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Background: Proton therapy (PRT) is an innovative radiotherapeutic modality for the treatment of cancer with unique ballistic properties. The depth-dose distribution of a proton beam reduces exposure of healthy tissues to radiations, compared with photon-therapy (XRT). To date, only few indications for proton-therapy, like pediatric cancers, chordomas, or intra-ocular neoplasms, are reimbursed by Health systems. There is no published or recruiting prospective study evaluating the impact of proton-therapy or conventional irradiation on neurocognitive function for meningioma patients. Notably, long-term cognitive or ocular impact of these modern irradiation schemes remains poorly known. Yet, these patients had a long life-expectancy, and are at risk of developing long-term sequelae. Thus, according to its ballistic advantage, an improvement of patient functional outcomes and a reduction of neurocognitive long-term toxicity are expected if tissue sparing proton-therapy is used .Randomized trial seems crucial to further assess proton-therapy indication for patients with cavernous sinus meningioma., Methods: COG-PROTON-01 is the first worldwide randomized phase III prospective study evaluating long-term toxicity of these two irradiation modalities (PRT and XRT)for the treatment of cavernous sinus meningioma. Primary objective is to compare long-term cognitive and/or functional (visual, hearing, neurological and/or endocrinological) deterioration between patients treated by fractionated proton-therapy (PRT) or photon radiotherapy (XRT), 5 years after the end of irradiation. The primary endpoint is based on the individual neurocognitive test scores (grouped into five cognitive domains: attention, executive functioning, verbal memory, working memory, information processing speed) and on visual, hearing, endocrinological and neurological evaluations, five years after radiotherapy. Eligible patients with low-grade cavernous sinus meningioma will be 1:1 randomised, with stratification on age, sex, MoCA score. Overall, the inclusion of 160 patients is planned (80 in each arm). To be considered as positive, asumming that 47% of patients will not develop long-term cognitive disabilities deficits after XRT radiotherapy,, thus at least 70% of the patients treated with PRT should not develop functional impairment. First inclusions started on September 2023 (NCT05895344 )., Trial Registration: The study was registered on clinicaltrials.gov on June 8, 2023 with the following number: NCT05895344., Competing Interests: Declarations. Ethical approval: This study has received ethical approval from the Comité de protection des personnes Ouest V and from National agency for medical and health products safety (Ref IDRCB 2023-A00401-44) in. All patients will give their written informed consent before any study relative assessment start. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: This study evaluates the gait analysis obtained by Inetial Measurement Units (IMU) before and after surgical management of Spastic Equino Varus Foot (SEVF) in hemiplegic post-stroke patients and to compare it with the functional results obtained in a monocentric prospective cohort., Methods: Patients with post-stroke SEVF, who underwent surgery in a single hospital between November 2019 and December 2021 were included. The follow-up duration was 6 months and included a functional analysis using Goal Attainment Scaling (GAS) and a Gait analysis using an innovative Multidimensional Gait Evaluation using IMU: the semiogram., Results: 20 patients had a gait analysis preoperatively and at 6 months postoperatively. 90% (18/20) patients had a functional improvement (GAS T score ≥ 50) and 50% (10/20) had an improvement in walking technique as evidenced by the cessation of the use of a walking aid (WA). In patients with functional improvement and modification of WA the change in the semiogram area was + 9.5%, sd = 27.5%, and it was + 15.4%, sd = 28%. In the group with functional improvement without change of WA. For the 3 experiences (two patients) with unfavorable results, the area under the curve changed by + 2.3%, -10.2% and - 9.5%. The measurement of the semiogram area weighted by average speed demonstrated very good reproducibility (ICC(1, 3) = 0.80)., Discussion: IMUs appear to be a promising solution for the assessment of post-stroke hemiplegic patients who have undergone SEVF surgery. They can provide a quantified, objective, reliable in individual longitudinal follow up automated gait analysis solution for routine clinical use. Combined with a functional scale such as the GAS, they can provide a global analysis of the effect of surgery., (© 2024. The Author(s).)

Background: Recently, the use of inertial measurement units (IMUs) in quantitative gait analysis has been widely developed in clinical practice. Numerous methods have been developed for the automatic detection of gait events (GEs). While many of them have achieved high levels of efficiency in healthy subjects, detecting GEs in highly degraded gait from moderate to severely impaired patients remains a challenge. In this paper, we aim to present a method for improving GE detection from IMU recordings in such cases., Methods: We recorded 10-meter gait IMU signals from 13 healthy subjects, 29 patients with multiple sclerosis, and 21 patients with post-stroke equino varus foot. An instrumented mat was used as the gold standard. Our method detects GEs from filtered acceleration free from gravity and gyration signals. Firstly, we use autocorrelation and pattern detection techniques to identify a reference stride pattern. Next, we apply multiparametric Dynamic Time Warping to annotate this pattern from a model stride, in order to detect all GEs in the signal., Results: We analyzed 16,819 GEs recorded from healthy subjects and achieved an F1-score of 100%, with a median absolute error of 8 ms (IQR [3-13] ms). In multiple sclerosis and equino varus foot cohorts, we analyzed 6067 and 8951 GEs, respectively, with F1-scores of 99.4% and 96.3%, and median absolute errors of 18 ms (IQR [8-39] ms) and 26 ms (IQR [12-50] ms)., Conclusions: Our results are consistent with the state of the art for healthy subjects and demonstrate a good accuracy in GEs detection for pathological patients. Therefore, our proposed method provides an efficient way to detect GEs from IMU signals, even in degraded gaits. However, it should be evaluated in each cohort before being used to ensure its reliability., (© 2024. The Author(s).)

Background: Vibrotactile stimulation is a promising venue in the field of prosthetics to retrain sensory feedback deficits following amputation. Discrimination is well established at the forearm level but not at the upper arm level. Moreover, the effects of combining vibration characteristics such as duration and intensity has never been investigated., Method: We conducted experiments on spatial discrimination (experiment 1) and tactile intensity perception (experiment 2), using 9 combinations of 3 intensities and 3 durations of vibror stimulations device. Those combinations were tested under 4 arrangements with an array of 6 vibrors. In both experiments, linear orientation aligned with the upper arm longitudinal axis were compared to circular orientation on the upper arm circumference. For both orientations, vibrors were placed either with 3cm space between the center of 2 vibrors or proportionally to the length or the circumference of the subject upper arm. Eleven heathy subjects underwent the 2 experiments and 7 amputees (humeral level) participated in the spatial discrimination task with the best arrangement found., Results: Experiment 1 revealed that circular arrangements elicited better scores than the linear ones. Arrangements with vibrors spaced proportionally elicited better scores (up to 75% correct) than those with 3 cm spacing. Experiment 2, showed that the perceived intensity of the vibration increases with the intensity of the vibrors' activation, but also with their duration of activation. The 7 patients obtained high scores (up to 91.67% correct) with the circular proportional (CP) arrangement., Discussion: These results highlight that discrete and short vibrations can be well discriminated by healthy subjects and people with an upper limb amputation. These new characteristics of vibrations have great potential for future sensory substitution application in closed-loop prosthetic control.

Background: Falling is the most common accident of daily living and the second most prevalent cause of accidental death in the world. The complex nature of risk factors associated with falling makes those at risk amongst the elderly population difficult to identify. Commonly used clinical tests have limitations when it comes to reliably detecting the risk of falling, but existing laboratory tests, such as force platform measurements, represent one method of overcoming this lack of a test. Despite their widespread use, however, Center of Pressure (COP) signal analysis techniques vary and there is currently no consensus on which features should be used diagnostically. Our objective is to identify, through a systematic review and meta-analysis, the COP characteristics of older adults (≥ 60 years old) during quiet bipedal stance which will allow fallers to be distinguished from non-fallers., Methods: The systematic review will include both prospective and retrospective articles. Five databases will be searched: PubMed, Cochrane CENTRAL, EMBASE, and ScienceDirect. In addition, a search of gray literature will be performed using Google Scholar and ClinicalTrials.gov. Searches will be circumscribed to include only older adults (aged over 60 years) who underwent a bipedal quiet standing measure of their balance and for whom the number of falls was reported. Two authors will independently assess the risk of bias for each included article using a 26-item checklist. Funnel plots will be drawn to attest of possible publication biases for each COP parameters. The results will be synthesized descriptively and a meta-analysis will be undertaken. When trial methodological heterogeneity is too great for pooling of the data into a meta-analysis, evidence strength will be evaluated using best evidence analysis., Discussion: Despite the numerous advantages of posturography, the diversity of studies exploring balance in older fallers has led to uncertainty regarding the method's ability to reliably identify fall-prone older adults. It is expected that the findings from this systematic review will help clinicians use bipedal quiet standing measures as a diagnostic test and allow researchers to explore COP characteristics to create better models for fall prevention care., Systematic Review Registration: PROSPERO CRD42018098671.

Background: Radiotherapy is one of the most important treatments of primary and metastatic brain tumors. Unfortunately, it can involve moderate to severe complications among which leukoencephalopathy is very frequent and implies cognitive deficits such as memory, attention and executive dysfunctions. However, the incidence of this complication is not well established and the risk factors and process are poorly understood. The main objective of the study is to improve knowledge on radio-induced leukoencephalopathy based on pluridisciplinar approaches combining cognitive, biologic, imagery and dosimetric investigations., Method/design: The EpiBrainRad study is a prospective cohort study including newly diagnosed high grade gliomas patients treated by radiotherapy and concomitant-adjuvant temozolomide chemotherapy. Patients are included between their surgery and first day of radio-chemotherapy, and the follow-up lasts for 3 years after treatment. Cognitive functioning assessments, specific blood biomarkers measures and magnetic resonance imagery are performed at different moment during the follow-up, and a specific dosimetric assessment of organs involved in the beam fields is performed. Firstly, leukoencephalopathy incidence rate will be estimated in this population. Secondly, correlations between cognitive impairments and dosimetry, biomarkers ranges and anomalies on imagery will be analyzed in order to better understand the onset and evolution of cognitive decrement associated with radiotherapy. Furthermore, a new cognitive test, quickly and easily performed, will be studied to determine its sensibility to detect leukoencephalopathy decrement., Discussion: With an original multidisciplinary approach, the EpiBrainRad study aims to improve knowledge on radio-induced leukoencephalopathy in order to improve its early diagnosis and prevention. The main challenge is to preserve quality-of-life after cancer treatments which imply to study the incidence of radiation-induced complications and their associated risk factors., Trial Registration: NCT02544178.

Background: There have been no previous studies of the long-term survival and temporal changes in plasma viral load among HIV-2 infected subjects., Methods: 133 HIV-2 infected and 158 HIV-uninfected subjects from a rural area in North-west Guinea-Bissau, West Africa were enrolled into a prospective cohort study in 1991 and followed-up to mid-2009. Data were collected on four occasions during that period on HIV antibodies, CD4% and HIV-2 plasma viral load., Results: Median age (interquartile range [IQR]) of HIV-2 infected subjects at time of enrollment was 47 (36, 60) years, similar to that of HIV-uninfected control subjects, 49 (38, 62) (p = 0.4). Median (IQR) plasma viral load and CD4 percentage were 347 (50, 4,300) copies/ml and 29 (22, 35) respectively.Overall loss to follow-up to assess vital status was small, at 6.7% and 6.3% for HIV-2 infected and uninfected subjects respectively. An additional 17 (12.8%) and 16 (10.1%) of HIV-2 infected and uninfected subjects respectively were censored during follow-up due to infection with HIV-1. The mortality rate per 100 person-years (95% CI) was 4.5 (3.6, 5.8) among HIV-2 infected subjects compared to 2.1 (1.6, 2.9) among HIV-uninfected (age-sex adjusted rate ratio 1.9 (1.3, 2.8, p < 0.001) representing a 2-fold excess mortality rate associated with HIV-2 infection.Viral load measurements were available for 98%, 78%, 77% and 61% HIV-2 infected subjects who were alive and had not become super-infected with HIV-1, in 1991, 1996, 2003 and 2006 respectively. Median plasma viral load (RNA copies per ml) (IQR) did not change significantly over time, being 150 (50, 1,554; n = 77) in 1996, 203 (50, 2,837; n = 47) in 2003 and 171 (50, 497; n = 31) in 2006. Thirty seven percent of HIV-2 subjects had undetectable viraemia (<100 copies/ml) at baseline: strikingly, mortality in this group was similar to that of the general population., Conclusions: A substantial proportion of HIV-2 infected subjects in this cohort have stable plasma viral load, and those with an undetectable viral load (37%) at study entry had a normal survival rate. However, the sequential laboratory findings need to be interpreted with caution given the number of individuals who could not be re-examined.