Markers of physical functioning and neuromuscular fatigue for the post-discharge follow-up of subjects already assisted in intensive care for COVID-19 and non-communicable diseases.

L'insorgenza di malattie non trasmissibili con incidenza neuromuscolare e il prolungato ricovero in terapia intensiva comportano implicazioni negative sulla capacità funzionale e l'autonomia dei pazienti. Queste alterazioni sono causate da fattori come l'immobilità prolungata, l'infiammazione sistemica, le disfunzioni neuromuscolari e gli effetti diretti della patologia stessa. Ciò porta a fatica e debolezza muscolare, contribuendo a un significativo declino nelle abilità motorie, ostacolando il recupero e peggiorando la qualità della vita dei pazienti. Le principali disfunzioni motorie si manifestano con l’alterata deambulazione, limitando l'autonomia nelle attività quotidiane. Tali disfunzioni sono causate dalla compromissione delle vie motorie del sistema nervoso e si manifestano già durante la fase acuta della malattia, peggiorando successivamente con il suo evolversi. Tale quadro clinico è aggravato ulteriormente dalla conseguente inattività fisica, favorita dalle condizioni psicofisiche dei singoli. Di conseguenza, tutto ciò incide notevolmente sulle proprietà contrattili dei muscoli, portando ad alterazioni critiche che influenzano la capacità del sistema nervoso centrale e periferico di reclutare e modulare l'attività delle unità motorie. Date le complessità associate a queste considerazioni, diventa fondamentale identificare marcatori in grado di quantificare e caratterizzare l’alterazione della capacità funzionale e l’insorgenza della debolezza muscolare e della fatica. Ciò faciliterebbe una diagnosi precoce e, in modo cruciale, il monitoraggio continuo di tali problematiche. Pertanto, l'obiettivo primario di questa ricerca di Dottorato è identificare e analizzare marcatori in grado di supportare efficacemente gli operatori sanitari nella progettazione e nell'implementazione di approcci terapeutici personalizzati per accelerare il recupero di questi individui. Nonostante, infatti, la pratica clinica attualmente in uso negli ospedali offra continui miglioramenti, questa presenta ancora delle limitazioni. Sebbene le valutazioni attualmente impiegate riescano ad identificare la presenza di fatica e debolezza muscolare nei pazienti post-ricovero in terapia intensiva o in soggetti affetti da malattie non trasmissibili, non riescono tuttavia ad indagare a fondo su quali siano le effettive cause che innescano la perdita della forza muscolare o ad esaminare in modo esaustivo i fattori centrali e/o periferici che contribuiscono all'insorgenza della fatica. Per colmare in modo esaustivo questa lacuna, lo studio ha condotto un'ampia ricerca combinando l'elettromiografia di superficie con la capacità di generare forza muscolare in diverse condizioni patologiche, includendo attivazioni muscolari sia volontarie che indotte elettricamente. Il muscolo oggetto di studio è stato il tibiale anteriore, scelto per il suo ruolo cruciale nella biomeccanica della deambulazione e quindi fondamentale per il mantenimento dell’autonomia motoria. I risultati hanno mostrato che le variazioni nella forza e nei parametri delle unità motorie possono servire da indicatori per le alterazioni neuromuscolari e il recupero progressivo, facilitando il monitoraggio a breve e lungo termine. Questo studio ha quindi un'importanza fondamentale per le popolazioni coinvolte e può suggerire approcci più ampi per la gestione delle alterazioni neuromuscolari in diversi contesti clinici. In particolare, sottolinea l'importanza di programmi di riabilitazione personalizzati e soggettivati alle esigenze specifiche di ciascun individuo.The onset of non-communicable neuromuscular diseases and prolonged stays in the intensive care unit have deep implications for physical functioning and neuromuscular health. These repercussions arise from muscle deconditioning, systemic inflammation, and the direct impact of the pathology. Moreover, resulting fatigue and acquired muscle weakness contribute to reduced muscular performance, significantly hampering recovery and diminishing overall quality of life. The predominant motor impairments observed in these patients primarily manifest in their ability to perform correct walking, substantially limiting their independent execution of daily activities. This compromised excitability in descending motor pathways becomes evident during the acute phase of the disease and intensifies as the condition progresses chronically, exacerbated by prolonged physical inactivity. Consequently, this significantly affects the muscle's contractile properties, leading to critical alterations that influence the nervous systems' capacity to recruit and modulate the activity of motor units, the fundamental functional units responsible for planning, executing, and maintaining motor gestures. Given these considerations, it becomes crucial to identify markers that enable the quantification and characterization of physical functioning impairment, muscle weakness and fatigue. This would facilitate early diagnosis and, crucially, the ongoing monitoring of these issues. Thus, the primary goal of this PhD research is to identify and analyze markers that can effectively support healthcare practitioners in devising and delivering personalized therapeutic approaches to expedite the recovery of these individuals. The overarching objective is to optimize the current clinical practice commonly employed in hospitals. Despite ongoing refinements, these practices still exhibit limitations. While standard assessments succeed in identifying the presence of fatigue and muscle weakness in ICU patients or those afflicted by non-communicable diseases, they fall short of investigating the root causes of muscle strength deterioration or thoroughly probing the central and/or peripheral factors contributing to the emergence of pathological fatigue. To comprehensively bridge this existing gap, the study undertook an extensive exploration by measuring concurrent joint torques and surface electromyography across various pathological conditions, encompassing both voluntary and electrically induced muscle activations. The focal point was the tibialis anterior muscle, chosen for its pivotal role in gait patterns and consequential influence on individual autonomy. The presented results were mainly achieved through the decomposition of signals recorded using the High-Density Surface EMG technique. This technique enabled the analysis of individual motor units recruited during motor tasks administered to patients within the studied populations. The process of data collection and analysis revealed that variations in muscle strength values and motor unit parameters can serve as indicators of neuromuscular system alterations and progressive recovery. These factors are pivotal for subsequent follow-up procedures. Indeed, by establishing a robust framework of markers, is possible to contribute to the development of evidence-based protocols that enhance the post-discharge care of these individuals. This study is not only pivotal for these specific cohorts but also holds the potential to inform broader strategies for managing physical impairment and neuromuscular challenges in diverse clinical settings. Notably, the study highlights that hospitalization in intensive care, as well as the onset of non-communicable pathologies with high motor impact, leads to specific alterations in parameters of both central and peripheral neuromuscular pathways. This underscores the imperative for devising personalized rehabilitation regimens tailored to each patient's needs

Sex-differences in the longitudinal recovery of neuromuscular function in COVID-19 associated acute respiratory distress syndrome survivors

IntroductionPatients admitted to the intensive care unit (ICU) following severe acute respiratory syndrome 2 (SARS-CoV-2) infection may have muscle weakness up to 1 year or more following ICU discharge. However, females show greater muscle weakness than males, indicating greater neuromuscular impairment. The objective of this work was to assess sex differences in longitudinal physical functioning following ICU discharge for SARS-CoV-2 infection.MethodsWe performed longitudinal assessment of physical functioning in two groups: 14 participants (7 males, 7 females) in the 3-to-6 month and 28 participants (14 males, 14 females) in the 6-to-12 month group following ICU discharge and assessed differences between the sexes. We examined self-reported fatigue, physical functioning, compound muscle action potential (CMAP) amplitude, maximal strength, and the neural drive to the tibialis anterior muscle.ResultsWe found no sex differences in the assessed parameters in the 3-to-6-month follow-up, indicating significant weakness in both sexes.Sex differences emerged in the 6-to-12-month follow-up. Specifically, females exhibited greater impairments in physical functioning, including lower strength, walking lower distances, and high neural input even 1 year following ICU-discharge.DiscussionFemales infected by SARS-CoV-2 display significant impairments in functional recovery up to 1 year following ICU discharge. The effects of sex should be considered in post-COVID neurorehabilitation

Electrophysiological neuromuscular alterations and severe fatigue predict long-term muscle weakness in survivors of COVID-19 acute respiratory distress syndrome

IntroductionLong-term weakness is common in survivors of COVID-19-associated acute respiratory distress syndrome (CARDS). We longitudinally assessed the predictors of muscle weakness in patients evaluated 6 and 12 months after intensive care unit discharge with in-person visits.MethodsMuscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, the compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), a 6-min walk test, severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength and Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for their essential role in ankle control.ResultsMVC improved at 12 months compared with 6 months. CMAP-TA-S100 (P = 0.016) and the presence of severe fatigue (P = 0.036) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT.DiscussionElectrical neuromuscular abnormalities and severe fatigue are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors

Tension reduction and re-lenghtening of muscle- tendon unit in young and old tibialis anterior

Purpose: During an alternating movement of a joint, the inversion of the rotational component of the joint movement happens for the contraction of the agonist muscle, and for the relaxation/re-lengthening of the previously active muscle that is now being configured as antagonist. Gait can be considered as a global alternating movement resulting by the combination of several joints alternating flex-extension sequences with an ordered sequence of agonist and antagonist muscles contraction/relaxation. The aim of the work is to compare young and old muscle- tendon unit deactivation/re-lengthening process which can affect the biomechanics of a daily life crucial gesture such as gait. Methods: The static contraction of tibialis anterior muscle of 20 young (Y) subjects (age 21–33 years old) and 20 older (O) adults (65–80 years old) was studied. A 3 s train of supra-maximal electrical stimulations (35 Hz) was delivered on tibialis anterior motor point while recording the output torque (T) and the muscle transverse dimensional variation, mirroring the re-lengthening process, thanks the laser detected surface mechano-myogram (MMG). During the relaxation phase a delay (D) can be observed between the end of the stimulation and the beginning of signals (T and MMG) decay: DT and DMMG. Using a 20 ms moving window along the collected signals during the off phase the maximum rates of torque and MMG reduction were calculated (RRT and RRMMG). These parameters were calculated also on the normalized signals (NRRT and NRRMMG). Results: DT in O and Y was 51.35 ± 15.21 ms and 22.51 ± 5.92 ms, respectively (p \0.001). DMMG in O and Y was 61.41 ± 18.42 ms and 27.38 ± 6.93 ms, respectively (p \0.001). RRT in O and Y was - 52.72 ± 32.12 Nm/s and 110.4 ± 45.56 Nm/s, respectively (p\ 0.001). RRMMG in O and Y was - 13.76 ± 6.54 mm/s and - 24.47 ± 10.95 mm/s, respectively (p\0.001). NRRT in O and Y was -1026.26 ± 267.76%/s and - 1256.16 ± 333.36%/s, respectively (p = 0.02). NRRMMG in O and Y was - 710.35 ± 178.84%/s and - 867.79%/s ± 148.67, respectively (p = 0.004). Conclusions: These functional data, easy to be obtained during the relaxation phase after static contraction, suggest that the reduction of the tension and the re-lengthening process take place later and slower in O vs Y and provide biomechanical evidences that may contribute to explain the longer gait phases and the reduction of the walking speed typical of the elderly subjects

First Perceptions of Hydroperiod Mapping and Assessment of Shallow Waters in Coastal Landscapes by Drone-Based Monitoring Activities: A Remote-Sensing and GIS Approach

Beyond the importance of ponds for aquatic and terrestrial life, pond networks seem to be crucial to providing a vital spatial resource in response to global climate change for all migrating and spreading taxa. Additionally, ponds offer sustainable solutions to issues of concern in water management, such as nutrient retention, rainfall interception, or carbon sequestration. Although the ecological role of shallow waters seems clear, significant work must be performed to set future guidelines and actions towards their conservation. The main aims of the present study are to (i) georeference all small temporary wetlands within the Tyrrhenian central Italy coastal area, (ii) evaluate their hydroperiod, and (iii) calculate their surface size variability. We found 137 wetlands, 53 of which were temporary and contained listed habitats. Each wetland’s status was assessed in relation to land use and proximity to stressors (e.g., urban centres, railways, roads) while observing the relationship between pond occurrence, lithology, and permeability. Amongst the detected wetlands, we selected and monitored 21 temporary ponds (homogeneously distributed within the study area) for 12 months using images collected by the non-professional drone Parrot Bebop 2. All images were then acquired in ArcGIS to georeference all temporary ponds. The analysis confirmed that the majority of the surveyed ponds are in close proximity to roads and tracks, which might have significant impacts on the preservation of such fragile habitats. Moreover, despite the wide variability of hydroperiod duration, the greater part of the pools fill with water in autumn and dry in summer, in alignment with the Mediterranean climate. This preliminary study allowed for the creation of the first temporary ponds’ database, which is useful for monitoring their status in central Italy and planning further studies to assess eventual detrimental effects caused by human-mediated activities

Assessment of neuromuscular damage in COVID-19 post-intensive care syndrome patients

Purpose: Following hospitalization, Covid-19 post-intensive care syndrome (PICS) patients acquired prolonged physical, mental and cognitive impairments due to the symptoms of the disease, prolonged immobility and neuromuscular complications. The study aims at evaluating the correlation between functional variables i.e. the maximal voluntary contraction (MVC), and electrophysiological variables i.e. the compound muscles action potential (CMAP) and the motor unit number index (MUNIX), to determine a strategy for assessing neuromuscular damage and fatigue in COVID-19 PICS patients both during and post-intensive care unit (ICU) hospitalization. Methods: Fifty-one critically ill patients (37 males, 14 females) were recruited from the ICU of Spedali Civili Hospital in Brescia and underwent a follow-up assessment at 3-, 6- and 12-months following ICU discharge. The protocol consisted of a stimulation and a voluntary protocol. During the stimulation protocol, the CMAP was estimated by stimulating the common peroneal nerve (CPN). During the voluntary protocol, patients performed submaximal isometric foot dorsiflexions at 30, 50, and 70% MVC. The MUNIX was calculated using the CMAP and the surface electromyographic interference patterns (SIP) recorded during the isometric contractions. The CMAP and the SIP were derived from the HD-sEMG signals recorded from the TA with a 64-channel matrix placed over the belly of the tibialis anterior. Results: The mean variations in MVC between 3- and 6-months follow-up (10.75%) and between 6- and 12-months (16%) following COVID-19 ICU discharge were paralleled by changes in CMAP for the same period (? 10.85% at 6 compared to 3 months, and ? 1.09% at 12 compared to 6 months). The linear regression analysis showed a moderate correlation between MVC and CMAP (R2= 0.20; p\0.001) and between MVC and MUNIX (R2= 0.18; p\0.001). Conclusions: The MVC was significantly correlated with CMAP and MUNIX estimations. The correlation between functional and electrophysiological variables allows to longitudinal assess the neuromuscular damage in COVID-19 PICS individuals and opens the possibility for an early clinical evaluation of non- collaborating patients admitted to the ICU and their subsequent follow-up

LSPE-STRIP scientific performance

This document summarizes the scientific performance of the LSPE-STRIP instrument