Aortic dimensions in women with previous pre-eclampsia.

BACKGROUND: Pre-eclampsia is a pregnancy related disorder associated with hypertension and vascular inflammation, factors that are also involved in the pathological pathway of aortic dilatation and aneurysm development. It is, however, unknown if younger women with previous pre-eclampsia have increased aortic dimensions. We tested the hypothesis that previous pre-eclampsia is associated with increased aortic dimensions in younger women. METHODS: The study was a cross-sectional cohort study of women with previous pre-eclampsia, aged 40-55, from the PRECIOUS population matched by age and parity with women from the general population. Using contrast-enhanced CT, aortic diameters were measured in the aortic root, ascending aorta, descending aorta, at the level of the diaphragm, suprarenal aorta, and infrarenal aorta. RESULTS: 1355 women (684 with previous pre-eclampsia and 671 from the general population), with a mean (standard deviation) age of 46.9 (4.4) were included. The pre-eclampsia group had larger mean (standard deviation) aortic diameters (mm) in all measured segments from the ascending to the infrarenal aorta (ascending: 33.4 (4.0) vs. 31.4 (3.7), descending: 23.9 (2.1) vs. 23.3 (2.0), diaphragm: 20.8 (1.8) vs. 20.4 (1.8), suprarenal: 22.9 (1.9) vs. 22.0 (2.0), infrarenal: 19.3 (1.6) vs. 18.6 (1.7), p â€‹< â€‹0.001 for all, also after adjustment for age, height, parity, menopause, dyslipidemia, smoking and chronic hypertension. Guideline-defined ascending aortic aneurysms were found in 8 vs 2 women (p â€‹= â€‹0.12). CONCLUSIONS: Women with previous pre-eclampsia have larger aortic dimensions compared with women from the general population. Pre-eclampsia was found to be an independent risk factor associated with a larger aortic diameter.

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.

Biological and Mechanical Performance of Dual-Setting Brushite-Silica Gel Cements.

Bone defects resulting from trauma, diseases, or surgical procedures pose significant challenges in the field of oral and maxillofacial surgery. The development of effective bone substitute materials that promote bone healing and regeneration is crucial for successful clinical outcomes. Calcium phosphate cements (CPCs) have emerged as promising candidates for bone replacement due to their biocompatibility, bioactivity, and ability to integrate with host tissues. However, there is a continuous demand for further improvements in the mechanical properties, biodegradability, and bioactivity of these materials. Dual setting of cements is one way to improve the performance of CPCs. Therefore, silicate matrices can be incorporated in these cements. Silicate-based materials have shown great potential in various biomedical applications, including tissue engineering and drug delivery systems. In the context of bone regeneration, silicate matrices offer unique advantages such as improved mechanical stability, controlled release of bioactive ions, and enhanced cellular responses. Comprehensive assessments of both the material properties and biological responses of our samples were conducted. Cytocompatibility was assessed through in vitro testing using osteoblastic (MG-63) and osteoclastic (RAW 264.7) cell lines. Cell activity on the surfaces was quantified, and scanning electron microscopy (SEM) was employed to capture images of the RAW cells. In our study, incorporation of tetraethyl orthosilicate (TEOS) in dual-curing cements significantly enhanced physical properties, attributed to increased crosslinking density and reduced pore size. Higher alkoxysilyl group concentration improved biocompatibility by facilitating greater crosslinking. Additionally, our findings suggest citrate's potential as an alternative retarder due to its positive interaction with the silicate matrix, offering insights for future dental material research. This paper aims to provide an overview of the importance of silicate matrices as modifiers for calcium phosphate cements, focusing on their impact on the mechanical properties, setting behaviour, and biocompatibility of the resulting composites.

Aortic aneurysms in a general population cohort: prevalence and risk factors in men and women.

BACKGROUND AND AIMS: The prevalence and difference in risk factors for having thoracic and abdominal aortic aneurysms in men compared to women in the general population is not well-described. This study aimed to test the hypotheses i) that cardiovascular risk factors for thoracic and abdominal aortic aneurysms differ and ii) that the prevalence of thoracic and abdominal aortic aneurysms is sex specific. METHODS: Aortic examination using computed tomography angiography was performed in 11,294 individuals (56% women), with a mean age of 62 [range 40-95] years participating in the Copenhagen General Population Study. Thoracic aortic aneurysms were defined as ascending aortic diameter ≥45 mm and descending aortic diameter ≥35 mm, abdominal aortic aneurysms were defined as abdominal aortic diameter ≥30 mm. Demographic data were obtained from questionnaires. RESULTS: Overall prevalence of aortic aneurysms in the study population included: total population 2.1%, men 4.0% and women 0.7% (p-test men vs. women p<0.001). Aortic aneurysms were independently associated with male sex, increasing age, and body surface area. While thoracic aortic aneurysms were associated with hypertension, odds ratio=2.0[95%CI:1.5-2.8], abdominal aortic aneurysms were associated with hypercholesterolemia and smoking, odds ratios=2.4[95%CI:1.6-3.6] and 3.2[95%CI:1.9-5.4]. CONCLUSIONS: Subclinical aortic aneurysms are four times more prevalent in men than women. In both sexes, increasing age and body surface area are risk factors for aortic aneurysms of any anatomical location. Whereas arterial hypertension is a risk factor for thoracic aortic aneurysms, hypercholesterolemia and smoking are risk factors for abdominal aortic aneurysms.

Early-onset vs late-onset preeclampsia and risk of coronary atherosclerosis later in life: a clinical follow-up study.

BACKGROUND: Younger women with previous preeclampsia have an increased risk of coronary atherosclerosis. It is unknown if this risk is associated with the time of onset of preeclampsia. OBJECTIVE: This study aimed to investigate if women with early-onset preeclampsia have a higher risk of coronary atherosclerosis compared with women with late-onset preeclampsia, independent of other perinatal risk factors. STUDY DESIGN: A total of 911 women with previous preeclampsia aged 35 to 55 years participated in a clinical follow-up study, including clinical examination, comprehensive questionnaires, and cardiac computed tomography scan 13 years (range, 0-28) after index pregnancy. Early- and late-onset preeclampsia were defined as gestational age at delivery of <34+0 and ≥34+0 gestational weeks, respectively. The primary outcome of the study was the presence of coronary atherosclerosis on the cardiac computed tomography. A logistic regression analysis was performed to investigate the association between time of onset of preeclampsia, perinatal risk factors, and the primary outcome. RESULTS: Women with early-onset preeclampsia (N=139) were older (46.2±5.7 vs 44.4±5.5 years; P<.001), more likely to have hypertension (51.1% vs 35.1%; P≤.001), and had a higher body mass index (27.9±6.3 vs 26.9±5.5 kg/m2; P=.051) compared with women with late-onset preeclampsia (N=772) at follow-up. The prevalence of the primary outcome (coronary atherosclerosis) on the cardiac computed tomography among women with early- and late-onset preeclampsia was 28.8% vs 22.2%, respectively (P=.088; adjusted odds ratio, 1.74; 95% confidence interval, 1.01-3.01; P=.045 after adjustment for maternal age at index pregnancy, prepregnancy body mass index, parity, diabetes in pregnancy, smoking in pregnancy, offspring birthweight and sex, and follow-up length). CONCLUSION: Women with early-onset preeclampsia had a slightly higher risk of coronary atherosclerosis compared with women with late-onset preeclampsia. However, according to the current evidence, it does not seem indicated to limit screening, diagnostic, and preventive measures for cardiovascular disease only to women with early-onset preeclampsia.

Non-unions and wound infections do not differ following intramedullary nailing and plate osteosynthesis for distal third femur fractures: a meta-analysis.

Purpose: The fixation method of distal, extra-articular femur fractures is a controversially discussed. To ensure better stability itself, earlier mobilization and to prevent blood loss - all these are justifications for addressing the femur via reamed intramedullary nailing (RIMN). Anatomical reposition of multifragmentary fractures followed by increased risks of non-union are compelling reasons against it. The purpose of this study was to systematically review the literature for rates of non-union and wound infection, as well as blood loss and time of surgery. Methods: According to the PRISMA guidelines we conducted this systematic review by searching the Cochrane, PubMed, Ovid, MedLine, and Embase databases. Inclusion criteria were the modified Coleman methodology score (mCMS) >60, age >18 years, and extra-articular fractures of the distal femur. Biomechanical and animal studies were excluded. By referring to title and abstract relevant articles were reviewed independently. In the consecutive meta-analysis, we compared 9 studies and 639 patients. Results: There is no statistically significant difference comparing superficial wound infections when RIMN was performed (OR = 0.50; 95% CI: 0.18 - 1.42; P = 0.19) as well as in deep wound infections (OR = 0.74; 95% CI: 0.19-2.81; P = 0.62). However, these results were not significant. We also calculated for potential differences in the rate of non-unions depending on the surgical treatment applied. Data of 556 patients revealed an overall number of 43 non-unions. There was no significant difference in rate of non-unions between both groups (OR = 0.97; 95% CI: 0.51-1.85; P = 0.92). Conclusion: No statistical difference was found in our study among RIMN and plate fixation in the treatment of distal femoral fractures with regard to the incidence of non-union and wound infections. Therefore, the indication for RIMN or plating should be made individually and based on the surgeon's experience.

Successful microvascular surgery in patients with thrombophilia in head and neck surgery: a case series.

BACKGROUND: In this case series, a perioperative anticoagulation protocol for microvascular head and neck surgery in patients with thrombophilia is presented. Microvascular free-flap surgery is a standard procedure in head and neck surgery with high success rates. Nevertheless, flap loss-which is most often caused by thrombosis-can occur and has far-reaching consequences, such as functional impairment, prolonged hospitalization, and increased costs. The risk of flap loss owing to thrombosis is significantly increased in patients with thrombophilia. Therefore, perioperative anticoagulation is mandatory. To date, no perioperative anticoagulation protocol exists for these high-risk patients. CASE PRESENTATION: We present three exemplary male Caucasian patients aged 53-57 years with free flap loss owing to an underlying, hidden thrombophilia. CONCLUSION: We present a modified anticoagulation protocol for microvascular surgery in these high-risk patients, enabling successful microsurgical reconstruction.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

Normal values of myocardial blood flow measured with dynamic myocardial computed tomography perfusion.

AIMS: Dynamic myocardial computed tomography (CT) perfusion (DM-CTP) can, in combination with coronary CT angiography (CCTA), provide anatomical and functional evaluation of coronary artery disease (CAD). However, normal values of myocardial blood flow (MBF) are needed to identify impaired myocardial blood supply in patients with suspected CAD. We aimed to establish normal values for MBF measured using DM-CTP, to assess the effects of age and sex, and to assess regional distribution of MBF. METHODS AND RESULTS: A total of 82 healthy individuals (46 women) aged 45-78 years with normal coronary arteries by CCTA underwent either rest and adenosine stress DM-CTP (n = 30) or adenosine-induced stress DM-CTP only (n = 52). Global and segmental MBF were assessed. Global MBF at rest and during stress were 0.93 ± 0.42 and 3.58 ± 1.14 mL/min/g, respectively. MBF was not different between the sexes (P = 0.88 at rest and P = 0.61 during stress), and no correlation was observed between MBF and age (P = 0.08 at rest and P = 0.82 during stress). Among the 16 myocardial segments, significant intersegmental differences were found (P < 0.01), which was not related to age, sex, or coronary dominance. CONCLUSION: MBF assessed by DM-CTP in healthy individuals with normal coronary arteries displays significant intersegmental heterogeneity which does not seem to be affected by age, sex, or coronary dominance. Normal values of MBF may be helpful in the clinical evaluation of suspected myocardial ischaemia using DM-CTP.

Detection of mcr-1-1 Positive Enteropathogenic Escherichia coli Isolates Associated with Post-Weaning Diarrhoea in an Organic Piglet-Producing Farm in Austria.

Postweaning diarrhoea (PWD) is a frequent multifactorial disease occurring in swine stocks worldwide. Since pathogenic Escherichia (E.) coli play a pivotal role in the pathogenesis of PWD and porcine E. coli are often resistant to different antibiotics, colistin is frequently applied to treat piglets with PWD. However, the application of colistin to livestock has been associated with the emergence of colistin resistance. This case report describes the detection of the colistin resistance gene mcr-1-1 in two E. coli isolated from piglets with PWD in an Austrian organic piglet-producing farm, which was managed by two farmers working as nurses in a hospital. Both mcr-1-positive E. coli were further analysed by Illumina short-read-sequencing, including assemblies and gene prediction. Both isolates belonged to the same clonal type and were positive for eaeH and espX5, which are both virulence genes associated with enteropathogenic E. coli (EPEC). Due to the detection of mcr-1-positive EPEC and based on the results of the antimicrobial resistance testing, the veterinarian decided to apply gentamicin for treatment instead of colistin, leading to improved clinical signs. In addition, after replacing faba beans with whey, PWD was solely observed in 2/10 weaned batches in the consecutive months.

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.

Plasma activin A rises with declining kidney function and is independently associated with mortality in patients with chronic kidney disease.

Background: Plasma (p-)activin A is elevated in chronic kidney disease-mineral and bone disorder (CKD-MBD). Activin A inhibition ameliorates CKD-MBD complications (vascular calcification and bone disease) in rodent CKD models. We examined whether p-activin A was associated with major adverse cardiovascular events (MACE), all-cause mortality and CKD-MBD complications in CKD patients. Methods: The study included 916 participants (741 patients and 175 controls) from the prospective Copenhagen CKD cohort. Comparisons of p-activin A with estimated glomerular filtration rate (eGFR), coronary and thoracic aorta Agatston scores, and bone mineral density (BMD) were evaluated by univariable linear regression using Spearman's rank correlation, analysis of covariance and ordinal logistic regression with adjustments. Association of p-activin A with rates of MACE and all-cause mortality was evaluated by the Aalen-Johansen or Kaplan-Meier estimator, with subsequent multiple Cox regression analyses. Results: P-activin A was increased by CKD stage 3 (124-225 pg/mL, P < .001) and correlated inversely with eGFR (r = -0.53, P < 0.01). P-activin A was associated with all-cause mortality [97 events, hazard ratio 1.55 (95% confidence interval 1.04; 2.32), P < 0.05] after adjusting for age, sex, diabetes mellitus (DM) and eGFR. Median follow-up was 4.36 (interquartile range 3.64-4.75) years. The association with MACE was not significant after eGFR adjustment. Agatston scores and BMD were not associated with p-activin A. Conclusion: P-activin A increased with declining kidney function and was associated with all-cause mortality independently of age, sex, DM and eGFR. No association with MACE, vascular calcification or BMD was demonstrated.

[Influence of the quadriceps muscles on the patellofemoral contact in patients with low flexion patellofemoral instability after MPFL reconstruction]. / Einfluss der Quadrizepsmuskulatur auf den patellofemoralen Kontaktmechanismus bei Patienten mit strecknaher patellofemoraler Instabilität nach MPFL-Rekonstruktion.

INTRODUCTION: MPFL reconstruction represents one of the most important surgical treatment options for recurrent patellar dislocations at low flexion angles associated with low flexion patellofemoral instability. Nevertheless, the role of quadriceps muscles in patients with patellofemoral instability before and after patellofemoral stabilization using MPFL reconstruction has not been fully elucidated. The present study investigates the influence of quadriceps muscles on the patellofemoral contact in patients with low flexion patellofemoral instability (PFI) before and after surgical patellofemoral stabilization using MPFL reconstruction using 3 T MRI datasets in early degrees of flexion (0-30°). METHODS: In this prospective cohort study, 15 patients with low flexion PFI before and after MPFL reconstruction and 15 subjects with healthy knee joints were studied using dynamic MRI scans. MRI scans were performed in a custom-made pneumatic knee loading device to determine the patellofemoral cartilage contact area (CCA) with and without quadriceps activation (50 N). Comparative measurements were performed using 3D cartilage and bone meshes in 0-30° knee flexion in the patients with patellofemoral instability preoperatively and postoperatively. RESULTS: The preoperative patellofemoral CCA of patients with low flexion PFI was 67.3 ± 47.3 mm2 in 0° flexion, 118.9 ± 56.6 mm2 in 15° flexion, and 267.6 ± 96.1 mm2 in 30° flexion. With activated quadriceps muscles (50 N), the contact area was 72.4 ± 45.9 mm2 in extension, 112.5 ± 54.9 mm2 in 15° flexion, and 286.1 ± 92.7 mm2 in 30° flexion without statistical significance. Postoperatively determined CCA revealed 159.3 ± 51.4 mm2 , 189.6 ± 62.2 mm2 and 347.3 ± 52.1 mm2 in 0°, 15° and 30° flexion. Quadriceps activation with 50 N showed a contact area in extension of 141.0 ± 63.8 mm2, 206.6 ± 67.7 mm2 in 15° flexion, and 353.5 ± 64.6 mm2 in 30° flexion, also without statistical difference compared with unloaded CCAs. Subjects with healthy knee joints showed an increase of 10.3% in CCA at 30° of flexion (p = 0.003). CONCLUSION: Although patellofemoral CCA increases significantly after isolated MPFL reconstruction in patients with low flexion patellofemoral instability, there is no significant influence of quadriceps muscles either preoperatively or postoperatively.

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.

Degradation and Bone-Contact Biocompatibility of Two Drillable Magnesium Phosphate Bone Cements in an In Vivo Rabbit Bone Defect Model.

The use of bone-cement-enforced osteosynthesis is a growing topic in trauma surgery. In this context, drillability is a desirable feature for cements that can improve fracture stability, which most of the available cement systems lack. Therefore, in this study, we evaluated a resorbable and drillable magnesium-phosphate (MgP)-based cement paste considering degradation behavior and biocompatibility in vivo. Two different magnesium-phosphate-based cement (MPC) pastes with different amounts of phytic acid (IP 6) as setting retarder (MPC 22.5 and MPC 25) were implanted in an orthotopic defect model of the lateral femoral condyle of New Zealand white rabbits for 6 weeks. After explantation, their resorption behavior and material characteristics were evaluated by means of X-ray diffraction (XRD), porosimetry measurement, histological staining, peripheral quantitative computed tomography (pQCT), cone-beam computed tomography (CBCT) and biomechanical load-to-failure tests. Both cement pastes displayed comparable results in mechanical strength and resorption kinetics. Bone-contact biocompatibility was excellent without any signs of inflammation. Initial resorption and bone remodeling could be observed. MPC pastes with IP 6 as setting retardant have the potential to be a valuable alternative in distinct fracture patterns. Drillability, promising resorption potential and high mechanical strength confirm their suitability for use in clinical routine.

Coronary Artery Disease in Persons With Human Immunodeficiency Virus Without Detectable Viral Replication.

Background: We aimed to determine the prevalence of coronary artery disease (CAD) in persons with human immunodeficiency virus (HIV; PWH) and investigate whether inflammatory markers, including interleukin 6, IL-1ß, and high-sensitivity C-reactive protein (hsCRP), were associated with CAD. Methods: From the Copenhagen Comorbidity in HIV Infection (COCOMO) study, we included virologically suppressed PWH who underwent coronary computed tomographic (CT) angiography. Any atherosclerosis was defined as >0% stenosis, and obstructive CAD as ≥50% stenosis. Results: Among 669 participants (mean age [standard deviation], 51 [11] years; 89% male), 300 (45%) had atherosclerosis, and 119 (18%) had obstructive CAD. The following risk factors were associated with any atherosclerosis and with obstructive CAD: age, male sex, hypertension, diabetes, smoking, dyslipidemia, time with HIV, and current protease inhibitor use. Interleukin 6 (IL-6) and hsCRP levels >2 mg/L were associated with any atherosclerosis and with obstructive CAD in univariable analyses but not after adjustment for traditional risk factors. IL-1ß was not associated with CAD. Conclusions: In a large population of PWH without viral replication, almost half had angiographically verified atherosclerosis. High concentrations of IL-6 and hsCRP were associated with CAD in univariable analyses, but adjustment for cardiovascular risk factors attenuated the association, suggesting that inflammation may mediate the association between traditional risk factors and CAD.

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.

Influence of Medial Patellofemoral Ligament Reconstruction on Patellofemoral Contact in Patients With Low-Flexion Patellar Instability: An MRI Study.

Background: Medial patellofemoral ligament (MPFL) reconstruction is a well-established procedure for the treatment of patients with patellofemoral instability (PFI) at low flexion angles (0°-30°). Little is known about the effect of MPFL surgery on patellofemoral cartilage contact area (CCA) during the first 30° of knee flexion. Purpose/Hypothesis: The purpose of this study was to investigate the effect of MPFL reconstruction on CCA using magnetic resonance imaging (MRI). We hypothesized that patients with PFI would have a lower CCA than patients with healthy knees and that CCA would increase after MPFL reconstruction over the course of low knee flexion. Study Design: Cohort study; Level of evidence, 2. Methods: In a prospective matched-paired cohort study, the CCA of 13 patients with low-flexion PFI was determined before and after MPFL reconstruction, and the data were compared with those of 13 healthy volunteers (controls). MRI was performed with the knee at 0°, 15°, and 30° of flexion in a custom-designed knee-positioning device. To suppress motion artifacts, motion correction was performed using a Moiré Phase Tracking system via a tracking marker attached to the patella. The CCA was calculated on the basis of semiautomatic cartilage and bone segmentation and registration. Results: The CCA (mean ± SD) at 0°, 15°, and 30° of flexion for the control participants was 1.38 ± 0.62, 1.91 ± 0.98, and 3.68 ± 0.92 cm2, respectively. In patients with PFI, the CCA at 0°, 15°, and 30° of flexion was 0.77 ± 0.49, 1.26 ± 0.60, and 2.89 ± 0.89 cm2 preoperatively and 1.65 ± 0.55, 1.97 ± 0.68, and 3.52 ± 0.57 cm2 postoperatively. Patients with PFI exhibited a significantly reduced preoperative CCA at all 3 flexion angles when compared with controls (P ≤ .045 for all). Postoperatively, there was a significant increase in CCA at 0° of flexion (P = .001), 15° of flexion (P = .019) and 30° of flexion (P = .026). There were no significant postoperative differences in CCA between patients with PFI and controls at any flexion angle. Conclusion: Patients with low-flexion patellar instability showed a significant reduction in patellofemoral CCA at 0°, 15°, and 30° of flexion. MPFL reconstruction increased the contact area significantly at all angles.

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.