Changes in body composition in early breast cancer patients treated with aromatase inhibitors.

PURPOSE: The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs). METHODS: This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors. RESULTS: A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively. CONCLUSION: Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients.

Negative pressure device used in pediatric patients with Hostile abdomen. Case series. / Dispositivo de presión negativa empleado en pacientes pediátricos con abdomen hostil: serie de casos.

INTRODUCTION: Hostile abdomen is a surgical condition characterized by loss of space between organs and structures in the abdomen. Negative pressure therapy use has been widely described in adults; the case is not the same for pediatric patients. The goal of this study is to present short-term results of negative pressure therapy use in pediatric patients with hostile abdomen due to different etiologies. MATERIAL AND METHODS: Pediatric hostile abdomen patients (< 18 years) who were treated Negative pressure therapy using ABTHERA were identified and retrospectively reviewed. RESULTS: 7 patients were included in this study. Median age was 16 (range: 9-17 yo). 5 (71.4%) were male and 2 (28.6%) females. 3 (43%) had significant past medical/surgical history (Systemic Lupus Erythematosus, complicated appendectomy and ventriculoperitoneal-shunt). The device was set at a continuous pressure ranging from -50 to -125 mmHg. Pre and post-surgical findings were reported using Bjork's classification. Devices were replaced every 4-7 days (median 5 days). Total amount of replacements was 1-4 (median 3). 5 (71.4%) patients required invasive mechanical ventilation during use of Negative pressure therapy based on clinical status. 4 (57%) patients received enteral nutrition. 1 (14%) patient required re-intervention posterior to definitive closure due to retroperitoneal abscess development. Outcome, evaluated by (oral tolerance, bowel movement and absence of pain), was favorable in all patients. CONCLUSION: Negative pressure therapy devices generate favorable results in hostile abdomen in pediatric population but further information is needed to assess pressure settings and device replacement frequency.

INTRODUCCION: El abdomen hostil es una patología quirúrgica caracterizada por una pérdida de espacio entre los órganos y estructuras del abdomen. La terapia de presión negativa se ha descrito de manera extensa en adultos, pero no así en pacientes pediátricos. El objetivo de este estudio es presentar los resultados a corto plazo de la terapia de presión negativa en pacientes pediátricos con abdomen hostil debido a distintas etiologías. MATERIAL Y METODOS: Identificación y análisis retrospectivo de los pacientes pediátricos con abdomen hostil (< 18 años) tratados con terapia de presión negativa ABTHERA. RESULTADOS: Se incluyó a 7 pacientes. La mediana de edad fue de 16 años (rango: 9-17). 5 (71,4%) eran niños y 2 (28,6%) niñas. 3 (43%) presentaban antecedentes médico-quirúrgicos de interés (lupus eritematoso sistémico, apendicectomía complicada y derivación ventriculoperitoneal). El dispositivo se empleó a presión constante, entre ­50 y ­125 mmHg. Los hallazgos preoperatorios y postoperatorios se notificaron mediante la clasificación de Bjork. Los dispositivos se sustituyeron cada 4-7 días (mediana de 5 días). La cantidad total de reemplazos fue de 1-4 (mediana de 3). 5 (71,4%) pacientes precisaron ventilación mecánica invasiva durante la terapia de presión negativa debido al estado clínico. 4 (57%) pacientes recibieron nutrición enteral. 1 (14%) paciente requirió reintervención posterior al cierre definitivo por el desarrollo de un absceso retroperitoneal. El resultado, evaluado en base a la tolerancia oral, el movimiento intestinal y la ausencia de dolor, fue favorable en todos los pacientes. CONCLUSION: Los dispositivos de terapia de presión negativa aportan resultados favorables en los pacientes pediátricos con abdomen hostil, aunque se necesita más información para evaluar los ajustes de presión y la frecuencia de reemplazo del dispositivo.

Dispositivo de presión negativa empleado en pacientes pediátricos con abdomen hostil: serie de casos / Negative pressure device used in pediatric patients with hostile abdomen. Case series

Introducción: El abdomen hostil es una patología quirúrgica caracterizada por una pérdida de espacio entre los órganos y estructuras del abdomen. La terapia de presión negativa se ha descrito de manera extensa en adultos, pero no así en pacientes pediátricos. El objetivo de este estudio es presentar los resultados a corto plazo de la terapia de presión negativa en pacientes pediátricos con abdomen hostil debido a distintas etiologías. Material y métodos: Identificación y análisis retrospectivo de los pacientes pediátricos con abdomen hostil (< 18 años) tratados con terapia de presión negativa ABTHERA. Resultados: Se incluyó a 7 pacientes. La mediana de edad fue de 16 años (rango: 9-17). 5 (71,4%) eran niños y 2 (28,6%) niñas. 3 (43%) presentaban antecedentes médico-quirúrgicos de interés (lupus eritematoso sistémico, apendicectomía complicada y derivación ventriculoperitoneal). El dispositivo se empleó a presión constante, entre–50 y –125 mmHg. Los hallazgos preoperatorios y postoperatoriosse notificaron mediante la clasificación de Bjork. Los dispositivos sesustituyeron cada 4-7 días (mediana de 5 días). La cantidad total dereemplazos fue de 1-4 (mediana de 3). 5 (71,4%) pacientes precisaronventilación mecánica invasiva durante la terapia de presión negativadebido al estado clínico. 4 (57%) pacientes recibieron nutrición enteral.1 (14%) paciente requirió reintervención posterior al cierre definitivopor el desarrollo de un absceso retroperitoneal. El resultado, evaluadoen base a la tolerancia oral, el movimiento intestinal y la ausencia dedolor, fue favorable en todos los pacientes.Conclusión: Los dispositivos de terapia de presión negativa aportanresultados favorables en los pacientes pediátricos con abdomen hostil,aunque se necesita más información para evaluar los ajustes de presióny la frecuencia de reemplazo del dispositivo.(AU)

Introduction: Hostile abdomen is a surgical condition characterized by loss of space between organs and structures in the abdomen. Negative pressure therapy use has been widely described in adults; the case is not the same for pediatric patients. The goal of this study is to present short-term results of negative pressure therapy use in pediatric patients with hostile abdomen due to different etiologies. Materials and methods: Pediatric hostile abdomen patients (< 18 years) who were treated Negative pressure therapy using ABTHERA were identified and retrospectively reviewed. Results: 7 patients were included in this study. Median age was 16 (range: 9-17 yo). 5 (71.4%) were male and 2 (28.6%) females. 3 (43%) had significant past medical/surgical history (Systemic Lupus Erythematosus, complicated appendectomy and ventriculoperitonealshunt). The device was set at a continuous pressure ranging from –50 to –125 mmHg. Pre and post-surgical findings were reported using Bjork’s classification. Devices were replaced every 4-7 days (median 5 days). Total amount of replacements was 1-4 (median 3). 5 (71.4%) patients required invasive mechanical ventilation during use of Negative pressure therapy based on clinical status. 4 (57%) patients received enteral nutrition. 1 (14%) patient required re-intervention posterior to definitive closure due to retroperitoneal abscess development. Outcome, evaluated by (oral tolerance, bowel movement and absence of pain), was favorable in all patients. Conclusion: Negative pressure therapy devices generate favorable results in hostile abdomen in pediatric population but further information is needed to assess pressure settings and device replacement frequency.(AU)

Heterogeneity in regional changes in body composition induced by androgen deprivation therapy in prostate cancer patients: potential impact on bone health-the BLADE study.

BACKGROUND: It is not clear whether changes in body composition induced by androgen deprivation therapy (ADT) in prostate cancer (PC) patients are uniform or vary in the different body districts and whether regional lean body mass (LBM) and fat body mass (FBM) could have an impact on bone health. OBJECTIVE: To prospectively evaluate the regional changes in LBM and FBM in PC patients submitted to degarelix; to explore the relationship of regional body composition and bone mineral density (BMD) and bone turnover markers. DESIGN, SETTING, AND PARTICIPANTS: 29 consecutive non metastatic PC patients enrolled from 2017 to 2019. FBM, LBM and bone mineral density (BMD) evaluated by dual-energy x-ray absorptiometry (DXA) at baseline and after 12-month of ADT. Alkaline phosphate (ALP) and C-terminal telopeptide of type I collagen (CTX) assessed at baseline, 6 and 12 months. INTERVENTION: All patients underwent degarelix administration. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: T-test or sign test and Pearson or Spearman test for continuous variables were used when indicated. RESULTS AND LIMITATIONS: Median percent increase in FBM ranged from + 14.5% in trunk to + 25.4% in the left leg after degarelix. LBM changes varied from + 2% in the trunk to - 4.9% in the right arm. LBM in both arms and legs and their variations after degarelix directly correlated with ALP and inversely correlated with CTX. Lean mass of limbs, trunk and legs significantly correlated with BMD of the hip, lean mass of the trunk significantly correlated with spine BMD. These are post-hoc analysis of a prospective study and this is the main limitation. CONCLUSIONS: an heterogeneous change in body composition among body district is observed after ADT and bone turnover is influenced by lean mass and its variation. A supervised physical activity is crucial to maintain general physical performance and preserving bone health.

Denosumab improves trabecular bone score in relationship with decrease in fracture risk of women exposed to aromatase inhibitors.

PURPOSE: Trabecular bone score (TBS) is a gray-level textural metric that has shown to correlate with risk of fractures in several forms of osteoporosis. The value of TBS in predicting fractures and the effects of bone-active drugs on TBS in aromatase inhibitors (AIs)-induced osteoporosis are still largely unknown. The primary objective of this retrospective study was to assess the effects of denosumab and bisphosphonates (BPs) on TBS and vertebral fractures (VFs) in women exposed to AIs. METHODS: 241 consecutive women (median age 58 years) with early breast cancer undergoing treatment with AIs were evaluated for TBS, bone mineral density (BMD) and morphometric VFs at baseline and after 18-24 months of follow-up. During the study period, 139 women (57.7%) received denosumab 60 mg every 6 months, 53 (22.0%) BPs, whereas 49 women (20.3%) were not treated with bone-active drugs. RESULTS: Denosumab significantly increased TBS values (from 1.270 to 1.323; P < 0.001) accompanied by a significant decrease in risk of VFs (odds ratio 0.282; P = 0.021). During treatment with BPs, TBS did not significantly change (P = 0.849) and incidence of VFs was not significantly different from women untreated with bone-active drugs (P = 0.427). In the whole population, women with incident VFs showed higher decrease in TBS vs. non-fractured women (P = 0.003), without significant differences in changes of BMD at any skeletal site. CONCLUSIONS: TBS variation predicts fracture risk in AIs treated women. Denosumab is effective to induce early increase of TBS and reduction in risk of VFs.

Body composition, trabecular bone score and vertebral fractures in subjects with Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS) frequently causes skeletal fragility characterized by profound alterations in bone microstructure with increased risk of fractures. Increased body fat mass associated with decreased body lean mass are frequent features of KS with possible detrimental effects on skeletal health. In this cross-sectional study, we evaluated the associations between body composition parameters, vertebral fractures (VFs) and trabecular bone score (TBS) in adult subjects with KS. METHODS: Seventy-one adult males (median age 41 years, range 18-64) with 47, XXY KS were consecutively enrolled by two Endocrinology and Andrology Units (IRCCS Humanitas Research Hospital in Milan and ASST Spedali Civili in Brescia). Dual-energy X-ray absorptiometry (DXA) was performed to assess bone mineral density (BMD) at lumbar spine, femoral neck and total hip, TBS and body composition. Prevalence of VFs was assessed by quantitative morphometry on lateral spine X-rays. RESULTS: VFs were detected in 14 patients (19.7%), without significant association with low BMD (p = 0.912). In univariate logistic regression analysis, VFs were significantly associated with truncal/leg fat ratio (OR 2.32 per tertile; 95% CI 1.05-5.15; p = 0.038), whereas impaired TBS (detected in 23.4% of subjects) was associated with older age at study entry (p = 0.001) and at diagnosis of disease (p = 0.015), body mass index (BMI; p = 0.001), waist circumference (p = 0.007), fat mass index (FMI; p < 0.001), FMI/lean mass index (LMI) ratio (p = 0.001). Prevalence of VFs was not significantly different between subjects with impaired TBS as compared to those with normal TBS (26.7 vs. 18.4%; p = 0.485). Skeletal end-points were not significantly associated with duration of testosterone replacement therapy and serum testosterone and 25hydroxyvitamin D values. CONCLUSION: Body composition might influence bone quality and risk of VFs in subjects with KS.

Splenogonadal fusion associated with Moebius and Poland syndromes: first case reported. / Fusión esplenogonadal asociada a síndrome de Moebius y Poland: primer caso reportado.

INTRODUCTION: Splenogonadal fusion is a rare congenital anomaly of unknown etiology caused by an abnormal fusion of the splenic tissue and the gonadal tissue. CASE REPORT: 2-year-old patient with paralysis of the 6th, 7th, and 9th cranial nerves, tent-shaped mouth, cleft palate, right pectoralis major hypoplasia, disruptive defect of the right upper limb, and a mass located at the left inguinal region. At inguinal hernia repair surgery, a processus vaginalis with non-reducible content was observed. When opening the hernia sac, a descending segment of splenic tissue merging with the upper pole of the left testis was found. The patient was diagnosed with splenogonadal fusion. The splenic tissue merging with the testis upper pole was resected, and the remaining splenic tissue was reduced towards the abdominal cavity. DISCUSSION: Splenogonadal fusion is difficult to diagnose. Being familiar with it allows unnecessary orchiectomies to be prevented.

INTRODUCCION: La fusión esplenogonadal es una anomalía congénita rara, de etiología desconocida, causada por la fusión anormal entre el tejido esplénico y gonadal. CASO CLINICO: Paciente de dos años, con parálisis del 6°, 7° y 9° nervio craneal, boca en tienda, paladar hendido, hipoplasia del músculo pectoral mayor derecho y defecto disruptivo de la extremidad superior derecha, masa visible en región inguinal izquierda. Al realizar la herniorrafia inguinal encontramos un conducto peritoneo vaginal con contenido no reductible y a la apertura del saco herniario observamos un segmento de tejido esplénico que desciende y se fusiona con el polo superior del testículo izquierdo. El paciente fue diagnosticado con fusión esplenogonadal. El tejido esplénico fusionado al polo superior del testículo es resecado y el resto del tejido esplénico se reduce hacia la cavidad abdominal. COMENTARIOS: La fusión esplenogonadal es una patología de difícil diagnóstico y su conocimiento puede evitar orquiectomías innecesarias.

Fusión esplenogonadal asociada a síndrome de Moebius y Poland: primer caso reportado / Splenogonadal fusion associated with Moebius and Poland syndromes: first case reported

Introducción: La fusión esplenogonadal es una anomalía congénitarara, de etiología desconocida, causada por la fusión anormal entre eltejido esplénico y gonadal. Caso clínico: Paciente de dos años, con parálisis del 6°, 7° y 9°nervio craneal, boca en tienda, paladar hendido, hipoplasia del músculopectoral mayor derecho y defecto disruptivo de la extremidad superior derecha, masa visible en región inguinal izquierda. Al realizar laherniorrafia inguinal encontramos un conducto peritoneo vaginal concontenido no reductible y a la apertura del saco herniario observamosun segmento de tejido esplénico que desciende y se fusiona con elpolo superior del testículo izquierdo. El paciente fue diagnosticado confusión esplenogonadal. El tejido esplénico fusionado al polo superiordel testículo es resecado y el resto del tejido esplénico se reduce haciala cavidad abdominal. Comentarios: La fusión esplenogonadal es una patología de difícildiagnóstico y su conocimiento puede evitar orquiectomías innecesarias.(AU)

Introduction: Splenogonadal fusion is a rare congenital anomalyof unknown etiology caused by an abnormal fusion of the splenic tissueand the gonadal tissue. Clinical case: 2-year-old patient with paralysis of the 6 th , 7 th , and9th cranial nerves, tent-shaped mouth, cleft palate, right pectoralis majorhypoplasia, disruptive defect of the right upper limb, and a mass locatedat the left inguinal region. At inguinal hernia repair surgery, a processusvaginalis with non-reducible content was observed. When opening thehernia sac, a descending segment of splenic tissue merging with theupper pole of the left testis was found. The patient was diagnosed withsplenogonadal fusion. The splenic tissue merging with the testis uppe pole was resected, and the remaining splenic tissue was reduced towardsthe abdominal cavity. Discussion: Splenogonadal fusion is difficult to diagnose. Beingfamiliar with it allows unnecessary orchiectomies to be prevented.(AU)

Only the Fastest Corticospinal Fibers Contribute to ß Corticomuscular Coherence.

Human corticospinal transmission is commonly studied using brain stimulation. However, this approach is biased to activity in the fastest conducting axons. It is unclear whether conclusions obtained in this context are representative of volitional activity in mild-to-moderate contractions. An alternative to overcome this limitation may be to study the corticospinal transmission of endogenously generated brain activity. Here, we investigate in humans (N = 19; of either sex), the transmission speeds of cortical ß rhythms (∼20 Hz) traveling to arm (first dorsal interosseous) and leg (tibialis anterior; TA) muscles during tonic mild contractions. For this purpose, we propose two improvements for the estimation of corticomuscular ß transmission delays. First, we show that the cumulant density (cross-covariance) is more accurate than the commonly-used directed coherence to estimate transmission delays in bidirectional systems transmitting band-limited signals. Second, we show that when spiking motor unit activity is used instead of interference electromyography, corticomuscular transmission delay estimates are unaffected by the shapes of the motor unit action potentials (MUAPs). Applying these improvements, we show that descending corticomuscular ß transmission is only 1-2 ms slower than expected from the fastest corticospinal pathways. In the last part of our work, we show results from simulations using estimated distributions of the conduction velocities for descending axons projecting to lower motoneurons (from macaque histologic measurements) to suggest two scenarios that can explain fast corticomuscular transmission: either only the fastest corticospinal axons selectively transmit ß activity, or else the entire pool does. The implications of these two scenarios for our understanding of corticomuscular interactions are discussed.SIGNIFICANCE STATEMENT We present and validate an improved methodology to measure the delay in the transmission of cortical ß activity to tonically-active muscles. The estimated corticomuscular ß transmission delays obtained with this approach are remarkably similar to those expected from transmission in the fastest corticospinal axons. A simulation of ß transmission along a pool of corticospinal axons using an estimated distribution of fiber diameters suggests two possible mechanisms by which fast corticomuscular transmission is achieved: either a very small fraction of the fastest descending axons transmits ß activity to the muscles or, alternatively, the entire population does and natural cancellation of slow channels occurs because of the distribution of axon diameters in the corticospinal tract.

Towards human motor augmentation by voluntary decoupling beta activity in the neural drive to muscle and force production.

Objective.Effective human motor augmentation should rely on biological signals that can be volitionally modulated without compromising natural motor control.Approach.We provided human subjects with real-time information on the power of two separate spectral bands of the spiking activity of motor neurons innervating the tibialis anterior muscle: the low-frequency band (<7 Hz), which is directly translated into natural force control, and the beta band (13-30 Hz), which is outside the dynamics of the neuromuscular system.Main Results.Subjects could gain control over the powers in these two bands to navigate a cursor towards specific targets in a 2D space (experiment 1) and to up- and down-modulate beta activity while keeping steady force contractions (experiment 2).Significance.Results indicate that beta projections to the spinal motor neuron pool can be voluntarily controlled partially decoupled from natural muscle contractions and, therefore, they could be valid control signals for implementing effective human motor augmentation platforms.

Spinal motoneurons of the human newborn are highly synchronized during leg movements.

Motoneurons of neonatal rodents show synchronous activity that modulates the development of the neuromuscular system. However, the characteristics of the activity of human neonatal motoneurons are largely unknown. Using a noninvasive neural interface, we identified the discharge timings of individual spinal motoneurons in human newborns. We found highly synchronized activities of motoneurons of the tibialis anterior muscle, which were associated with fast leg movements. Although neonates' motor units exhibited discharge rates similar to those of adults, their synchronization was significantly greater than in adults. Moreover, neonatal motor units showed coherent oscillations in the delta band, which is directly translated into force generation. These results suggest that motoneuron synchronization in human neonates might be an important mechanism for controlling fast limb movements, such as those of primitive reflexes. In addition to help revealing mechanisms of development, the proposed neural interface might monitor children at risk of developing motor disorders.

Pretreatment DWI with Histogram Analysis of the ADC in Predicting the Outcome of Advanced Oropharyngeal Cancer with Known Human Papillomavirus Status Treated with Chemoradiation.

BACKGROUND AND PURPOSE: The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has increased in the period from the 1970s to 2004, due to increase of infection with human papilloma virus (HPV). This study aimed to examine the role of histogram analysis of the ADC in treatment response and survival prediction of patients with oropharyngeal squamous cell carcinoma and known human papillomavirus status. MATERIALS AND METHODS: This was a retrospective single-center study. Following inclusion and exclusion criteria, data for 59 patients affected by T2-T4 (according to the 8th edition of the AJCC Cancer Staging Manual) oropharyngeal squamous cell carcinoma were retrieved. Twenty-eight had human papillomavirus-positive oropharyngeal squamous cell carcinoma, while 31 had human papillomavirus-negative oropharyngeal squamous cell carcinoma. All patients underwent a pretreatment MR imaging. Histogram analysis of ADC maps obtained by DWI (b = 0-1000 mm/s2) was performed on the central section of all of tumors. The minimum follow-up period was 2 years. Histogram ADC parameters were associated with progression-free survival and overall survival. Univariable and multivariable Cox models were applied to the data; P values were corrected using the Benjamini-Hochberg method. RESULTS: At univariable analysis, both human papillomavirus status and mean ADC were associated with progression-free survival (hazard ratio = 0.267, P < .05, and hazard ratio = 1.0028, P ≤ .05, respectively), while only human papillomavirus status was associated with overall survival (hazard ratio = 0.213, P ≤ .05) before correction. At multivariable analysis, no parameter was included (in fact, human papillomavirus status lost significance after correction). If we separated the patients into 2 subgroups according to human papillomavirus status, ADC entropy was associated with overall survival in the human papillomavirus-negative group (hazard ratio = 4.846, P = .01). CONCLUSIONS: ADC and human papillomavirus status are related to progression-free survival in patients treated with chemoradiation for advanced oropharyngeal squamous cell carcinoma; however, this association seems to result from the strong association between ADC and human papillomavirus status.

Tutorial: Analysis of motor unit discharge characteristics from high-density surface EMG signals.

Recent work demonstrated that it is possible to identify motor unit discharge times from high-density surface EMG (HDEMG) decomposition. Since then, the number of studies that use HDEMG decomposition for motor unit investigations has increased considerably. Although HDEMG decomposition is a semi-automatic process, the analysis and interpretation of the motor unit pulse trains requires a thorough inspection of the output of the decomposition result. Here, we report guidelines to perform an accurate extraction of motor unit discharge times and interpretation of the signals. This tutorial includes a discussion of the differences between the extraction of global EMG signal features versus the identification of motor unit activity for physiological investigations followed by a comprehensive guide on how to acquire, inspect, and decompose HDEMG signals, and robust extraction of motor unit discharge characteristics.

Real-Time Interface Algorithm for Ankle Kinematics and Stiffness From Electromyographic Signals.

Shortcomings in capabilities of below-knee (transtibial) prostheses, compared to their biological counterparts, still cause medical complications and functional deficit to millions of amputees around the world. Although active (powered actuation) transtibial prostheses have the potential to bridge these gaps, the current control solutions limit their efficacy. Here we describe the development of a novel interface for two degrees-of-freedom position and stiffness control for below-knee amputees. The developed algorithm for the interface relies entirely on muscle electrical signals from the lower leg. The algorithm was tested for voluntary position and stiffness control in eight able-bodied and two transtibial amputees and for voluntary stiffness control with foot position estimation while walking in eight able-bodied and one transtibial amputee. The results of the voluntary control experiment demonstrated a promising target reaching success rate, higher for amputees compared to the able-bodied individuals (82.5% and 72.5% compared to 72.5% and 68.1% for the position and position and stiffness matching tasks respectively). Further, the algorithm could provide the means to control four stiffness levels during walking in both amputee and able-bodied individuals while providing estimates of foot kinematics (gait cycle cross-correlation >75% for the sagittal and >90% for the frontal plane and gait cycle root mean square error <7.5° in sagittal and <3° in frontal plane for able-bodied and amputee individuals across three walking speeds). The results from the two experiments demonstrate the feasibility of using this novel algorithm for online control of multiple degrees of freedom and of their stiffness in lower limb prostheses.

Alemtuzumab treatment of multiple sclerosis in real-world clinical practice: A report from a single Italian center.

BACKGROUND: Alemtuzumab, is a compound approved for highly active MS, and, in Europe, employed after the use of other disease-modifying treatments (DMTs) with an escalation approach or used as a first therapeutic option. The occurrence of secondary autoimmune adverse events and or infections can differ depending on the employed approach. OBJECTIVE: To evaluate the efficacy and safety of alemtuzumab in real-world MS population that encompassed patients previously treated with other DMTs. METHODS: 35 patients, treated with alemtuzumab in a single MS Center, were followed for at least 36 months. The study investigated the prevalence of patients reaching the phase of the non-active disease (NEDA-3). All the adverse events were also reported, and correlations assessed. RESULTS: At the 36-month follow-up, 66,7% of patients achieved the NEDA-3 status, 90,5% of the patients were relapse-free, 85,7% showed no signs of disability progression, nor signs of MRI activity. Adverse events were observed in 45,7% of the patients and ranked as severe in 23% of them. Cases of autoimmune hemolytic anemia (AIHA), pancytopenia, viral hepatitis E, and noninfectious meningo-encephalomyelitis were found and reported. For these complications, the post hoc analysis showed possible interactive factors and causality related to previous DMT treatments. CONCLUSIONS: In a real-world MS population like the one investigated in our study, alemtuzumab was found to be an effective treatment when employed as an escalation or rescue therapy. The compound exhibits a variable safety profile and frequent adverse events that are likely depending on previous treatments and their impact on the immune system.

The human central nervous system transmits common synaptic inputs to distinct motor neuron pools during non-synergistic digit actions.

KEY POINTS: Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi-muscle EMG recordings. We quantified the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles during tasks that required the two hand muscles to exert matched or un-matched forces in different directions. We show that when the two hand muscles are concurrently activated, synaptic input to the two motor neuron pools is shared across all frequency bandwidths (representing cortical and spinal input) associated with force control. The observed connectivity indicates that motor neuron pools receive common input even when digit actions do not belong to a common behavioural repertoire. ABSTRACT: Neural connectivity between distinct motor neuronal modules in the spinal cord is classically studied through electrical stimulation or multi-muscle EMG recordings. Here we quantify the strength of correlation in the activity of two distinct populations of motor neurons innervating the thenar and first dorsal interosseous muscles in humans during voluntary contractions. To remove confounds associated with previous studies, we used a task that required the two hand muscles to exert matched or un-matched forces in different directions. Despite the force production task consisting of uncommon digit force coordination patterns, we found that synaptic input to motor neurons is shared across all frequency bands, reflecting cortical and spinal inputs associated with force control. The coherence between discharge timings of the two pools of motor neurons was significant at the delta (0-5 Hz), alpha (5-15 Hz) and beta (15-35 Hz) bands (P < 0.05). These results suggest that correlated input to motor neurons of two hand muscles can occur even during tasks not belonging to a common behavioural repertoire and despite lack of common innervation. Moreover, we show that the extraction of activity from motor neurons during voluntary force control removes cross-talk associated with global EMG recordings, thus allowing direct in vivo interrogation of spinal motor neuron activity.

Interfacing the neural output of the spinal cord: robust and reliable longitudinal identification of motor neurons in humans.

OBJECTIVE: Non-invasive electromyographic techniques can detect action potentials from muscle units with high spatial dimensionality. These technologies allow the decoding of large samples of motor units by using high-density grids of electrodes that are placed on the skin overlying contracting muscles and therefore provide a non-invasive representation of the human spinal cord output. APPROACH: From a sample of >1200 decoded motor neurons, we show that motor neuron activity can be identified in humans in the full muscle recruitment range with high accuracy. MAIN RESULTS: After showing the validity of decomposition with novel test parameters, we demonstrate that the same motor neurons can be tracked over a period of one-month, which allows for the longitudinal analysis of individual human neural cells. SIGNIFICANCE: These results show the potential of an accurate and reliable assessment of large populations of motor neurons in physiological investigations. We discuss the potential of this non-invasive neural interfacing technology for the study of the neural determinants of movement and man-machine interfacing.