Neuromuscular blocking agents during targeted temperature management for out-of-hospital cardiac arrest patients.

BACKGROUND: Neuromuscular blocking agents (NMBAs) can control shivering during targeted temperature management (TTM) of patients with cardiac arrest. However, the effectiveness of NMBA use during TTM on neurologic outcomes remains unclear. We aimed to evaluate the association between NMBA use during TTM and favorable neurologic outcomes after out-of-hospital cardiac arrest (OHCA). MATERIALS AND METHODS: A multicenter, prospective, observational cohort study from 2019 to 2021. It included OHCA patients who received TTM after hospitalization. We conducted overlap weight propensity-score analyses after multiple imputation to evaluate the effect of NMBAs during TTM. The primary outcome was a favorable neurological outcome, defined as a cerebral performance category of 1 or 2 at discharge. Subgroup analyses were conducted based on initial monitored rhythm and brain computed tomography findings. RESULTS: Of the 516 eligible patients, 337 received NMBAs during TTM. In crude analysis, the proportion of patients with favorable neurological outcome was significantly higher in the NMBA group (38.3% vs. 16.8%; risk difference (RD): 21.5%; 95% confidence interval (CI): 14.0% to 29.1%). In weighted analysis, a significantly higher proportion of patients in the NMBA group had a favorable neurological outcome compared to the non-NMBA group (32.7% vs. 20.9%; RD: 11.8%; 95% CI: 1.2% to 22.3%). In the subgroup with an initial shockable rhythm and no hypoxic encephalopathy, the NMBA group showed significantly higher proportions of favorable neurological outcomes. CONCLUSIONS: The use of NMBAs during TTM was significantly associated with favorable neurologic outcomes at discharge for OHCA patients. NMBAs may have benefits in selected patients with initial shockable rhythm and without poor prognostic computed tomography findings.

Characteristics of the pulmonary opacities on chest CT associated with difficulty in short-term liberation from veno-venous ECMO in patients with severe ARDS.

BACKGROUND: It is clinically important to predict difficulty in short-term liberation from veno-venous extracorporeal membrane oxygenation (V-V ECMO) in patients with severe acute respiratory distress syndrome (ARDS) at the time of initiation of the support. The aim of this study was to identify the characteristics of pulmonary opacities on chest CT that is associated with difficulty in short-term liberation from V-V ECMO (< 14 days). METHODS: This multicenter retrospective study was conducted in adult patients initiated on V-V ECMO for severe ARDS between January 2014 and June 2022. The pulmonary opacities on CT at the time of initiation of the ECMO support were evaluated in a blinded manner, focusing on the following three characteristics of the opacities: (1) their distribution (focal/diffuse on the dorso-ventral axis or unilateral/bilateral on the left-right axis); (2) their intensity (pure ground glass/pure consolidation/mixed pattern); and (3) the degree of fibroproliferation (signs of traction bronchiectasis or reticular opacities). RESULTS: Among the 153 patients, 72 (47%) were successfully liberated from ECMO in the short term, while short-term liberation failed in the remaining 81 (53%) patients. Multivariate logistic regression analysis showed that the presence of mixed-pattern pulmonary opacities and signs of traction bronchiectasis, but not the distribution of the opacities, were independently associated with difficulty in short-term liberation (OR [95% CI]; 4.8 [1.4-16.5] and 3.9 [1.4-11.2], respectively). CONCLUSIONS: The presence of a mixed pattern of the pulmonary opacities and signs of traction bronchiectasis on the chest CT were independently associated with difficulty in short-term liberation from V-V ECMO in severe ARDS patients.

[Initial Treatment of Cerebral Hemorrhage:Determining the Cause without Preconceived Notions].

In Japan, cerebral hemorrhage accounts for 19.5% of stroke patients, and its prognosis is poorer than that of cerebral infarction, with a mortality rate of 14.6%. In the initial treatment of cerebral hemorrhage, the airway, respiration, and circulation should be stabilized, and the intracranial pressure and body temperature should be controlled. Hypertensive cerebral hemorrhage is the most common cause; however, the cause should be carefully examined, and the treatment method should be selected according to the degree of urgency. Cerebral hemorrhage patients undergoing antithrombotic therapy show poor outcomes owing to increased hematoma. Therefore, antithrombotic drugs should be discontinued immediately. Blood products and neutralizing drugs should be administered in response to the administration of antithrombotic drugs. In young individuals, cerebrovascular disorders may be caused by the abuse of sympathomimetic drugs, such as stimulants and cocaine. Whether individuals or their family members are using illegal drugs should be confirmed.

Risk factors for bleeding complications during venovenous extracorporeal membrane oxygenation as a bridge to recovery.

BACKGROUND: Bleeding complications during venovenous extracorporeal membrane oxygenation (V-V ECMO) can be critical. However, there is limited information on the associated risk factors. This study investigated the risk factors for bleeding complications during V-V ECMO as a bridge to recovery. METHODS: This single-center retrospective study enrolled 59 patients (bleeding and non-bleeding groups) who received V-V ECMO from 2012 to 2020, to evaluate whether peak activated partial thromboplastin time (APTT) value, lowest platelet count, and mobilization to sitting on the edge of the bed during V-V ECMO were risk factors for bleeding complications, defined according to the Extracorporeal Life Support Organization guidelines. Age, sex, body mass index, Sequential Organ Failure Assessment score, and ECMO duration before bleeding complications were covariates in the multivariate logistic regression analysis. RESULTS: Thirty-one (53%) participants experienced 36 bleeding complications; the ECMO cannulation site, gastrointestinal tract, and nasopharyngeal region were the most common bleeding sites. The use of transfusion products and length of ECMO and intensive care unit stay were significantly and medical costs were non-significantly increased in the bleeding group. Peak APTT (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05, p < 0.01) was significantly associated whereas the lowest platelet count (OR 0.96, 95% CI 0.82-1.13, p = 0.66) was unassociated with bleeding complications during ECMO. Achieving mobilization (OR 0.14, 95% CI 0.02-1.17, p = 0.07) decreased the trend of risk for bleeding complications. CONCLUSIONS: Peak APTT might be an independent modifiable factor for bleeding complications during V-V ECMO. The protective effect of mobilization during V-V ECMO requires further investigation.

Severe caffeine poisoning successfully treated with high flow continuous hemodialysis.

In recent years, severe or lethal cases of caffeine poisoning after large or massive ingestion of caffeinated tablets have increased in Japan. Here we report the case of a 23-year-old male who ingested high-dose caffeine tablets (total: 32.4 g caffeine) in a suicide attempt. He was transferred to our hospital about 2 h after ingesting the tablets and presented with repeated vomiting and tremor in the trunk and extremities. His respiratory rate was 40 breaths/min, heart rate 240 beats/min, blood pressure 109/77 mmHg, and Glasgow Coma Scale E3V2M5. Blood tests revealed metabolic acidosis compensated with respiratory alkalosis, hyperlactatemia, hypokalemia, hyperglycemia, and leukocytosis. After tracheal intubation, gastric lavage was performed and activated charcoal was administered. The patient gradually became hypotensive (systolic blood pressure < 90 mmHg) with a heart rate > 250 beats/min, and non-sustained ventricular tachycardia frequently occurred. Given the lack of response to intravenous noradrenaline and landiolol, high flow continuous hemodialysis (CHD) was initiated 4 h after tablet ingestion with a blood flow rate of 150 mL/min and dialysate flow rate of 2000 mL/h. This dramatically improved his clinical signs and symptoms, especially during the first 3 h. His serum caffeine concentration was 240.9 µg/mL on admission and 344.0 µg/mL at the initiation of high flow CHD, but rapidly decreased to 153.8 µg/mL 3 h after initiating high flow CHD. Our findings suggest that high flow CHD may be effective in treating cases of severe caffeine poisoning with hemodynamics too unstable for intermittent hemodialysis.

Stacked Thiazole Orange Dyes in DNA Capable of Switching Emissive Behavior in Response to Structural Transitions.

Functional nucleic acids with the capability of generating fluorescence in response to hybridization events, microenvironment or structural changes are valuable as structural probes and chemical sensors. We now demonstrate the enzyme-assisted preparation of nucleic acids possessing multiple thiazole orange (TO) dyes and their fluorescent behavior, that show a spectral change from the typical monomer emission to the excimer-type red-shifted emission. We found that the fluorescent response and emission wavelength of the TO dyes were dependent on both the state of the DNA structure (single- or double-stranded DNA) and the arrangement of the TO dyes. We showed that the fluorescent behavior of the TO dyes can be applied for the detection of RNA molecules, suggesting that our approach for preparing the fluorescent nucleic acids functionalized with multiple TO dyes could be useful to design a fluorescence bioimaging and detection technique of biomolecules.

Accurate and quick predictor of necrotizing soft tissue infection: Usefulness of the LRINEC score and NSTI assessment score.

OBJECTIVE: The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score is a diagnostic tool for necrotizing soft tissue infection (NSTI), which is validated and is considered to have high diagnostic value. However, some experts criticize LRINEC score for consisting of laboratory test results only. METHODS: In this single-center retrospective study, we created a new scoring system (NSTI assessment score; NAS), which also incorporated vital signs as another diagnostic tool for NSTI using cases from our hospital and also evaluated diagnostic accuracy of LRINEC score. We identified NSTI predictors by comparing 24 NSTI patients and 80 non NSTI patients using uni- and multivariate logistic regression analysis, and created NAS based on odds ratio of variables which are statistically significant in the multivariate model. RESULTS: We identified mean arterial pressure, C-reactive protein, hemoglobin, serum creatinine, and glucose as a predictor for NSTI. The maximum value of NAS was 11 points with the cut-off value of 6. Sensitivity, specificity, positive predictive value, and negative predictive value of the NAS for diagnosis of NSTI were 87.5%, 91.3%, 75.0%, and 96.1%, respectively. Area under the receiver operating characteristic curve was 0.926 (0.851-1.00) for the NAS and 0.903 (0.833-0.973) for the LRINEC score, and they were not statistically different (p = 0.167). CONCLUSION: The NAS has high diagnostic accuracy in predicting NSTI, and is comparable with the LRINEC score. The NAS needs to be validated in other cohorts in the future.

Controlling Pyrene Association in DNA Duplexes by B- to Z-DNA Transitions.

B- to Z-DNA transitions play a crucial role in biological systems and have attracted the interest of researchers for their applications in DNA nanotechnology. DNA and DNA analogues have also been used as templates to construct helical chromophore associations with π interactions. In this work, the B- to Z-DNA transition-induced switching of pyrene in an association manner was evaluated using DNA duplexes with non-nucleosidic pyrene residues in the middle of d(CG) repeat sequences. One of the pyrene-labeled DNAs was shown to exhibit inverted exciton coupled circular dichroism signals upon pyrene association through a B- to Z-DNA transition. This observation indicates that pyrene association switches the DNA conformation from right- to left-handed. Interestingly, the fluorescence of the pyrene-labeled DNA duplex also dynamically changed upon switching of the pyrene in an association-based manner. Taken together, these studies demonstrate that pyrene-labeled DNA shows promise as a chiroptical molecular switch.

A Progressive Early Mobilization Program Is Significantly Associated With Clinical and Economic Improvement: A Single-Center Quality Comparison Study.

OBJECTIVES: To determine whether a progressive early mobilization protocol improves patient outcomes, including in-hospital mortality and total hospital costs. DESIGN: Retrospective preintervention and postintervention quality comparison study. SETTINGS: Single tertiary community hospital with a 12-bed closed-mixed ICU. PATIENTS: All consecutive patients 18 years old or older were eligible. Patients who met exclusion criteria or were discharged from the ICU within 48 hours were excluded. Patients from January 2014 to May 2015 were defined as the preintervention group (group A) and from June 2015 to December 2016 was the postintervention group (group B). INTERVENTION: Maebashi early mobilization protocol. MEASUREMENTS AND MAIN RESULTS: Group A included 204 patients and group B included 187 patients. Baseline characteristics evaluated include age, severity, mechanical ventilation, and extracorporeal membrane oxygenation, and in group B additional comorbidities and use of steroids. Hospital mortality was reduced in group B (adjusted hazard ratio, 0.25; 95% CI, 0.13-0.49; p < 0.01). This early mobilization protocol is significantly associated with decreased mortality, even after adjusting for baseline characteristics such as sedation. Total hospital costs decreased from $29,220 to $22,706. The decrease occurred soon after initiating the intervention and this effect was sustained. The estimated effect was $-5,167 per patient, a 27% reduction. Reductions in ICU and hospital lengths of stay, time on mechanical ventilation, and improvement in physical function at hospital discharge were also seen. The change in Sequential Organ Failure Assessment score and Sequential Organ Failure Assessment score at ICU discharge were significantly reduced after the intervention, despite a similar Sequential Organ Failure Assessment score at admission and at maximum. CONCLUSIONS: In-hospital mortality and total hospital costs are reduced after the introduction of a progressive early mobilization program, which is significantly associated with decreased mortality. Cost savings were realized early after the intervention and sustained. Further prospective studies to investigate causality are warranted.

Photocurrent enhancement by a local electric field on DNA-modified electrodes covered with gold nanoparticles.

We here describe a photocurrent generation system exploiting gold nanoparticles (AuNPs) that cover perylenediimide-DNA complexes on electrode surfaces. Enhanced photocurrents were generated by the irradiation of the AuNPs, attributed to the efficient excitation of the perylenediimides by a local electric field on the surface of the AuNPs.

Lessons Learned in Helicopter Operations During a Large Multiagency Disaster Prevention Drill in Japan.

OBJECTIVE: In 2018, the Cabinet Office executed a disaster prevention drill based on the scenario that Nankai had a megathrust earthquake and a large tsunami hit Tokushima Prefecture. The purpose of this study was to summarize the key lessons learned in the review of the Department of Aviation Operation for Tokushima Prefecture in this drill. METHODS: This report was based on a review using data from the Japan emergency medical information sharing system that can be accessed via the Internet. RESULTS: In the disaster drill, the doctor helicopter (DH) headquarters of Tokushima Prefecture at Takamatsu Airport was able to procure 2 actual DHs and 2 mock DHs. The Department of Aviation Operation within the Tokushima Prefectural Government was able to procure 1 actual helicopter belonging to the Coast Guard and 8 mock helicopters (4 belonging to the military and 4 to the fire department). There were 29 flights, including actual and mock flights, and 44 victims were medically transported. CONCLUSION: By making flight plans with each organization concerned, we were able to share the basic rules, concepts, and management approaches of flights among the responding organizations. Disaster planners should have at least a passing familiarity with the aviation capabilities of the local helicopter emergency medical service and other helicopter operations.

Rapid Electron Transfer of Stacked Heterodimers of Perylene Diimide Derivatives in a DNA Duplex.

The preparation of homo- and heterocomplexes composed of the parent perylene diimide (PH) and pyrrolidine-substituted perylene diimide (PN) in DNA and rapid electron transfer in these complexes, which has been analyzed by steady-state fluorescence and femtosecond transient absorption measurements, have been demonstrated. The DNA molecules possessing PH and PN were prepared through a recently developed method that involved the reaction of enzymatically generated abasic sites with the amino groups of the perylene diimide molecules, through which these molecules can be incorporated as base surrogates within the DNA base stack. Melting temperature analysis showed that the PH and PN monomers, and their homo- and heterodimers, contribute to the stabilization of the DNA duplex, and is comparable to that of natural base pairs. Fluorescence measurements showed that PH in a single-stranded oligopyrimidine showed a strong fluorescence, whereas the fluorescence of PH was completely quenched upon pairing with PN (PH/PN) through duplex formation. The transient absorption measurements showed that a rapid electron-transfer reaction in the stacked PH/PN heterodimer occurred on a sub-picosecond timescale, which allowed highly efficient fluorescence quenching. The PH/PN pair, which served as a fluorophore and quencher, were utilized to design molecular beacon probes with a high signal/noise ratio. The PH/PN pair was also capable of forming a stable, stacked dimer structure and induced rapid electron transfer that could serve as a good signal reporter for fluorescent nucleic acid detection.

Circularly polarized luminescence of helically assembled pyrene π-stacks on RNA and DNA duplexes.

In this report, we describe the circularly polarized luminescence (CPL) of the RNA duplexes having one to four 2'-O-pyrene modified uridines (Upy) and the DNA duplexes having two, four, and six pyrene modified non-nucleosidic linkers (Py). Both the pyrene π-stack arrays formed on the RNA and DNA double helical structures exhibited pyrene excimer fluorescence. In the pyrene-modified RNA systems, the RNA duplex having four Upys gives CPL emission with glum value of <0.01 at 480 nm. The structure of pyrene stacks on the RNA duplex may be rigidly regulated with increase in the Upy domains, which resulted in the CPL emission. In the DNA systems, the pyrene-modified duplexes containing two and four Pys exhibited CPL emission with glum values of <0.001 at 505 nm. The pyrene π-stack arrays presented here show CPL emission. However, the glum values are relatively small when compared with our previous system consisting of the pyrene-zipper arrays on RNA.

Photoresponsive Electrodes Modified with DNA Duplexes Possessing a Porphyrin Dimer.

This work describes the formation of a porphyrin (Por) dimer using a DNA duplex as a scaffold and photocurrent generation from electrodes modified with a monolayer of Por-DNA conjugates. The solid-phase click reaction between an azide-porphyrin and oligonucleotide labeled with an ethynyl group on CPG support was utilized to conjugate the Por to the DNA. UV/Vis absorption and circular dichroism (CD) spectral studies revealed that the Por dimer can be formed through DNA hybridization and that through-space electronic interactions, characterized from the exciton-coupled absorption and the bisignate CD, can occur between the two Por molecules. Photoelectrochemical experiments were performed for the electrodes functionalized with a monolayer composed of the Por-DNA conjugates. It was found that the Por dimer on the electrode, which was designed to resemble the special pair in natural photosynthesis, shows efficient photocurrent generation in the presence of electron-acceptor reagents compared with the Por monomer. These findings strongly support the idea that the DNA structures could be useful to construct Por arrays, which is essential for the design of photo- and bio-electronic devices.

Ferrocene conjugated oligonucleotide for electrochemical detection of DNA base mismatch.

We describe the synthesis, binding, and electrochemical properties of ferrocene-conjugated oligonucleotides (Fc-oligos). The key step for the preparation of Fc-oligos contains the coupling of vinylferrocene to 5-iododeoxyuridine via Heck reaction. The Fc-conjugated deoxyuridine phosphoramidite was used in the Fc-oligonucleotide synthesis. We show that thiol-modified Fc-oligos deposited onto gold electrodes possess potential ability in electrochemical detection of DNA base mismatch.

Ultrasound-Guided Resuscitative Endovascular Balloon Occlusion of the Aorta in the Resuscitation Area.

BACKGROUND: In trauma resuscitation with resuscitative endovascular balloon occlusion of the aorta (REBOA), urgent and accurate placement of the catheter in the resuscitation area without fluoroscopy can shorten the time from admission to REBOA, allowing rapid, temporary control of bleeding. DISCUSSION: The experience-based protocol in our center for ultrasound-guided REBOA in the resuscitation area without fluoroscopy is as follows: the femoral artery is punctured and a guidewire inserted; sonography is used to verify that the guidewire is in the abdominal aorta; the position of the balloon is confirmed with ultrasound after estimating the distance to the clavicle, and the pressure in the radial artery and sheath is used to monitor correct positioning; connect the pressure transducer to the catheter sheath for continuous monitoring of the blood pressure in the sheath, and inflate the balloon until the blood pressure tracing at the sheath has disappeared; check the pulse in the left radial artery, and withdraw the catheter slightly if the pulse in the radial artery is not palpable or is decreased (if this pulse is not palpable or decreased, the balloon is in the aortic arch). In this retrospective review of our REBOA protocol, between April 2012 and March 2016, 34 patients were enrolled. Two patients had complications, including dissection of the femoral artery in one and difficult percutaneous vascular access in another. Median time needed to complete the procedure was 8 min. Overall, 24 of 34 patients survived more than 24 h (72%), and overall mortality was 47%. Patients who lived more than 24 h, and then died had severe traumatic brain injury or septic shock. CONCLUSIONS: Ultrasound-guided REBOA is presented. Monitoring the blood pressure in the left radial artery allows us to determine adequate positioning of the balloon, and the blood pressure in the catheter sheath located in the femoral artery should also be monitored to prevent aortic injuries caused by the overinflation of the balloon.

DNA-Templated Synthesis of Perylenediimide Stacks Utilizing Abasic Sites as Binding Pockets and Reactive Sites.

DNA is considered to be a promising biomolecule as a template and scaffold for arranging and organizing functional molecules on the nanoscale. The construction and evaluation of DNAs containing multiple functional molecules that are useful for optoelectronic devices and sensors has been studied. In this paper we report the efficient incorporation of perylenediimide (PDI) units into DNA by using abasic sites both as binding sites and as reactive sites and the construction of PDI stacks within the DNA structure, accomplished through the preorganization of the PDI units in the hydrophobic pocket within the DNA. Our approach could become a valuable method for construction of DNA/chromophore hybrid structures potentially useful for the design of DNA-based devices and biosensors.

Helically Assembled Pyrene Arrays on an RNA Duplex That Exhibit Circularly Polarized Luminescence with Excimer Formation.

Circularly polarized luminescence (CPL) was observed in pyrene zipper arrays helically arranged on an RNA duplex. Hybridization of complementary RNA strands having multiple (two to five) 2'-O-pyrenylmethyl modified nucleosides affords an RNA duplex with normal thermal stability. The pyrene fluorophores are assembled like a zipper in a well-defined helical manner along the axis of RNA duplex, which, upon 350 nm UV illumination, resulted in CPL emission with pyrene excimer formation. CPL (glum ) levels observed for the pyrene arrays in dilute aqueous solution were +2×10(-2) -+3.5×10(-2) , which are comparable with |glum | for chiral organic molecules and related systems. The positive CPL signals are consistent with a right-handed helical structure. Temperature dependence on CPL emission indicates that the stable rigid RNA structure is responsible for the strong CPL signals. The single pyrene-modified RNA duplex did not show any CPL signal.

Donor-Acceptor Heterojunction Configurations Based on DNA-Multichromophore Arrays.

Multichromophore arrays of bis(2-thienyl)diketopyrrolopyrrole (DPP) and naphthalenediimide (NDI) with two Zn(II) -cyclens were constructed using thymidine DNA as a scaffold through the binding of the Zn(II) -cyclens with thymine bases. We demonstrate photocurrent generation in a donor-acceptor heterojunction configuration consisting of the DPP (donor) and NDI (acceptor) arrays co-immobilized on an Au electrode. The co-immobilized electrode exhibited good photocurrent responses because of the efficient charge separation between the DPP and NDI arrays. In contrast, an immobilized electrode consisting of randomly assembled DPP-NDI arrays generated no photocurrent response because DPP formed ground-state charge-transfer complexes with NDI in the randomly assembled arrays. Therefore, our approach to generate donor-acceptor heterojunctions based on DNA-multichromophore arrays is a useful method to efficiently generate photocurrent.

Photocurrent generation through charge-transfer processes in noncovalent perylenediimide/DNA complexes.

The charge-transfer process in noncovalent perylenediimide (PDI)/DNA complexes has been investigated by using nanosecond laser flash photolysis (LFP) and photocurrent measurements. The PDI/DNA complexes were prepared by inclusion of cationic PDI molecules into the artificial cavities created inside DNA. The LFP experiments showed that placement of the PDI chromophore at a specific site and included within the base stack of DNA led to the efficient generation of a charge-separated state with a long lifetime by photoexcitation. When two PDI chromophores were separately placed at different positions in DNA, the yield of the charge-separated state with a long lifetime was dependent upon the number of A-T base pairs between the PDIs, which was explained by electron hopping from one PDI to another. Photocurrent generation of the DNA-modified electrodes with the complex was also dependent upon the arrangement of the PDI chromophores. A good correlation was obtained between observed charge separation and photocurrent generation on the PDI/DNA-modified electrodes, which demonstrated the importance of the defined arrangement and assembly of organic chromophores in DNA for efficient charge separation and transfer in multichromophore arrays.