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Investigating nocifensive withdrawal reflexes as potential surrogate marker for the spinal excitation level may widen the understanding of maladaptive nociceptive processing after spinal cord injury (SCI). The aim of this prospective, explorative cross-sectional observational study was to investigate the response behavior of individuals with SCI to noxious radiant heat (laser) stimuli and to assess its relation to spasticity and neuropathic pain, two clinical consequences of spinal hyperexcitability/spinal disinhibition. Laser stimuli were applied at the sole and dorsum of the foot and below the fibula head. Corresponding reflexes were electromyography (EMG) recorded ipsilateral. Motor responses to laser stimuli were analyzed and related to clinical readouts (severity of injury/spasticity/pain), using established clinical assessment tools. Twenty-seven participants, 15 with SCI (age 18-63; 6.5 years post-injury; AIS-A through D) and 12 non-disabled controls, [non-disabled controls (NDC); age 19-63] were included. The percentage of individuals with SCI responding to stimuli (70-77%; p < 0.001), their response rates (16-21%; p < 0.05) and their reflex magnitude ( p < 0.05) were significantly higher compared to NDC. SCI-related reflexes clustered in two time-windows, indicating involvement of both A-delta- and C-fibers. Spasticity was associated with facilitated reflexes in SCI (Kendall-tau-b p ≤ 0.05) and inversely associated with the occurrence/severity of neuropathic pain (Fisher's exact p < 0.05; Eta-coefficient p < 0.05). However, neuropathic pain was not related to reflex behavior. Altogether, we found a bi-component motor hyperresponsiveness of SCI to noxious heat, which correlated with spasticity, but not neuropathic pain. Laser-evoked withdrawal reflexes may become a suitable outcome parameter to explore maladaptive spinal circuitries in SCI and to assess the effect of targeted treatment strategies. Registration: https://drks.de/search/de/trial/DRKS00006779., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Franz, Heutehaus, Tappe-Theodor, Weidner, Treede and Schuh-Hofer.)

Paresis after spinal cord injury (SCI) is caused by damage to upper and lower motoneurons (LMNs) and may differentially impact neurological recovery. This prospective monocentric longitudinal observational study investigated the extent and severity of LMN dysfunction and its impact on upper extremity motor recovery after acute cervical SCI. Pathological spontaneous activity at rest and/or increased discharge rates of motor unit action potentials recorded by needle electromyography (EMG) were taken as parameters for LMN dysfunction and its relation to the extent of myelopathy in the first available spine magnetic resonance imaging (MRI) was determined. Motor recovery was assessed by standardized neurological examination within the first four weeks (acute stage) and up to one year (chronic stage) after injury. Eighty-five muscles of 17 individuals with cervical SCI (neurological level of injury from C1 to C7) and a median age of 54 (28-59) years were examined. The results showed that muscles with signs of LMN dysfunction peaked at the lesion center (Χ 2 [2, n  = 85] = 6.6, p  = 0.04) and that the severity of LMN dysfunction correlated with T2-weighted hyperintense MRI signal changes in routine spine MRI at the lesion site (Spearman ρ = 0.31, p  = 0.01). Muscles exhibiting signs of LMN dysfunction, as indicated by pathological spontaneous activity at rest and/or increased discharge rates of motor unit action potentials, were associated with more severe paresis in both the acute and chronic stages after SCI (Spearman ρ acute = -0.22, p  = 0.04 and chronic = -0.31, p  = 0.004). Moreover, the severity of LMN dysfunction in the acute stage was also associated with a greater degree of paresis (Spearman ρ acute = -0.24, p  = 0.03 and chronic = -0.35, p  = 0.001). While both muscles with and without signs of LMN dysfunction were capable of regaining strength over time, those without LMN dysfunctions had a higher potential to reach full strength. Muscles with signs of LMN dysfunction in the acute stage displayed increased amplitudes of motor unit action potentials with chronic-stage needle EMG, indicating reinnervation through peripheral collateral sprouting as compensatory mechanism (Χ 2 [1, n  = 72] = 4.3, p  = 0.04). Thus, LMN dysfunction represents a relevant factor contributing to motor impairment and recovery in acute cervical SCI. Defined recovery mechanisms (peripheral reinnervation) may at least partially underlie spontaneous recovery in respective muscles. Therefore, assessment of LMN dysfunction could help refine prediction of motor recovery after SCI.

Background: Accurate prediction of walking function after a traumatic spinal cord injury (SCI) is crucial for an appropriate tailoring and application of therapeutical interventions. Long-term outcome of ambulation is strongly related to residual muscle function acutely after injury and its recovery potential. The identification of the underlying determinants of ambulation, however, remains a challenging task in SCI, a neurological disorder presented with heterogeneous clinical manifestations and recovery trajectories., Objectives: Stratification of walking function and determination of its most relevant underlying muscle functions based on stratified homogeneous patient subgroups., Methods: Data from individuals with paraplegic SCI were used to develop a prediction-based stratification model, applying unbiased recursive partitioning conditional inference tree (URP-CTREE). The primary outcome was the 6-minute walk test at 6 months after injury. Standardized neurological assessments ≤15 days after injury were chosen as predictors. Resulting subgroups were incorporated into a subsequent node-specific analysis to attribute the role of individual lower extremity myotomes for the prognosis of walking function., Results: Using URP-CTREE, the study group of 361 SCI patients was divided into 8 homogeneous subgroups. The node specific analysis uncovered that proximal myotomes L2 and L3 were driving factors for the differentiation between walkers and non-walkers. Distal myotomes L4-S1 were revealed to be responsible for the prognostic distinction of indoor and outdoor walkers (with and without aids)., Conclusion: Stratification of a heterogeneous population with paraplegic SCI into more homogeneous subgroups, combined with the identification of underlying muscle functions prospectively determining the walking outcome, enable potential benefit for application in clinical trials and practice.

Epidural electrical epinal cord stimulation (ESCS) is an established therapeutic option in various chronic pain conditions. In the last decade, proof-of-concept studies have demonstrated that ESCS in combination with task-oriented rehabilitative interventions can partially restore motor function and neurological recovery after spinal cord injury (SCI). In addition to the ESCS applications for improvement of upper and lower extremity function, ESCS has been investigated for treatment of autonomic dysfunction after SCI such as orthostatic hypotension. The aim of this overview is to present the background of ESCS, emerging concepts and its readiness to become a routine therapy in SCI beyond treatment of chronic pain conditions., (© 2023. The Author(s).)

Background: Robotic lower-limb exoskeletons have the potential to provide additional clinical benefits for persons with spinal cord injury (SCI). However, high variability between protocols does not allow the comparison of study results on safety and feasibility between different exoskeletons. We therefore incorporated key aspects from previous studies into our study protocol and accordingly conducted a multicentre study investigating the safety, feasibility and usability of the ABLE Exoskeleton in clinical settings., Methods: In this prospective pretest-posttest quasi-experimental study across two SCI centres in Germany and Spain, in- and outpatients with SCI were recruited into a 12-session training and assessment protocol, utilising the ABLE Exoskeleton. A follow-up visit after 4 weeks was included to assess after-training outcomes. Safety outcomes (device-related adverse events (AEs), number of drop-outs), feasibility and usability measures (level of assistance, donning/doffing-time) were recorded at every session together with changes in gait parameters and function. Patient-reported outcome measures including the rate of perceived exertion (RPE) and the psychosocial impact of the device were performed. Satisfaction with the device was evaluated in both participants and therapists., Results: All 24 participants (45 ± 12 years), with mainly subacute SCI (< 1 year after injury) from C5 to L3, (ASIA Impairment Scale A to D) completed the follow-up. In 242 training sessions, 8 device-related AEs (pain and skin lesions) were reported. Total time for don and doff was 6:50 ± 2:50 min. Improvements in level of assistance and gait parameters (time, steps, distance and speed, p < 0.05) were observed in all participants. Walking function and RPE improved in participants able to complete walking tests with (n = 9) and without (n = 6) the device at study start (p < 0.05). A positive psychosocial impact of the exoskeleton was reported and the satisfaction with the device was good, with best ratings in safety (participants), weight (therapists), durability and dimensions (both)., Conclusions: Our study results prove the feasibility of safe gait training with the ABLE Exoskeleton in hospital settings for persons with SCI, with improved clinical outcomes after training. Our study protocol allowed for consistent comparison of the results with other exoskeleton trials and can serve as a future framework towards the standardisation of early clinical evaluations. Trial Registration https://trialsearch.who.int/ , DRKS00023503, retrospectively registered on November 18, 2020., (© 2023. The Author(s).)

Cervical spinal cord injury (SCI) causes extensive impairments for individuals which may include dextrous hand function. Although prior work has focused on the recovery at the person-level, the factors determining the recovery of individual muscles are poorly understood. Here, we investigate the muscle-specific recovery after cervical spinal cord injury in a retrospective analysis of 748 individuals from the European Multicenter Study about Spinal Cord Injury (NCT01571531). We show associations between corticospinal tract (CST) sparing and upper extremity recovery in SCI, which improves the prediction of hand muscle strength recovery. Our findings suggest that assessment strategies for muscle-specific motor recovery in acute spinal cord injury are improved by accounting for CST sparing, and complement person-level predictions., (© 2023. The Author(s).)

Background: Ischemic spinal cord injury (SCI) belongs to the heterogeneous group of non-traumatic SCI, while the course of sensorimotor and functional recovery is comparable to traumatic SCI. Recently, we derived from data of patients with traumatic SCI a valid model to predict an independent and reliable bowel management one year after SCI., Aim: To evaluate the performance of this model to predict an independent and reliable bowel management one year following ischemic SCI., Design: Prognostic study - observational study., Setting: European Multicenter Study about Spinal Cord Injury (EMSCI) ClinicalTrials.gov: NCT01571531., Population: One hundred and forty-two patients with ischemic SCI of various level and severity of injury., Methods: The prediction model relied on a single predictor collected within 40 days from injury, the International Standards for Neurological Classification of Spinal Cord Injury total motor score. Bowel outcome one year after SCI derived from the dichotomization of the Spinal Cord Independence Measure (SCIM) item 7 scores. We defined a positive outcome as independent bowel management with regular movements and appropriate timing with no or rare accidents (score of 10 in SCIM version II and score of 8 or 10 in version III)., Results: The model showed a fair discrimination with an area under the receiver operating characteristic (ROC) curve of 0.780 (95% confidence interval=0.702-0.860). In addition, the model displayed an acceptable accuracy and calibration., Conclusions: The study extends the validity of our rule to patients with ischemic SCI, thus providing the first model to predict an independent and reliable bowel management in this population., Clinical Rehabilitation Impact: The model may be employed in clinical practice to counsel patients, to define the rehabilitation aims and to estimate the need of assistance after discharge, as well as in the research field for the optimization of patients' allocation in the design of future clinical trials.

Physical activity-based rehabilitative interventions represent the main treatment concept for people suffering from spinal cord injury (SCI). The role such interventions play in the relief of neuropathic pain (NP) states is emerging, along with underlying mechanisms resulting in SCI-induced NP (SCI-NP). Animal models have been used to investigate the benefits of activity-based interventions (ABI), such as treadmill training, wheel running, walking, swimming, and bipedal standing. These activity-based paradigms have been shown to modulate inflammatory-related alterations as well as induce functional and structural changes in the spinal cord gray matter circuitry correlated with pain behaviors. Thus far, the research available provides an incomplete picture of the cellular and molecular pathways involved in this beneficial effect. Continued research is essential for understanding how such interventions benefit SCI patients suffering from NP and allow the development of individualized rehabilitative therapies. This article reviews preclinical studies on this specific topic, goes over mechanisms involved in SCI-NP in relation to ABI, and then discusses the effectiveness of different activity-based paradigms as they relate to different forms, intensity, initiation times, and duration of ABI. This article also summarizes the mechanisms of respective interventions to ameliorate NP after SCI and provides suggestions for future research directions.

Background and Purpose: The multicentre EORTC 22922/10925 trial (ClinicalTrials.gov, NCT00002851) was conducted between 1996 and 2004. The trial evaluated the effect of irradiation of the internal mammary and medial supraclavicular lymph node chains (IM-MS) vs no further radiation therapy (RT) on survival and cause of death in breast cancer stage I-III patients. At 15.7 years of median follow-up, a significant reduction of breast cancer specific mortality (BCSM) and any recurrence, not translating in improved overall survival (OS), and low absolute rates of side effects were found. The aim of the current analysis was to evaluate the association of RT techniques of IM-MS lymph node irradiation with long-term outcomes., Patients and Methods: Three RT techniques were used for IM-MS: a standard technique using a fixed set-up combining photon/electron beams to the IM and tangential fields to the breast or chest wall vs a standard-modified technique with minor adaptation for beam settings vs a more individualised technique based on individual localisation of the IM. Techniques used were fixed per institution over the duration of the trial. We performed an exploratory and descriptive analysis of the outcomes after 15 years follow-up for the three RT techniques., Results: Between July 1996 and January 2004, 46 radiation oncology departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. The number of patients treated by each technique was 2440 (61%) by standard vs 635 (16%) by standard-modified vs 929 (23%) patients by individualised technique. The absolute improvements of oncological outcomes in terms of disease-free survival (DFS), OS and BCSM with IM-MS RT compared to no IM-MS RT were 6.8%, 4.9% and -5.8% for the individualised technique, vs 1.6%, 2.9% and -4.3% for modified standard and -1.4%, 1.1% and -3% for standard technique, respectively. The increase in 15-year rates of side effects due to IM-MS RT, both scored longitudinally and cross-sectionally, were similar among the techniques., Conclusion: Even though a straightforward comparison by technique is not possible because of variations in baseline characteristics between institutions, our findings suggest that the use of more individualised RT techniques is associated with higher rates of oncological improvements without increased risks for late side effects., Competing Interests: Conflicts of interest None. The funder of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication. None of the authors has a conflict of interest related to this work., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Seroconversion after COVID-19 vaccination is impaired in kidney transplant recipients. Emerging variants of concern such as the B.1.617.2 (delta) and the B.1.1.529 (omicron) variants pose an increasing threat to these patients. In this observational cohort study, we measured anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies three weeks after a third mRNA vaccine dose in 49 kidney transplant recipients and compared results to 25 age-matched healthy controls. In addition, vaccine-induced neutralization of SARS-CoV-2 wild-type, the B.1.617.2 (delta), and the B.1.1.529 (omicron) variants was assessed using a live-virus assay. After a third vaccine dose, anti-S1 IgG, surrogate neutralizing, and anti-receptor-binding domain antibodies were significantly lower in kidney transplant recipients compared to healthy controls. Only 29/49 (59%) sera of kidney transplant recipients contained neutralizing antibodies against the SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant and neutralization titers were significantly reduced compared to healthy controls (p < 0.001). Vaccine-induced cross-neutralization of the B.1.1.529 (omicron) variants was detectable in 15/35 (43%) kidney transplant recipients with seropositivity for anti-S1 IgG, surrogate neutralizing, and/or anti-RBD antibodies. Neutralization of the B.1.1.529 (omicron) variants was significantly reduced compared to neutralization of SARS-CoV-2 wild-type or the B.1.617.2 (delta) variant for both, kidney transplant recipients and healthy controls (p < .001 for all)., (© 2022 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.)

Purpose: For patients treated with partial breast irradiation (PBI), potential long-term treatment-related toxicities are important. The 1.5 T magnetic resonance guided linear accelerator (MRL) offers excellent tumor bed visualization and a daily treatment plan adaption possibility, but MRL-specific electron stream and return effects may cause increased dose deposition at air-tissue interfaces. In this study, we aimed to investigate the projected risk of radiation-induced secondary malignancies (RISM) in patients treated with PBI at the 1.5 T MRL., Methods: Projected excess absolute risk values (EARs) for the contralateral breast, lungs, thyroid and esophagus were estimated for 11 patients treated with PBI at the MRL and compared to 11 patients treated with PBI and 11 patients treated with whole breast irradiation (WBI) at the conventional linac (CTL). All patients received 40.05 Gy in 15 fractions. For patients treated at the CTL, additional dose due to daily cone beam computed tomography (CBCT) was simulated. The t‑test with Bonferroni correction was used for comparison., Results: The highest projected risk for a radiation-induced secondary cancer was found for the ipsilateral lung, without significant differences between the groups. A lower contralateral breast EAR was found for MRL-PBI (EAR = 0.89) compared to CTL-PBI (EAR = 1.41, p = 0.01), whereas a lower thyroid EAR for CTL-PBI (EAR = 0.17) compared to MRL-PBI (EAR = 0.33, p = 0.03) and CTL-WBI (EAR = 0.46, p = 0.002) was observed. Nevertheless, when adding the CBCT dose no difference between thyroid EAR for CTL-PBI compared to MRL-PBI was detected., Conclusion: Better breast tissue visualization and the possibility for daily plan adaption make PBI at the 1.5 T MRL particularly attractive. Our simulations suggest that this treatment can be performed without additional projected risk of RISM., (© 2022. The Author(s).)

The present analysis compares the esthetics assessment by the BCCT.core software in relation to patients' and physicians' ratings, based on the IMRT-MC2 trial. Within this trial, breast cancer patients received breast-conserving surgery (BCS) and adjuvant radiotherapy. At the baseline, 6 weeks, and 2 years after radiotherapy, photos of the breasts were assessed by the software and patients' and physicians' assessments were performed. Agreement rates of the assessments and their correlation with breast asymmetry indices were evaluated. The assessments of the software and the physicians were significantly correlated with asymmetry indices. Before and 6 weeks after radiotherapy, the patients' self-assessment was only correlated with the lower breast contour (LBC) and upward nipple retraction (UNR), while after 2 years, there was also a correlation with other indices. Only a slight agreement between the BCCT.core software and the physicians' or patients' assessment was seen, while a moderate and substantial agreement was detected between the physicians' and the patients' assessment after 6 weeks and 2 years, respectively. The BCCT.core software is a reliable tool to measure asymmetries, but may not sufficiently evaluate the esthetic outcome as perceived by patients. It may be more appropriate for a long-term follow-up, when symmetry appears to increase in importance.

Background: The epidemiological international landscape of traumatic spinal cord injury (SCI) has evolved over the last decades along with given inherent differences in acute care and rehabilitation across countries and jurisdictions. However, to what extent these differences may influence neurological and functional recovery as well as the integrity of international trials is unclear. The latter also relates to historical clinical data that are exploited to inform clinical trial design and as potential comparative data., Methods: Epidemiological and clinical data of individuals with traumatic and ischemic SCI enrolled in the European Multi-Center Study about Spinal Cord Injury (EMSCI) were analyzed. Mixed-effect models were employed to account for the longitudinal nature of the data, efficiently handle missing data, and adjust for covariates. The primary outcomes comprised demographics/injury characteristics and standard scores to quantify neurological (i.e., motor and sensory scores examined according to the International Standards for the Neurological Classification of Spinal Cord Injury) and functional recovery (walking function). We externally validated our findings leveraging data from a completed North American landmark clinical trial., Results: A total of 4601 patients with acute SCI were included. Over the course of 20 years, the ratio of male to female patients remained stable at 3:1, while the distribution of age at injury significantly shifted from unimodal (2001/02) to bimodal distribution (2019). The proportional distribution of injury severities and levels remained stable with the largest percentages of motor complete injuries. Both, the rate and pattern of neurological and functional recovery, remained unchanged throughout the surveillance period despite the increasing age at injury. The findings related to recovery profiles were confirmed by an external validation cohort (n=791). Lastly, we built an open-access and online surveillance platform ("Neurosurveillance") to interactively exploit the study results and beyond., Conclusions: Despite some epidemiological changes and considerable advances in clinical management and rehabilitation, the neurological and functional recovery following SCI has remained stable over the last two decades. Our study, including a newly created open-access and online surveillance tool, constitutes an unparalleled resource to inform clinical practice and implementation of forthcoming clinical trials targeting neural repair and plasticity in acute spinal cord injury., (© 2022. The Author(s).)

Sensorimotor function of patients with spinal cord injury (SCI) is commonly assessed according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). From the ISNCSCI segmental motor and sensory assessments, upper and lower extremity motor scores (UEMS and LEMS), sum scores of pinprick (PP) and light touch (LT) sensation, the neurological level of injury (NLI) and the classification of lesion severity according to the American Spinal Injury Association Impairment Scale (AIS) grade are derived. Changes of these parameters over time are used widely to evaluate neurological recovery. Evaluating recovery based on a single ISNCSCI scoring or classification variable, however, may misestimate overall recovery. Here, we propose an Integrated Neurological Change Score (INCS) based on the combination of normalized changes between two time points of UEMS, LEMS, and total PP and LT scores. To assess the agreement of INCS with clinical judgment of meaningfulness of neurological changes, changes of ISNCSCI variables between two time points of 88 patients from an independent cohort were rated by 20 clinical experts according to a five-categories Likert Scale. As for individual ISNCSCI variables, neurological change measured by INCS is associated with severity (AIS grade), age, and time since injury, but INCS better reflects clinical judgment about meaningfulness of neurological changes than individual ISNCSCI variables. In addition, INCS is related to changes in functional independence measured by the Spinal Cord Independence Measure (SCIM) in patients with tetraplegia. The INCS may be a useful measure of overall neurological change in clinical studies.

Background: New therapeutic approaches in neurological disorders are progressing into clinical development. Past failures in translational research have underlined the critical importance of selecting appropriate inclusion criteria and primary outcomes. Narrow inclusion criteria provide sensitivity, but increase trial duration and cost to the point of infeasibility, while broader requirements amplify confounding, increasing the risk of trial failure. This dilemma is perhaps most pronounced in spinal cord injury (SCI), but applies to all neurological disorders with low frequency and/or heterogeneous clinical manifestations., Objective: Stratification of homogeneous patient cohorts to enable the design of clinical trials with broad inclusion criteria., Methods: Prospectively-gathered data from patients with acute cervical SCI were analysed using an unbiased recursive partitioning conditional inference tree (URP-CTREE) approach. Performance in the 6-minute walk test at 6 months after injury was classified based on standardized neurological assessments within the first 15 days of injury. Functional and neurological outcomes were tracked throughout rehabilitation up to 6 months after injury., Results: URP-CTREE identified homogeneous outcome cohorts in a study group of 309 SCI patients. These cohorts were validated by an internal, yet independent, validation group of 172 patients. The study group cohorts identified demonstrated distinct recovery profiles throughout rehabilitation. The baseline characteristics of the analysed groups were compared to a reference group of 477 patients., Conclusion: URP-CTREE enables inclusive trial design by revealing the distribution of outcome cohorts, discerning distinct recovery profiles and projecting potential patient enrolment by providing estimates of the relative frequencies of cohorts to improve the design of clinical trials in SCI and beyond.

Objective : In spinal cord injury (SCI), heterotopic ossification is a frequent secondary complication, commonly associated with limited range of motion of affected joints, which could lead to secondary disability in activities of daily living. Additionally, heterotopic ossifications might challenge the effect of regeneration-promoting therapies on neurological and functional recovery. This study evaluated the impact of heterotopic ossification on clinical recovery within the first year after SCI. Methods : The study was conducted as a monocentric longitudinal paired cohort study. Recruitment was based on consecutive sampling in the framework of the European Multicenter about Spinal Cord Injury (EMSCI). Recovery profiles were determined using standardized neurological and functional clinical assessments within the 1st year following SCI. All study participants underwent at least two comprehensive standardized neurological and functional clinical examinations according to the International Standards for Neurological Classification of SCI and the Spinal Cord Independence Measure, respectively. Data regarding the diagnosis and treatment of heterotopic ossification were obtained by reviewing the patient medical records. The most similar "digital twin" from the entire EMSCI database were matched in terms of age, acute neurological and functional status to each individual with SCI, and heterotopic ossification. Results : Out of 25 participants diagnosed with heterotopic ossification, 13 individuals were enrolled and matched to control individuals. Most individuals presented with motor complete injury (75%). Ossifications were most frequently located at the hip joints (92%) and mainly occurred within the first 3 months after SCI. Individuals with heterotopic ossification achieved around 40% less functional improvement over time compared to their matched counterparts, whereas neurological recovery was not altered in individuals with SCI and heterotopic ossification. Conclusion : Heterotopic ossification-a common complication of SCI-unfavorably affects functional recovery, which in the end is most relevant for the best possible degree of independence in activities of daily living. Upon presentation with heterotopic ossification, neurological improvement achieved through potential restorative therapies might not translate into clinically meaningful functional improvement. Diagnostic algorithms and effective early prevention/treatment options for heterotopic ossification need to be established to ensure the best possible functional outcome. Clinical Trial Registration : NCT01571531 (https://clinicaltrials.gov)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Franz, Rust, Heutehaus, Rupp, Schuld and Weidner.)

Objectives: Since their introduction, electronic International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) calculators have evolved to powerful tools providing error-free ISNCSCI classifications in education, research and clinical practice. For increased accessibility and dissemination, a multilingual support is mandatory. The aim of this work was to setup a general multilingual framework for the freely available ISNCSCI calculator ( https://ais.emsci.org ) of the European Multicenter Study about Spinal Cord Injury (EMSCI)., Methods: The graphical user interface (GUI) and PDF export of the ISNCSCI worksheet were adapted for multilingual implementations. Their language-dependent content was identified. These two steps called internationalization have to be performed by a programmer in preparation of the translations of the English terms into the target language. This step following the internationalization is called localization and needs input by a bi-lingual clinical expert. Two EMSCI partners provided Standard Mandarin Chinese and Czech translations. Finally, the translations are made available in the application., Results: The GUI and PDF export of the ISNCSCI worksheet were internationalized. The default language of the calculator is set according to the user's preferences with the additional possibility for manual language selection. The Chinese as well as a Czech translation were provided freely to the SCI community., Conclusions: The possibility of multilingual implementations independent from software developers opens the use of ISNCSCI computer algorithms as an efficient training tool on a larger scale., (© 2021. The Author(s).)

Study Design: Prospective pre-post study., Objectives: International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) represents the most frequently used assessment to determine the level and severity of a spinal cord injury (SCI). The guidelines for ISNCSCI are complex and challenging. Knowledge of its correct execution needs to be imparted precisely. The aim of this study was to investigate whether hands-on instructional courses can increase the knowledge of the ISNCSCI examination guidelines., Setting: European Multicenter Study about SCI., Methods: Before and after the instructional courses, participants were asked to complete questionnaires. The set of questions covered the most important aspects of the examination guidelines. Attendees were asked to self-rate their occupation and experience in ISNCSCI., Results: The comparison of pretest and posttest results of 164 attendees from 2014 to 2018 revealed an improvement of knowledge reflected by an increase of correct answers from 66 ± 17% before to 89 ± 11% after the course (p < 0.01). The improvement was not associated with occupation (p > 0.1). However, the correctness of pretest results differed concerning both the period of experience with ISNCSCI (p < 0.05) and the course language (p < 0.01), while the frequency of execution resulted in differences in the posttest (p = 0.01)., Conclusions: Instructional courses substantially improve knowledge of the ISNCSCI examination guidelines. Differences in knowledge present before the course leveled off after the course. Comprehensive theoretical training is strongly recommended to ensure reliability and validity of ISNCSCI examinations in clinical routine and research. Albeit being practiced in the instructional courses, the benefit of hands-on training still needs to be systematically evaluated in future studies., (© 2020. The Author(s).)

Purpose: This retrospective analysis aims to address the toxicity and efficacy of a modified total nodal irradiation (TNI)-based conditioning regimen before haploidentical hematopoietic cell transplantation (HCT) in pediatric patients., Materials and Methods: Patient data including long-term follow-up were evaluated of 7 pediatric patients with malignant (n = 2) and non-malignant diseases (n = 5) who were treated by a primary TNI-based conditioning regimen. TNI was performed using anterior/posterior opposing fields. All patients received 7 Gy single-dose TNI combined with systemic agents followed by an infusion of peripheral blood stem cells (n = 7). All children had haploidentical family donors., Results: Engraftment was reached in 6/7 children after a median time of 9.5 days; 1 child had primary graft failure but was successfully reconditioned shortly thereafter. After an average follow-up time of 103.5 months (range 8.8-138.5 months), event-free (EFS) and overall survival (OS) rates were 71.4% and 85.7%, respectively. One child with a non-malignant disease died 8.8 months after transplantation due to a relapse and a multiple organ failure. Follow-up data was available for 5/6 long-term survivors with a median follow-up (FU) of 106.2 months (range 54.5-138.5 months). Hypothyroidism and deficiency of sexual hormones was present in 3/5 patients each. Mean forced expiratory volume in 1 s (FEV1) after TNI was 71%; mean vital capacity (VC) was 78%. Growth failure (< 10th percentile) occurred in 2/5 patients (height) and 1/5 patient (weight). No secondary malignancies were reported., Conclusion: In this group of patients, a primary single-dose 7 Gy TNI-based conditioning regimen before HCT in pediatric patients allowed sustained engraftment combined with a tolerable toxicity profile leading to long-term OS/EFS. Late toxicity after a median FU of over 9 years includes growth failure, manageable hormonal deficiencies, and acceptable decrease in lung function., (© 2021. The Author(s).)

Purpose: To evaluate the long-term efficacy of combined radiotherapy (RT) and hyperthermia (HT) in a large mono-institutional cohort of breast cancer (BC) patients affected by recurrent, newly diagnosed non-resectable or high risk resected tumor., Materials and Methods: Records of BC patients treated with RT + HT between 1995 and 2018 were retrospectively analyzed. RT doses of 50-70 Gy concurrent to a twice per week superficial HT were applied. For HT, a temperature between 41 and 42 °C was applied for approximately 1 h. Primary endpoint was local control (LC), secondary endpoints comprised toxicity, overall survival (OS), and progression-free survival (PFS)., Results: A total of 191 patients and 196 RT + HT treatments were analyzed. In 154 cases (78.6%) RT + HT was performed for patients with recurrent BC. Among these, 93 (47.4% of the entire cohort) had received RT prior to RT + HT. Median follow up was 12.7 years. LC at 2, 5, and 10 years was 76.4, 72.8, and 69.5%, respectively. OS at 2, 5, and 10 years was 73.5, 52.3, and 35.5%, respectively. PFS at 2, 5, and 10 years was 55.6, 41, and 33.6%, respectively. Predictive factors for LC were tumor stage, distant metastases, estrogen/progesterone receptor expression, resection status and number of HT fractions. At multivariate analysis tumor stage and receptor expression were significant. No acute or late toxicities higher than grade 3 were observed., Conclusion: Combined RT + HT offers long-term high LC rates with acceptable toxicity for patients with recurrent, newly diagnosed non-resectable or resected BC at high risk of relapse.

Six new "axial-bonding" type "phosphorus(V) porphyrin-naphthalene" conjugates have been prepared consisting of octaethylporphyrinatophosphorus(V) (POEP + )/tetraphenylporphyrinatophosphorus(V) (PTPP + ) and naphthalene (NP). The distance between the porphyrin and NP was systematically varied using polyether bridges. The unique structural topology of the octaethylporphyrinatophosphorus(V) (POEP + ) and tetraphenylporphyrinatophosphorus(V) (PTPP + ) enabled construction of mono- and disubstituted phosphorus(V) porphyrin-naphthalene conjugates, respectively. The steady-state and transient spectral properties were investigated as a function of redox properties, distance, and molecular topology. Strong electronic interactions between the phosphorus(V) porphyrin and NP in directly bound conjugates were observed. The established energy diagrams predicted reductive electron transfer involving singlet excited phosphorus(V) porphyrin and NP to generate high-energy (∼1.83-2.11 eV) charge-separated states (POEP/PTPP) • -(NP) •+ . Femtosecond transient absorption spectral studies revealed rapid deactivation of singlet excited phosphorus(V) porphyrin due to charge separation wherein the estimated forward rate constants were in the range of 10 9 -10 10 s -1 and were dependent on the distance between the NP and porphyrins units, as well as the redox potentials of the type of the phosphorus(V) porphyrin. Additionally, due to high exothermicity and low-lying triplet states, the charge recombination process was found to be rapid, leading to populating the triplet states of phosphorus(V) porphyrins.

Objective: In Germany, treatment paths for patients with acute spinal cord injury (SCI) differ considerably depending on intrinsic, disease-specific and extrinsic factors. Which of these factors are associated with improved outcome with fewer subsequent complications and inpatient re-admissions is not clear. The German-wide, patient-centered, web-based ParaReg registry will be implemented to improve the long-term quality of patient care and the planning of treatment paths with increased cost-effectiveness., Methods: In the 2017-18 conceptualization phase, the data model of the registry was developed in an iterative process of the ParaReg steering committee together with the extended DMGP board and patient representatives. In ParaReg, routine social and medical data as well as internationally established neurological, functional and participation scores will be documented. The assignment of a unique patient ID allows a lifelong, cross-center documentation of inpatient stays in one of the 27 SCI centers organized in the German-speaking Medical Society for SCI (DMGP). The ParaReg data protection concept and patient information/consent are based on the Open Source Registry for Rare Diseases (OSSE) which were extended by GDPR-relevant aspects., Results: In the realization phase, which started in 2019, the information technology infrastructure was implemented according to the clinical ID management module of the Technology and Methods Platform for Networked Medical Research (TMF). In parallel, the legal and ethical prerequisites for registry operation under the patronage of the DMGP were created. Recommendations of the working group data protection of the TMF were integrated into ParaReg's data protection concept. Based on the feedback from the alpha test phase with documentation of the hospitalization data of 40 patients, the ergonomics of the electronic case report forms were improved in particular for data entry on mobile devices., Conclusion: After completion of the monocentric alpha test phase, the multicenter data acquisition was started in 5 DMGP-SCI centers. The sustainability of ParaReg is ensured by the structural and financial support of the DMGP after expiry of the funding by the German Federal Ministry of Education and Research (BMBF)., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht. Die Autorinnen/Autoren erhalten eine finanzielle Förderung vom BMBF, der DMGP und des Universitätsklinikums Heidelberg., (Thieme. All rights reserved.)

Background: To assess the risk of aspiration, nutrient tolerance, and gastric emptying of patients in ICUs, gastric ultrasound can provide information about the gastric contents. Using established formulas, the gastric residual volume (GRV) can be calculated in a standardized way by measuring the gastric antrum. The purpose of this study was to determine the GRV in a cohort of enterally fed patients using a miniaturized ultrasound device to achieve knowledge about feasibility and the GRV over time during the ICU stay. The findings could contribute to the optimization of enteral nutrition (EN) therapy., Methods: A total of 217 ultrasound examinations with 3 measurements each (651 measurements in total) were performed twice daily (morning and evening) in a longitudinal observational study on 18 patients with EN in the interdisciplinary surgical ICU of Saarland University Medical Center. The measured values of the GRV were analyzed in relation to the clinical course, the nutrition, and other parameters., Results: Measurements could be performed without interrupting the flow of clinical care and without pausing EN. The GRV was significantly larger with sparsely auscultated bowel sounds than with normal and excited bowel sounds ( p < 0.01). Furthermore, a significantly larger GRV was present when using a high-caloric/low-protein nutritional product compared to an isocaloric product ( p = 0.02). The GRV at the morning and evening measurements showed no circadian rhythm. When comparing the first and last ultrasound examination of each patient, there was a tendency towards an increased GRV ( p = 0.07)., Conclusion: The GRV measured by miniaturized ultrasound devices can provide important information about ICU patients without restricting treatment procedures in the ICU. Measurements are possible while EN therapy is ongoing. Further studies are needed to establish gastric ultrasound as a management tool in nutrition therapy.

Background: Uncertainty about the benefit-risk ratio of regional lymph node irradiation led to varying clinical protocols. We investigated long-term late side effects after internal mammary and medial supraclavicular (IM-MS) lymph node irradiation to improve shared decision making., Methods: The multicenter European Organization for Research and Treatment of Cancer trial (ClinicalTrials.gov, NCT00002851) randomly assigned stage I-III breast cancer patients with involved axillary nodes and/or a medially located primary tumor. We analyzed late side effects both longitudinally at every follow-up and cross-sectionally at 5-year intervals. All statistical tests were 2-sided., Results: Between 1996 and 2004, 46 departments from 13 countries accrued 4004 patients. Median follow-up was 15.7 years. Longitudinal follow-up data showed cumulative incidence rates at 15 years of 2.9% (95% confidence interval [CI] = 2.2% to 3.8%) vs 5.7% (95% CI = 4.7% to 6.9%) (P < .001) for lung fibrosis, 1.1% (95% CI = 0.7% to 1.7%) vs 1.9% (95% CI = 1.3% to 2.6%) (P = .07) for cardiac fibrosis, and 9.4% (95% CI = 8.0% to 10.8%) vs 11.1% (95% CI = 9.6% to 12.7%) (P = .04) for any cardiac disease when treated without or with IM-MS lymph node irradiation. There was no evidence for differences between left- and right-sided breast cancer (Wald χ2 test of treatment by breast side interaction, P = .33 and P = .35, for cardiac fibrosis and for any cardiac disease, respectively). The cumulative incidence probabilities of cross-sectionally reported side effects with a score of 2 or greater at 15 years were 0.1% (95% CI = 0.0% to 0.5%) vs 0.8% (95% CI = 0.4% to 1.4%) for pulmonary (P = .02), 1.8% (95% CI = 1.1% to 2.8%) vs 2.6% (95% CI = 1.8% to 3.7%) for cardiac (P = .15), and 0.0% (95% CI not evaluated) vs 0.1% (95% CI = 0.0% to 0.4%) for esophageal (P = .16), respectively. No difference was observed in the incidence of second malignancies, contralateral breast cancer, or cardiovascular deaths., Conclusions: The incidence of late pulmonary side effects was statistically significantly higher after IM-MS lymph node irradiation, as were some of the cardiac events, without a difference between left- and right-sided treatments. Absolute rates and differences were very low, without increased non-breast cancer-related mortality, even before introducing heart-sparing techniques., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: We recently published 2-year results of the prospective, randomized IMRT-MC2 trial, showing non-inferior local control and cosmesis in breast cancer patients after conventionally fractionated intensity-modulated radiotherapy with simultaneously integrated boost (IMRT-SIB), compared to 3D-conformal radiotherapy with sequential boost (3D-CRT-seqB). Here, we report on 2-year quality of life results., Patients and Methods: 502 patients were enrolled and randomized to IMRT-SIB (50.4 Gy in 1.8 Gy fractions with a 64.4 Gy SIB to the tumor bed) or to 3D-CRT-seqB (50.4 Gy in 1.8 Gy fractions, followed by a sequential boost of 16 Gy in 2 Gy fractions). For quality of life (QoL) assessment, patients completed the QLQ-C30 and QLQ-BR23 questionnaires at baseline, 6 weeks and 2 years after radiotherapy., Results: Significant differences between treatment arms were seen 6 weeks after radiotherapy for pain (22.3 points for IMRT vs. 27.0 points for 3D-CRT-seqB; p = 0.033) and arm symptoms (18.1 points for IMRT vs. 23.6 points for 3D-CRT-seqB; p = 0.013), both favoring IMRT-SIB. Compared to baseline values, both arms showed significant improvement in global score (IMRT: p = 0.009; 3D-CRT: p = 0.001) after 2 years, with slight deterioration on the role (IMRT: p = 0.008; 3-D-CRT: p = 0.001) and social functioning (IMRT: p = 0.013, 3D-CRT: p = 0.001) as well as the future perspectives scale (IMRT: p = 0.003; 3D-CRT: p = 0.0034)., Conclusion: This is the first randomized phase III trial demonstrating that IMRT-SIB was associated with slightly superior QoL compared to 3-D-CRT-seqB. These findings further support the clinical implementation of SIB in adjuvant breast cancer treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Purpose: Hypofractionated radiotherapy is the standard of care for adjuvant whole breast radiotherapy (RT). However, adoption has been slow. The indication for regional nodal irradiation has been expanded to include patients with 0-3 involved lymph nodes. We investigated the impact of the publication of the updated German S3 guidelines in 2017 on adoption of hypofractionation and enrollment of patients with lymph node involvement within a randomized controlled phase III trial., Methods: In the experimental arm of the HYPOSIB trial (NCT02474641), hypofractionated RT with simultaneous integrated boost (SIB) was used. In the standard arm, RT could be given as hypofractionated RT with sequential boost (HF seq ), normofractionated RT with sequential boost (NF seq ), or normofractionated RT with SIB (NF SIB ). The cutoff date for the updated German S3 guidelines was December 17, 2017. Temporal trends were analyzed by generalized linear regression models. Multiple logistic regression models were used to investigate the influence of time (prior to/after guideline) and setting (university hospital/other institutions) on the fractionation patterns., Results: Enrollment of patients with involved lymph nodes was low throughout the trial. Adoption of HF seq increased over time and when using the guideline publication date as cutoff. Results of the multiple logistic regressions showed an interaction between time and setting. Furthermore, the use of HF seq was significantly more common in university hospitals., Conclusion: The use of HF seq in the standard arm increased over the course of the HYPOSIB trial and after publication of the S3 guideline update. This was primarily driven by patients treated in university hospitals. Enrolment of patients with lymph node involvement was low throughout the trial., (© 2020. The Author(s).)

Background: The extent to which children and adolescents contribute to SARS-CoV-2 transmission remains not fully understood. Novel high-capacity testing methods may provide real-time epidemiological data in educational settings helping to establish a rational approach to prevent and minimize SARS-CoV-2 transmission. We investigated whether pooling of samples for SARS-CoV-2 detection by RT-qPCR is a sensitive and feasible high-capacity diagnostic strategy for surveillance of SARS-CoV-2 infections in schools., Methods: In this study, students and school staff of 14 educational facilities in Germany were tested sequentially between November 9 and December 23, 2020, two or three times per week for at least three consecutive weeks. Participants were randomized for evaluation of two different age adjusted swab sampling methods (oropharyngeal swabs or buccal swabs compared to saliva swabs using a 'lolli method'). Swabs were collected and pooled for SARS-CoV-2 RT-qPCR. Individuals of positive pooled tests were retested by RT-qPCR the same or the following day. Positive individuals were quarantined while the SARS-CoV-2 negative individuals remained in class with continued pooled RT-qPCR surveillance. The study is registered with the German Clinical Trials register (registration number: DRKS00023911)., Findings: 5,537 individuals were eligible and 3970 participants were enroled and included in the analysis. In students, a total of 21,978 swabs were taken and combined in 2218 pooled RT-qPCR tests. We detected 41 positive pooled tests (1·8%) leading to 36 SARS-CoV-2 cases among students which could be identified by individual re-testing. The cumulative 3-week incidence for primary schools was 564/100,000 (6/1064, additionally 1 infection detected in week 4) and 1249/100,000 (29/2322) for secondary schools. In secondary schools, there was no difference in the number of SARS-CoV-2 positive students identified from pooled oropharyngeal swabs compared to those identified from pooled saliva samples (lolli method) (14 vs. 15 cases; 1·3% vs. 1·3%; OR 1.1; 95%-CI 0·5-2·5). A single secondary school accounted for 17 of 36 cases (47%) indicating a high burden of asymptomatic prevalent SARS-CoV-2 cases in the respective school and community., Interpretation: In educational settings, SARS-CoV-2 screening by RT-qPCR-based pooled testing with easily obtainable saliva samples is a feasible method to detect incident cases and observe transmission dynamics., Funding: Federal Ministry of education and research (BMBF; Project B-FAST in "NaFoUniMedCovid19"; registration number: 01KX2021)., Competing Interests: All authors declare no competing interests., (© 2021 The Authors.)

(1) Background: Reliable ultrasonographic measurements of optic nerve sheath diameter (ONSD) to detect increased intracerebral pressure (ICP) has not been established in awake patients with continuous invasive ICP monitoring. Therefore, in this study, we included fully awake patients with and without raised ICP and correlated ONSD with continuously measured ICP values. (2) Methods: In a prospective study, intracranial pressure (ICP) was continuously measured in 25 patients with an intraparenchymatic P-tel probe. Ultrasonic measurements were carried out three times for each optic nerve in vertical and horizontal directions. ONSD measurements and ICP were correlated. Patients with ICP of 2.0-10.0 mmHg were compared with patients suffering from an ICP of 10.1-24.2 mmHg. (3) Results: In all patients, the ONSD vertical and horizontal measurement for both eyes correlated well with the ICP (Pearson R = 0.68-0.80). Both measurements yielded similar results (Bland-Altman: vertical bias: -0.09 mm, accuracy: ±0.66 mm; horizontal bias: -0.06 mm, accuracy: ±0.48 mm). For patients with an ICP of 2.0-10.0 mmHg compared to an ICP of 10.1-24.2, ROC (receiver operating characteristic) analyses showed that ONSD measurement accurately predicts elevated ICP (optimal cut-off value 5.05 mm, AUC of 0.91, sensitivity 92% and specificity 90%, p < 0.001). (4) Conclusions: Ultrasonographic measurement of ONSD in awake, spontaneously breathing patients provides a valuable method to evaluate patients with suspected increased ICP. Additionally, it provides a potential tool for rapid assessment of ICP at the bedside and to identify patients at risk for a poor neurological outcome.

Study Design: Multicenter observational study., Objective: To describe the long-term outcome of functional independence and quality of life (QoL) for individuals with traumatic and ischemic SCI beyond the first year after injury., Setting: A multicenter study in Germany., Methods: Participants of the European multicenter study about spinal cord injury (EMSCI) of three German SCI centers were included and followed over time by the German spinal cord injury cohort study (GerSCI). Individuals' most recent spinal cord independence measure (SCIM) scores assessed by a clinician were followed up by a self-report (SCIM-SR) and correlated to selected items of the WHO short survey of quality of life (WHO-QoL-BREF)., Results: Data for 359 individuals were obtained. The average time passed the last clinical SCIM examination was 81.47 (SD 51.70) months. In total, 187 of the 359 received questionnaires contained a completely evaluable SCIM-SR. SCIM scores remained stable with the exception of reported management of bladder and bowel resulting in a slight decrease of SCIM-SR of -2.45 points (SD 16.81). SCIM-SR scores showed a significant correlation with the selected items of the WHO-QoL-BREF (p < 0.01) with moderate to strong influence., Conclusion: SCIM score stability over time suggests a successful transfer of acquired independence skills obtained during primary rehabilitation into the community setting paralleled by positively related QoL measurements but bladder and bowel management may need special attention., (© 2021. The Author(s).)

Objective: Revisiting the sharp/dull discrimination as clinical measure of spinothalamic tract function considering the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI). Three clinically relevant factors were evaluated as to their impact on reliability: (1) the localization of dermatomes in relation to the sensory level, (2) the examination tool, and (3) the threshold of correct answers for grading of a preserved sharp/dull discrimination. Design: Prospective monocentric psychometric study. Setting: Spinal Cord Injury Center, Heidelberg University Hospital, Germany. Participants: Convenient sample of 21 individuals with subacute spinal cord injury (age: 31-82 years) and 20 individuals without spinal cord injury (age: 24-63 years). Assessment: All participants underwent three assessments for sharp/dull discrimination, applying five commonly used examination tools in seven dermatomes, performed by three trained examiners under conditions in accordance with ISNCSCI. Main Outcome Measures: Assessment of interrater reliability by determining both the Fleiss kappa (κ) coefficient and the percentage agreement between raters. Data were dichotomized regarding the ISNCSCI threshold. Results: Interrater reliability in individuals with SCI was overall substantial (κ = 0.68; CI 0.679-0.681) and moderate (κ = 0.54; CI 0.539-0.543) in dermatomes below the sensory level. All applied tools led to at least moderate reliability below the sensory level (lowest κ = 0.44; CI 0.432-0.440), with the officially endorsed safety pin achieving the highest (substantial) reliability (κ = 0.64; CI 0.638-0.646). Percentage agreement differed between non-SCI (97.3%) and formally intact above level dermatomes in SCI (89.2%). Conclusions: Sharp/dull discrimination as a common clinical examination technique for spinothalamic tract function is a reliable assessment. Independent from the used examination tools, reliability was substantial, with the medium-sized safety pin delivering the most favorable results. Notwithstanding this, all other tools could be considered if a safety pin is not available. Regarding interrater reliability and guessing probability, a threshold of 80% correct responses for preserved sharp/dull discrimination appears to be most suitable, which is in line with current clinical approaches and ISNCSCI. The causal attribution of the identified differences in sharp/dull discrimination between clinically intact dermatomes of individuals with SCI and unaffected dermatomes of individuals without SCI requires future work. Clinical Trial Registration Number (German Clinical Trials Register): DRKS00015334 (https://www.drks.de)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Heutehaus, Schuld, Solinas, Hensel, Kämmerer, Weidner, Rupp and Franz.)

Decreased circulating 25-hydroxyvitamin D (25[OH]D) and increased inflammatory marker concentrations have been reported separately in canine cancer. Correlations between the two exist in humans, but little work has examined links in dogs. This study aimed to determine plasma 25(OH)D and inflammatory marker concentrations in healthy dogs and dogs with cancer and to assess correlations in each group. Newly diagnosed dogs with B-cell lymphoma (B-cell, n = 25), T-cell lymphoma (T-cell, n = 9), osteosarcoma (OSA, n = 21), and mast cell tumour (MCT, n = 26) presenting to a tertiary oncology centre, and healthy dogs (n = 25), were enrolled. Plasma samples were analysed for 25(OH)D, C-reactive protein (CRP), haptoglobin (HP), serum amyloid A (SAA), alpha-1-acid glycoprotein (AAG), and 13 chemokines and cytokines. Dogs with B-cell had decreased plasma 25(OH)D (P = .03), and increased plasma CRP, AAG, HP, KC-like and MCP-1 concentrations (P < =.001, .011, <.001, .013 and .009, respectively) compared with healthy dogs. Plasma CRP, HP and SAA concentrations were increased in dogs with OSA compared with healthy dogs (P = .001, .010 and .027, respectively). No differences were noted in dogs with T-cell and MCT. Negative correlations were observed between plasma 25(OH)D concentrations and: AAG concentrations in dogs with T-cell (R s  = -0.817, P = .007); GM-CSF concentrations (R s  = -0.569, P = .007) in dogs with OSA; and IL-7 concentrations (R s  = -0.548, P = .010) in dogs with OSA. Decreased 25(OH)D concentrations and increased concentrations of multiple inflammatory markers were observed in B-cell patients, supporting an association between 25(OH)D and inflammation. The cross-sectional study design meant the timing of changes could not be determined. Prospective cohort studies are warranted., (© 2020 John Wiley & Sons Ltd.)

Background: A central goal of rehabilitation in patients with paralysis syndromes after stroke or spinal cord injury (SCI) is to restore independent mobility as a pedestrian or wheelchair user. However, after acute rehabilitation, the mobility frequently deteriorates in the ambulatory setting, despite the delivery of rehabilitative interventions such as physical therapy or the prescription of assistive devices. The aim of the NeuroMoves study is to identify factors that are associated with changes of mobility in the ambulatory setting after acute inpatient rehabilitation, with a particular focus on participation according to the ICF (International Classification of Functioning, Disability and Health)., Methods: The NeuroMoves study is intended as a national multicenter observational cohort study with 9 clinical sites in Germany. A total of 500 patients with mobility-restricting paralysis syndromes (i.e. stroke or SCI) are to be recruited during acute inpatient rehabilitation prior to discharge to the ambulatory setting. Patients will have 8 months of follow-up in the ambulatory setting. Three study visits at the clinical sites (baseline, midterm, and final) are planned at 4-months intervals. The baseline visit is scheduled at the end of the acute inpatient rehabilitation. During the visits, demographical data, neurological, functional, quality of life, and implementation measures will be assessed. At baseline, each study participant receives an activity tracker (sensor for recording ambulatory mobility) along with a tablet computer for home use over the 8 months study duration. While mounted, the activity tracker records mobility data from which the daily distance covered by walking or wheelchair use can be calculated. Customized applications on the tablet computer remind the study participants to answer structured questionnaires about their health condition and treatment goals for physical therapy. Using the study participants' tablet, therapists will be asked to answer structured questionnaires concerning treatment goals and therapeutic measures they have applied. The primary analysis concerns the association between mobility (daily distance covered) and the degree of participation-oriented rehab interventions. Further exploratory analyses are planned., Discussion: The findings could inform healthcare decision-making regarding ambulatory care in Germany focusing on mobility-promoting interventions for patients with mobility-restricting paralysis syndromes., Study Registration: German Clinical Trials Register, DRKS-ID: DRKS00020487 (18.02.2020).

Background and Purpose: Cancer-related fatigue (CRF) is a common side effect of cancer treatment, particularly in breast cancer patients. Over the past decade, the multimodal management of breast cancer has undergone several changes, such as the establishment of postoperative hypofractionated radiotherapy (RT) as a new standard protocol and the reduced use of chemotherapy. The aim of the current study was to investigate the impact of these changes on quality of life (QoL) and CRF., Methods: A total of 66 patients was assessed for QoL and CRF using the FACIT‑F questionnaire. Patients were asked to complete the paper-based questionnaire before (TP1) and at the end of radiotherapy (TP2) as well as at follow-up (TP3). Subgroups were compared based on fractionation and previous application of chemotherapy., Results: For the entire cohort, no significant changes in the severity of fatigue were seen. A mild decrease of physical wellbeing (PWB) from TP1 to TP2 was observed (22.2 vs. 20.7, p = 0.007). Fatigue at TP1 was more severe in patients receiving chemotherapy before RT (37.9 vs. 30.5, p = 0.041). Only patients without preceding chemotherapy showed a significant worsening of fatigue from TP1 to TP2 (37.9 vs 34.8, p = 0.005). The same is true for physical wellbeing (PWB), with a decrease from TP1 to TP2 in chemotherapy-naïve patients only (23.5 vs. 21.4, p = 0.002). Fractionation did not impact any of the investigated endpoints., Conclusion: Patients undergoing postoperative RT for breast cancer constitute a heterogeneous patient population with varying risks of developing CRF influenced by previous treatments. Therefore, patient selection seems to be critical when interventional studies addressing CRF during radiotherapy are designed.

Purpose: In the modern era, improvements in radiation therapy techniques have paved the way for simultaneous integrated boost irradiation in adjuvant breast radiation therapy after breast conservation surgery. Nevertheless, randomized trials supporting the noninferiority of this treatment to historical standards of care approach are lacking., Methods: A prospective, multicenter, randomized phase 3 trial (NCT01322854) was performed to analyze noninferiority of conventional fractionated intensity modulated radiation therapy with simultaneous integrated boost (IMRT-SIB) to 3-D conformal radiation therapy with sequential boost (3-D-CRT-seqB) for breast cancer patients. Primary outcomes were local control (LC) rates at 2 and 5 years (noninferiority margin at hazard ratio [HR] of 3.5) as well as cosmetic results 6 weeks and 2 years after radiation therapy (evaluated via photo documentation calculating the relative breast retraction assessment [pBRA] score [noninferiority margin of 1.25])., Results: A total of 502 patients were randomly assigned from 2011 to 2015. After a median follow-up of 5.1 years, the 2-year LC for the IMRT-SIB arm was noninferior to the 3-D-CRT-seqB arm (99.6% vs 99.6%, respectively; HR, 0.602; 95% CI, 0.123-2.452; P = .487). In addition, noninferiority was also shown for cosmesis after IMRT-SIB and 3-D-CRT-seqB at both 6 weeks (median pBRA, 9.1% vs 9.1%) and 2 years (median pBRA, 10.4% vs 9.8%) after radiation therapy (95% CI, -0.317 to 0.107 %; P = .332). Cosmetic assessment according to the Harvard scale by both the patient and the treating physician as well as late-toxicity evaluation with the late effects normal tissues- subjective, objective, management, analytic criteria, a score for the evaluation of long-term adverse effects in normal tissue, revealed no significant differences between treatment arms. In addition, there was no difference in overall survival rates (99.6% vs 99.6%; HR, 3.281; 95% CI: -0.748 to 22.585; P = .148) for IMRT-SIB and 3-D-CRT-seqB, respectively., Conclusions: To our knowledge, this is the first prospective trial reporting the noninferiority of IMRT-SIB versus 3-D-CRT-seqB with respect to cosmesis and LC at 2 years of follow-up. This treatment regimen considerably shortens adjuvant radiation therapy times without compromising clinical outcomes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Study Design: Chart reviews were combined with neurological and functional outcome data obtained from the prospective European Multicenter Study on Spinal Cord Injury (EMSCI, www.emsci.org)., Objectives: To determine if strict physical isolation of multidrug-resistant organisms (MDRO)-positive patients negatively affects neurological recovery and functional outcome in the first year after acute spinal cord injury (SCI)., Setting: SCI Center Heidelberg University Hospital., Methods: Individuals with acute (< 6 weeks) traumatic or ischemic SCI were included. During primary comprehensive care, isolated MDRO-positive patients (n = 13) were compared with a MDRO-negative control group (n = 13) matched for functional (Spinal Cord Independence Measure-SCIM) and neurological impairment (motor scores based on the International Standards for Neurological Classification of Spinal Cord Injury-ISNCSCI) at an early stage up to 40 days after SCI. SCIM scores and motor scores were obtained at 12 weeks (intermediate stage) and 24 or 48 weeks (late stage) after SCI., Results: Isolated MDRO-positive (median duration of hospitalization: 175 days, 39% of inpatient stay under isolation measures) and non-isolated MDRO-negative (median duration of hospitalization: 161 days) patients showed functional and neurological improvements, which were not statistically different between groups at the intermediate and late stage., Conclusion: Prolonged isolation due to MDRO colonization for over a third of the inpatient comprehensive care period does not appear to impair neurological recovery and functional outcome within the first year after SCI., Competing Interests: The authors have declared that no competing interests exist.

In many preclinical spinal cord injury (SCI) studies, assessment of locomotion recovery is key to understanding the effectiveness of the experimental intervention. In such rat SCI studies, the most basic locomotor recovery scoring system is a subjective observation of animals freely roaming in an open field, the Basso Beattie Bresnahan (BBB) score. In comparison, CatWalk is an automated gait analysis system, providing further parameter specifications. Although together the CatWalk parameters encompass gait, studies consistently report single parameters, which differ in significance from other behavioral assessments. Therefore, we believe no single parameter produced by the CatWalk can represent the fully-coordinated motion of gait. Typically, other locomotor assessments, such as the BBB score, combine several locomotor characteristics into a representative score. For this reason, we ranked the most distinctive CatWalk parameters between uninjured and SC injured rats. Subsequently, we combined nine of the topmost parameters into an SCI gait index score based on linear discriminant analysis (LDA). The resulting combination was applied to assess gait recovery in SCI experiments comprising of three thoracic contusions, a thoracic dorsal hemisection, and a cervical dorsal column lesion model. For thoracic lesions, our unbiased machine learning model revealed gait differences in lesion type and severity. In some instances, our LDA was found to be more sensitive in differentiating recovery than the BBB score alone. We believe the newly developed gait parameter combination presented here should be used in CatWalk gait recovery work with preclinical thoracic rat SCI models., (Copyright © 2021 Timotius et al.)

Objective: The PORTEC-4a trial investigates molecular-integrated risk profile guided adjuvant treatment for endometrial cancer. The quality assurance programme included a dummy run for vaginal brachytherapy prior to site activation, and annual quality assurance to verify protocol adherence. Aims of this study were to evaluate vaginal brachytherapy quality and protocol adherence., Methods: For the dummy run, institutes were invited to create a brachytherapy plan on a provided CT-scan with the applicator in situ. For annual quality assurance, institutes provided data of one randomly selected brachytherapy case. A brachytherapy panel reviewed and scored the brachytherapy plans according to a checklist., Results: At the dummy run, 15 out of 21 (71.4%) institutes needed adjustments of delineation or planning. After adjustments, the mean dose at the vaginal apex (protocol: 100%; 7 Gy) decreased from 100.7% to 99.9% and range and standard deviation (SD) narrowed from 83.6-135.1 to 96.4-101.4 and 8.8 to 1.1, respectively. At annual quality assurance, 22 out of 27 (81.5%) cases had no or minor and 5 out of 27 (18.5%) major deviations. Most deviations were related to delineation, mean dose at the vaginal apex (98.0%, 74.7-114.2, SD 7.6) or reference volume length., Conclusions: Most feedback during the brachytherapy quality assurance procedure of the PORTEC-4a trial was related to delineation, dose at the vaginal apex and the reference volume length. Annual quality assurance is essential to promote protocol compliance, ensuring high quality vaginal brachytherapy in all participating institutes., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The hybrid magnetic resonance linear accelerator (MRL) has the potential to test novel concepts in breast cancer patients such as daily MR-guided real-time plan adaptation. Before starting clinical trials, preparatory studies for example of the MR-dependent electron stream effect (ESE) are necessary., Material and Methods: To prospectively investigate the ESE, data from 11 patients treated with partial breast irradiation (PBI) at the 1.5 T MRL were evaluated. A bolus was placed on the chin and in vivo dosimetry results were compared with the dose simulated by the treatment planning system (TPS). The same measurements were carried out for three patients treated at a conventional linac. Toxicity and cosmesis were evaluated., Results: Median doses measured and simulated on top/ underneath the bolus were 1.91 / 0.62 Gy and 2.82 / 0.63 Gy, respectively. Median differences between calculations and measurements were 0.8 Gy and 0.1 Gy. At the conventional linac, median measured doses on top/ underneath the bolus were 0.98 and 1.37 Gy. No acute toxicity exceeding grade 2 was recorded. Cosmesis was good or excellent and patient reported outcome measures were mostly scored as none or mild., Conclusion: The dose due to the ESE is low, correctly predicted by the TPS and effectively minimized by a bolus., Competing Interests: The MR-Linac research program is funded by the German Research Council (to D.T. and D.Z., ZI 736/2-1). Radiation Oncology Tübingen receives financial and technical support from Elekta AB (Stockholm, Sweden) under a research agreement. C.D.C. is supported by the Medical Faculty Tübingen (TüFF)., (© 2020 Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background: Cardiac manifestation of COVID-19 has been reported during the COVID pandemic. The role of cardiac arrhythmias in COVID-19 is insufficiently understood. This study assesses the incidence of cardiac arrhythmias and their prognostic implications in hospitalized COVID-19-patients., Methods: A total of 166 patients from eight centers who were hospitalized for COVID-19 from 03/2020-06/2020 were included. Medical records were systematically analyzed for baseline characteristics, biomarkers, cardiac arrhythmias and clinical outcome parameters related to the index hospitalization. Predisposing risk factors for arrhythmias were identified. Furthermore, the influence of arrhythmia on the course of disease and related outcomes was assessed using univariate and multiple regression analyses., Results: Arrhythmias were detected in 20.5% of patients. Atrial fibrillation was the most common arrhythmia. Age and cardiovascular disease were predictors for new-onset arrhythmia. Arrhythmia was associated with a pronounced increase in cardiac biomarkers, prolonged hospitalization, and admission to intensive- or intermediate-care-units, mechanical ventilation and in-hospital mortality. In multiple regression analyses, incident arrhythmia was strongly associated with duration of hospitalization and mechanical ventilation. Cardiovascular disease was associated with increased mortality., Conclusions: Arrhythmia was the most common cardiac event in association with hospitalization for COVID-19. Older age and cardiovascular disease predisposed for arrhythmia during hospitalization. Whereas in-hospital mortality is affected by underlying cardiovascular conditions, arrhythmia during hospitalization for COVID-19 is independently associated with prolonged hospitalization and mechanical ventilation. Thus, incident arrhythmia may indicate a patient subgroup at risk for a severe course of disease.

There is much controversy about the potential impact of spinal cord injury (SCI) on brain anatomy and function, which is mirrored in the substantial divergence of findings between animal models and human imaging studies. Given recent advances in quantitative magnetic resonance imaging (MRI) we sought to tackle the unresolved question about the link between the presumed injury associated volume differences and underlying brain tissue property changes in a cohort of chronic complete SCI patients. Using the established computational anatomy methods of voxel-based morphometry (VBM) and voxel-based quantification (VBQ), we performed statistical analyses on grey and white matter volumes as well as on parameter maps indicative for myelin, iron, and free tissue water content in the brain of complete SCI patients (n = 14) and healthy individuals (n = 14). Our regionally unbiased white matter analysis showed a significant volume reduction of the dorsal aspect at the junction between the most rostral part of the spinal cord and the medulla oblongata consistent with Wallerian degeneration of proprioceptive axons in the dorsal column tracts in SCI subjects. This observation strongly correlated with spinal cord atrophy assessed by quantification of the spinal cord cross-sectional area at the cervical level C2/3. These findings suggest that Wallerian degeneration of the dorsal column tracts represents a main contributor to the observed spinal cord atrophy, which is highly consistent with preclinical histological evidence of remote changes in the central nervous system secondary to SCI. Structural changes in other brain regions representing remote changes in the course of chronic SCI could neither be confirmed by conventional VBM nor by VBQ analysis. Whether and how MRI based brain morphometry and brain tissue property analysis will inform clinical decision making and clinical trial outcomes in spinal cord medicine remains to be determined., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Traumatic and non-traumatic spinal cord injury bears a high risk for thromboembolism in the first few months after injury. So far, there is no consented guideline regarding diagnostic and prophylactic measures to prevent thromboembolic events in spinal cord injury. Based on a Pubmed research of related original papers and review articles, international guidelines and a survey conducted in German-speaking spinal cord injury centers about best practice prophylactic procedures at each site, a consensus process was initiated, which included spinal cord medicine experts and representatives from medical societies involved in the comprehensive care of spinal cord injury patients. The recommendations comply with the German S3 practice guidelines on prevention of venous thromboembolism., Recommendations: Specific clinical or instrument-based screening methods are not recommended in asymptomatic SCI patients. Based on the severity of neurological dysfunction (motor completeness, ambulatory function) low dose low molecular weight heparins are recommended to be administered up to 24 weeks after injury. Besides, mechanical methods (compression stockings, intermittent pneumatic compression) can be applied. In chronic SCI patients admitted to the hospital, thromboembolism prophylactic measures need to be based on the reason for admission and the necessity for immobilization., Conclusions: Recommendations for thromboembolism diagnostic and prophylactic measures follow best practice in most spinal cord injury centers. More research evidence needs to be generated to administer more individually tailored risk-adapted prophylactic strategies in the future, which may help to further prevent thromboembolic events without causing major side effects. The present article is a translation of the guideline recently published online (https://www.awmf.org/uploads/tx&#95;szleitlinien/179-015l&#95;S1&#95;Thromboembolieprophylaxe-bei-Querschnittlaehmung&#95;2020-09.pdf)., Competing Interests: Competing interestsThe authors have stated that they have no conflict of interest according to the AWMF criteria., (© The Author(s) 2020.)

Study Design: Retrospective analysis of prospectively collected data., Objective: Central cord syndrome (CCS) is reported to have better outcomes than other cervical lesions, especially for ambulation and bladder recovery. However, a formal comparison between patients with CCS and other incomplete cervical spinal cord injuries (iCSCI) is lacking. Aim of the study is to investigate the neurological and functional outcomes in patients with or without CCS., Setting: European Multicenter Study., Methods: Data following SCI were derived from the European Multicenter Study about Spinal Cord Injury Database. CCS was diagnosed based on a difference of at least ten points of motor score in favour of the lower extremities. Patients were evaluated at 30 days, 6 months and 1 year from injury. The neurological and functional data were collected at each time point based on the International Standards for Neurological Classification of Spinal Cord injury (ISNSCI) and Spinal Cord Independence Measure (SCIM). Patients were selected with a matching procedure based on lesion severity, neurological level of injury (NLI) and age. Evaluation of the outcomes was performed by means of two-way Anova for repeated measures., Results: The matching produced 110 comparable dyads. At all time points, upper extremity motor scores remained lower than lower extremity motor scores in CCS compared with iCSCI. With regard to daily life independence, both cohorts achieved comparable improvements in self-care sub-scores between T0 and T2 (6.6 ± 6.5 in CCS vs 8.2 ± 6.9 in iCSCI, p = 0.15) but this sub-score was significantly lower in CCS compared with iCSCI (3.6 ± 5.2 in CCS vs 7.3 ± 7.0 in iCSCI at T0, 13.7 ± 6.2 vs 16.5 ± 5.7 at T2), while the other sub-scores were comparable., Conclusions: In contrast to previous reports, people with CCS have poorer outcomes of self-care ability compared with iCSCI.

Background: 10-year results from several studies showed improved disease-free survival and distant metastasis-free survival, reduced breast cancer-related mortality, and variable effects on overall survival with the addition of partial or comprehensive regional lymph node irradiation after surgery in patients with breast cancer. We present the scheduled 15-year analysis of the European Organisation for Research and Treatment of Cancer (EORTC) 22922/10925 trial, which aims to investigate the impact on overall survival of elective internal mammary and medial supraclavicular (IM-MS) irradiation., Methods: EORTC 22922/10925, a randomised, phase 3 trial done across 46 radiation oncology departments from 13 countries, included women up to 75 years of age with unilateral, histologically confirmed, stage I-III breast adenocarcinoma with involved axillary nodes or a central or medially located primary tumour. Surgery consisted of mastectomy or breast-conserving surgery and axillary staging. Patients were randomly assigned (1:1) centrally using minimisation to receive IM-MS irradiation at 50 Gy in 25 fractions (IM-MS irradiation group) or no IM-MS irradiation (control group). Stratification was done for institution, menopausal status, site of the primary tumour within the breast, type of breast and axillary surgery, and pathological T and N stage. Patients and investigators were not masked to treatment allocation. The primary endpoint was overall survival analysed according to the intention-to-treat principle. Secondary endpoints were disease-free survival, distant metastasis-free survival, breast cancer mortality, any breast cancer recurrence, and cause of death. Follow-up is ongoing for 20 years after randomisation. This study is registered with ClinicalTrials.gov, NCT00002851., Findings: Between Aug 5, 1996, and Jan 13, 2004, we enrolled 4004 patients, of whom 2002 were randomly assigned to the IM-MS irradiation group and 2002 to the no IM-MS irradiation group. At a median follow-up of 15·7 years (IQR 14·0-17·6), 554 (27·7%) patients in the IM-MS irradiation group and 569 (28·4%) patients in the control group had died. Overall survival was 73·1% (95% CI 71·0-75·2) in the IM-MS irradiation group and 70·9% (68·6-72·9) in the control group (HR 0·95 [95% CI 0·84-1·06], p=0·36). Any breast cancer recurrence (24·5% [95% CI 22·5-26·6] vs 27·1% [25·1-29·2]; HR 0·87 [95% CI 0·77-0·98], p=0·024) and breast cancer mortality (16·0% [14·3-17·7] vs 19·8% [18·0-21·7]; 0·81 [0·70-0·94], p=0·0055) were lower in the IM-MS irradiation group than in the control group. No significant differences in the IM-MS irradiation group versus the control group were seen for disease-free survival (60·8% [95% CI 58·4-63·2] vs 59·9% [57·5-62·2]; HR 0·93 [95% CI 0·84-1·03], p=0·18), or distant metastasis-free survival (70·0% [67·7-72·2] vs 68·2% [65·9-70·3]; 0·93 [0·83-1·04], p=0·18). Causes of death between groups were similar., Interpretation: The 15-year results show a significant reduction of breast cancer mortality and any breast cancer recurrence by IM-MS irradiation in stage I-III breast cancer. However, this is not converted to improved overall survival., Funding: US National Cancer Institute, Ligue Nationale contre le Cancer, and KWF Kankerbestrijding., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Study Design: Multicenter prospective cohort., Objective: To discern neurological- and functional recovery in patients with a traumatic thoracic spinal cord injury (TSCI), conus medullaris syndrome (CMS), and cauda equina syndrome (CES)., Setting: Specialized spinal cord injury centers in Europe., Method: Lower extremity motor score (LEMS) and spinal cord independent measure (SCIM) scores from patients with traumatic TSCI, CMS, and CES were extracted from the EMSCI database. Scores from admittance and during rehabilitation at 1, 3, 6, and 12 months were compared. Linear mixed models were used to statistically analyse differences in outcome, which were corrected for the ASIA Impairment Scale (AIS) in the acute phase., Results: Data from 1573 individuals were analysed. Except for the LEMS in patients with a CES AIS A, LEMS, and SCIM significantly improved over time for patients with a TSCI, CMS, and CES. Irrespectively of the AIS score, recovery in 12 months after trauma as measured by the LEMS showed a statistically significant difference between patients with a TSCI, CMS, and CES. Analysis of SCIM score showed no difference between patients with TSCI, CMS, or CES., Conclusion: Difference in recovery between patients with a traumatic paraplegia is based on neurological (motor) recovery. Regardless the ceiling effect in CES patients, patients with a mixed upper and lower motor neuron syndrome (CMS) showed a better recovery compared with patients with a upper motor neuron syndrome (TSCI). These findings enable stratifications of patients with paraplegia according to the level and severity of SCI.

Objective: The German Spinal Cord Injury Survey is part of the International Spinal Cord Injury Survey, which aims to collect data about the life experience of persons with spinal cord injury worldwide. This paper reports on the perceived environmental barriers of the German study population and their associations with quality of life., Design: Cross-sectional explorative observational study using survey data., Participants: A total of 1,479 persons with spinal cord injury aged 18 years and older., Methods: After descriptive analyses, exploratory factor analysis was used to build groups of environmental barriers. Logistic regressions were performed to assess correlates of perceived environmental barriers. Spearman's correlations were used to analyse the association between perceived barriers and quality of life., Results: Barriers regarding infrastructure had a relatively large impact. Barriers in relation to people's attitudes towards spinal cord injury and the equipment of people with spinal cord injury had a relatively small impact on the lives of people with spinal cord injury. Several subpopulations showed a higher risk in experiencing barriers. Quality of life decreased with increasing experience of barriers., Conclusion: The most life-hardening barriers were identified related to infrastructure, a category in which most barriers are modifiable, for example, buildings or transportation.

Purpose: Multiple organizations like UN and WHO call for the collection of internationally comparable data on living and supply conditions of people with disabilities. Furthermore, reliable national data are necessary for ensuring appropriate care. Regarding patients with Spinal Cord Injury (SCI) in Germany, only data on diagnostics or therapeutic interventions is currently available. The International Spinal Cord Injury Survey aims at collecting reliable data of people with SCI in 21 countries and developing recommendations for actions to be taken by policy-makers and other decision-makers., Methods: In 2017, eight specialized SCI-centers across Germany sent a standardized questionnaire to their patients who had diagnosis of SCI, and were older than 18 years (n=5,598). The questionnaire could be completed paper-based or online., Results: 1,479 patients participated in the study and were included in data analysis. On average, participants were 55.3 years (SD=14.6) old, ¾ were male. The mean time of onset of paralysis was 13.9 years. Two thirds of the spinal cord injury causes were traumatic. In 51.2% SCI was classified as paraplegia. The most frequently cited health problem was sexual dysfunction. Medical treatment for this problem was rarely used. Serious environmental barriers were the inadequate accessibility of private households and public places. 42.5% of the respondents in working age were employed, which is 10% less than in Switzerland., Discussion: Serious problems in environmental barriers, medical care and labor market participation were identified for people with SCI. The results will be reported to and discussed with political decision makers and further actors to create solutions. This requires extensive efforts, like modification in building law and home support., Competing Interests: Die finanzielle Förderung erfolgte durch die Manfred-Sauer-Stiftung. Der Stifter ist selbst querschnittgelähmt und Hersteller von Inkontinenzhilfsmitteln. Die Autoren geben an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background . The relative rarity of ischemic compared with traumatic spinal cord injury (SCI) has limited a comparison of the outcomes of these conditions. Objective . To investigate the neurological and functional recovery of ischemic compared with traumatic acute SCI. Methods . Data were derived from the European Multicenter Study Spinal Cord Injury database. Patients with ischemic (iSCI) or traumatic SCI (tSCI), aged 18 years or older were evaluated at different time points from incidence: at about 1 month, 3 months, and 6 months. The neurological status was assessed at each time point by the International Standards for Neurological Classification of Spinal Cord Injury and the functional status by the Spinal Cord Independence Measure. Walking ability was evaluated by Walking Index for Spinal Cord Injury, 10-Meter Walk Test, and 6-Minute Walk Test. Because of the imbalances of the 2 groups in respect to size and lesion severity, a matching procedure according to age, neurological level, and severity of injury was performed. Outcomes evaluation was performed by means of a 2-way repeated-measures ANOVA. Results . The matching procedure resulted in 191 pairs. Both groups significantly improved from about 15 days after the lesion to 6 months. No differences were found in the course of neurological and functional recovery of iSCI compared with tSCI. Conclusions . This analysis from a representative cohort of participants revealed that from 15 days following the cord damage onward, the outcomes after iSCI and tSCI are comparable. This finding supports the potential enrolment of patients with acute iSCI into clinical trials from that point in time after the event and an evaluation up to 6 months afterward.

Objective: The aim of the study was to assess factors determining the utilization of physical and occupational therapy in people with spinal cord injury., Design: Data from the German Spinal Cord Injury study conducted in 2017 were analyzed. The 12-mo prevalence of physical therapy and occupational therapy utilization was determined. To identify underlying determinants, multivariable logistic regression was used., Results: Of 1479 participants (response = 26.4%), 72.9% were male, with a mean (SD) age of 55.3 (14.6) yrs and a mean (SD) time since injury of 14.0 (12.0) yrs; 51.2% were people with paraplegia and 66.3% had an incomplete spinal cord injury. In the past 12 mos, 78.1% received physical and 29.3% occupational therapy. Physical therapy and occupational therapy were significantly associated with time since spinal cord injury occurrence, participation in lifelong care programs, and electric wheelchair dependency. Spinal cord injury characteristics, level of impairment, and time since spinal cord injury had a greater impact on occupational therapy than on physical therapy utilization., Conclusions: The use of physical therapy and occupational therapy is much higher in Germans with spinal cord injury than in the general population and in people with similar neurological conditions. Further research should focus on the frequency of use and the types of interventions. Guidelines for lifelong care should include recommendations on physical therapy and occupational therapy.

Introduction: External beam partial breast irradiation (PBI) provides equal oncological outcomes compared to whole breast irradiation when applied to patients with low risk tumours. Recently, linacs with an integrated magnetic resonance image-guidance system have become clinically available. Here we report the first-in-human PBI performed at the 1.5 T MR-Linac, with a focus on clinical feasibility and investigation of the air electron stream effect (ESE) and the electron return effect (ERE) in the presence of the 1.5 T magnetic field, which might influence the dose on the chin (out-of-field dose, due to the ESE), the skin and the lung/chest wall interface (in-field dose, ERE)., Methods: A 59 years old patient affected by a 15 mm unifocal grade 1 carcinoma not special type of the right breast staged pT1c pN0 cM0 was planned and treated at Unity 1.5 T MR-Linac. To investigate the ERE and the ESE, an MR-Linac treatment plan was simulated without considering the 1.5 T B field using a research version of Monaco (V. 5.19.03). In vivo dosimetry was performed using Gafchromic® EBT3 films placed on top and underneath a 1 cm bolus which was placed on the patient's chin. The plans with and without 1.5 T magnetic field were compared in terms of dose to the chin, to the skin and to the interface lung/chest wall. Finally, the dose on the chin measured with the in vivo dosimetry was compared with the dose calculated by Monaco., Results: PBI using the 1.5 T MR-Linac was successfully performed with a 7 MV photon 7-beams IMRT step-and-shoot plan. The treatment was well tolerated, the patient developed a slight acute toxicity, i.e. breast skin erythema and breast oedema CTC V.4 grade 1. The plan with 1.5 T magnetic field documented a fractional dose of 0.17 Gy in the chin area (2.6 Gy in 15 fractions), which was reduced to 0.05 Gy (0.75 in 15 fractions) by the presence of 1 cm bolus. The simulated plan without magnetic field showed a dose reduced by 2.3 Gy in the chin area. With the in vivo dosimetry a fractional dose of, respectively, 0.12 Gy and 0.034 Gy on top and underneath the bolus were measured (1.8 and 0.51 Gy in 15 fractions). The plan with 1.5 T magnetic field showed a skin D 2 of 40 Gy and a skin V 35 of 40.2%, which were reduced to, respectively, 39.7 Gy and 24.9% in the simulation without magnetic field. At the interface lung/chest there were no differences in DVH statistics., Conclusion: PBI with the 1.5 T MR-Linac was performed for the first time. ESE is accurately calculated by the treatment planning system, can be effectively reduced with a 1 cm bolus and is comparable to dose of cone beam-CT based position verification. The additional dose caused by ERE is not associated with an increased risk of acute toxicity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Study Design: A prospective single arm study., Objectives: Previously we have demonstrated that magnetic resonance (MR) defecography is feasible in participants with complete spinal cord injury (SCI). The main aim of this study is to evaluate whether MR defecography can provide objective parameters correlating with the clinical manifestations of neurogenic bowel dysfunction (NBD) in participants with SCI., Setting: A monocentric study in a comprehensive care university hospital Spinal Cord Injury Center., Methods: Previously published MR defecography parameters (anorectal angle (ARA), hiatal descent (M-line) and hiatal width (H-line)) of twenty participants with SCI were now compared to a standardized clinical assessment of NBD. Descriptive statistics, correlations and t-tests for independent samples were calculated., Results: The significantly higher values for the ARA at rest and M-line at rest in participants with SCI correlated with the clinical assessment of bowel incontinence. Furthermore, in nearly half of the investigated SCI cohort the normally positive difference between ARA, M-line and H-line at rest and during defecation became negative suggesting pelvic floor dyssynergia as a potential mechanism underlying constipation in people with complete SCI. In fact, these participants showed a more severe clinical presentation of NBD according to the total NBD score., Conclusions: MR defecography provides objective parameters correlating with clinical signs of NBD, such as constipation and bowel incontinence. Therefore, MR defecography can support pathophysiology-based decision-making with respect to specific therapeutic interventions, which should help to improve the management of NBD.