Publications by authors named "Anne-Mette Lebech"

99 Publications

Potential drug-drug interactions between antiretroviral drugs and comedications, including dietary supplements, among people living with HIV: A clinical survey.

HIV Med 2022 May 6. Epub 2022 May 6.

CREDID, Center for Research and Disruption of Infectious Diseases, Department of Infectious Diseases, Copenhagen University Hospital - Amager and Hvidovre, Hvidovre, Denmark.

Objective: Age-related comorbidities, polypharmacy and thereby the risk of potential drug-drug interactions (PDDIs) among people living with HIV (PLWH) have increased over the years. We estimated the prevalence of comedications, including dietary supplements, and evaluated PDDIs among PLWH receiving antiretroviral therapy (ART) in Denmark in an outpatient setting.

Methods: Information on prescription medication, over-the-counter medication and dietary supplements was obtained from adult PLWH receiving ART attending two outpatient clinics in Denmark. The PDDIs were identified using the University of Liverpool's drug interaction database. Associations between PDDIs and relevant variables were compared using logistic regression models.

Results: A total of 337 PLWH receiving ART with a median age of 53 years (interquartile range: 45-61) were included; 77% were male and 96% had a HIV-RNA viral load < 50 copies/mL. Twenty-six per cent of participants received five or more comedications and 56% consumed dietary supplements. Co-administration of drugs requiring dose adjustment or monitoring was identified in the medication lists of 52% of participants, and 4.5% were on drugs that should not be co-administered. Male sex [odds ratio (OR) = 1.9, 95% confidence interval (CI): 1.0-3.4], being on a protease inhibitor (OR = 4.3, 95% CI: 1.9-9.7), receiving five or more comedications (OR = 3.3, 95% CI: 1.5-7.2), taking over-the-counter medications (OR = 1.9, 95% CI: 1.1-3.3) and dietary supplements (OR = 2.0, 95% CI: 1.2-3.3) were independent predictors of PDDIs.

Conclusion: Potential drug-drug interactions were common among our study population Our study confirms that polypharmacy and being on a protease inhibitor-based regimen increase the risk of PDDIs considerably and highlights the importance of questioning PLWH about dietary supplement intake.
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http://dx.doi.org/10.1111/hiv.13321DOI Listing
May 2022

Neuropsychiatric and Cognitive Outcomes in Patients 6 Months After COVID-19 Requiring Hospitalization Compared With Matched Control Patients Hospitalized for Non-COVID-19 Illness.

JAMA Psychiatry 2022 05;79(5):486-497

Biological and Precision Psychiatry, Copenhagen Research Center for Mental Health, Mental Health Centre Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.

Importance: Prolonged neuropsychiatric and cognitive symptoms are increasingly reported in patients after COVID-19, but studies with well-matched controls are lacking.

Objective: To investigate cognitive impairment, neuropsychiatric diagnoses, and symptoms in survivors of COVID-19 compared with patients hospitalized for non-COVID-19 illness.

Design, Setting, And Participants: This prospective case-control study from a tertiary referral hospital in Copenhagen, Denmark, conducted between July 2020 and July 2021, followed up hospitalized COVID-19 survivors and control patients hospitalized for non-COVID-19 illness, matched for age, sex, and intensive care unit (ICU) status 6 months after symptom onset.

Exposures: Hospitalization for COVID-19.

Main Outcomes And Measures: Participants were investigated with the Mini-International Neuropsychiatric Interview, the Montreal Cognitive Assessment (MoCA), neurologic examination, and a semi-structured interview for subjective symptoms. Primary outcomes were total MoCA score and new onset of International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) psychiatric diagnoses. Secondary outcomes included specific psychiatric diagnoses, subjective symptoms, and neurologic examination results. All outcomes were adjusted for age, sex, ICU admission, admission length, and days of follow-up. Secondary outcomes were adjusted for multiple testing.

Results: A total of 85 COVID-19 survivors (36 [42%] women; mean [SD] age 56.8 [14] years) after hospitalization and 61 matched control patients with non-COVID-19 illness (27 [44%] women, mean age 59.4 years [SD, 13]) were enrolled. Cognitive status measured by total geometric mean MoCA scores at 6-month follow-up was lower (P = .01) among COVID-19 survivors (26.7; 95% CI, 26.2-27.1) than control patients (27.5; 95% CI, 27.0-27.9). The cognitive status improved substantially (P = .004), from 19.2 (95% CI, 15.2-23.2) at discharge to 26.1 (95% CI, 23.1-29.1) for 15 patients with COVID-19 with MoCA evaluations from hospital discharge. A total of 16 of 85 patients with COVID-19 (19%) and 12 of 61 control patients (20%) had a new-onset psychiatric diagnosis at 6-month follow-up, which was not significantly different (odds ratio, 0.93; 95% CI, 0.39-2.27; P = .87). In fully adjusted models, secondary outcomes were not significantly different, except anosmia, which was more common after COVID-19 (odds ratio, 4.56; 95% CI, 1.52-17.42; P = .006); but no longer when adjusting for multiple testing.

Conclusions And Relevance: In this prospective case-control study, cognitive status at 6 months was worse among survivors of COVID-19, but the overall burden of neuropsychiatric and neurologic signs and symptoms among survivors of COVID-19 requiring hospitalization was comparable with the burden observed among matched survivors hospitalized for non-COVID-19 causes.
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http://dx.doi.org/10.1001/jamapsychiatry.2022.0284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8943626PMC
May 2022

[Lyme neuroborreliosis in adults].

Ugeskr Laeger 2022 03;184(10)

Medicinsk Afdeling, Sjællands Universitetshospital Roskilde.

Lyme neuroborreliosis (LNB) caused by the spirochete bacteria Borrelia burgdorferi sensu lato complex is the most common bacterial neuroinfection in Denmark (180 cases per year). One of the main challenges to LNB is the diagnosis due to its variant manifestations often involving the skin, musculosceletal or nervous system affecting patient morbidity. Recent data shows a diagnostic delay of 21 days in laboratory-confirmed patients in Denmark. The aim of this review is to summarise current state of knowledge concerning clinical manifestations, diagnostic assessment, antibiotic therapy, and prognosis.
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March 2022

Oral and Anal Carriage of Streptococcus pneumoniae Among Sexually Active Men With HIV Who Have Sex With Men.

J Infect Dis 2022 May;225(9):1575-1580

Department of Infectious Diseases, Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.

People with HIV are at increased risk of pneumococcal disease. We investigate oral and anal carriage rates of Streptococcus pneumoniae by molecular methods among 82 men with HIV who have sex with men (MSM). A questionnaire, oral wash, and anal swab samples were obtained at baseline and 12 months. Oral carriage rates were 32.9% (27/82) at baseline and 41.7% (30/72) at follow-up. Anal carriage rates were 2.4% (2/82) at baseline and 2.9% (2/70) at follow-up. Genogroup 24 was predominant. Results suggest high oral carriage rates of S. pneumoniae among MSM living with HIV. A minority were anal carriers.
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http://dx.doi.org/10.1093/infdis/jiab512DOI Listing
May 2022

Brain Abscesses in a Patient with Disseminated Non-Small Cellular Lung Cancer: MRI Findings.

Diagnostics (Basel) 2021 Jun 18;11(6). Epub 2021 Jun 18.

Heart Centre, Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.

Brain abscesses caused by (LM) are very rare and carry a high mortality risk. We present a patient with disseminated non-small cellular lung cancer (NSCLC) and multiple unusual LM brain abscesses. These abscesses have multiple elongated peripherally enhancing lesions in a characteristic formation that is "worm or tramtrack-like" following the white matter fiber tracts.
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http://dx.doi.org/10.3390/diagnostics11061115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235038PMC
June 2021

Clinical characteristics of pyogenic vertebral osteomyelitis, and factors associated with inadequate treatment response.

Int J Infect Dis 2021 Jul 4;108:487-493. Epub 2021 Jun 4.

Department of Infectious Diseases, Heart Centre, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Objectives: Pyogenic vertebral osteomyelitis (PVO) is associated with a high burden of disease. Our study aimed to describe characteristics at presentation of PVO, the risk of inadequate treatment response (ITR), relapse, and death, and to determine risk factors for ITR.

Methods: Patients with an ICD-10 discharge code for PVO and admission to a major Danish university hospital between November 2016 and April 2019 were included. ITR was defined as clinical, microbiological, and/or radiological progression during treatment. Data were collected through review of medical records, and logistic regression was used to determine adjusted odds ratios (aOR).

Results: Of 106 patients included, 87% presented with pain in the spine, 97% elevated CRP, 14% severe sepsis, and 13% with a history of previous spinal surgery. 39% were infected with Staphylococcus aureus and 9% with Escherichia coli. 31% responded inadequately to treatment, and risk factors for ITR were previous spinal surgery (aOR 19.29; 95% confidence interval (CI) 2.20-169.08), severe sepsis (aOR 4.59; 95% CI 1.28-15.41), and infection with Escherichia coli (aOR 8.10; 95% CI 1.71-38.45). 13% experienced relapse within the first 2 years, while the 1-year crude mortality was 12%.

Conclusion: Staphylococcus aureus is still the main pathogen in PVO patients, and the risks of relapse and mortality remain high. Factors found to be associated with ITR were previous spinal surgery, severe sepsis, and infection with Escherichia coli.
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http://dx.doi.org/10.1016/j.ijid.2021.05.078DOI Listing
July 2021

Stimulated Immune Response by TruCulture Whole Blood Assay in Patients With European Lyme Neuroborreliosis: A Prospective Cohort Study.

Front Cell Infect Microbiol 2021 10;11:666037. Epub 2021 May 10.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Introduction: sensu lato complex () can cause a variety of clinical manifestations including Lyme neuroborreliosis. Following the tick-borne transmission, initially evade immune responses, later symptomatic infection is associated with occurrence of specific antibody responses. We hypothesized that 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.
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http://dx.doi.org/10.3389/fcimb.2021.666037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141554PMC
July 2021

Response to Aviv et al.

J Infect Dis 2021 08;224(3):559-561

Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

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http://dx.doi.org/10.1093/infdis/jiab249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8136013PMC
August 2021

Oral and anal carriage of Neisseria meningitidis among sexually active HIV-infected men who have sex with men in Denmark 2014-15.

Int J Infect Dis 2021 Apr 18;105:337-344. Epub 2021 Feb 18.

Department of Infectious Diseases, Copenhagen University Hospital - Hvidovre, Amager, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Introduction: Outbreaks of invasive meningococcal disease (IMD) among men who have sex with men (MSM) caused by a hypervirulent, non-encapsulated Neisseria meningitidis (Nm) clone belonging to genogroup C have been described. We aimed to determine the oral and anal carriage rates and genogroups of Nm among MSM living with HIV.

Methods: Sexually active MSM living with HIV were included. A questionnaire, an oral wash sample and an anal swab were collected at baseline and 12 months follow-up. Identification of Nm and genogrouping was performed using real-time polymerase chain reaction analysis.

Results: Among 82 MSM, the Nm carriage rate was 31.7% (95% CI 21.9-42.9) at baseline. The oral carriage rate was 24.4% (95% CI 15.6-35.1) and the anal rate was 11.0% (95% CI 5.1-19.8). Non-groupable Nm were most prevalent followed by genogroup B and genogroup Y. Rates were similar at follow-up.

Conclusion: Strains of Nm were detected in both oral washes and anal samples in our study. Our results suggest that Nm may be transmitted sexually among MSM. Non-groupable Nm were predominant in our population and no genogroup C Nm were detected.
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http://dx.doi.org/10.1016/j.ijid.2021.02.062DOI Listing
April 2021

Psychiatric Medication Use After Possible Neuroborreliosis-Reply.

JAMA Psychiatry 2021 03;78(3):340-341

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

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http://dx.doi.org/10.1001/jamapsychiatry.2020.4421DOI Listing
March 2021

Central and peripheral nervous system complications of COVID-19: a prospective tertiary center cohort with 3-month follow-up.

J Neurol 2021 Sep 13;268(9):3086-3104. Epub 2021 Jan 13.

Departments of Neurology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

Objective: To systematically describe central (CNS) and peripheral (PNS) nervous system complications in hospitalized COVID-19 patients.

Methods: We conducted a prospective, consecutive, observational study of adult patients from a tertiary referral center with confirmed COVID-19. All patients were screened daily for neurological and neuropsychiatric symptoms during admission and discharge. Three-month follow-up data were collected using electronic health records. We classified complications as caused by SARS-CoV-2 neurotropism, immune-mediated or critical illness-related.

Results: From April to September 2020, we enrolled 61 consecutively admitted COVID-19 patients, 35 (57%) of whom required intensive care (ICU) management for respiratory failure. Forty-one CNS/PNS complications were identified in 28 of 61 (45.9%) patients and were more frequent in ICU compared to non-ICU patients. The most common CNS complication was encephalopathy (n = 19, 31.1%), which was severe in 13 patients (GCS ≤ 12), including 8 with akinetic mutism. Length of ICU admission was independently associated with encephalopathy (OR = 1.22). Other CNS complications included ischemic stroke, a biopsy-proven acute necrotizing encephalitis, and transverse myelitis. The most common PNS complication was critical illness polyneuromyopathy (13.1%), with prolonged ICU stay as independent predictor (OR = 1.14). Treatment-related PNS complications included meralgia paresthetica. Of 41 complications in total, 3 were para/post-infectious, 34 were secondary to critical illness or other causes, and 4 remained unresolved. Cerebrospinal fluid was negative for SARS-CoV-2 RNA in all 5 patients investigated.

Conclusion: CNS and PNS complications were common in hospitalized COVID-19 patients, particularly in the ICU, and often attributable to critical illness. When COVID-19 was the primary cause for neurological disease, no signs of viral neurotropism were detected, but laboratory changes suggested autoimmune-mediated mechanisms.
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http://dx.doi.org/10.1007/s00415-020-10380-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803470PMC
September 2021

Characteristics and Long-term Prognosis of Danish Patients With Varicella Zoster Virus Detected in Cerebrospinal Fluid Compared With the Background Population.

J Infect Dis 2021 09;224(5):850-859

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: Risk factors for, and long-term outcomes following, detection of varicella zoster virus (VZV) DNA in the cerebrospinal fluid (CSF) are unknown.

Methods: We performed a nationwide population-based cohort study of all Danish residents who had VZV DNA detected in the CSF by polymerase chain reaction (PCR) between 1 January 1997 and 1 March 2016 (VZV cohort; n = 517) and an age- and sex- matched comparison cohort from the general Danish population (n = 9823). We examined potential risk factors and mortality, neurologic morbidity, psychiatric morbidity, redemptiom of prescriptions for nervous system medicine prescribed for the nervous system, and social outcomes.

Results: Prior hospital admission, redemption of immunosuppressive medicine, comorbidity, and immunosuppressive conditions were associated with detection of VZV DNA in the CSF. Mortality was increased in the VZV cohort, especially during the first year of observation and among patients with encephalitis. Patients in the VZV cohort had an increased risk of dementia and epilepsy. The redemption of antiepileptics and antidepressants was increased in the VZV cohort.

Conclusions: Immunosuppression and comorbidity are associated with increased risk of detection of VZV DNA in the CSF and the condition is associated with increased mortality and neurological morbidity.
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http://dx.doi.org/10.1093/infdis/jiab013DOI Listing
September 2021

CT and MR neuroimaging findings in patients with Lyme neuroborreliosis: A national prospective cohort study.

J Neurol Sci 2020 Dec 10;419:117176. Epub 2020 Oct 10.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen.

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.
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http://dx.doi.org/10.1016/j.jns.2020.117176DOI Listing
December 2020

Classification of patients referred under suspicion of tick-borne diseases, Copenhagen, Denmark.

Ticks Tick Borne Dis 2021 01 9;12(1):101591. Epub 2020 Oct 9.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.

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.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101591DOI Listing
January 2021

Echocardiographic abnormalities and predictors of mortality in hospitalized COVID-19 patients: the ECHOVID-19 study.

ESC Heart Fail 2020 10 22. Epub 2020 Oct 22.

Department of Respiratory Medicine and Infectious Diseases, Nordsjaellands Hospital, University of Copenhagen, Copenhagen, Denmark.

Aims: The present study had two aims: (i) compare echocardiographic parameters in COVID-19 patients with matched controls and (2) assess the prognostic value of measures of left (LV) and right ventricular (RV) function in relation to COVID-19 related death.

Methods And Results: In this prospective multicentre cohort study, 214 consecutive hospitalized COVID-19 patients underwent an echocardiographic examination (by pre-determined research protocol). All participants were successfully matched 1:1 with controls from the general population on age, sex, and hypertension. Mean age of the study sample was 69 years, and 55% were male participants. LV and RV systolic function was significantly reduced in COVID-19 cases as assessed by global longitudinal strain (GLS) (16.4% ± 4.3 vs. 18.5% ± 3.0, P < 0.001), tricuspid annular plane systolic excursion (TAPSE) (2.0 ± 0.4 vs. 2.6 ± 0.5, P < 0.001), and RV strain (19.8 ± 5.9 vs. 24.2 ± 6.5, P = 0.004). All parameters remained significantly reduced after adjusting for important cardiac risk factors. During follow-up (median: 40 days), 25 COVID-19 cases died. In multivariable Cox regression reduced TAPSE [hazard ratio (HR) = 1.18, 95% confidence interval (CI) [1.07-1.31], P = 0.002, per 1 mm decrease], RV strain (HR = 1.64, 95%CI[1.02;2.66], P = 0.043, per 1% decrease) and GLS (HR = 1.20, 95%CI[1.07-1.35], P = 0.002, per 1% decrease) were significantly associated with COVID-19-related death. TAPSE and GLS remained significantly associated with the outcome after restricting the analysis to patients without prevalent heart disease.

Conclusions: RV and LV function are significantly impaired in hospitalized COVID-19 patients compared with matched controls. Furthermore, reduced TAPSE and GLS are independently associated with COVID-19-related death.
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http://dx.doi.org/10.1002/ehf2.13044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755011PMC
October 2020

Cu-DOTATATE Positron Emission Tomography (PET) of Infection: Imaging of Macrophages in Experimental Model of Lyme Arthritis.

Diagnostics (Basel) 2020 Oct 6;10(10). Epub 2020 Oct 6.

Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, DK-2100 Copenhagen, Denmark.

Macrophages play a key role in the inflammatory response in Lyme arthritis (LA) and could be a target for diagnosing and monitoring active sensu lato () infection. Therefore, we evaluated the potential of macrophage imaging using Cu-DOTATATE PET/CT for detection of activity in a murine model of LA. LA was established in C3H/HeNRj mice infected with B31 strain ML23 pBBE22. Bioluminescence imaging was performed to detect migration of spirochetes and inflammatory phagocytes to the joints. Three weeks post-infection 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. Cu-DOTATATE uptake in infected joints was increased at the early ( < 0.0001) and late time points ( = 0.0005) compared with uptake in non-infected controls. No significant difference in plasma levels of CD163 was measured. 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 that Cu-DOTATATE PET could become a valuable diagnostic tool for in situ detection of infection-related inflammation.
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http://dx.doi.org/10.3390/diagnostics10100790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601205PMC
October 2020

Assessment of the Risk of Psychiatric Disorders, Use of Psychiatric Hospitals, and Receipt of Psychiatric Medication Among Patients With Lyme Neuroborreliosis in Denmark.

JAMA Psychiatry 2021 02;78(2):177-186

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Importance: The association of Lyme neuroborreliosis with the development of psychiatric disease is unknown and remains a subject of debate.

Objective: To investigate the risk of psychiatric disease, the percentage of psychiatric hospital inpatient and outpatient contacts, and the receipt of prescribed psychiatric medications among patients with Lyme neuroborreliosis compared with individuals in a matched comparison cohort.

Design, Setting, And Participants: This nationwide population-based matched cohort study included all residents of Denmark who received a positive result on an intrathecal antibody index test for Borrelia burgdorferi (patient cohort) between January 1, 1995, and December 31, 2015. Patients were matched by age and sex to a comparison cohort of individuals without Lyme neuroborreliosis from the general population of Denmark. Data were analyzed from February 2019 to March 2020.

Exposures: Diagnosis of Lyme neuroborreliosis, defined as a positive result on an intrathecal antibody index test for B burgdorferi.

Main Outcomes And Measures: The 0- to 15-year hazard ratios for the assignment of psychiatric diagnostic codes, the difference in the percentage of psychiatric inpatient and outpatient hospital contacts, and the difference in the percentage of prescribed psychiatric medications received among the patient cohort vs the comparison cohort.

Results: Among 2897 patients with Lyme neuroborreliosis (1646 men [56.8%]) and 28 970 individuals in the matched comparison cohort (16 460 men [56.8%]), the median age was 45.7 years (interquartile range [IQR], 11.5-62.0 years) for both groups. The risk of a psychiatric disease diagnosis and the percentage of hospital contacts for psychiatric disease were not higher among patients with Lyme neuroborreliosis compared with individuals in the comparison cohort. A higher percentage of patients with Lyme neuroborreliosis compared with individuals in the comparison cohort received anxiolytic (7.2% vs 4.7%; difference, 2.6%; 95% CI, 1.6%-3.5%), hypnotic and sedative (11.0% vs 5.3%; difference, 5.7%; 95% CI, 4.5%-6.8%), and antidepressant (11.4% vs 6.0%; difference, 5.4%; 95% CI, 4.3%-6.6%) medications within the first year after diagnosis, after which the receipt of psychiatric medication returned to the same level as the comparison cohort.

Conclusions And Relevance: In this population-based matched cohort study, patients with Lyme neuroborreliosis did not have an increased risk of developing psychiatric diseases that required hospital care or treatment with prescription medication. The increased receipt of psychiatric medication among patients with Lyme neuroborreliosis within the first year after diagnosis, but not thereafter, suggests that most symptoms associated with the diagnosis subside within a short period.
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http://dx.doi.org/10.1001/jamapsychiatry.2020.2915DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542530PMC
February 2021

Changes in Lyme neuroborreliosis incidence in Denmark, 1996 to 2015.

Ticks Tick Borne Dis 2020 11 25;11(6):101549. Epub 2020 Aug 25.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Lyme neuroborreliosis (LNB) has recently been added to the list of diseases under the European Union epidemiological surveillance in order to obtain updated information on incidence. The goal of this study was to identify temporal (yearly) variation, high risk geographical regions and risk groups, and seasonal variation for LNB in Denmark. This cohort-study investigated Danish patients (n = 2791) diagnosed with LNB (defined as a positive Borrelia burgdorferi sensu lato (s.l.) intrathecal antibody test) between 1996-2015. We calculated incidence and incidence ratios of LNB by comparing 4-yr groups of calendar-years, area of residency, sex and age, income and education groups, and the number of new LNB cases per month. The incidence of LNB was 2.2 per 100,000 individuals and year in 1996-1999, 2.7 in 2004-2007 and 1.1 per 100,000 individuals in 2012-2015. Yearly variations in LNB incidence were similar for most calendar-year groups. LNB incidence was highest in Eastern Denmark and among males and individuals who were 0-14 yrs old, who had a yearly income of >449,000 DKK, and who had a Master's degree or higher education. The number of LNB cases was highest from July to November (p < 0.001). In conclusion, based on Danish nationwide data of patients with positive B. burgdorferi s.l. intrathecal antibody index (1996-2015) the incidence of LNB was found to increase until 2004-2007 but thereafter to decline. European surveillance studies of Lyme borreliosis should be encouraged to monitor the incidence trend.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101549DOI Listing
November 2020

Long-Term Survival, Morbidity, Social Functioning and Risk of Disability in Patients with a Herpes Simplex Virus Type 1 or Type 2 Central Nervous System Infection, Denmark, 2000-2016.

Clin Epidemiol 2020 16;12:745-755. Epub 2020 Jul 16.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: The long-term prognosis following herpes simplex virus (HSV) central nervous system (CNS) infection is still debated.

Patients And Methods: We examined outcomes in all Danish residents who, during 2000-2016, tested PCR positive for HSV-1 (n=208) or HSV-2 (n=283) in the cerebrospinal fluid, compared to comparison cohorts from the general population (n=2080 and n=2830).

Results: One-year mortality was increased among HSV-1 patients (difference 19.3%; 95% CI: 13.6% to 25.0%) and HSV-2 patients (difference 5.3%; 95% CI: 2.5% to 8.1%), but thereafter mortality was not increased. After exclusion of persons diagnosed with cancer prior to study inclusion, one-year mortality difference for HSV-2 patients was 1.7% (-0.1% to 3.5%). After five years, HSV-1 patients had lower employment (difference -19.8%; 95% CI: -34.7% to -4.8%) and higher disability pension rates (difference 22.2%; 95% CI: 8.4% to 36.0%) than the comparison cohort, but similar number of inpatient days, outpatient visits, and sick leave. HSV-2 patients had employment and disability pension rates comparable to the comparison cohort, but more inpatient days (difference 1.5/year; 95% CI: -0.2 to 3.2), outpatient visits (difference 1.3/year; 95% CI: 0.3 to 3.2), and sick leave days (difference 9.1/year; 95% CI: 7.9 to 10.4).

Conclusion: HSV-1 and HSV-2 CNS infections differ substantially with respect to prognosis. HSV-1 CNS infection is followed by increased short-term mortality and long-term risk of disability. HSV-2 CNS infection has no substantial impact on mortality or working capability but is associated with increased morbidity.
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http://dx.doi.org/10.2147/CLEP.S256838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371560PMC
July 2020

Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy.

J Infect Dis 2020 09;222(7):1103-1107

Department of Infectious Diseases, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

The antiviral drug remdesivir has been shown clinically effective for treatment of COVID-19. We here demonstrate suppressive but not curative effect of remdesivir in an immunocompromised patient. A man in his fifties treated with chemoimmunotherapy for chronic lymphocytic leukemia experienced a 9-week course of COVID-19 with high fever and severe viral pneumonia. During two 10-day courses of remdesivir starting 24 and 45 days after fever onset, pneumonia and spiking fevers remitted, but relapsed after discontinuation. Kinetics of temperature, C-reactive protein, and lymphocyte counts mirrored the remitting/relapsing SARS-CoV-2 infection. Combination therapy or longer treatment duration may be needed in immunocompromised patients.
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http://dx.doi.org/10.1093/infdis/jiaa446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7454684PMC
September 2020

The clinical spectrum of tularemia-Two cases.

IDCases 2020 27;21:e00890. Epub 2020 Jun 27.

Department of Infectious Diseases, The National University Hospital, Rigshospitalet, Denmark.

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.
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http://dx.doi.org/10.1016/j.idcr.2020.e00890DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7350126PMC
June 2020

Pulmonary Arterial Enlargement in Well-Treated Persons With Human Immunodeficiency Virus.

J Infect Dis 2021 01;223(1):94-100

Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Pulmonary artery enlargement is a marker of pulmonary hypertension. We aimed to determine the proportion with pulmonary artery enlargement among well-treated persons with human immunodeficiency virus HIV (PWH) and uninfected controls.

Methods: PWH with a chest computed tomography were included from the ongoing Copenhagen Comorbidity in HIV Infection (COCOMO) study. Age and sex-matched uninfected controls were recruited from the Copenhagen General Population Study. Pulmonary artery enlargement was defined as a ratio of >1 between the diameter of the main pulmonary artery (at the level of its bifurcation) and the diameter of the ascending aorta.

Results: In total, 900 PWH were included, and 44 (5%) had a pulmonary artery-aorta ratio (PA:A) >1. After adjustment for age, sex, and body mass index, obesity (adjusted odds ratio, 4.33; 95% confidence interval, 1.76-10.65; P = .001) and injection drug use (IDU) (4.90; 1.00-18.46; P = .03) were associated with higher odds of having a PA:A >1, and pulmonary indices and smoking status were not. HIV seropositivity was borderline associated with a PA:A >1 (adjusted odds ratio, 1.89; 95% confidence interval, .92-3.85; P = .08).

Conclusions: A PA:A >1 was common in PWH. Obesity and IDU were independently associated with this finding and HIV serostatus was borderline associated with it, but HIV-related factors were not. Increased awareness may be appropriate in obese PWH and those with IDU.
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http://dx.doi.org/10.1093/infdis/jiaa339DOI Listing
January 2021

Soluble urokinase plasminogen activator receptor (suPAR) is lower in disease-free patients but cannot rule out incident disease in patients with suspected cancer.

Clin Biochem 2020 Oct 3;84:31-37. Epub 2020 Jun 3.

Department of Infectious Diseases, Copenhagen University Hospital Amager and Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark; Department of Clinical Medicine, University of Copenhagen, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark.

Background: Accurate first-line diagnostics are essential for early recognition of cancer but also to identify patients free of disease. The biomarker soluble urokinase plasminogen activator receptor (suPAR) is elevated in patients with cancer or non-malignant disease compared to disease-free patients. We tested if low suPAR could be used to identify disease-free patients in an accelerated cancer diagnostics program, including ruling out cancer.

Methods: Patients with serious nonspecific symptoms and signs of cancer (NSSC) were included at the Diagnostic Outpatient Clinic, Copenhagen University Hospital Hvidovre, Denmark. Data from a clinical examination, including blood tests and imaging, was combined with national registry data on diagnoses and mortality. The association between blood suPAR and the primary outcome of disease-free (i.e., absence of incident disease and mortality) within 1-year follow-up was analysed with logistic regression analysis.

Results: Of 1583 patients included, 349 (22.0%) were diagnosed with cancer, 837 (52.9%) with non-malignant disease, and 392 (25.8%) were disease-free within one year. Admission suPAR was significantly lower in disease-free patients compared to patients with cancer or non-malignant disease (P < 0.001), area under the curve 0.67 (95% confidence interval (CI): 0.64-0.70). The highest positive predictive value (PPV) for the outcome of disease-free was 0.55 (95% CI: 0.41-0.68) at a suPAR of 1.65 ng/mL. Patients who died had significantly higher suPAR compared to patients who survived in all disease subgroups. The AUC of suPAR for 1-year mortality was 0.80 (95% CI: 0.77-0.83).

Conclusions: suPAR was significantly lower in disease-free individuals compared to patients with cancer or other conditions, but the PPV was not sufficiently high to terminate further clinical investigation with appropriate safety. Elevated suPAR may be a useful prognostic marker for adverse outcomes.
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http://dx.doi.org/10.1016/j.clinbiochem.2020.06.001DOI Listing
October 2020

[Suspected toxoplasmosis in pregnancy].

Ugeskr Laeger 2020 04;182(18)

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.
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April 2020

Long-Term Survival, Health, Social Functioning, and Education in Patients With an Enterovirus Central Nervous System Infection, Denmark, 1997-2016.

J Infect Dis 2020 07;222(4):619-627

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.

Background: The long-term clinical course of patients with an enterovirus central nervous system infection (ECI) is poorly understood.

Methods: We performed a nationwide population-based cohort study of all Danish patients with ECI diagnosed 1997-2016 (n = 1745) and a comparison cohort from the general population individually matched on date of birth and sex (n = 17 450). Outcomes were categorized into mortality and risk of cancer and likely measures of neurological sequelae: neuropsychiatric morbidities, educational landmarks, use of hospital services, employment, receipt of disability pension, income, number of sick leave days, and nursing home residency.

Results: Mortality in the first year was higher among patients with ECI (mortality rate ratio [MRR] = 10.0; 95% confidence interval [CI], 4.17-24.1), but thereafter mortality was not higher (MMR = 0.94; 95% CI, 0.47-1.86). Long-term outcomes for patients with ECI were not inferior to those of the comparison cohort for risk of cancer, epilepsy, mental and behavioral disorders, dementia, depression, school start, school marks, high school education, use of hospital services, employment, receipt of disability pension, income, days of sick leave, or nursing home residency.

Conclusions: Diagnosis of an ECI had no substantial impact on long-term survival, health, or social/educational functioning.
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http://dx.doi.org/10.1093/infdis/jiaa151DOI Listing
July 2020

Lyme neuroborreliosis in adults: A nationwide prospective cohort study.

Ticks Tick Borne Dis 2020 07 24;11(4):101411. Epub 2020 Feb 24.

Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address:

The goal of this paper is to characterize the clinical presentation, serological results, current antibiotic treatment practice, including compliance with current European guidelines, and outcome in adults with Lyme neuroborreliosis (LNB) diagnosed at departments of infectious diseases in Denmark. Using a nationwide prospective cohort of patients with central nervous system infections, we identified all adults (≥ 18 years of age) treated for LNB at departments of infectious diseases in Denmark from 2015 through 2017. The database contains information on baseline demographics, history of tick bite, erythema migrans, clinical presentation, laboratory results of blood samples, and cerebrospinal (CSF) biochemistry (e.g. specific Borrelia burgdorferi sensu lato (s.l.) antibodies in serum, B. burgdorferi s.l. intrathecal antibody index) as well as antibiotic therapy. Outcome was assessed by the Glasgow Outcome Scale (GOS) and the presence of residual symptoms at follow-up one month after discharge. We included 194 LNB patients with a median age of 59 years (range 18-85 years, interquartile range [IQR] 47-69 years). The female-to-male ratio was 0.8. A total of 177 of 191 (93 %) of patients had early (second stage) LNB. A history of tick bite or erythema migrans was registered in 75 (39 %) and 49 (25 %) patients, respectively. The median duration of neurological symptoms before first hospital contact was 21 days (range 0-600 days, IQR 10-42 days). Predominant symptoms consisted of radicular pain in 135 of 194 (70 %), cranial nerve paresis in 88 of 194 (45 %), headache in 71 of 185 (38 %), and extremity paresis in 33 of 194 (17 %) patients. Serum-B. burgdorferi s.l. IgM and/or IgG antibodies were detectable in 166 of 181 (92 %) patients at the time of first CSF investigation. Median duration of antibiotic treatment was 14 days (range 10-35 days, IQR 14-21 days) and 59 (39 %) of the patients received intravenous ceftriaxone and/or benzylpenicillin G throughout treatment. At the 1-month follow-up, GOS was unfavorable (< 5) in 54 of 193 (28 %) patients. An unfavorable GOS score was more often registered in patients with ≥ 45 days of symptom duration (20 of 45 (44 %) vs. 34 of 145 (23 %); P = 0.006). In conclusion, a European cohort of adult patients with LNB diagnosed between 2015-2017 presented with classic symptoms and CSF findings. However, a substantial diagnostic delay was still observed. In disagreement with current guidelines, a substantial part of LNB patients were treated with antibiotics longer than 14 days and/or intravenously as route of administration.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101411DOI Listing
July 2020

Pericardial Adipose Tissue Volume Is Independently Associated With Human Immunodeficiency Virus Status and Prior Use of Stavudine, Didanosine, or Indinavir.

J Infect Dis 2020 06;222(1):54-61

Department of Infectious Diseases 8632, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.

Background: Increased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine whether human immunodeficiency virus (HIV) status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors.

Methods: Persons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 1:1 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac computed tomography.

Results: A total of 587 PWH and 587 controls were included. Median age was 52 years, and 88% were male. Human immunodeficiency virus status was independently associated with 17 mL (95% confidence interval [CI], 10-23; P < .001) larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine, and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating combination antiretroviral treatment (per 5-year use) was associated with l6 mL (95% CI, -6 to -25; P = .002) lower pericardial adipose tissue volume.

Conclusions: Human immunodeficiency virus status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine, and indinavir were associated with larger pericardial adipose tissue volume. Persons with HIV with prior exposure to these drugs may constitute a distinct cardiovascular risk population.
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http://dx.doi.org/10.1093/infdis/jiaa057DOI Listing
June 2020

Lyme Neuroborreliosis in a Patient with Breast Cancer: MRI and PET/CT Findings.

Diagnostics (Basel) 2020 Jan 9;10(1). Epub 2020 Jan 9.

Department of Infectious Diseases, Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark.

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 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 the 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 . 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.
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http://dx.doi.org/10.3390/diagnostics10010036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7169463PMC
January 2020

Impact of Human Immunodeficiency Virus-Related Gut Microbiota Alterations on Metabolic Comorbid Conditions.

Clin Infect Dis 2020 11;71(8):e359-e367

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Background: We aimed to identify a human immunodeficiency virus (HIV)-related microbiota signature, independent of sexual preferences and demographic confounders, in order to assess a possible impact of the microbiome on metabolic comorbid conditions.

Methods: Bacterial 16S ribosomal RNA analyses were performed on stool samples from 405 HIV-infected and 111 uninfected participants of the Copenhagen Comorbidity in HIV Infection (COCOMO) study. Individuals were stratified according to sexual behavior (men who have sex with men [MSM] vs non-MSM).

Results: After excluding MSM-associated microbiota traits and adjusting for confounders, we identified an HIV-related microbiota signature, consisting of lower biodiversity, increased relative abundance of the bacterial clades Gammaproteobacteria and Desulfovibrionaceae and decrease in several Clostridia. This microbiota profile was associated with a 2-fold excess risk of metabolic syndrome, driven by increase in Desulfovibrionaceae and decrease in Clostridia (Butyrivibrio, Coprococcus 2, Lachnospiraceae UCG-001 and CAG-56). This association was accentuated (5-fold excess risk) in individuals with previous severe immunodeficiency, which also modified the association between HIV-related microbiota signature and visceral adipose tissue (VAT) area (P for interaction = .01). Accordingly, HIV-related microbiota was associated with 30-cm2 larger VAT in individuals with history of severe immunodeficiency, but not in those without.

Conclusion: The HIV-related microbiota was associated with increased risk of metabolic syndrome and VAT accumulation, particularly in individuals with previous severe immunodeficiency, driven by increased Desulfovibrionaceae and lower abundance of several Clostridia. Our findings suggest a potential interplay between HIV-related microbiota, immune dysfunction and metabolic comorbid conditions. Interventions targeting the gut microbiome may be warranted to reduce cardiovascular risk, particularly in individuals with previous immunodeficiency.
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http://dx.doi.org/10.1093/cid/ciz1235DOI Listing
November 2020
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