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.

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.

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.

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.

A patient-derived iPSC model revealed oxidative stress increases facioscapulohumeral muscular dystrophy-causative DUX4.

Double homeobox 4 (DUX4), the causative gene of facioscapulohumeral muscular dystrophy (FSHD), is ectopically expressed in the skeletal muscle cells of FSHD patients because of chromatin relaxation at 4q35. The diminished heterochromatic state at 4q35 is caused by either large genome contractions [FSHD type 1 (FSHD1)] or mutations in genes encoding chromatin regulators, such as SMCHD1 [FSHD type 2 (FSHD2)]. However, the mechanism by which DUX4 expression is regulated remains largely unknown. Here, using a myocyte model developed from patient-derived induced pluripotent stem cells, we determined that DUX4 expression was increased by oxidative stress (OS), a common environmental stress in skeletal muscle, in both FSHD1 and FSHD2 myocytes. We generated FSHD2-derived isogenic control clones with SMCHD1 mutation corrected by clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated 9 (Cas9) and homologous recombination and found in the myocytes obtained from these clones that DUX4 basal expression and the OS-induced upregulation were markedly suppressed due to an increase in the heterochromatic state at 4q35. We further found that DNA damage response (DDR) was involved in OS-induced DUX4 increase and identified ataxia-telangiectasia mutated, a DDR regulator, as a mediator of this effect. Our results suggest that the relaxed chromatin state in FSHD muscle cells permits aberrant access of OS-induced DDR signaling, thus increasing DUX4 expression. These results suggest OS could represent an environmental risk factor that promotes FSHD progression.

Streptococcal toxic shock syndrome caused by ß-hemolytic streptococci: Clinical features and cytokine and chemokine analyses of 15 cases.

OBJECTIVES: ß-Hemolytic streptococci occasionally cause severe infections such as necrotizing fasciitis and streptococcal toxic shock syndrome (STSS). Here, we conducted a prospective study to investigate the production of cytokines and chemokines in patients with STSS to explore its pathogenesis in survivors and fatal cases. METHODS: From January 2013 through August 2015, all culture results from normally sterile sites were prospectively followed and screened for STSS. Clinical characteristics of the patients with STSS were evaluated and compared between survivors and fatal cases. Serum samples were collected on admission for quantification of various cytokines and chemokines. Bacterial strains were categorized by Lancefield grouping and analyzed for the emm type, and presence of speA, speB, speC, and speF. RESULTS: Fifteen patients received diagnosis of STSS. The median age of the patients was 60-year-old, and the mortality rate was 40% despite intensive treatment. Nine strains were categorized as group A, two belonged to group G, and four to group B. Group A contained various emm genotypes. Unexpectedly, potent proinflammatory cytokine levels such as TNF-α and IL-1ß were not significantly elevated, and comparison with surviving patients showed that IL-6, IL-8, and MCP-1 levels were significantly decreased and creatine kinase level was significantly elevated in fatally ill cases. CONCLUSION: Our results indicate that reduced production of proinflammatory cytokines and chemokines may be involved in STSS pathogenesis and critical for prognosis of patients with STSS.

Efficacy of Precordial Percussion Pacing Assessed in a Cardiac Standstill Microminipig Model.

BACKGROUND: Potential cardiovascular benefits of precordial percussion pacing (PPP) during cardiac standstill are unknown.Methods and Results:A cardiac standstill model in amicrominipigwas created by inducing complete atrioventricular block with a catheter ablation technique (n=7). Next, the efficacy of cardiopulmonary resuscitation by standard chest compressions (S-CPR), PPP and ventricular electrical pacing in this model were analyzed in series (n=4). To assess the mechanism of PPP, a non-selective, stretch-activated channel blocker, amiloride, was administered during PPP (n=3). Peak systolic and diastolic arterial pressures during S-CPR, PPP and ventricular electrical pacing were statistically similar. However, the duration of developed arterial pressure with PPP was comparable to that with ventricular electrical pacing, and significantly greater than that with S-CPR. Amiloride decreased the induction rate of ventricular electrical activity by PPP in a dose-related manner. Each animal survived without any neurological deficit at 24, 48 h and 1 week, even with up to 2 h of continuous PPP. CONCLUSIONS: In amicrominipigmodel of cardiac standstill, PPP can become a novel means to significantly improve physiological outcomes after cardiac standstill or symptomatic bradyarrhythmias in the absence of cardiac pacing. Activation of the non-selective stretch-activated channels may mediate some of the mechanophysiological effects of PPP. Further study of PPP by itself and together with S-CPR is warranted using cardiac arrest models of atrioventricular block and asystole.

Consideration of the Intracranial Pressure Threshold Value for the Initiation of Traumatic Brain Injury Treatment: A Xenon CT and Perfusion CT Study.

BACKGROUND: Monitoring of intracranial pressure (ICP) is considered to be fundamental for the care of patients with severe traumatic brain injury (TBI) and is routinely used to direct medical and surgical therapy. Accordingly, some guidelines for the management of severe TBI recommend that treatment be initiated for ICP values >20 mmHg. However, it remained to be accounted whether there is a scientific basis to this instruction. The purpose of the present study was to clarify whether the basis of ICP values >20 mmHg is appropriate. SUBJECT AND METHODS: We retrospectively reviewed 25 patients with severe TBI who underwent neuroimaging during ICP monitoring within the first 7 days. We measured cerebral blood flow (CBF), mean transit time (MTT), cerebral blood volume (CBV), and ICP 71 times within the first 7 days. RESULTS: Although the CBF, MTT, and CBV values were not correlated with the ICP value at ICP values ≤20 mmHg, the CBF value was significantly negatively correlated with the ICP value (r = -0.381, P < 0.05) at ICP values >20 mmHg. The MTT value was also significantly positively correlated with the ICP value (r = 0.638, P < 0.05) at ICP values >20 mmHg. CONCLUSION: The cerebral circulation disturbance increased with the ICP value. We demonstrated the cerebral circulation disturbance at ICP values >20 mmHg. This study suggests that an ICP >20 mmHg is the threshold to initiate treatments. An active treatment intervention would be required for severe TBI when the ICP was >20 mmHg.

Effect of ninjin'yoeito, a Kampo (traditional Japanese) medicine, on cognitive impairment and depression in patients with Alzheimer's disease: 2 years of observation.

BACKGROUND: Only a few approved drugs are capable of alleviating the cognitive and behavioural symptoms of people living with Alzheimer's disease (AD). In recent years, however, the number of studies examining the clinical effects of herbal medicines on cognitive function in patients with AD has increased considerably. This study evaluated the long-term effects of a traditional Japanese medicine (Kampo medicine) known as ninjin'yoeito (NYT) on cognitive impairment and mood status in patients with AD over a 2-year period. METHODS: Twenty-three patients with mild-to-moderate probable AD according to the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria were included. Each participant had exhibited an insufficient response to treatment with donepezil alone before the start of the trial. Eleven patients received treatment with donepezil alone, and the remaining patients received a combined treatment of donepezil and NYT for 2 years. Patients were assessed by the Mini-Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version for cognitive function, and the Neuropsychiatric Inventory was used to evaluate the patients' mood status at baseline and every 6 months for 2 years. RESULTS: The Mini-Mental State Examination results showed no significant differences between the two groups. Significant improvements were observed on the Alzheimer's Disease Assessment Scale-cognitive component-Japanese version and the Neuropsychiatric Inventory depression scores of patients who received the combined therapy with donepezil and NYT (Alzheimer's Disease Assessment Scale-cognitive component-Japanese version, 12 months: P < 0.01, 18 months: P = 0.04, 24 months: P < 0.01; Neuropsychiatric Inventory depression, 6 months: P < 0.05, 24 months: P < 0.05). CONCLUSIONS: A 2-year follow-up of patients receiving donepezil and NYT treatment showed an improved cognitive outcome and alleviation of AD-related depression.

Early cerebral circulation disturbance in patients suffering from different types of severe traumatic brain injury: a xenon CT and perfusion CT study.

INTRODUCTION: Traumatic brain injury (TBI) is widely known to cause dynamic changes in cerebral blood flow (CBF). In particular, secondary brain insults have been reported to decrease CBF. The purpose of this study was to clarify the cerebral circulation in different types of TBI. METHODS: Sixty-nine patients with TBI were divided into four groups, the subdural hematoma group, the contusion/intracerebral hematoma group, the diffuse axonal injury group, and the diffuse brain swelling group. In these patients, we simultaneously performed Xe-CT and perfusion CT to evaluate the cerebral circulation on post-injury days 1-3. We measured CBF using Xe-CT and mean transit time using perfusion CT and calculated the cerebral blood volume using the AZ-7000 W98 computer system. RESULTS: There were no significant differences in the Glasgow Coma Scale score on arrival or the Glasgow Outcome Scale score between the groups. The patients who had suffered focal TBI displayed more significant cerebral circulation disturbances than those that had suffered diffuse TBI. We were able to evaluate the cerebral circulation of TBI patients using these parameters. CONCLUSION: Moderate hypothermia therapy, which decreases CBF, the cerebral metabolic rate oxygen consumption (CMRO2), and intracranial pressure might be effective against the types of TBI accompanied by cerebral circulation disturbance. We have to use all possible measures including hypothermia therapy to treat severe TBI patients according to the type of TBI that they have suffered.

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.

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.

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.

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.

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.

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.

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.

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.