Human shoulder development is adapted to obstetrical constraints.

In humans, obstetrical difficulties arise from the large head and broad shoulders of the neonate relative to the maternal birth canal. Various characteristics of human cranial development, such as the relatively small head of neonates compared with adults and the delayed fusion of the metopic suture, have been suggested to reflect developmental adaptations to obstetrical constraints. On the other hand, it remains unknown whether the shoulders of humans also exhibit developmental features reflecting obstetrical adaptation. Here we address this question by tracking the development of shoulder width from fetal to adult stages in humans, chimpanzees, and Japanese macaques. Compared with nonhuman primates, shoulder development in humans follows a different trajectory, exhibiting reduced growth relative to trunk length before birth and enhanced growth after birth. This indicates that the perinatal developmental characteristics of the shoulders likely evolved to ease obstetrical difficulties such as shoulder dystocia in humans.

Impact of ultra-high-resolution imaging of the lungs on perceived diagnostic image quality using photon-counting CT.

OBJECTIVES: To compare clinical image quality and perceived impact on diagnostic interpretation of chest CT findings between ultra-high-resolution photon-counting CT (UHR-PCCT) and conventional high-resolution energy-integrating-detector CT (HR-EIDCT) using visual grading analysis (VGA) scores. MATERIALS AND METHODS: Fifty patients who underwent a UHR-PCCT (matrix 512 × 512, 768 × 768, or 1024 × 1024; FOV average 275 × 376 mm, 120 × 0.2 mm; focal spot size 0.6 × 0.7 mm) between November 2021 and February 2022 and with a previous HR-EIDCT within the last 14 months were included. Four readers evaluated central and peripheral airways, lung vasculature, nodules, ground glass opacities, inter- and intralobular lines, emphysema, fissures, bullae/cysts, and air trapping on PCCT (0.4 mm) and conventional EIDCT (1 mm) via side-by-side reference scoring using a 5-point diagnostic quality score. The median VGA scores were compared and tested using one-sample Wilcoxon signed rank tests with hypothesized median values of 0 (same visibility) and 2 (better visibility on PCCT with impact on diagnostic interpretation) at a 2.5% significance level. RESULTS: Almost all lung structures had significantly better visibility on PCCT compared to EIDCT (p < 0.025; exception for ground glass nodules (N = 2/50 patients, p = 0.157)), with the highest scores seen for peripheral airways, micronodules, inter- and intralobular lines, and centrilobular emphysema (mean VGA > 1). Although better visibility, a perceived difference in diagnostic interpretation could not be demonstrated, since the median VGA was significantly different from 2. CONCLUSION: UHR-PCCT showed superior visibility compared to HR-EIDCT for central and peripheral airways, lung vasculature, fissures, ground glass opacities, macro- and micronodules, inter- and intralobular lines, paraseptal and centrilobular emphysema, bullae/cysts, and air trapping. CLINICAL RELEVANCE STATEMENT: UHR-PCCT has emerged as a promising technique for thoracic imaging, offering improved spatial resolution and lower radiation dose. Implementing PCCT into daily practice may allow better visibility of multiple lung structures and optimization of scan protocols for specific pathology. KEY POINTS: • The aim of this study was to verify if the higher spatial resolution of UHR-PCCT would improve the visibility and detection of certain lung structures and abnormalities. • UHR-PCCT was judged to have superior clinical image quality compared to conventional HR-EIDCT in the evaluation of the lungs. UHR-PCCT showed better visibility for almost all tested lung structures (except for ground glass nodules). • Despite superior image quality, the readers perceived no significant impact on the diagnostic interpretation of the studied lung structures and abnormalities.

Association Between Vascular 18F-Fluorodeoxyglucose Uptake at Diagnosis and Change in Aortic Dimensions in Giant Cell Arteritis : A Cohort Study.

BACKGROUND: Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular 18F-fluorodeoxyglucose (FDG) uptake at diagnosis are at increased risk for thoracic aortic complications. OBJECTIVE: To measure the association between vascular FDG uptake at diagnosis and the change in aortic dimensions. DESIGN: Prospective cohort study. SETTING: University Hospitals Leuven. PATIENTS: 106 patients with GCA and FDG positron emission tomography (PET) imaging 3 days or less after initiation of glucocorticoids. MEASUREMENTS: Patients had PET and computed tomography (CT) imaging at diagnosis and CT imaging yearly for a maximum of 10 years. The PET scans were scored 0 to 3 in 7 vascular areas and summed to a total vascular score (TVS). The PET scan results were positive when FDG uptake was grade 2 or greater in any large vessel. The association between vascular FDG uptake and aortic dimensions was estimated by linear mixed-effects models with random intercept and slope. RESULTS: When compared with patients with a negative PET scan result, those with a positive scan result had a greater increase in the diameter of the ascending aorta (difference in 5-year progression, 1.58 mm [95% CI, 0.41 to 2.74 mm]), the diameter of the descending aorta (1.32 mm [CI, 0.38 to 2.26 mm]), and the volume of the thoracic aorta (20.5 cm³ [CI, 4.5 to 36.5 cm³]). These thoracic aortic dimensions were also positively associated with TVS. Patients with a positive PET scan result had a higher risk for thoracic aortic aneurysms (adjusted hazard ratio, 10.21 [CI, 1.25 to 83.3]). LIMITATION: The lengthy inclusion and follow-up period resulted in missing data and the use of different PET machines. CONCLUSION: Higher TVS was associated with greater yearly increase in thoracic aortic dimensions. Performing PET imaging at diagnosis may help to estimate the risk for aortic aneurysm formation. PRIMARY FUNDING SOURCE: None.

The hemodynamic interplay between pulmonary ischemia-reperfusion injury and right ventricular function in lung transplantation: a translational porcine model.

Lung transplantation (LTx) is a challenging procedure. Following the process of ischemia-reperfusion injury, the transplanted pulmonary graft might become severely damaged, resulting in primary graft dysfunction. In addition, during the intraoperative window, the right ventricle (RV) is at risk of acute failure. The interaction of right ventricular function with lung injury is, however, poorly understood. We aimed to address this interaction in a translational porcine model of pulmonary ischemia-reperfusion injury. Advanced pulmonary and hemodynamic assessment was used, including right ventricular pressure-volume loop analysis. The acute model was based on clamping and unclamping of the left lung hilus, respecting the different hemodynamic phases of a clinical lung transplantation. We found that forcing entire right ventricular cardiac output through a lung suffering from ischemia-reperfusion injury increased afterload (pulmonary vascular resistance from baseline to end experiment P < 0.0001) and induced right ventricular failure (RVF) in 5/9 animals. Notably, we identified different compensation patterns in failing versus nonfailing ventricles (arterial elastance P = 0.0008; stroke volume P < 0.0001). Furthermore, increased vascular pressure and flow produced by the right ventricle resulted in higher pulmonary injury, as measured by ex vivo CT density (correlation: pressure r = 0.8; flow r = 0.85). Finally, RV ischemia as measured by troponin-T was negatively correlated with pulmonary injury (r = -0.76); however, troponin-T values did not determine RVF in all animals. In conclusion, we demonstrate a delicate balance between development of pulmonary ischemia-reperfusion injury and right ventricular function during lung transplantation. Furthermore, we provide a physiological basis for potential benefit of extracorporeal life support technology.NEW & NOTEWORTHY In contrast to the abundant literature of mechanical pulmonary artery clamping to increase right ventricular afterload, we developed a model adding a biological factor of pulmonary ischemia-reperfusion injury. We did not only focus on the right ventricular behavior, but also on the interaction with the injured lung. We are the first to describe this interaction while addressing the hemodynamic intraoperative phases of clinical lung transplantation.

Validation of a semi-automatic method to measure total liver volumes in polycystic liver disease on computed tomography - high speed and accuracy.

OBJECTIVES: Polycystic liver disease (PLD) is characterized by growth of hepatic cysts, causing hepatomegaly. Disease severity is determined using total liver volume (TLV), which can be measured from computed tomography (CT). The gold standard is manual segmentation which is time-consuming and requires expert knowledge of the anatomy. This study aims to validate the commercially available semi-automatic MMWP (Multimodality Workplace) Volume tool for CT scans of PLD patients. METHODS: We included adult patients with one (n = 60) or two (n = 46) abdominal CT scans. Semi-automatic contouring was compared with manual segmentation, using comparison of observed volumes (cross-sectional) and growth (longitudinal), correlation coefficients (CC), and Bland-Altman analyses with bias and precision, defined as the mean difference and SD from this difference. Inter- and intra-reader variability were assessed using coefficients of variation (CV) and we assessed the time to perform both procedures. RESULTS: Median TLV was 5292.2 mL (IQR 3141.4-7862.2 mL) at baseline. Cross-sectional analysis showed high correlation and low bias and precision between both methods (CC 0.998, bias 1.62%, precision 2.75%). Absolute volumes were slightly higher for semi-automatic segmentation (manual 5292.2 (3141.4-7862.2) versus semi-automatic 5432.8 (3071.9-7960.2) mL, difference 2.7%, p < 0.001). Longitudinal analysis demonstrated that semi-automatic segmentation accurately measures liver growth (CC 0.908, bias 0.23%, precision 4.04%). Inter- and intra-reader variability were small (2.19% and 0.66%) and comparable to manual segmentation (1.21% and 0.63%) (p = 0.26 and p = 0.37). Semi-automatic segmentation was faster than manual tracing (19 min versus 50 min, p = 0.009). CONCLUSIONS: Semi-automatic liver segmentation is a fast and accurate method to determine TLV and liver growth in PLD patients. KEY POINTS: • Semi-automatic liver segmentation using the commercially available MMWP volume tool accurately determines total liver volume as well as liver growth over time in polycystic liver disease patients. • This method is considerably faster than manual segmentation through the use of Hounsfield unit settings. • We used a real-life CT set for the validation and showed that the semi-automatic tool measures accurately regardless of contrast used for the CT scan or not, presence of polycystic kidneys, liver volume, and previous invasive treatment for polycystic liver disease.

Development and characterization of a chick embryo chorioallantoic membrane (CAM) based platform for evaluation of vasoactive medications.

Among various anti-cancer therapies, tumor vascular disrupting agents (VDAs) play a crucial role, for which their off-targeting effects on normal vessels need also to be investigated. The purpose of this study was to set up an in-ovo platform that combines a laser speckle contrast imaging (LSCI) modality with chick embryo chorioallantoic membrane (CAM) to real-time monitor vascular diameters and perfusion without and with intravascular injection. Two eggshell windows for both observation or measurement and injection were opened. Dynamic blood perfusion images and corresponding statistic graphs were acquired by using a LSCI unit on CAMs from embryo date (ED) 9 to ED15. A dedicated fine needle catheter was made for slow intravascular administration over 30 min with simultaneous LSCI acquisition. To verify the connectivity between CAM vessels and the embryonic circulations in the egg, contrast-enhanced 3D micro computed tomography (µCT), 2D angiography and histology were executed. This platform was successfully established to acquire, quantify and demonstrate vascular and hemodynamic information from the CAM. Chick embryos even with air cell opened remained alive from ED9 to ED15. Through collecting LSCI derived CAM vascular diameter and perfusion parameters, ED12 was determined as the best time window for vasoactive drug studies. A reverse correlation between CAM vessel diameter and blood perfusion rate was found (p < 0.002). Intravascular infusion and simultaneous LSCI acquisition for 30 min in ovo proved feasible. Contrast-enhanced angiography and histomorphology could characterize the connectivity between CAM vasculature and embryonic circulation. This LSCI-CAM platform was proved effective for investigating the in-ovo hemodynamics, which paves the road for further preclinical research on vasoactive medications including VDAs.

Detection of pulmonary nodules with scoutless fixed-dose ultra-low-dose CT: a prospective study.

OBJECTIVES: To determine the accuracy of scoutless, fixed-dose ultra-low-dose (ULD) CT compared to standard-dose (SD) CT for pulmonary nodule detection and semi-automated nodule measurement, across different patient sizes. METHODS: Sixty-three patients underwent ULD and SD CT. Two readers examined all studies visually and with computer-aided detection (CAD). Nodules detected on SD CT were included in the reference standard by consensus and stratified into 4 categories (nodule category, NODCAT) from the Dutch-Belgian Lung Cancer Screening trial (NELSON). Effects of NODCAT and patient size on nodule detection were determined. For each nodule, volume and diameter were compared between both scans. RESULTS: The reference standard comprised 173 nodules. For both readers, detection rates on ULD versus SD CT were not significantly different for NODCAT 3 and 4 nodules > 50 mm3 (reader 1: 93% versus 89% (p = 0.257); reader 2: 96% versus 98% (p = 0.317)). For NODCAT 1 and 2 nodules < 50 mm3, detection rates on ULD versus SD CT dropped significantly (reader 1: 66% versus 80% (p = 0.023); reader 2: 77% versus 87% (p = 0.039)). Body mass index and chest circumference did not influence nodule detectability (p = 0.229 and p = 0.362, respectively). Calculated volumes and diameters were smaller on ULD CT (p < 0.0001), without altering NODCAT (84% agreement). CONCLUSIONS: Scoutless ULD CT reliably detects solid lung nodules with a clinically relevant volume (> 50 mm3) in lung cancer screening, irrespective of patient size. Since detection rates were lower compared to SD CT for nodules < 50 mm3, its use for lung metastasis detection should be considered on a case-by-case basis. KEY POINTS: • Detection rates of pulmonary nodules > 50 mm3are not significantly different between scoutless ULD and SD CT (i.e. volumes clinically relevant in lung cancer screening based on the NELSON trial), but were different for the detection of nodules < 50 mm3(i.e. volumes still potentially relevant in lung metastasis screening). • Calculated nodule volumes were on average 0.03 mL or 9% smaller on ULD CT, which is below the 20-25% interscan variability previously reported with software-based volumetry. • Even though a scoutless, fixed-dose ULD CT protocol was used (CTDIvol0.15 mGy), pulmonary nodule detection was not influenced by patient size.

Whole liver segmentation based on deep learning and manual adjustment for clinical use in SIRT.

PURPOSE: In selective internal radiation therapy (SIRT), an accurate total liver segmentation is required for activity prescription and absorbed dose calculation. Our goal was to investigate the feasibility of using automatic liver segmentation based on a convolutional neural network (CNN) for CT imaging in SIRT, and the ability of CNN to reduce inter-observer variability of the segmentation. METHODS: A multi-scale CNN was modified for liver segmentation for SIRT patients. The CNN model was trained with 139 datasets from three liver segmentation challenges and 12 SIRT patient datasets from our hospital. Validation was performed on 13 SIRT datasets and 12 challenge datasets. The model was tested on 40 SIRT datasets. One expert manually delineated the livers and adjusted the liver segmentations from CNN for 40 test SIRT datasets. Another expert performed the same tasks for 20 datasets randomly selected from the 40 SIRT datasets. The CNN segmentations were compared with the manual and adjusted segmentations from the experts. The difference between the manual segmentations was compared with the difference between the adjusted segmentations to investigate the inter-observer variability. Segmentation difference was evaluated through dice similarity coefficient (DSC), volume ratio (RV), mean surface distance (MSD), and Hausdorff distance (HD). RESULTS: The CNN segmentation achieved a median DSC of 0.94 with the manual segmentation and of 0.98 with the manually corrected CNN segmentation, respectively. The DSC between the adjusted segmentations is 0.98, which is 0.04 higher than the DSC between the manual segmentations. CONCLUSION: The CNN model achieved good liver segmentations on CT images of good image quality, with relatively normal liver shapes and low tumor burden. 87.5% of the 40 CNN segmentations only needed slight adjustments for clinical use. However, the trained model failed on SIRT data with low dose or contrast, lesions with large density difference from their surroundings, and abnormal liver position and shape. The abovementioned scenarios were not adequately represented in the training data. Despite this limitation, the current CNN is already a useful clinical tool which improves inter-observer agreement and therefore contributes to the standardization of the dosimetry. A further improvement is expected when the CNN will be trained with more data from SIRT patients.

Developmental evidence for obstetric adaptation of the human female pelvis.

The bony pelvis of adult humans exhibits marked sexual dimorphism, which is traditionally interpreted in the framework of the "obstetrical dilemma" hypothesis: Giving birth to large-brained/large-bodied babies requires a wide pelvis, whereas efficient bipedal locomotion requires a narrow pelvis. This hypothesis has been challenged recently on biomechanical, metabolic, and biocultural grounds, so that it remains unclear which factors are responsible for sex-specific differences in adult pelvic morphology. Here we address this issue from a developmental perspective. We use methods of biomedical imaging and geometric morphometrics to analyze changes in pelvic morphology from late fetal stages to adulthood in a known-age/known-sex forensic/clinical sample. Results show that, until puberty, female and male pelves exhibit only moderate sexual dimorphism and follow largely similar developmental trajectories. With the onset of puberty, however, the female trajectory diverges substantially from the common course, resulting in rapid expansion of obstetrically relevant pelvic dimensions up to the age of 25-30 y. From 40 y onward females resume a mode of pelvic development similar to males, resulting in significant reduction of obstetric dimensions. This complex developmental trajectory is likely linked to the pubertal rise and premenopausal fall of estradiol levels and results in the obstetrically most adequate pelvic morphology during the time of maximum female fertility. The evidence that hormones mediate female pelvic development and morphology supports the view that solutions of the obstetrical dilemma depend not only on selection and adaptation but also on developmental plasticity as a response to ecological/nutritional factors during a female's lifetime.

Creation of Abdominal Aortic Aneurysms in Sheep by Extrapolation of Rodent Models: Is It Feasible?

BACKGROUND: Abdominal aortic aneurysms (AAAs) are a potentially deathly disease, needing surgical or endovascular treatment. To evaluate potentially new diagnostic tools and treatments, a large animal model, which resembles not only the morphological characteristics but also the pathophysiological background, would be useful. METHODS: Rodent animal aneurysm models were extrapolated to sheep. Four groups were created: intraluminal infusion with an elastase-collagenase solution (n = 4), infusion with elastase-collagenase solution combined with proximal stenosis (n = 7), aortic xenograft (n = 3), and elastase-collagenase-treated xenograft (n = 4). At fixed time intervals (6, 12, and 24 weeks), computer tomography and autopsy with histological evaluation were performed. RESULTS: The described models had a high perioperative mortality (45%), due to acute aortic thrombosis or fatale hemorrhage. A maximum aortic diameter increase of 30% was obtained in the protease-stenosis group. In the protease-treated groups, some histological features of human AAAs, such as inflammation, thinning of the media, and loss of elastin could be reproduced. In the xenotransplant groups, a pronounced inflammatory reaction was visible at the start. In all models, inflammation decreased and fibrosis occurred at long follow-up, 24 weeks postoperatively. CONCLUSIONS: None of the extrapolated small animal aneurysm models could produce an AAA in sheep with similar morphological features as the human disease. Some histological findings of human surgical specimens could be reproduced in the elastase-collagenase-treated groups. Long-term histological evaluation indicated stabilization and healing of the aortic wall months after the initial stimulus.

Do we need 3D tube current modulation information for accurate organ dosimetry in chest CT? Protocols dose comparisons.

OBJECTIVES: To compare the lung and breast dose associated with three chest protocols: standard, organ-based tube current modulation (OBTCM) and fast-speed scanning; and to estimate the error associated with organ dose when modelling the longitudinal (z-) TCM versus the 3D-TCM in Monte Carlo simulations (MC) for these three protocols. METHOD: Five adult and three paediatric cadavers with different BMI were scanned. The CTDIvol of the OBTCM and the fast-speed protocols were matched to the patient-specific CTDIvol of the standard protocol. Lung and breast doses were estimated using MC with both z- and 3D-TCM simulated and compared between protocols. RESULTS: The fast-speed scanning protocol delivered the highest doses. A slight reduction for breast dose (up to 5.1%) was observed for two of the three female cadavers with the OBTCM in comparison to the standard. For both adult and paediatric, the implementation of the z-TCM data only for organ dose estimation resulted in 10.0% accuracy for the standard and fast-speed protocols, while relative dose differences were up to 15.3% for the OBTCM protocol. CONCLUSION: At identical CTDIvol values, the standard protocol delivered the lowest overall doses. Only for the OBTCM protocol is the 3D-TCM needed if an accurate (<10.0%) organ dosimetry is desired. KEY POINTS: • The z-TCM information is sufficient for accurate dosimetry for standard protocols. • The z-TCM information is sufficient for accurate dosimetry for fast-speed scanning protocols. • For organ-based TCM schemes, the 3D-TCM information is necessary for accurate dosimetry. • At identical CTDI vol , the fast-speed scanning protocol delivered the highest doses. • Lung dose was higher in XCare than standard protocol at identical CTDI vol .

Effects of resistance training at different loads on inflammatory markers in young adults.

PURPOSE: Suppressing inflammaging at an early stage in life via exercise might prevent chronic diseases later in life. The aim was to investigate the influence of resistance training at different external loads on inflammatory markers in healthy young adults. METHODS: Serum was collected for basal levels of cytokines (IL-1beta, IL-6, IL-8, sTNFR1, IL-1RA, IL-10 and GM-CSF) before and after 9 weeks exercise from 36 young (22 ± 2 years) healthy subjects who were randomized to three times weekly supervised resistance training at either HImax (n = 12, 1 × 10-12 repetitions at 80% 1RM), LO (n = 12, 1 × 10-12 repetitions at 40% 1RM), or LOmax (n = 12, 1 × 10-12 repetitions at 40% 1RM preceded by 60 repetitions at 20-25% 1RM) respectively. RESULTS: Overall, IL-8 increased (p < 0.001) and IL-6 decreased (p = 0.001) after training, but no significant time*group interaction was found (respectively, p = 0.283 and p = 0.058 for IL-8 and IL-6). When analyzed separately, IL-8 increased significantly in HImax (p = 0.022) and LOmax (p = 0.024); and IL-6 decreased significantly in LOmax (p = 0.009) and LO (p = 0.013). No significant overall time effect was observed for sTNFR1 and IL-1RA; however, in HImax sTNFR1 (p = 0.031) and IL-1RA (p = 0.014) increased significantly, but remained unchanged in LOmax and LO. IL-1beta, IL-10 and GM-CSF levels remained undetectable in most participants. CONCLUSIONS: Nine weeks of resistance training-irrespective of the external load-have beneficial effects on circulating IL-8 and IL-6. In addition, training at high external load increases the anti-inflammatory cytokines sTNFR1 and IL-1RA. The results of this study show that resistance training has anti-inflammatory effects in healthy young persons and that the response of the different inflammatory mediators depends on the magnitude of the external load.

Lanreotide Reduces Liver Volume, But Might Not Improve Muscle Wasting or Weight Loss, in Patients With Symptomatic Polycystic Liver Disease.

BACKGROUND & AIMS: Polycystic liver disease (PCLD) can induce malnutrition owing to extensive hepatomegaly and patients might require liver transplantation. Six months of treatment with the somatostatin analogue lanreotide (120 mg) reduces liver volume. We investigated the efficacy of a lower dose of lanreotide and its effects on nutritional status. METHODS: We performed an 18-month prospective study at 2 tertiary medical centers in Belgium from January 2011 through August 2012. Fifty-nine patients with symptomatic PCLD were given lanreotide (90 mg, every 4 weeks) for 6 months. Patients with reductions in liver volume of more than 100 mL (responders, primary end point) continued to receive lanreotide (90 mg) for an additional year (18 months total). Nonresponders were offered increased doses, up to 120 mg lanreotide, until 18 months. Liver volume and body composition were measured by computed tomography at baseline and at months 6 and 18. Patients also were assessed by the PCLD-specific complaint assessment at these time points. RESULTS: Fifty-three patients completed the study; 21 patients (40%) were responders. Nineteen of the responders (90%) continued as responders until 18 months. At this time point, they had a mean reduction in absolute liver volume of 430 ± 92 mL. In nonresponders (n = 32), liver volume increased by a mean volume of 120 ± 42 mL at 6 months. However, no further increase was observed after dose escalation in the 24 patients who continued to the 18-month end point. All subjects had decreased scores on all subscales of the PCLD-specific complaint assessment, including better food intake (P = .04). Subjects did not have a mean change in subcutaneous or visceral fat mass, but did have decreases in mean body weight (2 kg) and total muscle mass (1.06 cm(2)/h(2)). Subjects also had a significant mean reduction in their level of insulin-like growth factor 1, from 19% below the age-adjusted normal range level at baseline to 50% at 18 months (P = .002). CONCLUSIONS: In a prospective study, we observed that low doses of lanreotide (90 mg every 4 weeks) reduced liver volumes and symptoms in patients with PCLD. However, patients continued to lose weight and muscle mass. The effects of somatostatin analogues on sarcopenia require investigation. Clinicaltrials.gov: NCT01315795.

IgG4-related periaortitis vs idiopathic periaortitis: is there a role for atherosclerotic plaque in the pathogenesis of IgG4-related periaortitis?

OBJECTIVE: The diagnosis of (isolated) IgG4-related periaortitis is often based on elevated serum IgG4 levels since in tissues such as the aorta, biopsies cannot be easily performed. However, the role for serum IgG4 as a biomarker for IgG4-related periaortitis is indistinct. The main purpose of our study was to identify clinical differences between periaortitis with elevated vs normal serum IgG4 levels. METHODS: A retrospective study was performed on 68 non-infectious periaortitis patients. We compared demographic, clinical, biochemical and radiological data in patients with elevated serum IgG4 levels with data from patients with normal serum IgG4 levels. The calcium content of the aortic wall was calculated to determine the amount of atherosclerosis. RESULTS: After applying exclusion criteria, our study population consisted of nine IgG4-related periaortitis patients and eight idiopathic periaortitis patients. Striking significant differences were male predominance (P = 0.001) and multifocal organ involvement (P = 0.004) in IgG4-related periaortitis patients compared with the idiopathic periaortitis group. The calcium content of the total aortic wall was significantly higher in IgG4-related periaortitis patients (P = 0.005). No other significant differences were found. CONCLUSION: Elevated serum IgG4 levels, male gender, a higher calcium content of the aortic wall and multifocal organ involvement are features that might provide a higher probability for IgG4-related periaortitis compared with idiopathic periaortitis. Our study results might be compatible with the hypothesis of Mitchinson and Parums that atherosclerotic plaque plays a role in the pathogenesis of chronic periaortitis.

Integration between the face and the mandible of Pongo and the evolution of the craniofacial morphology of orangutans.

OBJECTIVES: Extant Pongo diverges from other hominids by a series of craniofacial morphological features, such as a concave face, a reduced supraorbital torus, or an upwardly orientated palate. These traits are not independent because the skull is a complex integrated structure. The aim of this study is to describe the relationship between the face and mandible of Pongo, in order to examine the link between mandibular structures and the set-up of the unique facial features of orangutans. MATERIALS AND METHODS: Using 3D geometric morphometrics, the morphological integration between face and mandible of Pongo is compared to that of the three extant hominids: Homo, Pan, and Gorilla. Pooled within-species partial least squares analyses are computed in order to quantify the patterns and levels of integration. RESULTS: The covariation analyses show unique patterns of integration and levels of correlation in Pongo when compared to other hominids. This study shows that the craniofacial features distinguishing Pongo from African great apes are related to differences in the patterns of integration and levels of correlation between facial and mandibular shape. DISCUSSION: Changes in important functions may play a part in these modifications of craniofacial integration. This study underlines the importance of the mandible and of the mandibular functions in the development of the unique craniofacial features of Pongo.

Low- and High-Resistance Exercise: Long-Term Adherence and Motivation among Older Adults.

BACKGROUND: In terms of motivation and long-term adherence, low-resistance exercise might be more suitable for older adults than high-resistance exercise. However, more data are needed to support this claim. OBJECTIVE: The objective was to investigate the effect of low- and high-resistance exercise protocols on long-term adherence and motivation. METHODS: This study was designed as an exploratory 24-week follow-up of a randomized 12-week resistance training intervention in older adults. Participants were free to decide whether or not they continued resistance training at their own expense following the intervention. Fifty-six older adults were randomly assigned to HIGH [2 × 10-15 repetitions at 80% of one repetition maximum (1RM)], LOW (1 × 80-100 repetitions at 20% of 1RM), or LOW+ (1 × 60 repetitions at 20% of 1RM + 1 × 10-20 repetitions at 40% 1RM). Motivation, self-efficacy and the perceived barriers for continuing resistance exercise were measured after cessation of each supervised intervention and at follow-up, while long-term adherence was probed retrospectively at follow-up. RESULTS: Participants reported high levels of self-determined motivation before, during, and after the supervised intervention, with no differences between groups (p > 0.05). Nevertheless, only few participants continued strength training after the intervention: 17% in HIGH, 21% in LOW+, and 11% in LOW (p > 0.05). The most commonly reported barriers for continuing resistance exercise were perceived lack of time (46%), being more interested in other physical activities (40%), seasonal reasons (40%), and financial cost (28%). CONCLUSION: The results suggest no difference in long-term adherence after the end of a supervised exercise intervention at high or low external resistances. Long-term adherence was limited despite high levels of self-determined motivation during the interventions. These findings highlight the importance of further research on developing strategies to overcome barriers of older adults to adhere to resistance exercise without supervision.

An electro-responsive hydrogel for intravascular applications: an in vitro and in vivo evaluation.

There is a growing interest in using hydrogels for biomedical applications, because of more favourable characteristics. Some of these hydrogels can be activated by using particular stimuli, for example electrical fields. These stimuli can change the hydrogel shape in a predefined way. It could make them capable of adaptation to patient-specific anatomy even post-implantation. This is the first paper aiming to describe in vivo studies of an electro-responsive, Pluronic F127 based hydrogel, for intravascular applications. Pluronic methacrylic acid hydrogel (PF127/MANa) was in vitro tested for its haemolytic and cytotoxic effects. Minimal invasive implantation in the carotid artery of sheep was used to evaluate its medium-term biological effects, through biochemical, macroscopic, radiographic, and microscopic evaluation. Indirect and direct testing of the material gave no indication of the haemolytic effects of the material. Determination of fibroblast viability after 24 h of incubation in an extract of the hydrogel showed no cytotoxic effects. Occlusion was obtained within 1 h following in vivo implantation. Evaluation at time of autopsy showed a persistent occlusion with no systemic effects, no signs of embolization and mild effects on the arterial wall. An important proof-of-concept was obtained showing biocompatibility and effectiveness of a pluronic based electro-responsive hydrogel for obtaining an arterial occlusion with limited biological impact. So the selected pluronic-methacrylic acid based hydrogel can be used as an endovascular occlusion device. More importantly it is the first step in further development of electro-active hydrogels for a broad range of intra-vascular applications (e.g. system to prevent endoleakage in aortic aneurysm treatment, intra-vascular drug delivery).

Development and validation of a polycystic liver disease complaint-specific assessment (POLCA).

BACKGROUND & AIMS: Polycystic liver disease (PCLD) may lead to extensive hepatomegaly and invalidating complaints. Therapeutic decisions, including somatostatin-analogues (SAs) and (non)-transplant surgery are besides the existence of hepatomegaly, also guided by the severity of complaints. We developed and validated a self-report instrument to capture the presence and severity of disease specific complaints for PCLD. METHODS: The study population consisted of 129 patients. Items for the PCLD-complaint-specific assessment (POLCA) were developed based on the chart review of symptomatic PCLD patients (n=68) and literature, and discussed during expert-consensus-meetings. 61 patients who needed therapy were asked to complete the POLCA and the short form health survey version 2 (SF36V2) at baseline and after 6 months of SA-treatment. CT-scans were used to calculate liver volumes (LV). Factor analysis was conducted to identify subscales and remove suboptimal items. Reliability was assessed by Cronbach's alpha. Convergent, criterion validity and responsiveness were tested using prespecified hypotheses. RESULTS: In the validation group (n=61), 47 received lanreotide (LAN) and 14 were offered LAN as bridge to liver transplantation (LTx). Factor analysis identified four subscales, which correlated with the physical component summary (PCS). Baseline POLCA scores were significantly higher in LTx-listed patients. In contrast to SF36V2, POLCA-paired observations in 47 patients demonstrated that 2 subscales were lowered significantly and 2 borderline. LV reduction of ⩾ 120 ml resulted in a numerical, more pronounced relative decrease of all scores. CONCLUSIONS: In contrast to SF36V2, the POLCA shows good validity and responsiveness to measure complaint severity in PCLD.

Phantom study of augmented reality framework to assist epicardial punctures.

Purpose: The objective of this study is to evaluate the accuracy of an augmented reality (AR) system in improving guidance, accuracy, and visualization during the subxiphoidal approach for epicardial ablation. Approach: An AR application was developed to project real-time needle trajectories and patient-specific 3D organs using the Hololens 2. Additionally, needle tracking was implemented to offer real-time feedback to the operator, facilitating needle navigation. The AR application was evaluated through three different experiments: examining overlay accuracy, assessing puncture accuracy, and performing pre-clinical evaluations on a phantom. Results: The results of the overlay accuracy assessment for the AR system yielded 2.36±2.04 mm. Additionally, the puncture accuracy utilizing the AR system yielded 1.02±2.41 mm. During the pre-clinical evaluation on the phantom, needle puncture with AR guidance showed 7.43±2.73 mm, whereas needle puncture without AR guidance showed 22.62±9.37 mm. Conclusions: Overall, the AR platform has the potential to enhance the accuracy of percutaneous epicardial access for mapping and ablation of cardiac arrhythmias, thereby reducing complications and improving patient outcomes. The significance of this study lies in the potential of AR guidance to enhance the accuracy and safety of percutaneous epicardial access.

Association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms in giant cell arteritis.

Background: A positive PET scan at diagnosis was associated with a greater yearly increase in ascending and descending aortic diameter and thoracic aortic volume in patients with giant cell arteritis (GCA). Radiologic and histopathologic vascular abnormalities persist in a subset of treated patients despite clinical remission. The aim of this study was to evaluate the association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms. Methods: We recently performed a prospective cohort study of 106 GCA patients, who underwent FDG PET and CT imaging at diagnosis and CT imaging yearly for a maximum of 10 years. In this post hoc analysis, GCA patients who also have had FDG PET imaging during follow-up were included. PET scans were visually scored (0-3) at 7 vascular areas. PET scans were considered positive in case of FDG uptake ≥grade 2 in any large vessel. Results: Eighty-eight repeat PET scans were performed in 52 out of 106 GCA patients, who were included in the original prospective cohort. Fifty-five (63%) PET scans were done at the time of a relapse and 33 (38%) were done while in remission. Nine out of ten patients with an incident thoracic aortic aneurysm had both a positive PET scan at diagnosis and during follow-up. Conclusion: In addition to the intensity and extent of the initial vascular inflammation, ongoing aortic inflammation may contribute to the development of thoracic aortic aneurysms in GCA. However, this hypothesis should be confirmed in a large prospective trial with repeat PET scans at predefined time points during follow-up.