Paediatric spine injuries in the thoracic and lumbar spine-results of the German multicentre CHILDSPINE study.

BACKGROUND: Paediatric thoracolumbar spine injuries are rare, and meaningful epidemiological data are lacking. OBJECTIVES: The aim of this study was to provide epidemiological data for paediatric patients with thoracolumbar spinal trauma in Germany with a view to enhancing future decision-making in relation to the diagnostics and treatment of these patients. MATERIALS AND METHODS: A retrospective multicentre study includes patients up to 16 years of age who were suffering from thoracolumbar spine injuries who had been treated in six German spine centres between 01/2010 and 12/2016. The clinical database was analysed for patient-specific data, trauma mechanisms, level of injury, and any accompanying injuries. Diagnostic imaging and subsequent treatment were investigated. Patients were divided into three age groups for further evaluation: age group I (0-6 years), age group II (7-9 years) and age group III (10-16 years). RESULTS: A total of 153 children with 345 thoracolumbar spine injuries met the inclusion criteria. The mean age at the time of hospitalization due to the injury was 12.9 (± 3.1) years. Boys were likelier to be affected (1:1.3). In all age groups, falls and traffic accidents were the most common causes of thoracolumbar spine injuries. A total of 95 patients (62.1%) were treated conservatively, while 58 (37.9%) of the children underwent surgical treatment. Minimally invasive procedures were the most chosen procedures. Older children and adolescents were likelier to suffer from higher-grade injuries according to the AOSpine classification. The thoracolumbar junction (T11 to L2) was the most affected level along the thoracolumbar spine (n = 90). Neurological deficits were rarely seen in all age groups. Besides extremity injuries (n = 52, 30.2%), head injuries represented the most common accompanying injuries (n = 53, 30.8%). Regarding spinal injuries, most of the patients showed no evidence of complications during their hospital stay (96.7%). CONCLUSIONS: The thoracolumbar junction was more frequently affected in older children and adolescents. The majority of thoracolumbar spinal column injuries were treated conservatively. Nevertheless, 37.9% of hospitalized children had to be treated surgically, and there was an acceptable complication rate for the surgeries that were performed.

MR imaging after patellar MACI and MPFL reconstruction: a comparison of isolated versus combined procedures.

OBJECTIVE: To qualitatively and quantitatively evaluate the 2.5-year MRI outcome after Matrix-associated autologous chondrocyte implantation (MACI) at the patella, reconstruction of the medial patellofemoral ligament (MPFL), and combined procedures. METHODS: In 66 consecutive patients (age 22.8 ± 6.4years) with MACI at the patella (n = 16), MPFL reconstruction (MPFL; n = 31), or combined procedures (n = 19) 3T MRI was performed 2.5 years after surgery. For morphological MRI evaluation WORMS and MOCART scores were obtained. In addition quantitative cartilage T2 and T1rho relaxation times were acquired. Several clinical scores were obtained. Statistical analyses included descriptive statistics, Mann-Whitney-U-tests and Pearson correlations. RESULTS: WORMS scores at follow-up (FU) were significantly worse after combined procedures (8.7 ± 4.9) than after isolated MACI (4.3 ± 3.6, P = 0.005) and after isolated MPFL reconstruction (5.3 ± 5.7, P = 0.004). Bone marrow edema at the patella in the combined group was the only (non-significantly) worsening WORMS parameter from pre- to postoperatively. MOCART scores were significantly worse in the combined group than in the isolated MACI group (57 ± 3 vs 88 ± 9, P < 0.001). Perfect defect filling was achieved in 26% and 69% of cases in the combined and MACI group, respectively (P = 0.031). Global and patellar T2 values were higher in the combined group (Global T2: 34.0 ± 2.8ms) and MACI group (35.5 ± 3.1ms) as compared to the MPFL group (31.1 ± 3.2ms, P < 0.05). T2 values correlated significantly with clinical scores (P < 0.005). Clinical Cincinnati scores were significantly worse in the combined group (P < 0.05). CONCLUSION: After combined surgery with patellar MACI and MPFL reconstruction inferior MRI outcomes were observed than after isolated procedures. Therefore, patients with need for combined surgery may be at particular risk for osteoarthritis.

Comparison of Extracellular Vesicles from Induced Pluripotent Stem Cell-Derived Brain Cells.

The pathophysiology of many neuropsychiatric disorders is still poorly understood. Identification of biomarkers for these diseases could benefit patients due to better classification and stratification. Exosomes excreted into the circulatory system can cross the blood-brain barrier and carry a cell type-specific set of molecules. Thus, exosomes are a source of potential biomarkers for many diseases, including neuropsychiatric disorders. Here, we investigated exosomal proteins produced from human-induced pluripotent stem cells (iPSCs) and iPSC-derived neural stem cells, neural progenitors, neurons, astrocytes, microglia-like cells, and brain capillary endothelial cells. Of the 31 exosome surface markers analyzed, a subset of biomarkers were significantly enriched in astrocytes (CD29, CD44, and CD49e), microglia-like cells (CD44), and neural stem cells (SSEA4). To identify molecular fingerprints associated with disease, circulating exosomes derived from healthy control (HC) individuals were compared against schizophrenia (SCZ) patients and late-onset Alzheimer's disease (LOAD) patients. A significant epitope pattern was identified for LOAD (CD1c and CD2) but not for SCZ compared to HC. Thus, analysis of cell type- and disease-specific exosome signatures of iPSC-derived cell cultures may provide a valuable model system to explore proteomic biomarkers for the identification of novel disease profiles.

Biomechanical Effects of Chronic Ankle Instability on the Talar Cartilage Matrix: The Value of T1ρ Relaxation Mapping Without and With Mechanical Loading.

BACKGROUND: T1ρ mapping has been proposed for the detection of early cartilage degeneration associated with chronic ankle instability (CAI). However, there are limited data surrounding the influence of ankle loading on T1ρ relaxation. PURPOSE: To evaluate T1ρ relaxation times of talar cartilage, as an indicator of early degenerative changes, associated with CAI and to investigate the influence of acute axial in situ loading on T1ρ values in CAI patients and healthy controls. STUDY TYPE: Prospective. SUBJECTS: A total of 9 patients (age = 21.8 ± 2.5 years, male/female = 2/7) with chronic ankle instability and 18 healthy control subjects (age = 22.8 ± 3.6 years, male/female = 5/13). FIELD STRENGTH: 3 T. SEQUENCE: 3D gradient echo fast low-angle shot (FLASH) sequence augmented with a variable spin-lock preparation period. ASSESSMENT: Ankle T1ρ mapping was performed without and with axial loading of 500 N. The talar cartilage was segmented in five coronal slices covering the central talocrural joint. Median talar T1ρ values were separately calculated for the medial and lateral facets. STATISTICAL TESTS: Mann-Whitney U and Wilcoxon signed-rank tests, significance level: P < 0.05. RESULTS: For the combined cohorts, the statistical analysis yielded significantly lower T1ρ values with loading compared to the no-load measurement for both the lateral (no load: [51.0 ± 4.0] msec, load: [49.5 ± 5.4] msec) as well as the medial compartment (no load: [50.0 ± 5.4] msec, load: [47.8 ± 6.8] msec). In the unloaded scans, the CAI patients showed significantly increased talar T1ρ values ([53.0 ± 7.4] mse ) compared to the healthy control subjects ([48.8 ± 4.1] msec) in the medial compartment. DATA CONCLUSION: Increased talar T1ρ relaxation times in CAI patients compared to healthy controls suggest that T1ρ relaxation is a sensitive biomarker for CAI-induced early-stage cartilage degeneration. However, the load-induced T1ρ change did not prove to be a viable marker for the altered biomechanical properties of the hyaline talar cartilage. LEVEL OF EVIDENCE: 2 LEVEL OF EFFICACY: Stage 2.

Application of diffusion microstructure imaging in musculoskeletal radiology - translation from head to shoulders.

OBJECTIVES: Quantitative MRI techniques, such as diffusion microstructure imaging (DMI), are increasingly applied for advanced tissue characterization. We determined its value in rotator cuff (RC) muscle imaging by studying the association of DMI parameters to isometric strength and fat fraction (FF). METHODS: Healthy individuals prospectively underwent 3T-MRI of the shoulder using DMI and chemical shift encoding-based water-fat imaging. RC muscles were segmented and quantitative MRI metrics (V-ISO, free fluid; V-intra, compartment inside of muscle fibers; V-extra, compartment outside of muscle fibers, and FF) were extracted. Isometric shoulder strength was quantified using specific clinical tests. Sex-related differences were assessed with Student's t. Association of DMI-metrics, FF, and strength was tested. A factorial two-way ANOVA was performed to compare the main effects of sex and external/internal strength-ratio and their interaction effects on quantitative imaging parameters ratios of infraspinatus/subscapularis. RESULTS: Among 22 participants (mean age: 26.7 ± 3.1 years, 50% female, mean BMI: 22.6 ± 1.9 kg/m2), FF of the individual RC muscles did not correlate with strength or DMI parameters (all p > 0.05). Subjects with higher V-intra (r = 0.57 to 0.87, p < 0.01) and lower V-ISO (r = -0.6 to -0.88, p < 0.01) had higher internal and external rotation strength. Moreover, V-intra was higher and V-ISO was lower in all RC muscles in males compared to female subjects (all p < 0.01). There was a sex-independent association of external/internal strength-ratio with the ratio of V-extra of infraspinatus/subscapularis (p = 0.02). CONCLUSIONS: Quantitative DMI parameters may provide incremental information about muscular function and microstructure in young athletes and may serve as a potential biomarker. KEY POINTS: • Diffusion microstructure imaging was successfully applied to non-invasively assess the microstructure of rotator cuff muscles in healthy volunteers. • Sex-related differences in the microstructural composition of the rotator cuff were observed. • Muscular microstructural metrics correlated with rotator cuff strength and may serve as an imaging biomarker of muscular integrity and function.

Association of lumbar vertebral bone marrow and paraspinal muscle fat composition with intervertebral disc degeneration: 3T quantitative MRI findings from the population-based KORA study.

OBJECTIVE: To assess the association of lumbar bone marrow adipose tissue fat fraction (BMAT-FF) and paraspinal muscle proton density fat fraction (PDFF) and their interplay with intervertebral disc degeneration (IVDD). METHODS: In this retrospective cross-sectional study based on a prospective population-based cohort, BMAT-FF and PDFF of asymptomatic individuals were calculated based on 3T-MRI dual-echo and multi-echo Dixon VIBE sequences. IVDD was assessed at motion segments L1 to L5 and dichotomized based on Pfirrmann grade ≥ 4 and/or presence of other severe degenerative changes or spinal abnormalities at least at one segment. Pearson's correlation coefficients were calculated for BMAT-FF and PDFF. Univariable and multivariable logistic regression models for IVDD were calculated. RESULTS: Among 335 participants (mean age: 56.2 ± 9.0 years, 43.3% female), the average BMI was 27.7 ± 4.5 kg/m2 and the prevalence of IVDD was high (69.9%). BMAT-FF and PDFF were significantly correlated (r = 0.31-0.34; p < 0.001). The risk for IVDD increased with higher PDFF (OR = 1.45; CI 1.03, 2.04) and BMAT-FF (OR = 1.56; CI 1.16, 2.11). Pairwise combinations of PDFF and BMAT-FF quartiles revealed a lower risk for IVDD in individuals in the lowest BMAT-FF and PDFF quartile (OR = 0.21; CI 0.1, 0.48). Individuals in the highest BMAT-FF and PDFF quartile showed an increased risk for IVDD (OR = 5.12; CI 1.17, 22.34) CONCLUSION: Lumbar BMAT-FF and paraspinal muscle PDFF are correlated and represent both independent and additive risk factors for IVDD. Quantitative MRI measurements of paraspinal myosteatosis and vertebral bone marrow fatty infiltration may serve as imaging biomarkers to assess the individual risk for IVDD. KEY POINTS: • Fat composition of the lumbar vertebral bone marrow is positively correlated with paraspinal skeletal muscle fat. • Higher fat-fractions of lumbar vertebral bone marrow and paraspinal muscle are both independent as well as additive risk factors for intervertebral disc degeneration. • Quantitative magnetic resonance imaging measurements of bone marrow and paraspinal muscle may serve as imaging biomarkers for intervertebral disc degeneration.

Odontoid fracture in geriatric patients - analysis of complications and outcome following conservative treatment vs. ventral and dorsal surgery.

BACKGROUND: Different treatment options are discussed for geriatric odontoid fracture. The aim of this study was to compare the treatment options for geriatric odontoid fractures. METHODS: Included were patients with the following criteria: age ≥ 65 years, identification of seniors at risk (ISAR score ≥ 2), and odontoid fracture type A/B according to Eysel and Roosen. Three groups were compared: conservative treatment, surgical therapy with ventral screw osteosynthesis or dorsal instrumentation. At a follow-up examination, the range of motion and the trabecular bone fracture healing rate were evaluated. Furthermore, demographic patient data, neurological status, length of stay at the hospital and at the intensive care unit (ICU) as well as the duration of surgery and occurring complications were analyzed. RESULTS: A total of 72 patients were included and 43 patients could be re-examined (range: 2.7 ± 2.1 months). Patients with dorsal instrumentation had a better rotation. Other directions of motion were not significantly different. The trabecular bone fracture healing rate was 78.6%. The patients with dorsal instrumentation were hospitalized significantly longer; however, their duration at the ICU was shortest. There was no significant difference in complications. CONCLUSION: Geriatric patients with odontoid fracture require individual treatment planning. Dorsal instrumentation may offer some advantages.

Pediatric cervical spine injuries-results of the German multicenter CHILDSPINE study.

OBJECTIVES: The aim of this study was to provide epidemiological data of pediatric patients suffering from cervical spinal trauma in Germany, in order to integrate these data in future decision-making processes concerning diagnosis and therapy. MATERIALS AND METHODS: Retrospective multicenter study includes all patients up to 16 years suffering from cervical spine injuries who were treated in six German spine centers between 01/2010 and 12/2016. The clinical databases were screened for specific trauma mechanism, level of injury as well as accompanying injuries. Diagnostic imaging and the chosen therapy were analyzed. Patients were divided into three age groups for further evaluation: age group I (0-6 years), age group II (7-9 years), age group III (10-16 years). RESULTS: A total of 214 children with 265 cervical spine injuries were included during the mentioned period. The mean age at the time of injury was 11.9 (± 3.9) years. In age group I, 24 (11.2%) patients were included, age group II consisted of 22 patients (10.3%), and 168 patients belonged to age group III (78.5%). Girls and boys were equally affected. In all age groups, falls and traffic accidents were the most common causes of cervical spine injuries. A total of 180 patients (84.1%) were treated conservatively, while 34 (15.9%) children underwent surgery. Distorsion/whiplash injury was the most common entity (n = 165; 68.2%). Children aged 0-9 years had significantly (p < 0.001) more frequent injuries of the upper cervical spine (C0-C2) compared to older age groups. Patients of age group III were more likely to suffer from injuries in subaxial localizations. Neurological deficits were rarely seen in all age groups. Head injuries did represent the most common accompanying injuries (39.8%, n = 92). CONCLUSIONS: The upper cervical spine was more frequently affected in young children. Older children more often suffered from subaxial pathologies. The majority of cervical spinal column injuries were treated conservatively. Nevertheless, 15% of the hospitalized children had to be treated surgically.

Single point imaging with radial acquisition and compressed sensing.

PURPOSE: To accelerate the Pointwise Encoding Time Reduction with Radial Acquisition (PETRA) sequence using compressed sensing while preserving the image quality for high-resolution MRI of tissue with ultra-short T2∗ values. METHODS: Compressed sensing was introduced in the PETRA sequence (csPETRA) to accelerate the time-consuming single point acquisition of the k-space center data. Random undersampling was applied to achieve acceleration factors up to Acc = 32. Phantom and in vivo images of the knee joint of six volunteers were measured at 3T using csPETRA sequence with Acc = 4, 8, 12, 16, 24, and 32. Images were compared against fully sampled PETRA data (Acc = 1) for structural similarity and normalized-mean-square-error. Qualitative and semi-quantitative analyses were performed to assess the effect of the acceleration on image artifacts, image quality, and delineation of anatomical structures at the knee. RESULTS: Even at high acceleration factors of Acc = 16 no aliasing artifacts were observed, and the anatomical details were preserved compared with the fully sampled data. The normalized-mean-square-error was less than 1% for Acc = 16, in which single point imaging acquisition time was reduced from 165 to 10 s, reducing the total scan time from 7.8 to 5.2 min. Semi-quantitative analyses suggest that Acc = 16 yields comparable diagnostic quality as the fully sampled data for knee imaging at a scan time of 5.2 min. CONCLUSION: csPETRA allows for ultra-short T2∗ imaging of the knee joint in clinically acceptable scan times while maintaining the image quality of original non-accelerated PETRA sequence.

Development and evaluation of machine learning models based on X-ray radiomics for the classification and differentiation of malignant and benign bone tumors.

OBJECTIVES: To develop and validate machine learning models to distinguish between benign and malignant bone lesions and compare the performance to radiologists. METHODS: In 880 patients (age 33.1 ± 19.4 years, 395 women) diagnosed with malignant (n = 213, 24.2%) or benign (n = 667, 75.8%) primary bone tumors, preoperative radiographs were obtained, and the diagnosis was established using histopathology. Data was split 70%/15%/15% for training, validation, and internal testing. Additionally, 96 patients from another institution were obtained for external testing. Machine learning models were developed and validated using radiomic features and demographic information. The performance of each model was evaluated on the test sets for accuracy, area under the curve (AUC) from receiver operating characteristics, sensitivity, and specificity. For comparison, the external test set was evaluated by two radiology residents and two radiologists who specialized in musculoskeletal tumor imaging. RESULTS: The best machine learning model was based on an artificial neural network (ANN) combining both radiomic and demographic information achieving 80% and 75% accuracy at 75% and 90% sensitivity with 0.79 and 0.90 AUC on the internal and external test set, respectively. In comparison, the radiology residents achieved 71% and 65% accuracy at 61% and 35% sensitivity while the radiologists specialized in musculoskeletal tumor imaging achieved an 84% and 83% accuracy at 90% and 81% sensitivity, respectively. CONCLUSIONS: An ANN combining radiomic features and demographic information showed the best performance in distinguishing between benign and malignant bone lesions. The model showed lower accuracy compared to specialized radiologists, while accuracy was higher or similar compared to residents. KEY POINTS: • The developed machine learning model could differentiate benign from malignant bone tumors using radiography with an AUC of 0.90 on the external test set. • Machine learning models that used radiomic features or demographic information alone performed worse than those that used both radiomic features and demographic information as input, highlighting the importance of building comprehensive machine learning models. • An artificial neural network that combined both radiomic and demographic information achieved the best performance and its performance was compared to radiology readers on an external test set.

Patellar instability MRI measurements are associated with knee joint degeneration after reconstruction of the medial patellofemoral ligament.

OBJECTIVE: To qualitatively and quantitatively evaluate the 2-year magnetic resonance imaging (MRI) outcome after MPFL reconstruction at the knee and to assess MRI-based risk factors that predispose for inferior clinical and imaging outcomes. MATERIALS AND METHODS: A total of 31 patients with MPFL reconstruction were included (22 ± 6 years, 10 female). MRI was performed preoperatively in 21/31 patients. Two-year follow-up MRI included quantitative cartilage T2 and T1rho relaxation time measurements at the ipsilateral and contralateral knee. T2relative was calculated as T2patellofemoral/T2femorotibial. Morphological evaluation was conducted via WORMS scores. Patellar instability parameters and clinical scores were obtained. Statistical analyses included descriptive statistics, t-tests, multivariate regression models, and correlation analyses. RESULTS: Two years after MPFL reconstruction, all patellae were clinically stable. Mean total WORMS scores improved significantly from baseline to follow-up (mean difference ± SEM, - 4.0 ± 1.3; P = 0.005). As compared to patients with no worsening of WORMS subscores over time (n = 5), patients with worsening of any WORMS subscore (n = 16) had lower trochlear depth, lower facetal ratio, higher tibial-tuberosity to trochlear groove (TTTG) distance, and higher postoperative lateral patellar tilt (P < 0.05). T2relative was higher at the ipsilateral knee (P = 0.010). T2relative was associated with preoperatively higher patellar tilt (P = 0.021) and higher TTTG distance (P = 0.034). TTTG distance, global T2 values, and WORMS progression correlated with clinical outcomes (P < 0.05). CONCLUSION: MPFL reconstruction is an optimal treatment strategy to restore patellar stability. Still, progressive knee joint degeneration and patellofemoral cartilage matrix degeneration may be observed, with patellar instability MRI parameters representing particular risk factors.

Individualized Mini-Panel Sequencing of ctDNA Allows Tumor Monitoring in Complex Karyotype Sarcomas.

Soft tissue sarcomas (STS) are rare tumors of mesenchymal origin with high mortality. After curative resection, about one third of patients suffer from distant metastases. Tumor follow-up only covers a portion of recurrences and is associated with high cost and radiation burden. For metastasized STS, only limited inferences can be drawn from imaging data regarding therapy response. To date there are no established and evidence-based diagnostic biomarkers for STS due to their rarity and diversity. In a proof-of-concept study, circulating tumor DNA (ctDNA) was quantified in (n = 25) plasma samples obtained from (n = 3) patients with complex karyotype STS collected over three years. Genotyping of tumor tissue was performed by exome sequencing. Patient-individual mini-panels for targeted next-generation sequencing were designed encompassing up to 30 mutated regions of interest. Circulating free DNA (cfDNA) was purified from plasma and ctDNA quantified therein. ctDNA values were correlated with clinical parameters. ctDNA concentrations correlated with the tumor burden. In case of full remission, no ctDNA was detectable. Patients with a recurrence at a later stage showed low levels of ctDNA during clinical remission, indicating minimal residual disease. In active disease (primary tumor or metastatic disease), ctDNA was highly elevated. We observed direct response to treatment, with a ctDNA decline after tumor resections, radiotherapy, and chemotherapy. Quantification of ctDNA allows for the early detection of recurrence or metastases and can be used to monitor treatment response in STS. Therapeutic decisions can be made earlier, such as the continuation of a targeted adjuvant therapy or the implementation of extended imaging to detect recurrences. In metastatic disease, therapy can be adjusted promptly in case of no response. These advantages may lead to a survival benefit for patients in the future.

Multitask Deep Learning for Segmentation and Classification of Primary Bone Tumors on Radiographs.

Background An artificial intelligence model that assesses primary bone tumors on radiographs may assist in the diagnostic workflow. Purpose To develop a multitask deep learning (DL) model for simultaneous bounding box placement, segmentation, and classification of primary bone tumors on radiographs. Materials and Methods This retrospective study analyzed bone tumors on radiographs acquired prior to treatment and obtained from patient data from January 2000 to June 2020. Benign or malignant bone tumors were diagnosed in all patients by using the histopathologic findings as the reference standard. By using split-sample validation, 70% of the patients were assigned to the training set, 15% were assigned to the validation set, and 15% were assigned to the test set. The final performance was evaluated on an external test set by using geographic validation, with accuracy, sensitivity, specificity, and 95% CIs being used for classification, the intersection over union (IoU) being used for bounding box placements, and the Dice score being used for segmentations. Results Radiographs from 934 patients (mean age, 33 years ± 19 [standard deviation]; 419 women) were evaluated in the internal data set, which included 667 benign bone tumors and 267 malignant bone tumors. Six hundred fifty-four patients were in the training set, 140 were in the validation set, and 140 were in the test set. One hundred eleven patients were in the external test set. The multitask DL model achieved 80.2% (89 of 111; 95% CI: 72.8, 87.6) accuracy, 62.9% (22 of 35; 95% CI: 47, 79) sensitivity, and 88.2% (67 of 76; CI: 81, 96) specificity in the classification of bone tumors as malignant or benign. The model achieved an IoU of 0.52 ± 0.34 for bounding box placements and a mean Dice score of 0.60 ± 0.37 for segmentations. The model accuracy was higher than that of two radiologic residents (71.2% and 64.9%; P = .002 and P < .001, respectively) and was comparable with that of two musculoskeletal fellowship-trained radiologists (83.8% and 82.9%; P = .13 and P = .25, respectively) in classifying a tumor as malignant or benign. Conclusion The developed multitask deep learning model allowed for accurate and simultaneous bounding box placement, segmentation, and classification of primary bone tumors on radiographs. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Carrino in this issue.

Long-term outcome and survival rate of monopolar radial head replacement.

BACKGROUND: The purposes of this study were (1) to report functional outcomes; (2) to assess complications, revisions, and survival rate; and (3) to assess differences in functional outcomes between removed and retained radial head arthroplasties (RHAs), early and delayed treatment, and type of RHA used at long-term follow-up after monopolar RHA for unreconstructible radial head fractures or their sequelae. METHODS: Seventy-eight patients (mean age, 59.2 years) who were at least 6 years postoperatively after monopolar RHA for unreconstructible RHFs or their sequelae were included. The Mayo Elbow Performance Score (MEPS); Quick Disability of the Arm, Shoulder, and Hand (QuickDASH) score; visual analog scale; postoperative satisfaction (1-6, 6 = highly unsatisfied); range of motion; complications; and revisions were assessed. Radiographic findings were reported. Kaplan-Meier survival analysis was performed. Subgroups (RHA type, early vs. delayed surgery, RHA removed vs. retained) were compared. RESULTS: At a median clinical follow-up of 9.5 years (range: 6.0-28.4 years), median MEPS was 80.0 (interquartile range [IQR]: 60.0-97.5), median QuickDASH was 22.0 (IQR: 4.6-42.6), median visual analog scale was 1 (IQR: 0-4), median postoperative satisfaction was 2 (IQR: 1-3), and median arc of extension/flexion was 110° (IQR: 80°-130°). Radiographic follow-up was available for 48 patients at a median of 7.0 years (range: 2.0-15.0 years). Heterotopic ossifications were seen in 14 (29.2%), moderate-to-severe capitellar osteopenia/abrasion in 3 (6.1%), moderate-to-severe ulnohumeral degeneration in 3 (6.1%), and periprosthetic radiolucencies in 17 (35.4%) patients. Twenty-nine patients (37.2%) had complications and 20 patients (25.6%) underwent RHA exchange or removal. Kaplan-Meier analysis with failure defined as RHA exchange or removal demonstrated survival of 75.1% (95% confidence interval: 63.7-83.3) at 18 years. The highest annual failure rate was observed in the first year in which the RHAs of 7 patients (9%) were exchanged or removed. No significant differences were detected between type of RHA in MEPS (Mathys: 82.5 [75.0-100] vs. Evolve: 80.0 [60.0-95.0]; P = .341) and QuickDASH (Mathys: 12.5 [0-34.4] vs. Evolve: 26.7 [6.9-46.2]; P = .112). Early surgery (≤3 weeks) yielded significantly superior MEPS (80.0 [70.0-100.0] vs. 52.5 [30.0-83.8]; P = .014) and QuickDASH (18.6 [1.5-32.6] vs. 46.2 [31.5-75.6]; P = .002) compared with delayed surgery (>3 weeks). Patients with retained RHAs had significantly better MEPS (80.0 [67.5-100] vs. 70.0 [32.5-82.5]; P = .016) and QuickDASH (18.1 [1.7-31.9] vs. 49.1 [22.1-73.8]; P = .007) compared with patients with removed RHAs. CONCLUSIONS: Long-term outcomes for RHA are satisfactory; however, there is a high complication and revision rate, resulting in implant survival of 75.1% at 18 years with the highest annual failure rate observed in the first postoperative year.

Coxsackievirus B3 Infection of Human iPSC Lines and Derived Primary Germ-Layer Cells Regarding Receptor Expression.

The association of members of the enterovirus family with pregnancy complications up to miscarriages is under discussion. Here, infection of two different human induced pluripotent stem cell (iPSC) lines and iPSC-derived primary germ-layer cells with coxsackievirus B3 (CVB3) was characterized as an in vitro cell culture model for very early human development. Transcriptomic analysis of iPSC lines infected with recombinant CVB3 expressing enhanced green fluorescent protein (EGFP) revealed a reduction in the expression of pluripotency genes besides an enhancement of genes involved in RNA metabolism. The initial distribution of CVB3-EGFP-positive cells within iPSC colonies correlated with the distribution of its receptor coxsackie- and adenovirus receptor (CAR). Application of anti-CAR blocking antibodies supported the requirement of CAR, but not of the co-receptor decay-accelerating factor (DAF) for infection of iPSC lines. Among iPSC-derived germ-layer cells, mesodermal cells were especially vulnerable to CVB3-EGFP infection. Our data implicate further consideration of members of the enterovirus family in the screening program of human pregnancies. Furthermore, iPSCs with their differentiation capacity into cell populations of relevant viral target organs could offer a reliable screening approach for therapeutic intervention and for assessment of organ-specific enterovirus virulence.

[The position of the head during treatment in the emergency room-an explorative analysis of immobilization of the cervical spine]. / Die Lagerung des Kopfes während der Behandlung im Schockraum ­ eine explorative Analyse über die Immobilisation der Halswirbelsäule.

BACKGROUND: Immobilization of the cervical spine is a standard procedure in emergency medicine mostly achieved via a cervical collar. In the emergency room other forms of immobilization are utilized as cervical collars have certain drawbacks. The present study aimed to provide preliminary data on the efficiency of immobilization in the emergency room by analyzing the residual spinal motion of the patient's head on different kinds of head rests. METHODS: In the present study biomechanical motion data of the cervical spine of a test subject were analyzed. The test subject was placed in a supine position on a mobile stretcher (Stryker M1 Roll-In System, Kalamazoo, MI, USA) wearing a cervical collar (Perfit ACE, Ballerup, Denmark). Three different head rests were tested: standard pillow, concave pillow and cavity pillow. The test subject carried out a predetermined motion protocol: right side inclination, left side inclination, flexion and extension. The residual spinal motion was recorded with wireless motion trackers (inertial measurement unit, Xsens Technologies, Enschede, The Netherlands). The first measurement was performed without a cervical collar or positioning on the pillows to measure the physiological baseline motion. Subsequently, three measurements were taken with the cervical collar applied and the pillows in place. From these measurements, a motion score was calculated that can represent the motion of the cervical spine. RESULTS: When the test subject's head was positioned on a standard pillow the physiological motion score was reduced from 69 to 40. When the test subject's head was placed on concave pillow the motion score was further reduced from 69 to 35. When the test subject's head was placed on cavity pillow the motion score was reduced from 69 to 59. The observed differences in the overall motion score of the cervical spine are mainly due to reduced flexion and extension rather than rotation or lateral inclination. CONCLUSION: The motion score of the cervical spine using motion sensors can provide important information for future analyses. The results of the present study suggest that trauma patients can be immobilized in the early trauma phase with a cervical collar and a head rest. The application of a cervical collar and the positioning on the concave pillow may achieve a good immobilization of the cervical spine in trauma patients in the early trauma phase.

DePicT Melanoma Deep-CLASS: a deep convolutional neural networks approach to classify skin lesion images.

BACKGROUND: Melanoma results in the vast majority of skin cancer deaths during the last decades, even though this disease accounts for only one percent of all skin cancers' instances. The survival rates of melanoma from early to terminal stages is more than fifty percent. Therefore, having the right information at the right time by early detection with monitoring skin lesions to find potential problems is essential to surviving this type of cancer. RESULTS: An approach to classify skin lesions using deep learning for early detection of melanoma in a case-based reasoning (CBR) system is proposed. This approach has been employed for retrieving new input images from the case base of the proposed system DePicT Melanoma Deep-CLASS to support users with more accurate recommendations relevant to their requested problem (e.g., image of affected area). The efficiency of our system has been verified by utilizing the ISIC Archive dataset in analysis of skin lesion classification as a benign and malignant melanoma. The kernel of DePicT Melanoma Deep-CLASS is built upon a convolutional neural network (CNN) composed of sixteen layers (excluding input and ouput layers), which can be recursively trained and learned. Our approach depicts an improved performance and accuracy in testing on the ISIC Archive dataset. CONCLUSIONS: Our methodology derived from a deep CNN, generates case representations for our case base to use in the retrieval process. Integration of this approach to DePicT Melanoma CLASS, significantly improving the efficiency of its image classification and the quality of the recommendation part of the system. The proposed method has been tested and validated on 1796 dermoscopy images. Analyzed results indicate that it is efficient on malignancy detection.

Injuries of the upper cervical spine-how can instability be identified?

OBJECTIVE: The diagnosis of instability of the injured upper cervical spine remains controversial, due to its complicated anatomical configuration and biomechanical property. Since identifying unstable injuries of the upper cervical spine is essential for immediate stabilizing therapy, this article reviews the current classification systems of upper cervical spine injuries and their statements towards instability. METHODS: A systematic review of literature concerning upper cervical spine injuries was performed on the PubMed database from inception to December 2019. An English literature search was conducted using various combinations of keyword terms. RESULTS: Numerous separate classification systems for each specific injury of the upper cervical spine were obtained. The early classifications are based primarily on injury morphology and mechanism. The recent classifications pay more attention to the investigation of ligamentous status. Various instability criteria were established as well. The determinants involve translation, vertical distraction, angulation, rotation, obliquity of fracture line, comminution, and ligamentous disruption. The status of crucial ligaments plays a key role in determining instability of upper cervical spine injuries. CT scan is more sensitive and reliable than X-ray in detecting misalignment of the upper cervical spine. CONCLUSION: Only a few classification systems support decision-making concerning instability leading to early operative treatment. The ligamentous integrity is the key element of impacting the stability of the upper cervical spine injuries. The transverse ligament serves as the most crucial element in determining the stability of occipital condyle fractures and atlas fractures as well as atlanto-axial injury. The integrity of anterior longitudinal ligament, disc, and facet joint attributes to the stability of axis fractures. The integrity of tectorial membrane and alar ligaments determines the stability of atlanto-occipital dislocation. The development of a newly classification system concerning ligamentous instability with a high clinical and scientific impact is recommended.

[Diagnostics and treatment of cervical spine trauma in pediatric patients : Recommendations from the Pediatric Spinal Trauma Group]. / Diagnostik und Therapie von Verletzungen der Halswirbelsäule im Kindesalter : Empfehlungen der AG Wirbelsäulentrauma im Kindesalter.

BACKGROUND: Severe cervical spine injuries in children under the age of 17 years are rare. Recommendations or even guidelines for the diagnostics and treatment of such injuries in children are currently not available. OBJECTIVE: The aim of the study was to formulate recommendations for diagnostics and treatment of injuries of the cervical spine in pediatric patients. MATERIAL AND METHODS: First, a search of primary and secondary literature on the topic complex of diagnostics and treatment of cervical spine injuries in children was carried out. An appropriate internal literature database was defined and maintained. Second, within the framework of 9 meetings from April 2017 to December 2019 the members of the Pediatric Spinal Trauma Group of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU) systematically formulated recommendations for the diagnostics and treatment of injuries of the cervical spine in pediatric patients by a consensus process. RESULTS: Recommendation for the diagnostics and treatment for injuries of the cervical spine could be formulated for three age groups (age group I: 0-6 years; age group II: 7-9 years; age group III: 10-16 years). The diagnostic and therapeutic principles known from adult patients suffering from injuries to the cervical spine cannot be easily transferred to pediatric patients. CONCLUSION: Injuries to the pediatric spine are rare and should be treated in specialized spine centers. Pediatric patients with a stable cardiopulmonary status should undergo magnetic resonance imaging (MRI) if a spinal trauma is suspected. Classification systems and therapeutic recommendations for injuries to the cervical spine known from adult patients could also be used for adolescent patients. This is not possible for children under the age of 10 years. Only few classification systems exist for this age group. Basic principles of the treatment of spinal trauma in children is the restoration of spinal stability and correct anatomical relationships as well as the protection of all neural structures.

[Diagnostics and treatment of thoracic and lumbar spine trauma in pediatric patients : Recommendations from the Pediatric Spinal Trauma Group]. / Diagnostik und Therapie von Verletzungen der Brust- und Lendenwirbelsäule im Kindesalter : Empfehlungen der AG Wirbelsäulentrauma im Kindesalter.

BACKGROUND: Spinal injuries in pediatric patients are overall very rare. Current reference studies including large patient numbers that enable the formulation of evidence-based recommendations on diagnostics and treatment of these injuries do not exist. OBJECTIVE: The aim of the current study was to formulate recommendations on the diagnostics and treatment for injuries of the thoracic and lumbar spine in pediatric patients. MATERIAL AND METHODS: Firstly, a search for primary and secondary literature on the topic of diagnostics and treatment of spinal injuries in children was carried out. From this, a literature database was established and maintained. Secondly, within the framework of 9 meetings in the time period from April 2017 to December 2019 the members of the Pediatric Spinal Trauma Group of the Spine Section of the German Society for Orthopaedics and Trauma (DGOU) documented recommendations on diagnostics and treatment of injuries of the thoracic and lumbar spine in pediatric patients by a consensus process. RESULTS: Recommendations on the diagnostics and treatment of injuries of the thoracic and lumbar spine could be given for 3 age groups (age group I: 0-6 years; age group II: 7-9 years; age group III: 10-16 years). Diagnostic and therapeutic principles known from adult patients suffering from injuries to the thoracic or lumbar spine cannot easily be transferred to pediatric patients. CONCLUSION: Spinal injuries in childhood are rare and should be treated in specialized spine centers. Pediatric patients with a stable cardiopulmonary status should undergo magnetic resonance imaging (MRI) if a spinal trauma is suspected. The basic principles of the treatment of spinal trauma in children is the restoration of spinal stability and correct anatomical parameters as well as the protection of all neural structures. The potential for correction and regeneration of the individual spinal sections depending on the age of the patient must be considered for deciding between operative vs. conservative treatment. Whenever operative treatment is needed, it should be performed by minimally invasive techniques as a sole instrumentation without spondylodesis. An early removal of the screw-rod-system should be performed.