The role of positron-emission tomography in the diagnosis of giant cell arteritis

Abstract Background: Giant cell arteritis (GCA) is an inflammatory disease of the larger vessels, typically affecting the temporal arteries, but involvement of the carotid and thoracic arteries is not uncommon. Serious complications such as blindness can occur if the disease is left untreated. Currently, the gold standard test for GCA is a temporal biopsy, but this invasive technique is not without risks and frequently inaccurate. We investigate the use of 18-fluoro-desoxyglucose (18F-FDG) positron emission tomography (PET) as a new diagnostic means in GCA. Methods: We performed a literature search in the MEDLINE database for original research articles written in the English language that discussed the use of PET in diagnosing GCA. After applying selection criteria, 9 articles were included for literature review and 4 of these were incorporated in a meta-analysis. Results: 18-FDG uptake in the extracranial arteries is correlated to the presence GCA within patients suspected for vasculitis. In our meta-analysis we found the following results: sensitivity 85% (95% CI; 74-92%, I2=0.0%), specificity 91% (95% CI; 82-96%, I2=31.2%), positive likelihood ratio 7.18 (95% CI; 3.43-15.06, I2 =10.1%) and negative likelihood ratio 0.19 (95% CI; 0.11-0.33, I2= 0.0%). Discussion: 18F-FDG-PET cannot replace temporal artery biopsy at the present time, because of its limited ability to visualise the cranial arteries. However, PET may be provide valuable information when extracranial involvement is suspected, specifically in biopsy-negative patients who are strongly suspected of having GCA

Traditional Cardiovascular Risk Factors Are Stronger Related to Carotid Intima-Media Thickness Than to Presence of Carotid Plaques in People Living With HIV

BACKGROUND: Cardiovascular disease is a major cause of morbidity and mortality in people living with HIV, who are at higher risk than the general population. We assessed, in a large cohort of people living with HIV, which cardiovascular, HIV-specific, and lipoproteomic markers were associated with carotid intima-media thickness (cIMT) and carotid plaque presence. We also studied guideline adherence on lipid-lowering medication in individuals with high and very high risk for cardiovascular disease. METHODS AND RESULTS: In 1814 individuals with a median (interquartile range) age of 53 (44–60) years, we found a carotid plaque in 909 (50.1%) and a median (interquartile range) intima-media thickness of 0.66 (0.57–0.76) mm. Ultrasonography was used for the assessment of cIMT and plaque presence. Univariable and multivariable regression models were used for associations with cIMT and presence of plaques. Age, Black race, body mass index, type 2 diabetes, and smoking (pack years) were all positively associated with higher cIMT. Levels of high-density lipoprotein cholesterol, specifically medium and large high-density lipoprotein subclasses, were negatively associated with higher cIMT. Only age and prior myocardial infarction were positively related to the presence of a carotid plaque. Lipid-lowering treatment was prescribed in one-third of people living with HIV, who are at high and very high risk for cardiovascular disease. CONCLUSIONS: Traditional cardiovascular risk factors were significantly associated with higher cIMT but not with carotid plaques, except for age. HIV-specific factors were not associated with both ultrasound measurements. Future studies are needed to elucidate which factors contribute to plaque formation. Improvement of guideline adherence on prescription of lipid-lowering treatment in high-and very high-risk patients for cardiovascular disease is recommended.</p

The risk of non-AIDS defining events is lower in ART-naive HIV controllers than in normal progressors on suppressive ART

Background. We aimed to compare the non-AIDS event (nADE) risk between normal progressors using antiretroviral therapy (NP-ART) and people with human immunodeficiency virus (HIV, PWH) who naturally control HIV infection (HIV controllers), as well as the risk of nADE following ART in HIV controllers. Methods. The primary end point was the composite of cardiovascular disease, non-AIDS malignancy, or all-cause mortality, whichever came first. The role of ART in HIV controllers was assessed as a time-varying covariate. Results. We included 1007 ART-naive HIV controllers (60 of them were elite controllers), 1510 early-ART (&lt;6 months after negative HIV test), and 15437 NP-ART (reference group), contributing 3813, 11 060, and 160 050 years of follow-up, respectively. HIV controllers had lower risk of the primary end point (hazard ratio [HR], 0.55; 95% confidence interval [CI]: .38-.81; P = .0023), all-cause mortality (adjusted HR [aHR], 0.45; 95% CI: .25-.79; P = .0054), and cardiovascular disease (aHR, 0.47; 95% CI: .22-.99; P = .046), but not non-AIDS malignancy (aHR, 0.74; 95% CI: .41-1.35; P = .33), compared with NP-ART. Among HIV controllers, each log(10 )lower baseline viral load further decreased the risk of a nADE (aHR, 0.54; 95% CI: .29-.99; P = .045). ART in HIV controllers did not reduce the risk of any nADE (aHR, 1.22; 95% CI: .66-2.29; P = .53). Conclusions. HIV controllers had a lower n ADE risk than NP-ART, especially in those with low plasma viral loads. ART did not alter the nADE risk in HIV controllers. Our findings help clinicians to decide on prescribing ART in HIV controllers

Cardiometabolic Differences in People Living with HIV Receiving Integrase Strand Transfer Inhibitors Compared to Non-nucleoside Reverse Transcriptase Inhibitors:Implications for Current ART Strategies

In people living with HIV (PLHIV), integrase strand transfer inhibitors (INSTIs) are part of the first-line combination antiretroviral therapy (cART), while non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens are alternatives. Distinct cART regimens may variably influence the risk for non-AIDS comorbidities. We aimed to compare the metabolome and lipidome of INSTI and NNRTI-based regimens. The 2000HIV study includes asymptomatic PLHIV (n = 1646) on long-term cART, separated into a discovery cohort with 730 INSTI and 617 NNRTI users, and a validation cohort encompassing 209 INSTI and 90 NNRTI users. Baseline plasma samples from INSTI and NNRTI users were compared using mass spectrometry-based untargeted metabolomic (n = 500) analysis. Perturbed metabolic pathways were identified using MetaboAnalyst software. Subsequently, nuclear magnetic resonance spectroscopy was used for targeted lipoprotein and lipid (n = 141) analysis. Metabolome homogeneity was observed between the different types of INSTI and NNRTI. In contrast, higher and lower levels of 59 and 45 metabolites, respectively, were found in the INSTI group compared to NNRTI users, of which 77.9% (81/104) had consistent directionality in the validation cohort. Annotated metabolites belonged mainly to ‘lipid and lipid-like molecules’, ‘organic acids and derivatives’ and ‘organoheterocyclic compounds’. In pathway analysis, perturbed ‘vitamin B1 (thiamin) metabolism’, ‘de novo fatty acid biosynthesis’, ‘bile acid biosynthesis’ and ‘pentose phosphate pathway’ were detected, among others. Lipoprotein and lipid levels in NNRTIs were heterogeneous and could not be compared as a group. INSTIs compared to individual NNRTI types showed that HDL cholesterol was lower in INSTIs compared to nevirapine but higher in INSTIs compared to doravirine. In addition, LDL size was lower in INSTIs and nevirapine compared to doravirine. NNRTIs show more heterogeneous cardiometabolic effects than INSTIs, which hampers the comparison between these two classes of drugs. Targeted lipoproteomic and lipid NMR spectroscopy showed that INSTI use was associated with a more unfavorable lipid profile compared to nevirapine, which was shifted to a more favorable profile for INSTI when substituting nevirapine for doravirine, with evidently higher fold changes. The cardiovascular disease risk profile seems more favorable in INSTIs compared to NNRTIs in untargeted metabolomic analysis using mass-spectrometry.</p

Liver Steatosis is Prevalent in Lean People With HIV and Associated With Exposure to Antiretroviral Treatment - A Cross-sectional Study

Background: Steatotic liver disease is suggested to have a higher prevalence and severity in people with HIV (PHIV), including in those with a normal body mass index (BMI). In this study, we used data from the 2000HIV cohort to (1) assess the prevalence of liver steatosis and fibrosis in lean versus overweight/obese PHIV and (2) assess associations in these subgroups between steatosis and fibrosis with traditional risk factors and HIV-specific characteristics. Methods: The 2000HIV study cohort comprises 1895 virally suppressed PHIV that were included between 2019 and 2021 in 4 HIV treatment centers in the Netherlands. The majority (58.5%) underwent vibration-controlled transient elastography for the assessment of liver steatosis and fibrosis. The prevalence of steatosis (controlled attenuation parameter ≥263 dB/m) and fibrosis (liver stiffness measurement ≥7.0 kPa) was estimated. Multiple factors including HIV characteristics and antiretroviral drugs were tested in a logistic regression model for association with steatosis and fibrosis. Analyses were performed separately for lean (Asian descent: BMI &lt; 23 kg/m2, other descent: BMI &lt; 25 kg/m2) and overweight/obese (other BMI) participants. Results: Of 1050 PHIV including 505 lean and 545 overweight/obese PHIV, liver steatosis was observed in 37.7% of the overall study population, 19.7% of lean, and 54% of overweight/obese PHIV, whereas fibrosis was observed in 9.0% of the overall study population, 5.9% of lean, and 12.0% of overweight/obese PHIV. All associations with fibrosis and most associations with steatosis concerned metabolic factors such as type 2 diabetes mellitus (overall population: adjusted odds ratio [aOR] for steatosis: 2.3 [1.21-4.4], P =. 011; aOR for fibrosis: 3.7 [1.82-7.53], P &lt;. 001). Furthermore, in lean PLHIV, liver steatosis was associated with CD4 and CD8 counts at enrollment, dual therapy, and history of treatment with raltegravir (aOR: 3.6 [1.53-8.47], P =. 003), stavudine (aOR: 3.73 [1.69-8.2], P =. 001), and indinavir (aOR: 3.86 [1.59-9.37], P =. 003). These associations were not observed in overweight/obese PHIV. Conclusions: Liver steatosis was highly prevalent, affecting approximately one-fifth of lean PHIV and half of overweight/obese PHIV. Fibrosis was observed in a minority. Both steatosis and fibrosis were associated with traditional metabolic risk factors. In addition, (prior) exposure to specific antiretroviral drugs was associated liver steatosis in lean, but not in overweight/obese PHIV. Implementing increased screening protocols could enhance the identification of steatotic liver disease in lean PHIV.</p

High-throughput proteomic analysis reveals systemic dysregulation in virally suppressed people living with HIV

BACKGROUND. People living with HIV (PLHIV) receiving antiretroviral therapy (ART) exhibit persistent immune dysregulation and microbial dysbiosis, leading to development of cardiovascular diseases (CVDs). We initially compared plasma proteomic profiles between 205 PLHIV and 120 healthy control participants (HCs) and validated the results in an independent cohort of 639 PLHIV and 99 HCs. Differentially expressed proteins (DEPs) were then associated to microbiome data. Finally, we assessed which proteins were linked with CVD development in PLHIV. METHODS. Proximity extension assay technology was used to measure 1,472 plasma proteins. Markers of systemic inflammation (C-reactive protein, D-dimer, IL-6, soluble CD14, and soluble CD163) and microbial translocation (IFABP) were measured by ELISA, and gut bacterial species were identified using shotgun metagenomic sequencing. Baseline CVD data were available for all PLHIV, and 205 PLHIV were recorded for development of CVD during a 5-year follow-up. RESULTS. PLHIV receiving ART had systemic dysregulation of protein concentrations, compared with HCs. Most of the DEPs originated from the intestine and lymphoid tissues and were enriched in immune- and lipid metabolism-related pathways. DEPs originating from the intestine were associated with specific gut bacterial species. Finally, we identified upregulated proteins in PLHIV (GDF15, PLAUR, RELT, NEFL, COL6A3, and EDA2R), unlike most markers of systemic inflammation, associated with the presence and risk of developing CVD during 5-year follow-up. CONCLUSION. Our findings suggest a systemic dysregulation of protein concentrations in PLHIV; some proteins were associated with CVD development. Most DEPs originated from the gut and were related to specific gut bacterial species.</p

Fabrication of cell container arrays with overlaid surface topographies

This paper presents cell culture substrates in the form of microcontainer arrays with overlaid surface topographies, and a technology for their fabrication. The new fabrication technology is based on microscale thermoforming of thin polymer films whose surfaces are topographically prepatterned on a micro- or nanoscale. For microthermoforming, we apply a new process on the basis of temporary back moulding of polymer films and use the novel concept of a perforated-sheet-like mould. Thermal micro- or nanoimprinting is applied for prepatterning. The novel cell container arrays are fabricated from polylactic acid (PLA) films. The thin-walled microcontainer structures have the shape of a spherical calotte merging into a hexagonal shape at their upper circumferential edges. In the arrays, the cell containers are arranged densely packed in honeycomb fashion. The inner surfaces of the highly curved container walls are provided with various topographical micro- and nanopatterns. For a first validation of the microcontainer arrays as in vitro cell culture substrates, C2C12 mouse premyoblasts are cultured in containers with microgrooved surfaces and shown to align along the grooves in the three-dimensional film substrates. In future stem-cell-biological and tissue engineering applications, microcontainers fabricated using the proposed technology may act as geometrically defined artificial microenvironments or niches

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo