Sepsis Induces Physical and Mental Impairments in a Mouse Model of Post-Intensive Care Syndrome

Post-intensive care syndrome (PICS) is a physical, cognitive, and mental impairment observed in intensive care unit (ICU) survivors. Although this is an emerging problem in the ICU, how sepsis induces the characteristic symptoms of PICS remains unclear. To develop a model of PICS, we induced sepsis in male C57/B6 mice via sublethal cecum slurry injection and subsequently treated them using ICU-like interventions. At 1–2 weeks post-sepsis induction, we simultaneously evaluated the abilities of the surviving mice using the following behavioral tests: (1) a grip strength test (GST) and a treadmill test for physical assessment, (2) a novel object recognition test (NORT) for cognitive assessment, and (3) an open field test (OFT) and a marble burying test (MBT) for mental assessment. The surviving mice showed a range of deficits, including muscle weakness with significantly decreased grip strength in the GST; decreased total mileage during the treadmill test; anxiety and decreased activity, with significantly decreased time in the central area, and increased duration of immobility in the OFT; and an increased number of buried marbles in the MBT. Given these physical and mental impairments in the surviving mice, our model has the potential to elucidate mechanistic insights and to discover therapeutic targets and new interventions for PICS.

Download Full-text

Grip Strength Correlates with Mental Health and Quality of Life after Critical Care: A Retrospective Study in a Post-Intensive Care Syndrome Clinic

Journal of Clinical Medicine ◽

10.3390/jcm10143044 ◽

2021 ◽

Vol 10 (14) ◽

pp. 3044

Author(s):

Kensuke Nakamura ◽

Ayako Kawasaki ◽

Noriyo Suzuki ◽

Sayaka Hosoi ◽

Takahiro Fujita ◽

...

Keyword(s):

Quality Of Life ◽

Mental Illness ◽

Critical Care ◽

Intensive Care ◽

Grip Strength ◽

Mental Status ◽

Depression Scale ◽

Disability Group ◽

Post Intensive Care Syndrome

Post-intensive care syndrome (PICS) is characterized by several prolonged symptoms after critical care, including physical and cognitive dysfunctions as well as mental illness. In clinical practice, the long-term follow-up of PICS is initiated after patients have been discharged from the intensive care unit, and one of the approaches used is a PICS clinic. Although physical dysfunction and mental illness often present in combination, they have not yet been examined in detail in PICS patients. Grip strength is a useful physical examination for PICS, and is reported to be associated with mental status in the elderly. We herein investigated the relationship between grip strength and the mental status using data from our PICS clinic. We primarily aimed to analyze the correlation between grip strength and the Hospital Anxiety and Depression Scale (HADS) score. We also analyzed the association between grip strength and the EuroQol 5 Dimension (EQ5D) score as quality of life (QOL). Subjects comprised 133 patients who visited the PICS clinic at one month after hospital discharge between August 2019 and December 2020. Total HADS scores were 7 (4, 13) and 10 (6, 16) (p = 0.029) and EQ5D scores were 0.96 (0.84, 1) and 0.77 (0.62, 0.89) (p ≤ 0.0001) in the no walking disability group and walking disability group, respectively. Grip strength negatively correlated with HADS and EQ5D scores. Correlation coefficients were r = −0.25 (p = 0.011) and r = −0.47 (p < 0.0001) for HADS and EQ5D scores, respectively. Grip strength was a useful evaluation that also reflected the mental status and QOL.

Download Full-text

Evaluation of the effectiveness of macaíba palm seed kernel (Acrocomia intumescens drude) on anxiolytic activity, memory preservation and oxidative stress in the brain of dyslipidemic rats

PLoS ONE ◽

10.1371/journal.pone.0246184 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0246184

Author(s):

Roberta Cristina de França Silva ◽

Mikaelle Albuquerque de Souza ◽

Jaielison Yandro Pereira da Silva ◽

Carolina da Silva Ponciano ◽

Vanessa Bordin Viera ◽

...

Keyword(s):

Oxidative Stress ◽

Elevated Plus Maze ◽

Open Field Test ◽

Central Area ◽

Seed Kernel ◽

Total Glutathione ◽

Object Recognition Test ◽

Plus Maze ◽

The Brain ◽

And Oxidative Stress

Macaíba palm seed kernel is a source of lipids and phenolic compounds. The objective of this study was to evaluate the effects of macaíba palm seed kernel on anxiety, memory, and oxidative stress in the brain of health and dyslipidemic rats. Forty rats were used, divided into 4 groups (n = 10 each): control (CONT), dyslipidemic (DG), kernel (KG), and Dyslipidemic kernel (DKG). Dyslipidemia was induced using a high fat emulsion for 14 days before treatment. KG and DKG received 1000 mg/kg of macaíba palm seed kernel per gavage for 28 days. After treatment, anxiety tests were carried out using the Open Field Test (OFT), Elevated Plus Maze (EPM), and the Object Recognition Test (ORT) to assess memory. In the animals’ brain tissue, levels of malondialdehyde (MDA) and total glutathione (GSH) were quantified to determine oxidative stress. The data were treated with Two Way ANOVA followed by Tukey (p <0.05). Results demonstrated that the animals treated with kernel realized more rearing. DG and KG groomed less compared with CONT and DKG compared with all groups in OFT. KG spent more time in aversive open arms compared with CONT and DKG compared with all groups in EPM. Only DKG spent more time in the central area in EMP. KG and DKG showed a reduction in the exploration rate and MDA values (p <0.05). Data showed that macaíba palm seed kernel consumption induced anxiolytic-like behaviour and decreased lipids peroxidation in rats’ brains. On the other hand, this consumption by healthy and dyslipidemic animals compromises memory.

Download Full-text

Syndrome Effects of Intensive Therapy – Post Intensive Care Syndrome (PICS)

Alexander Saltanov Intensive Care Herald ◽

10.21320/1818-474x-2018-2-12-23 ◽

2018 ◽

pp. 12-23 ◽

Cited By ~ 2

Author(s):

A.A. Belkin ◽

Keyword(s):

Intensive Care ◽

Intensive Therapy ◽

Post Intensive Care Syndrome

Download Full-text

Emotional Aspects of Pediatric Post-Intensive Care Syndrome Following Traumatic Brain Injury

Journal of Child & Adolescent Trauma ◽

10.1007/s40653-020-00332-y ◽

2021 ◽

Author(s):

Kathryn R. Bradbury ◽

Cydni Williams ◽

Skyler Leonard ◽

Emily Holding ◽

Elise Turner ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Intensive Care ◽

Brain Injury ◽

Emotional Aspects ◽

Post Intensive Care Syndrome

Download Full-text

Urinary Titin N-Fragment as a Biomarker of Muscle Atrophy, Intensive Care Unit-Acquired Weakness, and Possible Application for Post-Intensive Care Syndrome

Journal of Clinical Medicine ◽

10.3390/jcm10040614 ◽

2021 ◽

Vol 10 (4) ◽

pp. 614 ◽

Cited By ~ 1

Author(s):

Nobuto Nakanishi ◽

Rie Tsutsumi ◽

Kanako Hara ◽

Masafumi Matsuo ◽

Hiroshi Sakaue ◽

...

Keyword(s):

Intensive Care Unit ◽

Intensive Care ◽

Muscle Atrophy ◽

Critically Ill Patients ◽

Chronic Illnesses ◽

Rehabilitation Management ◽

Muscle Dystrophy ◽

Thin Filaments ◽

Thick Filaments ◽

Post Intensive Care Syndrome

Titin is a giant protein that functions as a molecular spring in sarcomeres. Titin interconnects the contraction of actin-containing thin filaments and myosin-containing thick filaments. Titin breaks down to form urinary titin N-fragments, which are measurable in urine. Urinary titin N-fragment was originally reported to be a useful biomarker in the diagnosis of muscle dystrophy. Recently, the urinary titin N-fragment has been increasingly gaining attention as a novel biomarker of muscle atrophy and intensive care unit-acquired weakness in critically ill patients, in whom titin loss is a possible pathophysiology. Furthermore, several studies have reported that the urinary titin N-fragment also reflected muscle atrophy and weakness in patients with chronic illnesses. It may be used to predict the risk of post-intensive care syndrome or to monitor patients’ condition after hospital discharge for better nutritional and rehabilitation management. We provide several tips on the use of this promising biomarker in post-intensive care syndrome.

Download Full-text

Post-intensive care syndrome after a critical COVID-19: cohort study from a Belgian follow-up clinic

Annals of Intensive Care ◽

10.1186/s13613-021-00910-9 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Anne-Françoise Rousseau ◽

Pauline Minguet ◽

Camille Colson ◽

Isabelle Kellens ◽

Sourour Chaabane ◽

...

Keyword(s):

Cohort Study ◽

Intensive Care ◽

Inpatient Rehabilitation ◽

Quadriceps Strength ◽

Biological Parameters ◽

Icu Stay ◽

Icu Discharge ◽

Prolonged Icu Stay ◽

Post Intensive Care Syndrome

Abstract Purpose Many patients with coronavirus disease 2019 (COVID-19) required critical care. Mid-term outcomes of the survivors need to be assessed. The objective of this single-center cohort study was to describe their physical, cognitive, psychological, and biological outcomes at 3 months following intensive care unit (ICU)-discharge (M3). Patients and methods All COVID-19 adults who survived an ICU stay ≥ 7 days and attended the M3 consultation at our multidisciplinary follow-up clinic were involved. They benefited from a standardized assessment, addressing health-related quality of life (EQ-5D-3L), sleep disorders (PSQI), and the three principal components of post-intensive care syndrome (PICS): physical status (Barthel index, handgrip and quadriceps strength), mental health disorders (HADS and IES-R), and cognitive impairment (MoCA). Biological parameters referred to C-reactive protein and creatinine. Results Among the 92 patients admitted to our ICU for COVID-19, 42 survived a prolonged ICU stay and 32 (80%) attended the M3 follow-up visit. Their median age was 62 [49–68] years, 72% were male, and nearly half received inpatient rehabilitation following ICU discharge. At M3, 87.5% (28/32) had not regained their baseline level of daily activities. Only 6.2% (2/32) fully recovered, and had normal scores for the three MoCA, IES-R and Barthel scores. The main observed disorders were PSQI > 5 (75%, 24/32), MoCA < 26 (44%, 14/32), Barthel < 100 (31%, 10/32) and IES-R ≥ 33 (28%, 9/32). Combined disorders were observed in 13/32 (40.6%) of the patients. The EQ-5D-3L visual scale was rated at 71 [61–80]. A quarter of patients (8/32) demonstrated a persistent inflammation based on CRP blood level (9.3 [6.8–17.7] mg/L). Conclusion The burden of severe COVID-19 and prolonged ICU stay was considerable in the present cohort after 3 months, affecting both functional status and biological parameters. These data are an argument on the need for closed follow-up for critically ill COVID-19 survivors.

Download Full-text

The Post-ICU presentation screen (PICUPS) and rehabilitation prescription (RP) for intensive care survivors part II: Clinical engagement and future directions for the national Post-Intensive care Rehabilitation Collaborative

Journal of the Intensive Care Society ◽

10.1177/1751143720988708 ◽

2021 ◽

pp. 175114372098870

Author(s):

Zudin Puthucheary ◽

Craig Brown ◽

Evelyn Corner ◽

Sarah Wallace ◽

Julie Highfield ◽

...

Keyword(s):

Intensive Care ◽

Critical Illness ◽

Inpatient Rehabilitation ◽

Service Evaluation ◽

Language Therapy ◽

Initial Development ◽

Related Data ◽

Acute Hospitals ◽

Rehabilitation Needs ◽

Post Intensive Care Syndrome

Background Many Intensive Care Unit (ICU) survivors suffer from a multi- system disability, termed the post-intensive care syndrome. There is no current national coordination of either rehabilitation pathways or related data collection for them. In the last year, the need for tools to systematically identify the multidisciplinary rehabilitation needs of severely affected COVID-19 survivors has become clear. Such tools offer the opportunity to improve rehabilitation for all critical illness survivors through provision of a personalised Rehabilitation Prescription (RP). The initial development and secondary refinement of such an assessment and data tools is described in the linked paper. We report here the clinical and workforce data that was generated as a result. Methods Prospective service evaluation of 26 acute hospitals in England using the Post-ICU Presentation Screen (PICUPS) tool and the RP. The PICUPS tool comprised items in domains of a) Medical and essential care, b) Breathing and nutrition; c) Physical movement and d) Communication, cognition and behaviour. Results No difference was seen in total PICUPS scores between patients with or without COVID-19 (77 (IQR 60-92) vs. 84 (IQR 68-97); Mann-Whitney z = −1.46, p = 0.144. A network analysis demonstrated that requirements for physiotherapy, occupational therapy, speech and language therapy, dietetics and clinical psychology were closely related and unaffected by COVID-19 infection status. A greater proportion of COVID-19 patients were referred for inpatient rehabilitation (13% vs. 7%) and community-based rehabilitation (36% vs.15%). The RP informed by the PICUPS tool generally specified a greater need for multi-professional input when compared to rehabilitation plans instituted. Conclusions The PICUPS tool is feasible to implement as a screening mechanism for post-intensive care syndrome. No differences are seen in the rehabilitation needs of patients with and without COVID-19 infection. The RP could be the vehicle that drives the professional interventions across the transitions from acute to community care. No single discipline dominates the rehabilitation requirements of these patients, reinforcing the need for a personalised RP for critical illness survivors.

Download Full-text

Altered mRNA Levels of Stress-Related Peptides in Mouse Hippocampus and Caudate-Putamen in Withdrawal after Long-Term Intermittent Exposure to Tobacco Smoke or Electronic Cigarette Vapour

International Journal of Molecular Sciences ◽

10.3390/ijms22020599 ◽

2021 ◽

Vol 22 (2) ◽

pp. 599

Author(s):

Lucia Carboni ◽

Luisa Ponzoni ◽

Daniela Braida ◽

Mariaelvina Sala ◽

Cecilia Gotti ◽

...

Keyword(s):

Public Health Problem ◽

Mrna Levels ◽

Obsessive Compulsive ◽

Bdnf Mrna ◽

Object Recognition Test ◽

Caudate Putamen ◽

Molecular Alterations ◽

Marble Burying ◽

Cigarette Withdrawal

Nicotine addiction is a severe public health problem. The aim of this study was to investigate the alterations in key neurotransmissions after 60 days of withdrawal from seven weeks of intermittent cigarette smoke, e-cigarette vapours, or an e-cigarette vehicle. In the nicotine withdrawal groups, increased depressive and anxiety/obsessive–compulsive-like behaviours were demonstrated in the tail suspension, sucrose preference and marble burying tests. Cognitive impairments were detected in the spatial object recognition test. A significant increase in Corticotropin-releasing factor (Crf) and Crf1 mRNA levels was observed, specifically after cigarette withdrawal in the caudate-putamen nucleus (CPu). The nociceptin precursor levels were reduced by cigarette (80%) and e-cigarette (50%) withdrawal in the CPu. The delta opioid receptor showed a significant reduction in the hippocampus driven by the exposure to an e-cigarette solubilisation vehicle, while the mRNA levels doubled in the CPu of mice that had been exposed to e-cigarettes. Withdrawal after exposure to e-cigarette vapour induced a 35% Bdnf mRNA decrease in the hippocampus, whereas Bdnf was augmented by 118% by cigarette withdrawal in the CPu. This study shows that long-term withdrawal-induced affective and cognitive symptoms associated to lasting molecular alterations in peptidergic signalling may determine the impaired neuroplasticity in the hippocampal and striatal circuitry.

Download Full-text