Microwave-assisted solvothermal synthesis of nanostructured Ga-Doped Li7La3Zr2O12 solid electrolyte with enhanced densification and Li-ion conductivity.

Garnet-type Li7La3Zr2O12 (LLZO) Li-ion solid electrolytes are promising candidates for safe, next-generation solid-state batteries. In this study, we synthesize Ga-doped LLZO (Ga-LLZO) electrolytes using a microwave-assisted solvothermal method followed by low-temperature heat treatment. The nanostructured precursor (<50 nm) produced by the microwave-assisted solvothermal process has a high surface energy, facilitating the reaction for preparing garnet-type Ga-LLZO powders (<800 nm) within a short time (<5 h) at a low calcination temperature (<700 °C). Additionally, the calcined nanostructured Ga-LLZO powder can be sintered to produce a high-density pellet with minimized grain boundaries under moderate sintering conditions (temperature: 1150 °C, duration: 10 h). The optimal doping concentration was determined to be 0.4 mol% Ga, which resulted significantly increased the ionic conductivity (1.04 × 10-3 S cm-1 at 25 °C) and stabilized the cycling performance over 1700 h at 0.4 mA cm-2. This approach demonstrates the potential to synthesize oxide-type solid electrolyte materials with improved properties for solid-state batteries.

Musical training does not enhance neural sound encoding at early stages of the auditory system: A large-scale multisite investigation.

Musical training has been associated with enhanced neural processing of sounds, as measured via the frequency following response (FFR), implying the potential for human subcortical neural plasticity. We conducted a large-scale multi-site preregistered study (n > 260) to replicate and extend the findings underpinning this important relationship. We failed to replicate any of the major findings published previously in smaller studies. Musical training was related neither to enhanced spectral encoding strength of a speech stimulus (/da/) in babble nor to a stronger neural-stimulus correlation. Similarly, the strength of neural tracking of a speech sound with a time-varying pitch was not related to either years of musical training or age of onset of musical training. Our findings provide no evidence for plasticity of early auditory responses based on musical training and exposure.

The Impact of Pembrolizumab as a Salvage Therapy Based on HER2 Expression in Advanced Gastric Cancer.

Immune checkpoint inhibitors (ICIs) are used as salvage treatments for advanced gastric cancer (AGC) regardless of HER2 status. This study assessed the efficacy of ICIs based on HER2 expression in AGC patients who received pembrolizumab as salvage monotherapy at Samsung Medical Center from November 2017 to March 2023. HER2 status was determined via immunohistochemistry, and tumor response and survival outcomes were compared accordingly. Among the 113 patients analyzed, with a median age of 61 years and 64.6% being male, 12 patients (10.6%) were HER2-positive, and 101 patients (89.4%) were HER2-negative. Of 92 evaluable patients, none had a complete response. However, 50% of HER2-positive patients had a partial response, compared to 4.9% of HER2-negative patients (p < 0.001). The disease control rate was 70% in HER2-positive and 37.8% in HER2-negative patients (p = 0.086). Median progression-free survival was 5.53 months for HER2-positive patients versus 1.81 months for HER2-negative patients (p = 0.037). Pembrolizumab as a salvage chemotherapy for the treatment of AGC demonstrated superior effectiveness in HER2-positive patients compared with HER2-negative patients.

Comparison of the risk of pneumothorax in COVID-19 and seasonal influenza.

Limited evidence exists regarding the link between coronavirus disease 2019 (COVID-19) and pneumothorax. Therefore, we aimed to evaluate the occurrence rate of pneumothorax in hospitalized patients with COVID-19 and compare the risk of pneumothorax between patients with COVID-19 and influenza. This retrospective cohort study used patient data from the National Health Insurance Service of South Korea. Patients diagnosed with COVID-19 (December 2019 to December 2021) and influenza (January 2019 to December 2021) who required hospitalization and respiratory support were included. We identified 46,460 patients with COVID-19 and 6,117 with influenza. The occurrence rate of pneumothorax was 0.74% in patients with COVID-19. In an inverse probability of treatment weighting matched cohort, the Cox proportional hazards regression model showed that COVID-19 was not associated with an increased risk of pneumothorax compared to influenza (hazard ratio, 1.22; 95% confidence interval, 0.75-1.99). However, the risk of pneumothorax associated with COVID-19 compared to influenza was significantly higher in patients without chronic lung disease than in those with (P for heterogeneity = 0.037). In conclusion, COVID-19, compared with influenza, is not associated with an increased risk of pneumothorax; however, it is associated with an increased risk in patients without chronic lung disease.

The clinical characteristics associated with the ratio between the main pulmonary artery and ascending aorta diameter in patients with acute exacerbation of chronic obstructive pulmonary disease.

Background: A pulmonary artery-to-aorta (PA/A) ratio of ≥1 is a reliable indicator of pulmonary hypertension and is associated with an increased risk of acute exacerbation of chronic obstructive pulmonary disease (COPD) and long-term mortality in patients with stable COPD. However, it is unclear whether a PA/A ratio of ≥1 is associated with mortality in patients hospitalized with acute exacerbation of COPD. The purpose of this study was to evaluate the clinical course and mortality of patients with PA/A ratios of ≥1 who were hospitalized with acute exacerbation of COPD. Methods: We retrospectively reviewed the medical charts of patients admitted to a tertiary referral hospital and a secondary hospital with acute exacerbation of COPD between 2016 and 2021. Chest computed tomography was used to measure the pulmonary artery (PA), aorta (A) diameter, and the PA/A ratio. The study involved 324 and 111 patients with PA/A ratios <1 and ≥1, respectively. Results: The average age in the two groups was 74.1 and 74.5 years, which was not significantly different. When compared with the group with PA/A ratios of <1, the group with PA/A ratios of ≥1 had a lower proportion of males (71.2% vs. 89.5%, P<0.001), more patients with type 2 respiratory failure (35.1% vs. 18.8%), higher high-flow nasal cannula use (10.8% vs. 4.6%), higher use of non-invasive ventilation (NIV) (21.6% vs. 7.7%), and longer hospital stay (10.9 vs. 9.5 days). In-hospital mortality was not significantly different between the two groups. A PA/A ratio of ≥1 was identified as an independent predictor of the need for high-flow nasal cannula, NIV, and intubation in COPD patients. Conclusions: Patients with PA/A ratios of ≥1 had a high incidence of type 2 acute respiratory failure and required advanced treatment, including high-flow nasal cannula, NIV, and intubation. Therefore, hospitalized patients with acute exacerbation of COPD and PA/A ratios of ≥1 require more aggressive treatment.

METTL3-STAT5B interaction facilitates the co-transcriptional m6A modification of mRNA to promote breast tumorigenesis.

Enhanced expression of methyltransferase-like 3 (METTL3) promotes the m6A modification of specific mRNAs, contributing to breast tumorigenesis. While the mRNA substrates targeted by METTL3 are well characterized, the factors dictating the selection of these specific mRNA remain elusive. This study aimed to examine the regulatory role of the transcription factor STAT5B in METTL3-induced m6A modification. METTL3 specifically interacts with STAT5B in response to mitogenic stimulation by epidermal growth factor (EGF). Chromatin immunoprecipitation and CRISPR/Cas9 mutagenesis showed that STAT5B recruits METTL3 to gene promoters like CCND1, where METTL3 interacts with RPB1, dependent on CDK9-mediated RPB1 (Ser2) phosphorylation during transcription elongation. Inhibition and depletion of either STAT5B or CDK9 prevented the EGF-induced m6A modification of CCND1. The translation efficiency of CCND1 was increased following m6A modification, thereby increasing cell proliferation. STAT5B facilitated METTL3-induced tumor formation by increasing CCND1 expression in an orthotopic mouse model. In clinical context, a positive correlation was observed between p-STAT5B and METTL3 expression in high-grade breast tumors. This study elucidates a novel mechanism that underlies the specificity of m6A modification in breast cancer cells, thereby underscoring its potential therapeutic value.

Association of baseline muscle mass with functional outcomes in intensive care unit survivors: A single-center retrospective cohort study in Korea.

In critical care settings, ultrasound (US) of the quadriceps muscle and Bioelectrical Impedance Analysis (BIA) are noninvasive and widely available tools to evaluate muscle mass. We studied whether baseline muscle mass affects physical function in intensive care unit (ICU) survivors after discharge. This retrospective review of a prospective cohort enrolled 30 patients admitted to the medical ICU between April 2016 and June 2018. On ICU admission, quadriceps muscle thickness and skeletal muscle mass were measured using US and BIA, respectively. Muscle strength and physical function were measured using handgrip dynamometry, the 6-min walk test, and the Barthel index questionnaire survey during every clinic visit at 1, 3, 6, and 12 months after hospital discharge. Skeletal muscle mass at ICU admission was statistically correlated with the 6-min walk distance (6MWD) and Barthel index score. The segmental lean mass of the right arm was also positively correlated with handgrip muscle strength at 6 months after discharge. Likewise, the correlation between quadriceps muscle thickness at ICU admission and 6MWD at 6 months after discharge was positive and statistically significant. Multivariate regression analysis showed that skeletal muscle mass was associated with a reduced 6MWD, but the length of ICU stay was not. The segmental lean mass of the right arm also showed a significant association with handgrip strength after discharge. Low muscle mass on ICU admission is associated with reduced muscle strength, causing impaired physical function after hospital discharge in ICU survivors.

CDK4/6 inhibition to resensitize BRAF/EGFR inhibitor in patient-derived BRAF/PTEN-mutant colon cancer cells.

Background: In v-raf murine sarcoma viral oncogene homolog B1 (BRAF)-mutant colorectal cancer (CRC), encorafenib-cetuximab has been established as standard second-line therapy, but not all patients respond and the duration of response is relatively short. Overcoming intrinsic or acquired resistance to BRAF/EGFR inhibitors is crucial for enhancing treatment outcomes in metastatic BRAF-mutated CRC. The aim of the study is to investigate the resistance mechanisms in BRAF-mutant CRC patient refractory to BRAF/EGFR targeted therapy. Methods: We established patient-derived cells (PDCs) from a patient with BRAF/PTEN-mutant metastatic colon cancer who progressed rapidly on encorafenib plus cetuximab. To explore potential treatment options for inherent resistance caused by simultaneous PTEN mutation in BRAF-mutated CRC, we conducted cell viability assays using PDCs treated with encorafenib-cetuximab in combination with a cyclin-dependent kinase-4 and 6 (CDK4/6) inhibitor. Results: The patient's tumor had concurrent PTEN loss-of-function alteration at diagnosis and PDCs were generated from ascites after resistance to the BRAF/EGFR inhibitor. The PDCs were resistant to the encorafenib-cetuximab combination even at a high concentration of cetuximab (up to 500 µg/mL). Adding the CDK4/6 inhibitor, ribociclib, to encorafenib-cetuximab showed a synergistic effect in a proliferation assay. Ribociclib plus encorafenib-cetuximab represented a significantly lower expression of Ki-67 compared to the dual combination alone. An MTS assay showed that triplet therapy with ribociclib, encorafenib, and cetuximab suppressed cell viability more efficiently than the two-drug combinations. Investigating the combined effect of triplet therapy using the calculated combination index (CI) showed that ribociclib had a synergistic effect with encorafenib-cetuximab when applied to PDCs with a concurrent BRAF/PTEN mutation. Conclusions: Our results suggest that combining the CDK4/6 inhibitor with the BRAF/EGFR inhibitor might be a novel treatment strategy for concomitant BRAF and PTEN-mutant CRC.

Increasing ductility beyond post-uniform deformation through Zn lamellae deformation in Al at room temperature.

The Zn element precipitates during aging in the Al-Zn binary alloy. Increased Zn content and prolonged aging leads to discontinuous Zn precipitation. The addition of 2 wt% Cu to the Al-43 wt%Zn alloy accelerates this discontinuous precipitation, resulting in decreased thickness of Zn layers and inter-distance between them. This acceleration is attributed to the influence of Cu solutes on the Zn phase, thereby reducing the interface energy between Zn precipitates and the Al matrix. The Al-Zn-Cu alloy demonstrates exceptional behavior during tensile tests, displaying a simultaneous increase in tensile strength and ductility alongside an 75 % reduction in area at room temperature drawing. Notably, despite the drawn beyond uniform deformation limit, there is an observed increase in total elongation. Our demonstration highlights this phenomenon, attributing it to the sustained coherent interface between the Zn layer and the Al matrix, as well as the uninterrupted continuity of Zn layers during drawing.

Prevalence of KRAS amplification in patients with metastatic cancer: Real-world next-generation sequencing analysis.

BACKGROUND: The Kirsten rat sarcoma virus (KRAS) is a prominent proto-oncogene. Several treatments for KRAS mutations have been developed. However, KRAS amplification, a KRAS alteration, is poorly understood, and there is currently no appropriate treatment other than conventional chemotherapy. This study aimed to elucidate the role of KRAS amplification in different types of cancers. METHODS: From October 2019 to June 2023, we performed next-generation sequencing using Trusight Oncology 500 on 3895 patients with 37 different cancer types at the Samsung Medical Center. We analyzed the distribution of KRAS amplification according to cancer type and its correlation with tumor mutation burden (TMB). Concomitant KRAS mutations were also identified. RESULTS: Of the total 3895 patients, 99 (2.5 %) had KRAS amplification. The highest frequency of KRAS amplification was detected in 2 % (27/1350) of patients with colorectal cancer, followed by 3.48 % (32/920) of patients with gastric cancer and 3.88 % (9/232) patients with of pancreatic cancer. MSI-High was not detected in patients with KRAS amplification. There was no correlation between KRAS copy number variation and TMB status. Among patients with KRAS amplification, 27.3 % (27/99) had a concomitant KRAS mutation. More than 50 % of patients had G12D or G12V mutations. In gastric cancer, patients with both KRAS amplification and mutation were extremely rare at 3.1 % (1/32); however, in colorectal cancer, more than half of the patients had KRAS amplification and mutation (51.9 %, 14/27). KRAS amplification and mutations are associated with mutations in tumor suppressor genes TP53, BRCA2, ARID1B, and PTCH1. CONCLUSIONS: Of the 3895 patients with metastatic solid tumors, 99 (2.5 %) had KRAS amplification, and next-generation sequencing analysis provided a deeper understanding of KRAS amplification.

Shortwave Infrared Imaging of a Quantum Dot-Based Magnetic Guidewire Toward Non-Fluoroscopic Peripheral Vascular Interventions.

Peripheral vascular interventions (PVIs) offer several benefits to patients with lower extremity arterial diseases, including reduced pain, simpler anesthesia, and shorter recovery time, compared to open surgery. However, to monitor the endovascular tools inside the body, PVIs are conducted under X-ray fluoroscopy, which poses serious long-term health risks to physicians and patients. Shortwave infrared (SWIR) imaging of quantum dots (QDs) has shown great potential in bioimaging due to the non-ionizing penetration of SWIR light through tissues. In this paper, a QD-based magnetic guidewire and its system is introduced that allows X-ray-free detection under SWIR imaging and precise steering via magnetic manipulation. The QD magnetic guidewire contains a flexible silicone tube encapsulating a QD polydimethylsiloxane (PDMS) composite, where HgCdSe/HgS/CdS/CdZnS/ZnS/SiO2 core/multi-shell QDs are dispersed in the PDMS matrix for SWIR imaging upon near-infrared excitation, as well as a permanent magnet for magnetic steering. The SWIR penetration of the QD magnetic guidewire is investigated within an artificial tissue model (1% Intralipid) and explore the potential for non-fluoroscopic PVIs within a vascular phantom model. The QD magnetic guidewire is biocompatible in its entirety, with excellent resistance to photobleaching and chemical alteration, which is a promising sign for its future clinical implementation.

Efficacy of chemotherapy containing bevacizumab in patients with metastatic colorectal cancer according to programmed cell death ligand 1.

BACKGROUND: Bevacizumab, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, inhibits angiogenesis and reduces tumor growth. Serum VEGF-C, lactate dehydrogenase, and inflammatory markers have been reported as predictive markers related to bevacizumab treatment. Programmed cell death ligand 1 (PD-L1) could act upon VEGF receptor 2 to induce cancer cell angiogenesis and metastasis. AIM: To investigate the efficacy of bevacizumab-containing chemotherapy in patients with metastatic colorectal cancer (CRC) according to the expression of PD-L1. METHODS: This analysis included CRC patients who received bevacizumab plus FOLFOX or FOLFIRI as first-line therapy between June 24, 2014 and February 28, 2022, at Samsung Medical Center (Seoul, South Korea). Analysis of patient data included evaluation of PD-L1 expression by the combined positive score (CPS). We analyzed the efficacy of bevacizumab according to PD-L1 expression status in patients with CRC. RESULTS: A total of 124 patients was included in this analysis. Almost all patients were treated with bevacizumab plus FOLFIRI or FOLFOX as the first-line chemotherapy. While 77% of patients received FOLFOX, 23% received FOLFIRI as backbone first-line chemotherapy. The numbers of patients with a PD-L1 CPS of 1 or more, 5 or more, or 10 or more were 105 (85%), 64 (52%), and 32 (26%), respectively. The results showed no significant difference in progression-free survival (PFS) and overall survival (OS) with bevacizumab treatment between patients with PD-L1 CPS less than 1 and those with PD-L1 CPS of 1 or more (PD-L1 < 1% vs PD-L1 ≥ 1%; PFS: P = 0.93, OS: P = 0.33), between patients with PD-L1 CPS less than 5 and of 5 or more (PD-L1 < 5% vs PD-L1 ≥ 5%; PFS: P = 0.409, OS: P = 0.746), and between patients with PD-L1 CPS less than 10 and of 10 or more (PD-L1 < 10% vs PD-L1 ≥ 10%; PFS: P = 0.529, OS: P = 0.568). CONCLUSION: Chemotherapy containing bevacizumab can be considered as first-line therapy in metastatic CRC irrespective of PD-L1 expression.

Magnetically Controlled Intraocular Delivery of Dexamethasone Using Silica-Coated Magnetic Nanoparticles.

Although the number of patients with eye diseases is increasing, efficient drug delivery to the posterior segment of the eyeball remains challenging. The reasons include the unique anatomy of the eyeball, the blood-aqueous barrier, the blood-retina barrier, and drug elimination via the anterior chamber and uveoscleral routes. Solutions to these obstacles for therapeutic delivery to the posterior segment will increase the efficacy, efficiency, and safety of ophthalmic treatment. Micro/nanorobots are promising tools to deliver therapeutics to the retina under the direction of an external magnetic field. Although many groups have evaluated potential uses of micro/nanorobots in retinal treatment, most experiments have been performed under idealized in vitro laboratory conditions and thus do not fully demonstrate the clinical feasibility of this approach. This study examined the use of magnetic nanoparticles (MNPs) to deliver dexamethasone, a drug widely used in retinal disease treatment. The MNPs allowed sustainable drug release and successful magnetic manipulation inside bovine vitreous humor and the vitreous humor of living rabbits. Therefore, controlled drug distribution via magnetic manipulation of MNPs is a promising strategy for targeted drug delivery to the retina.

Assessing the Efficacy of Bortezomib and Dexamethasone for Induction and Maintenance Therapy in Relapsed/Refractory Cutaneous T-Cell Lymphoma: A Phase II CISL1701/BIC Study.

Purpose: This multicenter, open-label, phase II trial evaluated the efficacy and safety of bortezomib combined with dexamethasone for the treatment of relapsed/refractory cutaneous T-cell lymphoma (CTCL) in previously treated patients across 14 institutions in South Korea. Patients and Methods: Between September 2017 and July 2020, 29 patients with histologically confirmed CTCL received treatment, consisting of eight 4-week cycles of induction therapy followed by maintenance therapy, contingent upon response, for up to one year. The primary endpoint was the proportion of patients achieving an objective global response. Results: Thirteen (44.8%) of the 29 patients achieved an objective global response, including two complete responses. The median progression-free survival (PFS) was 5.8 months, with responders showing a median PFS of 14.0 months. Treatment-emergent adverse events were generally mild, with a low incidence of peripheral neuropathy and hematologic toxicities. Despite the trend toward shorter PFS in patients with higher mutation burdens, genomic profiling before and after treatment showed no significant emergence of new mutations indicative of disease progression. Conclusion: This study supports the use of bortezomib and dexamethasone as a viable and safe treatment option for previously treated CTCL, demonstrating substantial efficacy and manageability in adverse effects. Further research with a larger cohort is suggested to validate these findings and explore the prognostic value of mutation profiles.

Radiologic study of the distance between the maxillary central incisor root and the incisive canal according to skeletal malocclusion classification.

The aim of this study was to evaluate the distance between the maxillary central incisor root and the incisive canal based on skeletal malocclusion classification and to analyze the morphology of the incisive canal using cone-beam computed tomography (CBCT). Skeletal malocclusion was categorized into Class I, II, and III using lateral cephalometric analysis. Measurements of the distance between the maxillary central incisor root and the incisive canal were taken at two levels: 2 mm (L1) and 4 mm (L2) superior to the labial cementoenamel junction of the maxillary central incisor. At L1, the distance was found to be closer in the Class II group compared to the Class I or Class III groups. Similarly, at L2, the Class II group exhibited a closer distance than the Class III group. Interestingly, females showed a closer distance compared to males at both L1 and L2. Further analysis revealed a significant gender difference in the Class I and III groups, but not in the Class II group. These findings emphasize the significance of evaluating the distance between the maxillary central incisor root and the incisive canal in patients with skeletal Class II malocclusion, regardless of gender.

Evaluation of the Current Urgency-Based Lung Allocation System in Korea with Simulation of the Eurotransplant Lung Allocation Score.

PURPOSE: Due to the shortage of lung donors relative to the number of patients waiting for lung transplantation (LTx), more than one-third of patients on the waitlist have died without receiving LTx in Korea. Therefore, the importance of fair and effective allocation policies has been emphasized. This study investigated the characteristics of the current urgency-based allocation system in Korea by simulating the Eurotransplant lung allocation score (ET-LAS) using a nationwide multi-institutional registry for LTx in Korea. MATERIALS AND METHODS: This study used data from the Korean Organ Transplantation Registry (KOTRY), along with additional retrospective data for ET-LAS calculation. A total of 194 patients were included in this study between January 2015 and December 2019. The Korean urgency definition classifies an LTx candidate as having statuses 0-3 according to urgency. The ET-LAS was analyzed according to the Korean urgency status. RESULTS: In total, 92 patients received lung transplants at status 0, 85 at status 1, and 17 at status 2/3. The ET-LAS showed a bimodal distribution with distinct peaks corresponding to status 0 and non-status 0. There was no significant difference in the ET-LAS among non-status 0 patients. In logistic and decision tree analyses, oxygen supplementation methods, particularly oxygen masks and high-flow nasal cannulas, were significantly associated with a high ET-LAS (≥50) among non-status 0 patients. CONCLUSION: Simulation of the ET-LAS with KOTRY data showed that the Korean urgency definition may not allocate lungs by urgency, especially for patients in non-status 0; therefore, it needs to be revised.

Sepsis Alert Systems, Mortality, and Adherence in Emergency Departments: A Systematic Review and Meta-Analysis.

Importance: Early detection and management of sepsis are crucial for patient survival. Emergency departments (EDs) play a key role in sepsis management but face challenges in timely response due to high patient volumes. Sepsis alert systems are proposed to expedite diagnosis and treatment initiation per the Surviving Sepsis Campaign guidelines. Objective: To review and analyze the association of sepsis alert systems in EDs with patient outcomes. Data Sources: A thorough search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane Library from January 1, 2004, to November 19, 2023. Study Selection: Studies that evaluated sepsis alert systems specifically designed for adult ED patients were evaluated. Inclusion criteria focused on peer-reviewed, full-text articles in English that reported on mortality, ICU admissions, hospital stay duration, and sepsis management adherence. Exclusion criteria included studies that lacked a control group or quantitative reports. Data Extraction and Synthesis: The review followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Two independent reviewers conducted the data extraction using a standardized form. Any disagreements were resolved through discussion. The data were synthesized using a random-effects model due to the expected heterogeneity among the included studies. Main Outcomes and Measures: Key outcomes included mortality, intensive care unit admissions, hospital stay duration, and adherence to the sepsis bundle. Results: Of 3281 initially identified studies, 22 (0.67%) met inclusion criteria, encompassing 19 580 patients. Sepsis alert systems were associated with reduced mortality risk (risk ratio [RR], 0.81; 95% CI, 0.71 to 0.91) and length of hospital stay (standardized mean difference [SMD], -0.15; 95% CI, -0.20 to -0.11). These systems were also associated with better adherence to sepsis bundle elements, notably in terms of shorter time to fluid administration (SMD, -0.42; 95% CI, -0.52 to -0.32), blood culture (SMD, -0.31; 95% CI, -0.40 to -0.21), antibiotic administration (SMD, -0.34; 95% CI, -0.39 to -0.29), and lactate measurement (SMD, -0.15; 95% CI, -0.22 to -0.08). Electronic alerts were particularly associated with reduced mortality (RR, 0.78; 95% CI, 0.67 to 0.92) and adherence with blood culture guidelines (RR, 1.14; 95% CI, 1.03 to 1.27). Conclusions and Relevance: These findings suggest that sepsis alert systems in EDs were associated with better patient outcomes along with better adherence to sepsis management protocols. These systems hold promise for enhancing ED responses to sepsis, potentially leading to better patient outcomes.

Clinical Efficacy and Safety of an Automatic Closed-Suction System in Mechanically Ventilated Patients with Pneumonia: A Multicenter, Prospective, Randomized, Non-Inferiority, Investigator-Initiated Trial.

Endotracheal suctioning is an essential but labor-intensive procedure, with the risk of serious complications. A brand new automatic closed-suction device was developed to alleviate the workload of healthcare providers and minimize those complications. We evaluated the clinical efficacy and safety of the automatic suction system in mechanically ventilated patients with pneumonia. In this multicenter, randomized, non-inferiority, investigator-initiated trial, mechanically ventilated patients with pneumonia were randomized to the automatic device (intervention) or conventional manual suctioning (control). The primary efficacy outcome was the change in the modified clinical pulmonary infection score (CPIS) in 3 days. Secondary outcomes were the frequency of additional suctioning and the amount of secretion. Safety outcomes included adverse events or complications. A total of 54 participants, less than the pre-determined number of 102, were enrolled. There was no significant difference in the change in the CPIS over 72 h (-0.13 ± 1.58 in the intervention group, -0.58 ± 1.18 in the control group, p = 0.866), but the non-inferiority margin was not satisfied. There were no significant differences in the secondary outcomes and safety outcomes, with a tendency for more patients with improved tracheal mucosal injury in the intervention group. The novel automatic closed-suction system showed comparable efficacy and safety compared with conventional manual suctioning in mechanically ventilated patients with pneumonia.

Flexible and Dynamic Light-Guided Electrochemiluminescence for Spatiotemporal Imaging of Photoelectrochemical Processes on Hematite.

Here, we report an electrochemiluminescence (ECL)-based approach for imaging of local photoelectrochemical processes on hematite in a spatially and temporally controlled manner. The local processes were guided by flexible and dynamic light illumination, not requiring any prepatterned conductive features or photomasks, with a digital micromirror device (DMD). The imaging approach was based on light-addressable electrochemical reactions on hematite, resulting in photoinduced ECL emission for spatiotemporally resolved imaging of photoelectrochemical processes selectively guided by light illumination. After clarifying the capability of hematite as a photosensitive electrode, we validated that the illuminated hematite exhibited stable light-guided ECL emission in correspondence with the illuminated area, with a spatial resolution of 0.8 µm and a temporal resolution of 1 µs, even over a long period of 6 h. More importantly, this study exemplified the simple yet effective ECL-based approach for electrochemical visualization of local photoelectrochemical processes guided by flexible and dynamic adjustment of light illumination in a spatiotemporally controlled way.

Early dose reduction of dasatinib does not compromise clinical outcomes in patients with chronic myeloid leukemia: A comparative analysis of two prospective trials.

Dasatinib is a potent second-generation tyrosine kinase inhibitor (TKI) used as a first-line treatment option for patients with chronic myeloid leukemia (CML). Currently, dose modification due to adverse events (AEs) is common in patients treated with dasatinib. This study compared the outcomes of two sequential prospective trials that enrolled patients with newly diagnosed chronic phase of CML (CP-CML) and initiated dasatinib at a starting dose of 100 mg daily. In the PCR-DEPTH study, CP-CML patients who started dasatinib 100 mg daily were enrolled and followed up, while in the DAS-CHANGE study, when patients achieved early molecular response with any grade of AEs were enrolled and treated with dasatinib 80 mg once daily. A total of 102 patients (PCR-DEPTH) and 90 patients (DAS-CHANGE) were compared. Although the median value of the relative dose intensity (RDI) of dasatinib was significantly higher in PCR-DEPTH than in DAS-CHANGE (99.6 % vs. 80.1 %, p <0.001), the MMR rate at 12months showed a trend toward superiority in DAS-CHANGE compared to PCR-DEPTH (77.1 % vs 65.2 %, p = 0.084). The frequencies of MR4.0 at 24 and 36 months were higher in DAS-CHANGE than in PCR-DEPTH (44.4 % vs 28.8 %, p = 0.052 and 63.6 % vs 40.3 %, p= 0.013, respectively). RDIs were not different according to the MMR, MR4.0 or MR4.5 in analyses using a pooled population. Our results suggest that early dose reduction of dasatinib does not compromise efficacy in patients achieving EMR at 3 months and could be an interventional strategy for improving long term outcomes.