Epidemiology of pediatric spinal trauma with neurological deficits in Catalonia: a 36-year experience.

PURPOSE: Existing literature on pediatric traumatic spinal cord injury (PTSCI) demonstrates large variations in characteristics, incidence, time-periods and etiology, worldwide. Epidemiological studies addressing injuries to the total spine, conducted in Southern European regions are remarkably scarce; therefore we aimed to investigate long-term trends analyzing etiology, fracture location and type, single or multiple fractures, associated lesions and neurological status in Catalonia, Spain. METHODS: We conducted a retrospective observational study. We analyzed post-acute patients after PTSCI, aged 0-17, admitted with neurological deficits between 1986 and 2022 to a specialized hospital in Catalonia. Neurological deficits were assessed using the American Spinal Injury Association Impairment Scale (AIS). RESULTS: Two hundred and forty nine children were included, 174 (69.9%) boys and 75 (30.1%) girls; mean age was 13.9 years (range, 2 months to 17 years). Two hundred and four children (82%) had ≥ 1 spinal fractures, 66 (26.5%) dislocations and 8 (3.2%) SCIWORA. Fractures were multilevel contiguous in 108 (43.4%) cases. Fracture types comprised 81 vertebral compactions (32.5%), 22 burst fractures (8.8%), 7 odontoid (2.8%) and 4 tear-drops (1.6%). There were ≥ 1 associated lesions in 112 cases (45%): in limbs in 23 cases (9.2%), thorax or abdomen in 59 (23.7%) and skull or face in 81 (32.5%). In 44 cases (39% of the 112) there were multiple lesions. Locations comprised cervical spine in 105 cases (42%), thoracic spine in 124 (49%), lumbar spine in 18 (7%), and sacrum in 2 (0.8%). Road traffic accidents (RTAs) were the main etiology (62.2%) over the whole period. However, from 2016 onwards, RTAs dropped below the rate of falls and sports injuries. The most common sites for injury in those aged 9 years or older were in the cervical (41.1%) and thoracic (50.7%) regions. Those aged 8 or under were far more likely to sustain a complete SCI (80.0%) or an accompanying traumatic brain injury (45.0%) likely due to higher numbers of pedestrian versus car RTAs. A significant peak in the occurrence of cases during 2006-2010 (20.1%) was identified with an absolute drop immediately after, during 2011-2015 (8.8%). A marked shift in trend is observed between 2016-2022 regarding age of injuries (an increase in 9 years or older), etiology (increase in falls and sports versus RTA), AIS grade (increase in incomplete lesions AIS B-D versus AIS A), severity (increase in tetraplegia versus paraplegia) and location (increase in cervical versus lumbar and thoracic injuries). CONCLUSIONS: A shift in trend is observed in the past 7 years regarding age of injuries (increase in those older than 9), etiology (increase in falls and sports versus RTA), AIS grade (increase in incomplete lesions AIS B-D versus AIS A), severity (increase in tetraplegia versus paraplegia) and location (increase in cervical). LEVEL OF EVIDENCE: IV.

Noninvasive Electromagnetic Neuromodulation of the Central and Peripheral Nervous System for Upper-Limb Motor Strength and Functionality in Individuals with Cervical Spinal Cord Injury: A Systematic Review and Meta-Analysis.

(1) Background: Restoring arm and hand function is one of the priorities of people with cervical spinal cord injury (cSCI). Noninvasive electromagnetic neuromodulation is a current approach that aims to improve upper-limb function in individuals with SCI. The aim of this study is to review updated information on the different applications of noninvasive electromagnetic neuromodulation techniques that focus on restoring upper-limb functionality and motor function in people with cSCI. (2) Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines were used to structure the search protocol. A systematic review of the literature was performed in three databases: the Cochrane Library, PubMed, and Physiotherapy Evidence Database (PEDro). (3) Results: Twenty-five studies were included: four were on transcranial magnetic stimulation (TMS), four on transcranial direct current stimulation (tDCS), two on transcutaneous spinal cord stimulation (tSCS), ten on functional electrical stimulation (FES), four on transcutaneous electrical nerve stimulation (TENS), and one on neuromuscular stimulation (NMS). The meta-analysis could not be completed due to a lack of common motor or functional evaluations. Finally, we realized a narrative review of the results, which reported that noninvasive electromagnetic neuromodulation combined with rehabilitation at the cerebral or spinal cord level significantly improved upper-limb functionality and motor function in cSCI subjects. Results were significant compared with the control group when tSCS, FES, TENS, and NMS was applied. (4) Conclusions: To perform a meta-analysis and contribute to more evidence, randomized controlled trials with standardized outcome measures for the upper extremities in cSCI are needed, even though significant improvement was reported in each non-invasive electromagnetic neuromodulation study.

Falls characteristics experienced by working-age adults during inpatient post-stroke rehabilitation and their impact on length of stay, discharge functional status, ambulation and destination.

BACKGROUND: In-hospital falls are frequent post-stroke medical complications and will remain of concern because it may not be possible to prevent all of them. We aimed to i) compare admission clinical and sociodemographic characteristics between fallers and non-fallers ii) determine falls characteristics iii) compare length of stay (LOS), discharge functional independence, ambulation and destination between fallers and non-fallers. METHODS: A matched case-control study, comparing individuals (n = 302) who fell during inpatient post-acute rehabilitation, matched (on time to admission, age and motor Functional Independence Measure (mFIM)) to individuals (n = 302) who didn´t fall, admitted within 3 months post-injury to a center between 2008 and 2023. Ambulation was assessed using the Functional Ambulation Category (FAC). RESULTS: Mean age at admission was 50±8 years. No baseline differences were seen between groups in the proportion of patients with aphasia, diabetes, dyslipidemia, hypertension, neglect, atrial fibrillation, dysphagia, dominant side affected, medication for depression, FAC assessment, body mass index and educational level. A first-fall in the first week was experienced by 22.2 % and in the first three weeks by 54.3 %. Most falls occurred at the patients' room (75.1 %) mostly due to distractions (55.3 %) and transferring without help (32.4 %) with 18 % occurring in the bathroom, fallers were alone in 68.6 % of the cases. Fallers had an 8-day longer mean LOS compared to non-fallers, yet there were no differences in discharge mFIM or FAC scores. While non-fallers had a higher proportion of poor mFIM outcomes (28.5 % vs. 17.9 %) and no ambulation (20.7 % vs. 12.4 %), fallers showed greater mFIM gains (26 vs. 22 points). Discharge destinations were similar across both groups. CONCLUSIONS: Despite no baseline differences, fallers experienced longer stays with comparable independence and ambulation scores at discharge. Most falls occurred in patients' rooms during unsupervised activities. Preventive recommendations have been provided to address these risks and enhance patient safety.

Towards using 3D cellular cultures to model the activation and diverse functions of macrophages.

The advent of 3D cell culture technology promises to enhance understanding of cell biology within tissue microenvironments. Whilst traditional cell culturing methods have been a reliable tool for decades, they inadequately portray the complex environments in which cells inhabit in vivo. The need for better disease models has pushed the development of effective 3D cell models, providing more accurate drug screening assays. There has been great progress in developing 3D tissue models in fields such as cancer research and regenerative medicine, driven by desires to recreate the tumour microenvironment for the discovery of new chemotherapies, or development of artificial tissues or scaffolds for transplantation. Immunology is one field that lacks optimised 3D models and the biology of tissue resident immune cells such as macrophages has yet to be fully explored. This review aims to highlight the benefits of 3D cell culturing for greater understanding of macrophage biology. We review current knowledge of macrophage interactions with their tissue microenvironment and highlight the potential of 3D macrophage models in the development of more effective treatments for disease.

Testing to sustain hepatitis C elimination targets in people who inject drugs: A network-based model.

Little is known about the level of testing required to sustain elimination of hepatitis C (HCV), once achieved. In this study, we model the testing coverage required to maintain HCV elimination in an injecting network of people who inject drugs (PWID). We test the hypothesis that network-based strategies are a superior approach to deliver testing. We created a dynamic injecting network structure connecting 689 PWID based on empirical data. The primary outcome was the testing coverage required per month to maintain prevalence at the elimination threshold over 5 years. We compared four testing strategies. Without any testing or treatment provision, the prevalence of HCV increased from the elimination threshold (11.68%) to a mean of 25.4% (SD 2.96%) over the 5-year period. To maintain elimination with random testing, on average, 4.96% (SD 0.83%) of the injecting network needs to be tested per month. However, with a 'bring your friends' strategy, this was reduced to 3.79% (SD 0.64%) of the network (p < .001). The addition of contact tracing improved the efficiency of both strategies. In conclusion, we report that network-based approaches to testing such as 'bring a friend' initiatives and contact tracing lower the level of testing coverage required to maintain elimination.

Falls During Inpatient Rehabilitation After Spinal Cord Injury: Characterization, Clock-Hour Visualization, and Time to Event Predictors.

OBJECTIVES: To (1) determine fall characteristics (eg, cause, location, witnesses) of inpatients with spinal cord injury (SCI) and whether they were different for ambulatory persons vs wheelchair users; (2) visualize the total number of daily falls per clock-hour for different inpatients' features (eg, cause of injury, age); (3) compare clinical and demographic characteristics of inpatients who experienced a first fall event vs inpatients who did not experience such event; and (4) identify first fall event predictors. DESIGN: Retrospective observational cohort study. SETTING: Institution for inpatient neurologic rehabilitation. PARTICIPANTS: Persons with SCI (N=1294) admitted to a rehabilitation facility between 2005 and 2022. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Functional independence measure (FIM), Hospital Anxiety and Depression Scale (HADS), American Spinal Injury Association Impairment Scale (AIS), and Spinal Cord Independence Measure (SCIM) at admission. Kaplan-Meier survival curves and Cox proportional hazards models were used. RESULTS: A total of 502 fall events were experienced by 369 ambulatory inpatients (19.8%) and wheelchair users (80.2%) in 63.9% of cases being alone, with cause, situation, and location significantly different in both groups. Clock-hour visualizations revealed an absolute peak at 12 AM (complete or incomplete injuries, with paraplegia or tetraplegia) but a relative peak at 9 AM mainly including incomplete patients with paraplegia. Of the (n=1294) included patients, 16.8% experienced at least 1 fall. Fallen patients reported higher levels of HADS depression, lower total SCIM, and longer time since injury to admission, with no differences in age, sex, educational level, FIM (quasi-significant), and AIS grade. Multivariable Cox proportional hazards identified time since injury to admission and AIS grade D as significant predictors of first fall event. CONCLUSIONS: Falls identification, characterization, and clock-hour visualization can support decisions for mitigation strategies specifically addressed to inpatients with SCI. Fall predictors were identified as a first step for future research.

Multicentric investigation on the safety, feasibility and usability of the ABLE lower-limb robotic exoskeleton for individuals with spinal cord injury: a framework towards the standardisation of clinical evaluations.

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.

Tele-rehabilitation on independence in activities of daily living after stroke: A Matched Case-Control Study.

OBJECTIVES: To compare independence in activities of daily living (ADLs) in post-acute patients with stroke following tele-rehabilitation and matched in-person controls. MATERIALS AND METHODS: Matched case-control study. A total of 35 consecutive patients with stroke who followed tele-rehabilitation were compared to 35 historical in-person patients (controls) matched for age, functional independence at admission and time since injury to rehabilitation admission (<60 days). The tele-rehabilitation group was also compared to the complete cohort of historical controls (n=990). Independence in ADLs was assessed using the Functional Independence Measure (FIM) and the Barthel Index (BI). We formally compared FIM and BI gains calculated as discharge score - admission scores, efficiency measured as gains / length of stay and effectiveness defined as (discharge score-admission score)/ (maximum score-admission score). We analyzed the minimal clinically important difference (MCID) for FIM and BI. RESULTS: The groups showed no significant differences in type of stroke (ischemic or hemorrhagic), location, severity, age at injury, length of stay, body mass index, diabetes, dyslipidemia, hypertension, aphasia, neglect, affected side of the body, dominance or educational level. The groups showed no significant differences in gains, efficiency nor effectiveness either using FIM or Barthel Index. We identified significant differences in two specific BI items (feeding and transfer) in favor of the in-person group. No differences were observed in the proportion of patients who achieved MCID. CONCLUSIONS: No significant differences were seen between total ADL scores for tele-rehabilitation and in-person rehabilitation. Future research studies should analyze a combined rehabilitation approach that utilizes both models.

Inpatient Rehabilitation Falls: Comparing Patients With Traumatic Brain Injury Versus Patients With Stroke.

BACKGROUND: Cognitively impaired neurological rehabilitation inpatients are at an increased risk for falls; yet, little is known regarding fall risk of different groups, such as stroke versus traumatic brain injury. OBJECTIVES: To determine if rehabilitation patients' fall characteristics differ for patients with stroke versus patients with traumatic brain injury. METHODS: This retrospective observational cohort study evaluates inpatients with stroke or traumatic brain injury admitted to a rehabilitation center in Barcelona, Spain, between 2005 and 2021. We assessed independence in daily activities with the Functional Independence Measure. We compared fallen versus nonfallen patients' features and examined the association between time to first fall and risk using Cox proportional hazards models. RESULTS: A total of 1,269 fall events were experienced by 898 different patients with traumatic brain injury ( n = 313; 34.9%) and stroke ( n = 585; 65.1%). A higher proportion of falls for patients with stroke occurred while performing rehabilitation activities (20.2%-9.8%), whereas falls were significantly higher for patients with traumatic brain injury during the night shift. Fall timing revealed completely different behaviors (stroke vs. traumatic brain injury), for example, an absolute peak at 6 a.m. due to young male traumatic patients. Nonfallen patients ( n = 1,363; 78.2%) were younger, with higher independence in daily activities scores, and having a larger time since injury to admission; all three were significant fall predictors. CONCLUSIONS: Patients with traumatic brain injury and stroke showed different fall behaviors. Knowledge of fall patterns and characteristics in the inpatient rehabilitation setting can help design management protocols to mitigate their risk.

Leukocyte Tetraspanin CD53 Restrains α3 Integrin Mobilization and Facilitates Cytoskeletal Remodeling and Transmigration in Mice.

The importance of tetraspanin proteins in regulating migration has been demonstrated in many diverse cellular systems. However, the function of the leukocyte-restricted tetraspanin CD53 remains obscure. We therefore hypothesized that CD53 plays a role in regulating leukocyte recruitment and tested this hypothesis by examining responses of CD53-deficient mice to a range of inflammatory stimuli. Deletion of CD53 significantly reduced neutrophil recruitment to the acutely inflamed peritoneal cavity. Intravital microscopy revealed that in response to several inflammatory and chemotactic stimuli, absence of CD53 had only minor effects on leukocyte rolling and adhesion in postcapillary venules. In contrast, Cd53-/- mice showed a defect in leukocyte transmigration induced by TNF, CXCL1 and CCL2, and a reduced capacity for leukocyte retention on the endothelial surface under shear flow. Comparison of adhesion molecule expression in wild-type and Cd53-/- neutrophils revealed no alteration in expression of ß2 integrins, whereas L-selectin was almost completely absent from Cd53-/- neutrophils. In addition, Cd53-/- neutrophils showed defects in activation-induced cytoskeletal remodeling and translocation to the cell periphery, responses necessary for efficient transendothelial migration, as well as increased α3 integrin expression. These alterations were associated with effects on inflammation, so that in Cd53-/- mice, the onset of neutrophil-dependent serum-induced arthritis was delayed. Together, these findings demonstrate a role for tetraspanin CD53 in promotion of neutrophil transendothelial migration and inflammation, associated with CD53-mediated regulation of L-selectin expression, attachment to the endothelial surface, integrin expression and trafficking, and cytoskeletal function.