Verifying the Japanese version of the Healthy Aging Brain Care Monitor self-report tool for evaluating post-intensive care syndrome.

BACKGROUND: Post-intensive care syndrome (PICS) requires the use of multiple assessment tools because it affects multiple domains: Cognitive, Functional, and Behavioural/Psychological. Therefore, this study translated the self-report (SR) version of the Healthy Aging Brain Care Monitor (HABC-M), spanning multiple domains, into Japanese and analysed its reliability and validity in a post-intensive care setting. METHODS: Patients aged 20 years or older and admitted to the adult intensive care unit from August 2019 to January 2021 were included and surveyed by questionnaire. The 21-item Dementia Assessment Sheet for the Regional Comprehensive Care System was used to validate cognitive and physical aspects, and the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, and the Post Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders 5th edition were used to validate emotional aspects. Reliability was assessed by Cronbach's alpha, and congruent validity by correlation analysis. Multivariate linear regression models were used to identify potential factors for PICS. RESULTS: A total of 104 patients (mean age: 64 ± 14 years) with 3 median mechanical ventilation days (interquartile range: 2-5) were enrolled. The Cognitive domain of the HABC-M SR was highly correlated with memory and disorientation (r = 0.77 for each), while the Functional domain was highly correlated with Instrumental Activities of Daily Living Scale (r = 0.75-0.79). The Behavioural/Psychological domain highly correlated with the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and Post Traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders 5th edition (r = 0.75-0.76). Multivariate analysis revealed longer ICU stays associated with lower Cognitive and Functional (p = 0.03 for each) domains and longer mechanical ventilation days with a lower Behavioural/Psychological domain (p < 0.01). CONCLUSION: The translated Japanese HABC-M SR showed high validity for assessment of the Cognitive, Functional, and Behavioural/Psychological domains of PICS. Therefore, we recommend that the Japanese version of the HABC-M SR be routinely used in the assessment of PICS.

Relation between nutrition therapy in the acute phase and outcomes of ventilated patients with COVID-19 infection: a multicenter prospective observational study.

BACKGROUND: Optimal nutrition therapy has not yet been established for the acute phase of severe coronavirus disease 2019 (COVID-19) infection. OBJECTIVES: We aimed to examine the effects of nutrition delivery in the acute phase on mortality and the long-term outcomes of post-intensive care syndrome (PICS). METHODS: A multicenter prospective study was conducted on adult patients with COVID-19 infection requiring mechanical ventilation during an intensive care unit (ICU) stay. Daily total energy (kcal/kg) and protein (g/kg) deliveries in the first week of the ICU stay were calculated. The questionnaire for PICS evaluation was mailed within a median of 6 mo after hospital discharge. The primary outcome was in-hospital mortality, and secondary outcomes were the PICS components of physical impairment, cognitive dysfunction, and mental illness. RESULTS: Among 414 eligible patients, 297 who received mechanical ventilation for 7 d or longer were examined. PICS was evaluated in 175 patients among them. High protein delivery on days 4-7 correlated with a low in-hospital mortality rate. In contrast, high protein delivery on days 1-3 correlated with physical impairment. A multivariate logistic regression analysis adjusted for age, sex, BMI, and severity revealed that average energy and protein deliveries on days 4-7 correlated with decreased in-hospital mortality (OR: 0.94; 95% CI: 0.89, 0.99; P = 0.013 and OR: 0.40; 95% CI: 0.17, 0.93; P = 0.031, respectively). Nutrition delivery did not correlate with PICS outcomes after adjustments. In the multivariate regression using a restricted cubic spline model, in-hospital mortality monotonically decreased with increases in average nutrition delivery on days 4-7. CONCLUSIONS: In patents with COVID-19 on mechanical ventilation for ≥7 d, nutrition delivery in the late period of the acute phase was monotonically associated with a decrease in in-hospital mortality. Adequate protein delivery is needed on days 4-7.This trial was registered at https://www.umin.ac.jp as UMIN000041276.

Nutrition therapy in the intensive care unit during the COVID-19 pandemic: Findings from the ISIIC point prevalence study.

BACKGROUND & AIMS: Nutrition therapy for Intensive Care Unit (ICU) patients involves complex decision-making, especially during the COVID-19 pandemic. We investigated the use of nutrition therapy in ICU patients with and without COVID-19 infections. METHODS: Nutrition therapy was evaluated during a world-wide one-day prevalence study focused on implementation of the ABCDEF bundle (A: regular pain assessment, B: both spontaneous awakening and breathing trials, C: regular sedation assessment, D: regular delirium assessment, E: early mobility and exercise, and F: family engagement and empowerment) during the COVID-19 pandemic. Basic ICU and patient demographics including nutrition therapy delivery were collected on the survey day. Physical activity for patients with and without COVID infections was categorized using the ICU mobility scale (IMS). Multivariable regression analysis of nutrition was conducted using ICU parameters. RESULTS: The survey included 627 non-COVID and 602 COVID patients. A higher proportion of COVID-19 patients received energy ≥20 kcal/kg/day (55% vs. 45%; p = 0.0007) and protein ≥1.2 g/kg/day (45% vs. 35%; p = 0.0011) compared to non-COVID patients. Enteral nutrition was provided to most COVID patients even with prone positioning (91%). Despite nutrition therapy, IMS was extremely low in both groups; median IMS was 1 in non-COVID patients and 0 in COVID patients. The rate of energy delivery ≥20 kcal/kg/day was significantly higher in patients with COVID-19 infections in the subgroup of ICU days ≤5 days and IMS ≤2. Having a dedicated ICU nutritionist/dietitian was significantly associated with appropriate energy delivery in patients both with and without COVID-19 infections, but not with protein delivery. CONCLUSION: During the COVID-19 pandemic, patients with COVID-19 infections received higher energy and protein delivery. Generally low mobility levels highlight the need to optimize early mobilization with nutrition therapy in all ICU patients.

Novel protocol combining physical and nutrition therapies, Intensive Goal-directed REhabilitation with Electrical muscle stimulation and Nutrition (IGREEN) care bundle.

BACKGROUND: Although the combination of rehabilitation and nutrition may be important for the prevention of intensive care unit (ICU)-acquired weakness, a protocolized intervention of this combination has not yet been reported. We herein developed an original combined protocol and evaluated its efficacy. METHODS: In this single-center historical control study, we enrolled adult patients admitted to the ICU. Patients in the control group received standard care, while those in the intervention group received the protocol-based intervention. The ICU mobility scale was used to set goals for early mobilization and a neuromuscular electrical stimulation was employed when patients were unable to stand. The nutritional status was assessed for nutritional therapy, and target calorie delivery was set at 20 or 30 kcal/kg/day and target protein delivery at 1.8 g/kg/day in the intervention group. The primary endpoint was a decrease in femoral muscle volume in 10 days assessed by computed tomography. RESULTS: Forty-five patients in the control group and 56 in the intervention group were included in the analysis. Femoral muscle volume loss was significantly lower in the intervention group (11.6 vs 14.5%, p = 0.03). The absolute risk difference was 2.9% (95% CI 0.1-5.6%). Early mobilization to a sitting position by day 10 was achieved earlier (p = 0.03), and mean calorie delivery (20.1 vs. 16.8 kcal/kg/day, p = 0.01) and mean protein delivery (1.4 vs. 0.8 g/kg/day, p < 0.01) were higher in the intervention group. CONCLUSION: The protocolized intervention, combining early mobilization and high-protein nutrition, contributed to the achievement of treatment goals and prevention of femoral muscle volume loss. TRIAL REGISTRATION NUMBER: The present study is registered at the University Hospital Medical Information Network-clinical trials registry (UMIN000040290, Registration date: May 7, 2020).

Urinary Titin N-Fragment Evaluation in a Randomized Controlled Trial of Beta-Hydroxy-Beta-Methylbutyrate for Acute Mild Trauma in Older Adults.

The effects of beta-hydroxy-beta-methylbutyrate (HMB) complex administration and the significance of titin, a biomarker of muscle injury, in elderly minor trauma patients in acute phase has not been established. In this single-center, randomized controlled study, trauma patients aged ≥ 70 years with an injury severity score < 16 were included. Titin values on days 1 and 3 were measured and the intervention group received HMB complex (2.4 g of HMB + 14 g of glutamine + 14 g of arginine) and the control group received glutamine complex (7.2 g of protein including 6 g of glutamine). The cross-sectional area of the rectus femoris (RFCSA) on ultrasound, grip strength, and the Barthel Index were assessed on the first day of rehabilitation and after 2 weeks. We analyzed 24 HMB and 25 control participants. Titin values on day 3 correlated with grip strength (r = -0.34, p = 0.03) and the Barthel Index (r = -0.39, p = 0.01) at follow-up. HMB complex supplementation had no effect on the RFCSA (2.41 vs. 2.45 cm2, p = 0.887), grip strength (13.3 vs. 13.1 kg, p = 0.946), or the Barthel Index (20.0 vs. 50.0, p = 0.404) at follow-up. Titin values might associate with subsequent physical function. Short-term HMB complex supplementation from acute phase did not ameliorate muscle injury.

High protein versus medium protein delivery under equal total energy delivery in critical care: A randomized controlled trial.

BACKGROUND: Appropriate protein delivery amounts during the acute phase of critical care are unknown. Along with nutrition, early mobilization and the combination are important. We conducted a randomized controlled trial during critical care to assess high-protein and medium-protein delivery under equal total energy delivery with and without active early rehabilitation. METHODS: ICU patients of August 2018-September 2019 were allocated to a high-protein group (target energy 20 kcal/kg/day, protein 1.8 g/kg/day) or a medium-protein group (target energy 20 kcal/kg/day, protein 0.9 g/kg/day) with the same nutrition protocol by day 10. By dividing the study period, standard rehabilitation was administered during the initial period. Rehabilitation with belt-type electrical muscle stimulation was given from day 2 in the latter as a historical comparison. Femoral muscle volume was evaluated on day 1 and day 10 using computed tomography. RESULTS: This study analyzed 117 eligible patients with similar characteristics assigned to a high-protein or medium-protein group. Total energy delivery was around 20 kcal/kg/day in both groups, but protein delivery was 1.5 g/kg/day and 0.8 g/kg/day. As a primary outcome, femoral muscle volume loss was 12.9 ± 8.5% in the high-protein group and 16.9 ± 7.0% in the medium-protein group, with significant difference (p = 0.0059). Persistent inflammation, immunosuppression, and catabolism syndrome were significantly less frequent in the high-protein group. Muscle volume loss was significantly less in the high-protein group only during the electrical muscle stimulation period. CONCLUSIONS: For critical care, high protein delivery provided better muscle volume maintenance, but only with active early rehabilitation. REGISTRATION: University Hospital Medical Information Network, UMIN000033783 Registered on 16 Aug 2018. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000038538.

Cardiac Variation of Internal Jugular Vein as a Marker of Volume Change in Hemorrhagic Shock.

BACKGROUND: Fluid resuscitation, which is critical to counter acute hemorrhagic shock, requires prompt and accurate intravascular volume estimation for optimal fluid administration. This study aimed to evaluate whether cardiac variation of internal jugular vein (IJV), evaluated by ultrasonography, could detect hypovolemic status and predict response to fluid resuscitation. METHODS: Patients undergoing autologous blood transfusion for elective surgery who were prospectively enrolled at the study blood donation center between August 2014 and January 2015. Vertical B-mode ultrasonography movies of IJV were recorded at five timepoints during blood donation: before donation, during donation, end of donation, end of fluid replacement, and after hemostasis. Cardiac variation of the IJV area and circumference were objectively measured using an automated extraction program together with blood pressure and heart rate. RESULTS: A total of 140 patients were screened, and data from 104 patients were included in the final analyses. Among the variables analyzed, only collapse index area and collapse index circumference could detect both intravascular volume loss and response to fluid administration. CONCLUSIONS: Cardiac variation of IJV may be a reliable indicator of intravascular volume loss and response to fluid administration in hemorrhagic shock.

ß-Hydroxy-ß-methylbutyrate, Arginine, and Glutamine Complex on Muscle Volume Loss in Critically Ill Patients: A Randomized Control Trial.

BACKGROUND: ß-Hydroxy-ß-methylbutyrate (HMB), a metabolite of leucine, can strongly induce muscle protein synthesis. We evaluated the efficacy of HMB complex on muscle volume loss during critical care. METHODS: For this prospective, single-center, randomized control trial, we created control and HMB groups by random assignment of intensive care unit (ICU) patients for whom enteral nutrition could be performed. From 164 ICU patients, 88 severely ill patients were included and assigned: 43 to control and 45 to HMB. From day 2 after admission, HMB group were administered 3 g HMB, 14 g arginine, and 14 g glutamine daily in addition to standard nutrition therapy. Early rehabilitation with electrical muscle stimulation was started from day 2 in both groups. As a primary outcome, we evaluated femoral muscle volume using computed tomography on days 1 and 10. RESULTS: Femoral muscle volumes of 24 control and 26 HMB group participants were analyzed as per protocol. Volumes decreased significantly during days 1-10 (P < 0.0001). Volume loss rates were 14.4 ± 7.1% for control participants and 11.4 ± 8.1% for HMB participants (P = 0.18). In a subgroup of the sequential organ failure assessment scores <10, femoral muscle volume loss was 14.0 ± 6.9% for control participants and 8.7 ± 6.4% for HMB (P = 0.0474). Results of intention-to-treat analysis of the 2 groups showed no differences in basic characteristics or outcomes. CONCLUSIONS: For critically ill patients, HMB complex supplementation from the acute phase of intensive care does not inhibit muscle volume loss.

Pectin-containing liquid enteral nutrition for critical care: a historical control and propensity score matched study.

BACKGROUND AND OBJECTIVES: Pectin-containing liquid enteral nutrition (PCLEN) contains pectin, which becomes solid in the stomach and therefore mitigates vomiting and diarrhea. Its efficacy for use in critical care medicine was evaluated. METHODS AND STUDY DESIGN: We used liquid enteral nutrition (LEN) (traditional LEN (TLEN)) as the primary LEN at the emergency and critical care center. We adopted PCLEN as the primary LEN from 2014. During 2012-2016, 954 patients admitted to intensive care units and emergency wards were given PCLEN or TLEN. We conducted propensity score matching for 693 eligible patients for age, sex, and organ dysfunctions for six organs. RESULTS: We included 199 PCLEN patients and 199 TLEN patients. Severity was higher in the PCLEN group. The enteral nutrition failure rate was significantly lower for PCLEN than for TLEN. The diarrhea incidence rates were 28.1% vs 38.2% (p=0.033), and the incidence rates of nosocomial pneumonia were 4.5% and 9.6% (p=0.048). For PCLEN, the enteral nutrition failure rates were not different for patients with gastric acid inhibitors and without them. CONCLUSIONS: PCLEN can be used effectively for critically ill patients irrespective of the use of gastric acid inhibitors. It can decrease the incidence of enteral nutrition failure and diarrhea.

Hypercalcemia in a Dog with Chronic Ingestion of Maxacalcitol Ointment.

A miniature dachshund male with severe azotemia of unknown cause was referred. Serum biochemistry revealed severe azotemia and hypercalcemia, but serum intact parathormone and parathormone-related protein were normal. Although the owner reported that the dog had never ingested any drugs or supplements, it was revealed that the owner's son used antipsoriatic ointment, maxacalcitol, which contained an active vitamin D3 analogue, daily and the dog often ate the son's dander and licked his skin, especially after he applied the maxacalcitol ointment. After the dog was insulated from the maxacalcitol ointment and the son as much as possible, the hypercalcemia and azotemia improved gradually and had mostly resolved at 3 mo. The dog has been generally free of clinical signs without any treatment for over 2 yr.

Data Mining Methods for Omics and Knowledge of Crude Medicinal Plants toward Big Data Biology.

Molecular biological data has rapidly increased with the recent progress of the Omics fields, e.g., genomics, transcriptomics, proteomics and metabolomics that necessitates the development of databases and methods for efficient storage, retrieval, integration and analysis of massive data. The present study reviews the usage of KNApSAcK Family DB in metabolomics and related area, discusses several statistical methods for handling multivariate data and shows their application on Indonesian blended herbal medicines (Jamu) as a case study. Exploration using Biplot reveals many plants are rarely utilized while some plants are highly utilized toward specific efficacy. Furthermore, the ingredients of Jamu formulas are modeled using Partial Least Squares Discriminant Analysis (PLS-DA) in order to predict their efficacy. The plants used in each Jamu medicine served as the predictors, whereas the efficacy of each Jamu provided the responses. This model produces 71.6% correct classification in predicting efficacy. Permutation test then is used to determine plants that serve as main ingredients in Jamu formula by evaluating the significance of the PLS-DA coefficients. Next, in order to explain the role of plants that serve as main ingredients in Jamu medicines, information of pharmacological activity of the plants is added to the predictor block. Then N-PLS-DA model, multiway version of PLS-DA, is utilized to handle the three-dimensional array of the predictor block. The resulting N-PLS-DA model reveals that the effects of some pharmacological activities are specific for certain efficacy and the other activities are diverse toward many efficacies. Mathematical modeling introduced in the present study can be utilized in global analysis of big data targeting to reveal the underlying biology.

Efficacy prediction of jamu formulations by PLS modeling.

Indonesian herbal medicines made from mixtures of several plants are called "Jamu." The efficacy of a particular Jamu is determined by its ingredients i.e. the composition of the plants. Thus, we modeled the ingredients of Jamu formulas using Partial Least Squares Discriminant Analysis (PLS-DA) in order to predict their efficacy. The plants used in each Jamu medicine served as the predictors, whereas the efficacy of each Jamu provided the responses. Utilizing response predictions obtained from PLS-DA, we predicted the efficacies of Jamu formulations using two methods: maximum response prediction and maximum probability. In predictions of Jamu efficacy, the maximum response prediction method produced a smaller error than that the maximum probability method. Furthermore, utilizing the PLS-DA coefficient matrix, we determined the efficacy for which a plant is most useful, based on its largest coefficients.

KNApSAcK family databases: integrated metabolite-plant species databases for multifaceted plant research.

A database (DB) describing the relationships between species and their metabolites would be useful for metabolomics research, because it targets systematic analysis of enormous numbers of organic compounds with known or unknown structures in metabolomics. We constructed an extensive species-metabolite DB for plants, the KNApSAcK Core DB, which contains 101,500 species-metabolite relationships encompassing 20,741 species and 50,048 metabolites. We also developed a search engine within the KNApSAcK Core DB for use in metabolomics research, making it possible to search for metabolites based on an accurate mass, molecular formula, metabolite name or mass spectra in several ionization modes. We also have developed databases for retrieving metabolites related to plants used for a range of purposes. In our multifaceted plant usage DB, medicinal/edible plants are related to the geographic zones (GZs) where the plants are used, their biological activities, and formulae of Japanese and Indonesian traditional medicines (Kampo and Jamu, respectively). These data are connected to the species-metabolites relationship DB within the KNApSAcK Core DB, keyed via the species names. All databases can be accessed via the website http://kanaya.naist.jp/KNApSAcK_Family/. KNApSAcK WorldMap DB comprises 41,548 GZ-plant pair entries, including 222 GZs and 15,240 medicinal/edible plants. The KAMPO DB consists of 336 formulae encompassing 278 medicinal plants; the JAMU DB consists of 5,310 formulae encompassing 550 medicinal plants. The Biological Activity DB consists of 2,418 biological activities and 33,706 pairwise relationships between medicinal plants and their biological activities. Current statistics of the binary relationships between individual databases were characterized by the degree distribution analysis, leading to a prediction of at least 1,060,000 metabolites within all plants. In the future, the study of metabolomics will need to take this huge number of metabolites into consideration.

Metabolomics of medicinal plants: the importance of multivariate analysis of analytical chemistry data.

Metabolomics, the comprehensive and global analysis of diverse metabolites produced in cells and organisms, has greatly expanded metabolite fingerprinting and profiling as well as the selection and identification of marker metabolites. The methodology typically employs multivariate analysis to statistically process the massive amount of analytical chemistry data resulting from high-throughput and simultaneous metabolite analysis. Although the technology of plant metabolomics has mainly developed with other post-genomics in systems biology and functional genomics, it is independently applied to the evaluation of the qualities of medicinal plants, based on the diversity of metabolite fingerprints resulting from multivariate analysis of non-targeted or widely targeted metabolite analysis. One advantage of applying metabolomics is that medicinal plants are evaluated based not only on the limited number of metabolites that are pharmacologically important chemicals, but also on the fingerprints of minor metabolites and bioactive chemicals. In particular, score plot and loading plot analyses e.g. principal component analysis (PCA), partial-least-squares discriminant analysis (PLS-DA), and discrimination map analysis such as batch-learning self-organizing map (BL-SOM) analysis, are often employed for the reduction of a metabolite fingerprint and the classification of analyzed samples. Based on recent studies, we now understand that metabolomics can be an effective approach for comprehensive evaluation of the qualities of medicinal plants. In this review, we describe practical cases in which metabolomic study was performed on medicinal plants, and discuss the utility of metabolomics for this research field, with focus on multivariate analysis.