54,614 results on '"Immunosuppression therapy"'
Search Results
2. Effect of Immunosuppressive Regimens on Metabolic Dysfunction-associated Fatty Liver Disease Following Liver Transplantation
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Kang, Jing, Zhu, Ji-Qiao, Wang, Yan, and He, Qiang
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- 2025
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3. Circadian control of tumor immunosuppression affects efficacy of immune checkpoint blockade
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Fortin, Bridget M, Pfeiffer, Shannon M, Insua-Rodríguez, Jacob, Alshetaiwi, Hamad, Moshensky, Alexander, Song, Wei A, Mahieu, Alisa L, Chun, Sung Kook, Lewis, Amber N, Hsu, Alex, Adam, Isam, Eng, Oliver S, Pannunzio, Nicholas R, Seldin, Marcus M, Marazzi, Ivan, Marangoni, Francesco, Lawson, Devon A, Kessenbrock, Kai, and Masri, Selma
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Digestive Diseases ,Genetics ,Immunotherapy ,Cancer ,Sleep Research ,Colo-Rectal Cancer ,2.1 Biological and endogenous factors ,Inflammatory and immune system ,Animals ,Mice ,Immune Checkpoint Inhibitors ,Myeloid-Derived Suppressor Cells ,Circadian Clocks ,B7-H1 Antigen ,Mice ,Inbred C57BL ,Circadian Rhythm ,CD8-Positive T-Lymphocytes ,Colorectal Neoplasms ,Tumor Microenvironment ,Immune Tolerance ,Humans ,Female ,Cell Line ,Tumor ,Single-Cell Analysis ,Immunosuppression Therapy ,Cytokines ,Male ,Biochemistry and cell biology - Abstract
The circadian clock is a critical regulator of immunity, and this circadian control of immune modulation has an essential function in host defense and tumor immunosurveillance. Here we use a single-cell RNA sequencing approach and a genetic model of colorectal cancer to identify clock-dependent changes to the immune landscape that control the abundance of immunosuppressive cells and consequent suppression of cytotoxic CD8+ T cells. Of these immunosuppressive cell types, PD-L1-expressing myeloid-derived suppressor cells (MDSCs) peak in abundance in a rhythmic manner. Disruption of the epithelial cell clock regulates the secretion of cytokines that promote heightened inflammation, recruitment of neutrophils and the subsequent development of MDSCs. We also show that time-of-day anti-PD-L1 delivery is most effective when synchronized with the abundance of immunosuppressive MDSCs. Collectively, these data indicate that circadian gating of tumor immunosuppression informs the timing and efficacy of immune checkpoint inhibitors.
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- 2024
4. Skin cancer incidence in Mexican renal transplant recipients: a cohort over 56 years.
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Malagón‐Liceaga, Andrea, Bermúdez‐Rodríguez, Samantha Paola, Romero‐Aguila, Jesús Alejandro, Carolina, Lopez‐Jimenez Fanny, Palafox‐Romo, Rebeca, Díaz‐Sánchez, Verónica Monserrat, Marino‐Vazquez, Lluvia, Morales‐Buenrostro, Luis Eduardo, Alberú Gómez, Josefina, Domínguez‐Cherit, Judith, and Ruelas‐Villavicencio, Ana Lilia
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BASAL cell carcinoma , *ERGONOMICS , *HUMAN papillomavirus , *SUNSHINE , *SKIN grafting , *SKIN cancer - Abstract
Background: Skin cancer is a primary health concern in renal transplant recipients (RTRs). Existing research mainly stems from North America, Europe, and Australia, with limited data from Latin America. Methods: This 56‐year (1967–2023) retrospective cohort study explores skin cancer incidence in Mexican RTRs. Our objective was to assess the long‐term incidence of malignant cutaneous neoplasms in Mexican RTRs. Results: Over 56 years, 1642 RTRs (58% male) were studied. Median follow‐up was 8.4 years; median age at transplantation was 32.6 years. Skin cancer incidence was 6.6% (95% CI: 5.5–7.9), with an incidence density rate of 6.5 (95% CI: 5.4–7.9) per 1000 person‐years and a median latency of 9.8 years. Incidence increased with longer transplantation‐related immunosuppression (TRI), with a relative risk for >30 years of TRI of 4.8 (95% CI: 2.6–9.1) for any skin cancer and 7.5 (95% CI: 3.8–14.6) for squamous cell carcinoma (SCC). SCC was the most common malignancy (76.1%), followed by basal cell carcinomas (BCC), with a 3.6:1 ratio. Metastatic SCC occurred in 6.5% of skin cancer patients, with a skin cancer‐related mortality rate of 2.7%. Limitations of the study include its single‐center and retrospective design and unassessed factors such as human papillomavirus infection and sun exposure. Conclusions: Our study provides unique insights into the epidemiology of skin cancer among Mexican RTRs. It constitutes the largest cohort of skin cancer cases among RTRs in Mexico and, to our knowledge, in Latin America. Despite the lack of recognition of a high skin cancer incidence in non‐White RTRs, our 6.6% incidence underscores the need to enhance surveillance programs. [ABSTRACT FROM AUTHOR]
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- 2024
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5. Adherencia al Tratamiento Inmunosupresor en Pacientes Trasplantados Renales en una Institución de Salud de la Ciudad de Corrientes, entre 2018-2023.
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Briend, Patricio, Giménez, Luciana, Medina, Óscar, and Romero, Romina
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KIDNEY transplantation ,PATIENT compliance ,HEALTH services accessibility ,CROSS-sectional method ,MEDICAL care use ,IMMUNOSUPPRESSIVE agents ,PATIENTS ,TRANSPLANTATION of organs, tissues, etc. ,SCIENTIFIC observation ,QUESTIONNAIRES ,SEX distribution ,QUANTITATIVE research ,DESCRIPTIVE statistics ,AGE distribution ,RESEARCH methodology ,DRUGS ,HEALTH facilities ,COMPARATIVE studies ,DATA analysis software ,PATIENTS' attitudes ,HEALTH care rationing ,IMMUNOSUPPRESSION - Abstract
Copyright of Nursing Notes. Notas de Enfermería is the property of Sanatorio Allende and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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6. Lupusnephritis im Kindes- und Jugendalter.
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Suhlrie, Adriana and Haffner, Dieter
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Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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7. Nierentransplantation bei Kindern und Jugendlichen.
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Pape, Lars
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Copyright of Monatsschrift Kinderheilkunde is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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8. Animal models for transplant immunology: bridging bench to bedside
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Minseok Kang, Hwon Kyum Park, Kyeong Sik Kim, and Dongho Choi
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animal models ,graft rejection ,immunosuppression therapy ,immune tolerance ,xenotransplantation ,Specialties of internal medicine ,RC581-951 ,Surgery ,RD1-811 - Abstract
The progress of transplantation has been propelled forward by animal experiments. Animal models have not only provided opportunities to understand complex immune mechanisms in transplantation but also served as a platform to assess therapeutic interventions. While small animals have been instrumental in uncovering new therapeutic concepts related to immunosuppression and immune tolerance, the progression to human trials has largely been driven by studies in large animals. Recent research has begun to explore the potential of porcine organs to address the shortage of available organs. The consistent progress in transplant immunology research can be attributed to a thorough understanding of animal models. This review provides a comprehensive overview of the available animal models, detailing their modifications, strengths, and weaknesses, as well as their historical applications, to aid researchers in selecting the most suitable model for their specific research needs.
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- 2024
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9. Telomere length and immunosuppression in non-idiopathic pulmonary fibrosis interstitial lung disease
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Zhang, David, Adegunsoye, Ayodeji, Oldham, Justin M, Kozlitina, Julia, Garcia, Nicole, Poonawalla, Maria, Strykowski, Rachel, Linderholm, Angela L, Ley, Brett, Ma, Shwu-Fan, Noth, Imre, Strek, Mary E, Wolters, Paul J, Garcia, Christine Kim, and Newton, Chad A
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Biomedical and Clinical Sciences ,Cardiovascular Medicine and Haematology ,Rare Diseases ,Lung ,2.1 Biological and endogenous factors ,Respiratory ,Good Health and Well Being ,Humans ,Azathioprine ,Retrospective Studies ,Lung Diseases ,Interstitial ,Idiopathic Pulmonary Fibrosis ,Immunosuppressive Agents ,Connective Tissue Diseases ,Immunosuppression Therapy ,Telomere ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology - Abstract
BackgroundStudies suggest a harmful pharmacogenomic interaction exists between short leukocyte telomere length (LTL) and immunosuppressants in idiopathic pulmonary fibrosis (IPF). It remains unknown if a similar interaction exists in non-IPF interstitial lung disease (ILD).MethodsA retrospective, multicentre cohort analysis was performed in fibrotic hypersensitivity pneumonitis (fHP), unclassifiable ILD (uILD) and connective tissue disease (CTD)-ILD patients from five centres. LTL was measured by quantitative PCR for discovery and replication cohorts and expressed as age-adjusted percentiles of normal. Inverse probability of treatment weights based on propensity scores were used to assess the association between mycophenolate or azathioprine exposure and age-adjusted LTL on 2-year transplant-free survival using weighted Cox proportional hazards regression incorporating time-dependent immunosuppressant exposure.ResultsThe discovery and replication cohorts included 613 and 325 patients, respectively. In total, 40% of patients were exposed to immunosuppression and 22% had LTL
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- 2023
10. Incidence of serious respiratory tract infections and associated characteristics in a population exposed to immunosuppressive therapies: a register-based population study
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Cindy Etienne, Ana-Maria Vilcu, Flora Finet, Sylvain Chawki, Thierry Blanchon, Olivier Steichen, and Thomas Hanslik
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Respiratory tract infections ,Pneumonia ,Streptococcus pneumoniae ,Pneumocystis ,Immunosuppression therapy ,Biological therapy ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background Immunosuppressive therapies are associated with a risk of infections. Nevertheless, their incidence in this population remains unclear. This study aims to determine the incidence of serious respiratory tract infections (SRI) in a population exposed to immunosuppressive therapies. Methods Data from a representative sample of the French healthcare claims from 01/01/2014 to 12/31/2019 were analyzed. Exposure to immunosuppressive therapy was defined by the dispensation of drugs through community pharmacies or in hospitals. SRI diagnosis was based on ICD-10 codes from hospitalization records. A cohort analysis was performed to estimate standardized SRI incidence rates. A nested case-control analysis within this cohort was used to study the characteristics associated with SRI. Results We identified 24,122 individuals exposed to immunosuppressive therapies, among which 1,559 developed SRI, resulting in a standardized incidence rate of 1,398 per 100,000 person-years. In this population, the risk of SRI was associated with a history of cancer (OR 2.68, 95% Confidence Intervals (CI) 2.24–3.21; p
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- 2024
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11. Fulminant Myocarditis in Patients With Autoimmune Disease That Requires Extracorporeal Membrane Oxygenation Support
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Filip Depta, MD, PhD, Ingrid Olejárová, MD, PhD, Dušan Rybár, MD, PhD, Pavol Murín, MD, PhD, Marián Švajdler, MD, PhD, and Tomáš Grendel, MD, PhD
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myocarditis ,autoimmunity ,extracorporeal membrane oxygenation ,immunosuppression therapy ,connective tissue diseases ,polymyositis ,lupus erythematosus, systemic ,immunoglobulin g4-related disease ,Diseases of the circulatory (Cardiovascular) system ,RC666-701 - Abstract
Myocarditis is a potentially life-threatening inflammatory disease of the myocardium, often resulting from infectious and immune-mediated responses. Clinical presentation in severe cases often results in a devastating illness requiring extracorporeal membrane oxygenation support as a result of cardiogenic shock. Although endomyocardial biopsy is still considered the gold standard for diagnosis, it often reveals nonspecific lymphocytic infiltration. Because the precise cause is usually unknown, the initial treatment typically involves immunosuppression and frequent assessment of myocardial contractility. This report presents 3 rare cases of autoimmune diseases (polymyositis, immunoglobulin G4–related disease, and systemic lupus erythematosus) that require extracorporeal membrane oxygenation support as a result of fulminant myocarditis, including their follow-up periods.
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- 2024
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12. Incidence of serious respiratory tract infections and associated characteristics in a population exposed to immunosuppressive therapies: a register-based population study.
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Etienne, Cindy, Vilcu, Ana-Maria, Finet, Flora, Chawki, Sylvain, Blanchon, Thierry, Steichen, Olivier, and Hanslik, Thomas
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IMMUNOSUPPRESSIVE agents ,RESPIRATORY infections ,PNEUMOCYSTIS pneumonia ,MENTAL illness ,ANTIRHEUMATIC agents ,NON-communicable diseases - Abstract
Background: Immunosuppressive therapies are associated with a risk of infections. Nevertheless, their incidence in this population remains unclear. This study aims to determine the incidence of serious respiratory tract infections (SRI) in a population exposed to immunosuppressive therapies. Methods: Data from a representative sample of the French healthcare claims from 01/01/2014 to 12/31/2019 were analyzed. Exposure to immunosuppressive therapy was defined by the dispensation of drugs through community pharmacies or in hospitals. SRI diagnosis was based on ICD-10 codes from hospitalization records. A cohort analysis was performed to estimate standardized SRI incidence rates. A nested case-control analysis within this cohort was used to study the characteristics associated with SRI. Results: We identified 24,122 individuals exposed to immunosuppressive therapies, among which 1,559 developed SRI, resulting in a standardized incidence rate of 1,398 per 100,000 person-years. In this population, the risk of SRI was associated with a history of cancer (OR 2.68, 95% Confidence Intervals (CI) 2.24–3.21; p < 0.001), chronic respiratory disease (2.62, 95%CI 2.17–3.16; p < 0.001), end-stage renal failure (2.38, 95%CI 1.37–4.13; p = 0.003), neurodegenerative diseases (1.52, 95%CI 1.07–2.17; p = 0.026), diabetes (1.44, 95%CI 1.14–1.82; p < 0.001), psychiatric diseases (1.27, 95%CI 1.06–1.52; p < 0.001), and cardiovascular diseases (1.26, 95%CI 1.04–1.52; p = 0.002). Compared to corticosteroids alone, the risk of SRI was lower in individuals treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARD) only (0.44, 95%CI 0.25–0.78; p < 0.001). Conclusion: In the population exposed to immunosuppressive therapies, a history of chronic disease is associated with an increased risk of SRI. This risk is lower in those receiving csDMARD alone than corticosteroids alone. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Immunomodulatory Effect of Adipose Stem Cell-Derived Extra-Cellular Vesicles on Cytokine Expression and Regulatory T Cells in Patients with Asthma.
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Jung, Jae Hoon, Kang, Shin Ae, Park, Ji-Hwan, Kim, Sung-Dong, Yu, Hak Sun, Mun, Sue Jean, and Cho, Kyu-Sup
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MONONUCLEAR leukocytes , *REGULATORY T cells , *MESENCHYMAL stem cells , *CELL analysis , *FAT cells , *T cells - Abstract
Although mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) are as effective as MSCs in the suppression of allergic airway inflammation, few studies have evaluated the immunomodulatory capacity of MSC-derived EVs in patients with asthma. Thus, we assessed the effects of adipose stem cell (ASC)-derived EVs on cytokine expression and regulatory T cells (Tregs) in peripheral blood mononuclear cells (PBMCs) of asthmatic patients. PBMCs (1 × 106 cells/mL) were isolated from asthmatic patient and healthy controls and co-cultured with 1 μg/mL of ASC-derived EVs. Th (T helper) 1-, Th2-, and Treg-related cytokine expression, fluorescence-activated cell sorting analysis of CD4+CD25+FOXP3+ T cells, and co-stimulatory molecules were analyzed before and after ASC-derived EV treatment. The expression levels of IL-4 and costimulatory molecules such as CD83 and CD86 were significantly higher in PBMCs of asthmatic patients than in control PBMCs. However, ASC-derived EV treatment significantly decreased the levels of interleukin (IL)-4 and co-stimulatory molecules such as CD83 and CD86 in the phytohemagglutinin (PHA)-stimulated PBMC of asthmatic patients. Furthermore, ASC-derived EVs remarkably increased the transforming growth factor-β (TGF-β) levels and expression of Tregs in the PBMC of asthmatic patients. ASC-derived EVs induce Treg expansion and have immunomodulatory effects by downregulating IL-4 and upregulating TGF-β in PBMCs of asthmatic patients. [ABSTRACT FROM AUTHOR]
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- 2024
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14. Diagnostic criteria and core outcome set development for necrotising otitis externa: the COSNOE Delphi consensus study.
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Lodhi, Sirat, Dodgson, Kirsty, Dykes, Michael, Vishwanath, Veena, Bazaz, Rohit, Mathur, Sachin, Watson, Glen, Cartwright, Katherine, Pearson, Amy, Wearmouth, Deborah, List, Richard, Yates, Phillip, Dixon, Joanna, Puveendran, Arullendran, Wilson, Margarita, Watson, Katherine, Cullinan, Milo, Mentias, Youssef, Capper, Ruth, and Jewes, Linda
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CONSENSUS (Social sciences) , *MEDICAL protocols , *MEDICAL information storage & retrieval systems , *ANTIBIOTICS , *PATIENT compliance , *PATIENT readmissions , *OSTEOMYELITIS , *TREATMENT effectiveness , *DESCRIPTIVE statistics , *TREATMENT duration , *SYSTEMATIC reviews , *MEDLINE , *ONLINE information services , *DISEASE relapse , *TREATMENT effect heterogeneity , *OTITIS externa , *HEALTH care teams , *DIABETES , *IMMUNOSUPPRESSION , *COMORBIDITY - Abstract
Objective: Evidence for necrotising otitis externa (NOE) diagnosis and management is limited, and outcome reporting is heterogeneous. International best practice guidelines were used to develop consensus diagnostic criteria and a core outcome set (COS). Methods: The study was pre-registered on the Core Outcome Measures in Effectiveness Trials (COMET) database. Systematic literature review identified candidate items. Patient-centred items were identified via a qualitative study. Items and their definitions were refined by multidisciplinary stakeholders in a two-round Delphi exercise and subsequent consensus meeting. Results: The final COS incorporates 36 items within 12 themes: Signs and symptoms; Pain; Advanced Disease Indicators; Complications; Survival; Antibiotic regimes and side effects; Patient comorbidities; Non-antibiotic treatments; Patient compliance; Duration and cessation of treatment; Relapse and readmission; Multidisciplinary team management. Consensus diagnostic criteria include 12 items within 6 themes: Signs and symptoms (oedema, otorrhoea, granulation); Pain (otalgia, nocturnal otalgia); Investigations (microbiology [does not have to be positive], histology [malignancy excluded], positive CT and MRI); Persistent symptoms despite local and/or systemic treatment for at least two weeks; At least one risk factor for impaired immune response; Indicators of advanced disease (not obligatory but mut be reported when present at diagnosis). Stakeholders were unanimous that there is no role for secondary, graded, or optional diagnostic items. The consensus meeting identified themes for future research. Conclusion: The adoption of consensus-defined diagnostic criteria and COS facilitates standardised research reporting and robust data synthesis. Inclusion of patient and professional perspectives ensures best practice stakeholder engagement. [ABSTRACT FROM AUTHOR]
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- 2024
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15. Immune reactions following intestinal transplantation: Mechanisms and prevention.
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Zhang, Junhao, Zhan, Hanxiang, Song, Zifang, and Liu, Shanglong
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For patients with intestinal failure, small bowel transplantation remains one of the most effective treatments despite continuous advancements in parenteral nutrition techniques. Long-term use of parenteral nutrition can result in serious complications that lead to metabolic dysfunction and organ failure. However, the small intestine is a highly immunogenic organ with a large amount of mucosa-associated lymphoid tissue and histocompatibility antigens; therefore, the small intestine is highly susceptible to severe immune rejection. This article discusses the mechanisms underlying immune rejection after small bowel transplantation and presents various options for prevention and treatment. Our findings offer new insights into the development of small bowel transplantation. [ABSTRACT FROM AUTHOR]
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- 2024
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16. Immune Status and SARS-CoV-2 Viral Dynamics
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Li, Yijia, Moser, Carlee, Aga, Evgenia, Currier, Judith S, Wohl, David A, Daar, Eric S, Ritz, Justin, Greninger, Alexander L, Sieg, Scott, Parikh, Urvi M, Coombs, Robert W, Hughes, Michael D, Eron, Joseph J, Smith, Davey M, Chew, Kara W, Li, Jonathan Z, Hosey, Lara, Roa, Jhoanna, Patel, Nilam, Degli-Angeli, Emily, Goecker, Erin, Daza, Glenda, Harb, Socorro, Dragavon, Joan, Aldrovandi, Grace, Murtaugh, William, Cooper, Marlene, Gutzman, Howard, Knowles, Kevin, Bowman, Rachel, Erhardt, Bill, Warring, Lorraine, Hessinger, Diane, and Adams, Stacey
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Biomedical and Clinical Sciences ,Immunology ,Clinical Research ,Infectious Diseases ,Coronaviruses ,Emerging Infectious Diseases ,Clinical Trials and Supportive Activities ,Infection ,Good Health and Well Being ,Humans ,COVID-19 ,Immunocompromised Host ,Immunosuppression Therapy ,Kinetics ,SARS-CoV-2 ,RNA ,immunocompromise ,ACTIV-2/A5401 Study Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
Immunocompromised individuals are disproportionately affected by severe coronavirus disease 2019, but immune compromise is heterogenous, and viral dynamics may vary by the degree of immunosuppression. In this study, we categorized ACTIV-2/A5401 participants based on the extent of immunocompromise into none, mild, moderate, and severe immunocompromise. Moderate/severe immunocompromise was associated with higher nasal viral load at enrollment (adjusted difference in means: 0.47 95% confidence interval, .12-.83 log10 copies/mL) and showed a trend toward higher cumulative nasal RNA levels and plasma viremia compared to nonimmunocompromised individuals. Immunosuppression leads to greater viral shedding and altered severe acute respiratory syndrome coronavirus 2 viral decay kinetics. Clinical Trials Registration. NCT04518410.
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- 2023
17. Syk inhibition reprograms tumor-associated macrophages and overcomes gemcitabine-induced immunosuppression in pancreatic ductal adenocarcinoma
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Rohila, Deepak, Park, In Hwan, Pham, Timothy V, Weitz, Jonathan, de Mendoza, Tatiana Hurtado, Madheswaran, Suresh, Ishfaq, Mehreen, Beaman, Cooper, Tapia, Elisabette, Sun, Siming, Patel, Jay, Tamayo, Pablo, Lowy, Andrew M, and Joshi, Shweta
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Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Immunotherapy ,Orphan Drug ,Rare Diseases ,Digestive Diseases ,Cancer ,Pancreatic Cancer ,5.1 Pharmaceuticals ,5.2 Cellular and gene therapies ,2.1 Biological and endogenous factors ,Mice ,Animals ,Humans ,Gemcitabine ,Tumor-Associated Macrophages ,Carcinoma ,Pancreatic Ductal ,Pancreatic Neoplasms ,Immune Tolerance ,Immunosuppression Therapy ,Tumor Microenvironment ,Cell Line ,Tumor ,Oncology & Carcinogenesis ,Biochemistry and cell biology ,Oncology and carcinogenesis - Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an insidious disease with a low 5-year survival rate. PDAC is characterized by infiltration of abundant tumor-associated macrophages (TAM), which promote immune tolerance and immunotherapeutic resistance. Here we report that macrophage spleen tyrosine kinase (Syk) promotes PDAC growth and metastasis. In orthotopic PDAC mouse models, genetic deletion of myeloid Syk reprogrammed macrophages into immunostimulatory phenotype, increased the infiltration, proliferation, and cytotoxicity of CD8+ T cells, and repressed PDAC growth and metastasis. Furthermore, gemcitabine (Gem) treatment induced an immunosuppressive microenvironment in PDAC by promoting protumorigenic polarization of macrophages. In contrast, treatment with the FDA-approved Syk inhibitor R788 (fostamatinib) remodeled the tumor immune microenvironment, "re-educated" protumorigenic macrophages towards an immunostimulatory phenotype and boosted CD8+ T-cell responses in Gem-treated PDAC in orthotopic mouse models and an ex vivo human pancreatic slice culture model. These findings illustrate the potential of Syk inhibition for enhancing the antitumor immune responses in PDAC and support the clinical evaluation of R788 either alone or together with Gem as a potential treatment strategy for PDAC.SignificanceSyk blockade induces macrophage polarization to an immunostimulatory phenotype, which enhances CD8+ T-cell responses and improves gemcitabine efficacy in pancreatic ductal adenocarcinoma, a clinically challenging malignancy.
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- 2023
18. Clinical course of multiple sclerosis and patient experiences during breast cancer treatment.
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Nylander, Alyssa N, Singh, Jessica, Poole, Shane, Anderson, Annika, Marrie, Ruth Ann, Rugo, Hope, and Bove, Riley
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Humans ,Breast Neoplasms ,Neoplasm Recurrence ,Local ,Multiple Sclerosis ,Disease Progression ,Middle Aged ,Female ,Patient Outcome Assessment ,Multiple sclerosis ,breast neoplasms ,comorbidity ,immunosuppression therapy ,prognosis ,qualitative research ,retrospective studies ,Autoimmune Disease ,Neurodegenerative ,Clinical Research ,Neurosciences ,Prevention ,Breast Cancer ,Brain Disorders ,Cancer ,4.1 Discovery and preclinical testing of markers and technologies ,Detection ,screening and diagnosis ,Neurological ,Clinical Sciences ,Neurology & Neurosurgery - Abstract
BackgroundOver one-third of multiple sclerosis (MS) patients are post-menopausal women, the primary demographic affected by breast cancer. After breast cancer diagnosis, there is little information about patients' clinical experiences with both diseases.ObjectiveUtilize a case series of MS patients diagnosed with breast cancer to characterize oncologic and MS trajectories, and generate novel insights about clinical considerations using qualitative analysis.MethodsA single-center retrospective review was performed on medical record data of patients with MS and breast cancer. Thematic analysis was used to characterize experiences with the concurrent diagnoses.ResultsFor the 43 patients identified, mean age was 56.7 years at cancer diagnosis and MS duration was 16.5 years. Approximately half were treated with MS disease modifying therapy at cancer diagnosis, and half of these subsequently discontinued or changed therapy. Altogether 14% experienced MS relapse(s) during follow-up (with 2 relapses in the first 2 years), with mean annualized relapse rate of 0.03. Cohort Expanded Disability Status Scale (EDSS) scores remained stable during follow-up. Qualitative insights unique to this population were identified regarding immunosuppression use and neurologic symptoms.ConclusionsMS relapses were infrequent, and there was modest progression during breast cancer treatment. Oncologic outcomes were comparable to non-MS patients with similarly staged cancer.
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- 2023
19. Concurrent immune checkpoint inhibition and selective immunosuppressive therapy in patients with immune-related enterocolitis.
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Badran, Yousef R, Zou, Fangwen, Durbin, Sienna M, Dutra, Barbara E, Abu-Sbeih, Hamzah, Thomas, Anusha S, Altan, Mehmet, Thompson, John A, Qiao, Wei, Leet, Donna E, Lai, Po-Ying, Horick, Nora K, Postow, Michael A, Faleck, David M, Wang, Yinghong, and Dougan, Michael
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Humans ,Enterocolitis ,Retrospective Studies ,Infliximab ,Antineoplastic Agents ,Immunological ,Immune Checkpoint Inhibitors ,Immunosuppression Therapy ,Autoimmunity ,Immunotherapy ,Inflammation ,Digestive Diseases ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals - Abstract
PurposeImmune checkpoint inhibitor (ICI) therapy is often suspended because of immune-related enterocolitis (irEC). We examined the effect of resumption of ICIs with or without concurrent selective immunosuppressive therapy (SIT) on rates of symptom recurrence and survival outcomes.MethodsThis retrospective, multicenter study examined patients who were treated with ICI and developed irEC requiring SIT (infliximab or vedolizumab) for initial symptom control or to facilitate steroid tapering between May 2015 and June 2020. After symptom resolution, patients were restarted either on ICI alone or on concurrent ICI and SIT at the discretion of the treating physicians. The associations between irEC recurrence and treatment group were assessed via univariate analyses and multivariate logistic regression. Cox proportional hazards model was used for survival analysis.ResultsOf the 138 included patients who required SIT for initial irEC symptom control, 61 (44.2%) patients resumed ICI without concurrent SIT (control group) and 77 (55.8%) patients resumed ICI therapy with concurrent SIT: 33 with infliximab and 44 with vedolizumab. After symptom resolution, patients in the control group were more commonly restarted on a different ICI regimen (65.6%) compared with those receiving SIT (31.2%) (p
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- 2023
20. Kutane Ulzerationen bei Dermatomyositis: Fallberichte mit positivem Anti-NXP2/Anti-TIF1-gamma-Antikörper-Status
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Wald, Caroline, Simon, Jan-Christoph, and Treudler, Regina
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- 2025
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21. Prolonged remission after cyclophosphamide or tacrolimus treatment in childhood nephrotic syndrome: a cohort study
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Robinson, Cal H., Aman, Nowrin, Banh, Tonny, Brooke, Josefina, Chanchlani, Rahul, Dhillon, Vaneet, Langlois, Valerie, Levin, Leo, Licht, Christoph, McKay, Ashlene, Noone, Damien, Parikh, Alisha, Pearl, Rachel, Radhakrishnan, Seetha, Rowley, Veronique, Teoh, Chia Wei, Vasilevska-Ristovska, Jovanka H., and Parekh, Rulan S.
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- 2024
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22. Periodontal Indices in Patients with Rheumatoid Arthritis Undergoing Immunosuppressive Therapy
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Ilnaz Frahoudi, Afsaneh Enteshari-Moghaddam, and Zakiyeh Movahedzadeh
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periodontal index ,rheumatoid arthritis ,antirheumatic agents ,immunosuppression therapy ,Medicine ,Medicine (General) ,R5-920 - Abstract
Background and Objective: Periodontitis and rheumatoid arthritis are two chronic inflammatory diseases that are interrelated. Given the similarities between these conditions, the medications used by patients with rheumatoid arthritis (RA) may affect their periodontal indices. This study aimed to evaluate the periodontal index status in patients with RA undergoing immunosuppressive therapy. Methods: This comparative cross-sectional study was conducted on 68 patients with RA in three treatment groups (20 on monotherapy, 24 on dual therapy, and 24 on triple treatment) and 20 healthy individuals with a plaque index (PI) below 35% in Ardabil, Iran during the second half of 2021. The monotherapy group included methotrexate or hydroxychloroquine; the dual therapy group included combinations of methotrexate with hydroxychloroquine, adalimumab, or infliximab; and the triple therapy group included combinations of methotrexate and hydroxychloroquine with adalimumab, etanercept, sulfasalazine, or leflunomide. Periodontal indices, including Plaque Index (PI), Clinical Attachment Loss (CAL), Gingival Index (GI), and Bleeding on Probing (BOP), were assessed. Results: There were no statistically significant differences in periodontal indices among the three treatment groups (monotherapy, dual therapy, and triple therapy). The mean BOP index in the control group was significantly higher compared to the three medication groups (P
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- 2024
23. Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study
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Hugo Bes-Berlandier, Benjamin Coiffard, Julien Bermudez, Nadine Demazes-dufeu, Bérengère Coltey, Céline Boschi, Philippe Colson, Sami Hraiech, Martine Reynaud-Gaubert, and Nadim Cassir
- Subjects
Lung transplantation ,COVID-19 ,SARS-CoV-2 ,Immunosuppression therapy ,Risk factors ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes. Methods We performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes. Results Overall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), p = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), p = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), p = 0.047). Conclusion The administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity.
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- 2024
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24. CD73-Dependent Adenosine Signaling through Adora2b Drives Immunosuppression in Ductal Pancreatic Cancer.
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Faraoni, Erika Y, Singh, Kanchan, Chandra, Vidhi, Le Roux, Olivereen, Dai, Yulin, Sahin, Ismet, O'Brien, Baylee J, Strickland, Lincoln N, Li, Le, Vucic, Emily, Warner, Amanda N, Pruski, Melissa, Clark, Trent, Van Buren, George, Thosani, Nirav C, Bynon, John S, Wray, Curtis J, Bar-Sagi, Dafna, Poulsen, Kyle L, Vornik, Lana A, Savage, Michelle I, Sei, Shizuko, Mohammed, Altaf, Zhao, Zhongming, Brown, Powel H, Mills, Tingting, Eltzschig, Holger K, McAllister, Florencia, and Bailey-Lundberg, Jennifer M
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Animals ,Humans ,Mice ,Carcinoma ,Pancreatic Ductal ,Pancreatic Neoplasms ,5'-Nucleotidase ,Adenosine ,Cancer Vaccines ,Immunotherapy ,Tumor Microenvironment ,Immunosuppression Therapy ,Pancreatic Cancer ,Cancer ,Rare Diseases ,Genetics ,Digestive Diseases ,5.1 Pharmaceuticals ,Aetiology ,Development of treatments and therapeutic interventions ,2.1 Biological and endogenous factors ,Oncology and Carcinogenesis ,Oncology & Carcinogenesis - Abstract
The microenvironment that surrounds pancreatic ductal adenocarcinoma (PDAC) is profoundly desmoplastic and immunosuppressive. Understanding triggers of immunosuppression during the process of pancreatic tumorigenesis would aid in establishing targets for effective prevention and therapy. Here, we interrogated differential molecular mechanisms dependent on cell of origin and subtype that promote immunosuppression during PDAC initiation and in established tumors. Transcriptomic analysis of cell-of-origin-dependent epithelial gene signatures revealed that Nt5e/CD73, a cell-surface enzyme required for extracellular adenosine generation, is one of the top 10% of genes overexpressed in murine tumors arising from the ductal pancreatic epithelium as opposed to those rising from acinar cells. These findings were confirmed by IHC and high-performance liquid chromatography. Analysis in human PDAC subtypes indicated that high Nt5e in murine ductal PDAC models overlaps with high NT5E in human PDAC squamous and basal subtypes, considered to have the highest immunosuppression and worst prognosis. Multiplex immunofluorescent analysis showed that activated CD8+ T cells in the PDAC tumor microenvironment express high levels of CD73, indicating an opportunity for immunotherapeutic targeting. Delivery of CD73 small-molecule inhibitors through various delivery routes reduced tumor development and growth in genetically engineered and syngeneic mouse models. In addition, the adenosine receptor Adora2b was a determinant of adenosine-mediated immunosuppression in PDAC. These findings highlight a molecular trigger of the immunosuppressive PDAC microenvironment elevated in the ductal cell of origin, linking biology with subtype classification, critical components for PDAC immunoprevention and personalized approaches for immunotherapeutic intervention.SignificanceDuctal-derived pancreatic tumors have elevated epithelial and CD8+GZM+ T-cell CD73 expression that confers sensitivity to small-molecule inhibition of CD73 or Adora2b to promote CD8+ T-cell-mediated tumor regression. See related commentary by DelGiorno, p. 977.
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- 2023
25. A systematic evidence map of chronic inflammation and immunosuppression related to per- and polyfluoroalkyl substance (PFAS) exposure
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Zhang, Luoping, Louie, Allen, Rigutto, Gabrielle, Guo, Helen, Zhao, Yun, Ahn, Stacy, Dahlberg, Sarah, Sholinbeck, Michael, and Smith, Martyn T
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Biological Sciences ,Environmental Sciences ,Chemical Sciences ,Endocrine Disruptors ,Prevention ,2.1 Biological and endogenous factors ,Alkanesulfonic Acids ,Fluorocarbons ,Carcinogens ,Immunosuppression Therapy ,Environmental Pollutants ,Immunotoxicity ,Inflammasome ,PFOA ,PFOS ,Environmental exposures ,PFOA/PFOS ,Toxicology ,Biological sciences ,Chemical sciences ,Environmental sciences - Abstract
BackgroundThe ability to induce chronic inflammation and immunosuppression are two key characteristics of carcinogens and important forms of immunotoxicity. The National Toxicology Program (NTP) evaluated the immunotoxicity of two per- and polyfluoroalkyl substances (PFASs), PFOA (perfluorooctanoic acid) and PFOS (perfluorooctane sulfonate), in 2016. However, the potential pro-inflammatory and immunosuppressive effects of other PFASs remain largely uncharacterized.MethodsWe developed an expanded set of search terms pertaining to the chronic inflammatory and immunosuppressive effects of PFASs based on those of the International Agency for Research on Cancer (IARC) and NTP. To confirm searching effectiveness and scope, we compared our search term results with those of IARC and NTP for both PFASs and two other known carcinogens, chromium (VI) and benzene. Systematic evidence maps (SEMs) were also produced using Tableau to visualize the distribution of study numbers and types reporting immunotoxic effects and specific biomarkers elicited by PFAS exposures.ResultsIn total, 1155 PFAS studies were retrieved, of which 321 qualified for inclusion in our dataset. Using our search terms, we identified a greater number of relevant studies than those obtained using IARC and NTP's search terms. From the SEM findings, increased cytokine production strengthened an association between PFAS exposure and chronic inflammation, and decreased B-cell activation and altered levels of T-cell subtypes and immunoglobulins confirmed PFAS-induced immunosuppression.ConclusionOur SEM findings confirm that several PFASs commonly found in both in the environment, including those that are lesser-known, may induce immunosuppression and chronic inflammation, two key characteristics of carcinogens. This approach, including development of search terms, study screening process, data coding, and evidence mapping visualizations, can be applied to other key characteristics of chemical carcinogens.
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- 2023
26. وضعیت شاخصهای پریودنتال در مبتالیان به آرتریت روماتوئید تحت درمان با داروهای سرکوب کننده سیستم ایمنی.
- Author
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دکتر ایلناز فرهو, دکتر افسانه انتش, and دکتر زکیه موحدزا
- Abstract
Background and Objective: Periodontitis and rheumatoid arthritis are two chronic inflammatory diseases that are interrelated. Given the similarities between these conditions, the medications used by patients with rheumatoid arthritis (RA) may affect their periodontal indices. This study aimed to evaluate the periodontal index status in patients with RA undergoing immunosuppressive therapy. Methods: This comparative cross-sectional study was conducted on 68 patients with RA in three treatment groups (20 on monotherapy, 24 on dual therapy, and 24 on triple treatment) and 20 healthy individuals with a plaque index (PI) below 35% in Ardabil, Iran during the second half of 2021. The monotherapy group included methotrexate or hydroxychloroquine; the dual therapy group included combinations of methotrexate with hydroxychloroquine, adalimumab, or infliximab; and the triple therapy group included combinations of methotrexate and hydroxychloroquine with adalimumab, etanercept, sulfasalazine, or leflunomide. Periodontal indices, including Plaque Index (PI), Clinical Attachment Loss (CAL), Gingival Index (GI), and Bleeding on Probing (BOP), were assessed. Results: There were no statistically significant differences in periodontal indices among the three treatment groups (monotherapy, dual therapy, and triple therapy). The mean BOP index in the control group was significantly higher compared to the three medication groups (P<0.05). There were no statistically significant differences in the mean CAL and GI indices between the control group and the medication groups. The median PI in the control group was 29.6, and in the dual therapy group, it was 42.3, which was statistically significant (P<0.05). Conclusion: The use of immunosuppressive drugs did not have a significant effect on the periodontal indices of patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]
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- 2024
27. Expert views on screening for tuberculosis infection in patients commencing treatment with a biologic agent.
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Sultana, Adiba, Battista Migliori, Giovanni, D’Ambrosio, Lia, García-García, José-María, Rossato Silva, Denise, Adrian Rendon, Luis, Codecasa, Luigi R., Blanc, Francois-Xavier, Tiberi, Simon, Ong, Catherine W. M., Heffernan13a, Courtney, Sotgiu, Giovanni, Centis, Rosella, and Dobler, Claudia Caroline
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LATENT tuberculosis ,BIOLOGICAL products ,MEDICAL screening ,BIOLOGICALS ,TUBERCULOSIS patients - Abstract
Objective: Many biologic agents cause some degree of immunosuppression, which can increase the risk of reactivation of tuberculosis infection (TBI). This risk is variable between individual biologics. We aimed to assess current (and recommended) clinical practice of TBI screening and treatment among patients initiating treatment with biologic agents. Methods: An online questionnaire was distributed via email to members of the Global Tuberculosis Network and associated professional organisations to seek insights into the screening for and treatment of TBI in patients treated with biologics. Results: A total of 163 respondents in 27 countries answered at least one question. For all biologics described in the questionnaire, respondents advised increasing screening relative to current practice. Observed and supported TBI screening rates in patients treated with TNF-α inhibitors were high, especially for older TNF-α inhibitors. Most participants supported TBI screening in patients treated with B- or T-cell inhibitors but not in those treated with interleukin inhibitors. Guideline awareness was higher for TNF-α inhibitors than for other biologic classes (79% vs. 34%). Conclusions: Although respondents stated that TBI screening rates are lower than what they consider ideal, there was a tendency to recommend TBI screening in patients treated with biologics not known to be associated with an increased risk of TBI. As a result, there is a potential risk of over-screening and over-treatment of TBI, potentially causing harm, in patients treated with biologics other than TNF-α inhibitors. There is a need to research the risk of TBI associated with biologics and for guidelines to address the spectrum of TBI risk across all types of biologics. [ABSTRACT FROM AUTHOR]
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- 2024
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28. Impact of COVID-19 vaccination on clinical outcomes in kidney transplant patients.
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Vieira Ferreira de Assis, Ana Flâvia, de Oliveira Santos, Leticia, Almeida Botelho, Mariana, Nascimento, Evaldo, and Fabreti-Oliveira, Raquel A.
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SARS-CoV-2 , *COVID-19 , *VACCINATION complications , *COVID-19 pandemic , *COVID-19 vaccines , *KIDNEY transplantation - Abstract
Introduction: The global health crisis caused by the COVID-19 pandemic has resulted in severe mortality and morbidity. Immunosuppressed patients, such as kidney transplant recipients, are particularly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Objective: The aim of this cohort study was to evaluate the impact of COVID-19 vaccination on clinical outcomes in patients with kidney transplants. Materials and methods: In this retrospective study, 254 patients with kidney transplants were vaccinated against SARS-CoV-2 and a fraction of these contracted COVID-19. The diagnosis of COVID-19 was carried out by reverse transcriptase-polymerase chain reaction testing, and the patients received treatment involving immunosuppressive and COVID-19-specific protocols. Results: SARS-CoV-2 infection was diagnosed in 38 (14.96%) patients before the COVID-19 vaccine was administered. After vaccination, an additional 29 (11.42%) patients were diagnosed with COVID-19. Risk factors for hospitalization included age, body mass index (BMI), comorbidities, and time elapsed since renal transplantation (p 0.025, 0.038, 0.012, and 0.046, respectively). COVID-19 vaccination resulted in a significant decrease in the rate of hospital-acquired SARS-CoV-2 infection from 63.16% to 34.48% (p = 0.020). The proportion of patients from this cohort placed in intensive care units decreased from 23.68% to zero. Allograft rejections exhibited a decreasing trend from 13.16% to 6.90% (p = 0.690). This patient cohort displayed 15.79% mortality prior to COVID-19 vaccination that was reduced to nil after immunization. Conclusion: COVID-19 vaccination significantly reduced COVID-19 severity and mortality in this cohort of patients with kidney transplants. The risk factors for hospitalization were determined to be age, BMI, comorbidities, and time since renal transplantation. COVID-19 vaccination resulted in a clinical outcome of reduced hospitalization and a decrease in clinical complications. The COVID-19 vaccination-derived adverse effects in this cohort were found to be comparable to those in the immunocompetent population. [ABSTRACT FROM AUTHOR]
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- 2024
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29. Successful treatment with tofacitinib for anti-melanoma differentiation-associated gene 5 antibody-positive juvenile dermatomyositis: case reports and review of the literature.
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Yamazaki, Susumu, Shimizu, Masaki, Yakabe, Ayane, Inage, Eisuke, Jimbo, Keisuke, Suzuki, Mitsuyoshi, Miyaoka, Futaba, Kaneko, Shuya, Irabu, Hitoshi, Shimbo, Asami, Ohtomo, Yoshiyuki, Mori, Masaaki, Morio, Tomohiro, and Shimizu, Toshiaki
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LITERATURE reviews ,MELANOMA ,DERMATOMYOSITIS ,INTERSTITIAL lung diseases ,TREATMENT effectiveness ,JAPANESE people ,CUTANEOUS manifestations of general diseases - Abstract
Although the clinical efficacy of tofacitinib has been reported in adult patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (Ab+) dermatomyositis, data on its use in refractory juvenile dermatomyositis (JDM) are scarce. We describe two female Japanese patients with anti-MDA5 Ab + JDM and rapidly progressive interstitial lung disease who achieved remission by adding tofacitinib to existing immunosuppressive drugs and present a literature review. While both patients received various immunosuppressive or anti-inflammatory treatments for induction therapy, remission could not be achieved. Subsequently, tofacitinib was administered to reduce the Krebs von den Lungen-6 level 5 months after diagnosis in one patient; the other patient received tofacitinib 4 months after diagnosis to reduce ferritin levels and skin manifestations. Subsequently, both patients achieved remission, and prednisolone was withdrawn. Tofacitinib reduced the interferon signature associated with dermatomyositis/JDM disease progression and exerted a therapeutic effect on dermatomyositis/JDM. We found six published cases from five articles of tofacitinib for refractory anti-MDA5 Ab + JDM. Except for one case of herpes simplex meningitis, the other cases, including ours, had improved disease activity without severe adverse events, and steroids and immunosuppressive medicines could be tapered. Tofacitinib could be considered an available therapy for refractory anti-MDA5 Ab + JDM. [ABSTRACT FROM AUTHOR]
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- 2024
- Full Text
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30. Management of immunosuppression in lung transplant recipients and COVID-19 outcomes: an observational retrospective cohort-study.
- Author
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Bes-Berlandier, Hugo, Coiffard, Benjamin, Bermudez, Julien, Demazes-dufeu, Nadine, Coltey, Bérengère, Boschi, Céline, Colson, Philippe, Hraiech, Sami, Reynaud-Gaubert, Martine, and Cassir, Nadim
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LUNG transplantation ,COVID-19 ,CHRONIC kidney failure ,IMMUNOSUPPRESSION ,HIERARCHICAL clustering (Cluster analysis) - Abstract
Background: The aim of this study was to assess the impact of immunosuppression management on coronavirus disease 2019 (COVID-19) outcomes. Methods: We performed a single-center retrospective study in a cohort of 358 lung transplant recipients (LTx) over the period from March 2020 to April 2022. All included symptomatic patients had at least one positive SARS-CoV-2 rt-PCR. We used a composite primary outcome for COVID-19 including increased need for oxygen since the hospital admission, ICU transfer, and in-hospital mortality. We assessed by univariate and multivariate analyses the risk factors for poor outcomes. Results: Overall, we included 91 LTx who contracted COVID-19. The COVID-19 in-hospital mortality rate reached 4.4%. By hierarchical clustering, we found a strong and independent association between the composite poor outcome and the discontinuation of at least one immunosuppressive molecule among tacrolimus, cyclosporine, mycophenolate mofetil, and everolimus. Obesity (OR = 16, 95%CI (1.96; 167), p = 0.01) and chronic renal failure (OR = 4.6, 95%CI (1.4; 18), p = 0.01) were also independently associated with the composite poor outcome. Conversely, full vaccination was protective (OR = 0.23, 95%CI (0.046; 0.89), p = 0.047). Conclusion: The administration of immunosuppressive drugs such as tacrolimus, cyclocporine or everolimus can have a protective effect in LTx with COVID-19, probably related to their intrinsic antiviral capacity. [ABSTRACT FROM AUTHOR]
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- 2024
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31. Ishod bolesnika s IgA-nefropatijom ovisno o modalitetu liječenja.
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Kovačić, Ines Bosnić, Maksimović, Bojana, Jureković, Željka, Zibar, Lada, Šimunov, Bojana, Čingel, Branislav, Šulc, Snježana, Margeta, Ivan, Šimić, Ksenija Vučur, Ljubanović, Danica Galešić, Šenjug, Petar, Ivković, Vanja, Knotek, Mladen, and Laganović, Mario
- Abstract
Copyright of Lijecnicki Vjesnik is the property of Croatian Medical Association and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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32. Expert views on screening for tuberculosis infection in patients commencing treatment with a biologic agent
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Adiba Sultana, Giovanni Battista Migliori, Lia D’Ambrosio, José-María García-García, Denise Rossato Silva, Luis Adrian Rendon, Luigi R Codecasa, Francois-Xavier Blanc, Simon Tiberi, Catherine W M Ong, Courtney Heffernan, Giovanni Sotgiu, Rosella Centis, and Claudia Caroline Dobler
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Latent tuberculosis ,Biological products ,Immunosuppression therapy ,Recurrence ,Mass screening ,Diseases of the respiratory system ,RC705-779 - Abstract
ABSTRACT Objective: Many biologic agents cause some degree of immunosuppression, which can increase the risk of reactivation of tuberculosis infection (TBI). This risk is variable between individual biologics. We aimed to assess current (and recommended) clinical practice of TBI screening and treatment among patients initiating treatment with biologic agents. Methods: An online questionnaire was distributed via email to members of the Global Tuberculosis Network and associated professional organisations to seek insights into the screening for and treatment of TBI in patients treated with biologics. Results: A total of 163 respondents in 27 countries answered at least one question. For all biologics described in the questionnaire, respondents advised increasing screening relative to current practice. Observed and supported TBI screening rates in patients treated with TNF-a inhibitors were high, especially for older TNF-a inhibitors. Most participants supported TBI screening in patients treated with B- or T-cell inhibitors but not in those treated with interleukin inhibitors. Guideline awareness was higher for TNF-a inhibitors than for other biologic classes (79% vs. 34%). Conclusions: Although respondents stated that TBI screening rates are lower than what they consider ideal, there was a tendency to recommend TBI screening in patients treated with biologics not known to be associated with an increased risk of TBI. As a result, there is a potential risk of over-screening and over-treatment of TBI, potentially causing harm, in patients treated with biologics other than TNF-a inhibitors. There is a need to research the risk of TBI associated with biologics and for guidelines to address the spectrum of TBI risk across all types of biologics.
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- 2024
- Full Text
- View/download PDF
33. The Perspectives of General Nephrologists Toward Transitions of Care and Management of Failing Kidney Transplants
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Alhamad, Tarek, Murad, Haris, Dadhania, Darshana M, Pavlakis, Martha, Parajuli, Sandesh, Concepcion, Beatrice P, Singh, Neeraj, Murakami, Naoka, Casey, Michael J, Ji, Mengmeng, Lubetzky, Michelle, Tantisattamo, Ekamol, Alomar, Omar, Faravardeh, Arman, Blosser, Christopher D, Basu, Arpita, Gupta, Gaurav, Adler, Joel T, Adey, Deborah, Woodside, Kenneth J, Ong, Song C, Parsons, Ronald F, and Lentine, Krista L
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Biomedical and Clinical Sciences ,Clinical Sciences ,Clinical Research ,Kidney Disease ,Transplantation ,Organ Transplantation ,Renal and urogenital ,Adult ,Humans ,Nephrologists ,Kidney Transplantation ,Nephrology ,Immunosuppression Therapy ,Surveys and Questionnaires ,re-transplantation ,failing kidney allograft ,transition of care ,immunosuppression management ,multidisciplinary team ,Surgery ,Clinical sciences - Abstract
The management of failing kidney allograft and transition of care to general nephrologists (GN) remain a complex process. The Kidney Pancreas Community of Practice (KPCOP) Failing Allograft Workgroup designed and distributed a survey to GN between May and September 2021. Participants were invited via mail and email invitations. There were 103 respondents with primarily adult nephrology practices, of whom 41% had an academic affiliation. More than 60% reported listing for a second kidney as the most important concern in caring for patients with a failing allograft, followed by immunosuppression management (46%) and risk of mortality (38%), while resistant anemia was considered less of a concern. For the initial approach to immunosuppression reduction, 60% stop antimetabolites first, and 26% defer to the transplant nephrologist. Communicating with transplant centers about immunosuppression cessation was reported to occur always by 60%, and sometimes by 29%, while 12% reported making the decision independently. Nephrologists with academic appointments communicate with transplant providers more than private nephrologists (74% vs. 49%, p = 0.015). There are heterogeneous approaches to the care of patients with a failing allograft. Efforts to strengthen transitions of care and to develop practical practice guidelines are needed to improve the outcomes of this vulnerable population.
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- 2023
34. A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes.
- Author
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Wisel, Steven A, Posselt, Andrew M, Szot, Gregory L, Nunez, Miguel, Santos-Parker, Keli, Gardner, James M, Worner, Giulia, Roll, Garrett R, Syed, Shareef, Kelly, Yvonne, Ward, Casey, Tavakol, Medhi, Johnson, Kristina, Masharani, Umesh, and Stock, Peter G
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Humans ,Diabetes Mellitus ,Type 1 ,Insulin ,Calcineurin ,Immunosuppressive Agents ,Pancreas Transplantation ,Islets of Langerhans Transplantation ,Calcineurin Inhibitors ,Immunosuppression Therapy ,immune tolerance ,immunosuppression ,insulin independence ,islet transplant ,pancreas transplant ,Clinical Research ,Diabetes ,Transplantation ,Kidney Disease ,Metabolic and endocrine ,Clinical Sciences ,Surgery - Abstract
Long-term success in beta-cell replacement remains limited by the toxic effects of calcineurin inhibitors (CNI) on beta-cells and renal function. We report a multi-modal approach including islet and pancreas-after-islet (PAI) transplant utilizing calcineurin-sparing immunosuppression. Ten consecutive non-uremic patients with Type 1 diabetes underwent islet transplant with immunosuppression based on belatacept (BELA; n = 5) or efalizumab (EFA; n = 5). Following islet failure, patients were considered for repeat islet infusion and/or PAI transplant. 70% of patients (four EFA, three BELA) maintained insulin independence at 10 years post-islet transplant, including four patients receiving a single islet infusion and three patients undergoing PAI transplant. 60% remain insulin independent at mean follow-up of 13.3 ± 1.1 years, including one patient 9 years after discontinuing all immunosuppression for adverse events, suggesting operational tolerance. All patients who underwent repeat islet transplant experienced graft failure. Overall, patients demonstrated preserved renal function, with a mild decrease in GFR from 76.5 ± 23.1 mL/min to 50.2 ± 27.1 mL/min (p = 0.192). Patients undergoing PAI showed the greatest degree of renal impairment following initiation of CNI (56% ± 18.7% decrease in GFR). In our series, repeat islet transplant is ineffective at maintaining long-term insulin independence. PAI results in durable insulin independence but is associated with impaired renal function secondary to CNI dependence.
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- 2023
35. Synthetic cytokine circuits that drive T cells into immune-excluded tumors
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Allen, Greg M, Frankel, Nicholas W, Reddy, Nishith R, Bhargava, Hersh K, Yoshida, Maia A, Stark, Sierra R, Purl, Megan, Lee, Jungmin, Yee, Jacqueline L, Yu, Wei, Li, Aileen W, Garcia, K Christopher, El-Samad, Hana, Roybal, Kole T, Spitzer, Matthew H, and Lim, Wendell A
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Immunology ,Cancer ,Inflammatory and immune system ,Humans ,Immunotherapy ,Adoptive ,Interleukin-2 ,Neoplasms ,Receptors ,Antigen ,T-Cell ,T-Lymphocytes ,Tumor Microenvironment ,Animals ,Mice ,Receptors ,Chimeric Antigen ,Cell Engineering ,Receptors ,Notch ,Immunosuppression Therapy ,General Science & Technology - Abstract
Chimeric antigen receptor (CAR) T cells are ineffective against solid tumors with immunosuppressive microenvironments. To overcome suppression, we engineered circuits in which tumor-specific synNotch receptors locally induce production of the cytokine IL-2. These circuits potently enhance CAR T cell infiltration and clearance of immune-excluded tumors, without systemic toxicity. The most effective IL-2 induction circuit acts in an autocrine and T cell receptor (TCR)- or CAR-independent manner, bypassing suppression mechanisms including consumption of IL-2 or inhibition of TCR signaling. These engineered cells establish a foothold in the target tumors, with synthetic Notch-induced IL-2 production enabling initiation of CAR-mediated T cell expansion and cell killing. Thus, it is possible to reconstitute synthetic T cell circuits that activate the outputs ultimately required for an antitumor response, but in a manner that evades key points of tumor suppression.
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- 2022
36. Malnutrition and immune cell subsets in children undergoing kidney transplantation.
- Author
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Shaw, Brian, Lee, Hui-Jie, Ettenger, Robert, Grimm, Paul, Reed, Elaine, Sarwal, Minnie, Stempora, Linda, Warshaw, Barry, Zhao, Congwen, Martinez, Olivia, MacIver, Nancie, Kirk, Allan, and Chambers, Eileen
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immunosuppression ,immunosuppressive treatment ,induction ,kidney ,Humans ,Kidney Transplantation ,Immunosuppression Therapy ,CD8-Positive T-Lymphocytes ,Malnutrition ,Obesity - Abstract
BACKGROUND: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immune system responds to the insult of both immunosuppression and allotransplantation is unknown. We examined the relationship of nutritional status with post-transplant outcomes and characterized the peripheral immune cell phenotypes of children from the Immune Development of Pediatric Transplant (IMPACT) study. METHODS: Ninety-eight patients from the IMPACT study were classified as having obesity, undernutrition, or normal nutrition-based pre-transplant measurements. Incidence of infectious and alloimmune outcomes at 1-year post-transplantation was compared between nutritional groups using Grays test and Fine-Gray subdistribution hazards model. Event-free survival was estimated by Kaplan-Meier method and compared between groups. Differences in immune cell subsets between nutritional groups over time were determined using generalized estimating equations accounting for the correlation between repeated measurements. RESULTS: We did not observe that nutritional status was associated with infectious or alloimmune events or event-free survival post-transplant. We demonstrated that children with obesity had distinct T-and B-cell signatures relative to those with undernutrition and normal nutrition, even when controlling for immunosuppression. Children with obesity had a lower frequency of CD8 Tnaive cells 9-month post-transplant (p
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- 2022
37. Inhibitory effect of rapamycin-deep eutectic solvent eye drops on corneal allograft rejection in mice and its mechanism
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YANG Yang, HUANG Cixin, ZENG Fanxing, SUN Yaru, WEI Chao, WANG Hongwei, GAO Hua
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corneal transplantation ,transplantation, homologous ,immunosuppression therapy ,sirolimus ,deep eutectic dolvents ,drug carriers ,Medicine - Abstract
Objective To investigate the inhibitory effect of rapamycin (RAPA)-deep eutectic solvent (DES) eye drops on corneal allograft rejection in mice and its mechanism. Methods CCK-8 assay was used to measure the influence of 10 types of DES on the viability of human corneal epithelial cells (HCECs), and the DES with a significantly higher cell viability than the control group was selected for characterization to obtain the most suitable DES. BALB/c mice and New Zealand white rabbits were used to evaluate the biocompatibility of the most suitable DES. The mice were randomly divided into normal group, phosphate solution (PBS) group, DES group, and RAPA-DES group. The mice in normal group were fed normally, and those in the PBS group, the DES group, and the RAPA-DES group were administrated PBS, DES, and RAPA-DES solution, respectively, to the right eye after corneal transplantation. On the next day, a slit lamp was used to observe the survival of corneal grafts, and the survival percentage of corneal grafts was analyzed to plot the survival curve of corneal grafts. On days 7 and 16 after transplantation, the eyeballs of the mice were collected, and HE staining was used to observe corneal edema and inflammatory cell infiltration under a microscope. On day 16 after transplantation, RT-qPCR was used to measure the mRNA expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12α (IL-12α), and interleukin-17α (IL-17α) in corneal tissue, and Western blot was used to measure the protein expression levels of IL-6 and IL-17α in corneal tissue. Results CCK-8 assay showed that compared with the control group, the DES-1 group and the DES-2 group had a significant increase in cell viability (P0.05); compared with the PBS group and the DES group, the RAPA-DES group had significantly lower mRNA expression levels of IL-1β, IL-6, and IL-10 (P
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- 2024
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38. Successful treatment with tofacitinib for anti-melanoma differentiation-associated gene 5 antibody-positive juvenile dermatomyositis: case reports and review of the literature
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Susumu Yamazaki, Masaki Shimizu, Ayane Yakabe, Eisuke Inage, Keisuke Jimbo, Mitsuyoshi Suzuki, Futaba Miyaoka, Shuya Kaneko, Hitoshi Irabu, Asami Shimbo, Yoshiyuki Ohtomo, Masaaki Mori, Tomohiro Morio, and Toshiaki Shimizu
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Anti-melanoma differentiation-associated gene 5 ,Janus kinase inhibitors ,juvenile dermatomyositis ,immunosuppression therapy ,tofacitinib ,methylprednisolone ,Immunologic diseases. Allergy ,RC581-607 - Abstract
AbstractAlthough the clinical efficacy of tofacitinib has been reported in adult patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive (Ab+) dermatomyositis, data on its use in refractory juvenile dermatomyositis (JDM) are scarce. We describe two female Japanese patients with anti-MDA5 Ab + JDM and rapidly progressive interstitial lung disease who achieved remission by adding tofacitinib to existing immunosuppressive drugs and present a literature review. While both patients received various immunosuppressive or anti-inflammatory treatments for induction therapy, remission could not be achieved. Subsequently, tofacitinib was administered to reduce the Krebs von den Lungen-6 level 5 months after diagnosis in one patient; the other patient received tofacitinib 4 months after diagnosis to reduce ferritin levels and skin manifestations. Subsequently, both patients achieved remission, and prednisolone was withdrawn. Tofacitinib reduced the interferon signature associated with dermatomyositis/JDM disease progression and exerted a therapeutic effect on dermatomyositis/JDM. We found six published cases from five articles of tofacitinib for refractory anti-MDA5 Ab + JDM. Except for one case of herpes simplex meningitis, the other cases, including ours, had improved disease activity without severe adverse events, and steroids and immunosuppressive medicines could be tapered. Tofacitinib could be considered an available therapy for refractory anti-MDA5 Ab + JDM.
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- 2024
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39. Emergence of SARS-CoV-2 with Dual-Drug Resistant Mutations During a Long-Term Infection in a Kidney Transplant Recipient
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Tanino Y, Nishioka K, Yamamoto C, Watanabe Y, Daidoji T, Kawamoto M, Uda S, Kirito S, Nakagawa Y, Kasamatsu Y, Kawahara Y, Sakai Y, Nobori S, Inaba T, Ota B, Fujita N, Hoshino A, Nukui Y, and Nakaya T
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sars-cov-2 ,sotrovimab ,remdesivir ,drug resistance ,immunosuppression therapy ,Infectious and parasitic diseases ,RC109-216 - Abstract
Yoko Tanino,1,2,* Keisuke Nishioka,1,* Chie Yamamoto,2,* Yohei Watanabe,1,3 Tomo Daidoji,1,4 Masataka Kawamoto,5 Sayaka Uda,6 Shoko Kirito,1 Yuta Nakagawa,2 Yu Kasamatsu,2 Yoshiyuki Kawahara,7 Yuri Sakai,7 Shuji Nobori,8 Tohru Inaba,2 Bon Ota,9 Naohisa Fujita,7 Atsushi Hoshino,10 Yoko Nukui,2 Takaaki Nakaya1 1Department of Infectious Diseases, Kyoto Prefectural University of Medicine, Kyoto, Japan; 2Department of Infection Control and Laboratory Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 3JST, MIRAI, Tokyo, Japan; 4School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan; 5Department of Forensics Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 6Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 7Kyoto Prefectural Institute of Public Health and Environment, Kyoto, Japan; 8Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kyoto, Japan; 9Department of Emergency Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan; 10Department of Cardiovascular Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan*These authors contributed equally to this workCorrespondence: Takaaki Nakaya; Yohei Watanabe, Department of Infectious Diseases, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan, Tel +81-75-251-5325, Fax +81-75-251-5328, Email tnakaya@koto.kpu-m.ac.jp; nabe@koto.kpu-m.ac.jpIntroduction: Various therapeutic agents are being developed for the treatment of coronavirus disease 2019 (COVID-19). Therefore, it is crucial to accumulate information regarding the features of drug-resistant viruses to these antiviral drugs.Methods: We investigated the emergence of dual-drug resistance in a kidney transplant recipient who received sotrovimab (from day 0) and remdesivir (RDV) (from day 8 to day 17). We sequenced the whole viral genomes from nasopharyngeal swabs taken on day 0 and seven points after starting treatment (on days 12, 19, 23, 37, 43, 48, and 58). The genetic traits of the wild-type (day 0) and descendant viruses (after day 12) were determined by comparing the genomes with those of a Wuhan strain and the day 0 wild-type strain, respectively. Three viral isolates (from samples collected on days 0, 23, and 37) were investigated for their escape ability and growth kinetics in vitro.Results: The sotrovimab resistant mutation (S:E340K) and the RDV resistant mutation RdRp:V792I (nt: G15814A) emerged within 12 days (day 12) and 11 days (day 19) after the treatment, respectively. The day 23 isolate harboring S:E340K/RdRp:V791I was resistant to both sotrovimab and RDV, showing 364- and 2.73-fold higher resistance respectively, compared with the wild-type. Moreover, compared with the day 23 isolate, the day 37 isolate accumulated multiple additional mutations and had a higher level of resistance to both drugs.Conclusion: Drug-resistant variants with double mutations (S:E340K/RdRp:V791I) became dominant within 23 days after starting treatment, suggesting that even a combination therapy involving sotrovimab and RDV, dual-drug resistant viruses may emerge rapidly in immunocompromised patients. The dual-resistant variants had lower virus yields than those of the wild-type virus in vitro, suggesting that they paid a fitness cost.Keywords: SARS-CoV-2, sotrovimab, remdesivir, drug resistance, immunosuppression therapy
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- 2024
40. Reduced Cell Surface Levels of C-C Chemokine Receptor 5 and Immunosuppression in Long Coronavirus Disease 2019 Syndrome
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Gaylis, Norman B, Ritter, Angela, Kelly, Scott A, Pourhassan, Nader Z, Tiwary, Meenakshi, Sacha, Jonah B, Hansen, Scott G, Recknor, Christopher, and Yang, Otto O
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Clinical Research ,Clinical Trials and Supportive Activities ,6.1 Pharmaceuticals ,Evaluation of treatments and therapeutic interventions ,Good Health and Well Being ,COVID-19 ,Chemokines ,CC ,Humans ,Immunosuppression Therapy ,Receptors ,CCR5 ,CCR5 ,leronlimab ,long COVID ,immunosuppression ,Biological Sciences ,Medical and Health Sciences ,Microbiology - Abstract
In an exploratory trial treating "long COVID" with the CCR5-binding antibody leronlimab, we observed significantly increased blood cell surface CCR5 in treated symptomatic responders but not in nonresponders or placebo-treated participants. These findings suggest an unexpected mechanism of abnormal immune downmodulation in some persons that is normalized by leronlimab. Clinical Trials Registration. NCT04678830.
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- 2022
41. Impact of solid organ transplant status on outcomes of hospitalized patients with COVID-19 infection.
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Schaenman, Joanna, Byford, Hannah, Grogan, Tristan, Motwani, Yash, Beaird, Omer E, Kamath, Megan, Lum, Erik, Meneses, Katherine, Sayah, David, Vucicevic, Darko, and Saab, Sammy
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Humans ,Organ Transplantation ,Pandemics ,Transplant Recipients ,COVID-19 ,Immunosuppression Therapy ,comorbidities ,solid organ transplant ,Transplantation ,Clinical Research ,Patient Safety ,Good Health and Well Being ,Clinical Sciences ,Surgery - Abstract
BackgroundThe COVID-19 pandemic has caused significant morbidity and mortality in solid organ transplant (SOT) recipients. However, it remains unclear whether the risk factor for SOT patients is the immunosuppression inherent to transplantation versus patient comorbidities.MethodsWe reviewed outcomes in a cohort of SOT (n = 129) and non-SOT (NSOT) patients (n = 708) admitted to the University of California, Los Angeles for COVID-19 infection. Data analyses utilized multivariate logistic regression to evaluate the impact of patient demographics, comorbidities, and transplant status on outcomes. SOT patients were analyzed by kidney SOT (KSOT) versus nonkidney SOT (NKSOT) groups.ResultsSOT and NSOT patients with COVID-19 infection differed in terms of patient age, ethnicity, and comorbidities. NKSOT patients were the most likely to experience death, with a mortality rate of 16.2% compared with 1.8% for KSOT and 8.3% for NSOT patients (p = .013). Multivariable analysis of hospitalized patients revealed that patient age (odds ratio [OR] 2.79, p = .001) and neurologic condition (OR 2.66, p
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- 2022
42. Impfempfehlungen bei Immunsupprimierten
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Tobudic, Selma
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- 2024
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43. Advances in the pharmacological management of systemic lupus erythematosus.
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Tsoi, Alexander, Nikolopoulos, Dionysis, and Parodis, Ioannis
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PHARMACOLOGY ,SYSTEMIC lupus erythematosus ,RHEUMATOLOGY ,CLINICAL trials ,DRUG therapy - Abstract
Despite setbacks in clinical trials for systemic lupus erythematosus (SLE), three drugs have been approved for SLE and lupus nephritis (LN) treatment in the past decade. Several ongoing clinical trials, some viewed optimistically by the scientific community, underscore the evolving landscape. Emerging clinical data have established specific therapeutic targets in routine clinical practice for treating SLE, aiming to improve long-term outcomes. Research related to treatment of SLE and LN is discussed, focusing on randomized clinical trials during the last 5 years and recommendations for the management of SLE published by the European Alliance of Associations for Rheumatology (EULAR), American College of Rheumatology (ACR), Asia Pacific League of Associations for Rheumatology (APLAR), and Pan-American League of Associations of Rheumatology (PANLAR). The landscape of SLE and LN treatments is evolving, as new drugs and combination treatment approaches redefine the traditional concepts of induction and maintenance treatment phases. As the therapeutic armamentarium in SLE continues to expand, the research focus is shifting from the imperative for new therapies to advancing our understanding of optimal treatment selection for individual patients, steering toward precision medicine strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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44. Progressive multifocal leukoencephalopathy associated with systemic lupus erythematosus: longitudinal observation of lymphocytes, JC virus in cerebrospinal fluid, and brain magnetic resonance imaging.
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Yamada, Hidetada, Toko, Megumi, Nakamori, Masahiro, Ueno, Hiroki, Aoki, Shiro, Sugimoto, Tomohiro, Yasutomi, Hiroko, Nakamichi, Kazuo, and Maruyama, Hirofumi
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PROGRESSIVE multifocal leukoencephalopathy , *VITAMIN B12 deficiency , *SYSTEMIC lupus erythematosus , *MAGNETIC resonance imaging , *JOHN Cunningham virus , *NATALIZUMAB - Abstract
Progressive multifocal leukoencephalopathy (PML) rarely occurs in patients with systemic lupus erythematosus (SLE). This report presents the case of a patient who developed PML due to SLE-associated multiple factors. A 60-year-old woman diagnosed with SLE undergoing multiple immunosuppressive therapies, including azathioprine, presented with cerebral cortical symptoms, lymphocytopenia, and vitamin B12 deficiency and was subsequently diagnosed with SLE-associated PML. We evaluated the cause and disease activity of PML, focusing on the longitudinal assessment of lymphocytopenia, JC virus (JCV) DNA copy number in the cerebrospinal fluid, and magnetic resonance imaging (MRI) findings. Discontinuing azathioprine and initiating alternative immunosuppressive treatments with intramuscular vitamin B12 injections affected lymphocytopenia and disease management. However, despite recovery from lymphopenia and JCV DNA copy number being low, the large hyperintense and punctate lesions observed on the fluid-attenuated inversion recovery (FLAIR) images exhibited varying behaviors, indicating that the balance between contributing factors for PML may have fluctuated after the initial treatment. Clinicians should be meticulous when assessing the underlying pathology of the multifactorial causes of PML due to SLE. The difference in the transition pattern of these lesions on FLAIR images may be one of the characteristics of MRI findings in PML associated with SLE, reflecting fluctuations in disease activity and the progression stage of PML. [ABSTRACT FROM AUTHOR]
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- 2024
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45. Therapie der Autoimmunhepatitis – Erst‑, Zweit- und Drittlinientherapie.
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Taubert, Richard and Engel, Bastian
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Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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46. Immunglobulin-A-Nephropathie – neue therapeutische Möglichkeiten.
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Girndt, Matthias
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Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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47. Emergency department evaluation of transplanted children with COVID-19.
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Barreiro Pérez, Sagrario, Molina Gutiérrez, Miguel Ángel, Antoñanzas Bernar, Valeria, Storch-de-Gracia, Pilar, and Mesa García, Sofía
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Children usually have an asymptomatic or mild course of SARS-CoV-2 infection, studies in immunocompromised patients have shown a different evolution. The aim of this study was to describe the clinical, laboratory, and radiologic manifestations of pediatric solid organ transplant (SOT) and hematopoietic stem cell transplant (HSCT) patients testing positive for SARS-CoV-2. A multicenter retrospective, observational descriptive study was conducted in 3 tertiary hospitals in Madrid (Spain) between March 2020 and December 2022. Consecutive patients aged 0–18 attending the corresponding pediatric emergency departments with a positive result in the real-time polymerase chain reaction test or antigenic test to detect SARS-CoV-2 in the nasopharyngeal sample were included. A total of 31 children were included in the study. Sixteen (51.6%) were patients with HSCT and 15 (48.3) were patients with SOT. The median time from transplantation to COVID-19 was 1.2 years (IQR:0.5–5.1). The SOT cohort included liver (n = 4, 12.9%), kidney (n = 4, 12.9%), heart (n = 3, 9.7%), multivisceral (n = 3, 9.7%), and lung (n = 1, 3.2%). Of the 31 patients, only one was asymptomatic. The most common symptom on presentation was fever (76.7%). Abnormalities were seen on chest X-ray in 8 (66.6%) of the 12 patients. There was no significant difference in clinical manifestations, lymphopenia and radiological findings regardless of the type of transplantation or immunosuppression status. Thirteen patients (41.9%) were hospitalized. There were no patient deaths. In our study, we found that the clinical course and outcome of SOT and HSCT pediatric patients with COVID-19 were generally favorable. [ABSTRACT FROM AUTHOR]
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- 2024
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48. Immunglobulin-A-Vaskulitis.
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Adler, Sabine
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Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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- 2024
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49. Immunogenicity, Effectiveness, and Safety of COVID-19 Vaccines among Patients with Immune-Mediated Dermatological Diseases: A Systematic Review and Meta-analysis
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Sonphet Chirasuthat, Yanisa Ratanapokasatit, Kunlawat Thadanipon, and Kumutnart Chanprapaph
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COVID-19 Vaccines ,Immune System Diseases ,Immunosuppression Therapy ,Meta-Analysis ,Skin Diseases ,Dermatology ,RL1-803 - Abstract
Immunocompromised individuals, primarily attributable to using immunosuppressants, face heightened COVID-19 risks. Despite the proven efficacy of COVID-19 vaccines, their impact on patients with immune-mediated dermatological diseases remains unclear. This study aims to thoroughly examine vaccine immunogenicity, effectiveness, and safety in immune-mediated dermatological disease patients. Clinical studies in adults that compared vaccinated immune-mediated dermatological disease patients with vaccinated healthy controls or unvaccinated immune-mediated dermatological disease patients in terms of vaccine immunogenicity, COVID-19 infection, adverse events, or exacerbation of immune-mediated dermatological diseases were searched via electronic databases. Seventeen studies (1,348,690 participants) were included. Seroconversion rates between immune-mediated dermatological disease patients and healthy controls were not different. However, among individuals aged ≤55 years, immune-mediated dermatological disease patients had lower mean anti-SARS-CoV-2 IgG levels. Immunosuppressed immune-mediated dermatological disease patients also had lower titres and were less likely to achieve T-cell response. In terms of safety, the risk of adverse events was higher in atopic dermatitis patients, but those with psoriasis had a reduced risk. Additionally, immunosuppressed patients had fewer adverse events. Vaccinated immune-mediated dermatological disease patients had a lower risk of COVID-19 infection than unvaccinated patients but a higher risk than healthy controls; however, disease exacerbation may be induced. In conclusion, immune-mediated dermatological diseases showed a reduced vaccine response in our meta-analysis, yet vaccination remained effective against COVID-19 infection and well tolerated.
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- 2024
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50. Kidney invasion occurred 2 years following liver transplantation for hepatic alveolar echinococcosis: a case report
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Qirui Hu, Simin Chen, Yichen Fan, Qian Lu, Manjun Deng, and Haining Fan
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Alveolar echinococcosis ,Liver transplantation ,Albendazole ,Case report ,Immunosuppression therapy ,Infectious and parasitic diseases ,RC109-216 - Abstract
Abstract Background The organ most commonly invaded in echinococcosis is the liver; the lungs, brain, kidneys, heart, and spleen are rarely invaded, and multi-organ involvement in echinococcosis is even rarer. No studies have reported renal invasion after liver transplantation for hepatic alveolar echinococcosis. Case presentation We report here a case of renal invasion 2 years after allogeneic liver transplantation in a 53-year-old female patient with hepatic alveolar echinococcosis combined with lung metastases. At the time of the first consultation, the lesion had been found to involve the second hepatic hilum combined with lung metastases, but the patient requested conservative treatment, and the lesion was not controlled by taking albendazole for 3 years. After discussion in the treatment group, it was decided to use allogeneic liver transplantation and lung segmental resection for surgical treatment, after which the patient was put on long-term oral immunosuppression. She was hospitalized 2 years later for low back pain and diagnosed with renal alveolar echinococcosis. Due to significant compression and left-sided renal insufficiency, the final option was to remove the diseased kidney. It is worth mentioning that signs of unexplained urinary tract infection were present throughout the course of treatment. Conclusion This study suggests that extra attention should be paid to the presence of cryptogenic lesions in patients with hepatic alveolar echinococcosis who already have definite metastatic lesions. Immunosuppressive drugs after liver transplantation in patients with hepatic echinococcosis may cause occult lesions to develop into active ones. In clinical practice, particular attention should be paid to patients with hepatic alveolar echinococcosis with long-term concomitant signs of unexplained urinary tract infections, which may be a precursor clinical feature of cryptogenic renal alveolar echinococcosis.
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- 2023
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