Gut Microbiota Alterations and Circulating Imidazole Propionate Levels Are Associated With Obstructive Coronary Artery Disease in People With HIV.

BACKGROUND: The impact of gut microbiota and its metabolites on coronary artery disease (CAD) in people with human immunodeficiency virus (PWH) is unknown. Emerging evidence suggests that imidazole propionate (ImP), a microbial metabolite, is linked with cardiometabolic diseases. METHODS: Fecal samples from participants of the Copenhagen Comorbidity in HIV infection (COCOMO) study were processed for 16S rRNA sequencing and ImP measured with liquid chromatography-tandem mass spectrometry. CAD severity was investigated by coronary computed tomography-angiography, and participants grouped according to obstructive CAD (n = 60), nonobstructive CAD (n = 80), or no CAD (n = 114). RESULTS: Participants with obstructive CAD had a gut microbiota with lower diversity and distinct compositional shift, with increased abundance of Rumiococcus gnavus and Veillonella, known producers of ImP. ImP plasma levels were associated with this dysbiosis, and significantly elevated in participants with obstructive CAD. However, gut dysbiosis but not plasma ImP was independently associated with obstructive CAD after adjustment for traditional and HIV-related risk factors (adjusted odds ratio, 2.7; 95% confidence interval, 1.1-7.2; P = .048). CONCLUSIONS: PWH with obstructive CAD displays a distinct gut microbiota profile and increased circulating ImP plasma levels. Future studies should determine whether gut dysbiosis and related metabolites such as ImP are predictive of incident cardiovascular events.

Subclinical Coronary Atherosclerosis and Risk for Myocardial Infarction in a Danish Cohort : A Prospective Observational Cohort Study.

BACKGROUND: Coronary atherosclerosis may develop at an early age and remain latent for many years. OBJECTIVE: To define characteristics of subclinical coronary atherosclerosis associated with the development of myocardial infarction. DESIGN: Prospective observational cohort study. SETTING: Copenhagen General Population Study, Denmark. PARTICIPANTS: 9533 asymptomatic persons aged 40 years or older without known ischemic heart disease. MEASUREMENTS: Subclinical coronary atherosclerosis was assessed with coronary computed tomography angiography conducted blinded to treatment and outcomes. Coronary atherosclerosis was characterized according to luminal obstruction (nonobstructive or obstructive [≥50% luminal stenosis]) and extent (nonextensive or extensive [one third or more of the coronary tree]). The primary outcome was myocardial infarction, and the secondary outcome was a composite of death or myocardial infarction. RESULTS: A total of 5114 (54%) persons had no subclinical coronary atherosclerosis, 3483 (36%) had nonobstructive disease, and 936 (10%) had obstructive disease. Within a median follow-up of 3.5 years (range, 0.1 to 8.9 years), 193 persons died and 71 had myocardial infarction. The risk for myocardial infarction was increased in persons with obstructive (adjusted relative risk, 9.19 [95% CI, 4.49 to 18.11]) and extensive (7.65 [CI, 3.53 to 16.57]) disease. The highest risk for myocardial infarction was noted in persons with obstructive-extensive subclinical coronary atherosclerosis (adjusted relative risk, 12.48 [CI, 5.50 to 28.12]) or obstructive-nonextensive (adjusted relative risk, 8.28 [CI, 3.75 to 18.32]). The risk for the composite end point of death or myocardial infarction was increased in persons with extensive disease, regardless of degree of obstruction-for example, nonobstructive-extensive (adjusted relative risk, 2.70 [CI, 1.72 to 4.25]) and obstructive-extensive (adjusted relative risk, 3.15 [CI, 2.05 to 4.83]). LIMITATION: Mostly White persons were studied. CONCLUSION: In asymptomatic persons, subclinical, obstructive coronary atherosclerosis is associated with a more than 8-fold elevated risk for myocardial infarction. PRIMARY FUNDING SOURCE: AP Møller og Hustru Chastine Mc-Kinney Møllers Fond.

Biological and mechanical performance of calcium phosphate cements modified with phytic acid.

Calcium phosphate cements, primarily brushite cements, require the addition of setting retarders to ensure adequate processing time and processability. So far, citric acid has been the primary setting retarder used in this context. Due to the poor biocompatibility, it is crucial to explore alternative options for better processing. In recent years, the setting retarder phytic acid (IP6) has been increasingly investigated. This study investigates the biological behaviour of calcium phosphate cements with varying concentrations of IP6, in addition to their physical properties. Therefore cytocompatibility in vitro testing was performed using osteoblastic (MG-63) and osteoclastic (RAW 264.7 differentiated with RANKL) cells. We could demonstrate that the physical properties like the compressive strength of specimens formed with IP6 (brushite_IP6_5 = 11.2 MPa) were improved compared to the reference (brushite = 9.8 MPa). In osteoblast and osteoclast assays, IP6 exhibited significantly better cytocompatibility in terms of cell activity and cell number for brushite cements up to 11 times compared to the brushite reference. In contrast, the calcium-deficient hydroxyapatite (CDHA) cements produced similar results for IP6 (CDHA_IP6_0.25 = 27.0 MPa) when compared to their reference (CDHA = 21.2 MPa). Interestingly, lower doses of IP6 were found to be more effective than higher doses with up to 3 times higher. Additionally, IP6 significantly increased degradation in both passive and active resorption. For these reasons, IP6 is emerging as a strong new competitor to established setting retarders such as citric acid. These cements have potential applications in bone augmentation, the stabilisation of non-load bearing fractures (craniofacial), or the cementation of metal implants.

Genetic risk of fatty liver disease and mortality in the general population: A Mendelian randomization study.

BACKGROUND & AIMS: Fatty liver disease has been associated with higher all-cause as well as liver-related, ischemic heart disease (IHD)-related and extrahepatic cancer-related mortality in observational epidemiological studies. We tested the hypothesis that fatty liver disease is a causal risk factor for higher mortality. METHODS: We genotyped seven genetic variants known to be associated with fatty liver disease (in PNPLA3, TM6SF2, HSD17B13, MTARC1, MBOAT7, GCKR, and GPAM) in 110 913 individuals from the Danish general population. Hepatic steatosis was measured by hepatic computed tomography in n = 6965. Using a Mendelian randomization framework, we tested whether genetically proxied hepatic steatosis and/or elevated plasma alanine transaminase (ALT) was associated with liver-related mortality. RESULTS: During a median follow-up of 9.5 years, 16 119 individuals died. In observational analyses, baseline elevated plasma ALT was associated with higher all-cause (1.26-fold), liver-related (9-fold), and extrahepatic cancer-related (1.25-fold) mortality. In genetic analyses, the risk alleles in PNPLA3, TM6SF2, and HSD17B13 were individually associated with higher liver-related mortality. The largest effects were seen for the PNPLA3 and TM6SF2 risk alleles, for which homozygous carriers had 3-fold and 6-fold, respectively, higher liver-related mortality than non-carriers. None of the risk alleles, individually or combined into risk scores, were robustly associated with all-cause, IHD-related, or extrahepatic cancer-related mortality. In instrumental variable analyses, genetically proxied hepatic steatosis and higher plasma ALT were associated with liver-related mortality. CONCLUSIONS: Human genetic data support that fatty liver disease is a causal driver of liver-related mortality.

Composite grafts made of polycaprolactone fiber mats and oil-based calcium phosphate cement pastes for the reconstruction of cranial and maxillofacial defects.

OBJECTIVES: Synthetic bone substitutes which can be adapted preoperatively and patient specific may be helpful in various bony defects in the field of oral- and maxillofacial surgery. For this purpose, composite grafts made of self-setting and oil-based calcium phosphate cement (CPC) pastes, which were reinforced with 3D-printed polycaprolactone (PCL) fiber mats were manufactured. MATERIALS AND METHODS: Bone defect models were acquired using patient data from real defect situations of patients from our clinic. Using a mirror imaging technique, templates of the defect situation were fabricated via a commercially available 3D-printing system. The composite grafts were assembled layer by layer, aligned on top of these templates and fitted into the defect situation. Besides, PCL-reinforced CPC samples were evaluated regarding their structural and mechanical properties via X-ray diffraction (XRD), infrared (IR) spectroscopy, scanning electron microscopy (SEM), and 3-point-bending testing. RESULTS: The process sequence including data acquisition, template fabrication, and manufacturing of patient specific implants proved to be accurate and uncomplicated. The individual implants consisting mainly of hydroxyapatite and tetracalcium phosphate displayed good processability and a high precision of fit. The mechanical properties of the CPC cements in terms of maximum force and stress load to material fatigue were not negatively affected by the PCL fiber reinforcement, whereas clinical handling properties increased remarkably. CONCLUSION: PCL fiber reinforcement of CPC cements enables the production of very freely modelable three-dimensional implants with adequate chemical and mechanical properties for bone replacement applications. CLINICAL RELEVANCE: The complex bone morphology in the region of the facial skull often poses a great challenge for a sufficient reconstruction of bony defects. A full-fledged bone replacement here often requires the replication of filigree three-dimensional structures partly without support from the surrounding tissue. With regard to this problem, the combination of smooth 3D-printed fiber mats and oil-based CPC pastes represents a promising method for fabricating patient specific degradable implants for the treatment of various craniofacial bone defects.

Wideband TDoA Positioning Exploiting RSS-Based Clustering.

The accuracy of radio-based positioning is heavily influenced by a dense multipath (DM) channel, leading to poor position accuracy. The DM affects both time of flight (ToF) measurements extracted from wideband (WB) signals-specifically, if the bandwidth is below 100 MHz-as well as received signal strength (RSS) measurements, due to the interference of multipath signal components onto the information-bearing line-of-sight (LoS) component. This work proposes an approach for combining these two different measurement technologies, leading to a robust position estimation in the presence of DM. We assume that a large ensemble of densely-spaced devices is to be positioned. We use RSS measurements to determine "clusters" of devices in the vicinity of each other. Joint processing of the WB measurements from all devices in a cluster efficiently suppresses the influence of the DM. We formulate an algorithmic approach for the information fusion of the two technologies and derive the corresponding Cramér-Rao lower bound (CRLB) to gain insight into the performance trade-offs at hand. We evaluate our results by simulations and validate the approach with real-world measurement data. The results show that the clustering approach can halve the root-mean-square error (RMSE) from about 2 m to below 1 m, using WB signal transmissions in the 2.4 GHz ISM band at a bandwidth of about 80 MHz.

Discharging the medial knee compartment: comparison of pressure distribution and kinematic shifting after implantation of an extra-capsular absorber system (ATLAS) and open-wedge high tibial osteotomy-a biomechanical in vitro analysis.

PURPOSE: Young and active patients suffering early degenerative changes of the medial compartment with an underlying straight-leg axis do face a therapeutical gap as unloading of the medial compartment cannot be achieved by high tibial osteotomy. Extracapsular absorbing implants were developed to close this existing therapeutical gap. Purpose of the present cadaveric biomechanical study was to compare the unloading effect of the knee joint after implantation of an extra-articular absorber system (ATLAS) in comparison to open-wedge high tibial osteotomy (OW-HTO) under physiological conditions. The hypothesis of the study was that implantation of an extra-capsular absorber results in an unloading effect comparable to the one achievable with OW-HTO. METHODS: Eight fresh-frozen cadaveric knees were tested under isokinetic flexion-extension motions and physiological loading using a biomechanical knee simulator. Tibiofemoral area contact and peak contact pressures were measured using pressure-sensitive film in the untreated medial compartment. The tibiofemoral superior-inferior, latero-medial translation and varus/valgus rotation were measured with a 3D tracking system Polaris. Pressures and kinematics changes were measured after native testing, ATLAS System implantation and OW-HTO (5° and 10° correction angles) performed with an angular stable internal fixator (TomoFix). RESULTS: The absorber device decreased the pressure in the medial compartment near full extension moments. Implantation of the ATLAS absorbing system according to the manufacturers' instruction did not result in a significant unloading effect. Deviating from the surgery manual provided by the manufacturer the implantation of a larger spring size while applying varus stress before releasing the absorber resulted in a significant pressure diminution. Contact pressure decreased significantly Δ0.20 ± 0.04 MPa p = 0.044. Performing the OW-HTO in 5° correction angle resulted in significant decreased contact pressure (Δ0.25 ± 0.10 MPa, p = 0.0036) and peak contact pressure (Δ0.39 ± 0.38 MPa, p = 0.029) compared with the native test cycle. With a 10° correction angle, OW-HTO significantly decreased area contact pressure by Δ0.32 ± 0.09 MPa, p = 0.006 and peak contact pressure by Δ0.48 ± 0.12 MPa, p = 0.0654 compared to OW-HTO 5°. Surgical treatment did not result in kinematic changes regarding the superior-inferior translation of the medial joint section. A significant difference was observed for the translation towards the lateral compartment for the ATLAS system Δ1.31 ± 0.54 MPa p = 0.022 and the osteotomy Δ3.51 ± 0.92 MPa p = 0.001. Furthermore, significant shifting varus to valgus rotation of the treated knee joint was verified for HTO 5° about Δ2.97-3.69° and for HTO 10° Δ4.11-5.23° (pHTO 5 = 0.0012; pHTO 10 = 0.0007) over the entire extension cycle. CONCLUSION: OW-HTO results in a significant unloading of the medial compartment. Implantation of an extra-capsular absorbing device did not result in a significant unloading until the implantation technique was applied against the manufacturer's recommendation. While the clinical difficulty for young and active patients with straight-leg axis and early degenerative changes of the medial compartment persists further biomechanical research to develop sufficient unloading devices is required.

Prevalence of non-alcoholic fatty liver disease in patients with chronic kidney disease: a cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and represents a wide spectrum ranging from mild steatosis to non-alcoholic steatohepatitis with or without fibrosis to overt cirrhosis. Patients with NAFLD have a high risk of developing cardiovascular disease and chronic kidney disease (CKD). So far there has been scarce evidence of the prevalence of NAFLD among patients with CKD. We investigated the prevalence of moderate-severe hepatic steatosis graded according to the definition of NAFLD in a cohort of patients with CKD. METHODS: Hepatic liver fat content was evaluated by computed tomography (CT) scan in 291 patients from the Copenhagen CKD Cohort Study and in 866 age- and sex-matched individuals with normal kidney function from the Copenhagen General Population Study. Liver attenuation density <48 HU was used as a cut-off value for moderate-severe hepatic steatosis. RESULTS: The prevalence of moderate-severe hepatic steatosis was 7.9 and 10.7% (P = 0.177) among patients with CKD and controls, respectively. No association between liver fat content and CKD stage was found. In the pooled dataset from both cohorts, adjusted odds ratios for moderate-severe hepatic steatosis among persons with diabetes, overweight and obesity were 3.1 [95% confidence interval (CI) 1.6-5.9], 14.8 (95% CI 4.6-47.9) and 42.0 (95% CI 12.9-136.6), respectively. CONCLUSIONS: In a cohort of 291 patients with CKD, kidney function was not associated with the prevalence of moderate-severe hepatic steatosis as assessed by CT scan.

Task sharing in an interprofessional medication management program - a survey of general practitioners and community pharmacists.

BACKGROUND: Pharmacist-led medication review and medication management programs (MMP) are well-known strategies to improve medication safety and effectiveness. If performed interprofessionally, outcomes might even improve. However, little is known about task sharing in interprofessional MMP, in which general practitioners (GPs) and community pharmacists (CPs) collaboratively perform medication reviews and continuously follow-up on patients with designated medical and pharmaceutical tasks, respectively. In 2016, ARMIN (Arzneimittelinitiative Sachsen-Thüringen) an interprofessional MMP was launched in two German federal states, Saxony and Thuringia. The aim of this study was to understand how GPs and CPs share tasks in MMP when reviewing the patients' medication. METHODS: This was a cross-sectional postal survey among GPs and CPs who participated in the MMP. Participants were asked who completed which MMP tasks, e.g., checking drug-drug interactions, dosing, and side effects. In total, 15 MMP tasks were surveyed using a 5-point Likert scale ranging from "I complete this task alone" to "GP/CP completes this task alone". The study was conducted between 11/2020 and 04/2021. Data was analyzed using descriptive statistics. RESULTS: In total, 114/165 (69.1%) GPs and 166/243 (68.3%) CPs returned a questionnaire. The majority of GPs and CPs reported (i) checking clinical parameters and medication overuse and underuse to be completed by GPs, (ii) checking storage conditions of drugs and initial compilation of the patient's medication including brown bag review being mostly performed by CPs, and (iii) checking side-effects, non-adherence, and continuous updating of the medication list were carried out jointly. The responses differed most for problems with self-medication and adding and removing over-the-counter medicines from the medication list. In addition, the responses revealed that some MMP tasks were not sufficiently performed by either GPs or CPs. CONCLUSIONS: Both GPs' and CPs' expertise are needed to perform MMP as comprehensively as possible. Future studies should explore how GPs and CPs can complement each other in MMP most efficiently.

HIV infection is associated with thoracic and abdominal aortic aneurysms: a prospective matched cohort study.

AIMS: Little is known about the prevalence of aortic aneurysms among people living with HIV (PLWH). We investigated whether HIV status is independently associated with having aortic aneurysms. Furthermore, we determined risk factors associated with aortic aneurysms in PLWH. METHODS AND RESULTS: PLWH aged ≥40 years (n = 594) were recruited from the Copenhagen Comorbidity in HIV Infection study and matched for age and sex with uninfected controls (n = 1188) from the Copenhagen General Population Study. Aortic dimensions were assessed using contrast enhanced computed tomography. Aortic aneurysms were defined according to the European Society of Cardiology guidelines, i.e. an aortic dilation of ≥50% or an infrarenal aortic diameter of ≥30 mm. Among PLWH and uninfected controls, the median (interquartile range) age was 52 (47-60) and 52 (48-61) and 88% and 90% were male, respectively. We found 46 aneurysms in 42 (7.1%) PLWH and 31 aneurysms in 29 (2.4%) uninfected controls (P < 0.001). PLWH had a significantly higher prevalence of ascending aortic aneurysms and infrarenal aortic aneurysms. In an adjusted model, HIV was independently associated with aortic aneurysms (adjusted odds ratio; 4.51 [95% confidence interval 2.56-8.08], P < 0.001). Within PLWH, obesity and hepatitis B co-infection were associated with aortic aneurysms. CONCLUSION: PLWH had four-fold higher odds of aortic aneurysms compared to uninfected controls, and HIV status was independently associated with aortic aneurysms. Among PLWH, age, obesity and hepatitis B co-infection were associated with higher odds of aortic aneurysms. Our findings suggest that increased attention to aortic aneurysms in PLWH may be beneficial.

Interobserver reliability is higher for assessments with 3D software-generated models than with conventional MRI images in the classification of trochlear dysplasia.

PURPOSE: Trochlear dysplasia is a significant risk factor for patellofemoral instability. The severity of trochlear dysplasia is commonly evaluated based on the Dejour classification in axial MRI slices. However, this often leads to heterogeneous assessments. A software to generate MRI-based 3D models of the knee was developed to ensure more standardized visualization of knee structures. The purpose of this study was to assess the intra- and interobserver agreements of 2D axial MRI slices and an MRI-based 3D software generated model in classification of trochlear dysplasia as described by Dejour. METHODS: Four investigators independently assessed 38 axial MRI scans for trochlear dysplasia. Analysis was made according to Dejour's 4 grade classification as well as differentiating between 2 grades: low-grade (types A + B) and high-grade trochlear dysplasia (types C + D). Assessments were repeated following a one-week interval. The inter- and intraobserver agreement was determined using Cohen's kappa (κ) and Fleiss kappa statistic (κ). In addition, the proportion of observed agreement (po) was calculated for assessment of intraobserver agreement. RESULTS: The assessment of the intraobserver reliability with regard to the Dejour-classification showed moderate agreement values both in the 2D (κ = 0.59 ± 0.08 SD) and in the 3D analysis (κ = 0.57 ± 0.08 SD). Considering the 2-grade classification, the 2D (κ = 0.62 ± 0.12 SD) and 3D analysis (κ = 0.61 ± 0.19 SD) each showed good intraobserver matches. The analysis of the interobserver reliability also showed moderate agreement values with differences in the subgroups (2D vs. 3D). The 2D evaluation showed correspondences of κ = 0.48 (Dejour) and κ = 0.46 (high / low). In the assessment based on the 3D models, correspondence values of κ = 0.53 (Dejour) and κ = 0.59 (high / low) were documented. CONCLUSION: Overall, moderate-to-good agreement values were found in all groups. The analysis of the intraobserver reliability showed no relevant differences between 2 and 3D representation, but better agreement values were found in the 2-degree classification. In the analysis of interobserver reliability, better agreement values were found in the 3D compared to the 2D representation. The clinical relevance of this study lies in the superiority of the 3D representation in the assessment of trochlear dysplasia, which is relevant for future analytical procedures as well as surgical planning. LEVEL OF EVIDENCE: Level II.

Bone regeneration capacity of newly developed spherical magnesium phosphate cement granules.

OBJECTIVES: Magnesium phosphate-based cements begin to catch more attention as bone substitute materials and especially as alternatives for the more commonly used calcium phosphates. In bone substitutes for augmentation purposes, atraumatic materials with good biocompatibility and resorbability are favorable. In the current study, we describe the in vivo testing of novel bone augmentation materials in form of spherical granules based on a calcium-doped magnesium phosphate (CaMgP) cement. MATERIALS AND METHODS: Granules with diameters between 500 and 710 µm were fabricated via the emulsification of CaMgP cement pastes in a lipophilic liquid. As basic material, two different CaMgP formulations were used. The obtained granules were implanted into drill hole defects at the distal femoral condyle of 27 New Zealand white rabbits for 6 and 12 weeks. After explantation, the femora were examined via X-ray diffraction analysis, histological staining, radiological examination, and EDX measurement. RESULTS: Both granule types display excellent biocompatibility without any signs of inflammation and allow for proper bone healing without the interposition of connective tissue. CaMgP granules show a fast and continuous degradation and enable fully adequate bone regeneration. CONCLUSIONS: Due to their biocompatibility, their degradation behavior, and their completely spherical morphology, these CaMgP granules present a promising bone substitute material for bone augmentation procedures, especially in sensitive areas. CLINICAL RELEVANCE: The mostly insufficient local bone supply after tooth extractions complicates prosthetic dental restoration or makes it even impossible. Therefore, bone augmentation procedures are oftentimes inevitable. Spherical CaMgP granules may represent a valuable bone replacement material in many situations.

Evaluation of advanced platelet-rich fibrin (PRF) as a bio-carrier for ampicillin/sulbactam.

OBJECTIVES: Mechanisms of wound healing are often impaired in patients with osteonecrosis of the jaw (ONJ). According to the guidelines for the treatment of this disease, early surgical intervention is indicated. However, surgery often faces complications such as wound healing disorders. The application of platelet-rich fibrin (PRF) after necrosectomy between bone and mucosa may constitute a promising approach to improve surgical results. An aspect that was not investigated until now is that PRF acts as a "bio-carrier" for antibiotics previously applied intravenously. MATERIALS AND METHODS: We investigated the antimicrobial properties of PRF in 24 patients presenting ONJ undergoing systemic antibiosis with ampicillin/sulbactam. We measured the concentration of ampicillin/sulbactam in plasma and PRF and performed agar diffusion tests. Ampicillin/sulbactam was applied intravenously to the patient 10 minutes for blood sampling for PRF. No further incorporation of patients' blood or PRF product with antibiotic drugs was obtained. Four healthy patients served as controls. RESULTS: Our results revealed that PRF is highly enriched with ampicillin/sulbactam that is released to the environment. The antibiotic concentration in PRF was comparable to the plasma concentration of ampicillin/sulbactam. The inhibition zone (IZ) of PRF was comparable to the standard ampicillin/sulbactam discs used in sensitivity testing. CONCLUSIONS: The results of our study demonstrated that PRF is a reliable bio-carrier for systemic applied antibiotics and exhibits a large antimicrobial effect. CLINICAL RELEVANCE: We describe a clinically useful feature of PRF as a bio-carrier for antibiotics. Especially when applied to poorly perfused tissues and bone such as in ONJ, the local release of antibiotics can reduce wound healing disorders like infections.

10-year follow-up of the Columbus knee prostheses system in a prospective multicenter study.

INTRODUCTION: As endpoint of a prospective multicenter 10-year documentation using the Columbus system, this evaluation carried out results of clinical scores (Knee Society Score and Oxford Knee Score), an evaluation of radiological imaging, survival rates and a collection of complication statistics. MATERIALS AND METHODS: There was a multicenter prospective recruitment of consecutive patients with the indication for total knee replacement (TKR). Preoperatively and 10 years after implantation, clinical scores, range of motion and radiological imaging was performed. During this period, a detailed documentation of complications was made. RESULTS: A total of 210 patients were recruited in 5 centers. 140 patients were available for endpoint examination 10 years after surgery. A survival rate of 96.6% (CI 95%) for the implanted Columbus prostheses after 10 years was demonstrated. Cumulative KSS showed an improvement of 75.3 (± 38.1) points and was highly significant (p < 0.0001, t test). The average functional improvement in the Oxford score was 20.6 (± 9.5) points and was also highly significant (p < 0.0001). The ROM improved from 106.5° (± 20.5) preoperatively to 116.0° (± 11.5) (p < 0.0001, t test). There were no implant-related complications as well as no new complication documented between 5- and 10-year follow-up. CONCLUSIONS: The endpoint analysis after an observation period of 10 years provided good clinical and radiographic results. In particular, an excellent survival rate of 96.6% after 10 years was demonstrated. The data published in this study are the first to be available in a prospective multicenter study on this system, which leads to a high level of clinical significance.

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

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.

[Recommendations for the prevention, diagnosis, and therapy of addiction in the elderly]. / Recommandations pour la prévention, le diagnostic et la thérapie des addictions à l'âge avancé.

In old age, the chronic use of substances such as alcohol and sedatives, and more recently opioids, is a major public health and personal problem. Despite this, relatively little attention has been paid to the disorders associated with the use of these substances. These recommendations have been formulated by the Swiss Society for Elderly Psychiatry and Psychotherapy (SPPA) in collaboration with the Swiss Nurses' Association (SNA) and the Swiss Society for Addiction Medicine (SSAM). They provide a summary of the knowledge about addiction disorders in old age for the benefit of those working with patients, with the aim of strengthening prevention, early detection and appropriate interventions.

À l'âge avancé, la consommation chronique de substances comme l'alcool et les sédatifs, et plus récemment les opioïdes, représente un important problème pour les personnes concernées et de santé publique. Malgré cela, relativement peu d'attention a été accordée aux troubles associés à la consommation de ces substances. Les présentes recommandations ont été formulées par la Société suisse de psychiatrie et psychothérapie de la personne âgée (SPPA) en collaboration avec l'Association suisse des infirmières et infirmiers (ASI) et la Société suisse de médecine de l'addiction (SSMA). Elles mettent à la disposition des intervenants auprès des patients un résumé des connaissances au sujet des troubles addictifs à l'âge avancé, avec comme objectif de renforcer la prévention et le dépistage précoce, et des interventions adaptées.

Persistence with Biologic Treatment in Patients with Inflammatory Bowel Disease: A German Claims Data Analysis.

OBJECTIVES: This study aimed to assess the real-world rates of treatment discontinuation and switching of biologic therapies in patients with inflammatory bowel disease (IBD). METHODS: A retrospective claims data analysis on all continuously insured adult IBD patients with initiation of a biologic therapy was conducted. Observation started with the date of the first prescription of index tumor necrosis factor α-inhibitors (anti-TNFα) or vedolizumab (VDZ) therapy and lasted 12 months. Non-persistence was assumed in case of a switch to another biologic or a treatment gap of >90 days. RESULTS: We included 1,248 IBD biologic treatment starters (502 adalimumab, 77 golimumab, 441 infliximab, 228 VDZ); 837/411 were biologic-naïve (bio-naïve)/ biologic-experienced (bio-experienced). Mean age of bio-naïve/bio-experienced anti-TNFα patients was 39.2/38.1 years (54.9%/56.7% female) and 42.6/37.8 years for VDZ patients (56.3%/54.9% female). Seven hundred and seventy-two patients (61.9%) were persistent with their index biologic therapy after 12 months (61.9%/61.8% bio-naïve/bio-experienced). Percentage of persistent patients was 69.7% for VDZ (65.6%/71.3%) and 60.1% for anti-TNFα (61.4%/55.5%). VDZ was associated with later non-persistence in a multivariable Cox regression analysis (hazard ratio 0.675; p = 0.003) compared to anti-TNFα. CONCLUSIONS: Only 60-70% of IBD -patients are still persistent with their biologic therapy after 12 months. VDZ therapy is associated with a higher persistence than anti-TNFα therapy in this analysis.

Prevalence and Risk Factors of Moderate-to-Severe Hepatic Steatosis in Human Immunodeficiency Virus Infection: The Copenhagen Co-morbidity Liver Study.

BACKGROUND: People with human immunodeficiency virus (PWH) may be at risk of nonalcoholic fatty liver disease. We compared the prevalence of moderate-to-severe hepatic steatosis (M-HS) in PWH with human immunodeficiency virus (HIV)-uninfected controls and determined risk factors for M-HS in PWH. METHODS: The Copenhagen Co-Morbidity in HIV Infection study included 453 participants, and the Copenhagen General Population Study included 765 participants. None had prior or current viral hepatitis or excessive alcohol intake. Moderate-to-severe hepatic steatosis was assessed by unenhanced computed tomography liver scan defined by liver attenuation ≤48 Hounsfield units. Adjusted odds ratios (aORs) were computed by adjusted logistic regression. RESULTS: The prevalence of M-HS was lower in PWH compared with uninfected controls (8.6% vs 14.2%, P < .01). In multivariable analyses, HIV (aOR, 0.44; P < .01), female sex (aOR, 0.08; P = .03), physical activity level (aOR, 0.09; very active vs inactive; P < .01), and alcohol (aOR, 0.89 per unit/week; P = .02) were protective factors, whereas body mass index (BMI) (aOR, 1.58 per 1 kg/m2; P < .01), alanine transaminase (ALT) (aOR, 1.76 per 10 U/L; P < .01), and exposure to integrase inhibitors (aOR, 1.28 per year; P = .02) were associated with higher odds of M-HS. CONCLUSIONS: Moderate-to-severe hepatic steatosis is less common in PWH compared with demographically comparable uninfected controls. Besides BMI and ALT, integrase inhibitor exposure was associated with higher prevalence of steatosis in PWH.

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

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.

Elucidation of the functional roles of the Q and I motifs in the human chromatin-remodeling enzyme BRG1.

The Snf2 proteins, comprising 53 different enzymes in humans, belong to the SF2 family. Many Snf2 enzymes possess chromatin-remodeling activity, requiring a functional ATPase domain consisting of conserved motifs named Q and I-VII. These motifs form two recA-like domains, creating an ATP-binding pocket. Little is known about the function of the conserved motifs in chromatin-remodeling enzymes. Here, we characterized the function of the Q and I (Walker I) motifs in hBRG1 (SMARCA4). The motifs are in close proximity to the bound ATP, suggesting a role in nucleotide binding and/or hydrolysis. Unexpectedly, when substituting the conserved residues Gln758 (Q motif) or Lys785 (I motif) of both motifs, all variants still bound ATP and exhibited basal ATPase activity similar to that of wildtype BRG1 (wtBRG1). However, all mutants lost the nucleosome-dependent stimulation of the ATPase domain. Their chromatin-remodeling rates were impaired accordingly, but nucleosome binding was retained and still comparable with that of wtBRG1. Interestingly, a cancer-relevant substitution, L754F (Q motif), displayed defects similar to the Gln758 variant(s), arguing for a comparable loss of function. Because we excluded a mutual interference of ATP and nucleosome binding, we postulate that both motifs stimulate the ATPase and chromatin-remodeling activities upon binding of BRG1 to nucleosomes, probably via allosteric mechanisms. Furthermore, mutations of both motifs similarly affect the enzymatic functionality of BRG1 in vitro and in living cells. Of note, in BRG1-deficient H1299 cells, exogenously expressed wtBRG1, but not BRG1 Q758A and BRG1 K785R, exhibited a tumor suppressor-like function.