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  1. Article: IP-10 (CXCL10) Can Trigger Emergence of Dormant Breast Cancer Cells in a Metastatic Liver Microenvironment.

    Clark, Amanda M / Heusey, Haley L / Griffith, Linda G / Lauffenburger, Douglas A / Wells, Alan

    Frontiers in oncology

    2021  Volume 11, Page(s) 676135

    Abstract: Metastatic breast cancer remains a largely incurable and fatal disease with liver involvement bearing the worst prognosis. The danger is compounded by a subset of disseminated tumor cells that may lie dormant for years to decades before re-emerging as ... ...

    Abstract Metastatic breast cancer remains a largely incurable and fatal disease with liver involvement bearing the worst prognosis. The danger is compounded by a subset of disseminated tumor cells that may lie dormant for years to decades before re-emerging as clinically detectable metastases. Pathophysiological signals can drive these tumor cells to emerge. Prior studies indicated CXCR3 ligands as being the predominant signals synergistically and significantly unregulated during inflammation in the gut-liver axis. Of the CXCR3 ligands, IP-10 (CXCL10) was the most abundant, correlated significantly with shortened survival of human breast cancer patients with metastatic disease and was highest in those with triple negative (TNBC) disease. Using a complex
    Language English
    Publishing date 2021-05-27
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2021.676135
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Responsiveness of Critically Ill Adults With Multimorbidity to Rehabilitation Interventions: A Patient-Level Meta-Analysis Using Individual Pooled Data From Four Randomized Trials.

    Jones, Jennifer R A / Karahalios, Amalia / Puthucheary, Zudin A / Berry, Michael J / Files, D Clark / Griffith, David M / McDonald, Luke A / Morris, Peter E / Moss, Marc / Nordon-Craft, Amy / Walsh, Timothy / Berney, Sue / Denehy, Linda

    Critical care medicine

    2023  Volume 51, Issue 10, Page(s) 1373–1385

    Abstract: Objective: To explore if patient characteristics (pre-existing comorbidity, age, sex, and illness severity) modify the effect of physical rehabilitation (intervention vs control) for the coprimary outcomes health-related quality of life (HRQoL) and ... ...

    Abstract Objective: To explore if patient characteristics (pre-existing comorbidity, age, sex, and illness severity) modify the effect of physical rehabilitation (intervention vs control) for the coprimary outcomes health-related quality of life (HRQoL) and objective physical performance using pooled individual patient data from randomized controlled trials (RCTs).
    Data sources: Data of individual patients from four critical care physical rehabilitation RCTs.
    Study selection: Eligible trials were identified from a published systematic review.
    Data extraction: Data sharing agreements were executed permitting transfer of anonymized data of individual patients from four trials to form one large, combined dataset. The pooled trial data were analyzed with linear mixed models fitted with fixed effects for treatment group, time, and trial.
    Data synthesis: Four trials contributed data resulting in a combined total of 810 patients (intervention n = 403, control n = 407). After receiving trial rehabilitation interventions, patients with two or more comorbidities had HRQoL scores that were significantly higher and exceeded the minimal important difference at 3 and 6 months compared with the similarly comorbid control group (based on the Physical Component Summary score (Wald test p = 0.041). Patients with one or no comorbidities who received intervention had no HRQoL outcome differences at 3 and 6 months when compared with similarly comorbid control patients. No patient characteristic modified the physical performance outcome in patients who received physical rehabilitation.
    Conclusions: The identification of a target group with two or more comorbidities who derived benefits from the trial interventions is an important finding and provides direction for future investigations into the effect of rehabilitation. The multimorbid post-ICU population may be a select population for future prospective investigations into the effect of physical rehabilitation.
    MeSH term(s) Humans ; Adult ; Multimorbidity ; Critical Illness/rehabilitation ; Randomized Controlled Trials as Topic ; Quality of Life ; Critical Care
    Language English
    Publishing date 2023-05-30
    Publishing country United States
    Document type Meta-Analysis ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 197890-1
    ISSN 1530-0293 ; 0090-3493
    ISSN (online) 1530-0293
    ISSN 0090-3493
    DOI 10.1097/CCM.0000000000005936
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Engagement with Traditional Healers for Early Detection of Plague in Uganda.

    Apangu, Titus / Candini, Gordian / Abaru, Janet / Candia, Bosco / Okoth, Felix J / Atiku, Linda A / Griffith, Kevin S / Hayden, Mary H / Zielinski-Gutiérrez, Emily / Schwartz, Amy M / McCormick, David W / Mead, Paul S / Kugeler, Kiersten J

    The American journal of tropical medicine and hygiene

    2023  Volume 109, Issue 5, Page(s) 1129–1136

    Abstract: In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can ...

    Abstract In rural Uganda, many people who are ill consult traditional healers prior to visiting the formal healthcare system. Traditional healers provide supportive care for common illnesses, but their care may delay diagnosis and management of illnesses that can increase morbidity and mortality, hinder early detection of epidemic-prone diseases, and increase occupational risk to traditional healers. We conducted open-ended, semi-structured interviews with a convenience sample of 11 traditional healers in the plague-endemic West Nile region of northwestern Uganda to assess their knowledge, practices, and attitudes regarding plague and the local healthcare system. Most were generally knowledgeable about plague transmission and its clinical presentation and expressed willingness to refer patients to the formal healthcare system. We initiated a public health outreach program to further improve engagement between traditional healers and local health centers to foster trust in the formal healthcare system and improve early identification and referral of patients with plaguelike symptoms, which can reflect numerous other infectious and noninfectious conditions. During 2010-2019, 65 traditional healers were involved in the outreach program; 52 traditional healers referred 788 patients to area health centers. The diagnosis was available for 775 patients; malaria (37%) and respiratory tract infections (23%) were the most common diagnoses. One patient had confirmed bubonic plague. Outreach to improve communication and trust between traditional healers and local healthcare settings may result in improved early case detection and intervention not only for plague but also for other serious conditions.
    MeSH term(s) Humans ; Uganda/epidemiology ; Traditional Medicine Practitioners ; Plague/diagnosis ; Plague/epidemiology ; Plague/therapy ; Delivery of Health Care ; Referral and Consultation ; Medicine, African Traditional
    Language English
    Publishing date 2023-10-02
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 2942-7
    ISSN 1476-1645 ; 0002-9637
    ISSN (online) 1476-1645
    ISSN 0002-9637
    DOI 10.4269/ajtmh.23-0101
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Identification of missense MAB21L1 variants in microphthalmia and aniridia.

    Seese, Sarah E / Reis, Linda M / Deml, Brett / Griffith, Christopher / Reich, Adi / Jamieson, Robyn V / Semina, Elena V

    Human mutation

    2021  Volume 42, Issue 7, Page(s) 877–890

    Abstract: Microphthalmia, coloboma, and aniridia are congenital ocular phenotypes with a strong genetic component but often unknown cause. We present a likely causative novel variant in MAB21L1, c.152G>T p.(Arg51Leu), in two family members with microphthalmia and ... ...

    Abstract Microphthalmia, coloboma, and aniridia are congenital ocular phenotypes with a strong genetic component but often unknown cause. We present a likely causative novel variant in MAB21L1, c.152G>T p.(Arg51Leu), in two family members with microphthalmia and aniridia, as well as novel or rare compound heterozygous variants of uncertain significance, c.184C>T p.(Arg62Cys)/c.-68T>C, and c.658G>C p.(Gly220Arg)/c.*529A>G, in two additional probands with microphthalmia, coloboma and/or cataracts. All variants were predicted as damaging by in silico programs. In vitro studies of coding variants revealed normal subcellular localization but variable stability for the corresponding mutant proteins. In vivo complementation assays using the zebrafish mab21l2
    MeSH term(s) Animals ; Aniridia/genetics ; Coloboma/genetics ; Eye Proteins ; Homeodomain Proteins/genetics ; Humans ; Intracellular Signaling Peptides and Proteins ; Microphthalmos/genetics ; Zebrafish/genetics ; Zebrafish Proteins/genetics
    Chemical Substances Eye Proteins ; Homeodomain Proteins ; Intracellular Signaling Peptides and Proteins ; MAB21L1 protein, human ; Zebrafish Proteins ; mab21l2 protein, zebrafish
    Language English
    Publishing date 2021-05-24
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1126646-6
    ISSN 1098-1004 ; 1059-7794
    ISSN (online) 1098-1004
    ISSN 1059-7794
    DOI 10.1002/humu.24218
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Extensive intrathecal T cell renewal following hematopoietic transplantation for multiple sclerosis.

    Harris, Kristina M / Lim, Noha / Lindau, Paul / Robins, Harlan / Griffith, Linda M / Nash, Richard A / Turka, Laurence A / Muraro, Paolo A

    JCI insight

    2020  Volume 5, Issue 2

    Abstract: A recent study of autologous hematopoietic stem cell transplantation (AHSCT) for active relapsing-remitting multiple sclerosis (RRMS) showed efficacy in preventing disease worsening. However, the immunologic basis for efficacy remains poorly defined. ... ...

    Abstract A recent study of autologous hematopoietic stem cell transplantation (AHSCT) for active relapsing-remitting multiple sclerosis (RRMS) showed efficacy in preventing disease worsening. However, the immunologic basis for efficacy remains poorly defined. Multiple sclerosis pathology is known to be driven by inflammatory T cells that infiltrate the CNS. Therefore, we hypothesized that the preexisting T cell repertoire in the intrathecal compartment of active RRMS participants was ablated and replaced with new clones following AHSCT. T cell repertoires were assessed using high-throughput TCRβ chain sequencing in paired cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T cells from participants that underwent AHSCT, before and up to 4 years following transplantation. More than 90% of the preexisting CSF repertoire in participants with active RRMS was removed following AHSCT and replaced with clonotypes predominantly generated from engrafted autologous stem cells. Of the preexisting clones in CSF, approximately 60% were also detected in blood before therapy, and concordant treatment effects were observed for clonotypes in both compartments following AHSCT. These results indicate that replacement of the preexisting TCR repertoire in active RRMS is a mechanism for AHSCT efficacy and suggest that peripheral blood could serve as a surrogate for CSF to define mechanisms associated with efficacy in future studies of AHSCT.
    MeSH term(s) Autografts ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/immunology ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Multiple Sclerosis, Relapsing-Remitting/cerebrospinal fluid ; Multiple Sclerosis, Relapsing-Remitting/immunology ; Multiple Sclerosis, Relapsing-Remitting/therapy ; T-Lymphocytes ; Transplantation, Autologous/methods
    Language English
    Publishing date 2020-01-30
    Publishing country United States
    Document type Journal Article
    ISSN 2379-3708
    ISSN (online) 2379-3708
    DOI 10.1172/jci.insight.127655
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Application of a gut-immune co-culture system for the study of N-glycan-dependent host-pathogen interactions of Campylobacter jejuni.

    Zamora, Cristina Y / Ward, Elizabeth M / Kester, Jemila C / Chen, Wen Li Kelly / Velazquez, Jason G / Griffith, Linda G / Imperiali, Barbara

    Glycobiology

    2020  Volume 30, Issue 6, Page(s) 374–381

    Abstract: An in vitro gut-immune co-culture model with apical and basal accessibility, designed to more closely resemble a human intestinal microenvironment, was employed to study the role of the N-linked protein glycosylation pathway in Campylobacter jejuni ... ...

    Abstract An in vitro gut-immune co-culture model with apical and basal accessibility, designed to more closely resemble a human intestinal microenvironment, was employed to study the role of the N-linked protein glycosylation pathway in Campylobacter jejuni pathogenicity. The gut-immune co-culture (GIC) was developed to model important aspects of the human small intestine by the inclusion of mucin-producing goblet cells, human enterocytes and dendritic cells, bringing together a mucus-containing epithelial monolayer with elements of the innate immune system. The utility of the system was demonstrated by characterizing host-pathogen interactions facilitated by N-linked glycosylation, such as host epithelial barrier functions, bacterial invasion and immunogenicity. Changes in human intestinal barrier functions in the presence of 11168 C. jejuni (wildtype) strains were quantified using GICs. The glycosylation-impaired strain 11168 ΔpglE was 100-fold less capable of adhering to and invading this intestinal model in cell infectivity assays. Quantification of inflammatory signaling revealed that 11168ΔpglE differentially modulated inflammatory responses in different intestinal microenvironments, suppressive in some but activating in others. Virulence-associated outer membrane vesicles produced by wildtype and 11168ΔpglE C. jejuni were shown to have differential composition and function, with both leading to immune system activation when provided to the gut-immune co-culture model. This analysis of aspects of C. jejuni infectivity in the presence and absence of its N-linked glycome is enabled by application of the gut-immune model, and we anticipate that this system will be applicable to further studies of C. jejuni and other enteropathogens of interest.
    MeSH term(s) Animals ; Campylobacter jejuni/immunology ; Coculture Techniques ; Gastrointestinal Microbiome/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Polysaccharides/chemistry ; Polysaccharides/immunology
    Chemical Substances Polysaccharides
    Language English
    Publishing date 2020-01-18
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 1067689-2
    ISSN 1460-2423 ; 0959-6658
    ISSN (online) 1460-2423
    ISSN 0959-6658
    DOI 10.1093/glycob/cwz105
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The Vaginal Microbiome as a Tool to Predict rASRM Stage of Disease in Endometriosis: a Pilot Study.

    Perrotta, Allison R / Borrelli, Giuliano M / Martins, Carlo O / Kallas, Esper G / Sanabani, Sabri S / Griffith, Linda G / Alm, Eric J / Abrao, Mauricio S

    Reproductive sciences (Thousand Oaks, Calif.)

    2020  Volume 27, Issue 4, Page(s) 1064–1073

    Abstract: Endometriosis remains a challenge to understand and to diagnose. This is an observational cross-sectional pilot study to characterize the gut and vaginal microbiome profiles among endometriosis patients and control subjects without the disease and to ... ...

    Abstract Endometriosis remains a challenge to understand and to diagnose. This is an observational cross-sectional pilot study to characterize the gut and vaginal microbiome profiles among endometriosis patients and control subjects without the disease and to explore their potential use as a less-invasive diagnostic tool for endometriosis. Overall, 59 women were included, n = 35 with endometriosis and n = 24 controls. Rectal and vaginal samples were collected in two different periods of the menstrual cycle from all subjects. Gut and vaginal microbiomes from patients with different rASRM (revised American Society for Reproductive Medicine) endometriosis stages and controls were analyzed. Illumina sequencing libraries were constructed using a two-step 16S rRNA gene PCR amplicon approach. Correlations of 16S rRNA gene amplicon data with clinical metadata were conducted using a random forest-based machine-learning classification analysis. Distribution of vaginal CSTs (community state types) significantly differed between follicular and menstrual phases of the menstrual cycle (p = 0.021, Fisher's exact test). Vaginal and rectal microbiome profiles and their association to severity of endometriosis (according to rASRM stages) were evaluated. Classification models built with machine-learning methods on the microbiota composition during follicular and menstrual phases of the cycle were built, and it was possible to accurately predict rASRM stages 1-2 verses rASRM stages 3-4 endometriosis. The feature contributing the most to this prediction was an OTU (operational taxonomic unit) from the genus Anaerococcus. Gut and vaginal microbiomes of women with endometriosis have been investigated. Our findings suggest for the first time that vaginal microbiome may predict stage of disease when endometriosis is present.
    MeSH term(s) Adult ; Cross-Sectional Studies ; Disease Progression ; Endometriosis/diagnosis ; Endometriosis/microbiology ; Female ; Humans ; Menstrual Cycle ; Microbiota ; Middle Aged ; Pilot Projects ; ROC Curve ; Rectum/microbiology ; Vagina/microbiology ; Young Adult
    Language English
    Publishing date 2020-01-06
    Publishing country United States
    Document type Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2276411-2
    ISSN 1933-7205 ; 1933-7191
    ISSN (online) 1933-7205
    ISSN 1933-7191
    DOI 10.1007/s43032-019-00113-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: An immune-competent human gut microphysiological system enables inflammation-modulation by Faecalibacterium prausnitzii.

    Zhang, Jianbo / Huang, Yu-Ja / Trapecar, Martin / Wright, Charles / Schneider, Kirsten / Kemmitt, John / Hernandez-Gordillo, Victor / Yoon, Jun Young / Poyet, Mathilde / Alm, Eric J / Breault, David T / Trumper, David L / Griffith, Linda G

    NPJ biofilms and microbiomes

    2024  Volume 10, Issue 1, Page(s) 31

    Abstract: Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering ... ...

    Abstract Crosstalk of microbes with human gut epithelia and immune cells is crucial for gut health. However, there is no existing system for a long-term co-culture of human innate immune cells with epithelium and oxygen-intolerant commensal microbes, hindering the understanding of microbe-immune interactions in a controlled manner. Here, we established a gut epithelium-microbe-immune (GuMI) microphysiological system to maintain the long-term continuous co-culture of Faecalibacterium prausnitzii/Faecalibacterium duncaniae with colonic epithelium, antigen-presenting cells (APCs, herein dendritic cells and macrophages), and CD4
    MeSH term(s) Humans ; Faecalibacterium prausnitzii/physiology ; Microphysiological Systems ; Toll-Like Receptor 1 ; Cytokines ; Inflammation
    Chemical Substances Toll-Like Receptor 1 ; Cytokines
    Language English
    Publishing date 2024-03-29
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2817021-0
    ISSN 2055-5008 ; 2055-5008
    ISSN (online) 2055-5008
    ISSN 2055-5008
    DOI 10.1038/s41522-024-00501-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Synthetic extracellular matrices and astrocytes provide a supportive microenvironment for the cultivation and investigation of primary pediatric gliomas.

    Rota, Christopher M / Brown, Alexander T / Addleson, Emily / Ives, Clara / Trumper, Ella / Pelton, Kristine / Teh, Wei Pin / Schniederjan, Matthew J / Castellino, Robert Craig / Buhrlage, Sara / Lauffenburger, Douglas A / Ligon, Keith L / Griffith, Linda G / Segal, Rosalind A

    Neuro-oncology advances

    2022  Volume 4, Issue 1, Page(s) vdac049

    Abstract: Background: Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic ... ...

    Abstract Background: Pediatric gliomas comprise a diverse set of brain tumor entities that have substantial long-term ramifications for patient survival and quality of life. However, the study of these tumors is currently limited due to a lack of authentic models. Additionally, many aspects of pediatric brain tumor biology, such as tumor cell invasiveness, have been difficult to study with currently available tools. To address these issues, we developed a synthetic extracellular matrix (sECM)-based culture system to grow and study primary pediatric brain tumor cells.
    Methods: We developed a brain-like sECM material as a supportive scaffold for the culture of primary, patient-derived pediatric glioma cells and established patient-derived cell lines. Primary juvenile brainstem-derived murine astrocytes were used as a feeder layer to support the growth of primary human tumor cells.
    Results: We found that our culture system facilitated the proliferation of various primary pediatric brain tumors, including low-grade gliomas, and enabled ex vivo testing of investigational therapeutics. Additionally, we found that tuning this sECM material allowed us to assess high-grade pediatric glioma cell invasion and evaluate therapeutic interventions targeting invasive behavior.
    Conclusion: Our sECM culture platform provides a multipurpose tool for pediatric brain tumor researchers that enables both a wide breadth of biological assays and the cultivation of diverse tumor types.
    Language English
    Publishing date 2022-04-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 3009682-0
    ISSN 2632-2498 ; 2632-2498
    ISSN (online) 2632-2498
    ISSN 2632-2498
    DOI 10.1093/noajnl/vdac049
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report.

    Mohiuddin, Muhammad M / Singh, Avneesh K / Scobie, Linda / Goerlich, Corbin E / Grazioli, Alison / Saharia, Kapil / Crossan, Claire / Burke, Allen / Drachenberg, Cinthia / Oguz, Cihan / Zhang, Tianshu / Lewis, Billeta / Hershfeld, Alena / Sentz, Faith / Tatarov, Ivan / Mudd, Sarah / Braileanu, Gheorghe / Rice, Kathryn / Paolini, John F /
    Bondensgaard, Kent / Vaught, Todd / Kuravi, Kasinath / Sorrells, Lori / Dandro, Amy / Ayares, David / Lau, Christine / Griffith, Bartley P

    Lancet (London, England)

    2023  Volume 402, Issue 10399, Page(s) 397–410

    Abstract: Background: A genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ... ...

    Abstract Background: A genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ineligible for an allograft. This report details our current understanding of factors important to the xenotransplantation outcome.
    Methods: Physiological and biochemical parameters critical for the care of all heart transplant recipients were collected in extensive clinical monitoring in an intensive care unit. To ascertain the cause of xenograft dysfunction, we did extensive immunological and histopathological studies, including electron microscopy and quantification of porcine cytomegalovirus or porcine roseolovirus (PCMV/PRV) in the xenograft, recipient cells, and tissue by DNA PCR and RNA transcription. We performed intravenous immunoglobulin (IVIG) binding to donor cells and single-cell RNA sequencing of peripheral blood mononuclear cells.
    Findings: After successful xenotransplantation, the graft functioned well on echocardiography and sustained cardiovascular and other organ systems functions until postoperative day 47 when diastolic heart failure occurred. At postoperative day 50, the endomyocardial biopsy revealed damaged capillaries with interstitial oedema, red cell extravasation, rare thrombotic microangiopathy, and complement deposition. Increased anti-pig xenoantibodies, mainly IgG, were detected after IVIG administration for hypogammaglobulinaemia and during the first plasma exchange. Endomyocardial biopsy on postoperative day 56 showed fibrotic changes consistent with progressive myocardial stiffness. Microbial cell-free DNA testing indicated increasing titres of PCMV/PRV cell-free DNA. Post-mortem single-cell RNA sequencing showed overlapping causes.
    Interpretation: Hyperacute rejection was avoided. We identified potential mediators of the observed endothelial injury. First, widespread endothelial injury indicates antibody-mediated rejection. Second, IVIG bound strongly to donor endothelium, possibly causing immune activation. Finally, reactivation and replication of latent PCMV/PRV in the xenograft possibly initiated a damaging inflammatory response. The findings point to specific measures to improve xenotransplant outcomes in the future.
    Funding: The University of Maryland School of Medicine, and the University of Maryland Medical Center.
    MeSH term(s) Humans ; Male ; Transplantation, Heterologous ; Compassionate Use Trials ; Leukocytes, Mononuclear ; Immunoglobulins, Intravenous ; Heart ; Graft Rejection/prevention & control
    Chemical Substances Immunoglobulins, Intravenous
    Language English
    Publishing date 2023-06-29
    Publishing country England
    Document type Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 3306-6
    ISSN 1474-547X ; 0023-7507 ; 0140-6736
    ISSN (online) 1474-547X
    ISSN 0023-7507 ; 0140-6736
    DOI 10.1016/S0140-6736(23)00775-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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