Critical Illness Polyneuropathy Research Articles

The role of zinc and matrix metalloproteinases in myofibrillar protein degradation in critical illness myopathy

Due to an unexpected activation of different zinc (Zn) transporters in a recent prospective clinical study, we have revisited the role of Zn homeostasis and the activation of matrix metalloproteinases (MMPs) in skeletal muscle exposed to the intensive care unit (ICU) condition (immobilization and mechanical ventilation). ICU patients exposed to 12 days ICU condition were followed longitudinally with six repeated muscle biopsies while they showed a progressive preferential myosin loss, i.e., the hallmark of Critical Illness Myopathy (CIM), in parallel with the activation of Zn-transporters. In this study, we have revisited the expression of Zn-transporters and the activation of MMPs in clinical as well as in experimental studies using an established ICU model. MMPs are a group Zn-dependent endopeptidases which do not only target and cleave extracellular proteins but also intracellular proteins including multiple sarcomeric proteins. MMP-9 is of specific interest since the hallmark of CIM, the preferential myosin loss, has also been reported in dilated cardiomyopathy and coupled to MMP-9 activation. Transcriptional activation of Zn-transporters was observed in both clinical and experimental studies as well as the activation of MMPs, in particular MMP-9, in various limb and respiratory muscles in response to long-term exposure to the ICU condition. The activation of Zn-transporters was paralleled by increased Zn levels in skeletal muscle which in turn showed a negative linear correlation with the preferential myosin loss associated with CIM, offering a potential intervention strategy. Thus, activation of Zn-transporters, increased intramuscular Zn levels, and activation of the Zn-dependent MMPs are forwarded as a probable mechanism involved in CIM pathophysiology. These effects were confirmed in different rat strains subjected to a model of CIM and exacerbated by old age. This is of specific interest since old age and muscle wasting are the two factors most strongly associated with ICU mortality.

Tracheostomy-related data from an intensive care unit for two consecutive years before the COVID-19 pandemic.

Tracheostomy is commonly used in intensive care unit (ICU) patients who are expected to be on long-term mechanical ventilation or suffer from emergency upper airway obstruction. However, some studies have conflicting findings regarding the optimal technique and its timing and benefits. To provide evidence of practice, characteristics, and outcome concerning tracheostomy in an ICU of a tertiary care hospital. This was a retrospective cohort study including adult critical care patients in a single ICU for two consecutive years. Patients' demographic characteristics, severity of illness (APACHE II score), level of consciousness [Glasgow Coma Scale (GCS)], comorbidities, timing and type of tracheostomy procedure performed and outcome were recorded. We defined late as tracheostomy placement after 8 days or no tracheotomy. Data of 660 patients were analyzed (median age of 60 years), median APACHE II score of 19 and median GCS score of 12 at admission. Tracheostomy was performed in 115 patients, of whom 63 had early and 52 late procedures. Early tracheostomy was mainly executed in case of altered level of consciousness and severe critical illness polyneuromyopathy, however there were no significant statistical results (47.6% vs 36.5%, P = 0.23) and (23.8% vs 19.2%, P = 0.55) respectively. Regarding the method selected, early surgical tracheostomy (ST) was conducted in patients with maxillofacial injuries (50.0% vs 0.0%, P = 0.033), whereas late surgical tracheostomy was selected for patients with goiter (44.4% vs 0.0% P = 0.033). Patients with early tracheostomy spent significantly fewer days on mechanical ventilation (15.3 ± 8.5 vs 22.8 ± 9.6, P < 0.001) and in ICU in general (18.8 ± 9.1 vs 25.4 ± 11.5, P < 0.001). Percutaneous dilatation tracheostomy (PDT) vs ST was preferable in older critical care patients in the case of Central Nervous System underlying cause of admission (62.5% vs 26.3%, P = 0.004). ST was the method of choice in compromised airway (31.6%, vs 7.3% P = 0.008). A large proportion of patients (88/115) with tracheostomy managed to wean from mechanical ventilation and were transferred out of the ICU (100% vs 17.4%, P < 0.001). PDT was performed more frequently in our cohort. This technique did not affect mechanical ventilation days, ventilator-associated pneumonia (VAP), ICU length of stay, or survival. No complications were observed in the percutaneous or surgical tracheostomy groups. Patients undergoing early tracheostomy benefited in terms of mechanical ventilation days and ICU length of stay but not of discharge status, presence of VAP, or survival.

Electrophysiological Screening to Assess Foot Drop Syndrome in Severe Acquired Brain Injury in Rehabilitative Settings.

Foot drop syndrome (FDS), characterized by severe weakness and atrophy of the dorsiflexion muscles of the feet, is commonly found in patients with severe acquired brain injury (ABI). If the syndrome is unilateral, the cause is often a peroneal neuropathy (PN), due to compression of the nervous trunk on the neck of the fibula at the knee level; less frequently, the cause is a previous or concomitant lumbar radiculopathy. Bilateral syndromes are caused by polyneuropathies and myopathies. Central causes, due to brain or spinal injury, mimic this syndrome but are usually accompanied by other symptoms, such as spasticity. Critical illness polyneuropathy (CIP) and myopathy (CIM), isolated or in combination (critical illness polyneuromyopathy, CIPNM), have been shown to constitute an important cause of FDS in patients with ABI. Assessing the causes of FDS in the intensive rehabilitation unit (IRU) has several limitations, which include the complexity of the electrophysiological tests, limited availability of neurophysiology consultants, and the severe disturbance in consciousness and lack of cooperation from patients. We sought to propose a simplified electrophysiological screening that identifies FDS causes, particularly PN and CIPNM, to help clinicians to recognize the significant clinical predictors of poor outcomes in severe ABI at admission to IRU. This prospective, single-center study included 20 severe ABI patients with FDS (11 females/9 males, mean age 55.10 + 16.26; CRS-R= 11.90 + 6.32; LCF: 3.30 + 1.30; DRS: 21.45 + 3.33), with prolonged rehabilitation treatment (≥2 months). We applied direct tibialis anterior muscle stimulation (DMS) associated with peroneal nerve motor conduction evaluation, across the fibular head (NCS), to identify CIP and/or CIM and to exclude demyelinating or compressive unilateral PN. At admission to IRU, simplified electrophysiological screening reported four unilateral PN, four CIP and six CIM with a CIPNM overall prevalence estimate of about 50%. After 2 months, the CIPNM group showed significantly poorer outcomes compared to other ABI patients without CIPNM, as demonstrated by the lower probability of achieving endotracheal-tube weaning (20% versus 90%) and lower CRS-R and DRS scores. Due to the subacute rehabilitation setting of our study, it was not possible to evaluate the motor results of recovery of the standing position, functional walking and balance, impaired by the presence of unilateral PN. The implementation of the proposed simplified electrophysiological screening may enable the early identification of unilateral PN or CIPNM in severe ABI patients, thereby contributing to better functional prognosis in rehabilitative settings.

Compound Muscle Action Potential (CMAP) Duration and Myosin Loss in Patients with Critical Illness Myopathy: Correlation and Prognostication (P1-11.005)

Compound Muscle Action Potential (CMAP) Duration and Myosin Loss in Patients with Critical Illness Myopathy: Correlation and Prognostication (P1-11.005)

New Measurement in the Diagnosis of Critical Illness Myopathy: Stimulus Intensity and Compound Muscle Action Potential Duration Relationship (P1-11.013)

New Measurement in the Diagnosis of Critical Illness Myopathy: Stimulus Intensity and Compound Muscle Action Potential Duration Relationship (P1-11.013)

Outcome, predictors and longitudinal trajectories of subjects with critical illness polyneuropathy and myopathy (CINAMOPS): study protocol of an observational cohort study in a clinical and post-clinical setting

IntroductionCritical illness polyneuropathy and myopathy (CIP/CIM) are frequent complications in the intensive care unit (ICU) with major consequences for the progress and outcome of subjects. CIP/CIM delays the weaning process,...

COVID-19 and Neuromuscular Involvement: A Case Series and Brief Review of Literature

Background: Tough COVID-19 predominantly affects the respiratory tract, and extra-pulmonary manifestations, including neuromuscular complaints have been associated with this disorder. It is vital to monitor COVID-19 cases for the occurrence of Neuromuscular Disorders (NMDs), which could be overshadowed by severe respiratory and cardiovascular symptoms. In this study, we reported electrophysiological findings of a series of COVID-19 patients with complaints of paresthesia and weakness.&#x0D; Methods: In this case series, the Electrodiagnostic studies (EDX) of 36 patients with recent complaints of weakness or paresthesia and a history of COVID-19 before symptoms were reported.&#x0D; Results: 12 cases (33.3%) had abnormal EDX, five males and seven females, with a mean age of 51.42±11.49 years, history of hospitalization in five cases (41.7%), and ICU admission in four (33.3%). Seven cases were concluded as having a predominantly axonal type polyneuropathy (five sensory-motor and two sensory polyneuropathies). Of these seven, one was suggestive of Critical Illness Neuropathy (CIN). Three cases demonstrated a myopathic pattern with a history of ICU admission, hence the impression of Critical Illness Myopathy (CIM). In addition, one of these three, developed both myopathy and neuropathy and thus, is considered as having CIM/N. One case was diagnosed with Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). The last case demonstrated an inflammatory involvement of lumbosacral roots (COVID-19-related radiculitis).&#x0D; Conclusion: COVID-19 could be associated with a wide range of NMDs. In this study, the presence of axonal polyneuropathy, CIDP, and myopathy was demonstrated following SAR-COV-2 infection. Also, CIN/M was observed in COVID-19 patients with a history of ICU admission

CHRONIC CRITICAL ILLNESS-INDUCED MUSCLE ATROPHY: INSIGHTS FROM A TRAUMA MOUSE MODEL AND POTENTIAL MECHANISM MEDIATED VIA SERUM AMYLOID A.

Background: Chronic critical illness (CCI), which was characterized by persistent inflammation, immunosuppression, and catabolism syndrome (PICS), often leads to muscle atrophy. Serum amyloid A (SAA), a protein upregulated in critical illness myopathy, may play a crucial role in these processes. However, the effects of SAA on muscle atrophy in PICS require further investigation. This study aims to develop a mouse model of PICS combined with bone trauma to investigate the mechanisms underlying muscle weakness, with a focus on SAA. Methods: Mice were used to examine the effects of PICS after bone trauma on immune response, muscle atrophy, and bone healing. The mice were divided into two groups: a bone trauma group and a bone trauma with cecal ligation and puncture group. Tibia fracture surgery was performed on all mice, and PICS was induced through cecal ligation and puncture surgery in the PICS group. Various assessments were conducted, including weight change analysis, cytokine analysis, hematological analysis, grip strength analysis, histochemical staining, and immunofluorescence staining for SAA. In vitro experiments using C2C12 cells (myoblasts) were also conducted to investigate the role of SAA in muscle atrophy. The effects of inhibiting receptor for advanced glycation endproducts (RAGE) or JAK2 on SAA-induced muscle atrophy were examined. Bioinformatic analysis was conducted using a dataset from the GEO database to identify differentially expressed genes and construct a coexpression network. Results: Bioinformatic analysis confirmed that SAA was significantly upregulated in muscle tissue of patients with intensive care unit-induced muscle atrophy. The PICS animal models exhibited significant weight loss, spleen enlargement, elevated levels of proinflammatory cytokines, and altered hematological profiles. Evaluation of muscle atrophy in the animal models demonstrated decreased muscle mass, grip strength loss, decreased diameter of muscle fibers, and significantly increased expression of SAA. In vitro experiment demonstrated that SAA decreased myotube formation, reduced myotube diameter, and increased the expression of muscle atrophy-related genes. Furthermore, SAA expression was associated with activation of the FOXO signaling pathway, and inhibition of RAGE or JAK2/STAT3-FOXO signaling partially reversed SAA-induced muscle atrophy. Conclusions: This study successfully develops a mouse model that mimics PICS in CCI patients with bone trauma. Serum amyloid A plays a crucial role in muscle atrophy through the JAK2/STAT3-FOXO signaling pathway, and targeting RAGE or JAK2 may hold therapeutic potential in mitigating SAA-induced muscle atrophy.

The use of muscle ultrasound to detect critical illness myopathy in patients with sepsis: an observational cohort study

BackgroundCritical illness myopathy (CIM) has negative impact on patient outcomes. We aimed to explore the diagnostic value of bedside ultrasonography for early identification of CIM in septic patients and its correlation with other diagnostic methods. This prospective observational study included 40 ICU patients diagnosed with sepsis on admission or within 48 h later according to the third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3). They were evaluated using muscle ultrasound, electrodiagnostic and clinical muscle assessment (Medical Research Council, MRC) at two time points, the first was between days 2 and 5 and the second was between days 10 and 15.ResultsThere was significant deterioration of neuromuscular function between the two evaluation points demonstrated by decline in MRC, abnormal nerve conduction and electromyography (EMG) and increased muscle echogenicity on ultrasonography (P ≤ 0.001). Sepsis-Related Organ Failure Assessment (SOFA) score significantly correlated with different neuromuscular assessment tools. MRC had significant correlation with myopathic EMG (P ≤ 0.001, r = − 0.869) and increased muscle echogenicity (P ≤ 0.001, r = − 0.715). Abnormal ultrasonographic muscle architecture had sensitivity of 100%, specificity of 75% and positive likelihood ratio of 4 in detecting muscle dysfunction compared to myopathic EMG.ConclusionsBedside peripheral muscle ultrasound echogenicity grade could be used as an additional screening test in ICU septic patients for early detection of CIM.

Exercise reconditioning in the post-acute phase of COVID-19 rehabilitation in patients with chronic respiratory insufficiency: a retrospective observational study

INTRODUCTION: The COVID-19 pandemic has had a profound impact on a global scale, affecting various aspects of society, health, and well-being. It has strained healthcare systems and led to social and welfare repercussions. In the context of post-acute COVID-19 rehabilitation, there is a need to explore effective interventions for individuals, particularly those with chronic respiratory insufficiency. This study aims to evaluate the effectiveness of exercise reconditioning as a rehabilitation strategy in this specific population METHODS: A retrospective observational study was conducted at the Rehabilitation Unit in an Italian hospital between March 2020 and May 2022. The study included individuals who had been diagnosed with COVID-19 pneumonia, required hospitalization in the COVID-19 unit or intensive care unit (ICU) due to severe respiratory failure and with “post-COVID pathology syndrome” (PCS) picture. Various assessments, including the 6 Minutes Walking Test (6MWT), were conducted to determine exercise capacity. A personalized reconditioning program based on international guidelines was designed for each patient, focusing on aerobic training. Measurements of vital signs were taken during training sessions. RESULTS: A total of 24 individuals, with a mean age of 65.41 years, were included in the study. The average duration of hospitalization in the rehabilitation department was 53.17 days. Most participants had pre-existing respiratory and non-respiratory pathologies. All individuals developed COVID-19 interstitial pneumonia, and some required intensive interventions such as intubation or ECMO support. Pulmonary fibrosis and Critical Illness Myopathy (CIM) were observed in a significant portion of the participants. Significant improvements were observed in the 6MWT distance traveled, Functional Independence Measure (FIM) scale score, fraction of inhaled oxygen (FiO2), and dyspnea scores. Perceived exerction measures also showed positive changes. DISCUSSION AND CONCLUSION: The findings of this study indicate that personalized reconditioning plan is effective in improving the functional capacity and overall condition and quality of life of individuals with post-COVID pathology syndrome. These findings highlight the importance of an interdisciplinary approach and tailored rehabilitation programs in this population. Further research is needed to explore the long-term effects of exercise reconditioning in this population.

Management of Neuromuscular Blocking Agents in Critically Ill Patients with Lung Diseases.

The use of neuromuscular blocking agents (NMBAs) is common in the intensive care unit (ICU). NMBAs have been used in critically ill patients with lung diseases to optimize mechanical ventilation, prevent spontaneous respiratory efforts, reduce the work of breathing and oxygen consumption, and avoid patient-ventilator asynchrony. In patients with acute respiratory distress syndrome (ARDS), NMBAs reduce the risk of barotrauma and improve oxygenation. Nevertheless, current guidelines and evidence are contrasting regarding the routine use of NMBAs. In status asthmaticus and acute exacerbation of chronic obstructive pulmonary disease, NMBAs are used in specific conditions to ameliorate patient-ventilator synchronism and oxygenation, although their routine use is controversial. Indeed, the use of NMBAs has decreased over the last decade due to potential adverse effects, such as immobilization, venous thrombosis, patient awareness during paralysis, development of critical illness myopathy, autonomic interactions, ICU-acquired weakness, and residual paralysis after cessation of NMBAs use. The aim of this review is to highlight current knowledge and synthesize the evidence for the effects of NMBAs for critically ill patients with lung diseases, focusing on patient-ventilator asynchrony, ARDS, status asthmaticus, and chronic obstructive pulmonary disease.

Desmin Degradation in the Skeletal Muscle of Patients with Chronic Critical Illness

Chronically critically ill patients lose a significant amount of muscle mass during their stay in the intensive care unit, which can have long-term detrimental consequences. This, among other factors, leads to the degradation of the muscle cytoskeleton’s integrity, and at present there are no comprehensive studies that describe the mechanisms b-ehind the development of this process. The purpose of this study was to investigate the signaling processes that contribute to the degradation of desmin in patients with critical illness myopathy (CIM). Incisional muscle biopsies were taken from the soleus muscle from 6 patients undergoing treatment at the A.L. Polenov Russian Research Institute - branch of the Almazov National Medical Research Center, with chronic impairment of consciousness (lasting at least 2 months). Muscle biopsies taken from healthy men using a needle biopsy technique were used as controls. Biopsies were frozen in liquid nitrogen for subsequent Western blot and PCR analysis, as well as immunohistochemical studies. The analysis showed that fibers with an altered histological pattern of desmin were visually identified in 4 out of 6 patients studied. We also observed a significant decrease in desmin content by 69% and a 24% decrease in its mRNA content in patients with CIM. Desmin breakdown may be associated with increased calpain activity and activation of the ubiquitin-proteasome system. In this study, the content of calpain-1 increased under conditions of CIM at the protein level, but remained unchanged at the mRNA level. We observed changes in GSK3-β (Ser9) phosphorylation, which is a crucial step in the d-epolymerization of desmin filaments by calpain-1. A study on ubiquitin ligases revealed a significant 155% increase in the expression of Trim32, along with a decrease in the e-xpression of Atrogin1 and MuRF1. Thus, in this study, we observed a decrease in desmin content under conditions of CIM. The breakdown of desmin may be due to increased phosphorylation by GSK3β and subsequent cleavage by calpain-1. In addition, we observed an increase in the expression of the E3 ubiquitin ligase Trim32, the activity of which, according to literature, also increases after phosphorylation of desmin.

Severe axonal motor neuropathy after heat stroke

A 22-year-old healthy man experienced heat stroke while hiking and collapsed, resulting in multiorgan failure, cerebral edema, and prolonged intensive care unit stay. He developed flaccid tetraplegia, facial weakness, and dysphagia, and was diagnosed with severe axonal sensorimotor polyneuropathy. Rehabilitation improved dysphagia, but he remained dependent on daily activities and required assistance for transfers. The prognosis of critical illness polyneuropathy is typically good in young, healthy individuals. Peripheral neuropathy is a rare complication of heat stroke due to hyperthermia-induced neuronal injury. As global temperatures continue to rise, it is essential to recognize the potential impact of climate change on the incidence of heat stroke and to implement public health interventions to mitigate its effects.

Lower serum cholesterol levels as a risk factor for critical illness polyneuropathy: a matched case–control study

Critical illness polyneuropathy (CIP) is a frequent and underdiagnosed phenomenon among intensive care unit patients. The lipophilic nature of neuronal synapses may result in the association of low serum cholesterol levels with a higher rate of CIP development. We aimed to investigate this issue in critically ill patients. All cases diagnosed with CIP in our tertiary care hospital between 2013 and 2017 were 1:1 matched with controls without the condition by age, sex, and ICD diagnoses. The main risk factors examined were the differences in change between initial and minimum serum total cholesterol levels, and minimum serum total cholesterol levels between matched pairs. Other predictors were serum markers of acute inflammation. We included 67 cases and 67 controls (134 critically ill patients, 49% female, 46% medical). Serum total cholesterol levels decreased more profoundly in cases than controls (median: −74 (IQR −115 to −24) vs. −39 (IQR −82 to −4), median difference: −28, 95% CI [−51, −5]), mg/dl). Minimum serum total cholesterol levels were lower in the cases (median difference: −24, 95% CI [−39, −9], mg/dl). We found significant median differences across matched pairs in maximum serum C-reactive protein (8.9, 95% CI [4.6, 13.2], mg/dl), minimum albumin (−4.2, 95% CI [−6.7, −1.7], g/l), decrease in albumin (−3.9, 95% CI [−7.6, −0.2], g/l), and lowest cholinesterase levels (−0.72, 95% CI [−1.05, −0.39], U/l). Subsequently, more pronounced decreases in serum total cholesterol levels and lower minimum total cholesterol levels during critical care unit hospitalizations may be a risk factor for CIP.

Overcoming the Challenges of Prolonged Ventilation and Critical Illness Polyneuropathy in Severe ARDS Patients Due to Extensive Viral Pneumonia: A Case Report

ARDS is a life-threatening condition requiring intensive care unit monitoring. We present a 46-year-old male patient with ARDS and its complications, ventilator-associated pneumonia (VAP) and critcal illness polyneuropathy after extensive bilateral viral pneumonia. The objective of this case report is to understand better and manage the complications of ARDS. This study addresses ARDS and its complications, providing a comprehensive clinical understanding. It details a 46-year-old male patient’s case, treatment strategies, complications, weaning processes, and rehabilitation and emphasises the importance of physical therapy. This case report discusses the successful management and weaning of a patient with extensive viral pneumonia complicated with acute respiratory distress syndrome (ARDS), impending organ dysfunction, and critical illness polyneuropathy. The patient had a medical history of diabetes, hypertension, and dyslipidemia. Initial treatment involved oxygen therapy, nebulization, and empirical antiviral for seasonal flu. However, the patient required invasive ventilation with sedation and muscle relaxants following the ARDSNET protocol due to worsening respiratory status and extensive lung infiltrates. Secondary bacterial infections were also identified and treated accordingly. The weaning process was initiated but was complicated by re-intubation and the development of critical illness polyneuropathy. After successful weaning and recovery from ARDS and associated lung infections, physical therapy was provided for polyneuropathy regularly to overcome the manifest weakness all over the body muscles, including respiratory muscle weakness. The case report highlights the successful management of a patient with viral pneumonia, ARDS, and critical illness polyneuropathy, highlighting the importance of comprehensive treatment and physical therapy.

Serum neurofilament light chain as an early diagnostic biomarker for critical illness polyneuropathy.

Critical illness polyneuropathy (CIP) commonly occurs in critical care unit (CCU) patients, but timely diagnosis can be challenging. Therefore, new biomarkers, such as serum neurofilament light chain (sNfL), could help to improve early identification of patients with this condition. CIP was diagnosed or excluded with neurological assessment and nerve conduction measurement in a prospective study of CCU patients. sNfL and secondary predictors for neuropathy (neuron-specific enolase (NSE), S100, folic acid, and vitamin B<inf>12</inf>) were measured at admission. Cases and controls were compared regarding the predictors. Nineteen patients met the inclusion criteria. CIP was considered definitely or most likely present in seven (37%, cases) and definitely or most likely absent in 12 individuals (63%, controls). At admission, sNfL levels were significantly higher in the cases than in the controls: 405 (IQR 77 to 835) vs. 27 (IQR 12 to 90) pg/mL; difference of medians 375, 95% confidence interval [14, 736], pg/mL; P=0.04. We found no significant differences regarding the secondary predictors at baseline. Cases had longer durations of CCU stay (median 19 (IQR 11 to 44) vs. 8 (IQR five to ten) and increased mortality (57% vs. 33% deceased) compared to controls. Levels of serum neurofilament light chain are higher in patients who develop CIP soon after CCU admission and might be helpful in identifying those individuals early.

Total Psoas Area and Psoas Density Assessment in COVID-19 Patients Using CT Imaging – Could Muscle Mass Alteration During Intensive Care Hospitalization be Determined?

Abstract Background Since its debut, as reported by the first published studies, COVID-19 has been linked to life-threatening conditions that needed vital assistance and admission to the intensive care unit. Skeletal muscle is a core element in an organism’s health due to its ability to keep energy balance and homeostasis. Many patients with prolonged hospitalization are characterized by a greater probability prone to critical illness myopathy or intensive care unit-acquired weakness. Objective The main aim of this study was to assess the skeletal muscle in a COVID-19 cohort of critically ill patients by measuring the psoas area and density. Material and methods This is a retrospective study that included critically ill adult patients, COVID-19 positive, mechanically ventilated, with an ICU stay of over 24 hours, and who had 2 CT scans eligible for psoas muscle evaluation. In these patients, correlations between different severity scores and psoas CT scans were sought, along with correlations with the outcome of the patients. Results Twenty-two patients met the inclusion criteria. No statistically significant differences were noticed regarding the psoas analysis by two blinded radiologists. Significant correlations were found between LOS in the hospital and in ICU with psoas area and Hounsfield Units for the first CT scan performed. With reference to AUC-ROC and outcome, it is underlined that AUC-ROC is close to 0.5 values, for both the psoas area and HU, indicating that the model had no class separation capacity. Conclusion The study suggested that over a short period, the psoas muscle area, and the psoas HU decline, for both the left and the right sight, in adult COVID-19 patients in ICU conditions, yet not statistically significant. Although more than two-thirds of the patients had a negative outcome, it was not possible to demonstrate an association between the SARS-COV2 infection and psoas muscle impairment. These findings highlight the need for further larger investigations.

Baseline Characteristics and Outcomes for People With and Without COVID-19 Diagnoses Receiving Inpatient Rehabilitation Care Across the US in 2020-2021

ObjectiveTo assess sociodemographic, medical complexity, and outcomes of persons receiving care at inpatient rehabilitation facilities (IRFs) with and without a diagnosis of COVID-19. DesignA retrospective cohort study using electronic medical record (EMR) data from 138 IRFs across 34 states and Puerto Rico. SettingN/A. ParticipantsIRF EMR data for 212,663 patients discharged between 04/01/2020 and 05/31/2021 (N=212,663), of which 16,199 (COVID-19 group) had a primary or secondary COVID-19 diagnosis based upon ICD codes set (ICD-10 codes U07.1, B94.8, Z86.19, Z86.16). Main Outcome MeasuresFour categories: (a) sociodemographic, (b) medical complexity, (c) process, that is, standard IRF processes, and clinical outcomes (collected routinely as part of administrative reporting), and (d) functional outcomes. Patients with missing functional data associated with short/incomplete stays (n=623) were excluded from analysis of functional outcomes category only. Standard descriptive analysis techniques were employed for comparing categorical and continuous variables between groups. ResultsStatistically significant differences were noted between the COVID-19 group and non-COVID groups for race (26.0% vs 19.7% non-minority, P<.001), Case Mix Index (1.49 vs 1.46, P<.001), Center for Medicare and Medicaid Services 60% rule qualification (79.0% vs 73.4%, P<.001), time to onset (24.3 vs 18.0 days, P<.001), length of stay (14.2 vs 12.9 days, P<.001), and discharge disposition (to community: 75.3% vs 81%, P<.001; to acute care facility: 15.6% vs 10.8%, P<.001). The COVID-19 group had higher frequency of respiratory and cardiovascular disease, diabetes, encephalopathy, morbid obesity, and critical illness neuropathy and myopathy. Clinically insignificant differences were noted for age, sex, depression, and cognitive assessment. Ability to participate and functional outcomes were comparable between the groups. ConclusionThere are significant differences between the COVID-19 and non-COVID group in some sociodemographic, medical complexity, process and clinical outcomes, but not in functional outcomes. The ability to participate in the IRF-required intensity of therapy services along with attainment of comparable levels of functional outcomes supports the benefit of IRFs for persons with COVID-19.

Single fibre cytoarchitecture in ventilator-induced diaphragm dysfunction (VIDD) assessed by quantitative morphometry second harmonic generation imaging: Positive effects of BGP-15 chaperone co-inducer and VBP-15 dissociative corticosteroid treatment.

Ventilator-induced diaphragm dysfunction (VIDD) is a common sequela of intensive care unit (ICU) treatment requiring mechanical ventilation (MV) and neuromuscular blockade (NMBA). It is characterised by diaphragm weakness, prolonged respirator weaning and adverse outcomes. Dissociative glucocorticoids (e.g., vamorolone, VBP-15) and chaperone co-inducers (e.g., BGP-15) previously showed positive effects in an ICU-rat model. In limb muscle critical illness myopathy, preferential myosin loss prevails, while myofibrillar protein post-translational modifications are more dominant in VIDD. It is not known whether the marked decline in specific force (force normalised to cross-sectional area) is a pure consequence of altered contractility signaling or whether diaphragm weakness also has a structural correlate through sterical remodeling of myofibrillar cytoarchitecture, how quickly it develops, and to which extent VBP-15 or BGP-15 may specifically recover myofibrillar geometry. To address these questions, we performed label-free multiphoton Second Harmonic Generation (SHG) imaging followed by quantitative morphometry in single diaphragm muscle fibres from healthy rats subjected to five or 10days of MV + NMBA to simulate ICU treatment without underlying confounding pathology (like sepsis). Rats received daily treatment of either Prednisolone, VBP-15, BGP-15 or none. Myosin-II SHG signal intensities, fibre diameters (FD) as well as the parameters of myofibrillar angular parallelism (cosine angle sum, CAS) and in-register of adjacent myofibrils (Vernier density, VD) were computed from SHG images. ICU treatment caused a decline in FD at day 10 as well as a significant decline in CAS and VD from day 5. Vamorolone effectively recovered FD at day 10, while BGP-15 was more effective at day 5. BGP-15 was more effective than VBP-15 in recovering CAS at day 10 although not to control levels. In-register VD levels were restored at day 10 by both compounds. Our study is the first to provide quantitative insights into VIDD-related myofibrillar remodeling unravelled by SHG imaging, suggesting that both VBP-15 and BGP-15 can effectively ameliorate the structure-related dysfunction in VIDD.

The Importance of Neuropsychology in the Early Rehabilitation of Patients with Critical Illness after Acute COVID Infection

Abstract: The current literature has insufficiently examined the potential benefits of implementing early neuropsychological interventions for critically ill patients who have experienced COVID-19. To address this research gap, we conducted a descriptive analysis of clinical and neuropsychological data from N = 29 critically ill patients with COVID-19 admitted to an early neurological rehabilitation facility. Most patients had been diagnosed with critical illness polyneuropathy (CIP), and one-third exhibited additional brain damage. Upon admission, all patients exhibited severe cognitive impairments, demonstrating significant improvement following neuropsychological therapy. Nonetheless, the neurocognitive outcomes at discharge displayed a high cognitive and psychoemotional status variability. This paper presents the neuropsychological treatment concept we employed and discusses challenges encountered while treating critically ill patients with cognitive impairments.