Automated MRI perfusion-diffusion mismatch estimation may be significantly different in individual patients when using different software packages.

OBJECTIVE: To compare two established software applications in terms of apparent diffusion coefficient (ADC) lesion volumes, volume of critically hypoperfused brain tissue, and calculated volumes of perfusion-diffusion mismatch in brain MRI of patients with acute ischemic stroke. METHODS: Brain MRI examinations of 81 patients with acute stroke due to large vessel occlusion of the anterior circulation were analyzed. The volume of hypoperfused brain tissue, ADC volume, and the volume of perfusion-diffusion mismatch were calculated automatically with two different software packages. The calculated parameters were compared quantitatively using formal statistics. RESULTS: Significant difference was found for the volume of hypoperfused tissue (median 91.0 ml vs. 102.2 ml; p < 0.05) and the ADC volume (median 30.0 ml vs. 23.9 ml; p < 0.05) between different software packages. The volume of the perfusion-diffusion mismatch differed significantly (median 47.0 ml vs. 67.2 ml; p < 0.05). Evaluation of the results on a single-subject basis revealed a mean absolute difference of 20.5 ml for hypoperfused tissue, 10.8 ml for ADC volumes, and 27.6 ml for mismatch volumes, respectively. Application of the DEFUSE 3 threshold of 70 ml infarction core would have resulted in dissenting treatment decisions in 6/81 (7.4%) patients. CONCLUSION: Volume segmentation in different software products may lead to significantly different results in the individual patient and may thus seriously influence the decision for or against mechanical thrombectomy. KEY POINTS: • Automated calculation of MRI perfusion-diffusion mismatch helps clinicians to apply inclusion and exclusion criteria derived from randomized trials. • Infarct volume segmentation plays a crucial role and lead to significantly different result for different computer programs. • Perfusion-diffusion mismatch estimation from different computer programs may influence the decision for or against mechanical thrombectomy.

Interference and problem size effect in multiplication fact solving: Individual differences in brain activations and arithmetic performance.

In the development of math ability, a large variability of performance in solving simple arithmetic problems is observed and has not found a compelling explanation yet. One robust effect in simple multiplication facts is the problem size effect, indicating better performance for small problems compared to large ones. Recently, behavioral studies brought to light another effect in multiplication facts, the interference effect. That is, high interfering problems (receiving more proactive interference from previously learned problems) are more difficult to retrieve than low interfering problems (in terms of physical feature overlap, namely the digits, De Visscher and Noël, 2014). At the behavioral level, the sensitivity to the interference effect is shown to explain individual differences in the performance of solving multiplications in children as well as in adults. The aim of the present study was to investigate the individual differences in multiplication ability in relation to the neural interference effect and the neural problem size effect. To that end, we used a paradigm developed by De Visscher, Berens, et al. (2015) that contrasts the interference effect and the problem size effect in a multiplication verification task, during functional magnetic resonance imaging (fMRI) acquisition. Forty-two healthy adults, who showed high variability in an arithmetic fluency test, participated in our fMRI study. In order to control for the general reasoning level, the IQ was taken into account in the individual differences analyses. Our findings revealed a neural interference effect linked to individual differences in multiplication in the left inferior frontal gyrus, while controlling for the IQ. This interference effect in the left inferior frontal gyrus showed a negative relation with individual differences in arithmetic fluency, indicating a higher interference effect for low performers compared to high performers. This region is suggested in the literature to be involved in resolution of proactive interference. Besides, no correlation between the neural problem size effect and multiplication performance was found. This study supports the idea that the interference due to similarities/overlap of physical traits (the digits) is crucial in memorizing arithmetic facts and in determining individual differences in arithmetic.

Detection and volume estimation of artificial hematomas in the subcutaneous fatty tissue: comparison of different MR sequences at 3.0 T.

In legal medicine, reliable localization and analysis of hematomas in subcutaneous fatty tissue is required for forensic reconstruction. Due to the absence of ionizing radiation, magnetic resonance imaging (MRI) is particularly suited to examining living persons with forensically relevant injuries. However, there is limited experience regarding MRI signal properties of hemorrhage in soft tissue. The aim of this study was to evaluate MR sequences with respect to their ability to show high contrast between hematomas and subcutaneous fatty tissue as well as to reliably determine the volume of artificial hematomas. Porcine tissue models were prepared by injecting blood into the subcutaneous fatty tissue to create artificial hematomas. MR images were acquired at 3T and four blinded observers conducted manual segmentation of the hematomas. To assess segmentability, the agreement of measured volume with the known volume of injected blood was statistically analyzed. A physically motivated normalization taking into account partial volume effect was applied to the data to ensure comparable results among differently sized hematomas. The inversion recovery sequence exhibited the best segmentability rate, whereas the T1T2w turbo spin echo sequence showed the most accurate results regarding volume estimation. Both sequences led to reproducible volume estimations. This study demonstrates that MRI is a promising forensic tool to assess and visualize even very small amounts of blood in soft tissue. The presented results enable the improvement of protocols for detection and volume determination of hemorrhage in forensically relevant cases and also provide fundamental knowledge for future in-vivo examinations.

Contrast of artificial subcutaneous hematomas in MRI over time.

In clinical forensic medicine, hematomas and other externally visible injuries build the basis for the reconstruction of events. However, dating of subcutaneous hematomas based on their external aspect is difficult. Magnetic resonance imaging (MRI) has proven its use in dating intracranial hemorrhage. Thus, the aim was to investigate if MRI can also be used for dating subcutaneous hematomas and to analyze an eventual influence of the hematoma shape. In 20 healthy volunteers (11 females, 9 males, aged 26.9 ± 3.8 years), 4 ml of autologous blood were injected subcutaneously in the thigh. The hematoma was scanned immediately after the injection, after 3 and 24 h and 3, 7, and 14 days using three sequences with different contrast. Data was analyzed by measuring signal intensities of the hematoma, the muscle, and the subcutaneous tissue over time, and the Michelson contrast coefficients between the tissues were calculated. In the analysis, hematoma shape was considered. Signal intensity of blood in the proton density-weighted sequence reached its maximum 3 h after the injection with a subsequent decrease, whereas the signal intensities of muscle and fatty tissue remained constant. The time course of the Michelson coefficient of blood versus muscle decreased exponentially with a change from hyperintensity to hypointensity at 116.9 h, depending on hematoma shape. In the other sequences, either variability was large or contrast coefficients stayed constant over time. The observed change of contrast of blood versus muscle permits a quick estimate of a hematoma's age. The consideration of the hematoma shape is expected to further enhance dating using MRI.

Age determination of soft tissue hematomas.

In clinical forensic medicine, the estimation of the age of injuries such as externally visible subcutaneous hematomas is important for the reconstruction of violent events, particularly to include or exclude potential suspects. Since the estimation of the time of origin based on external inspection is unreliable, the aim of this study was to use contrast in MRI to develop an easy-to-use model for hematoma age estimation. In a longitudinal study, artificially created subcutaneous hematomas were repetitively imaged using MRI over a period of two weeks. The hemorrhages were created by injecting autologous blood into the subcutaneous tissue of the thigh in 20 healthy volunteers. For MRI, standard commercially available sequences, namely proton-density-weighted, T2 -weighted and inversion recovery sequences, were used. The hematomas' MRI data were analyzed regarding their contrast behavior using the most suitable sequences to derive a model allowing an objective estimation of the age of soft tissue hematomas. The Michelson contrast between hematoma and muscle in the proton-density-weighted sequence showed an exponentially decreasing behavior with a dynamic range of 0.6 and a maximum standard deviation of 0.1. The contrast of the inversion recovery sequences showed increasing characteristics and was hypointense for TI = 200ms and hyperintense for TI =1000ms. These sequences were used to create a contrast model. The cross-validation of the model finally yielded limits of agreement for hematoma age determination (corresponding to ±1.96 SD) of ±38.7h during the first three days and ±54 h for the entire investigation period. The developed model provides lookup tables which allow for the estimation of a hematoma's age given a single contrast measurement applicable by a radiologist or a forensic physician. This is a first step towards an accurate and objective dating method for subcutaneous hematomas, which will be particularly useful in child abuse.

Wall Enhancement of Coiled Intracranial Aneurysms Is Associated with Aneurysm Recanalization: A Cross-Sectional Study.

BACKGROUND AND PURPOSE: Wall enhancement of untreated intracranial aneurysms on MR imaging is thought to predict aneurysm instability. Wall enhancement or enhancement of the aneurysm cavity in coiled intracranial aneurysms is discussed controversially in the literature regarding potential healing mechanisms or adverse inflammatory reactions. Our aim was to compare the occurrence of aneurysm wall enhancement and cavity enhancement between completely occluded intracranial aneurysms and recanalized aneurysms after initially complete coil embolization. MATERIALS AND METHODS: In this single-center cross-sectional study, we evaluated intracranial aneurysms after successful coil embolization for aneurysm recanalization, wall enhancement, and cavity enhancement with 3T MR imaging. We then compared the incidence of wall enhancement and cavity enhancement of completely occluded aneurysms with aneurysms with recanalization using the χ2 test and performed a multivariate linear regression analysis with recanalization size as an independent variable. RESULTS: We evaluated 59 patients (mean age, 54.7 [SD, 12.4] years; 48 women) with 60 intracranial aneurysms and found a significantly higher incidence of wall enhancement in coiled aneurysms with recanalization (n=38) compared with completely occluded aneurysms (n = 22, P = .036). In addition, there was a significantly higher incidence of wall enhancement in aneurysms with recanalization of >3 mm (P = .003). In a multivariate linear regression analysis, wall enhancement (P = .010) and an increase of overall aneurysm size after embolization (P < .001) were significant predictors of recanalization size (corrected R 2= 0.430, CI 95%). CONCLUSIONS: The incidence of aneurysm wall enhancement is increased in coiled intracranial aneurysms with recanalization and is associated with recanalization size.

A perspective on muscle phenotyping in musculoskeletal research.

Musculoskeletal research should synergistically investigate bone and muscle to inform approaches for maintaining mobility and to avoid bone fractures. The relationship between sarcopenia and osteoporosis, integrated in the term 'osteosarcopenia', is underscored by the close association shown between these two conditions in many studies, whereby one entity emerges as a predictor of the other. In a recent workshop of Working Group (WG) 2 of the EU Cooperation in Science and Technology (COST) Action 'Genomics of MusculoSkeletal traits Translational Network' (GEMSTONE) consortium (CA18139), muscle characterization was highlighted as being important, but currently under-recognized in the musculoskeletal field. Here, we summarize the opinions of the Consortium and research questions around translational and clinical musculoskeletal research, discussing muscle phenotyping in human experimental research and in two animal models: zebrafish and mouse.

Fever and pneumonitis induced by enteric-coated mycophenolate sodium in a patient after kidney transplantation.

Here, we report on a patient after kidney transplantation, who developed fever and pneumonitis due to mycophenolic acid (MPA) treatment. Decreasing MPA dosages improved the symptoms, but after rechallenge with higher MPA doses the symptoms recurred. Discontinuation of MPA resulted in a complete resolution of fever within 24 h and a rapid improvement in pneumonitis. In vitro, the patient's polymorphonuclear neutrophils (PMNs) developed increased oxidative burst when incubated with MPA and N-formyl Met-Leu-Phe. We first report on MPA-induced pneumonitis and show that MPA can induce a pro-inflammatory response in kidney-transplanted patients. These pro-inflammatory changes might be due to paradoxical activation of PMNs.

Information extraction from German radiological reports for general clinical text and language understanding.

Recent advances in deep learning and natural language processing (NLP) have opened many new opportunities for automatic text understanding and text processing in the medical field. This is of great benefit as many clinical downstream tasks rely on information from unstructured clinical documents. However, for low-resource languages like German, the use of modern text processing applications that require a large amount of training data proves to be difficult, as only few data sets are available mainly due to legal restrictions. In this study, we present an information extraction framework that was initially pre-trained on real-world computed tomographic (CT) reports of head examinations, followed by domain adaptive fine-tuning on reports from different imaging examinations. We show that in the pre-training phase, the semantic and contextual meaning of one clinical reporting domain can be captured and effectively transferred to foreign clinical imaging examinations. Moreover, we introduce an active learning approach with an intrinsic strategic sampling method to generate highly informative training data with low human annotation cost. We see that the model performance can be significantly improved by an appropriate selection of the data to be annotated, without the need to train the model on a specific downstream task. With a general annotation scheme that can be used not only in the radiology field but also in a broader clinical setting, we contribute to a more consistent labeling and annotation process that also facilitates the verification and evaluation of language models in the German clinical setting.

The Pre-Treatment Platelet-to-Lymphocyte Ratio as a Prognostic Factor for Loco-Regional Control in Locally Advanced Rectal Cancer.

Chronic inflammatory reactions have been proven to represent relevant mechanisms for the development and progression of cancer in numerous tumor entities. There is evidence that the platelet-to-lymphocyte ratio (PLR) is associated with the prognostic outcome. In rectal cancer, the prognostic role of this parameter has not yet been conclusively clarified. The aim of this study was to further clarify the prognostic significance of the pre-treatment PLR in patients with locally advanced rectal cancer (LARC). In the present study, 603 patients with LARC, who were treated with neoadjuvant chemoradiotherapy (nCRT) and subsequent surgical resection between 2004 and 2019, were retrospectively evaluated. The influence of clinico-pathological and laboratory factors on locoregional control (LC), metastasis-free survival (MFS) and overall survival (OS) was investigated. In univariate analyses, high PLR was significantly associated with worse LC (p = 0.017) and OS (p = 0.008). In multivariate analyses, the PLR remained an independent parameter for the LC (HR = 1.005, 95% CI: 1.000-1.009, p = 0.050). Pre-treatment lactate dehydrogenase (LDH) (HR: 1.005 95% CI:1.002-1.008; p = 0.001) and carcinoembryonic antigen (CEA) (HR: 1.006, 95% CI:1.003-1.009; p < 0.001) were independent predictors for MFS; additionally, age (HR: 1.052, 95% CI:1.023-1.081; p < 0.001), LDH (HR: 1.003, 95% CI:1.000-1.007; p = 0.029) and CEA (HR: 1.006, 95% CI:1.003-1.009; p < 0.001) independently predicted OS. Pre-treatment PLR before nCRT is an independent prognostic factor for LC in LARC, which could be used to further individualize tumor treatment.

Reproducibility of artificial intelligence models in computed tomography of the head: a quantitative analysis.

When developing artificial intelligence (AI) software for applications in radiology, the underlying research must be transferable to other real-world problems. To verify to what degree this is true, we reviewed research on AI algorithms for computed tomography of the head. A systematic review was conducted according to the preferred reporting items for systematic reviews and meta-analyses. We identified 83 articles and analyzed them in terms of transparency of data and code, pre-processing, type of algorithm, architecture, hyperparameter, performance measure, and balancing of dataset in relation to epidemiology. We also classified all articles by their main functionality (classification, detection, segmentation, prediction, triage, image reconstruction, image registration, fusion of imaging modalities). We found that only a minority of authors provided open source code (10.15%, n 0 7), making the replication of results difficult. Convolutional neural networks were predominantly used (32.61%, n = 15), whereas hyperparameters were less frequently reported (32.61%, n = 15). Data sets were mostly from single center sources (84.05%, n = 58), increasing the susceptibility of the models to bias, which increases the error rate of the models. The prevalence of brain lesions in the training (0.49 ± 0.30) and testing (0.45 ± 0.29) datasets differed from real-world epidemiology (0.21 ± 0.28), which may overestimate performances. This review highlights the need for open source code, external validation, and consideration of disease prevalence.

Incidence of Developmental Venous Anomalies in Patients With Multiple Sclerosis: A 3 Tesla MRI Study.

Objectives: There is evidence of involvement of the venous system in multiple sclerosis (MS). If this bears also an association with the frequency and extent of developmental venous anomalies (DVA) still has to be determined. We therefore investigated this in patients with different phenotypes of MS and in comparison, to a control population. Methods: We analyzed the contrast-enhanced T1-weighted MR scans of 431 patients (clinically isolated syndrome-CIS, n = 108; MS, n = 323) and of 162 control individuals for the presence of a DVA. We also measured the size of the DVA and draining vein and compared the DVA frequency between MS phenotypes. Results: A DVA was found in 38 (8.8 %) of patients with CIS or MS and in 11 (6.8%) controls (p = 0.4). DVA frequency was highest in CIS (14.8%) and lowest in progressive MS (4.0%). The mean cranio-caudal and axial extension of the DVA was significantly lower in MS patients than controls (p < 0.05). Conclusions: The frequency of DVA in MS patients is comparable to that in controls. Whether DVA size and appearance may change over time will have to be investigated in a longitudinal manner and with larger sample size.

Can Pre-Treatment Inflammatory Parameters Predict the Probability of Sphincter-Preserving Surgery in Patients with Locally Advanced Low-Lying Rectal Cancer?

There is evidence suggesting that pre-treatment clinical parameters can predict the probability of sphincter-preserving surgery in rectal cancer; however, to date, data on the predictive role of inflammatory parameters on the sphincter-preservation rate are not available. The aim of the present cohort study was to investigate the association between inflammation-based parameters and the sphincter-preserving surgery rate in patients with low-lying locally advanced rectal cancer (LARC). A total of 848 patients with LARC undergoing radiotherapy from 2004 to 2019 were retrospectively reviewed in order to identify patients with rectal cancer localized ≤6 cm from the anal verge, treated with neo-adjuvant radiochemotherapy (nRCT) and subsequent surgery. Univariable and multivariable analyses were used to investigate the role of pre-treatment inflammatory parameters, including the C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) for the prediction of sphincter preservation. A total of 363 patients met the inclusion criteria; among them, 210 patients (57.9%) underwent sphincter-preserving surgery, and in 153 patients (42.1%), an abdominoperineal rectum resection was performed. Univariable analysis showed a significant association of the pre-treatment CRP value (OR = 2.548, 95% CI: 1.584-4.097, p < 0.001) with sphincter preservation, whereas the pre-treatment NLR (OR = 1.098, 95% CI: 0.976-1.235, p = 0.120) and PLR (OR = 1.002, 95% CI: 1.000-1.005, p = 0.062) were not significantly associated with the type of surgery. In multivariable analysis, the pre-treatment CRP value (OR = 2.544; 95% CI: 1.314-4.926; p = 0.006) was identified as an independent predictive factor for sphincter-preserving surgery. The findings of the present study suggest that the pre-treatment CRP value represents an independent parameter predicting the probability of sphincter-preserving surgery in patients with low-lying LARC.

Sex-Specific Association of Serum Anti-Oxidative Capacity and Leukocyte Telomere Length.

Telomeres are a crucial factor in the preservation of genomic integrity, and an elevated risk for diseases such as cancer and cardiovascular events is related to shortened telomeres. However, telomere deterioration could be caused by factors such as chronic oxidative stress and inflammation, which are promoted by an imbalance among reactive oxygen species (ROS) and antioxidants. In this cross-sectional study, we investigated the relationship between telomeres and oxidative stress. The serum leucocyte telomer length (LTL), serum total antioxidant capacity (TAC) and the total serum lipid panel of 180 healthy athletic volunteers (90 males, 90 females) were measured Additionally, a questionnaire about sports behaviour and the type of training was completed. We observed a positive significant relation between serum LTL and TAC in the male group (cc = 3.4/p = 0.001) but not in females. There was no statistically significant correlation between age and physical activity and LTL in both groups. This is the first cross sectional study demonstrating an association between total serum TAC and LTL in healthy males, but interestingly, not in the females. Nevertheless, these results should be interpreted as preliminary, and further studies in independent cohorts are needed to investigate the sex-specific effects of oxidative stress on telomere length and telomerase activity.

Investigation of the Relationship between the Mid_Thigh Adipose Tissue Distribution Measured by MRI and Serum Osteocalcin-A Sex-Based Approach.

Osteocalcin, in its non-carboxylated form, has a positive effect on glucose metabolism. Additionally, osteocalcin levels are related to body composition, especially muscle mass. The relation to the distribution of different adipose tissue types, such as subcutaneous, intermuscular, and visceral adipose tissue, is unclear. This study aimed to investigate associations between serum osteocalcin and the distribution of subcutaneous and intermuscular adipose tissue of the mid-thigh. Furthermore, the influence of different training methods on osteocalcin levels was investigated. We performed adipose tissue quantification of subcutaneous adipose tissue (SAT) and intramuscular adipose tissue (IMAT) using MRI measurements of the mid-thigh in 128 volunteers (63 male/65 female). Laboratory analysis included blood lipid panel, serum insulin, adiponectin, and osteocalcin measurements. The main observation was a significant correlation of total serum osteocalcin (TOC) and the distribution of adipose tissue of the mid-thigh (SAT/(SAT + IMAT)) (cc = -0.29/p-value = 0.002), as well as the cross-sectional muscle area (MA), increasing with the weekly resistance training duration in males. Additionally, TOC (p-value = 0.01) and MA (p-value = 0.03) were negatively related to serum insulin. The significant relationship between TOC and SAT/(SAT + IMAT) is a new finding and confirms the negative influence of IMAT on glucose metabolism in a sex-specific approach. We could substantiate this by the negative relation of TOC with serum insulin.

Acute suppurative thyroiditis due to Streptococcus anginosus leading to sepsis and acute respiratory distress syndrome: a case report.

Acute suppurative thyroiditis (AST) is a rare but potentially life-threatening thyroid disease with a high mortality if left untreated. Thus, differentiation from other thyroid disorders is highly important in clinical practice. A 22-year-old male patient was admitted to a tertiary care hospital with cervical pain, palpitations, thyrotoxicosis, and an inhomogeneously enlarged right thyroid lobe. In view of the clinical findings, subacute thyroiditis (SAT) was suspected and treatment with glucocorticoids was started. After initial amelioration, the patient developed cervical erythema, fever, and recurrent pain. A CT scan showed extensive phlegmonous inflammation and abscess formation, suggestive of AST. We started immediate empiric antibiotic therapy and performed surgical drainage of the abscess formations. Subsequently, the patient developed hypoxic respiratory failure, leading to ICU admission and intermittent need for non-invasive ventilation. Blood and abscess cultures were positive for Streptococcus anginosus. If left untreated, AST represents a potentially life-threatening disease. Thus, in clinically doubtful cases, liberal further assessment by means of cervical CT scans or fine needle aspiration biopsy are strongly advised.

Distribution of subcutaneous and intermuscular fatty tissue of the mid-thigh measured by MRI-A putative indicator of serum adiponectin level and individual factors of cardio-metabolic risk.

Obesity and metabolic syndrome (MetS) are associated with hypoadiponectinemia. On the contrary, studies revealed correlations between the amount of subcutaneous adipose tissue (SAT) and higher serum adiponectin levels. Furthermore, independent association of intermuscular adipose tissue (IMAT) deposit in the thigh with cardiometabolic risk factors (including total blood cholesterol, low-density lipoprotein (LDL), and triglycerides), and decreased insulin sensitivity, as MetS components, are sufficiently described. The combined relationship of thigh IMAT and SAT with serum adiponectin, leptin levels, and cardiometabolic risk factors have not been investigated till date. Since both SAT and IMAT play a role in fat metabolism, we hypothesized that the distribution pattern of SAT and IMAT in the mid-thigh might be related to adiponectin, leptin levels, and serum lipid parameters. We performed adipose tissue quantification using magnetic resonance imaging (MRI) of the mid-thigh in 156 healthy volunteers (78 male/78 female). Laboratory measurements of lipid panel, serum adiponectin, and leptin levels were conducted. Total serum adiponectin level showed a significant correlation with the percentage of SAT of the total thigh adipose tissue (SAT/ (IMAT+SAT)) for the whole study population and in sex-specific analysis. Additionally, SAT/(IMAT+SAT) was negatively correlated with known cardiometabolic risk factors such as elevated total blood cholesterol, LDL, and triglycerides; but positively correlated with serum high-density lipoprotein. In multiple linear regression analysis, (SAT/(IMAT+SAT)) was the most strongly associated variable with adiponectin. Interestingly, leptin levels did not show a significant correlation with this ratio. Adipose tissue distribution in the mid-thigh is not only associated to serum adiponectin levels, independent of sex. This proposed quantitative parameter for adipose tissue distribution could be an indicator for individual factors of a person`s cardiometabolic risk and serve as additional non-invasive imaging marker to ensure the success of lifestyle interventions.

Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals - including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing -omics data in order to advance musculoskeletal research and move towards "personalised medicine".

Clinical parameters predictive for sphincter-preserving surgery and prognostic outcome in patients with locally advanced low rectal cancer.

BACKGROUND: Although controversial, there are data suggesting that clinical parameters can predict the probability of sphincter preserving procedures in rectal cancer. The purpose of this study was to investigate the association between clinical parameters and the sphincter-preserving surgery rate in patients who had undergone neoadjuvant combination therapy for advanced low rectal cancer. METHODS: In this single center study, the charts of 540 patients with locally advanced rectal cancer who had been treated with induction chemotherapy-and/or neoadjuvant concomitant radiochemotherapy (nRCT) over an 11-year period were reviewed in order to identify patients with rectal cancer ≤6 cm from the anal verge, who had received the prescribed nRCT only. Univariate and multivariate analyses were used to identify pretreatment patient- and tumor associated parameters correlating with sphincter preservation. Survival rates were calculated using Kaplan-Meier analyses. RESULTS: Two hundred eighty of the 540 patients met the selection criteria. Of the 280 patients included in the study, 158 (56.4%) underwent sphincter-preserving surgery. One hundred sixty-four of 280 patients (58.6%) had a downsizing of the primary tumor (ypT < cT) and 39 (23.8%) of these showed a complete histopathological response (ypT0 ypN0). In univariate analysis, age prior to treatment, Karnofsky performance status, clinical T-size, relative lymphocyte value, CRP value, and interval between nRCT and surgery, were significantly associated with sphincter-preserving surgery. In multivariate analysis, age (hazard ratio (HR) = 1.05, CI95%: 1.02-1.09, p = 0.003), relative lymphocyte value (HR = 0.94, CI95%: 0.89-0.99, p = 0.029), and interval between nRCT and surgery (HR = 2.39, CI95%: 1.17-4.88, p = 0.016) remained as independent predictive parameters. CONCLUSIONS: These clinical parameters can be considered in the prognostication of sphincter-preserving surgery in case of low rectal adenocarcinoma. More future research is required in this area.

Relationship between stroke etiology and collateral status in anterior circulation large vessel occlusion.

BACKGROUND AND PURPOSE: Clinical outcome after mechanical thrombectomy (MT) for large vessel occlusion (LVO) stroke is influenced by the intracerebral collateral status. We tested the hypothesis that patients with preexisting ipsilateral extracranial carotid artery stenosis (CAS) would have a better collateral status compared to non-CAS patients. Additionally, we evaluated MT-related adverse events and outcome for both groups. METHODS: Over a 7-year period, we identified all consecutive anterior circulation MT patients (excluding extracranial carotid artery occlusion and dissection). Patients were grouped into those with CAS ≥ 50% according to the NASCET criteria and those without significant carotid stenosis (non-CAS). Collateral status was rated on pre-treatment CT- or MR-angiography according to the Tan Score. Furthermore, we assessed postinterventional infarct size, adverse events and functional outcome at 90 days. RESULTS: We studied 281 LVO stroke patients, comprising 46 (16.4%) with underlying CAS ≥ 50%. Compared to non-CAS stroke patients (n = 235), patients with CAS-related stroke more often had favorable collaterals (76.1% vs. 46.0%). Recanalization rates were comparable between both groups. LVO stroke patients with underlying CAS more frequently had adverse events after MT (19.6% vs. 6.4%). Preexisting CAS was an independent predictor for favorable collateral status in multivariable models (Odds ratio: 3.3, p = 0.002), but post-interventional infarct size and functional 90-day outcome were not different between CAS and non-CAS patients. CONCLUSIONS: Preexisting CAS ≥ 50% was associated with better collateral status in LVO stroke patients. However, functional 90-day outcome was independent from CAS, which could be related to a higher rate of adverse events.