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Neuromuscular weakness resulting in severe functional impairment is common in critical care survivors. This study aimed to evaluate effects of an early progressive rehabilitation intervention in mechanically ventilated adults at risk. This was a parallel, two-arm, assessor-blinded, randomised controlled trial with 6-months follow-up that was conducted in a mixed ICU of an academic centre in Switzerland. Previously independent, mechanically ventilated, critically ill adults with expected critical care stay ≥72 hours (n = 115) were randomised to a control group receiving standard physiotherapy including early mobilisation or to an experimental group with early endurance and resistance training combined with mobilisation. Primary endpoints were functional capacity (6-Minute Walk Distance) and functional independence (Functional Independence Measure) at hospital discharge. Secondary endpoints including muscle strength were assessed at critical care discharge. Safety was monitored closely by standard monitoring and predefined adverse events. Physiotherapy started within 48 hours of critical care admission while 97% of participants were still ventilated and 68% on inotropes. Compared to the control group (n = 57), the experimental group (n = 58) received significantly more physiotherapy (sessions: 407 vs 377, p<0.001; time/session: 25min vs 18min, p<0.001) and had less days with sedation (p<0.001). Adverse events were rare (0.6%) and without consequences. There were no significant between-group differences in 6-Minute Walk Distance (experimental 123m (IQR 25-280) vs control 100m (IQR 0-300); p = 0.542) or functional independence (98 (IQR 66-119) vs 98 (IQR 18-115); p = 0.308). Likewise, no differences were found for the secondary outcomes, except a trend towards improved mental health in the experimental group after 6 months (84 (IQR 68-88) vs 70 (IQR 64-76); p = 0.023). Early endurance and resistance training in mechanically ventilated, intensive care patients does not improve functional capacity or independence at hospital discharge compared to early standard physiotherapy but may improve mental health 6-months after critical care discharge. German Clinical Trials Register (DRKS): DRKS00004347, registered on 10 September 2012.

Background Intensive care unit acquired-weakness syndrome (ICUAWS) leaves several complications in functional movements of patients such as severe walking disability. Objective Assessment of functional outcomes of 1-month inspiratory muscle training (IMT) in elderly with ICUAWS and severe walking disability was our aim. The design, setting, participants, and intervention. This study is a randomized controlled trial. ICUAWS patients who complained of severe walking disability on the Modified Functional Ambulatory Category Test (MFACT) were randomly assigned into the IMT group or control group, n  = 20 for each group. Both groups received the traditional physical therapy program. Results The results showed that the post-therapy between-group comparison of ICUAWS sufferers/groups’ parameters showed a significant improvement toward the IMT group in six-minute walk test, inspiratory and expiratory muscle strength, forced vital capacity, time up and go test, 10-m walk test, forced expiratory volume in the first second, 30-s sit-to-stand test, partial pressure of arterial blood oxygen and carbon dioxide, MFACT, oxygen saturation of arterial blood, physical, and mental summary of short form 36. Conclusion In conclusion, IMT improves functional outcomes in ICUAWS patients with walking disability. Trial registration number The clinical trial ID of this ICUAWS trial is NCT06210763.

Patients with sepsis and immobility in the intensive care unit are associated with muscle weakness, and early mobilisation can counteract it. However, during septic shock, mobilisation is often delayed due to the severity of the illness. Neuromuscular electrical stimulation (NMES) may be an alternative to mobilise these patients early. This study aims to identify whether NMES performed within the first 72 hours of septic shock diagnosis or later is safe from a metabolic perspective. This is the analysis of two randomised controlled crossover studies. Patients with acute septic shock (within the first 72 hours of diagnosis) and sepsis and septic shock in the late phase (after 72 hours of diagnosis) were eligible. Patients were submitted in a random order to the intervention protocol (dorsal decubitus position with the lower limbs raised and NMES) and control (dorsal decubitus position with the lower limbs raised without NMES). The patients were allocated in group 1 (intervention and control) or group 2 (control and intervention) with a wash-out period of 4 to 6 hours. Metabolic variables were evaluated by indirect calorimetry. Sixteen patients were analysed in the acute septic shock study and 21 in the late sepsis/septic shock study. There were no significant differences between Oxygen Consumption (VO2) values in the acute phase of septic shock when the baseline period, intervention, and control protocols were compared (186.59 ± 46.10; 183.64 ± 41.39; 188.97 ± 44.88, p>0.05- expressed in mL/Kg/min). The same was observed when the VO2 values in the late phase were compared (224.22 ± 53.09; 226.20 ± 49.64; 226.79 ± 58.25, p>0.05). The other metabolic variables followed the same pattern, with no significant differences between the protocols. When metabolic variables were compared between acute to late phase, significant differences were observed (p<0.05). As metabolic rates in septic shock patients had no increase during NMES, either in the first 72 hours of diagnosis or later, NMES can be considered safe from a metabolic viewpoint, even despite the higher metabolic demand in the acute phase of shock. NCT03193164; NCT03815994. Registered on June 5, 2017; November 13, 2018 (clinicaltrials.gov/).

Background Intensive care unit-acquired weakness (ICUAW) is a prevalent secondary disorder in critically ill patients, characterized by significant loss of muscle mass and strength, often leading to prolonged ICU stays, increased mortality, and reduced post-discharge quality of life. Despite guidelines recommending early mobilization, logistical challenges and inconclusive efficacy have limited its impact on ICUAW prevalence. This study aims to assess the feasibility, safety, and clinical efficacy of exclusively passive physiotherapeutic interventions, including blood flow restriction/ischemic preconditioning (BFR/IPC) and electromyostimulation (EStim), as potential alternatives for muscle preservation in ICU patients who are often sedated or unable to participate in active rehabilitation. Methods This prospective, randomized controlled trial will recruit 120 patients from the surgical ICU at the University Hospital Bonn, who meet the inclusion criteria of a > 48-h ICU stay. Patients will be randomized into four groups: Sham-Control, BFR/IPC, EStim, and combined BFR/IPC + EStim. The study’s primary endpoints include feasibility and safety metrics, such as patient compliance and stress response, alongside secondary endpoints related to clinical outcomes like ICU length of stay, ICUAW prevalence, muscle mass preservation, and rehabilitation efficacy. Measurements include non-invasive assessments of muscle mass, intramuscular microdialysis to monitor metabolic and inflammatory markers, and health-related quality of life evaluations post-discharge. Discussion Preliminary literature and a systematic review underscore the need for resource-efficient, non-invasive interventions in ICU settings. BFR/IPC and EStim present promising results, but existing data on their efficacy in ICU populations are limited. This study’s findings will provide foundational data on the viability of passive physiotherapy techniques in ICU settings, potentially improving patient outcomes and reducing healthcare costs associated with prolonged ICU stays. If successful, these results will inform a multicenter randomized trial to further evaluate these interventions. This research represents a crucial step in developing feasible rehabilitation protocols to mitigate ICUAW, addressing a critical gap in critical care management and rehabilitation. Trial registration ClinicalTrials.gov DRKS00033592. Registered on March 05, 2024.

Objective. To identify the clinical correlations between plasma growth differentiation factor-15 (GDF-15), skeletal muscle function, and acute muscle wasting in ICU patients with mechanical ventilation. In addition, to investigate its diagnostic value for ICU-acquired weakness (ICU-AW) and its predictive value for 90-day survival in mechanically ventilated patients. Methods. 95 patients with acute respiratory failure, who required mechanical ventilation therapy, were randomly selected among hospitalized patients from June 2017 to January 2019. The plasma GDF-15 level was detected by ELISA, the rectus femoris cross-sectional area (RFcsa) was measured by ultrasound, and the patient’s muscle strength was assessed using the British Medical Research Council (MRC) muscle strength score on day 1, day 4, and day 7. Patients were divided into an ICU-AW group and a non-ICU-AW group according to their MRC-score on the 7th day. The differences in plasma GDF-15 level, MRC-score, and RFcsa between the two groups were compared on the 1st, 4th, and 7th day after being admitted to the ICU. Then, the correlations between plasma GDF-15 level, RFcsa loss, and MRC-score on day 7 were investigated. The receiver operating characteristic curve (ROC) was used to analyze the plasma GDF-15 level, RFcsa loss, and % decrease in RFcsa on the 7th day to the diagnosis of ICU-AW in mechanically ventilated patients. Moreover, the predictive value of GDF-15 on the 90-day survival status of patients was assessed using patient survival curves. Results. Based on whether the 7th day MRC-score was <48, 50 cases were included in the ICU-AW group and 45 cases in the non-ICU-AW group. The length of mechanical ventilation, ICU length of stay, and hospital length of stay were significantly longer in the ICU-AW group than in the non-ICU-AW group (all P<0.05), while the other baseline indicators were not statistically significant between the two groups. As the treatment time increased, the plasma GDF-15 level was significantly increased, the ICU-AW group demonstrated a significant decreasing trend in the MRC-score and RFcsa, while no significant changes were found in the non-ICU-AW group. In the ICU-AW group, the plasma GDF-15 level was significantly higher than that in the non-ICU-AW group, while the RFcsa and the MRC-score were significantly lower than those in the non-ICU-AW group (GDF-15 (pg/ml): 2542.44 ± 629.38 vs. 1542.86 ± 502.86; RFcsa (cm2): 2.04 ± 0.64 vs. 2.34 ± 0.61; MRC-score: 41.22 ± 3.42 vs. 51.42 ± 2.72, all P<0.001). The plasma GDF-15 level was significantly negatively correlated with the MRC-score (r = −0.60), while it was significantly positively correlated with the RFcsa loss (r = 0.18) and the % decrease in RFcsa (r = 0.16). Moreover, the RFcsa loss was significantly negatively correlated with the MRC-score (r = −0.27) (all P<0.001). The ROC curve analysis showed that plasma GDF-15 level, RFcsa loss, and % decrease in RFcsa on day 7 had predictive value for ICU-AW diagnosis in mechanically ventilated patients. More specifically, the area under the ROC curve (AUC) of GDF-15 was 0.904, the AUC of RFcsa loss was 0.873, and the AUC of % decrease in RFcsa was 0.886 (all P<0.001). The 90-day survival curve demonstrated that the survival rate of the high plasma GDF-15 level group was 54.00%, while that of the low plasma GDF-15 level group was 75.56%. The difference between the two groups was statistically significant (P<0.05). Conclusion. The plasma GDF-15 concentration level was significantly associated with skeletal muscle function and muscle wasting on day 7 in ICU patients with mechanical ventilation. Therefore, it can be concluded that the plasma GDF-15 level on the 7th day has a high diagnostic yield for ICU-acquired muscle weakness, and it can predict the 90-day survival status of ICU mechanically ventilated patients.

Arterial ischaemic stroke (AIS) can cause disabling hemiparesis in children. We aimed to test whether contralesional, inhibitory repetitive transcranial magnetic stimulation (rTMS) could affect interhemispheric inhibition to improve hand function in chronic subcortical paediatric AIS. Patients were eligible for this parallel, randomised trial if they were in the SickKids Children's Stroke Program and had subcortical AIS more than 2 years previously, had transcallosal sparing, were more than 7 years of age, had hand motor impairment, had no seizures or dyskinesia, and were taking no drugs that alter cortical excitability. Patients were paired for age and weakness and were randomised within each pair to sham treatment or inhibitory, low-frequency rTMS over contralesional motor cortex (20 min, 1200 stimuli) once per day for 8 days. An occupational therapist did standardised tests of hand function at days 1 (baseline), 5, 10, and 17 (1 week post-treatment), and the primary outcomes were changes in grip strength and the Melbourne assessment of upper extremity function (MAUEF) between baseline and day 10. Patients, parents, and occupational therapists were blinded to treatment allocation. Analysis was per protocol. Ten patients with paediatric stroke were enrolled (median age 13·25 [IQR 10·08–16·78] years, mean time post-stroke 6·33 [SD 3·56] years): four with mild weakness, two with moderate weakness, and four with severe weakness. A repeated-measures ANOVA showed a significant interaction between time and the effect of treatment on grip strength (p=0·03). At day 10, grip strength was 2·28 (SD 1·01) kg greater than baseline in the rTMS group and 2·92 (1·20) kg less than baseline in the sham group (p=0·009). Benefits in mean grip strength persisted at day 17 (2·63 [0·56] kg greater than baseline with rTMS and 1·00 [0·70] kg less than baseline with sham treatment; p=0·01). Day 10 MAUEF score improved by more in the rTMS group than in the sham group (7·25 [3·8] vs 0·79 [1·3] points greater than baseline; p=0·002), but this benefit did not persist to day 17. Function of the unaffected hand remained stable. rTMS was well tolerated with no serious adverse events. Contralesional inhibitory rTMS was safe and feasible for patients with paediatric subcortical AIS, and seemed to improve hand function in patients with hemiparesis. Further studies are required to confirm the potential role of rTMS in paediatric neurorehabilitation. Canadian Stroke Consortium; Canadian Institutes of Health Research; American Academy of Neurology Foundation; Alberta Heritage Foundation for Medical Research.

Aims/Introduction This study examined the effects of high‐intensity interval walking training (IWT) compared to moderate‐intensity continuous walking training (CWT) on muscle strength, walking ability, and health‐related quality of life (QOL) in people with diabetes accompanied by lower extremity weakness. Materials and Methods People with diabetes accompanied by low isometric knee extensor strength using a simple manual dynamometer (n = 50) were screened and randomly divided into 2 groups: CWT (n = 25) and IWT (n = 25). Both groups were instructed by a physical therapist to perform walking training with the goal of 120 min/week over a 5‐month period. The primary outcome, mean change of isometric knee extensor strength, and secondary outcomes, such as gait speed and health‐related QOL, were measured at baseline and the end of the intervention. Results At the end of the intervention, there was no significant difference in the degree of change in isometric knee extension strength between the two groups. However, there was a significant increase in changes in gait speed and physical QOL in the IWT group (gait speed, P < 0.01; physical QOL, P < 0.05). Conclusions The present study showed that IWT for people with diabetes accompanied by lower extremity weakness did not improve knee extension muscle strength compared to CWT but did improve walking ability and physical QOL. This study examined the effects of high‐intensity interval fast walking training (IWT) compared to moderate‐intensity continuous walking training (CWT) on muscle strength, walking ability, and QOL in people with diabetes accompanied by lower extremity weakness. This study showed that IWT for people with diabetes accompanied by lower extremity weakness did not increase the lower extremity strength compared to CWT. However, the IWT group showed an improved gait speed and physical QOL compared to the CWT.

Prolonged vibration stimulation to normal individuals could lead to muscle weakness attributable to attenuation of afferent feedback. This weakness is neurophysiologically similar to that seen in patients with knee injury. Theoretically, increasing input to gamma motor neurons could reverse this weakness. Sensory input to these neurons from skin could indirectly increase Ia afferent feedback. The present study examined the effect of this tactile stimulation in the form of Kinesiology tape on muscle weakness attributable to attenuation of afferent feedback. Randomized, crossover design. All participants were measured their eccentric maximal voluntary contractions under the 2 conditions (taping and non-taping). First, maximal voluntary contraction during eccentric contraction was measured as baseline. For the taping condition, Kinesiology tape was applied around each subject's knee joint during maximal voluntary contraction measurement after vibration. For the non-taping condition, tape was not applied during maximal voluntary contraction measurement after vibration. Mean percentage changes between pre- and post-vibration stimulation were compared between two conditions. Maximal voluntary contraction and average electromyography of taping condition was significantly larger than that of non-taping condition. Our results suggest that tactile stimulation in the form of Kinesiology tape inhibits the decline of both strength and electromyography. Alpha motor neuron activity attenuated by prolonged vibration would thus be partially rescued by tactile stimulation. These results indirectly suggest that stimulation of skin around the knee could counter quadriceps femoris weakness due to attenuated Ia afferent activity.

Primary coenzyme Q10 (CoQ10) deficiency results from mutations in genes involved in the CoQ10 biosynthetic pathway. In humans, at least 10 genes (PDSS1, PDSS2 to COQ10) are required for the biosynthesis of functional CoQ10, a mutation in any one of which can result in a deficit in CoQ10 status and present as primary CoQ10 deficiency. Furthermore, the genes NDUFA9 and HPDL, whilst not part of the PDSS1, PDSS2 to COQ10 gene sequence, have also been shown to have a crucial role in CoQ10 biosynthesis. A major problem in treating primary CoQ10 deficiencies is the poor bioavailability of supplemental CoQ10, both in terms of lack of absorption from the digestive tract and inability to cross the human blood–brain barrier. Bypass strategies aim to circumvent this problem by using more bioavailable precursor analogues that can enter the cell and be incorporated into the CoQ10 synthesis pathway downstream of the affected enzyme, examples being 4-hydroxybenzoic acid, 2,4-dihydroxybenzoic acid or vanillic acid, which, in contrast to CoQ10, are small, water-soluble molecules. In this article, we have, therefore, reviewed potential bypass mechanisms for primary CoQ10 deficiencies, PDSS1, PDSS2 to COQ10, together with NDUFA9 and HPDL, using such precursors. Most of the published data relating to the bypass therapy of primary CoQ10 deficiency is derived from cell lines or animal models, and few human studies have so far been undertaken. In addition, further research is required to investigate the potential mechanisms by which bypass compounds such as 4-HB may access the human blood–brain barrier (BBB), for example, using in vitro co-culture BBB model systems incorporating CoQ10-deficient neurons. Overall, the objective of this article is, therefore, to systematically review the available data for each of the primary CoQ10 deficiencies, PDSS1, PDSS2 to COQ10 together with NDUFA9 and HPDL, in particular to identify the clinical potential of such studies.

During radiofrequency bursts of energy are applied to nervous tissue. The clinical advantages of this treatment remain unclear. We compared the effectiveness and pain relief for idiopathic trigeminal neuralgia (TN) after continuous radiofrequency (CRF), pulsed radiofrequency (PRF), and combined continuous and pulsed radiofrequency (CCPRF) treatment of the Gasserian ganglion (GG). We conducted a randomized prospective study. Forty-three patients were included. Eleven patients were treated with PRF at 42°C for 10 minutes (PRF group), 12 patients received CRF for 270 seconds at 75 °C (CRF group), and 20 patients received PRF for 10 minutes at 42°C followed by CRF for at 60°C for 270 seconds (CCPRF group). Assuit University Hospital, Pain and Neurology outpatient clinics. Patients were assessed for pain, satisfaction, and consumption of analgesics at baseline and 7 days, one month, 6 months, 12 months, and 24 months after the procedure. The incidence of complications, anesthesia dolorosa, weakness of muscles of mastication, numbness, and technical complications, was evaluated after the procedure. Excellent pain relief was achieved after 6, 12, and 24 months, respectively in 95%, 85%, and 70% of patients with CCPRF; 75%, 75%, and reduced to 50% among patients with CRF; and 82%, reduced to 9.1%, and 0% of patients with PRF. No complications were recorded in 75% of patients in the CCPRF and PRF groups. There was one case of anesthesia dolorosa, 4 cases of masseter muscle weakness, and 5 cases of severe numbness recorded in the CRF group. There was a small number of patients in each group. The best results were observed in the CCPRF group, followed by the CRF group, and then the PRF group.Key words: Pulsed, continuous, radiofrequency, trigeminal neuralgia, Gasserian ganglion.