Nutritional therapy for the prevention of post-intensive care syndrome.

Post-intensive care syndrome (PICS) is a triad of physical, cognitive, and mental impairments that occur during or following the intensive care unit (ICU) stay, affecting the long-term prognosis of the patient and also the mental health of the patient's family. While the severity and duration of the systemic inflammation are associated with the occurrence of ICU-acquired weakness (ICU-AW), malnutrition and immobility during the treatment can exacerbate the symptoms. The goal of nutrition therapy in critically ill patients is to provide an adequate amount of energy and protein while addressing specific nutrient deficiencies to survive the inflammatory response and promote recovery from organ dysfunctions. Feeding strategy to prevent ICU-AW and PICS as nutrition therapy involves administering sufficient amounts of amino acids or proteins later in the acute phase after the hyperacute phase has passed, with specific attention to avoid energy overfeeding. Physiotherapy can also help mitigate muscle loss and subsequent physical impairment. However, many questions remain to be answered regarding the potential role and methods of nutrition therapy in association with ICU-AW and PICS, and further research is warranted.

Long-term follow-up in pediatric intensive care-a narrative review.

Pediatric intensive care is a rapidly developing medical specialty and with evolving understanding of pediatric pathophysiology and advances in technology, most children in the developed world are now surviving to intensive care and hospital discharge. As mortality rates for children with critical illness continue to improve, increasing PICU survivorship is resulting in significant long-term consequences of intensive care in these vulnerable patients. Although impairments in physical, psychosocial and cognitive function are well documented in the literature and the importance of establishing follow-up programs is acknowledged, no standardized or evidence-based approach to long-term follow-up in the PICU exists. This narrative review explores pediatric post-intensive care syndrome and summarizes the multifactorial deficits and morbidity that can occur in these patients following recovery from critical illness and subsequent discharge from hospital. Current practices around long-term follow-up are explored with discussion focusing on gaps in research and understanding with suggested ways forward and future directions.

Effects of early enteral nutrition on persistent inflammation, immunosuppression, and catabolism syndrome in critically ill patients: A claims database study using a propensity score analysis.

BACKGROUND & AIMS: Early enteral nutrition (EEN) potentially improves immune-related outcomes via the maintenance of intestinal immunity; however, the effects of EEN on clinical outcomes, including infectious complications, are controversial. Therefore, we herein investigated whether EEN affected persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which represents the immunocompromised state after critical illness. METHODS: This retrospective cohort study utilized the administrative claims database of inpatients and laboratory findings. Patients admitted to and treated in the intensive care unit (ICU) for more than 3 consecutive days were included. The primary outcome, a composite of PICS or mortality on day 14 after admission, was compared between the EEN group, which received enteral nutrition (EN) on the first 3 days (day 0, 1, or 2), and the late enteral nutrition (LEN) group, which did not receive EN on the first 3 days, but then received EN on days 3 through 7, using a propensity score-matched analysis. Secondary outcomes included the composite outcome on day 28, in-hospital mortality, the Barthel index, and laboratory data. Patients who met at least two of the following conditions were diagnosed with PICS: CRP >2.0 mg/dL, albumin <3.0 g/dL, and a lymphocyte count <800/µL. RESULTS: A total of 7530 matched pairs were generated after propensity score matching. The primary outcome was significantly lower in the EEN group (risk difference -3.0%, 95% confidence interval (CI) -4.5 to -1.4%), whereas mortality did not significantly differ. The 28-day composite outcome was similar in the 2 groups (risk difference -1.5%, 95% CI -2.8% to -0.2%, no significant difference in mortality). There was no significant difference in in-hospital mortality between the EEN and LEN groups; however, the Barthel index at discharge was higher in the EEN group (the medians, 50 vs 45, P = 0.001). Laboratory data showed lower Albumin and CRP on day 14 in the EEN group, but no other significant differences. CONCLUSIONS: In patients admitted to the ICU, EEN was associated with a lower incidence of PICS on days 14 and 28, but was not associated with mortality. This positive association was not observed in sepsis, cardiac diseases, or gastrointestinal diseases.

The Tri-Steps Model of Critical Conditions in Intensive Care: Introducing a New Paradigm for Chronic Critical Illness.

Background: The prevailing model for understanding chronic critical illness is a biphasic model, suggesting phases of acute and chronic critical conditions. A major challenge within this model is the difficulty in determining the timing of the process chronicity. It is likely that the triad of symptoms (inflammation, catabolism, and immunosuppression [ICIS]) could be associated with this particular point. We aimed to explore the impact of the symptom triad (inflammation, catabolism, immunosuppression) on the outcomes of patients hospitalized in intensive care units (ICUs). Methods: The eICU-CRD database with 200,859 ICU admissions was analyzed. Adult patients with the ICIS triad, identified by elevated CRP (>20 mg/L), reduced albumin (<30 g/L), and low lymphocyte counts (<0.8 × 109/L), were included. The cumulative risk of developing ICIS was assessed using the Nelson-Aalen estimator. Results: This retrospective cohort study included 894 patients (485 males, 54%), with 60 (6.7%) developing ICIS. The cumulative risk of ICIS by day 21 was 22.5%, with incidence peaks on days 2-3 and 10-12 after ICU admission. Patients with the ICIS triad had a 2.5-fold higher mortality risk (p = 0.009) and double the likelihood of using vasopressors (p = 0.008). The triad onset day did not significantly affect mortality (p = 0.104). Patients with ICIS also experienced extended hospital (p = 0.041) and ICU stays (p < 0.001). Conclusions: The symptom triad (inflammation, catabolism, immunosuppression) during hospitalization increases mortality risk by 2.5 times (p = 0.009) and reflects the chronicity of the critical condition. Identifying two incidence peaks allows the proposal of a new Tri-steps model of chronic critical illness with acute, extended, and chronic phases.

Functional outcome after interdisciplinary, acute rehabilitation in COVID-19 patients: a retrospective study.

BACKGROUND: Survivors of severe COVID-19 often exhibit a variety of sequelae including loss of mobility and ADL (activities of daily living) capacity. Acute rehabilitation (AR) is an interdisciplinary rehabilitation intervention applied early while still in a hospital setting. The goal of AR is to improve functional limitations and to increase functional independence at discharge. It is established in the treatment of patients with other severe diseases such as sepsis, polytrauma, or stroke. Data concerning AR in COVID-19 are sparse. AIM: To evaluate the changes in physical function during AR in patients after severe COVID-19. METHODS: This monocentric, retrospective observational study examined the functional outcomes of a sample of COVID-19-patients who received interdisciplinary AR at a university hospital. Inclusion criteria were a positive SARS-CoV-2 test in 05/2020-01/2022 and transfer to AR after intensive care treatment. 87 patients were elegible for evaluation, 3 of whom were excluded because of death during AR. Data were extracted from the hospital information system. In a pre-post analysis, mobility (Charité Mobility Index), ADL (Barthel Index), and oxygen demand were assessed. In addition, discharge location after AR, factors associated with AR unit length of stay, and functional improvements were analyzed. RESULTS: Data of 84 patients were analyzed. Mobility increased significantly from a median of 4 [1.25-6] CHARMI points at admission to a median of 9 [8.25-9] at discharge (p < 0.001). ADL increased significantly from a median of 52.5 [35.0-68.75] Barthel Index points at admission to a median of 92.5 [85-95] at discharge (p < 0.001). Oxygen demand decreased from 80.7 to 30.5% of patients. The majority (55.9%) of patients were discharged home, while 36.9% received direct follow-up rehabilitation. Older age correlated significantly with lower scores on the discharge assessment for mobility (Spearman's ϱ = -0.285, p = 0.009) and ADL (Spearman's ϱ = -0.297, p = 0.006). CONCLUSION: Acute rehabilitation is a viable option for COVID-19 patients with severe functional deficits after ICU treatment to achieve functional progress in mobility and ADL, reduce oxygen requirements and enable follow-up rehabilitation. TRIAL REGISTRATION NUMBER AND DATE OF REGISTRATION FOR PROSPECTIVELY REGISTERED TRIALS: Trial registration number: DRKS00025239. Date of registration: 08 Sep 2021.

From the Intensive Care Unit to Recovery: Managing Post-intensive Care Syndrome in Critically Ill Patients.

Post-intensive care syndrome (PICS) is the term used to describe the decline in the physical, cognitive, and/or mental condition of individuals who have been discharged from the intensive care unit (ICU). This complication could result in a significant reduction in quality of life, with some patients experiencing symptoms of prolonged weakness, depression, anxiety, and post-traumatic stress disorder (PTSD). Intensive care advancement over the years has resulted in an increase in ICU survival rates and a proportional increase in PICS, creating a need for more in-depth research into the prevention and management of the disease. Hence, this study aims to examine the present body of literature on PICS, encompassing its underlying physiological processes and elements that contribute to its development, methods for evaluating and diagnosing the condition, current treatment choices as well as potential new approaches, and the constraints in managing PICS and the necessity for further investigation. In this article, studies were compiled from several databases, including, but not limited to, Google Scholar, PubMed, and Cochrane Library. These studies were reviewed, and their data were used to highlight important aspects regarding the efficacy of current PICS screening tools, the optimization and limitations of both pharmacologic and non-pharmacologic treatment methods, and the feasibility and safety of emerging treatments and technologies. The major conclusions of this review were centered around the need for multidisciplinary management of PICS. From pharmacological management using analgesia to non-pharmacological management using early mobilization and exercise therapy, the effective treatment of PICS requires a multifaceted approach. Patient follow-up and its importance were touched upon, including strategies and policies to bolster proper follow-up, thereby increasing favorable outcomes. Lastly, the importance of family involvement and the increased need for research into this topic were highlighted.

Comparison of the Incidence of Post-intensive Care Syndrome (PICS) Between Elderly and Non-elderly Patients: A Subgroup Analysis of the Japan-PICS Study.

AIM: The aging society is expanding, and more elderly patients are admitted to intensive care units (ICUs). Elderly patients may have increased ICU mortality and are thought to have a high incidence of post-intensive care syndrome (PICS). There are few studies of PICS in the elderly. This study hypothesized that the elderly have an increased incidence of PICS compared to the non-elderly. METHODS: This is a subgroup analysis of a previous multicenter prospective observational study (Prevalence of post-intensive care syndrome among Japanese intensive care unit patients: The Japan-PICS study) conducted from April 2019 to September 2019. Ninety-six patients were included who were over 18 years old, admitted to the ICU, and expected to require mechanical ventilation for more than 48 hours. Physical component scales (PCS), mental component scales (MCS), and Short-Memory Questionnaire (SMQ) scores of included patients were compared before admission to the ICU and six months later. The diagnosis of PICS required one of the following: (1) the PCS score decreased ≧10 points, (2) the MCS score decreased ≧10 points, or (3) the SMQ score decreased by >40 points. Patients were classified as non-elderly (<65 years old) or elderly (≧65 years old), and the incidence of PICS was compared between these two groups. RESULTS: The non-elderly (N=27) and elderly (N=69) groups had incidences of PICS: 67% and 62% (p=0.69), respectively. CONCLUSION: There is no statistically significant difference in the incidence of PICS in the non-elderly and elderly.

Parental emotional, social and transitional health in the first 6 months after childhood critical illness: A longitudinal qualitative study.

AIM: To explore the experiences and support needs of parents in the first 6 months after paediatric critical care. DESIGN: Longitudinal qualitative design. METHODS: Sequential semi-structured qualitative interviews were conducted with a sample of 28 parents in succession at 1 month and at 6 months (n = 22) after their child's discharge from paediatric critical care using purposive sampling. Data were analysed using the adapted five-stage framework analysis. RESULTS: Data were developed into eight synthesized themes, three domains and an overarching theme: Regaining Normalcy. Families of children requiring medical treatment at 6 months showed signs of adaption to daily care routines. The two domains were Parental Emotional Health and Parental Social Health. Parental Transitional Health, a third domain, was added to the Post Intensive Care Syndrome-paediatric framework. Parents were forward-looking and discussed emotional health, relating to current caregiving issues. Emotional attention was related to present challenges and concerns about current health and possible readmission to the hospital. In terms of Parental Social Health, families isolated themselves for infection control while remaining connected with families using chat applications. Parents were selective to whom they allowed access to their lives. The impact of parental transitional health was evident and emphasized the daily challenges associated with integration back to home life. Flexible work arrangements allowed working parents to support caregiving needs in the first 6 months after discharge. CONCLUSION: In the first 6 months after paediatric critical illness, most families reported having moved past the experiences while having provoking memories of the admission period. Parents viewed the point of normalcy as child returned to school or when all medications were discontinued. Extension of transitional support can facilitate discharge experiences between paediatric critical care and normalcy. The findings highlight the importance of understanding the medium- and longer-term impact of paediatric critical care. IMPACT: What problem did the study address? ○ Limited understanding of long-term parental experiences and support needs after PICU discharge. What were the main findings? ○ Most families regained normalcy when child returns to school or when medications were discontinued. Some families continued to show signs of adaptations at 6 months after PICU discharge. Where and on whom did the research have an impact? ○ The research has an impact on improving the understanding of long-term parental experiences and support needs after PICU discharge, informing clinical practice, guiding policy development and shaping parental support programs. REPORTING METHOD: We reported this study using the COREQ guidelines. PATIENT OR PUBLIC CONTRIBUTION: Prior to confirming the interview guide, three parents of critically ill children actively participated by reviewing and providing feedback on its content. They provided suggestions to refine the wording and ensure clarity to enhance the participants' understanding. By including the perspectives of these parents, we aimed to improve the overall quality and relevance of the interview guide.

Charting the course for improved outcomes in chronic critical illness: therapeutic strategies for persistent inflammation, immunosuppression, and catabolism syndrome (PICS).

Enhanced critical care delivery has led to improved survival rates in critically ill patients, yet sepsis remains a leading cause of multiorgan failure with variable recovery outcomes. Chronic critical illness, characterised by prolonged ICU stays and persistent end-organ dysfunction, presents a significant challenge in patient management, often requiring multifaceted interventions. Recent research, highlighted in a comprehensive review in the British Journal of Anaesthesia, focuses on addressing the pathophysiological drivers of chronic critical illness, such as persistent inflammation, immunosuppression, and catabolism, through targeted therapeutic strategies including immunomodulation, muscle wasting prevention, nutritional support, and microbiome modulation. Although promising avenues exist, challenges remain in patient heterogeneity, treatment timing, and the need for multimodal approaches.

Urea to creatinine ratio as a predictor of persistent critical illness.

INTRODUCTION: Persistent critical illness (PCI) is a syndrome in which the acute presenting problem has been stabilized, but the patient's clinical state does not allow ICU discharge. The burden associated with PCI is substantial. The most obvious marker of PCI is prolonged ICU length of stay (LOS), usually greater than 10 days. Urea to Creatinine ratio (UCr) has been suggested as an early marker of PCI development. METHODS: A single-center retrospective study. Data of patients admitted to a general mixed medical-surgical ICU during Jan 1st 2018 till Dec 31st 2022 was extracted, including demographic data, baseline characteristics, daily urea and creatinine results, renal replacement therapy (RRT) provided, and outcome measures - length of stay, and mortality (ICU, and 90 days). Patients were defined as PCI patients if their LOS was >10 days. We used Fisher exact test or Chi-square to compare PCI and non-PCI patients. The association between UCr with PCI development was assessed by repeated measures linear model. Multivariate Cox regression was used for 1 year mortality assessment. RESULTS: 2098 patients were included in the analysis. Patients who suffered from PCI were older, with higher admission prognostic scores. Their 90-day mortality was significantly higher than non-PCI patients (34.58% vs 12.18%, p < 0.0001). A significant difference in UCr was found only on the first admission day among all patients. This was not found when examining separately surgical, trauma, or transplantation patients. We did not find a difference in UCr in different KDIGO (Kidney Disease Improving Global Outcomes) stages. Elevated UCr and PCI were found to be significantly associated with 1 year mortality. CONCLUSION: In this single center retrospective cohort study, UCr was not found to be associated with PCI development.

A scoping review of incidence and assessment tools for post-intensive care syndrome following cardiac surgery.

BACKGROUND: Post-intensive care syndrome is a new or worsening persistent deterioration in cognitive, mental, and/or physical health following a prolonged admission to an intensive care unit. Post-intensive care syndrome remains underexplored following cardiac surgery, with a lack of understanding of the incidence and tools used to measure the symptoms. A scoping review was conducted to determine the incidence and to identify the tools commonly used to measure symptoms of post-intensive care syndrome following cardiac surgery. METHODS: The electronic databases Medline (Ovid), EMBASE (Ovid), PsycINFO (Ovid), Scopus, and CINAHL (EBSCOhost) and Google Scholar were searched with keywords and controlled vocabulary to describe both cardiac surgery and post-intensive care syndrome (cardiac surgical procedures, heart surgery, and post-intensive care symptoms) and symptoms (delirium, depression, mobility and quality of life). Included were articles written in English and published after 2005 that described cognitive, mental, and physical symptoms of post-intensive care syndrome following cardiac surgery. 3,131 articles were found, with 565 duplicates, leaving 2,566 articles to be screened. Of these, seven unique studies were included. RESULTS: Five studies explored cognitive health, three mental health, one cognitive and mental health, and none physical health. No identified studies reported the overall incidence of post-intensive care syndrome following cardiac surgery. The incidence of cognitive health issues ranged from 21% to 38%, and mental health issues ranged from 16% to 99%. In total, 17 different tools were identified - 14 for cognitive health and three for mental health. No identified studies used the same tools to measure symptoms. No single tool was found to measure all three domains. CONCLUSION: This scoping review identified a literature gap specific to the incidence and inconsistency of assessment tools for post-intensive care syndrome in cardiac surgery patients. CLINICAL IMPLICATIONS: This work impacts clinical practice for the bedside nurse by raising awareness of an emerging health issue.

Optimization of quenched fluorescent peptide substrates of SARS-CoV-2 3CLpro main protease (Mpro) from proteomic identification of P6-P6' active site specificity.

SARS-CoV-2 3C-like main protease (3CLpro) is essential for protein excision from the viral polyprotein. 3CLpro inhibitor drug development to block SARS-CoV-2 replication focuses on the catalytic non-prime (P) side for specificity and potency, but the importance of the prime (P') side in substrate specificity and for drug development remains underappreciated. We determined the P6-P6' specificity for 3CLpro from >800 cleavage sites that we identified using Proteomic Identification of Cleavage site Specificity (PICS). Cleavage occurred after the canonical P1-Gln and non-canonical P1-His and P1-Met residues. Moreover, P3 showed a preference for Arg/Lys and P3' for His. Essential H-bonds between the N-terminal Ser1 of protomer-B in 3CLpro dimers form with P1-His, but not with P1-Met. Nonetheless, cleavage occurs at P1-Met456 in native MAP4K5. Elevated reactive oxygen species in SARS-CoV-2 infection oxidize methionines. Molecular simulations revealed P1-MetOX forms an H-bond with Ser1 and notably, strong positive cooperativity between P1-Met with P3'-His was revealed, which enhanced peptide-cleavage rates. The highly plastic S3' subsite accommodates P3'-His that displays stabilizing backbone H-bonds with Thr25 lying central in a "'threonine trio" (Thr24-Thr25-Thr26) in the P'-binding domain I. Molecular docking simulations unveiled structure-activity relationships impacting 3CLpro-substrate interactions, and the role of these structural determinants was confirmed by MALDI-TOF-MS cleavage assays of P1'- and P3'-positional scanning peptide libraries carrying a 2nd optimal cut-site as an internal positive control. These data informed the design of two new and highly soluble 3CLproquenched-fluorescent peptide substrates for improved FRET monitoring of 3CLpro activity with 15× improved sensitivity over current assays.IMPORTANCEFrom global proteomics identification of >800 cleavage sites, we characterized the P6-P6' active site specificity of SARS-CoV-2 3CLpro using proteome-derived peptide library screens, molecular modeling simulations, and focussed positional peptide libraries. In P1', we show that alanine and serine are cleaved 3× faster than glycine and the hydrophobic small amino acids Leu, Ile, or Val prevent cleavage of otherwise optimal non-prime sequences. In characterizing non-canonical non-prime P1 specificity, we explored the unusual P1-Met specificity, discovering enhanced cleavage when in the oxidized state (P1-MetOX). We unveiled unexpected amino acid cooperativity at P1-Met with P3'-His and noncanonical P1-His with P2-Phe, and the importance of the threonine trio (Thr24-Thr25-Thr26) in the prime side binding domain I in defining prime side binding in SARS-CoV-2 3CLpro. From these analyses, we rationally designed quenched-fluorescence natural amino acid peptide substrates with >15× improved sensitivity and high peptide solubility, facilitating handling and application for screening of new antiviral drugs.

Quantitative 3D Analysis of Levator Ani Muscle Subdivisions in Nulliparous Women: MRI Feasibility Study.

BACKGROUND: The levator ani muscle (LAM) is crucial for pelvic floor stability, yet its quantitative MRI assessment is only a recent focus. Our study aims to standardize the quantitative analysis of the LAM morphology within the 3D Pelvic Inclination Correction System (3D-PICS). METHODS: We analyzed 35 static MR datasets from nulliparous women examining the pubovisceral (PVM), iliococcygeal (ICM), coccygeal (COC), and puborectal muscle (PRM). The PVM consists of three origin-insertion pairs, namely the puboanal (PAM), puboperineal (PPM) and pubovaginal muscle (PVaM). The analysis included a quantitative examination of the morphology of LAM, focusing on the median location (x/y/z) (x: anterior-posterior, y: superior-inferior, z: left-right) of the origin and insertion points (a), angles (b) and lengths (c) of LAM. Inter-rater reliability was calculated. RESULTS: Interindividual variations in 3D coordinates among muscle subdivisions were shown. In all, 93% of all origin and insertion points were found within an SD of <8 mm. Angles to the xz-plane range between -15.4° (right PRM) and 40.7° (left PAM). The PRM is the largest pelvic muscle in static MRI. The ICC indicated moderate-to-good agreement between raters. CONCLUSIONS: The accurate morphometry of the LAM and its subdivisions, along with reliable inter-rater agreement, was demonstrated, enhancing the understanding of normal pelvic anatomy in young nulliparous women.

High-Molecular-Weight Hyaluronic Acid Can Be Used as a Food Additive to Improve the Symptoms of Persistent Inflammation, Immunosuppression and Catabolism Syndrome (PICS).

Hyaluronic acid (HA) is a new functional food additive which has the potential to ameliorate persistent inflammation, immunosuppression and catabolism syndrome (PICS), but the biological effects of HA with various molecular weights differ dramatically. To systematically investigate the efficacy of HA in altering PICS symptoms, medium-molecular-weight (MMW) HA was specifically selected to test its intervention effect on a PICS mouse model induced by CLP through oral administration, with high-molecular-weight (HMW) and low-molecular-weight (LMW) HA also participating in the experimental validation process. The results of pathological observations and gut flora showed that MMW HA rapidly alleviated lung lesions and intestinal structural changes in PICS mice in the short term. However, although long-term MMW HA administration significantly reduced the proportions of harmful bacteria in gut flora, inflammatory responses in the intestines and lungs of PICS mice were significantly higher in the MMW HA group than in the HMW HA and LMW HA groups. The use of HMW HA not only rapidly reduced the mortality rate of PICS mice but also improved their grip strength and the recovery of spleen and thymus indices. Furthermore, it consistently promoted the recovery of lung and intestinal tissues in PICS mice, and it also assisted in the sustained restoration of their gut microbiota. These effects were superior to those of LMW HA and MMW HA. The experimental results indicate that HMW weight HA has the greatest potential to be an adjunct in alleviating PICS as a food additive, while the safety of other HAs requires further attention.

Intensive care unit follow-up clinic activities: a scoping review.

The importance of ongoing post-discharge follow-up to prevent functional impairment in patients discharged from intensive care units (ICUs) is being increasingly recognized. Therefore, we conducted a scoping review, which included existing ICU follow-up clinic methodologies using the CENTRAL, MEDLINE, and CINAHL databases from their inception to December 2022. Data were examined for country or region, outpatient name, location, opening days, lead profession, eligible patients, timing of the follow-up, and assessment tools. Twelve studies were included in our review. The results obtained revealed that the methods employed by ICU follow-up clinics varied among countries and regions. The names of outpatient follow-up clinics also varied; however, all were located within the facility. These clinics were mainly physician or nurse led; however, pharmacists, physical therapists, neuropsychologists, and social workers were also involved. Some clinics were limited to critically ill patients with sepsis or those requiring ventilation. Ten studies reported the first outpatient visit 1-3 months after discharge. All studies assessed physical function, cognitive function, mental health, and the health-related quality of life. This scoping review revealed that an optimal operating format for ICU follow-up clinics needs to be established according to the categories of critically ill patients.

[Results of a cohort single-center randomized study of the modulating effect of the drug Mexidol in the rehabilitation of patients who suffered acute cerebral insufficiency]. / Rezul'taty kogortnogo odnotsentrovogo randomizirovannogo issledovaniya moduliruyushchego effekta preparata Meksidol v reabilitatsii patsientov, perenesshikh ostruyu tserebral'nuyu nedostatochnost'.

OBJECTIVE: Evaluation of the effect of pharmacological modulation of the rehabilitation process with the drug mexidol as an adjuvant component of the rehabilitation treatment of cognitive-emotional disorders in patients who have suffered acute cerebral insufficiency (ACI) due to acute cerebrovascular accident or traumatic brain injury. MATERIAL AND METHODS: The study was conducted as a randomized interventional prospective study and consisted of 5 visits. Patients were divided into 2 groups: main (n=30, standard therapy + Mexidol IV 500 mg per day for 10 days, followed by Mexidol FORTE 250 orally, 1 tablet 3 times a day for 8 weeks) and control (n=30, standard therapy for 66 days). RESULTS: The study randomized 60 patients who underwent ACN and received rehabilitation treatment in accordance with regional routing. In the main group, there was an improvement in cognitive functions comparable to the control group (p<0.001, in both groups there was an improvement in the Schulte test «work efficiency¼ and «total execution time¼, according to the MoCA scale (visit 5 - 23.8±2.6 vs 22.9±31, p=0.227). A significant superiority of the main group over the control group was shown in such indicators as a decrease in anxiety (according to the HADS scale) (visit 4 - 2.6±2.4 vs 4.4±2.4, p=0.004), a decrease in the severity of depression (according to the Beck scale) (visit 3 - 7.5±4.5 vs 11.4±5.6, p=0.005). There was a tendency for the main group to be superior in terms of muscle strength (according to the MRC scale (visit 4 - 3.3±5.1 vs 2.1±2.2, p=0.051), level of vital activity (according to the ShRM - visit 5 - 2.9±0.7 vs 3.3±0.6, p=0.053). A statistically significant increase in the level of mobility of patients in the group using the drug Mexidol was proven compared to the control group (the difference in the Rivermead index at the 5th visit was 10.3±2.8 and 8.0±2.8, respectively, p=0.006), the average increase in the Rivermead index by visit 5 (5.4±2.1 vs 3.4±1.6, p<0.001). A decrease in intensive care aftereffects syndrome (ITS) scores was detected in both groups; a statistically significant decrease in the severity of ITS in relation to the previous visit was detected only in the group using the drug Mexidol (p<0.001). In the main group, the best indicators of the dynamics of systolic cerebral blood flow velocity and overshoot coefficient were also determined, compared to the control group. There were no adverse events recorded in the study. CONCLUSION: A positive modulating effect of Mexidol has been demonstrated in terms of accelerating the restoration of tolerance to cognitive loads, improving the psycho-emotional background by reducing symptoms of anxiety and depression, and secondary improving the results of motor rehabilitation in the early recovery period in patients who have undergone ACI, including those with manifestations of PIT syndrome. During the study, no adverse events were recorded, as well as significant differences in vital functions in the study groups, which indicates comparable safety of therapy in the control and main groups.

Risk factors, biomarkers, and mechanisms for persistent inflammation, immunosuppression, and catabolism syndrome (PICS): a systematic review and meta-analysis.

INTRODUCTION: Persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been proposed as an endotype of chronic critical illness (CCI). The aim of this systematic review is to synthesise the available evidence of risk factors, biomarkers, and biological mechanisms underlying PICS. METHODS: MEDLINE, CENTRAL, and EMBASE were searched on June 2, 2023. Our population of interest was adult intensive care unit survivors. The exposure group was patients with PICS and the comparator group was patients with no PICS, CCI, or rapid recovery. Mean differences were pooled for each biomarker using a random effects DerSimonian-Laird method. Risk of bias assessment was done using the Newcastle-Ottawa Scale. RESULTS: Six papers were included. Five were single-centre retrospective cohort studies, and one was a prospective cohort study, with sample sizes ranging from 22 to 391 patients. Two studies showed an increased incidence of PICS with age, and two studies showed an association between PICS and Charlson Comorbidity Index scores. PICS was associated with requiring mechanical ventilation in four studies. Meta-analysis showed a 34.4 mg L-1 higher C-reactive protein (95% confidence interval [CI] 12.7-56.2 mg L-1; P<0.01), a 4.4 g L-1 lower albumin (95% CI 0.5-8.3 g L-1; P<0.01), and a 0.36×109 L-1 lower lymphocyte count (95% CI 0.25-0.47×109 L-1; P=0.01) in the PICS compared with the non-PICS group. There are a large variety of other potential biomarkers but limited validation studies. The overall quality of evidence is limited, and these results should be interpreted accordingly. CONCLUSIONS: While older patients and those with co-morbidities could be at greater risk for PICS, acquired risk factors, such as injury severity, are potentially more predictive of PICS than intrinsic patient characteristics. There are many potential biomarkers for PICS, but limited validation studies have been conducted. Persistent myeloid-derived suppressor cell expansion, the continual release of danger-associated molecular patterns and pathogen-associated molecular patterns propagating inflammation, and bioenergetic failure are all mechanisms underlying PICS that could offer potential for novel biomarkers and therapeutic interventions. CLINICAL TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO; CRD42023427749).

A shift towards targeted post-ICU treatment: Multidisciplinary care for cardiac arrest survivors.

Intensive Care Unit (ICU) survivorship comprises a burgeoning area of critical care medicine, largely due to our improved understanding of and concern for patients' recovery trajectory, and efforts to mitigate the post-acute complications of critical illness. Expansion of care beyond hospitalization is necessary, yet evidence for post-ICU clinics remains limited and mixed, as both interventions and target populations studied to date are too heterogenous to meaningfully demonstrate efficacy. Here, we briefly present the existing evidence and limitations related to post-ICU clinics, identify cardiac arrest survivors as a unique ICU subpopulation warranting further investigation and treatment, and propose a clinical framework that addresses the multifaceted needs of this well-defined patient population.

Hermetic Bags: A Short-Term Solution to Preserve High-Moisture Maize during Grain Drying.

Maintaining maize quality while drying during a rainy season is a major challenge for smallholder farmers in developing countries. We conducted a study to evaluate the impact of temporarily storing wet maize of 18, 21, and 24% moisture content (m.c.) in hermetic Purdue Improved Crop Storage (PICS) and polypropylene (PP) woven (control) bags for 21 days. Oxygen and carbon dioxide concentrations were monitored, and m.c., germination, and visual mold were assessed. In PICS bags, oxygen dropped below 1% within 7, 11.5, and 21 days for maize at 24, 21, and 18% m.c., respectively. After 21 days, the m.c. of maize stored in PICS bags remained constant, but decreased in PP bags. Germination of maize in PICS bags decreased by 0.5, 6.2, and 95.5 percentage points for 18, 21, and 24% m.c., respectively. In PP bags, germination decreased by 17.5, 15.2, and 39.5 percentage points for the respective moisture levels. After 21 days of storage, visible mold was present on maize stored in PP bags at both 21 and 24% m.c. No mold was observed on maize stored in PICS bags, but a fermentation smell was released from maize at 21 and 24% m.c. The results indicate that maize can be effectively stored in PICS bags at 21% m.c. or below for 21 days with minimal germination loss or mold growth. These findings highlight the potential of using hermetic bags for short-term grain quality preservation just before and during drying. This new utility adds to the current use of hermetic bags for protection against pests during long-term storage. Hermetic bags' dual functionality could significantly improve postharvest management on smallholder farms, thereby enhancing food and nutritional security and safety. Field testing is required in order to integrate this approach under smallholder farmers' conditions (e.g., temperature, m.c., drying practices, etc.).

A survivor with unexplained chest scars.

This case illustrates chest scars after piston-based chest compression device resuscitation and raises the awareness of the potential benefits of following up survivors of critical illness.