878-1810 ; 1532-6543
ISSN	1931-5244
DOI	10.1016/j.trsl.2020.02.005
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Article: The robust and rapid role of molecular testing in precision fungal diagnostics: A case report

Steinbrink, Julie M / Hong, David K / Bergin, Stephen P / Al-Rohil, Rami N / Perfect, John R / Maziarz, Eileen K

Medical mycology case reports. 2020 Mar., v. 27

2020

Abstract	Diagnosis of invasive fungal disease remains an ongoing challenge for clinicians, while continuously evolving treatment regimens increase patient risk for invasive infection. This case highlights how molecular testing led to the diagnosis of co-infection with two fungal pathogens producing invasive disease in a hematopoietic stem cell transplant recipient with graft-versus-host disease (GVHD).
Keywords	case studies ; diagnostic techniques ; fungi ; hematopoietic stem cells ; mixed infection ; pathogens ; patients
Language	English
Dates of publication	2020-03
Size	p. 77-80.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	2211-7539
DOI	10.1016/j.mmcr.2020.02.003
Database	NAL-Catalogue (AGRICOLA)

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