Two cyanobacterial response regulators with diguanylate cyclase activity, Rre2 and Rre8, participate in biofilm formation.

Phototrophic bacteria face diurnal variations of environmental conditions such as light and osmolarity that affect their carbon metabolism and ability to generate organic compounds. The model cyanobacterium, Synechocystis sp. PCC 6803 forms a biofilm when it encounters extreme conditions like high salt stress, but the molecular mechanisms involved in perception of environmental changes that lead to biofilm formation are unknown. Here, we studied two two-component regulatory systems (TCSs) that contain diguanylate cyclases (DGCs), which produce the second messenger c-di-GMP, as potential components of the biofilm-inducing signaling pathway in Synechocystis. Analysis of single mutants provided evidence for involvement of the response regulators, Rre2 and Rre8 in biofilm formation. A bacterial two-hybrid assay showed that Rre2 and Rre8 each formed a TCS with a specific histidine kinase, Hik12 and Hik14, respectively. The in vitro assay showed that Rre2 had DGC activity regardless of its de/phosphorylation status, whereas Rre8 required phosphorylation for DGC activity. Hik14-Rre8 likely functioned as an inducible sensing system in response to environmental change. Biofilm assays with Synechocystis mutants suggested that pairs of hik12-rre2 and hik14-rre8 responded to high salinity-induced biofilm formation. Inactivation of hik12-rre2 and hik14-rre8 did not affect the performance of the light reactions of photosynthesis. These data suggest that Hik12-Rre2 and Hik14-Rre8 participate in biofilm formation in Synechocystis by regulating c-di-GMP production via the DGC activity of Rre2 and Rre8.

Zoobiquity experiments show the importance of the local MMP9-plasminogen axis in inflammatory bowel diseases in both dogs and patients.

Using a zoobiquity concept, we directly connect animal phenotypes to a human disease mechanism: the reduction of local plasminogen levels caused by matrix metalloproteinase-9 (MMP9) activity is associated with the development of inflammation in the intestines of dogs and patients with inflammatory bowel disease. We first investigated inflammatory colorectal polyps (ICRPs), which are a canine gastrointestinal disease characterized by the presence of idiopathic chronic inflammation, in Miniature Dachshund (MD) and found 31 missense disease-associated SNPs by whole-exome sequencing. We sequenced them in 10 other dog breeds and found five, PLG, TCOF1, TG, COL9A2 and COL4A4, only in MD. We then investigated two rare and breed-specific missense SNPs (T/T SNPs), PLG: c.477G > T and c.478A>T, and found that ICRPs with the T/T SNP risk alleles showed less intact plasminogen and plasmin activity in the lesions compared to ICRPs without the risk alleles but no differences in serum. Moreover, we show that MMP9, which is an NF-κB target, caused the plasminogen reduction and that intestinal epithelial cells expressing plasminogen molecules were co-localized with epithelial cells expressing MMP9 in normal colons with the risk alleles. Importantly, MMP9 expression in patients with ulcerous colitis or Crohn's disease also co-localized with epithelial cells showing enhanced NF-κB activation and less plasminogen expression. Overall, our zoobiquity experiments showed that MMP9 induces the plasminogen reduction in the intestine, contributing to the development of local inflammation and suggesting the local MMP9-plasminogen axis is a therapeutic target in both dogs and patients. Therefore, zoobiquity-type experiments could bring new perspectives for biomarkers and therapeutic targets.

Regional Collaboration for Heart Failure Patients Certified as Needing Support or Care in Long-Term Care Insurance System.

BACKGROUND: Heart failure (HF) patients with complex care needs often experience exacerbations during the transitional phase as care providers and settings change. Regional collaboration aims to ensure continuity of care; however, its impact on vulnerable patients certified as needing support or care under the Japanese long-term care insurance (LTCI) system remains unclear. METHODS AND RESULTS: We implemented a regional collaborative program for HF patients involving 3 pillars of transitional care with general practitioners and nursing care facilities: (1) standardized health monitoring using a patient diary and identification of exacerbation warning signs; (2) standardized information sharing among care providers; and (3) standardized HF management manuals. We evaluated outcomes within 1 year of discharge for patients hospitalized with HF and referred to other facilities for outpatient follow-up in 2017-2018 before program implementation (n=110) and in 2019-2020 after implementation (n=126). Patients with LTCI frequently received non-cardiologist follow up and care services and had a higher risk of all-cause mortality and HF readmission compared with those without LTCI (P<0.05). Program implementation was significantly associated with a greater reduction in HF readmissions among patients with LTCI compared with those without (P<0.05 for interaction), although mortality rates remained unchanged. CONCLUSIONS: A regional collaborative program significantly reduces HF readmissions in HF patients with LTCI who are at high risk of worsening HF.

The polymyxin-B direct hemoperfusion OPTimal Initiation timing with Catecholamine PMX-OPTIC study: A multicenter retrospective observational study.

BACKGROUND: Polymyxin-B direct hemoperfusion (PMX-DHP) is an endotoxin adsorption column-based blood purification therapy. Since one of the most potent effects of PMX-DHP is blood pressure elevations, it may be the most effective when it is introduced at the time when the need for vasopressors is the greatest, which, in turn, may reduce mortality. METHODS: A multicenter retrospective study was conducted at 24 ICUs in Japan. In each ICU, the 20 most recent consecutive cases of septic shock treated with PMX-DHP were analyzed. The duration between the time of the peak vasopressive agent dose, expressed as the noradrenaline equivalent dose (NEq), and the time of PMX initiation was evaluated. The primary outcome was 28-day mortality, and a multivariable analysis was performed to investigate factors associated with mortality. RESULTS: A total of 480 septic shock patients were included in the analysis. Among all patients, the 28-day mortality group was older, more severely ill, and had a higher body mass index. The NEq peak and NEq on PMX-DHP initiation were both higher in deceased patients. Regarding the timing of PMX-DHP initiation from the NEq peak, -4 << 4 h had more survivors (229/304, 75.3%) than ≤-4 h (50/75, 66.7%) and ≥4 h (66/101, 65.4%) (p = 0.085). When -4 << 4 h was assigned as a reference, the timing of PMX-DHP initiation from the NEq peak of ≤-4 h had an odds ratio of 1.96 (1.07-3.58), p = 0.029, while ≥4 h had an odds ratio of 1.64 (0.94-2.87), p = 0.082 for 28-day mortality, in the multivariable regression analysis. A spline curve of the relationship between the probability of death and the timing of PMX-DHP initiation from the NEq peak showed a downward convex curve with a nadir at timing = 0. The odds ratios of the timing of PMX-DHP initiation other than -4 << 4 h were significantly higher in an older age, male sex, lower BMI, more severe illness, and higher oxygenation. CONCLUSIONS: The induction of PMX-DHP at the time of the peak vasopressor dose correlated with lower mortality. PMX-DHP is one of the options available for elevating blood pressure in septic shock, and its initiation either too early or late for shock peak may not improve the outcome.

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.

Relationship between critical care nutrition and post-intensive care syndrome in surviving ventilated patients with COVID-19: a multicenter prospective observational study.

The impact of nutrition therapy in the acute phase on post-intensive care syndrome (PICS) remains unclear. We conducted a multicenter prospective study on adult patients with COVID-19 who required mechanical ventilation for more than three days. The questionnaire was mailed after discharge. Physical PICS, defined as less than 90 points on the Barthel index (BI), was assigned as the primary outcome. We examined the types of nutrition therapy in the first week that affected PICS components. 269 eligible patients were evaluated 10 months after discharge. Supplemental parenteral nutrition (SPN) >400 kcal/day correlated with a lower occurrence of physical PICS (10% vs 21.92%, p = 0.042), whereas the amounts of energy and protein provided, early enteral nutrition, and a gradual increase in nutrition delivery did not, and none correlated with cognitive or mental PICS. A multivariable regression analysis revealed that SPN had an independent impact on physical PICS (odds ratio 0.33, 95% CI 0.12-0.92, p = 0.034), even after adjustments for age, sex, body mass index and severity. Protein provision ≥1.2 g/kg/day was associated with a lower occurrence of physical PICS (odds ratio 0.42, 95% CI 0.16-1.08, p = 0.071). In conclusion, SPN in the acute phase had a positive impact on physical PICS for ventilated patients with COVID-19.

Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for adult convulsive status epilepticus: a multicentre non-inferiority randomised control trial.

OBJECTIVE: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is crucial. Although fosphenytoin (FPHT) is recommended as a second-line treatment, levetiracetam (LEV) reportedly has similar efficacy, but higher safety. Therefore, we herein compared LEV with FPHT in adult SE. METHODS: We initiated a multicentre randomised control trial in emergency departments with adult patients with convulsive SE. Diazepam was initially administered, followed intravenously by FPHT at 22.5 mg/kg or LEV at 1000-3000 mg. The primary outcome was assigned as the seizure cessation rate within 30 min of the administration of the study drug. RESULTS: A total of 176 adult patients with SE were enrolled (82 FPHT and 94 LEV), and 3 were excluded from the full analysis set. Seizure cessation rates within 30 min were 83.8% (67/80) in the FPHT group and 89.2% (83/93) in the LEV group. The difference in these rates was 5.5% (95% CI -4.7 to 15.7, p=0.29). The non-inferiority of LEV to FPHT was confirmed with p<0.001 by the Farrington-Manning test. No significant differences were observed in the seizure recurrence rate or intubation rate within 24 hours. Serious adverse events developed in three patients in the FPHT group and none in the LEV group (p=0.061). CONCLUSION: The efficacy of LEV was similar to that of FPHT for adult SE following the administration of diazepam. LEV may be recommended as a second-line treatment for SE along with phenytoin/FPHT. TRIAL REGISTRATION NUMBER: jRCTs031190160.

The Vasopressin Loading for Refractory septic shock (VALOR) study: a prospective observational study.

BACKGROUND: Vasopressin is a second-line vasoactive agent for refractory septic shock. Vasopressin loading is not generally performed because of the lack of evidence for its effects and safety. However, based on our previous findings, we hypothesized it can predict the responsibility to vasopressin infusion with safety, and prospectively examined it in the present study. METHODS: Vasopressin loading was performed via the intravenous administration of a bolus of 1 U, followed by its continuous infusion at 1U/h in patients with septic shock treated with ≥ 0.2 µg/kg/min noradrenaline. An arterial pressure wave analysis was conducted, and endocrinological tests were performed immediately prior to vasopressin loading. We classified patients into responders/non-responders based on mean arterial pressure (MAP) changes after vasopressin loading. Based on our previous findings, the lower tertile of MAP changes was selected as the cut-off. The change in the catecholamine index (CAI) after 6 h was assigned as the primary outcome. Digital ischemia, mesenteric ischemia, and myocardial ischemia during the admission period were prospectively and systematically recorded as adverse events. RESULTS: Ninety-two patients were registered during the study period and examined. Sixty-two patients with a MAP change > 22 mmHg were assigned as responders and the others as non-responders. Blood adrenocorticotropic hormone levels were significantly higher in non-responders. Stroke volume variations were higher in responders before loading, while stroke volume and dP/dtmax were higher in responders after loading. Median CAI changes were - 10 in responders and 0 in non-responders, which was significantly lower in the former (p < 0.0001). AUROC of MAP change with vasopressin loading to predict CAI change < 0 after continuous infusion was 0.843 with sensitivity of 0.92 and specificity of 0.77. Ischemia events were observed in 5 cases (5.4%). CONCLUSIONS: Vasopressin loading may be safely introduced for septic shock. Vasopressin loading may be used to predict responses to its continuous infusion and select appropriate strategies to increase blood pressure.

Instruments to assess post-intensive care syndrome assessment: a scoping review and modified Delphi method study.

BACKGROUND: The assessment of post-intensive care syndrome (PICS) is challenging due to the numerous types of instruments. We herein attempted to identify and propose recommendations for instruments to assess PICS in intensive care unit (ICU) survivors. METHODS: We conducted a scoping review to identify PICS follow-up studies at and after hospital discharge between 2014 and 2022. Assessment instruments used more than two times were included in the modified Delphi consensus process. A modified Delphi meeting was conducted three times by the PICS committee of the Japanese Society of Intensive Care Medicine, and each score was rated as not important (score: 1-3), important, but not critical (4-6), and critical (7-9). We included instruments with ≥ 70% of respondents rating critical and ≤ 15% of respondents rating not important. RESULTS: In total, 6972 records were identified in this scoping review, and 754 studies were included in the analysis. After data extraction, 107 PICS assessment instruments were identified. The modified Delphi meeting reached 20 PICS assessment instrument recommendations: (1) in the physical domain: the 6-min walk test, MRC score, and grip strength, (2) in cognition: MoCA, MMSE, and SMQ, (3) in mental health: HADS, IES-R, and PHQ-9, (4) in the activities of daily living: the Barthel Index, IADL, and FIM, (5) in quality of life: SF-36, SF-12, EQ-5D-5L, 3L, and VAS (6), in sleep and pain: PSQI and Brief Pain Inventory, respectively, and (7) in the PICS-family domain: SF-36, HADS, and IES-R. CONCLUSION: Based on a scoping review and the modified Delphi method, 20 PICS assessment instruments are recommended to assess physical, cognitive, mental health, activities of daily living, quality of life, sleep, and pain in ICU survivors and their families.

Explorative Clustering of the Nitrogen Balance Trajectory in Critically Ill Patients: A Preliminary post hoc Analysis of a Single-Center Prospective Observational Study.

BACKGROUND: The nitrogen balance estimates a protein net difference. However, since it has a number of limitations, it is important to consider the trajectory of the nitrogen balance in the clinical course of critically ill patients. OBJECTIVES: We herein exploratively classified the nitrogen balance trajectory using a machine learning method. METHOD: This is a post hoc analysis of a single-center prospective study for the patients admitted to our Emergency and Critical Center ICU. The nitrogen balance was evaluated with 24-h urine collection from ICU days 1-10 with 9 points. K-means clustering was performed to classify the nitrogen balance trajectory. We also evaluated factors associated with uncovered clusters. RESULTS: Seventy-six eligible patients were included in the present study. After clustering, the nitrogen balance trajectory was classified into 4 classes. Class 1 was trajected as a negative balance over 10 days (24 patients). Class 2 had a positive conversion on day 3 or 4 (8 patients). Class 3 had a positive conversion on day 8 or 9 (28 patients). Class 4 initially had a positive balance and then converted to a negative balance (16 patients). Sepsis complication and steroid use were associated with negative nitrogen balance trajectory. Class 2 was associated with lower length of hospital stay and femoral muscle volume loss, however, frequently had frailty and sarcopenia on admission. Active nutrition therapy intention was not correlated with positive trajectory. CONCLUSIONS: The nitrogen balance trajectory in critically ill patients may be classified into 4 classes for clinical practice. Among patients emergently admitted to the ICU, the positive conversion of the nitrogen balance might be delayed over 10 days.

The nitrogen load is affected by high protein provision according to kidney function in critically ill patients.

Adequate protein delivery is recommended in the acute phase of critical illness with kidney dysfunction. However, the influence of the protein and nitrogen loads has not yet been clarified. Patients admitted to the intensive care unit were included. In the former period, patients received standard care (0.9 g/kg/day protein). In the latter, patients received the intervention of active nutrition therapy with high protein delivery (1.8 g/kg/day protein). Fifty patients in the standard care group and 61 in the intervention group were examined. Maximum blood urea nitrogen (BUN) on days 7-10 were 27.9 (17.3, 38.6) vs 33 (26.3, 51.8) (mg/dl) (p = 0.031). The maximum difference in BUN increased [31.3 (22.8, 55) vs 50 (37.3, 75.9) mg/dl (p = 0.047)] when patients were limited to an estimated glomerular filtration rate (eGFR) <50 ml/min/1.73 m2. This difference increased further when patients were limited to eGFR <30 ml/min/1.73 m2. No significant differences were observed in maximum Cre or in the use of RRT. In conclusion, the provision of 1.8 g/kg/day protein was associated with an increase in BUN in critically ill patients with kidney dysfunction; however, it was tolerated without the need for RRT.

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.

Mobilization and Rehabilitation Practice in ICUs During the COVID-19 Pandemic.

BACKGROUND: Mobilization and acute rehabilitation are essential in the intensive care unit (ICU), with substantial evidence supporting their benefits. This study aimed to characterize ICU mobilization practices during the COVID-19 pandemic for patients with and without COVID-19. METHODS: This was a secondary analysis of an international point prevalence study. All ICUs across the world were eligible to participate and were required to enroll all patients in each ICU on the survey date, 27 January 2021. The primary outcome was the achievement of mobilization at the level of sitting over the edge of the bed. Independent factors associated with mobilization, including COVID-19 infection, were analyzed by multivariable analysis. RESULTS: A total of 135 ICUs in 33 countries participated, for inclusion of 1229 patients. Among patients who were not receiving mechanical ventilation (MV), those with COVID-19 infection were mobilized more than those without COVID-19 (60% vs. 34%, p < 0.001). Among patients who were receiving MV, mobilization was low in both groups (7% vs. 9%, p = .56). These findings were consistent irrespective of ICU length of stay. Multivariable analysis showed that COVID-19 infection was associated with achievement of mobilization in patients without (adjusted odds ratio [aOR] = 4.48, 95% confidence interval [CI] = 2.71-7.42) and with MV (aOR = 2.13, 95% CI = 1.00-4.51). Factors that prevented mobilization were prone positioning in patients without MV and continuous use of neuromuscular blockade and sedation agents in patients with MV, whereas facilitating factors were the presence of targets/goals in both groups. CONCLUSION: Mobilization rates for ICU patients across the globe are severely low, with the greatest immobility observed in mechanically ventilated patients. Although COVID-19 is not an independent barrier to the mobilization of patients with or without MV, this study has highlighted the current lack of mobility practice for all ICU patients during the COVID-19 pandemic.(299 words).

Performance of the new FilmArray Blood Culture Identification 2 panel and its potential impact on clinical use in patients with Gram-negative bacteremia.

INTRODUCTION: Rapid diagnostic tests have been developed recently for rapid species or resistance genes identification, offering the potential to improve the selection of appropriate antibiotics. The newly developed FilmArray Blood Culture Identification 2 (BCID2) panel, which can identify more species and resistance genes, such as extended-spectrum beta-lactamase, is expected to make an impact on antimicrobial practice. METHODS: The consecutive 50 inpatients with Gram-negative bacilli bacteremia were enrolled to this retrospective single-center study. In addition to the existing FilmArray Blood Culture Identification (BCID) panel, we have implemented BCID2 panel for positive blood culture. The sensitivity and specificity of BCID and BCID2 panel were respectively calculated, and a simulation study of time to effective, optimal and de-escalation therapy was performed based on BCID or BCID2 result. RESULTS: A total of 52 Gram-negative organisms in 50 patients were identified from blood cultures. Of these, 45 (87%) organisms were detected by BCID2 panel, which was more than BCID panel (41 organisms, 79%). BCID2 panel detected 5 CTX-M genes, which were concordant with conventional method. The time to effective therapy did not differ between BCID arm and BCID2 arm; however, the median time to optimal therapy (34 h in BCID arm and 26 h in BCID2 arm, P = 0.0007) and the median time to de-escalation therapy (42 h in BCID arm and 22 h in BCID2 arm, P = 0.0005) were significantly shortened. CONCLUSIONS: This simulation study of BCID2 panel showed high sensitivity and specificity, and the potential impact on shortening the time to optimal and de-escalation therapy.

Effective Synthesis and Antifouling Activity of Dolastatin 16 Derivatives.

Some derivatives of dolastatin 16, a depsipeptide natural product first obtained from the sea hare Dolabella auricularia, were synthesized through second-generation synthesis of two unusual amino acids, dolaphenvaline and dolamethylleuine. The second-generation synthesis enabled derivatizations such as functionalization of the aromatic ring in dolaphenvaline. The derivatives of fragments and whole structures were evaluated for antifouling activity against the cypris larvae of Amphibalanus amphitrite. Small fragments inhibited the settlement of the cypris larvae at potent to moderate concentrations (EC50 = 0.60-4.62 µg/mL), although dolastatin 16 with a substituent on the aromatic ring (24) was much less potent than dolastatin 16.

Simple Score to Predict Treatment Response to Low-Dose Tolvaptan in Patients with Heart Failure.

The recommended starting dose of Tolvaptan for heart failure (HF) is 7.5 mg/day in Japan; the recommended dose is 3.75 mg/day for older patients to avoid excessive diuresis and hypernatremia. However, low-dose Tolvaptan may delay the release of congestion in some patients. We aimed to develop a score to predict treatment responders to 3.75 mg tolvaptan.We retrospectively analyzed 106 patients with HF who initially received 3.75 mg/day of Tolvaptan in the derivation cohort (April 2013-December 2017) and 63 patients receiving 3.75 mg/day of Tolvaptan in the validation cohort (January 2018-April 2021). Treatment responders to 3.75 mg tolvaptan did not require dose escalation of Tolvaptan for congestion relief. In multivariate analysis, blood urea nitrogen (BUN) < 39 mg/dL and hematocrit > 35% were selected as variables to predict treatment responders. These were assigned 1 point each, and patients were stratified into groups with 2 points (n = 32), 1 point (n = 39), and 0 points (n = 35). The frequency of treatment responders was 82.9% in the 2-point group, 61.5% in the 1-point group, and 34.4% in the 0-point group (P < 0.05). The predictive ability of the score was acceptable with an area under the receiving operator characteristic curve (AUC) 0.726 (P < 0.05); its performance was maintained in the validation cohort (AUC 0.733, P < 0.05).A simple score using BUN and hematocrit could identify treatment responders to 3.75 mg tolvaptan, which may help determine the appropriate starting dose of Tolvaptan, balancing efficiency with safety for older patients with HF.

Resolution of Signs of Epiglottic Retroversion Following Medical Management of Hyperadrenocorticism in a Dog.

A 6 yr old spayed female Chihuahua was referred for a 10 mo history of chronic respiratory compromise. Decreased serum thyroxine and thyroid-stimulating hormone concentrations had been confirmed at a primary clinic, but no treatment was initiated. Serum biochemistries revealed elevated alkaline phosphatase and cholesterol concentrations. An adrenocorticotropic hormone-stimulating test revealed elevated preserum and postserum cortisol concentrations. Fluoroscopy revealed marked epiglottic retroversion (ER) during inhalation. Enlarged bilateral adrenal glands were found on abdominal ultrasonography. Based on these findings, ER and hyperadrenocorticism (HAC) were diagnosed and surgical correction of the ER was planned. Trilostane administration was initiated before surgery to reduce the risk of thrombosis due to HAC. Seven days after the initiation of trilostane therapy, clinical signs of chronic respiratory compromise were resolved. The patient had remained clinically stable without recurrence of respiratory compromise for at least 15 mo at the time of this case report. This case suggests that HAC could contribute to the development of clinical signs of ER, which could potentially be successfully controlled by medical treatment of HAC.

Impact of oligomeric enteral nutrition with low-molecular-weight whey peptides on diarrhea in critical care nutrition.

Diarrhea is one of the most common complications associated with enteral nutrition in hospitalized patients. Oligomeric enteral nutrition has been considered to reduce the incidence of diarrhea. We herein introduced and examined the effects of a specific oligomeric enteral nutrition with the low-molecular-weight whey peptides, Peptino|® in critically ill patients with refractory diarrhea or at high risk of mesenteric ischemia. A retrospective study of a consecutive case series was conducted. Patients were divided into two groups: enteral nutrition products were switched to Peptino|® (switching group) and Peptino|® was the initial enteral nutrition product (first initiation group). Sixty-eight patients were administered Peptino|® in the ICU. Diarrhea occurred in 28.3% of patients in the switching group and 13.3% in the first initiation group. EN failure with gastrointestinal intolerance was observed in 6 patients (8.8%). Diarrhea resolved in 29 out of the 35 patients (82.9%) with diarrhea prior to the switch to Peptino|®. Diarrhea cessation within 24 h of the initiation of Peptino|® was achieved in 11 patients (31.4%) and within 24-48 h in 12 (34.3%). Mesenteric ischemia was not detected in any patients. In conclusion, Peptino|® may be effective against diarrhea and gastrointestinal intolerance in critical care nutrition.

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).

Clinical performance of early warning scoring systems for identifying sepsis among anti-hypertensive agent users.

BACKGROUND: Little is known about the accuracy of the quick Sequential Organ Failure Assessment (qSOFA) and the National Early Warning Score (NEWS) in identifying sepsis patients with a history of hypertension on anti-hypertensive agents, which affect vital signs as components of the scoring systems. We aimed to examine the ability of qSOFA and NEWS to predict sepsis among anti-hypertensive agent users by comparing them with non-users. METHODS: We retrospectively identified adult patients (aged ≥18years) with suspected infection who presented to an emergency department (ED) of a large tertiary medical center in Japan between April 2018 and March 2020. Suspected infection was defined based on the chief complaint of fever, high body temperature, or the clinical context on arrival at the ED. We excluded patients who had trauma or cardiac arrest, those who were transported to other hospitals after arrival at the ED, and those whose vital signs data were mostly missing. The predictive performances of qSOFA and NEWS based on initial vital signs were examined separately for sepsis, ICU admission, and in-hospital mortality and compared between anti-hypertensive agent users and non-users. RESULTS: Among 2900 patients with suspected infection presenting to the ED, 291 (10%) had sepsis, 1023 (35%) were admitted to the ICU, and 188 (6.5%) died. The prediction performances of qSOFA and NEWS for each outcome among anti-hypertensive agent users were lower than that among non-users (e.g., c-statistics of qSOFA for sepsis, 0.66 vs. 0.71, p = 0.07; and for ICU admission, 0.70 vs. 0.75, p = 0.01). For identifying sepsis, the sensitivity and specificity of qSOFA ≥2 were 0.43 and 0.77 in anti-hypertensive agent users and 0.51 and 0.82 in non-users. Similar associations were observed for identifying ICU admission and in-hospital mortality. Regardless of the use of anti-hypertensive agents, NEWS had better prediction abilities for each outcome than qSOFA. CONCLUSION: The clinical performance of qSOFA and NEWS for identifying sepsis among anti-hypertensive agent users was likely lower than that among non-users.