Citations

Abstract Background Survival in patients with IDH1/2-mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related to outcome in IDH1/2mt anaplastic astrocytoma patients. Methods The CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/− concurrent and/or adjuvant temozolomide. The presence of necrosis and/or microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were used for genome-wide DNA methylation analysis and the determination of copy number variations (CNV). Two DNA methylation-based tumor classifiers were used for risk stratification. Next-generation sequencing (NGS) was performed using 1 of the 2 glioma-tailored NGS panels. The primary endpoint was overall survival measured from the date of randomization. Results Full analysis (genome-wide DNA methylation and NGS) was successfully performed on 654 tumors. Of these, 432 tumors were IDH1/2mt anaplastic astrocytomas. Both epigenetic classifiers identified poor prognosis patients that partially overlapped. A predictive prognostic Cox proportional hazard model identified that independent prognostic factors for IDH1/2mt anaplastic astrocytoma patients included; age, mini-mental state examination score, treatment with concurrent and/or adjuvant temozolomide, the epigenetic classifiers, PDGFRA amplification, CDKN2A/B homozygous deletion, PI3K mutations, and total CNV load. Independent recursive partitioning analysis highlights the importance of these factors for patient prognostication. Conclusion Both clinical and molecular factors identify IDH1/2mt anaplastic astrocytoma patients with worse outcome. These results will further refine the current WHO criteria for glioma classification.

The development of a wide range of novel antineoplastic therapies has improved the prognosis for patients with a wide range of malignancies, which has increased the number of cancer survivors substantially. Despite the oncological benefit, cancer survivors are exposed to short- and long-term adverse cardiovascular toxicities associated with anticancer therapies. Systemic hypertension, the most common comorbidity among cancer patients, is a major contributor to the increased risk for developing these adverse cardiovascular events. Cancer and hypertension have common risk factors, have overlapping pathophysiological mechanisms and hypertension may also be a risk factor for some tumor types. Many cancer therapies have prohypertensive effects. Although some of the mechanisms by which these antineoplastic agents lead to hypertension have been characterized, further preclinical and clinical studies are required to investigate the exact pathophysiology and the optimal management of hypertension associated with anticancer therapy. In this way, monitoring and management of hypertension before, during, and after cancer treatment can be improved to minimize cardiovascular risks. This is vital to optimize cardiovascular health in patients with cancer and survivors, and to ensure that advances in terms of cancer survivorship do not come at the expense of increased cardiovascular toxicities.

Abstract Background Our understanding of the functional anatomy of the face is constantly improving. To date, it is unclear whether the anatomic location of the line of ligaments has any functional importance during normal facial movements such as smiling. Objectives The authors sought to identify differences in facial movements between the medial and lateral midface by means of skin vector displacement analyses derived from 3-dimensional (3D) imaging and to further ascertain whether the line of ligaments has both a structural and functional significance in these movements. Methods The study sample consisted of 21 healthy volunteers (9 females and 12 males) of Caucasian ethnic background with a mean age of 30.6 (8.3) years and mean BMI of 22.57 (2.5) kg/m2. 3D images of the volunteers’ faces in repose and during smiling (Duchenne type) were taken. 3D imaging-based skin vector displacement analyses were conducted. Results The mean horizontal skin displacement was 0.08 (2.0) mm in the medial midface (lateral movement) and was −0.08 (1.96) mm in the lateral midface (medial movement) (P = 0.711). The mean vertical skin displacement (cranial movement of skin toward the forehead/temple) was 6.68 (2.4) mm in the medial midface, whereas it was 5.20 (2.07) mm in the lateral midface (P = 0.003). Conclusions The results of this study provide objective evidence for an antagonistic skin movement between the medial and lateral midface. The functional boundary identified by 3D imaging corresponds to the anatomic location of the line of ligaments. Level of Evidence: 4

Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with a life-time risk of 1 in 350 people and an unmet need for disease-modifying therapies. We conducted a cross-ancestry GWAS in ALS including 29,612 ALS patients and 122,656 controls which identified 15 risk loci in ALS. When combined with 8,953 whole-genome sequenced individuals (6,538 ALS patients, 2,415 controls) and the largest cortex-derived eQTL dataset (MetaBrain), analyses revealed locus-specific genetic architectures in which we prioritized genes either through rare variants, repeat expansions or regulatory effects. ALS associated risk loci were shared with multiple traits within the neurodegenerative spectrum, but with distinct enrichment patterns across brain regions and cell-types. Of the environmental and life-style risk factors obtained from literature, Mendelian randomization analyses indicated a causal role for high cholesterol levels. All ALS associated signals combined reveal a role for perturbations in vesicle mediated transport and autophagy, and provide evidence for cell-autonomous disease initiation in glutamatergic neurons.

Abstract: When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and comprehensive presentation of consensus on the status for personalized treatment with MPA, this report was prepared following an initiative from members of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT). Topics included are the criteria for analytics, methods to estimate exposure including pharmacometrics, the potential influence of pharmacogenetics, development of biomarkers, and the practical aspects of implementation of target concentration intervention. For selected topics with sufficient evidence, such as the application of limited sampling strategies for MPA area under the curve, graded recommendations on target ranges are presented. To provide a comprehensive review, this report also includes updates on the status of potential biomarkers including those which may be promising but with a low level of evidence. In view of the fact that there are very few new immunosuppressive drugs under development for the transplant field, it is likely that MPA will continue to be prescribed on a large scale in the upcoming years. Discontinuation of therapy due to adverse effects is relatively common, increasing the risk for late rejections, which may contribute to graft loss. Therefore, the continued search for innovative methods to better personalize MPA dosage is warranted.

Abstract Background Since the emergence of the COVID-19 pandemic facecovers have become a common sight. The effect of facecovers on the gaze when looking at faces has not yet been assessed. Objectives The aim of the present study was to investigate any potential differences in eye movement pattern in observers exposed to images showing a face without and with a facecover to identify if there is truly a change of gaze when identifying (masked) facial features. Methods The eye movement of 64 study participants (28 males and 36 females) with a mean [standard deviation] age of 31.84 [9.0] years was analyzed in this cross-sectional observational study. Eye movement analysis was conducted based on positional changes of eye features within an x- and y-coordinate system while two images (face without/with facecover) were displayed for 8 seconds. Results The results of this study revealed that the sequence of focusing on facial regions was not altered when wearing a facecover and followed the sequence: perioral, nose, periorbital. Wearing a facecover significantly increased the time spent focusing on the periorbital region and also increased the number of repeated eye fixations during the 8-second visual stimulus presentation. No statistically significant differences were observed between male and female participants in their eye movement pattern across all investigated variables (P > 0.433). Conclusions The altered eye movement pattern caused by wearing facecoverings that this study has revealed suggests that, during the COVID-19 pandemic, aesthetic practitioners might consider developing marketing and treatment strategies that principally target the periorbital area.

Abstract Background The temple has been identified as one of the most compelling facial regions in which to seek aesthetic improvement—both locally and in the entire face—when injecting soft tissue fillers. Objective The objective of this study is to identify influences of age, gender, and body mass index (BMI) on temporal parameters to better understand clinical observations and to identify optimal treatment strategies for treating temporal hollowing. Methods The sample consisted of 28 male and 30 female individuals with a median age of 53 (34) years and a median BMI of 27.00 (6.94) kg/m2. The surface area of temporal skin, the surface area of temporal bones, and the temporal soft tissue volume were measured utilizing postprocessed computed tomography (CT) images via the Hausdorff minimal distance algorithm. Differences between the investigated participants related to age, BMI, and gender were calculated. Results Median skin surface area was greater in males compared with females 5,100.5 (708) mm2 versus 4,208.5 (893) mm2 (p < 0.001) as was the median bone surface area 5,329 (690) mm2 versus 4,477 (888) mm2 (p < 0.001). Males had on average 11.04 mL greater temporal soft tissue volume compared with age and BMI-matched females with p < 0.001. Comparing the volume between premenopausal versus postmenopausal females, the median temporal soft tissue volume was 46.63 mL (11.94) versus 40.32 mL (5.69) (p = 0.014). Conclusion The results of this cross-sectional CT imaging study confirmed previous clinical and anatomical observations and added numerical evidence to those observations for a better clinical integration of the data.

AbstractThe evaluation of neuromodulator treatment outcomes can be performed by noninvasive surface-derived facial electromyography (fEMG) which can detect cumulative muscle fiber activity deep to the skin. The objective of the present study is to identify the most reliable facial locations where the motor unit action potentials (MUAPs) of various facial muscles can be quantified during fEMG measurements. The study population consisted of five males and seven females (31.0 [12.9] years, body mass index of 22.15 [1.6] kg/m2). Facial muscle activity was assessed in several facial regions in each patient for their respective muscle activity utilizing noninvasive surface-derived fEMG. Variables of interest were the average root mean square of three performed muscle contractions (= signal) (µV), mean root mean square between those contraction with the face in a relaxed facial expression (= baseline noise) (µV), and the signal to noise ratio (SNR). A total of 1,709 processed fEMG signals revealed one specific reliable location in each investigated region based on each muscle's anatomy, on the highest value of the SNR, on the lowest value for the baseline noise, and on the practicability to position the sensor while performing a facial expression. The results of this exploratory study may help guiding future researchers and practitioners in designing study protocols and measuring individual facial MUAP when utilizing fEMG. The locations presented herein were selected based on the measured parameters (SNR, signal, baseline noise) and on the practicability and reproducibility of sensor placement.