Lower extremity robotic exoskeleton devices for overground ambulation recovery in acquired brain injury—A review

Acquired brain injury (ABI) is a leading cause of ambulation deficits in the United States every year. ABI (stroke, traumatic brain injury and cerebral palsy) results in ambulation deficits with residual gait and balance deviations persisting even after 1 year. Current research is focused on evaluating the effect of robotic exoskeleton devices (RD) for overground gait and balance training. In order to understand the device effectiveness on neuroplasticity, it is important to understand RD effectiveness in the context of both downstream (functional, biomechanical and physiological) and upstream (cortical) metrics. The review identifies gaps in research areas and suggests recommendations for future research. We carefully delineate between the preliminary studies and randomized clinical trials in the interpretation of existing evidence. We present a comprehensive review of the clinical and pre-clinical research that evaluated therapeutic effects of RDs using various domains, diagnosis and stage of recovery

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

The Cholecystectomy As A Day Case (CAAD) Score: A Validated Score of Preoperative Predictors of Successful Day-Case Cholecystectomy Using the CholeS Data Set

Background Day-case surgery is associated with significant patient and cost benefits. However, only 43% of cholecystectomy patients are discharged home the same day. One hypothesis is day-case cholecystectomy rates, defined as patients discharged the same day as their operation, may be improved by better assessment of patients using standard preoperative variables. Methods Data were extracted from a prospectively collected data set of cholecystectomy patients from 166 UK and Irish hospitals (CholeS). Cholecystectomies performed as elective procedures were divided into main (75%) and validation (25%) data sets. Preoperative predictors were identified, and a risk score of failed day case was devised using multivariate logistic regression. Receiver operating curve analysis was used to validate the score in the validation data set. Results Of the 7426 elective cholecystectomies performed, 49% of these were discharged home the same day. Same-day discharge following cholecystectomy was less likely with older patients (OR 0.18, 95% CI 0.15–0.23), higher ASA scores (OR 0.19, 95% CI 0.15–0.23), complicated cholelithiasis (OR 0.38, 95% CI 0.31 to 0.48), male gender (OR 0.66, 95% CI 0.58–0.74), previous acute gallstone-related admissions (OR 0.54, 95% CI 0.48–0.60) and preoperative endoscopic intervention (OR 0.40, 95% CI 0.34–0.47). The CAAD score was developed using these variables. When applied to the validation subgroup, a CAAD score of ≤5 was associated with 80.8% successful day-case cholecystectomy compared with 19.2% associated with a CAAD score >5 (p < 0.001). Conclusions The CAAD score which utilises data readily available from clinic letters and electronic sources can predict same-day discharges following cholecystectomy

Kinetic Gait Changes after Robotic Exoskeleton Training in Adolescents and Young Adults with Acquired Brain Injury

Background. Acquired brain injury (ABI) is one of the leading causes of motor deficits in children and adults and often results in motor control and balance impairments. Motor deficits include abnormal loading and unloading, increased double support time, decreased walking speed, control, and coordination. These deficits lead to diminished functional ambulation and reduced quality of life. Robotic exoskeletons (RE) for motor rehabilitation can provide the user with consistent, symmetrical, goal-directed repetition of movement, as well as balance and stability. Purpose. The goal of this preliminary prospective before and after study is to evaluate the therapeutic effect of RE training on the loading/unloading and spatial-temporal characteristics in adolescents and young adults with chronic ABI. Method. Seven participants diagnosed with ABI between the ages of 14 and 27 years participated in the study. All participants received twelve 45 minute sessions of RE gait training. The bilateral loading (linearity of loading and rate of loading), speed, step length, swing time, stance time, and total time were collected using Zeno™ walkway (ProtoKinetics, Havertown, PA, USA) before and after RE training. Results. Results from the study showed improved step length, speed, and an overall progression towards healthy bilateral loading, with linearity of loading showing a significant therapeutic effect (p<0.05). Conclusion. These preliminary results suggest that high dose, repetitive, consistent gait training using RE has the potential to induce recovery of function in adolescents and young adults diagnosed with ABI

Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. To investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes, we developed two cellular models where normal oral keratinocytes were chronically exposed to cigarette smoke and chewing tobacco for a period of 8 months. Cellular assays reveal that OKF6/TERT1 cells acquire an oncogenic phenotype after chronic exposure to cigarette smoke/chewing tobacco.  We employed both whole exome sequencing (WES) and quantitative proteomics approaches to investigate the molecular alterations in oral keratinocytes (OKF6/TERT1) chronically exposed to smoke and chewing tobacco. Exome sequencing revealed a much higher rate of C&gt;A transversions in smoke exposed cells in conjunction with previous studies. In contrast, C&gt;G transversions were observed to be higher in chewing tobacco exposed cells. Diverse mutations in both treated cells further highlight the distinct effects of each exposure. Distinct proteomic alterations were observed in smoke and chewing tobacco exposed cells compared to parental cells. In addition, we observe enrichment of different signaling cascades in transformed oral cells upon chronic exposure to either cigarette smoke or chewing tobacco. Current analysis defines a clear distinction in the molecular dysregulation in oral cells in response to different tobacco-based insults. Future studies are needed to validate some of the genetic and proteomic alterations unique to each form of tobacco exposure. This study can serve as a reference for fundamental damage on oral cells as a consequence of exposure to different forms of tobacco

Molecular alterations associated with chronic exposure to cigarette smoke and chewing tobacco in normal oral keratinocytes

Tobacco usage is a known risk factor associated with development of oral cancer. It is mainly consumed in two different forms (smoking and chewing) that vary in their composition and methods of intake. Despite being the leading cause of oral cancer, molecular alterations induced by tobacco are poorly understood. We therefore sought to investigate the adverse effects of cigarette smoke/chewing tobacco exposure in oral keratinocytes (OKF6/TERT1). OKF6/TERT1 cells acquired oncogenic phenotype after treating with cigarette smoke/chewing tobacco for a period of 8&nbsp;months. We employed whole exome sequencing (WES) and quantitative proteomics to investigate the molecular alterations in oral keratinocytes chronically exposed to smoke/ chewing tobacco. Exome sequencing revealed distinct mutational spectrum and copy number alterations in smoke/ chewing tobacco treated cells. We also observed differences in proteomic alterations. Proteins downstream of MAPK1 and EGFR were dysregulated in smoke and chewing tobacco exposed cells, respectively. This study can serve as a reference for fundamental damages on oral cells as a consequence of exposure to different forms of tobacco

Chronic Exposure to Chewing Tobacco Induces Metabolic Reprogramming and Cancer Stem Cell-Like Properties in Esophageal Epithelial Cells

Tobacco in its smoke and smokeless form are major risk factors for esophageal squamous cell carcinoma (ESCC). However, molecular alterations associated with smokeless tobacco exposure are poorly understood. In the Indian subcontinent, tobacco is predominantly consumed in chewing form. An understanding of molecular alterations associated with chewing tobacco exposure is vital for identifying molecular markers and potential targets. We developed an in vitro cellular model by exposing non-transformed esophageal epithelial cells to chewing tobacco over an eight-month period. Chronic exposure to chewing tobacco led to increase in cell proliferation, invasive ability and anchorage independent growth, indicating cell transformation. Molecular alterations associated with chewing tobacco exposure were characterized by carrying out exome sequencing and quantitative proteomic profiling of parental cells and chewing tobacco exposed cells. Quantitative proteomic analysis revealed increased expression of cancer stem cell markers in tobacco treated cells. In addition, tobacco exposed cells showed the Oxidative Phosphorylation (OXPHOS) phenotype with decreased expression of enzymes associated with glycolytic pathway and increased expression of a large number of mitochondrial proteins involved in electron transport chain as well as enzymes of the tricarboxylic acid (TCA) cycle. Electron micrographs revealed increase in number and size of mitochondria. Based on these observations, we propose that chronic exposure of esophageal epithelial cells to tobacco leads to cancer stem cell-like phenotype. These cells show the characteristic OXPHOS phenotype, which can be potentially targeted as a therapeutic strategy