23 results on '"Ørbaek M"'
Search Results
2. Risk factors during pregnancy and birth-related complications in HIV-positive versus HIV-negative women in Denmark, 2002–2014
- Author
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Ørbæk, M., Thorsteinsson, K., Moseholm Larsen, E., Katzenstein, T. L., Storgaard, M., Johansen, I. S., Pedersen, G., Bach, D., Helleberg, M., Weis, N., Lebech, A. M., Ørbæk, M., Thorsteinsson, K., Moseholm Larsen, E., Katzenstein, T. L., Storgaard, M., Johansen, I. S., Pedersen, G., Bach, D., Helleberg, M., Weis, N., and Lebech, A. M.
- Abstract
Objectives: We aimed to compare risk factors for adverse pregnancy outcomes in women living with HIV (WLWH) with those in women of the general population (WGP) in Denmark. Further, we estimated risk of pregnancy- or birth-related complications. Methods: A retrospective cohort study including all WLWH who delivered a live-born child from 2002 to 2014 and WGP, matched by origin, age, year and parity, was carried out. We compared risk factors during pregnancy and estimated risk of pregnancy- and birth-related complications using multivariate logistic regression. Results: A total of 2334 pregnancies in 304 WLWH and 1945 WGP were included in the study. WLWH had more risk factors present than WGP during pregnancy: previous caesarean section (CS) (24.7% versus 16.3%, respectively; P = 0.0001), smoking (14.2% versus 7.5%, respectively; P = 0.0001) and previous perinatal/neonatal death (2.3% versus 0.9%, respectively; P = 0.03). We found no difference between groups regarding gestational diabetes, hypertensive disorders, low birth weights or premature delivery. More children of WLWH had intrauterine growth retardation (IUGR) [adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.1–3.2; P = 0.02]. Median gestational age and birth weight were lower in children born to WLWH. WLWH had a higher risk of emergency CS (EmCS) (aOR 1.6; 95% CI 1.2–2.1; P = 0.0005) and postpartum haemorrhage (aOR 1.4; 95% CI 1.0–1.9; P = 0.02) but not infection, amniotomy, failure to progress, low activity-pulse-grimace-appearance-respiration (APGAR) score or signs of asphyxia. Conclusions: WLWH had more risk factors present during pregnancy, similar risks of most pregnancy- and birth-related complications but a higher risk of postpartum haemorrhage and EmCS compared with WGP. Children born to WLWH had lower median birth weights and gestational ages and were at higher risk of IUGR.
- Published
- 2020
3. Are women living with HIV in increased risk of complications to birth when planning elective caesarean section? A Danish nation wide population based study
- Author
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Ørbæk, M., Thorsteinsson, K., Larsen, E. M., Katzenstein, T. L., Storgaard, M., isik somuncu johansen, Pedersen, G., Helleberg, M., Weis, N., and A-M, Lebech
- Subjects
HIV ,Mother-to-Child transmission ,Elective Caesarean Section - Abstract
Regardless of viral suppression two-thirds of women living with HIV (WLWH) in Denmark deliver by caesarean section (CS) and half of the elective CS (ECS) are performed due to mothers request. The aim of the study was to investigate if planning ECS increases risk of obstetric complications compared to planning vaginal delivery in WLWH.
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- 2019
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4. Risk factors during pregnancy and birth‐related complications in HIV‐positive versus HIV‐negative women in Denmark, 2002–2014
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Ørbæk, M, primary, Thorsteinsson, K, additional, Moseholm Larsen, E, additional, Katzenstein, TL, additional, Storgaard, M, additional, Johansen, IS, additional, Pedersen, G, additional, Bach, D, additional, Helleberg, M, additional, Weis, N, additional, and Lebech, A‐M, additional
- Published
- 2019
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5. Risk factors during pregnancy and birth‐related complications in HIV‐positive versus HIV‐negative women in Denmark, 2002–2014.
- Author
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Ørbæk, M, Thorsteinsson, K, Moseholm Larsen, E, Katzenstein, TL, Storgaard, M, Johansen, IS, Pedersen, G, Bach, D, Helleberg, M, Weis, N, and Lebech, A‐M
- Subjects
- *
FETAL growth retardation , *HEMORRHAGE risk factors , *HIV infection complications , *PERINATAL death , *APGAR score , *ASPHYXIA , *BIRTH weight , *CESAREAN section , *COMPARATIVE studies , *CONFIDENCE intervals , *FETAL membranes , *GESTATIONAL age , *INDUCED labor (Obstetrics) , *LONGITUDINAL method , *PREGNANCY complications , *PUERPERAL disorders , *RISK assessment , *SMOKING , *WOMEN'S health , *MULTIPLE regression analysis , *RETROSPECTIVE studies , *ODDS ratio , *DISEASE risk factors ,RISK factors - Abstract
Objectives: We aimed to compare risk factors for adverse pregnancy outcomes in women living with HIV (WLWH) with those in women of the general population (WGP) in Denmark. Further, we estimated risk of pregnancy‐ or birth‐related complications. Methods: A retrospective cohort study including all WLWH who delivered a live‐born child from 2002 to 2014 and WGP, matched by origin, age, year and parity, was carried out. We compared risk factors during pregnancy and estimated risk of pregnancy‐ and birth‐related complications using multivariate logistic regression. Results: A total of 2334 pregnancies in 304 WLWH and 1945 WGP were included in the study. WLWH had more risk factors present than WGP during pregnancy: previous caesarean section (CS) (24.7% versus 16.3%, respectively; P = 0.0001), smoking (14.2% versus 7.5%, respectively; P = 0.0001) and previous perinatal/neonatal death (2.3% versus 0.9%, respectively; P = 0.03). We found no difference between groups regarding gestational diabetes, hypertensive disorders, low birth weights or premature delivery. More children of WLWH had intrauterine growth retardation (IUGR) [adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.1–3.2; P = 0.02]. Median gestational age and birth weight were lower in children born to WLWH. WLWH had a higher risk of emergency CS (EmCS) (aOR 1.6; 95% CI 1.2–2.1; P = 0.0005) and postpartum haemorrhage (aOR 1.4; 95% CI 1.0–1.9; P = 0.02) but not infection, amniotomy, failure to progress, low activity‐pulse‐grimace‐appearance‐respiration (APGAR) score or signs of asphyxia. Conclusions: WLWH had more risk factors present during pregnancy, similar risks of most pregnancy‐ and birth‐related complications but a higher risk of postpartum haemorrhage and EmCS compared with WGP. Children born to WLWH had lower median birth weights and gestational ages and were at higher risk of IUGR. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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6. Neoehrlichia mikurensis is uncommon in rheumatological patients receiving tumour necrosis factor inhibitors and in blood donors: a retrospective cohort study.
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Gynthersen R, Ørbæk M, Høgdall E, Glintborg B, Ostrowski SR, Harritshøj L, Hetland ML, Lebech AM, and Mens H
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- Humans, Female, Middle Aged, Male, Tumor Necrosis Factor Inhibitors, Blood Donors, Retrospective Studies, Anaplasmataceae Infections diagnosis, Anaplasmataceae Infections epidemiology, Anaplasmataceae Infections microbiology, Anaplasmataceae genetics, Arthritis, Rheumatoid diagnosis, Arthritis, Rheumatoid drug therapy, Arthritis, Rheumatoid epidemiology
- Abstract
Introduction: Neoehrlichia mikurensis is a tick-borne bacterium that primarily causes disease in immunocompromised patients. The bacterium has been detected in ticks throughout Europe, with a 0%-25% prevalence. N. mikurensis infection presents unspecific symptoms, which can easily be mistaken for inflammatory disease activity. We aimed to determine the prevalence of N. mikurensis in rheumatological patients receiving tumour necrosis factor inhibitors (TNFi) and a cohort of healthy individuals., Materials and Methods: This retrospective cohort study included 400 rheumatological patients treated with TNFi and 400 healthy blood donors. Plasma samples were retrieved from the Danish Rheumatological Biobank and the Danish Blood Donor Study between 2015 and 2022. Age, sex, diagnosis and duration of TNFi treatment were recovered from the Danish Rheumatological Database, DANBIO. Data on age and sex were available for the blood donors. One plasma sample per individual was tested for N. mikurensis DNA-specific real-time PCR targeting the groEL gene., Results: In the rheumatological patients, the median age was 61 years (IQR 55-68 years), 62% were women, and 44% had a diagnosis of seropositive rheumatoid arthritis. In total, 54% of the patients were treated with infliximab. The median time from TNFi initiation to blood sampling was 20 months (IQR, 5-60 months). N. mikurensis DNA was not detected in any samples from patients or blood donors., Conclusion: N. mikurensis infection does not appear to represent a prevalent risk in Danish rheumatological patients receiving TNFi or in blood donors., Competing Interests: Competing interests: This work was supported as part of NorthTick, an Interreg project supported by the North Sea Programme of the European Regional Development Fund of the European Union (Grant number 38-2-7-19). The funding bodies had no role in writing the manuscript. Outside of the present work: MØ has received an unrestricted research grant from Rigshospitalets Forskningspuljer. AML discloses speaker honoraria and advisory board activities from Gilead, ViiV/GSK, and Pfizer. AML reports a grant from The Lundbeck Foundation (R366-2021-127) and Aase and Ejnar Danielsen’s Foundation. BG discloses research grants (paid to institution) from AbbVie, Sandoz. MLH discloses research grants (paid to institution) from AbbVie, Biogen, BMS, Celltrion, Eli Lilly, Janssen Biologics B.V, Lundbeck Foundation, MSD, Pfizer, Roche, Samsung Biopsies, Sandoz and Novartis. MLH discloses honoraria (paid to institution) from Pfizer, Medac, and Sandoz. MLH has chaired the steering committee of the Danish Rheumatology Quality Registry (DANBIO, DRQ), which receives public funding from hospital owners and funding from pharmaceutical companies. MLH co-chairs EuroSpA, which generates real-world evidence of treatment of psoriatic arthritis and axial spondyloarthritis based on secondary data and is partly funded by Novartis. The other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2024
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7. Plasma neurofilament light significantly decreases following treatment in Lyme neuroborreliosis and is not associated with persistent symptoms.
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Mens H, Fjordside L, Gynthersen R, Ørbaek M, Andersen ÅB, Andreasson U, Blennow K, Sellebjerg F, Zetterberg H, and Lebech AM
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- Humans, Infant, Prospective Studies, Retrospective Studies, Intermediate Filaments, Anti-Bacterial Agents therapeutic use, Biomarkers, Lyme Neuroborreliosis drug therapy, Lyme Neuroborreliosis complications, Lyme Neuroborreliosis diagnosis
- Abstract
Background and Purpose: Currently there is an unmet need for a highly standardized blood biomarker test to monitor treatment response in Lyme neuroborreliosis (LNB). Differentiating between active or past infection is challenged by the relatively high frequency of persistent symptoms after the end of antibiotic treatment (estimated 15%-20%), the variable clinical course and the long-lasting Borrelia burgdorferi antibodies. The aim was therefore to evaluate plasma neurofilament light chain (pNfL) as a marker for disease activity in LNB., Methods: This was a prospective cohort of definite LNB (N = 36) with blood samples and clinical evaluation including Glasgow Outcome Score at treatment initiation and 3 and 6 months' follow-up. Consecutive plasma was retrospectively analysed for the content of neurofilament light chain by Quanterix® kits (Simoa® NF-light Kit)., Results: Plasma neurofilament light chain significantly decreased between treatment initiation and the 3-month follow-up (median 83 pg/ml vs. median 14 pg/ml (25 pairs), p < 0.0001). No significant change was observed between 3 and 6 months' follow-up (median 14 pg/ml vs. median 12 pg/ml (21 pairs), p = 0.33). At treatment initiation 90% had pNfL above the age-defined reference compared to only 23% and 7% respectively at 3 and 6 months' follow-up. Decreases in pNfL were mirrored by increasing Glasgow Outcome Score. Reporting persistent symptoms at the 6-month follow-up was not associated with pNfL (relative change from reference or actual values) at baseline or at 6 months' follow-up., Conclusion: Plasma neurofilament light chain decreases following antibiotic treatment in LNB and is not associated with reporting persistent symptoms. It was therefore speculated that it may prove useful as a treatment response biomarker in LNB., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)
- Published
- 2023
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8. Cerebrospinal fluid levels of the macrophage-specific biomarker sCD163 are diagnostic for Lyme neuroborreliosis: An observational cohort study.
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Ørbæk M, Gynthersen RMM, Mens H, Brandt C, Stenør C, Wiese L, Andersen ÅB, Møller HJ, and Lebech AM
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- Adult, Humans, ROC Curve, Cohort Studies, Biomarkers cerebrospinal fluid, Cerebrospinal Fluid, Lyme Neuroborreliosis diagnosis, Lyme Neuroborreliosis cerebrospinal fluid, Nervous System Diseases, Meningitis
- Abstract
Objectives: We aimed to investigate levels of the macrophage-specific marker, sCD163, in cerebrospinal fluid and plasma in patients with Lyme neuroborreliosis. We tested the diagnostic value of CSF-sCD163 and ReaScan-CXCL13 and analyzed if plasma-sCD163 could monitor treatment response., Methods: An observational cohort study: Cohort 1-Cerebrospinal fluid from adults with neuroborreliosis (n = 42), bacterial meningitis (n = 16), enteroviral meningitis (n = 29), and controls (n = 33); Cohort 2-Plasma from 23 adults with neuroborreliosis collected at diagnosis, three, and six months. sCD163 was determined using an in-house sandwich ELISA. ReaScan-CXCL13 measured semiquantitative concentrations of CXCL13, cut-off ≥ 250 pg/ml diagnosed neuroborreliosis. Receiver Operating Characteristics analyzed the diagnostic strength. A linear mixed model including follow-up as categorical fixed effect analyzed differences in plasma-sCD163., Results: CSF-sCD163 was higher in neuroborreliosis (643 µg/l) than in enteroviral meningitis (106 µg/l, p < 0.0001) and controls (87 µg/l, p < 0.0001), but not bacterial meningitis (669 µg/l, p = 0.9). The optimal cut-off was 210 µg/l, area under the curve (AUC) 0.85. ReaScan-CXCL13 had an AUC of 0.83. Combining ReaScan-CXCL13 with CSF-sCD163 increased AUC significantly to 0.89. Plasma-sCD163 showed little variation and was not elevated during the 6 months of follow-up., Conclusion: CSF-sCD163 is diagnostic for neuroborreliosis with an optimal cut-off of 210 µg/l. Combining ReaScan-CXCL13 with CSF-sCD163 increases AUC. Plasma-sCD163 cannot monitor treatment response., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Outside of the present work: AML report speakers honorarium/travel grants/advisory board activities from Gilead and GSK, and honorarium/advisory board activity from Pfizer. The other authors declare that they have no competing interests., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2023
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9. Exploration of the induced cytokine responses in European Lyme neuroborreliosis: A longitudinal cohort study.
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Gynthersen RMM, Ørbæk M, Mens H, Stenør C, Wiese L, Ostrowski SR, Nielsen SD, and Lebech AM
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- Humans, Longitudinal Studies, Europe epidemiology, Interleukin-17, Cytokines
- Abstract
Lyme neuroborreliosis (LNB) is a prevalent tick-borne disease in Europe caused by Borrelia burgdorferi sensu lato complex. Slightly suppressed induced Th1- and Th17-responses are seen at diagnosis. The induced immune response following antibiotic therapy is unknown. We hypothesized that the immune responses normalize after completing antibiotic treatment. An observational longitudinal cohort study investigating the induced immune response in adult patients with LNB at diagnosis, three and six months after treatment. Whole blood was added to three TruCulture® (Myriad RBM, Austin, USA) tubes each containing one stimulation. An additional TruCulture® tube was without stimulation representing the in vivo activation of blood immune cells. Nine cytokines were measured using Luminex (LX200, R&D Systems, BIO-Teche LTD). Changes in immune response were analyzed with linear mixed model including follow-up as categorical fixed effect. A total of 21 patients with 55 samples were included. All had clinical improvement, but 5/21 patients reported residual symptoms after six months. The non-induced release of IL-17A and IL-1β increased significantly from diagnosis to six month follow-up. Six months after treatment only IFN-α and TNF-α were below the reference range. Minor variations in the induced immune responses were seen during the study period. Th1- and Th17-responses continued to be low with low IFN-γ, IL-12p40, and IL-17A in multiple stimulations. Overall little dynamic was observed. The changes in the cytokine responses are most likely not linked to LNB pathogenesis and our results do not support the implementation of TruCulture® in the diagnostics or follow-up of LNB., Competing Interests: Competing interests Outside of the present work: AML reports speaker honorarium/travel grants from Gilead, GSK, and Pfizer, and advisory board activity from Gilead, GSK, and Pfizer. SDN reports speaker honorarium/travel grants from Gilead and ViiV/GSK and advisory board activity from Gilead. CS reports speaker honorarium from Boehringer Ingelheim and travel grants from Biogen. The other authors declare that they have no competing interests., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2023
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10. A novel Borrelia-specific real-time PCR assay is not suitable for diagnosing Lyme neuroborreliosis.
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Pedersen RR, Kragh KN, Fritz BG, Ørbæk M, Østrup Jensen P, Lebech AM, and Bjarnsholt T
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- Biological Assay, Humans, Real-Time Polymerase Chain Reaction, Borrelia, Borrelia burgdorferi Group genetics, Lyme Neuroborreliosis microbiology
- Abstract
Background: Diagnosing Lyme neuroborreliosis (LNB) is complicated by a lack of adequate test systems and by the complex culturing conditions required to grow the causative pathogens in the Borrelia sensu lato complex. Improved testing methods are urgently needed. Here, we evaluate the applicability of a novel commercially available Borrelia-specific real-time PCR assay to diagnose LNB., Materials and Methods: The specificity and sensitivity of the novel alphaCube Borrelia real-time PCR assay (Mikrogen) and the well-tested Micro-Dx™ real-time PCR assay (Molzym) were evaluated in cerebrospinal fluid (CSF) spiked with known amounts of Borrelia garinii and CSF from 19 patients with definite or possible LNB. CSF from patients diagnosed with neurosyphilis or enterovirus meningitis served as controls., Results: The alphaCube assay specifically identified Borrelia down to 93 B garinii cells/mL in spiked CSF samples. The Micro-Dx™ real-time PCR assay was able to identify the presence of bacteria down to 9300 cells/mL in spiked samples. In CSF from patients diagnosed with LNB the sensitivity of the alphaCube assay was 0.00 and 0.00 for the Micro-DX., Conclusion: Although the alphaCube Borrelia assay was able to identify down to 93 cells/mL in spiked CSF samples, the inability to identify Borrelia in CSF samples from patients with LNB suggests that this type of infection carries a bacterial load in CSF below this detection level. Based on these results, neither the alphaCube Borrelia real-time PCR assay nor the Micro-Dx™ real-time PCR assay can be recommended for routine diagnostics of LNB using CSF samples., (Copyright © 2022. Published by Elsevier GmbH.)
- Published
- 2022
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11. The Danish HIV Birth Cohort (DHBC) - a nationwide, prospective cohort.
- Author
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Weis N, Katzenstein TL, Ørbæk M, Storgaard M, Pedersen G, Johansen IS, and Moseholm E
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- Cesarean Section, Child, Denmark epidemiology, Female, Humans, Pregnancy, Prospective Studies, HIV Infections complications, HIV Infections drug therapy, HIV Infections epidemiology, Pregnancy Complications, Infectious drug therapy, Pregnancy Complications, Infectious epidemiology
- Abstract
Purpose: The purpose of the Danish HIV Birth Cohort (DHBC) is to investigate the significance of HIV-1 infection in pregnancy and after delivery in women living with HIV (WLWH) in Denmark and their children, in the era of antiretroviral therapy and other interventions for treatment and prophylaxis., Participants: All WLWH giving birth to one or more children in Denmark after 31 December 1999 are included, with consecutive ongoing enrolment, if they are living with HIV and pregnant, or if they are diagnosed with HIV in relation to pregnancy, delivery or shortly after delivery., Findings to Date: DHBC has been used to describe trends in the management of pregnancies in WLWH and their outcomes on a nationwide basis, mode of delivery and predictors of emergency caesarean section as well as risk factors during pregnancy in WLWH for birth-related complications compared with women from the general population (WGP). We have found that HIV-exposed, but uninfected (HEU) children born to WLWH had a lower median birth weight and gestational age and were at higher risk of intrauterine growth retardation than children born to WGP. We have investigated risk of in-hospital admission and use of antibiotics during the first 4 years of life among HEU children and showed that HEU children had an increased risk of overall hospital admission compared with a matched control group of unexposed children.Further, we compared anthropometric outcomes in children with a matched control group of children not exposed to HIV., Future Plans: To continuously investigate the significance of HIV infection and antiretroviral therapy in pregnancy and after delivery in WLWH in Denmark and their HEU children and compare these findings with children born to WGP., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
- Published
- 2021
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12. Stimulated Immune Response by TruCulture ® Whole Blood Assay in Patients With European Lyme Neuroborreliosis: A Prospective Cohort Study.
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Ørbæk M, Gynthersen RMM, Mens H, Stenør C, Wiese L, Brandt C, Ostrowski SR, Nielsen SD, and Lebech AM
- Subjects
- Adult, Cohort Studies, Humans, Immunity, Interleukin-12, Prospective Studies, Lyme Disease, Lyme Neuroborreliosis
- Abstract
Introduction: Borrelia burgdorferi sensu lato complex ( B. burgdorferi ) can cause a variety of clinical manifestations including Lyme neuroborreliosis. Following the tick-borne transmission, B. burgdorferi initially evade immune responses, later symptomatic infection is associated with occurrence of specific antibody responses. We hypothesized that B. burgdorferi induce immune hyporesponsiveness or immune suppression and aimed to investigate patients with Lyme neuroborreliosis ability to respond to immune stimulation., Methods: An observational cohort study investigating the stimulated immune response by standardized whole blood assay (TruCulture
® ) in adult patients with Lyme neuroborreliosis included at time of diagnosis from 01.09.2018-31.07.2020. Reference intervals were based on a 5-95% range of cytokine concentrations from healthy individuals (n = 32). Patients with Lyme neuroborreliosis and references were compared using Mann-Whitney U test. Heatmaps of cytokine responses were generated using the webtool Clustvis., Results: In total, 22 patients with Lyme neuroborreliosis (19 definite, 3 probable) were included. In the unstimulated samples, the concentrations of cytokines in patients with Lyme neuroborreliosis were comparable with references, except interferon (IFN)-α, interleukin (IL)-17A, IL-1β and IL-8, which were all significantly below the references. Patients with Lyme neuroborreliosis had similar concentrations of most cytokines in all stimulations compared with references. IFN-α, IFN-γ, IL-12 and IL-17A were lower than references in multiple stimulations., Conclusion: In this exploratory cohort study, we found lower or similar concentrations of circulating cytokines in blood from patients with Lyme neuroborreliosis at time of diagnosis compared with references. The stimulated cytokine release in blood from patients with Lyme neuroborreliosis was in general slightly lower than in the references. Specific patterns of low IL-12 and IFN-γ indicated low Th1-response and low concentrations of IL-17A did not support a strong Th17 response. Our results suggest that patients with Lyme neuroborreliosis elicit a slightly suppressed or impaired immune response for the investigated stimulations, however, whether the response normalizes remains unanswered., Competing Interests: Outside of the present work: AM-L reports speakers honorarium/travel grants from Gilead, speakers honorarium/travel grants from GSK, travel grants from MSD and advisory board activity from Gilead. SN reports speakers honorarium/travel grants from Gilead and ViiV/GSK and advisory board activity from Gilead. CS reports speaker honorarium from Boehringer Ingelheim and travel grants from Biogen. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ørbæk, Gynthersen, Mens, Stenør, Wiese, Brandt, Ostrowski, Nielsen and Lebech.)- Published
- 2021
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13. Classification of patients referred under suspicion of tick-borne diseases, Copenhagen, Denmark.
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Gynthersen RMM, Tetens MM, Ørbæk M, Haahr R, Fana V, Hansen K, Mens H, Andersen ÅB, and Lebech AM
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- Adolescent, Adult, Aged, Aged, 80 and over, Denmark epidemiology, Female, Humans, Lyme Disease complications, Lyme Disease epidemiology, Male, Middle Aged, Prevalence, Prospective Studies, Tick-Borne Diseases classification, Tick-Borne Diseases epidemiology, Tick-Borne Diseases microbiology, Young Adult, Lyme Disease diagnosis, Tick-Borne Diseases diagnosis
- Abstract
To provide better care for patients suspected of having a tick-transmitted infection, the Clinic for Tick-borne Diseases at Rigshospitalet, Copenhagen, Denmark was established. The aim of this prospective cohort study was to evaluate diagnostic outcome and to characterize demographics and clinical presentations of patients referred between the 1st of September 2017 to 31st of August 2019. A diagnosis of Lyme borreliosis was based on medical history, symptoms, serology and cerebrospinal fluid analysis. The patients were classified as definite Lyme borreliosis, possible Lyme borreliosis or post-treatment Lyme disease syndrome. Antibiotic treatment of Lyme borreliosis manifestations was initiated in accordance with the national guidelines. Patients not fulfilling the criteria of Lyme borreliosis were further investigated and discussed with an interdisciplinary team consisting of specialists from relevant specialties, according to individual clinical presentation and symptoms. Clinical information and demographics were registered and managed in a database. A total of 215 patients were included in the study period. Median age was 51 years (range 17-83 years), and 56 % were female. Definite Lyme borreliosis was diagnosed in 45 patients, of which 20 patients had erythema migrans, 14 patients had definite Lyme neuroborreliosis, six had acrodermatitis chronica atrophicans, four had multiple erythema migrans and one had Lyme carditis. Furthermore, 12 patients were classified as possible Lyme borreliosis and 12 patients as post-treatment Lyme disease syndrome. A total of 146 patients (68 %) did not fulfil the diagnostic criteria of Lyme borreliosis. Half of these patients (73 patients, 34 %) were diagnosed with an alternative diagnosis including inflammatory diseases, cancer diseases and two patients with a tick-associated disease other than Lyme borreliosis. A total of 73 patients (34 %) were discharged without sign of somatic disease. Lyme borreliosis patients had a shorter duration of symptoms prior to the first hospital encounter compared to patients discharged without a specific diagnosis (p<0.001). When comparing symptoms at presentation, patients discharged without a specific diagnosis suffered more often from general fatigue and cognitive dysfunction. In conclusion, 66 % of all referred patients were given a specific diagnosis after ended outpatient course. A total of 32 % was diagnosed with either definite Lyme borreliosis, possible Lyme borreliosis or post-treatment Lyme disease syndrome; 34 % was diagnosed with a non-tick-associated diagnosis. Our findings underscore the complexity in diagnosing Lyme borreliosis and the importance of ruling out other diseases through careful examination., (Copyright © 2020 The Authors. Published by Elsevier GmbH.. All rights reserved.)
- Published
- 2021
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14. CT and MR neuroimaging findings in patients with Lyme neuroborreliosis: A national prospective cohort study.
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Ørbæk M, Bodilsen J, Gynthersen RMM, Shekhrajka N, Nordberg CL, Larsen L, Storgaard M, Brandt C, Wiese L, Hansen BR, Luttichau HR, Andersen AB, Mens H, Nielsen H, and Lebech AM
- Subjects
- Adult, Aged, Cohort Studies, Humans, Magnetic Resonance Imaging, Neuroimaging, Prospective Studies, Tomography, X-Ray Computed, Lyme Neuroborreliosis complications, Lyme Neuroborreliosis diagnostic imaging, Lyme Neuroborreliosis epidemiology
- Abstract
Background: We aimed to describe the use and findings of cranial computerized tomography (CT-head), spine and brain magnetic resonance imaging (MRI-spine/MRI-brain) in Lyme neuroborreliose (LNB)., Methods: Patients with LNB were identified using a nationwide, population-based prospective cohort of all adults treated for neuroinfections at departments of infectious diseases in Denmark from 2015 to 2019. Multivariate logistic regression analyses assessed associations between clinical characteristics and MRI-findings consistent with LNB., Results: We included 368 patients (272 definite LNB and 96 probable LNB), 280 scans were performed in 198 patients. Neuroimaging was associated with older age (59 vs. 57, p = 0.03), suspicion of other diseases (77% vs. 37%, p < 0.0001), no history of tick bites (58% vs. 43%, p = 0.01), physical/cognitive deficits prior to admission (15% vs 5%, p = 0.006), peripheral palsy (10% vs. 2%, p = 0.0008), encephalitis (8% vs. 1%, p = 0.0007) and cognitive impairment (8% vs. 2%, p = 0.03) compared with those without neuroimaging. Normal or incidental findings were common (93/98 CT-head and 154/182 MRI). 1/98 CT-head, 19/131 MRI-brain and 6/51 MRI-spine had findings consistent with LNB. Symptoms ≥45 days was associated with MRI-findings consistent with LNB (adjusted odds ratio (aOR) 4.2, 95%confidence interval 1.2-14.4, p = 0.02)., Conclusion: In this Danish cohort including 368 LNB-patients, use of neuroimaging was common and often performed in older comorbid patients without previous tick-bite intended to investigate alternative diagnoses. The results were in general without pathology and neuroimaging cannot exclude LNB or replace lumbar puncture. MRI is of value when investigating alternative neurological diseases and may support suspicion of LNB in cases with meningeal/leptomeningeal/neural enhancement., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2020
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15. 64 Cu-DOTATATE Positron Emission Tomography (PET) of Borrelia Burgdorferi Infection: In Vivo Imaging of Macrophages in Experimental Model of Lyme Arthritis.
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Skovsbo Clausen A, Ørbæk M, Renee Pedersen R, Oestrup Jensen P, Lebech AM, and Kjaer A
- Abstract
Macrophages play a key role in the inflammatory response in Lyme arthritis (LA) and could be a target for diagnosing and monitoring active Borrelia burgdorferi sensu lato ( Bb ) infection. Therefore, we evaluated the potential of macrophage imaging using
64 Cu-DOTATATE PET/CT for detection of Bb activity in a murine model of LA. LA was established in C3H/HeNRj mice infected with Bb B31 strain ML23 pBBE22 luc . Bioluminescence imaging was performed to detect migration of spirochetes and inflammatory phagocytes to the joints. Three weeks post-infection64 Cu-DOTATATE PET/CT imaging was performed at an early (3 h) and late (48 h) time point. Plasma levels of a systemic macrophage marker in plasma CD163 were measured.64 Cu-DOTATATE uptake in infected joints was increased at the early ( p < 0.0001) and late time points ( p = 0.0005) compared with uptake in non-infected controls. No significant difference in plasma levels of CD163 was measured.64 Cu-DOTATATE PET allows for in vivo detection and quantification of LA locally in the joints through non-invasive visualization of macrophages. In contrast, measurement of a systemic macrophage marker in plasma, CD163, did not allow to detect disease. We suggest that64 Cu-DOTATATE PET could become a valuable diagnostic tool for in situ detection of Bb infection-related inflammation.- Published
- 2020
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16. The clinical spectrum of tularemia-Two cases.
- Author
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Ørbæk M, Lebech AM, and Helleberg M
- Abstract
We report two cases of tularemia with different clinical manifestations, both suspected of tick-borne transmission and with near-complete remission of all symptoms within 3 months after antimicrobial treatment. The first patient presented with a classical ulceroglandular manifestation; general malaise, an ulcer and lymphadenopathy, occurring two weeks after a tick bite. Diagnosis was established by polymerase chain reaction of a skin biopsy from the ulcer. The second patient presented with a rare systemic manifestation including bacteremia and myocarditis resulting in severe clinical heart failure, pulmonary edema and secondary kidney failure. Previous tick bites were elucidated after the bacteremia was discovered. The cases underscore the heterogeneity of manifestations, the diagnostic approach and the importance of thorough medical history including recent exposures especially in cases with infection of unknown origin., Competing Interests: Outside the submitted work: AML reports personal fees/travel grants and advisory board activity from 10.13039/100005564Gilead, personal fees/travel grants from 10.13039/501100002066GSK and travel grants from 10.13039/501100013236MSD; MH was supported by 10.13039/501100001732DNRF grant #126 and granted research funding from Gilead and honoraria from 10.13039/100002491Bristol-Myers Squibb, Janssen and 10.13039/501100002066GSK. MO have nothing to declare., (© 2020 The Author(s).)
- Published
- 2020
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17. [Suspected toxoplasmosis in pregnancy].
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Ørbæk M, Kjær ASL, Nielsen HV, Lebech M, Katzenstein T, and Lebech AM
- Subjects
- Female, Humans, Pregnancy, Pregnancy Complications, Infectious diagnosis, Pregnancy Complications, Infectious drug therapy, Pregnancy Complications, Parasitic diagnosis, Pregnancy Complications, Parasitic drug therapy, Toxoplasma, Toxoplasmosis diagnosis, Toxoplasmosis drug therapy, Toxoplasmosis, Congenital diagnosis, Toxoplasmosis, Congenital drug therapy
- Abstract
Primary infection with Toxoplasma gondii in pregnant women can lead to vertical transmission of the parasites resulting in congenital toxoplasmosis. The frequency of foetal infection increases with gestational age at maternal infection, but the risk of developing clinical sequelae decreases. Data on antiparasitic treatment suggest, that maternal treatment reduces the risk of serious neurological sequelae or death in congenitally infected offspring. Aspects of diagnosis and antimicrobial treatment of T. gondii infection during pregnancy are summarised in this review.
- Published
- 2020
18. Risk factors during pregnancy and birth-related complications in HIV-positive versus HIV-negative women in Denmark, 2002-2014.
- Author
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Ørbaek M, Thorsteinsson K, Moseholm Larsen E, Katzenstein TL, Storgaard M, Johansen IS, Pedersen G, Bach D, Helleberg M, Weis N, and Lebech AM
- Subjects
- Adult, Case-Control Studies, Cesarean Section statistics & numerical data, Denmark epidemiology, Female, Fetal Diseases etiology, Gestational Age, HIV Infections complications, Humans, Maternal Age, Multivariate Analysis, Pregnancy, Retrospective Studies, Risk Factors, Fetal Diseases epidemiology, HIV Infections epidemiology, Pregnancy Outcome epidemiology
- Abstract
Objectives: We aimed to compare risk factors for adverse pregnancy outcomes in women living with HIV (WLWH) with those in women of the general population (WGP) in Denmark. Further, we estimated risk of pregnancy- or birth-related complications., Methods: A retrospective cohort study including all WLWH who delivered a live-born child from 2002 to 2014 and WGP, matched by origin, age, year and parity, was carried out. We compared risk factors during pregnancy and estimated risk of pregnancy- and birth-related complications using multivariate logistic regression., Results: A total of 2334 pregnancies in 304 WLWH and 1945 WGP were included in the study. WLWH had more risk factors present than WGP during pregnancy: previous caesarean section (CS) (24.7% versus 16.3%, respectively; P = 0.0001), smoking (14.2% versus 7.5%, respectively; P = 0.0001) and previous perinatal/neonatal death (2.3% versus 0.9%, respectively; P = 0.03). We found no difference between groups regarding gestational diabetes, hypertensive disorders, low birth weights or premature delivery. More children of WLWH had intrauterine growth retardation (IUGR) [adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.1-3.2; P = 0.02]. Median gestational age and birth weight were lower in children born to WLWH. WLWH had a higher risk of emergency CS (EmCS) (aOR 1.6; 95% CI 1.2-2.1; P = 0.0005) and postpartum haemorrhage (aOR 1.4; 95% CI 1.0-1.9; P = 0.02) but not infection, amniotomy, failure to progress, low activity-pulse-grimace-appearance-respiration (APGAR) score or signs of asphyxia., Conclusions: WLWH had more risk factors present during pregnancy, similar risks of most pregnancy- and birth-related complications but a higher risk of postpartum haemorrhage and EmCS compared with WGP. Children born to WLWH had lower median birth weights and gestational ages and were at higher risk of IUGR., (© 2019 British HIV Association.)
- Published
- 2020
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19. Lyme Neuroborreliosis in a Patient with Breast Cancer: MRI and PET/CT Findings.
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Ørbæk M, Klausen C, Lebech AM, and Mens H
- Abstract
We present a case demonstrating the performance of different radiographical and nuclear medicine imaging modalities in the diagnostic work-up of a patient with Lyme neuroborreliosis. The patient presented in late summer 2019 with radicular pains followed by a foot drop and peripheral facial palsy, both right-sided. Due to a history of breast cancer, disseminated malignant disease was initially suspected. Bone metastasis was ruled out by skeletal scintigraphy. Magnetic resonance imaging (MRI) of the neuroaxis and a whole body
18 F-FDG PET-CT was performed within 48 hours. The MRI revealed a strong contrast enhancement of the conus medullaris and fibers of the cauda equina, while the18 F-FDG PET/CT was without pathological findings. Examination of cerebrospinal fluid led to the definitive diagnosis of Lyme neuroborreliosis with monocytic pleocytosis and a positive intrathecal test for Borrelia burgdorferi . The patient became pain-free after 10 days of ceftriaxone, and the paralysis slowly regressed the following month. This case highlights the difficulty of the diagnosis of Lyme neuroborreliosis and discusses the relevant imaging findings., Competing Interests: The authors declare no conflict of interest.- Published
- 2020
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20. 18 F-FDG PET/MR-imaging in a Göttingen Minipig model of atherosclerosis: Correlations with histology and quantitative gene expression.
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Ludvigsen TP, Pedersen SF, Vegge A, Ripa RS, Johannesen HH, Hansen AE, Löfgren J, Schumacher-Petersen C, Kirk RK, Pedersen HD, Christoffersen BØ, Ørbæk M, Forman JL, Klausen TL, Olsen LH, and Kjaer A
- Subjects
- Animals, Atherosclerosis genetics, Correlation of Data, Disease Models, Animal, Gene Expression, Male, Swine, Swine, Miniature, Atherosclerosis diagnostic imaging, Fluorodeoxyglucose F18, Magnetic Resonance Imaging methods, Positron-Emission Tomography methods, Radiopharmaceuticals
- Abstract
Background and Aims: The advantage of combining molecular and morphological imaging, e.g. positron emission tomography and magnetic resonance imaging (PET/MRI), is reflected in the increased use of these modalities as surrogate end-points in clinical trials. This study aimed at evaluating plaque inflammation using
18 F-fluorodeoxyglucose (18 F-FDG)-PET/MRI, and gene expression in a minipig model of atherosclerosis., Methods: Göttingen Minipigs were fed for 60 weeks with fat/fructose/cholesterol-rich diet (FFC), chow (Control) or FFC-diet changed to chow midway (diet normalization group; DNO). In all groups,18 F-FDG-PET/MRI of the abdominal aorta was assessed midway and at study-end. The aorta was analyzed using histology and gene expression., Results: At study-end, FFC had significantly higher FDG-uptake compared to Control (target-to-background maximal uptake, TBRMax (95% confidence interval) CITBRMax : 0.092; 7.32) and DNO showed significantly decreased uptake compared to FFC (CITBRMax : -5.94;-0.07). No difference was observed between DNO and Control (CITBRMax : -2.71; 4.11). FFC displayed increased atherosclerosis and gene expression of inflammatory markers, including vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 68 (CD68), matrix metalloproteinase 9 (MMP9), cathepsin K (CTSK) and secreted phosphoprotein 1 (SPP1) compared to Control and DNO (all, p < 0.05). FDG-uptake correlated with gene expression of inflammatory markers, including CD68, ρs = 0.58; MMP9, ρs = 0.46; SPP1, ρs = 0.44 and CTSK, ρs = 0.49; (p ≤ 0.01 for all)., Conclusions: In a model of atherosclerosis,18 F-FDG-PET/MRI technology allows for detection of inflammation in atherosclerotic plaques, consistent with increased inflammatory gene expression. Our findings corroborate clinical data and are important in pre-clinical drug development targeting plaque inflammation., (Copyright © 2019. Published by Elsevier B.V.)- Published
- 2019
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21. Assessment of mode of delivery and predictors of emergency caesarean section among women living with HIV in a matched-pair setting with women from the general population in Denmark, 2002-2014.
- Author
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Ørbaek M, Thorsteinsson K, Helleberg M, Moseholm E, Katzenstein TL, Storgaard M, Johansen IS, Pedersen G, Weis N, and Lebech AM
- Subjects
- Adult, Denmark, Female, Humans, Infant, Newborn, Male, Pregnancy, Retrospective Studies, Risk Assessment, Cesarean Section statistics & numerical data, Delivery, Obstetric methods, Emergency Medical Services statistics & numerical data, HIV Infections, Pregnancy Complications, Infectious
- Abstract
Objectives: We aimed to assess mode of delivery and predictors of emergency caesarean section (EmCS) in women living with HIV (WLWH) in a matched-pair setting with women from the general population (WGP) in Denmark. Further, we analysed birth plan in WLWH., Methods: All WLWH giving birth to live-born children from 2002 to 2014 were included in the study. Data were retrieved from medical records and national registries. WLWH were matched 1:5 by age, birth year, parity and ethnicity to WGP. Multivariate logistic regression was used to estimate predictors., Results: We included 389 WLWH and 1945 WGP in the study. At delivery, all WLWH were on antiretroviral therapy and 85.6% had HIV RNA <40 HIV-1 RNA copies/mL. Mean age was 32.7 years [95% confidence interval (CI) 32.1-33.2 years]. Mode of delivery differed significantly between WLWH and WGP [vaginal delivery, 33.4% versus 73.3%, respectively; elective caesarean section (ECS), 40.6% versus 9.7%, respectively; EmCS, 26% versus 17%, respectively; P < 0.0001]. Age > 40 years [adjusted odds ratio (aOR) 2.3; 95% CI 1.5-3.5], asphyxia (aOR 3.2; 95% CI 2.4-4.1), delivery during the evening and at night [aOR 2.3 (95% CI 1.7-3.0) and aOR 2.0 (95% CI 1.5-2.7), respectively], preterm delivery (aOR 3.8; 95% CI 2.6-5.6) and premature rupture of membranes (aOR 3.0; 95% CI 2.1-4.4) predicted EmCS. WLWH had a higher risk of EmCS compared with WGP [2002-2006, aOR 2.0 (95% CI 1.2-3.3); 2007-2008, aOR 2.9 (95% CI 1.4-5.9); 2009-2014, aOR 2.6 (95% CI 1.7-3.9)]. After 2007, more than half of WLWH planned to deliver vaginally. Prior caesarean section was associated with ECS (aOR 11.0; 95% CI 4.5-26.8). No mother-to-child transmission occurred., Conclusions: Increasing numbers of WLWH deliver vaginally. Despite virological suppression, more WLWH plan and deliver by ECS than WGP. WLWH had a twofold higher risk of EmCS compared with WGP., (© 2017 British HIV Association.)
- Published
- 2017
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22. Comparison of the Peripheral Reactive Hyperemia Index with Myocardial Perfusion Reserve by 82 Rb PET/CT in HIV-Infected Patients.
- Author
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Ørbæk M, Hasbak P, Sejersten Ripa R, Kjær A, Lebech AM, and Knudsen A
- Abstract
After the introduction of antiretroviral therapy (ART) the life expectancy of patients infected with human immunodeficiency virus (HIV) is now approaching that of the general population and the importance of non-AIDS co-morbidities is increasing. Specifically, the risk of coronary artery disease (CAD) seems to be higher in HIV-infected patients and an accurate risk prediction of CAD is of high importance for optimal long term treatment. In this study, we assessed the correlation of the endoPAT, which is an office-based CVD screening tool with the myocardial perfusion reserve by
82 -rubidium PET/CT. We measured the reactive hyperemia index, which is a measure of the endothelial responsiveness, by the use of an endoPAT device (Itamar Medical, Caesarea, Israel) in 48 ART treated HIV-infected patients with high CD 4 cell counts and viral suppression (HIV-RNA < 20 copies/mL), who had previously undergone measurement of the myocardial perfusion reserve by82 -rubidium PET/CT for study purposes. We found an inverse correlation between the reactive hyperemia index and the myocardial perfusion reserve which most likely indicates different vascular physiology. This study did not find evidence to suggest the immediate implementation of the reactive hyperemia index as a screening tool for early coronary artery disease in well-treated HIV-infected patients pending further validation in larger prospective studies., Competing Interests: The authors declare no conflict of interest.- Published
- 2017
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23. (18)F-FDG PET/CT Findings in Acute Epstein-Barr Virus Infection Mimicking Malignant Lymphoma.
- Author
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Ørbæk M, Graff J, Markova E, Kronborg G, and Lebech AM
- Abstract
We present a case demonstrating the diagnostic work-up and follow-up of a patient with acute Epstein-Barr virus (EBV) infection in which the clinical picture and imaging on (18)F-FDG PET/CT mimicked malignant lymphoma. Follow-up (18)F-FDG PET/CT scan in the patient performed 7 weeks after the abnormal scan revealed complete resolution of the metabolically active disease in the neck, axillas, lung hili, and spleen. This case highlights inflammation as one of the most well established false positives when interpreting (18)F-FDG PET/CT scans.
- Published
- 2016
- Full Text
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