SACrA score to predict the initiation of renal replacement therapy in critically ill patients: a single-center retrospective study.

BACKGROUND: Acute kidney injury (AKI) is a prevalent complication in critically ill patients that affects the timing of renal replacement therapy (RRT) initiation. This study aimed to develop and validate the SACrA score for predicting non-emergent initiations (BUN ≥112 mg/dL or oliguria for >72 h) of RRT in critically ill patients. METHODS: We conducted a retrospective cohort study using data from two cohorts. The derivation cohort included patients admitted to the ICU between November 2021 and December 2023, whereas the validation cohort included patients admitted between September 2019 and October 2021. The primary outcome was non-emergent RRT initiation. The multivariate logistic regression with stepwise selection based on the Akaike information criterion finalized the model, including the variables, such as sex, albumin (Alb), creatinine (Cr), and APACHE II score (SACrA). RESULTS: The derivation and validation cohorts comprised 470 and 476 patients, respectively. The SACrA score showed a strong predictive performance for non-emergent RRT initiation in both the cohorts. Cohort 1 had an ROC-AUC of 0.971, with a calibration slope of 0.982 and an intercept of 0.009, whereas cohort 2 had an ROC-AUC of 0.918, with a calibration slope of 0.988 and an intercept of 0.004. CONCLUSIONS: The SACrA score is a robust tool for predicting non-emergent RRT initiation in critically ill patients using readily available clinical variables. Though additional data are needed to validate the SACrA score, our analysis suggests the tool may help clinicians make informed decisions, reduce unnecessary RRT, and thereby improve patient outcomes.

Early Mobilization Using a Mobile Patient Lift in the ICU: A Randomized Controlled Trial.

OBJECTIVES: To ascertain whether a mobile patient lift facilitates early mobilization in ventilated ICU patients. DESIGN: A single-center, open-label, randomized controlled trial. SETTING: An academic ICU in Tokyo. PATIENTS: Eighty patients were admitted to ICU and expected ventilation for at least 48 hours. INTERVENTIONS: In the intervention group, in addition to the rehabilitation protocol received by the control group, patients were assisted in sitting, standing, transfers, and walking using the mobile patient lift. MEASUREMENTS AND MAIN RESULTS: The intervention group predominantly stood faster than the control group (1.0 vs. 3.0 d, p < 0.01). The Intervention group also had significantly higher Functional Status Score-ICU scores at ICU discharge. However, the Medical Research Council score and Barthel index at discharge, length of ICU stay, and number of ventilator-free days did not differ between the two groups. CONCLUSIONS: The use of mobile patient lifts facilitates the earlier standing of patients on ventilators. This may contribute to patients improved physical function in the ICU. TRIAL REGISTRATION: The study protocol was registered with the University Hospital Medical Information Network (UMIN) under the registration number UMIN000044965. Registered July 30, 2021.

Is epigenome editing non-inheritable? Implications for ethics and the regulation of human applications.

Epigenome editing offers ethical advantages with non-inheritable gene expression control. However, concerns arise regarding potential transgenerational effects in humans. Ethical and regulatory evaluation is crucial, considering recent advancements and enhanced understanding of transgenerational epigenetics in both mammals and humans.

A simplified model to estimate nonlinear turbulent transport by linear dynamics in plasma turbulence.

A simplified model to estimate nonlinear turbulent transport only by linear calculations is proposed, where the turbulent heat diffusivity in tokamak ion temperature gradient(ITG) driven turbulence is reproduced for a wide parameter range including near- and far-marginal ITG stability. The optimal nonlinear functional relation(NFR) between the turbulent diffusivity, the turbulence intensity [Formula: see text], and the zonal-flow intensity [Formula: see text] is determined by means of mathematical optimization methods. Then, an extended modeling for [Formula: see text] and [Formula: see text] to incorporate the turbulence suppression effects and the temperature gradient dependence is carried out. The simplified transport model is expressed as a modified nonlinear function composed of the linear growth rate and the linear zonal-flow decay time. Good accuracy and wide applicability of the model are demonstrated, where the regression error of [Formula: see text] indicates improvement by a factor of about 1/4 in comparison to that in the previous works.

Improved Neurological Outcome of Perampanel for Hypoxic-Ischemic Encephalopathy in Patients After Out-of-Hospital Cardiac Arrest Resuscitation.

BACKGROUND: Although the resuscitation rate for out-of-hospital cardiac arrest (OHCA) patients in Japan is increasing due to the widespread use of automated external defibrillators, the proportion of patients who can return to society remains low at approximately 7%. Many patients have poor neurological outcomes and cannot return to society because of post-resuscitation hypoxic-ischemic encephalopathy. While the resumption of cardiac rhythm is important for patients with OHCA, improving neurological outcomes and returning to society are also important. OBJECTIVES: To investigate whether perampanel, an antiepileptic drug that provides neurological protection against stroke and head injury, could improve neurological outcomes in patients resuscitated after OHCA. METHODS: The participants included 33 patients with OHCA admitted to our hospital from January 2021 to June 2022 and 33 patients admitted before that time. Perampanel was administered to the patients in the intervention group immediately after resuscitation. We defined a Cerebral Performance Category (CPC) score of 1.2 as a good neurological outcome. RESULTS: There was no significant difference in neurological outcomes at intensive care unit discharge between the intervention and non-intervention groups (number of CPC 1.2: 16/33 vs. 9/33); however, neurological outcomes at hospital discharge were significantly better in the intervention group (number of CPC 1.2: 19/33 vs. 9/33 P = 0.01). CONCLUSION: The α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor inhibitory and neuronal protective effects of perampanel may have inhibited the progression of hypoxic-ischemic encephalopathy, which develops after the resumption of cardiac rhythm, and suppressed neuronal damage. Early administration of perampanel after resuscitation of patients with OHCA may improve neurological outcomes.

Use of Maximum Tongue Pressure Values to Examine the Presence of Dysphagia after Extubation and Prevent Aspiration Pneumonia in Elderly Emergency Patients.

Background: Tongue pressure values in patients with dysphagia are reported to be significantly lower than those in healthy controls. The aim of this study was to measure the maximum tongue pressure (MTP) values after extubation in order to assess the presence of post-extubation dysphagia for the safe initiation of oral intake in elderly patients. Methods: Data from 90 patients who were extubated after mechanical ventilation under tracheal intubation were collected retrospectively. The patients were divided into two groups as follows: normal group (those who did not develop aspiration pneumonia after extubation; median age 62 years) and aspiration group (those who developed aspiration during the evaluation period; median age 75 years). The MTP values were measured at 6 h, 24 h, 3 days, and 7 days after extubation. Results: The values were significantly increased 24 h after extubation in the normal group (p < 0.05). Alternatively, no increase was observed even after 1 week of extubation in the aspiration group, and the values were significantly lower than those in the normal group. The cutoff values at 6 and 24 h after extubation, which were measured using the receiver operator characteristic (ROC) curve, were 17.8 and 23.2 kpa, respectively; furthermore, the results of these assessments were strongly related to the development of aspiration 6 h after extubation (χ2-value: 6.125; p = 0.0133). Conclusions: The presence of post-extubation dysphagia in patients who are intubated for ≥24 h can be predicted based on age and the MTP values at 6 h after extubation.

Urinary liver-type fatty acid-binding protein: A hemodynamic index during extracorporeal membrane oxygenation.

We discuss a case in which urinary L-FABP measurements were used to manage a 46-year-old male patient receiving V-A ECMO support. His mean blood pressure was ≥75 mmHg for the first 24 h after the initiation of V-A ECMO, and he experienced a rapid decrease in urinary L-FABP levels.

Intramucosal esophageal dissection caused by gastric tube insertion.

We experienced a case of iatrogenic intramucosal esophageal dissection in a patient who had difficulty inserting a gastric tube. CT is useful for diagnosis.

Heart Rate and Mortality After Resuscitation in Patients With Out-of-Hospital Cardiac Arrest　- Insights From the SOS-KANTO Registry.

BACKGROUND: Heart rate (HR) predicts outcomes in patients with acute coronary syndrome (ACS), whereas the impact of HR on outcomes after out-of-hospital cardiac arrest (OHCA) remains unclear. This study aimed to investigate the impact of HR after resuscitation on outcomes after OHCA and whether the impact differs with OHCA etiology.Methods and Results: Of 16,452 patients suffering from OHCA, this study analyzed 741 adults for whom HR after resuscitation was recorded by 12-lead electrocardiogram upon hospital arrival. Etiology of OHCA was categorized into 3 groups: ACS, non-ACS, and non-cardiac. Patients in each etiology group were further divided into tachycardia (>100 beats/min) and non-tachycardia (≤100 beats/min). The impact of HR on outcomes was evaluated in each group. Among the 741 patients, the mean age was 67.6 years and 497 (67.1%) patients were male. The primary outcome - 3-month all-cause mortality - was observed in 55.8% of patients. Tachycardia after resuscitation in patients with ACS was significantly associated with higher all-cause mortality at 3 months (P=0.002), but there was no significant association between tachycardia and mortality in non-ACS and non-cardiac etiology patients. In a multivariate analysis model, the incidence of tachycardia after resuscitation independently predicted higher 3-month all-cause mortality in OHCA patients with ACS (hazard ratio: 2.17 [95% confidence interval: 1.05-4.48], P=0.04). CONCLUSIONS: Increased HR after resuscitation was associated with higher mortality only in patients with ACS.

Early mobilisation using a mobile patient lift in the intensive care unit: protocol for a randomised controlled trial.

INTRODUCTION: It is important to prevent the deterioration of activities of daily living to improve the long-term prognoses of patients in the intensive care unit (ICU). The patients' conditions, along with the lack of human and technical resources, often become barriers to achieving early mobilisation after the introduction of mechanical ventilation. We plan to verify the usefulness of a mobile patient lift for early mobilisation. METHODS AND ANALYSIS: We will conduct a single-centre, open-label, randomised controlled trial. The inclusion criteria are as follows: age ≥18 years, independent walking before admission and expected mechanical ventilation for at least 48 hours. The participants will be randomly divided into groups with (intervention group) or without (control group) a mobile lift protocol. A mobile lift will be used in the intervention group. The primary endpoint will be the number of days required to achieve an ICU mobility scale of ≥4 (standing position). The results of the two groups will be analysed using the Student's t-test. ETHICS AND DISSEMINATION: This study will be conducted in accordance with the Declaration of Helsinki and with the approval of the Toho University Omori Medical Center Ethics Committee (approval number M20259). The results of this study will be presented internationally at academic conferences and published in the literature. TRIAL REGISTRATION NUMBER: UMIN000044965.

Association of red blood cell and platelet transfusions with persistent inflammation, immunosuppression, and catabolism syndrome in critically ill patients.

The objective of this single-center retrospective cohort study was to investigate the relationship between blood transfusion and persistent inflammation, immunosuppression, and catabolism syndrome (PIICS). The study was conducted at the Critical Care Center at Toho University Omori Medical Center, Japan. We included 391 patients in the PIICS group (hospitalization for > 15 days, C-reactive protein > 3.0 mg/dL or albumin < 3.0 mg/dL or lymph < 800/µL on day 14) and 762 patients in the non-PIICS group (hospitalization for > 15 days and not meeting the PIICS criteria). We performed univariate and multivariate logistic regression analyses using PIICS as the objective variable and red blood cell (RBC) or fresh frozen plasma or platelet (PLT) transfusion and other confounding factors as explanatory variables. In addition, we conducted a sensitivity analysis using propensity score matching analysis. The multivariate and propensity score analyses showed that RBC and PLT transfusions were significantly associated with PIICS. This is the first study to report an association between RBC and PLT transfusions and PIICS. Our findings have contributed to better understanding the risk factors of PIICS and suggest that physicians should consider the risk of PIICS occurrence when administering blood transfusions in intensive care unit (ICU) patients.

Penetrating vertebral artery injury treated by combining the "zone" approach and imaging tests: A case report.

Patients with vertebral artery injury from penetrating neck trauma may not present with signs of vascular injury because of anatomical characteristics and concomitant conditions, such as hypothermia and shock. If patients are hemodynamically stable, imaging tests should be performed to examine the posterior components, including the vertebral artery.

Urinary liver-type fatty acid-binding protein variation as a predictive value of short-term mortality in intensive care unit patients.

BACKGROUND: Predicting the prognosis of intensive care unit (ICU) patients is crucial because it may lead to patient stratification that would in turn help in appropriately distributing limited medical resources. This study, therefore, aimed to investigate the use of the urinary liver-type fatty acid-binding protein (L-FABP) semi-quantitative kit in rapidly predicting the prognosis of patients admitted to the ICU. METHODS: We conducted a single-center, prospective, observational study wherein 100 consecutive patients admitted to the ICU with an indwelling bladder catheter were enrolled between April and October 2020. Urine specimens were collected at the time of admission (T1) and after 6 h (T2), and urinary L-FABP levels were semi-quantitatively measured. Based on the results, an L-FABP variation was defined as the change in L-FABP (negative, weakly positive, or strongly positive) from T1 to T2. Patients were divided into three groups (L-FABP decreased group, unchanged group, or increased group), following which we compared their 14-day mortality. RESULTS: Finally, a total of 79 patients were included in the analysis. In multivariate analysis, urinary L-FABP variation [Odds ratio (OR) = 14.327, 95% confidence interval (CI) = 1.819-112.868, p = 0.01] and lactate (OR = 1.234, 95%CI = 1.060-1.437, p = 0.01) were significantly associated with 14-day mortality. CONCLUSION: Urinary L-FABP variation at 6 h after admission was significantly associated with 14-day mortality.

Characterization of hiPSC-Derived Muscle Progenitors Reveals Distinctive Markers for Myogenic Cell Purification Toward Cell Therapy.

The transplantation of muscle progenitor cells (MuPCs) differentiated from human induced pluripotent stem cells (hiPSCs) is a promising approach for treating skeletal muscle diseases such as Duchenne muscular dystrophy (DMD). However, proper purification of the MuPCs before transplantation is essential for clinical application. Here, by using MYF5 hiPSC reporter lines, we identified two markers for myogenic cell purification: CDH13, which purified most of the myogenic cells, and FGFR4, which purified a subset of MuPCs. Cells purified with each of the markers showed high efficiency for regeneration after transplantation and contributed to the restoration of dystrophin expression in DMD-immunodeficient model mice. Moreover, we found that MYF5 regulates CDH13 expression by binding to the promoter regions. These findings suggest that FGFR4 and CDH13 are strong candidates for the purification of hiPSC-derived MuPCs for therapeutical application.

A case of cardiopulmonary arrest due to left ventricular free wall rupture successfully treated with sutureless repair supported by venoarterial extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation for cardiopulmonary arrest due to left ventricular free wall rupture is considered effective, because it enables rapid cardiopulmonary support and introduction of targeted temperature management.

Plasma filtration with dialysis for the treatment of capillary leak syndrome occurring secondary to surgery for colon cancer-related perforating peritonitis.

The use of plasma filtration with dialysis (PDF) may be considered when treating the acute phase of capillary leak syndrome (CLS). To the best of our knowledge, this is the first report using PDF for CLS.

Nanopore direct RNA sequencing detects DUX4-activated repeats and isoforms in human muscle cells.

Facioscapulohumeral muscular dystrophy (FSHD) is an inherited muscle disease caused by misexpression of the DUX4 gene in skeletal muscle. DUX4 is a transcription factor, which is normally expressed in the cleavage-stage embryo and regulates gene expression involved in early embryonic development. Recent studies revealed that DUX4 also activates the transcription of repetitive elements such as endogenous retroviruses (ERVs), mammalian apparent long terminal repeat (LTR)-retrotransposons and pericentromeric satellite repeats (Human Satellite II). DUX4-bound ERV sequences also create alternative promoters for genes or long non-coding RNAs, producing fusion transcripts. To further understand transcriptional regulation by DUX4, we performed nanopore long-read direct RNA sequencing (dRNA-seq) of human muscle cells induced by DUX4, because long reads show whole isoforms with greater confidence. We successfully detected differential expression of known DUX4-induced genes and discovered 61 differentially expressed repeat loci, which are near DUX4-ChIP peaks. We also identified 247 gene-ERV fusion transcripts, of which 216 were not reported previously. In addition, long-read dRNA-seq clearly shows that RNA splicing is a common event in DUX4-activated ERV transcripts. Long-read analysis showed non-LTR transposons including Alu elements are also transcribed from LTRs. Our findings revealed further complexity of DUX4-induced ERV transcripts. This catalogue of DUX4-activated repetitive elements may provide useful information to elucidate the pathology of FSHD. Also, our results indicate that nanopore dRNA-seq has complementary strengths to conventional short-read complementary DNA sequencing.

Effect of high-protein nutrition in critically ill patients: A retrospective cohort study.

BACKGROUND & AIMS: Early provision of a high-protein nutrition improves the prognosis of patients in intensive care units (ICUs). However, high protein intake increases blood urea nitrogen (BUN). No study has compared outcomes according to protein intake, and the clinical significance of changes in BUN (ΔBUN) in ICU patients is unclear. Here, we investigated the association of high protein intake with outcomes and BUN and assessed the clinical significance of ΔBUN. METHODS: This was a single-center retrospective cohort study. Between 1 January 2016 and 30 September 2019, 295 ICU patients received enteral nutrition for at least 3 days while undergoing mechanical ventilation. After applying the exclusion criteria of an age of <18 years, gastrointestinal disease, maintenance dialysis, renal replacement therapy after admission, kidney transplantation, and death within 7 days of commencing enteral nutrition, 206 patients remained. INTERVENTIONS: Participants were divided into those receiving >1.2 g/kg/day of protein (high-protein group; n = 111) and those receiving ≤1.2 g/kg/day of protein (non-high-protein group; n = 95). The groups were balanced by propensity score matching. The primary endpoint was 28-day mortality, and the secondary endpoints were 90-day mortality, length of ICU stay, number of ventilator-free days in the first 28 days, and ΔBUN. RESULTS: The high-protein group had significantly lower 28- and 90-day mortality and significantly greater ΔBUN, including after propensity score matching. ΔBUN might not be associated with outcomes. CONCLUSIONS: Provision of >1.2 g/kg/day of protein may be associated with lower mortality of tube-fed and mechanically ventilated patients. Furthermore, while high protein intake may be associated with higher BUN, these changes may not be adversely associated with outcomes.

Generation of a transgene-free iPSC line and genetically modified line from a facioscapulohumeral muscular dystrophy type 2 (FSHD2) patient with SMCHD1 p.Lys607Ter mutation.

Facioscapulohumeral muscular dystrophy type2 (FSHD2), which constitutes approximately 5% of total FSHD cases and develops the same symptoms as FSHD type 1 (FSHD1), is caused by various mutations in genes including SMCHD1. We report the generation and characterization of an iPSC line derived from an FSHD2 patient carrying the SMCHD1 p.Lys607Ter mutation and its gene-corrected iPSC line which are free from transgene. These iPSC lines maintained normal karyotype, presented typical morphology, expressed endogenous pluripotency markers, and could be differentiated into ectodermal, mesodermal and endodermal cells, confirming their pluripotency.