Regional Gene Expression of LOX-1, VCAM-1, and ICAM-1 in Aorta of HIV-1 Transgenic Rats

BACKGROUND: Increased prevalence of atherosclerotic cardiovascular disease in HIV-infected patients has been observed. The cause of this accelerated atherosclerosis is a matter of controversy. As clinical studies are complicated by a multiplicity of risk-factors and a low incidence of hard endpoints, studies in animal models could be attractive alternatives. METHODOLOGY/PRINCIPAL FINDINGS: We evaluated gene expression of lectin-like oxidized-low-density-lipoprotein receptor-1 (LOX-1), vascular cell adhesion molecule-1 (VCAM-1), and intercellular adhesion molecule-1 (ICAM-1) in HIV-1 transgenic (HIV-1Tg) rats; these genes are all thought to play important roles in early atherogenesis. Furthermore, the plasma level of sICAM-1 was measured. We found that gene expressions of LOX-1 and VCAM-1 were higher in the aortic arch of HIV-1Tg rats compared to controls. Also, the level of sICAM-1 was elevated in the HIV-1Tg rats compared to controls, but the ICAM-1 gene expression profile did not show any differences between the groups. CONCLUSIONS/SIGNIFICANCE: HIV-1Tg rats have gene expression patterns indicating endothelial dysfunction and accelerated atherosclerosis in aorta, suggesting that HIV-infection per se may cause atherosclerosis. This transgenic rat model may be a very promising model for further studies of the pathophysiology behind HIV-associated cardiovascular disease

Comparison of the Peripheral Reactive Hyperemia Index with Myocardial Perfusion Reserve by ⁸²Rb PET/CT in HIV-Infected Patients

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 by 82-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

Decreased Heart Rate Variability in HIV Positive Patients Receiving Antiretroviral Therapy: Importance of Blood Glucose and Cholesterol

The presence of autonomic dysfunction in HIV patients is largely unknown. Early studies found autonomic dysfunction in patients with AIDS. Antiretroviral combination therapy (ART) has dramatically changed the course of the disease and improved prognosis and decreased morbidity

Feasibility of simultaneous PET/MR of the carotid artery: first clinical experience and comparison to PET/CT

The study aimed at comparing PET/MR to PET/CT for imaging the carotid arteries in patients with known increased risk of atherosclerosis. Six HIV-positive men underwent sequential PET/MR and PET/CT of the carotid arteries after injection of 400 MBq of (18)F-FDG. PET/MR was performed a median of 131 min after injection. Subsequently,PET/CT was performed. Regions of interest (ROI) were drawn slice by slice to include the carotid arteries and standardized uptake values (SUV) were calculated from both datasets independently. Quantitative comparison of (18)F-FDG uptake revealed a high congruence between PET data acquired using the PET/MR system compared to the PET/CT system. The mean difference for SUV(mean) was -0.18 (p < 0.001) and -0.14 for SUV(max) (p < 0.001) indicating a small but significant bias towards lower values using the PET/MR system. The 95% limits of agreement were -0.55 to 0.20 for SUV(mean) and -0.93 to 0.65 for SUV(max). The image quality of the PET/MR allowed for delineation of the carotid vessel wall. The correlations between (18)F-FDG uptake from ROI including both vessel wall and vessel lumen to ROI including only the wall were strong (r = 0.98 for SUV(mean) and r = 1.00 for SUV(max)) indicating that the luminal (18)F-FDG content had minimal influence on the values. The study shows for the first time that simultaneous PET/MR of the carotid arteries is feasible in patients with increased risk of atherosclerosis. Quantification of (18)F-FDG uptake correlated well between PET/MR and PET/CT despite difference in method of PET attenuation correction, reconstruction algorithm, and detector technology

Antibiotic therapy of neuroborreliosis:A survey among infectious disease specialists and neurologists in Norway, Sweden, and Denmark

Introduction: Neuroborreliosis (NB) is a prevalent tick-borne neuroinfection in Europe. To delineate current practice in antimicrobial management of adults with NB and to prioritize future trials needed to optimize treatment recommendations, a questionnaire-based survey was performed. Methods: A self-administered Internet-based survey of NB treatment practices among specialists in infectious diseases and neurology based in Norway, Sweden, and Denmark was carried out between October 2021 and February 2022. The participants were also asked to prioritize four pre-defined research questions for randomized controlled trials (RCTs) on therapy for NB. Results: In total, 290 physicians (45% female) from Norway (30%), Sweden (40%), and Denmark (30%) participated in the survey. Of the responders, 230 (79%) were infectious disease specialists and 56 (19%) were neurologists. The preferred antibiotic treatment for patients with early NB was oral doxycycline (n = 225, 78%). Intravenous (IV) penicillin, ceftriaxone, or cefotaxime for the full treatment course was favored by 12%. A preferred treat- ment duration of 10–14 days for patients with NB was reported by 245 respondents (85%), most common among participants from Sweden (97%). A total of 170 (59%) responders reported having local hospital guidelines on the treatment of NB, most often with recommendation of oral doxycycline (92%) for 10–14 days (90%) as first line treatment. The prioritization score for future RCTs was highest for adjunctive prednisone therapy in NB patients with facial palsy (median 5; IQR 4–6) and for placebo versus repeated antibiotics in patients with persistent symptoms after completed antibiotic therapy for NB (median 5, IQR 3–6). Conclusion: In Sweden, all respondents preferred treating NB with oral doxycycline for 10–14 days, whereas 5% in Norway and 19% in Denmark still treat NB with IV antibiotics for the entire treatment course. RCTs to define the role of adjunctive prednisolone in NB patients with facial palsy and repeated antibiotics in patients with persistent symptoms are prioritized for future research.publishedVersio

Neurofilament Light in Cerebrospinal Fluid is Associated With Disease Staging in European Lyme Neuroborreliosis

BACKGROUND: Drivers of differences in disease presentation and symptom duration in Lyme neuroborreliosis (LNB) are currently unknown. OBJECTIVES: We hypothesized that neurofilament light (NfL) in cerebrospinal fluid (CSF) would predict disease location and sequelae in a historic LNB cohort. DESIGN: Using a cross-sectional design and archived CSF samples from 185 patients diagnosed with LNB, we evaluated the content of NfL in the total cohort and in a subgroup of 84 patients with available clinical and paraclinical information. METHODS: Individuals were categorized according to disease location: a. Central nervous system (CNS) with stroke (N=3), b. CNS without stroke (N=11), c. Peripheral nervous system (PNS) with cranial nerve palsy (CNP) (N=40) d. PNS without CNP (N=30). Patients with hospital follow-up more than 6 months after completed antibiotic therapy were categorized as having LNB associated sequelae (N=15). RESULTS: At diagnosis concentration of NfL exceeded the upper reference level in 60% (105/185), especially among individuals above 30 years. Age-adjusted NfL was not found to be associated with symptom duration. Age-adjusted NfL was significantly higher among individuals with CNS involvement. Category a. (stroke) had significantly higher NfL concentrations in CSF compared to all other categories, category b. (CNS involvement without stroke) had significantly higher values compared to the categories of PNS involvement. We found no significant difference between the categories with PNS involvement (with or without CNP). Significantly higher NfL was found among patients with follow-up in hospital setting. CONCLUSION: Comparison of NfL concentrations between the 4 groups of LNB disease manifestations based on clinical information revealed a hierarchy of neuron damage according to disease location and suggested evolving mechanisms with accelerated injury especially when disease is complicated by stroke. Higher values of NfL among patients with need of follow-up in hospital setting suggest NfL could be useful to identify rehabilitative needs