Radiomics workflow definition & challenges - German priority program 2177 consensus statement on clinically applied radiomics.

OBJECTIVES: Achieving a consensus on a definition for different aspects of radiomics workflows to support their translation into clinical usage. Furthermore, to assess the perspective of experts on important challenges for a successful clinical workflow implementation. MATERIALS AND METHODS: The consensus was achieved by a multi-stage process. Stage 1 comprised a definition screening, a retrospective analysis with semantic mapping of terms found in 22 workflow definitions, and the compilation of an initial baseline definition. Stages 2 and 3 consisted of a Delphi process with over 45 experts hailing from sites participating in the German Research Foundation (DFG) Priority Program 2177. Stage 2 aimed to achieve a broad consensus for a definition proposal, while stage 3 identified the importance of translational challenges. RESULTS: Workflow definitions from 22 publications (published 2012-2020) were analyzed. Sixty-nine definition terms were extracted, mapped, and semantic ambiguities (e.g., homonymous and synonymous terms) were identified and resolved. The consensus definition was developed via a Delphi process. The final definition comprising seven phases and 37 aspects reached a high overall consensus (> 89% of experts "agree" or "strongly agree"). Two aspects reached no strong consensus. In addition, the Delphi process identified and characterized from the participating experts' perspective the ten most important challenges in radiomics workflows. CONCLUSION: To overcome semantic inconsistencies between existing definitions and offer a well-defined, broad, referenceable terminology, a consensus workflow definition for radiomics-based setups and a terms mapping to existing literature was compiled. Moreover, the most relevant challenges towards clinical application were characterized. CRITICAL RELEVANCE STATEMENT: Lack of standardization represents one major obstacle to successful clinical translation of radiomics. Here, we report a consensus workflow definition on different aspects of radiomics studies and highlight important challenges to advance the clinical adoption of radiomics. KEY POINTS: Published radiomics workflow terminologies are inconsistent, hindering standardization and translation. A consensus radiomics workflow definition proposal with high agreement was developed. Publicly available result resources for further exploitation by the scientific community.

Cooperative AI training for cardiothoracic segmentation in computed tomography: An iterative multi-center annotation approach.

PURPOSE: Radiological reporting is transitioning to quantitative analysis, requiring large-scale multi-center validation of biomarkers. A major prerequisite and bottleneck for this task is the voxelwise annotation of image data, which is time-consuming for large cohorts. In this study, we propose an iterative training workflow to support and facilitate such segmentation tasks, specifically for high-resolution thoracic CT data. METHODS: Our study included 132 thoracic CT scans from clinical practice, annotated by 13 radiologists. In three iterative training experiments, we aimed to improve and accelerate segmentation of the heart and mediastinum. Each experiment started with manual segmentation of 5-25 CT scans, which served as training data for a nnU-Net. Further iterations incorporated AI pre-segmentation and human correction to improve accuracy, accelerate the annotation process, and reduce human involvement over time. RESULTS: Results showed consistent improvement in AI model quality with each iteration. Resampled datasets improved the Dice similarity coefficients for both the heart (DCS 0.91 [0.88; 0.92]) and the mediastinum (DCS 0.95 [0.94; 0.95]). Our AI models reduced human interaction time by 50 % for heart and 70 % for mediastinum segmentation in the most potent iteration. A model trained on only five datasets achieved satisfactory results (DCS > 0.90). CONCLUSIONS: The iterative training workflow provides an efficient method for training AI-based segmentation models in multi-center studies, improving accuracy over time and simultaneously reducing human intervention. Future work will explore the use of fewer initial datasets and additional pre-processing methods to enhance model quality.

Tissue-specific inflammation and insulin sensitivity in subjects with obesity.

Obesity is associated with low-grade inflammation and insulin resistance (IR). The contribution of adipose tissue (AT) and hepatic inflammation to IR remains unclear. We conducted a study across three cohorts to investigate this relationship. The first cohort consists of six women with normal weight and twenty with obesity. In women with obesity, we found an upregulation of inflammatory markers in subcutaneous and visceral adipose tissue, isolated AT macrophages, and the liver, but no linear correlation with tissue-specific insulin sensitivity. In the second cohort, we studied 24 women with obesity in the upper vs lower insulin sensitivity quartile. We demonstrated that several omental and mesenteric AT inflammatory genes and T cell-related pathways are upregulated in IR, independent of BMI. The third cohort consists of 23 women and 18 men with obesity, studied before and one year after bariatric surgery. Weight loss following surgery was associated with downregulation of multiple immune pathways in subcutaneous AT and skeletal muscle, alongside notable metabolic improvements. Our results show that obesity is characterised by systemic and tissue-specific inflammation. Subjects with obesity and IR show a more pronounced inflammation phenotype, independent of BMI. Bariatric surgery-induced weight loss is associated with reduced inflammation and improved metabolic health.

Impact of the coronavirus disease 2019 (COVID-19) pandemic on the presentation of paediatric acute appendicitis: an observational study.

AIM: To determine whether there were differences in the clinical presentation of patients imaged to evaluate for acute appendicitis in 2020 compared to 2019 with the hope that this information might better identify patients who should undergo imaging work-up and those who should not. MATERIALS AND METHODS: This retrospective observational study included patients <18 years who were evaluated for appendicitis between 1 March and 31 May 2019 and 2020. A total of 465 patients were stratified by final diagnosis (appendicitis versus not appendicitis) and compared based on presenting symptoms, physical examination findings, vital signs, and laboratory test results. RESULTS: Symptoms and physical examination findings that were significant in the positive cohort in both years included right lower quadrant pain, pain with movement, migration of pain, right lower quadrant tenderness, and peritoneal findings. Reporting upper respiratory symptoms was an independent predictor of negative results among all patients and in 2019. Both negative cohorts were more likely to have negative physical examinations. Anorexia and nausea/vomiting were more likely among positive cases in 2019 whereas diarrhoea was more likely among positive cases in 2020. CONCLUSIONS: The COVID-19 pandemic did not significantly change the presenting features of acute appendicitis. The results of the present study emphasise the importance of the physical examination. The ambiguity of symptoms that mimic gastroenteritis justifies imaging in these patients.

Quantitative evaluation of the influence of multiple MRI sequences and of pathological tissues on the registration of longitudinal data acquired during brain tumor treatment.

Registration methods facilitate the comparison of multiparametric magnetic resonance images acquired at different stages of brain tumor treatments. Image-based registration solutions are influenced by the sequences chosen to compute the distance measure, and the lack of image correspondences due to the resection cavities and pathological tissues. Nonetheless, an evaluation of the impact of these input parameters on the registration of longitudinal data is still missing. This work evaluates the influence of multiple sequences, namely T1-weighted (T1), T2-weighted (T2), contrast enhanced T1-weighted (T1-CE), and T2 Fluid Attenuated Inversion Recovery (FLAIR), and the exclusion of the pathological tissues on the non-rigid registration of pre- and post-operative images. We here investigate two types of registration methods, an iterative approach and a convolutional neural network solution based on a 3D U-Net. We employ two test sets to compute the mean target registration error (mTRE) based on corresponding landmarks. In the first set, markers are positioned exclusively in the surroundings of the pathology. The methods employing T1-CE achieves the lowest mTREs, with a improvement up to 0.8 mm for the iterative solution. The results are higher than the baseline when using the FLAIR sequence. When excluding the pathology, lower mTREs are observable for most of the methods. In the second test set, corresponding landmarks are located in the entire brain volumes. Both solutions employing T1-CE obtain the lowest mTREs, with a decrease up to 1.16 mm for the iterative method, whereas the results worsen using the FLAIR. When excluding the pathology, an improvement is observable for the CNN method using T1-CE. Both approaches utilizing the T1-CE sequence obtain the best mTREs, whereas the FLAIR is the least informative to guide the registration process. Besides, the exclusion of pathology from the distance measure computation improves the registration of the brain tissues surrounding the tumor. Thus, this work provides the first numerical evaluation of the influence of these parameters on the registration of longitudinal magnetic resonance images, and it can be helpful for developing future algorithms.

Anisotropic 3D Multi-Stream CNN for Accurate Prostate Segmentation from Multi-Planar MRI.

BACKGROUND AND OBJECTIVE: Accurate and reliable segmentation of the prostate gland in MR images can support the clinical assessment of prostate cancer, as well as the planning and monitoring of focal and loco-regional therapeutic interventions. Despite the availability of multi-planar MR scans due to standardized protocols, the majority of segmentation approaches presented in the literature consider the axial scans only. In this work, we investigate whether a neural network processing anisotropic multi-planar images could work in the context of a semantic segmentation task, and if so, how this additional information would improve the segmentation quality. METHODS: We propose an anisotropic 3D multi-stream CNN architecture, which processes additional scan directions to produce a high-resolution isotropic prostate segmentation. We investigate two variants of our architecture, which work on two (dual-plane) and three (triple-plane) image orientations, respectively. The influence of additional information used by these models is evaluated by comparing them with a single-plane baseline processing only axial images. To realize a fair comparison, we employ a hyperparameter optimization strategy to select optimal configurations for the individual approaches. RESULTS: Training and evaluation on two datasets spanning multiple sites show statistical significant improvement over the plain axial segmentation (p<0.05 on the Dice similarity coefficient). The improvement can be observed especially at the base (0.898 single-plane vs. 0.906 triple-plane) and apex (0.888 single-plane vs. 0.901 dual-plane). CONCLUSION: This study indicates that models employing two or three scan directions are superior to plain axial segmentation. The knowledge of precise boundaries of the prostate is crucial for the conservation of risk structures. Thus, the proposed models have the potential to improve the outcome of prostate cancer diagnosis and therapies.

Automated density-based counting of FISH amplification signals for HER2 status assessment.

BACKGROUND: Automated image analysis can make quantification of FISH signals in histological sections more efficient and reproducible. Current detection-based methods, however, often fail to accurately quantify densely clustered FISH signals. METHODS: We propose a novel density-based approach to quantifying FISH signals. Instead of detecting individual signals, this approach quantifies FISH signals in terms of the integral over a density map predicted by Deep Learning. We apply the density-based approach to the task of counting and determining ratios of ERBB2 and CEN17 signals and compare it to common detection-based and area-based approaches. RESULTS: The ratios determined by our approach were strongly correlated with results obtained by manual annotation of individual FISH signals (Pearson's r = 0.907). In addition, they were highly consistent with cutoff-scores determined by a pathologist (balanced concordance = 0.971). The density-based approach generally outperformed the other approaches. Its superiority was particularly evident in the presence of dense signal clusters. CONCLUSIONS: The presented approach enables accurate and efficient automated quantification of FISH signals. Since signals in clusters can hardly be detected individually even by human observers, the density-based quantification performs better than detection-based approaches.

Evaluation of deep learning methods for parotid gland segmentation from CT images.

The segmentation of organs at risk is a crucial and time-consuming step in radiotherapy planning. Good automatic methods can significantly reduce the time clinicians have to spend on this task. Due to its variability in shape and low contrast to surrounding structures, segmenting the parotid gland is challenging. Motivated by the recent success of deep learning, we study the use of two-dimensional (2-D), 2-D ensemble, and three-dimensional (3-D) U-Nets for segmentation. The mean Dice similarity to ground truth is ∼ 0.83 for all three models. A patch-based approach for class balancing seems promising for false-positive reduction. The 2-D ensemble and 3-D U-Net are applied to the test data of the 2015 MICCAI challenge on head and neck autosegmentation. Both deep learning methods generalize well onto independent data (Dice 0.865 and 0.88) and are superior to a selection of model- and atlas-based methods with respect to the Dice coefficient. Since appropriate reference annotations are essential for training but often difficult and expensive to obtain, it is important to know how many samples are needed for training. We evaluate the performance after training with different-sized training sets and observe no significant increase in the Dice coefficient for more than 250 training cases.

Deep learning nuclei detection: A simple approach can deliver state-of-the-art results.

BACKGROUND: Deep convolutional neural networks have become a widespread tool for the detection of nuclei in histopathology images. Many implementations share a basic approach that includes generation of an intermediate map indicating the presence of a nucleus center, which we refer to as PMap. Nevertheless, these implementations often still differ in several parameters, resulting in different detection qualities. METHODS: We identified several essential parameters and configured the basic PMap approach using combinations of them. We thoroughly evaluated and compared various configurations on multiple datasets with respect to detection quality, efficiency and training effort. RESULTS: Post-processing of the PMap was found to have the largest impact on detection quality. Also, two different network architectures were identified that improve either detection quality or runtime performance. The best-performing configuration yields f1-measures of 0.816 on H&E stained images of colorectal adenocarcinomas and 0.819 on Ki-67 stained images of breast tumor tissue. On average, it was fully trained in less than 15,000 iterations and processed 4.15 megapixels per second at prediction time. CONCLUSIONS: The basic PMap approach is greatly affected by certain parameters. Our evaluation provides guidance on their impact and best settings. When configured properly, this simple and efficient approach can yield equal detection quality as more complex and time-consuming state-of-the-art approaches.

Auditory display for fluorescence-guided open brain tumor surgery.

PURPOSE: Protoporphyrin (PpIX) fluorescence allows discrimination of tumor and normal brain tissue during neurosurgery. A handheld fluorescence (HHF) probe can be used for spectroscopic measurement of 5-ALA-induced PpIX to enable objective detection compared to visual evaluation of fluorescence. However, current technology requires that the surgeon either views the measured values on a screen or employs an assistant to verbally relay the values. An auditory feedback system was developed and evaluated for communicating measured fluorescence intensity values directly to the surgeon. METHODS: The auditory display was programmed to map the values measured by the HHF probe to the playback of tones that represented three fluorescence intensity ranges and one error signal. Ten persons with no previous knowledge of the application took part in a laboratory evaluation. After a brief training period, participants performed measurements on a tray of 96 wells of liquid fluorescence phantom and verbally stated the perceived measurement values for each well. The latency and accuracy of the participants' verbal responses were recorded. The long-term memorization of sound function was evaluated in a second set of 10 participants 2-3 and 7-12 days after training. RESULTS: The participants identified the played tone accurately for 98% of measurements after training. The median response time to verbally identify the played tones was 2 pulses. No correlation was found between the latency and accuracy of the responses, and no significant correlation with the musical proficiency of the participants was observed on the function responses. Responses for the memory test were 100% accurate. CONCLUSION: The employed auditory display was shown to be intuitive, easy to learn and remember, fast to recognize, and accurate in providing users with measurements of fluorescence intensity or error signal. The results of this work establish a basis for implementing and further evaluating auditory displays in clinical scenarios involving fluorescence guidance and other areas for which categorized auditory display could be useful.

Data-Driven Discovery of Immune Contexture Biomarkers.

Background: Features characterizing the immune contexture (IC) in the tumor microenvironment can be prognostic and predictive biomarkers. Identifying novel biomarkers can be challenging due to complex interactions between immune and tumor cells and the abundance of possible features. Methods: We describe an approach for the data-driven identification of IC biomarkers. For this purpose, we provide mathematical definitions of different feature classes, based on cell densities, cell-to-cell distances, and spatial heterogeneity thereof. Candidate biomarkers are ranked according to their potential for the predictive stratification of patients. Results: We evaluated the approach on a dataset of colorectal cancer patients with variable amounts of microsatellite instability. The most promising features that can be explored as biomarkers were based on cell-to-cell distances and spatial heterogeneity. Both the tumor and non-tumor compartments yielded features that were potentially predictive for therapy response and point in direction of further exploration. Conclusion: The data-driven approach simplifies the identification of promising IC biomarker candidates. Researchers can take guidance from the described approach to accelerate their biomarker research.

Hypothermia does not influence liver damage and function in a porcine polytrauma model.

BACKGROUND: Previous studies revealed evidence that induced hypothermia attenuates ischemic organ injuries after severe trauma. In the present study, the effect of hypothermia on liver damage was investigated in a porcine long term model of multi-system injury, consisting of blunt chest trauma, penetrating abdominal trauma, musculoskeletal injury, and hemorrhagic shockMETHODS: In 30 pigs, a standardized polytrauma including blunt chest trauma, penetrating abdominal trauma, musculoskeletal injury, and hemorrhagic shock of 45% of total blood volume was induced. Following trauma, hypothermia of 33∘C was induced for 12 h and intensive care treatment was evaluated for 48 h. As outcome parameters, we assessed liver function and serum transaminase levels as well as a histopathological analysis of tissue samples. A further 10 animals served as controls. RESULTS: Serum transaminase levels were increased at the end of the observation period following hypothermia without reaching statistical significance compared to normothermic groups. Liver function was preserved (p⩽ 0.05) after the rewarming period in hypothermic animals but showed no difference at the end of the observation period. In H&E staining, cell death was slightly increased hypothermic animals and caspase-3 staining displayed tendency towards more apoptosis in hypothermic group as well. CONCLUSIONS: Induction of hypothermia could not significantly improve hepatic damage during the first 48 h following major trauma. Further studies focusing on multi-organ failure including a longer observation period are required to illuminate the impact of hypothermia on hepatic function in multiple trauma patients.

Different patterns of longitudinal brain and spinal cord changes and their associations with disability progression in NMO and MS.

OBJECTIVE: To investigate the longitudinal spinal cord and brain changes in neuromyelitis optica (NMO) and multiple sclerosis (MS) and their associations with disability progression. PATIENTS AND METHODS: We recruited 28 NMO, 22 MS, and 20 healthy controls (HC), who underwent both spinal cord and brain MRI at baseline. Twenty-five NMO and 20 MS completed 1-year follow-up. Baseline spinal cord and brain lesion loads, mean upper cervical cord area (MUCCA), brain, and thalamus volume and their changes during a 1-year follow-up were measured and compared between groups. All the measurements were also compared between progressive and non-progressive groups in NMO and MS. RESULTS: MUCCA decreased significantly during the 1-year follow-up in NMO not in MS. Percentage brain volume changes (PBVC) and thalamus volume changes in MS were significantly higher than NMO. MUCCA changes were significantly different between progressive and non-progressive groups in NMO, while baseline brain lesion volume and PBVC were associated with disability progression in MS. MUCCA changes during 1-year follow-up showed association with clinical disability in NMO. CONCLUSION: Spinal cord atrophy changes were associated with disability progression in NMO, while baseline brain lesion load and whole brain atrophy changes were related to disability progression in MS. KEY POINTS: • Spinal cord atrophy progression was observed in NMO. • Spinal cord atrophy changes were associated with disability progression in NMO. • Brain lesion and atrophy were related to disability progression in MS.

Cardiac Depression in Pigs after Multiple Trauma - Characterization of Posttraumatic Structural and Functional Alterations.

The purpose of this study was to define the relationship between cardiac depression and morphological and immunological alterations in cardiac tissue after multiple trauma. However, the mechanistic basis of depressed cardiac function after trauma is still elusive. In a porcine polytrauma model including blunt chest trauma, liver laceration, femur fracture and haemorrhage serial trans-thoracic echocardiography was performed and correlated with cellular cardiac injury as well as with the occurrence of extracellular histones in serum. Postmortem analysis of heart tissue was performed 72 h after trauma. Ejection fraction and shortening fraction of the left ventricle were significantly impaired between 4 and 27 h after trauma. H-FABP, troponin I and extracellular histones were elevated early after trauma and returned to baseline after 24 and 48 h, respectively. Furthermore, increased nitrotyrosine and Il-1ß generation and apoptosis were identified in cardiac tissue after trauma. Main structural findings revealed alteration of connexin 43 (Cx43) and co-translocation of Cx43 and zonula occludens 1 to the cytosol, reduction of α-actinin and increase of desmin in cardiomyocytes after trauma. The cellular and subcellular events demonstrated in this report may for the first time explain molecular mechanisms associated with cardiac dysfunction after multiple trauma.

Methods for quantifying adipose tissue insulin resistance in overweight/obese humans.

BACKGROUND/OBJECTIVES: Insulin resistance of adipose tissue is an important feature of obesity-related metabolic disease. However, assessment of lipolysis in humans requires labor-intensive and expensive methods, and there is limited validation of simplified measurement methods. We aimed to validate simplified methods for the quantification of adipose tissue insulin resistance against the assessment of insulin sensitivity of lipolysis suppression during hyperinsulinemic-euglycemic clamp studies. SUBJECTS/METHODS: We assessed the insulin-mediated suppression of lipolysis by tracer-dilution of [1,1,2,3,3-2H5]glycerol during hyperinsulinemic-euglycemic clamp studies in 125 overweight or obese adults (85 men, 40 women; age 50±11 years; body mass index 38±7 kg m-2). Seven indices of adipose tissue insulin resistance were validated against the reference measurement method. RESULTS: Low-dose insulin infusion resulted in suppression of the glycerol rate of appearance ranging from 4% (most resistant) to 85% (most sensitive), indicating a good range of adipose tissue insulin sensitivity in the study population. The reference method correlated with (1) insulin-mediated suppression of plasma glycerol concentrations (r=0.960, P<0.001), (2) suppression of plasma non-esterified fatty acid (NEFA) concentrations (r=0.899, P<0.001), (3) the Adipose tissue Insulin Resistance (Adipo-IR) index (fasting plasma insulin-NEFA product; r=-0.526, P<0.001), (4) the fasting plasma insulin-glycerol product (r=-0.467, P<0.001), (5) the Adipose Tissue Insulin Resistance Index (fasting plasma insulin-basal lipolysis product; r=0.460, P<0.001), (6) the Quantitative Insulin Sensitivity Check Index (QUICKI)-NEFA index (r=0.621, P<0.001), and (7) the QUICKI-glycerol index (r=0.671, P<0.001). Bland-Altman plots showed no systematic errors for the suppression indices but proportional errors for all fasting indices. Receiver-operator characteristic curves confirmed that all indices were able to detect adipose tissue insulin resistance (area under the curve ⩾0.801, P<0.001). CONCLUSIONS: Adipose tissue insulin sensitivity (that is, the antilipolytic action of insulin) can be reliably quantified in overweight and obese humans by simplified index methods. The sensitivity and specificity of the Adipo-IR index and the fasting plasma insulin-glycerol product, combined with their simplicity and acceptable agreement, suggest that these may be most useful in clinical practice.

Semi-automated delineation of breast cancer tumors and subsequent materialization using three-dimensional printing (rapid prototyping).

OBJECTIVE: Three-dimensional (3D) printing has become widely available, and a few cases of its use in clinical practice have been described. The aim of this study was to explore facilities for the semi-automated delineation of breast cancer tumors and to assess the feasibility of 3D printing of breast cancer tumors. METHODS: In a case series of five patients, different 3D imaging methods-magnetic resonance imaging (MRI), digital breast tomosynthesis (DBT), and 3D ultrasound-were used to capture 3D data for breast cancer tumors. The volumes of the breast tumors were calculated to assess the comparability of the breast tumor models, and the MRI information was used to render models on a commercially available 3D printer to materialize the tumors. RESULTS: The tumor volumes calculated from the different 3D methods appeared to be comparable. Tumor models with volumes between 325 mm3 and 7,770 mm3 were printed and compared with the models rendered from MRI. The materialization of the tumors reflected the computer models of them. CONCLUSION: 3D printing (rapid prototyping) appears to be feasible. Scenarios for the clinical use of the technology might include presenting the model to the surgeon to provide a better understanding of the tumor's spatial characteristics in the breast, in order to improve decision-making in relation to neoadjuvant chemotherapy or surgical approaches. J. Surg. Oncol. 2017;115:238-242. © 2016 Wiley Periodicals, Inc.

Comparative study on the treatment of Rockwood type III acute acromioclavicular dislocation: Clinical results from the TightRope® technique vs. K-wire fixation.

BACKGROUND AND HYPOTHESIS: The aim of this study was to address the inconsistency regarding the operative treatment of Rockwood type III acromioclavicular joint separation. We compared results after single- and double TightRope® reduction with results after acromioclavicular transfixation via K-wires only and additional ligament augmentation in acute acromioclavicular (AC) joint separations graded Rockwood type III, and hypothesized that the TightRope® technique leads to better clinical and radiological results. MATERIALS AND METHODS: We conducted a retrospective clinical cohort study and included 42 consecutive patients (mean age 43 years [24-66]) diagnosed and operatively treated between 2004 and 2012 (mean follow-up was 54.6 months [15-118]). Specific shoulder scores as well as scores reflecting the patients' overall mental and physical health status were used. Radiological evaluation was also performed. RESULTS: The SF12 test revealed comparability between all subgroups. Specific shoulder tests and a visual analogue scale demonstrated comparable results. Radiographic measurements showed a significant reduction in the AC distance and CC distance after surgery in all subgroups. The early complication rate was 9.5% for all patients, while late complications occurred in 14.3% of all cases. CONCLUSIONS: Compared to the established methods, the operative TightRope® procedures represent a safe alternative in Rockwood III injuries. All investigated techniques predominantly led to good and excellent clinical results in acute Rockwood type III AC joint instabilities. Avoidance of material removal and shorter hospital stays appear to speak in favour for the TightRope® technique. LEVEL OF EVIDENCE: IV.

[The rotationally stable screw-anchor with trochanteric stabilizing plate (RoSA/TSP) : First results in unstable trochanteric femur fractures]. / Der Rotationsstabile Schraubanker mit winkelstabiler Stützplatte (RoSA/TAP) : Erste klinische Evaluation bei instabilen trochantären Frakturen.

BACKGROUND: In unstable trochanteric fractures, the extramedullary rotationally stable screw-anchor (RoSA) combines the benefits of the load and rotational stability of the blade with the advantages of the screw (pull-out resistance, compression capability) in a single load carrier, and was designed to prevent femoral neck shortening by using an additional locked trochanteric stabilizing plate (TSP). OBJECTIVES: The aim of the current prospective cohort study was the clinical evaluation of the RoSA/TSP system regarding the mechanical re-operation rate and the amount of postoperative femoral neck shortening. METHODS: From September 2011 to January 2014 80 patients with unstable trochanteric fractures underwent internal extramedullary fixation with the RoSA/TSP (Königsee Implantate GmbH, Allendorf, Germany). Due to fracture stability and after induction of compression, additional long locked antitelescoping screws (AT, n = 1-4) were placed reaching the femoral head. Radiological (femoral neck shortening) and clinical re-examination of patients (n = 61) was performed 6-10 weeks and 6-10 months later. RESULTS: In the 61 re-examined patients (76 %) femoral neck shortening was very low with 2 mm 6-10 months after operation. Re-operations occurred in 8 % (n = 6) and in 4 % (n = 3) as prophylactic surgical intervention. Whereas one-third (4 %) of re-operations occurred due to iatrogenic surgical problems from the first operation two-thirds of patients (8 %) had a re-operation due to delay of bone union (3× nonunion, 3 planned removals of AT-screws to improve healing). The in-hospital mortality was 3 % (n = 2). CONCLUSIONS: The fixation of unstable trochanteric femur fractures using the RoSA/TSP in a first clinical setting led to a great primary stability, with significant advantages with regard to limited femoral neck shortening. However, the rigidity of the construct with its consequences regarding bone healing can be challenging for the surgeon. Nevertheless, in some cases of revision it could be beneficial for stability.

Characterization of blunt chest trauma in a long-term porcine model of severe multiple trauma.

Chest trauma has a significant relevance on outcome after severe trauma. Clinically, impaired lung function typically occurs within 72 hours after trauma. However, the underlying pathophysiological mechanisms are still not fully elucidated. Therefore, we aimed to establish an experimental long-term model to investigate physiological, morphologic and inflammatory changes, after severe trauma. Male pigs (sus scrofa) sustained severe trauma (including unilateral chest trauma, femur fracture, liver laceration and hemorrhagic shock). Additionally, non-injured animals served as sham controls. Chest trauma resulted in severe lung damage on both CT and histological analyses. Furthermore, severe inflammation with a systemic increase of IL-6 (p = 0.0305) and a local increase of IL-8 in BAL (p = 0.0009) was observed. The pO2/FiO2 ratio in trauma animals decreased over the observation period (p < 0.0001) but not in the sham group (p = 0.2967). Electrical Impedance Tomography (EIT) revealed differences between the traumatized and healthy lung (p < 0.0001). In conclusion, a clinically relevant, long-term model of blunt chest trauma with concomitant injuries has been developed. This reproducible model allows to examine local and systemic consequences of trauma and is valid for investigation of potential diagnostic or therapeutic options. In this context, EIT might represent a radiation-free method for bedside diagnostics.

The vitamin D metabolites 25(OH)D and 1,25(OH)2D are not related to either glucose metabolism or insulin action in obese women.

AIM: Vitamin D deficiency has been proposed to be involved in obesity-induced metabolic disease. However, data on the relationship between 25-hydroxycholecalciferol (25(OH)D) and insulin resistance have been inconsistent, and few studies have investigated the active vitamin D metabolite, 1,25-dihydroxycholecalciferol (1,25(OH)2D). This study aimed to determine the relationship between circulating levels of both 25(OH)D and 1,25(OH)2D and direct measures of glucose metabolism and insulin action in obese women. METHODS: Serum levels of 25(OH)D and 1,25(OH)2D, and glucose metabolism and tissue-specific insulin action, as assessed in the basal state and during a two-step euglycaemic-hyperinsulinaemic clamp study with [6,6-2H2]glucose infusion, were measured in 37 morbidly obese women (age: 43±10 years; body mass index: 44±6kg/m2). RESULTS: Sixteen subjects had circulating 25(OH)D levels<50nmol/L, consistent with vitamin D deficiency, and 21 had normal 25(OH)D levels. There were no differences in either baseline characteristics or parameters of glucose metabolism and insulin action between the groups. Serum 25(OH)D, but not 1,25(OH)2D, was negatively correlated with both body mass index (r=-0.42, P=0.01) and total body fat (r=-0.46, P<0.01). Neither 25(OH)D nor 1,25(OH)2D levels were related to any measured metabolic parameters, including fasting glucose, fasting insulin, basal endogenous glucose production, and hepatic, adipose-tissue and skeletal muscle insulin sensitivity. CONCLUSION: Obesity was associated with lower levels of circulating 25(OH)D, but not with the hormonally active metabolite 1,25(OH)2D. Neither 25(OH)D nor 1,25(OH)2D were related to glucose metabolism and tissue-specific insulin sensitivity in obese women, suggesting that vitamin D does not play a major role in obesity-related insulin resistance.