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The frequency of MET and HER2 amplification being detected by next generation sequencing (NGS) is increasing due to NGS being increasingly adopted for molecular profiling of cancers. However, the accuracy of NGS in detecting these gene amplifications remains uncertain due to conflicting reports in the scientific literature. We studied the accuracy of an amplicon-based large panel NGS assay in detecting MET and HER2 amplification in lung and breast cancers, respectively, by comparing it against conventional testing methods. Amongst 48 lung cancers, four of five cancers that were MET amplified on fluorescence in situ hybridisation (FISH) were classified as amplified on NGS while 42 of the remaining 43 non-amplified cancers were classified as non-amplified on NGS, giving a sensitivity of 80%, specificity of 97.7% and overall concordance of 95.8%. Of the 46 breast cancers tested, only six of the nine cancers that were HER2-positive on immunohistochemistry (IHC)/FISH were HER2-positive on NGS, while all the remaining HER2-negative cases were negative on NGS, giving a sensitivity of 66.7%, specificity of 100% and overall concordance of 93.5%. All the false-negative cases had low level gene amplification (MET:CEP7 or HER2:CEP17 FISH ratio of <3). The low sensitivity for HER2 amplification may be confounded by the small sample size and disproportionate number of cases with low level amplification. In summary, the NGS assay has good concordance with conventional testing methods but may be less sensitive in detecting low level gene amplification., (Copyright © 2023 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.)

Objectives: The need for interoperability at the national level was highlighted in Korea, leading to a consensus on the importance of establishing national standards that align with international technological standards and reflect contemporary needs. This article aims to share insights into the background of the recent national health data standardization policy, the activities of the Health Data Standardization Taskforce, and the future direction of health data standardization in Korea., Methods: To ensure health data interoperability, the Health Data Standardization Taskforce was jointly organized by the public and private sectors in December 2022. The taskforce operated three working groups. It reviewed international trends in interoperability standardization, assessed the current status of health data standardization, discussed its vision, mission, and strategies, engaged in short-term standardization activities, and established a governance system for standardization., Results: On September 15, 2023, the notice of "Health Data Terminology and Transmission Standards" in Korea was thoroughly revised to improve the exchange of health information between information systems and ensure interoperability. This notice includes the Korea Core Data for Interoperability (KR CDI) and the Korea Core Data Transmission Standard (HL7 FHIR KR Core), which are outcomes of the taskforce's efforts. Additionally, to reinforce the standardized governance system, the Health-Data Standardization Promotion Committee was established., Conclusions: Active interest and support from medical informatics experts are needed for the development and widespread adoption of health data standards in Korea.

Background/aims: Four-week treatment of linvencorvir (RO7049389) was generally safe and well tolerated, and showed anti-viral activity in chronic hepatitis B (CHB) patients. This study evaluated the efficacy, safety, and pharmacokinetics of 48-week treatment with linvencorvir plus standard of care (SoC) in CHB patients., Methods: This was a multicentre, non-randomized, non-controlled, open-label phase 2 study enrolling three cohorts: nucleos(t)ide analogue (NUC)-suppressed patients received linvencorvir plus NUC (Cohort A, n=32); treatment-naïve patients received linvencorvir plus NUC without (Cohort B, n=10) or with (Cohort C, n=30) pegylated interferon-α (Peg-IFN-α). Treatment duration was 48 weeks, followed by NUC alone for 24 weeks., Results: 68 patients completed the study. No patient achieved functional cure (sustained HBsAg loss and unquantifiable HBV DNA). By Week 48, 89% of treatment-naïve patients (10/10 Cohort B; 24/28 Cohort C) reached unquantifiable HBV DNA. Unquantifiable HBV RNA was achieved in 92% of patients with quantifiable baseline HBV RNA (14/15 Cohort A, 8/8 Cohort B, 22/25 Cohort C) at Week 48 along with partially sustained HBV RNA responses in treatment-naïve patients during follow-up period. Pronounced reductions in HBeAg and HBcrAg were observed in treatment-naïve patients, while HBsAg decline was only observed in Cohort C. Most adverse events were grade 1-2, and no linvencorvir-related serious adverse events were reported., Conclusion: 48-week linvencorvir plus SoC was generally safe and well tolerated, and resulted in potent HBV DNA and RNA suppression. However, 48-week linvencorvir plus NUC with or without Peg-IFN did not result in the achievement of functional cure in any patient.

Purpose: In patients with out-of-hospital cardiac arrest (OHCA), early and accurate outcome prediction is crucial for making treatment decisions and informing their relatives. A previous study reported an association between high phosphate levels and unfavorable neurological outcomes after return of spontaneous circulation (ROSC); however, its prognostic value was insufficient when used independently. Therefore, this study aimed to validate the usefulness of the phosphate-to-albumin ratio (PAR) in predicting neurological outcomes and in-hospital mortality by incorporating albumin, another known prognostic indicator., Materials and Methods: This multicenter observational study included adult OHCA survivors from October 2015 to June 2021. The primary endpoint was an unfavorable neurological outcome at hospital discharge, defined as a cerebral performance category score of 3-5. The in-hospital mortality rates were also evaluated., Results: Of the 2397 adult OHCA survivors, PAR differed significantly between the unfavorable and favorable neurological outcome groups, as well as between the non-survival and survival to hospital discharge groups (2.4 vs 1.4, 2.5 vs 1.6, respectively). The area under the receiver operating characteristic curve (AUROC) value of the PAR for predicting unfavorable neurological outcome was 0.81 (95% confidence interval [CI], 0.79-0.83), and the AUROC value for predicting in-hospital mortality was 0.76 (95% CI, 0.74-0.78). In multivariable analysis, the PAR was independently associated with unfavorable neurological outcome (odds ratio [OR] 1.30, 95% CI 1.15-1.37; p < 0.001) and in-hospital mortality (OR 1.24, 95% CI 1.12-1.38; p < 0.001)., Conclusion: The PAR is a readily obtainable and independent prognostic indicator for patients with ROSC after OHCA, helping healthcare providers in predicting outcomes., Competing Interests: Declaration of Competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: To present three cases of acute endophthalmitis following intravitreal sustained-release dexamethasone (Ozurdex) with atypical presentation and to discuss the management of these patients., Methods: A retrospective case series of three patients with endophthalmitis following intravitreal sustained-release dexamethasone (Ozurdex) implantation who presented between July 2020 and August 2020., Results: Two of three patients who were treated with topical steroid and antibiotic therapy alone showed favorable outcomes and were managed without the need for intravitreal antibiotics or implant removal. One patient who showed initial response to topical therapy subsequently required pars plana vitrectomy, implant removal, and a single empirical dose of intravitreal antibiotics and antifungal agent due to persistent inflammation., Conclusion: Postintravitreal Ozurdex endophthalmitis, although a rare entity, can present with atypical features of a painless white eye and a delayed onset intraocular inflammation. Although all cases of endophthalmitis should be treated as infective until proven otherwise, it is fair to consider a trial of conservative treatment with topical steroids and antibiotics initially with close monitoring. In cases with poor response to topical therapy, pars planar vitrectomy and implant removal should be strongly considered., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Opthalmic Communications Society, Inc.)

Sex differences in the in-hospital management of sepsis exist. Previous studies either included patients with sepsis that was defined using previous definitions of sepsis or evaluated the 3-h bundle therapy. Therefore, this study sought to assess sex differences in 1-h bundle therapy and in-hospital management among patients with sepsis and septic shock, defined according to the Sepsis-3 definitions. This observational study used data from Korean Shock Society (KoSS) registry, a prospective multicenter sepsis registry. Adult patients with sepsis between June 2018 and December 2021 were included in this study. The primary outcome was adherence to 1-h bundle therapy. Propensity score matching (PSM) and multivariable logistic regression analyses were performed. Among 3264 patients with sepsis, 3129 were analyzed. PSM yielded 2380 matched patients (1190 men and 1190 women). After PSM, 1-h bundle therapy was performed less frequently in women than in men (13.0% vs. 19.2%; p < 0.001). Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently in women than in men (25.4% vs. 31.6%, p < 0.001), whereas adequate fluid resuscitation was performed more frequently in women than in men (96.8% vs. 95.0%, p = 0.029). In multivariable logistic regression analysis, 1-h bundle therapy was performed less frequently in women than in men [adjusted odds ratio (aOR) 1.559; 95% confidence interval (CI) 1.245-1.951; p < 0.001] after adjustment. Among the bundle therapy components, broad-spectrum antibiotics were administered less frequently to women than men (aOR 1.339, 95% CI 1.118-1.605; p = 0.002), whereas adequate fluid resuscitation was performed more frequently for women than for men (aOR 0.629, 95% CI 0.413-0.959; p = 0.031). Invasive arterial blood pressure monitoring was performed less frequently in women than in men. Resuscitation fluid, vasopressor, steroid, central-line insertion, ICU admission, length of stay in the emergency department, mechanical ventilator use, and renal replacement therapy use were comparable for both the sexes. Among patients with sepsis and septic shock, 1-h bundle therapy was performed less frequently in women than in men. Continuous efforts are required to increase adherence to the 1-h bundle therapy and to decrease sex differences in the in-hospital management of patients with sepsis and septic shock., (© 2024. The Author(s).)

Axillary odor is a malodor produced by bacterial metabolism near the apocrine glands, which often causes discomfort in an individual's daily life and social interactions. A deodorant is a personal care product designed to alleviate or mask body odor. Currently, most deodorants contain antimicrobial chemicals and fragrances for odor management; however, direct application to the underarm skin can result in irritation or sensitivity. Therefore, there is a growing interest in technologies that enable disinfection and odor control without the antiperspirants or perfumes. The cold atmospheric plasma temporally generates reactive radicals that can eliminate bacteria and surrounding odors. In this study, cultured Staphylococcus hominis and Corynebacterium xerosis, the causative bacteria of axillary bromhidrosis, were killed after 90% plasma exposure for 3 min. Moreover, the electronic nose system indicated a significant reduction of approximately 51% in 3-hydroxy-3-methylhexanoic acid and approximately 34% in 3-methyl-3-sulfanylhexan-1-ol, the primary components of axillary odor, following a 5-min plasma exposure. These results support the dual function of our deodorant in eliminating bacteria and axillary odors without the chemical agents. Therefore, cold atmospheric plasma-applied deodorant devices have great potential for the treatment and management of axillary odors as a non-contact approach without chemical use in daily life., (© 2024. The Author(s).)

Carbon monoxide (CO) poisoning is difficult to diagnose owing to its nonspecific symptoms. Multiwave pulse oximetry can be used to quickly screen patients for CO poisoning. However, few studies have analyzed patients with CO poisoning who presented to the emergency department (ED). The primary aim of our study was to determine the correlation between COHb levels measured in blood gas analysis and COHb levels measured in multiwave pulse oximetry. Secondary aims were the sensitivity and specificity of the COHb level cutoff value using multiwave pulse oximetry to predict a 25% COHb level in blood gas analysis. This single-center retrospective observational study included patients with CO poisoning who visited the ED of a university-affiliated hospital in Seoul, Korea between July 2021 and June 2023. COHb poisoning was determined using blood gas analysis and multiwave pulse oximetry. The correlation of COHb levels between the two tests was evaluated using correlation analysis. The area under the receiver operating characteristic curve (AUC) of multiwave pulse oximetry was calculated to predict COHb levels from the blood gas analysis. The optimal cutoff values, sensitivity, and specificity of COHb were determined. A total of 224 patients who had COHb levels measured using both multiwave pulse oximetry and blood gas analysis were included in the analysis. In the correlation analysis, COHb showed a high positive correlation with COHb measured using blood gas analysis (Spearman correlation coefficient = 0.86, p < 0.001). The AUC of COHb measured by multiwave pulse oximetry to predict 25% of the COHb level (which can be an indication of hyperbaric oxygen treatment) measured by blood gas analysis was 0.916. When the COHb levels measured with multiwave pulse oximetry were 20% the sensitivity was 81% and the specificity was 83%, and when the COHb levels were 25% the sensitivity was 50% and the specificity was 95%. The COHb value measured using multiwave pulse oximetry blood gas analysis showed a high correlation. However, additional research using large-scale studies is required for validation.

Background: There is a need to update the cardiovascular (CV) Sequential Organ Failure Assessment (SOFA) score to reflect the current practice in sepsis. We previously proposed the modified CV SOFA score from data on blood pressure, norepinephrine equivalent dose, and lactate as gathered from emergency departments. In this study, we externally validated the modified CV SOFA score in multicenter intensive care unit (ICU) patients., Methods: A multicenter retrospective observational study was conducted on ICU patients at six hospitals in Korea. We included adult patients with sepsis who were admitted to ICUs. We compared the prognostic performance of the modified CV/total SOFA score and the original CV/total SOFA score in predicting 28-day mortality. Discrimination and calibration were evaluated using the area under the receiver operating characteristic curve (AUROC) and the calibration curve, respectively., Results: We analyzed 1,015 ICU patients with sepsis. In overall patients, the 28-day mortality rate was 31.2%. The predictive validity of the modified CV SOFA (AUROC, 0.712; 95% confidence interval [CI], 0.677-0.746; P < 0.001) was significantly higher than that of the original CV SOFA (AUROC, 0.644; 95% CI, 0.611-0.677). The predictive validity of modified total SOFA score for 28-day mortality was significantly higher than that of the original total SOFA (AUROC, 0.747 vs. 0.730; 95% CI, 0.715-0.779; P = 0.002). The calibration curve of the original CV SOFA for 28-day mortality showed poor calibration. In contrast, the calibration curve of the modified CV SOFA for 28-day mortality showed good calibration., Conclusion: In patients with sepsis in the ICU, the modified SOFA score performed better than the original SOFA score in predicting 28-day mortality., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

An acute brain lesion (ABL) identified by brain magnetic resonance imaging (MRI) after acute carbon monoxide (CO) poisoning is a strong prognostic factor for the development of delayed neuropsychiatric syndrome (DNS). This study aimed to identify predictors of ABLs on MRI in patients with acute CO poisoning. This was a multicenter prospective registry-based observational study conducted at two tertiary hospitals. A total of 1,034 patients were included. Multivariable logistic regression analysis showed that loss of consciousness (LOC) (adjusted odds ratio [aOR] 2.68, 95% Confidence Interval [CI]: 1.49-5.06), Glasgow Coma Scale (GCS) score < 9 (aOR 2.41, 95% CI: 1.49-3.91), troponin-I (TnI) (aOR 1.22, 95% CI: 1.08-1.41), CO exposure duration (aOR 1.09, 95% CI: 1.05-1.13), and white blood cell (WBC) (aOR 1.05, 95% CI: 1.01-1.09) were independent predictors of ABLs on MRI. LOC, GCS score, TnI, CO exposure duration, and WBC count can be useful predictors of ABLs on MRI in patients with acute CO poisoning, helping clinicians decide the need for an MRI scan or transfer the patient to an appropriate institution for MRI or hyperbaric oxygen therapy., (© 2023. The Author(s).)

Background: This study aimed to investigate the diagnostic performance of the rapid antigen test (RAT) for screening patients with cycle threshold (Ct) values of SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) in the emergency department. Previous studies have shown that Ct values could be used as indicators of infectiousness. Therefore, we considered the Ct value an indicator of potential infectiousness., Methods: This single-center retrospective observational study was conducted between January 1, 2020, and March 31, 2022. Patients who underwent both RT-PCR and RAT for the diagnosis of COVID-19 were included. Patients with negative RT-PCR results were excluded. Patients with Ct values lower than 26 and 30 were considered potentially infectious for COVID-19., Result: A total of 386 patients were analyzed. At Ct value cutoffs of 26 and 30, the result of the RAT showed a sensitivity of 82% and 74%, specificity of 84% and 89%, and area under the curve (AUC) of 0.829 and 0.813, respectively, in the receiver operating characteristic curve. However, the NPV was relatively low at 55% and 25%., Conclusion: The RAT might be a rapid screening tool for detecting patients with the infectiousness of SARS-CoV-2. However, considering the low NPV, it is challenging to depend only on a negative test result from an antigen test to terminate quarantine. Clinicians should consider additional factors, such as the duration of symptoms and the immunocompromised state, for SARS-CoV-2 transmission., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Inc.)

Background & Aims: RG6346 is an N-acetyl-D-galactosamine (GalNAc)-conjugated, double-stranded RNA interference agent targeting the HBV genome S-region. We investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of RG6346 in healthy volunteers and patients with chronic HBV infection (CHB)., Methods: This first-in-human, adaptive, randomized, double-blinded, phase I study recruited three groups of participants: Group A, 30 healthy volunteers received single-dose RG6346 at 0.1, 1.5, 3.0, 6.0, or 12.0 mg/kg, or placebo; Group B, nucleos(t)ide analogue-naïve participants with CHB received single-dose RG6346 at 3.0 mg/kg (n = 6) or placebo (n = 3); Group C, participants with nucleos(t)ide-suppressed CHB received four doses (every 28 days) of RG6346 at 1.5, 3.0, or 6.0 mg/kg (n = 4 in each cohort) or placebo (n = 6)., Results: RG6346 treatment for up to 4 months was safe and well tolerated. The most common adverse event was a mild injection site reaction. Several nucleos(t)ide-naïve participants exhibited self-resolving transaminase elevations with preserved liver function. By the end of RG6346 treatment in Group C (Day 112), the mean reduction from baseline in hepatitis B surface antigen (HBsAg) was 1.39, 1.80, and 1.64 log 10 IU/ml in the 1.5, 3.0, and 6.0 mg/kg cohorts, respectively. Of the 12 participants in Group C, 11 (91.7%) achieved a ≥1 log 10 IU/ml reduction in HBsAg (3 of 11 [27.3%] had the response sustained at conditional follow-up Day 448). No dose-response relationship was apparent between RG6346 and serum HBsAg levels. The RG6346-induced HBsAg response was independent of hepatitis B e antigen status. Moderate-to-marked sustained reductions of hepatitis B core-related antigen, HBV RNA, HBV DNA (in nucleos[t]ide analogue-naïve participants), and hepatitis B e antigen levels were observed., Conclusions: These favorable safety and pharmacodynamic data support the clinical development of RG6346 as the backbone of a finite antiviral treatment regimen, with the goal of sustained HBsAg loss (functional cure) in patients with CHB., Clinical Trial Number: ClinicalTrials.gov NCT03772249., Impact and Implications: Currently available therapies for chronic HBV infection are associated with low rates of functional cure and new, more efficacious treatments are needed. This first-in-human study of RG6346, an RNA interference therapy, showed a favorable safety profile as well as marked and durable reductions in hepatitis B surface antigen levels. These results support the continued development of RG6346 as the backbone of a finite treatment regimen targeting high functional cure rates and are important for HBV researchers and physicians., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

While prior scholarship on preventive health behaviors has focused on identifying their cognitive predictors, emerging literature suggests that emotion may also be an important determinant of health behaviors. Drawing from appraisal theory and the discrete-emotions models of affect, the current study establishes emotional pathways to support for COVID-19 policies and social distancing behavior. Analyses of survey data collected in the U.S. and South Korea demonstrate that negative emotion experienced following partisan media use increases support for COVID-19 policies and social distancing behavior. Particularly, fear and anxiety toward the pandemic emerged as strong mediators in both countries while sadness also mediated the pathways in the U.S.

Background Context: Excessive production of epidural fibrosis in the nerve root can be a pain source after laminectomy. Pharmacotherapy is a minimally invasive treatment option to attenuate epidural fibrosis by suppressing proliferation and activation of fibroblasts, inflammation, and angiogenesis, and inducing apoptosis., Purpose: We reviewed and tabulated pharmaceuticals with their respective signaling axes implicated in reducing epidural fibrosis. Additionally, we summarized current literature for the feasibility of novel biologics and microRNA to lessen epidural fibrosis., Study Design/setting: Systematic Review., Methods: According to the PRISMA guidelines, we systematically reviewed the literature in October 2022. The exclusion criteria included duplicates, nonrelevant articles, and insufficient detail of drug mechanism., Results: We obtained a total of 2,499 articles from PubMed and Embase databases. After screening the articles, 74 articles were finally selected for the systematic review and classified based on the functions of drugs and microRNAs which included inhibition of fibroblast proliferation and activation, pro-apoptosis, anti-inflammation, and antiangiogenesis. In addition, we summarized various pathways to prevent epidural fibrosis., Conclusion: This study allows a comprehensive review of pharmacotherapies to prevent epidural fibrosis during laminectomy., Clinical Significance: We expect that our review would enable researchers and clinicians to better understand the mechanism of anti-fibrosis drugs for the clinical application of epidural fibrosis therapies., Competing Interests: Declaration of Competing Interest One or more of the authors declare financial or professional relationships on ICMJE-TSJ disclosure forms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The present work aims to predict the degradation in the performance of a solid oxide fuel cell (SOFC) cathode owing to cation interdiffusion between the electrolyte and cathode and surface segregation. Cation migration in the (La 0.60 Sr 0.40 ) 0.95 Co 0.20 Fe 0.80 O 3- x (LSCF)-Gd 0.10 Ce 0.90 O 1.95 (GDC) composite cathode is evaluated in relation to time up to 1000 h using scanning transmission electron microscopy (STEM)-energy-dispersive X-ray spectroscopy (EDXS). The resulting insulating phase formed within the GDC interlayer is quantified by means of the volume fraction using a two-dimensional (2D) image analysis technique. For the very first time, the amount of the insulating phase in the GDC interlayer is quantified, and the corresponding performance degradation of the LSCF cathode is predicted. Mathematical relationships are established for the estimation of degradation due to surface segregation of the cathode. The ohmic resistance between the cathode and the GDC interlayer/electrolyte interface and the polarization resistance of the cathode, characterized by electrochemical impedance spectroscopy (EIS), show an excellent match with the predicted results. The combined degradation analysis and modeling for the cathode lifetime prediction provide a systematic understanding of the time-dependent cation migration and segregation behavior.

Solid oxide fuel cells (SOFCs) are highly efficient, low-emission, and fuel-flexible energy conversion devices. However, their commercialization has lagged due to the lack of long-term durability. Among several performance degradation mechanisms, cathode degradation and elemental inter-diffusion of the electrolyte and cathode has been identified as the predominant factors. In the most common SOFC systems, a cobalt-based perovskite material is used, for example LSC or LSCF. These cobalt-based materials offer mixed conductivity and higher concentration of oxygen vacancies as compared to LSM at lower operating temperature leading to favorable reduction kinetics. However, the presence of cobalt results in higher cost, higher thermal expansion co-efficient (TEC) mismatch and most importantly leads to rapid degradation. Various elements like strontium, cobalt, cerium, chromium, or zirconium accumulate or deposit at the electrode-electrolyte interface, which results in sluggish reaction kinetics of the oxygen reduction reaction (ORR). These elements react to form secondary phases that have lower ionic and electronic conductivity, cover active reaction sites, and eventually lead to cell and system deterioration. Over the past decade, several studies have focused on preventative and protective measures to prolong SOFC lifetime which includes novel fabrication techniques, introduction of new layers, addition of thin films to block the cation transport. Such efforts to prevent the formation of insulating phases and decomposition of the cathode have resulted in a remarkable improvement in long-term stability. In this review paper, current research on leading mechanisms responsible for the degradation of cobaltite cathode of solid oxide fuel cell has been summarized and durability improvement strategies of cobalt-based SOFC cathodes have been discussed., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Out-of-hospital cardiac arrest (OHCA) is a major public health problem and a leading cause of death worldwide. Previous studies have focused on improving the survival of people who have had OHCA by analyzing short-term survival outcomes, such as the return of spontaneous circulation, 30-day survival, and survival to discharge. Research has been conducted on prehospital prognostic factors to improve the survival of patients with OHCA, among which the association between socioeconomic status (SES) and survival has been reported. SES could affect bystander cardiopulmonary resuscitation rates and whether OHCA is witnessed, and low cardiopulmonary resuscitation education rates are associated with low SES. It has been reported that areas with high SES have shorter hospital transfer times and more public defibrillators per person. Previous studies have shown the impact of SES disparities on the short-term survival of patients with OHCA. However, understanding the impact of SES on the long-term prognosis of OHCA survivors remains limited. As long-term outcomes are more indicative of a patient's ongoing health care needs and the burden on public health than short-term outcomes, understanding the long-term prognosis of OHCA survivors is important., Objective: This study aimed to identify whether SES influenced the long-term outcomes of OHCA., Methods: Using health claims data obtained from the National Health Insurance (NHI) service in Korea, we included OHCA survivors who were hospitalized between January 2005 and December 2015. The patients were divided into 2 groups: NHI and Medical Aid (MA) groups, with the MA group defined as having a low SES. Cumulative mortality was estimated using the Kaplan-Meier method, and a Cox proportional hazards model was used to evaluate the impact of SES on long-term mortality. A subgroup analysis was performed based on whether cardiac procedures were performed., Results: We followed 4873 OHCA survivors for up to 14 years (median of 3.3 years). The Kaplan-Meier survival curve showed that the MA group had a significantly decreased long-term survival rate compared to the NHI group. With an adjusted hazard ratio (aHR) of 1.52 (95% CI 1.35-1.72), low SES was associated with increased long-term mortality. The overall mortality rate of the patients who underwent cardiac procedures in the MA group was significantly higher than that of the NHI group (aHR 1.72, 95% CI 1.05-2.82). The overall mortality rate of patients without cardiac procedures was also increased in the MA group compared to the NHI group (aHR 1.39, 95% CI 1.23-1.58)., Conclusions: OHCA survivors with low SES had an increased risk of poor long-term outcomes compared with those with higher SES. OHCA survivors with low SES who have undergone cardiac procedures need considerable care for long-term survival., (©Kyung Hun Yoo, Yongil Cho, Jaehoon Oh, Juncheol Lee, Byuk Sung Ko, Hyunggoo Kang, Tae Ho Lim, Sang Hwan Lee. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 11.07.2023.)

Human cord blood-derived γδ T cells (CB γδ ) display a highly diverse TCR γδ repertoire and have a unique subtype composition different from fetal or adult peripheral blood counterparts. We expanded CB γδ in vitro using an irradiated Epstein-Barr virus-transformed feeder cell-based modified rapid expansion protocol (REP). Single-cell RNA sequencing tracked progressive differentiation of naïve CB γδ into cells expressing neoantigen-reactive tumor-infiltrating lymphocyte as well as tissue-resident memory precursor-like and antigen-presenting cell-like gene signatures. TCR γδ clonal tracing revealed a bias toward cytotoxic effector differentiation in a much larger proportion of V δ 2 - clones compared to V δ 2 + clones, resulting in the former being more cytotoxic at the population level. These clonotype-specific differentiation dynamics were not restricted to REP and were recapitulated upon secondary nonviral antigen stimulations. Thus, our data showed intrinsic cellular differences between major subtypes of human γδ T cells already in operation at early postnatal stage and highlighted key areas of consideration in optimizing cell manufacturing processes.

The knowledge of optimal treatments for patients with intracranial solitary fibrous tumor (SFT) is limited, with inconclusive results from previous studies. In this study, we conducted a meta-analysis of relevant studies to identify the prognostic impact of the extent of resection (EOR) and postoperative radiotherapy (PORT) on survival outcomes of patients with intracranial SFT. We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) to identify relevant studies published till April 2022. Progression-free survival (PFS) and overall survival (OS) were the outcomes of interest. Differences between two cohorts (gross total resection [GTR] vs. subtotal resection [STR] and PORT vs. surgery only) were estimated by calculating hazard ratios. Twenty-seven studies were selected for the meta-analysis, including data of 1348 patients (GTR, n = 819 vs. STR, n = 381 and PORT, n = 723 vs. surgery only, n = 578). Pooled hazard ratios of PFS (1, 3, 5, and 10 years) and OS (3, 5, and 10 years) revealed that the GTR cohort showed sustained superiority over the STR cohort. In addition, the PORT cohort was superior to the surgery-only cohort with respect to all PFS periods. Although the 10-year OS between the two cohorts was not statistically different, PORT showed significantly better 3- and 5-year OS than surgery only. The study findings suggest that GTR and PORT provide significant benefits for PFS and OS. Aggressive surgical resection of tumors to achieve GTR followed by PORT should be implemented as optimal treatments for all patients with intracranial SFT when feasible., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Currently, there is no consensus on the number of defibrillation attempts that should be made before transfer to a hospital in patients with out-of-hospital cardiac arrest (OHCA). This study aimed to evaluate the association between the number of defibrillations and a sustained prehospital return of spontaneous circulation (ROSC)., Methods: A retrospective analysis of a multicentre, prospectively collected, registry-based study in Republic of Korea was conducted for OHCA patients with prehospital defibrillation. The primary outcome was sustained prehospital ROSC, and the secondary outcome was a good neurological outcome at hospital discharge, defined as Cerebral Performance Category score 1 or 2. Cumulative incidence of sustained prehospital ROSC and good neurological outcome according to number of defibrillations were examined. Multivariable logistic regression analysis was used to examine whether the number of defibrillations was independently associated with the outcomes., Results: Excluding 172 patients with missing data, a total of 1983 OHCA patients who received prehospital defibrillation were included. The median time from arrest to first defibrillation was 10 (IQR 7-15) min. The numbers of patients with sustained prehospital ROSC and good neurological outcome were 738 (37%) and 549 (28%), respectively. Sustained ROSC rates decreased as the number of defibrillation attempts increased from the first to the sixth (16%, 9%, 5%, 3%, 2% and 1%, respectively). The cumulative sustained ROSC rate, and good neurological outcome rate from initial defibrillation to sixth defibrillation were 16%, 25%, 30%, 34%, 36%, 36% and 11%, 18%, 22%, 25%, 26%, 27%, respectively. With adjustment for clinical characteristics and time to defibrillation, a higher number of defibrillations was independently associated with a lower chance of a sustained ROSC (OR 0.81, 95% CI 0.76 to 0.86) and a lower chance of good neurological outcome (OR 0.86, 95% CI 0.80 to 0.92)., Conclusions: We observed no significant increase in ROSC after five defibrillations, and no absolute increase in ROSC after seven defibrillations. These data provide a starting point for determination of the optimal defibrillation strategy prior to consideration for prehospital extracorporeal cardiopulmonary resuscitation (ECPR) or conveyance to a hospital with an ECPR capability., Trial Registration Number: NCT03222999., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Delayed neuropsychiatric sequelae (DNS) are a severe complication of carbon monoxide (CO) poisoning, and predicting DNS is difficult. This study aimed to investigate whether cardiac markers can be used as biomarkers to predict DNS occurrence following acute CO poisoning., Methods: This was a retrospective observational study that included patients with acute CO poisoning who visited two emergency medical centers in Korea from January 2008 to December 2020. The primary outcome was whether the occurrence of DNS was associated with laboratory results., Results: Of the 1327 patients with CO poisoning, 967 patients were included. Troponin I and BNP were significantly higher in the DNS group. As a result of multivariate logistic regression analysis, it was found that troponin I, mentality, creatine kinase, brain natriuretic peptide, and lactate levels independently influenced DNS occurrence in CO poisoning patients. The adjusted odds ratios for DNS occurrence were 2.12 (95% CI 1.31-3.47, p = 0.002) for troponin I and 2.80 (95% CI 1.81-3.47, p < 0.001) for BNP., Conclusion: Troponin I and BNP might be useful biomarkers for predicting the occurrence of DNS in patients with acute CO poisoning. This finding can help to identify high-risk patients who require close monitoring and early intervention to prevent DNS.

Poly-L-lactic acid (PLLA) fillers correct cutaneous volume loss by stimulating fibroblasts to synthesize collagen and by augmenting the volume. PLLA triggers the macrophage-induced activation of fibroblasts that secrete transforming growth factor-β (TGF-β). However, whether M2 macrophage polarization is involved in PLLA-induced collagen synthesis via fibroblast activation in aged skin is not known. Therefore, we evaluated the effect of PLLA on dermal collagen synthesis via M2 polarization in an H 2 O 2 -induced cellular senescence model and aged animal skin. H 2 O 2 -treated macrophages had increased expression levels of the M1 marker CD80 and decreased expression levels of the M2 marker CD163, which were reversed by PLLA. The expression levels of interleukin (IL)-4 and IL-13, which mediate M2 polarization, were decreased in H 2 O 2 -treated macrophages and increased upon the PLLA treatment. CD163, IL-4, and IL-13 expression levels were decreased in aged skin, but increased after the PLLA treatment. The expression levels of TGF-β, pSMAD2/SMAD2, connective tissue growth factor (CTGF), alpha-smooth muscle actin (α-SMA), collagen type 1A1 (COL1A1), and COL3A1 were also decreased in aged skin, but increased after the PLLA treatment. Moreover, PLLA upregulated phosphatidylinositol 3-kinase p85α (PI3-kinase p85α)/protein kinase B (AKT) signaling, leading to fibroblast proliferation. PLLA decreased the expression of matrix metalloproteinase (MMP) 2 and MMP3, which destroy collagen and elastin fibers in aged skin. The amount of collagen and elastin fibers in aged skin increased following the PLLA treatment. In conclusion, PLLA causes M2 polarization by increasing IL-4 and IL-13 levels and upregulating TGF-β expression and collagen synthesis in aged skin.

Detection and analysis of viral genomes with Nanopore sequencing has shown great promise in the surveillance of pathogen outbreaks. However, the number of virus detection pipelines supporting Nanopore sequencing is very limited. Here, we present VirPipe, a new pipeline for the detection of viral genomes from Nanopore or Illumina sequencing input featuring streamlined installation and customization., Availability and Implementation: VirPipe source code and documentation are freely available for download at https://github.com/KijinKims/VirPipe, implemented in Python and Nextflow., (© The Author(s) 2023. Published by Oxford University Press.)

Burn-related injuries are devastating injuries with a high mortality rate that affect people of all ages worldwide. We assessed the effectiveness of plasma jet treatment in altering the expression of genes involved in wound healing in a prospective longitudinal observational animal study. Six male Sprague-Dawley rats weighing 350 g were used, and burn wounds were made by applying a preheated brass comb (100°C) to the back of the rats, resulting in four full-thickness burn wounds separated by three interspaces. A total of 18 burn wounds were induced on three rats. One side of the burn, on each rat received plasma treatment (plasma group), while the other side did not (control group). The interspaces were subjected to the plasma jet for 2 minutes per day until 7 days post-wounding. Plasma treatment significantly decreased the expression of proinflammatory cytokines. Furthermore, an increase in the expression of anti-inflammatory cytokines was observed in the plasma group. We showed that plasma jet treatment could improve burn wound healing by altering the expression of genes involved in the development of wound healing., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Burn Association.)

Background: Chronic discogenic pain includes degeneration-driven changes under the mechanical macroenvironment of an internal disc, which leads to the progressive changes of biochemical microenvironment that induce abnormal ingrowth of the nociceptor. The propriety of the animal model reflecting the pathologic natural history has not been assessed., Objectives: This study investigated the biochemical evidence of chronic discogenic pain by employing a discogenic pain animal model induced by shear force., Study Design: Animal study utilizing rats in vivo model of a shear force device., Methods: Fifteen rats were divided into 3 groups (n = 5/group) according to the period for which sustained dorsoventral shear force was applied (1 week or 2 weeks); the control group received the spinous attachment unit, without a spring. Pain data were collected using von Frey hairs on the hind paws. Growth factor and cytokine abundance was analyzed in the dorsal root ganglion (DRG) and plasma., Results: After the shear force devices were installed, the significant variables were found to markedly increase in the DRG tissues of the 2-week group; however, they were not altered in the 1-week group. Specifically, interleukin (IL)-6, neurogrowth factor (NGF), transforming growth factor (TGF)-alpha, platelet-derived growth factor (PDGF)-beta, and vascular endothelial growth factor (VEGF) were increased. Meanwhile, the plasma levels of tumor necrosis factor-alpha, IL-1beta, IL-5, IL-6, IL-12, and NGF were increased in the 1-week group; whereas, TGF-alpha, PDGF-beta, and VEGF were increased in the 2-week group., Limitations: The limitations include the general limitations of quadrupedal animals, the poor precision and flexural deformation of shear force devices, inaccuracies regarding the evaluation of histological denaturation, and short intervention and observational periods., Conclusions: This animal model effectively generated biochemical responses to shear loading with evidence of neurological changes induced without direct macrodamage to the outer annulus fibrosus. Chemical internals were induced by mechanical externals among the contributing factors of chronic discogenic pain.

Importance: The recent American Heart Association guidelines added a sixth link in the chain of survival highlighting recovery and emphasized the importance of psychiatric outcome and recovery for survivors of out-of-hospital cardiac arrest (OHCA). The prevalence of psychiatric disorders among this population was higher than that in the general population., Objective: To examine the prevalence of depression or anxiety and the association of these conditions with long-term mortality among individuals who survive OHCA., Design, Setting, and Participants: A longitudinal population-based cohort study was conducted to analyze long-term prognosis in patients hospitalized for OHCA between January 1, 2005, and December 31, 2015, who survived for 1 year or longer. Patients with cardiac arrest due to traumatic or nonmedical causes, such as injuries, poisoning, asphyxiation, burns, or anaphylaxis, were excluded. Data were extracted on depression or anxiety diagnoses in this population within 1 year from the database of the Korean National Health Insurance Service and analyzed April 7, 2022, and reanalyzed January 19 to 20, 2023., Main Outcomes and Measures: Follow-up data were obtained for up to 14 years, and the primary outcome was long-term cumulative mortality. Long-term mortality among patients with and without a diagnosis of depression or anxiety were evaluated., Results: The analysis included 2373 patients; 1860 (78.4%) were male, and the median age was 53.0 (IQR, 44.0-62.0) years . A total of 397 (16.7%) patients were diagnosed with depression or anxiety, 251 (10.6%) were diagnosed with depression, and 227 (9.6%) were diagnosed with anxiety. The incidence of long-term mortality was significantly higher in the group diagnosed with depression or anxiety than in the group without depression or anxiety (141 of 397 [35.5%] vs 534 of 1976 [27.0%]; P = .001). With multivariate Cox proportional hazards regression analysis, the adjusted hazard ratio of long-term mortality for total patients with depression or anxiety was 1.41 (95% CI, 1.17-1.70); depression, 1.44 (95% CI, 1.16-1.79); and anxiety, 1.20 (95% CI, 0.94-1.53)., Conclusions and Relevance: In this study, among the patients who experienced OHCA, those diagnosed with depression or anxiety had higher long-term mortality rates than those without depression or anxiety. These findings suggest that psychological and neurologic rehabilitation intervention for survivors of OHCA may be needed to improve long-term survival.

Objective: The COVID-19 pandemic might have adversely affected outcomes of patients in emergency departments (EDs). The aim of this study is to evaluate the impact of the COVID-19 pandemic on in patients admitted through the emergency department., Methods: This study is a single-center, retrospective, observational cohort study. We compared the prognosis of patients admitted through the ED before the COVID-19 pandemic (November 2018 to June 2019) and after COVID-19 (November 2020 to June 2021). The primary outcome was in-hospital mortality. Multivariable logistic regression analysis was performed to determine whether the COVID-19 pandemic was independently associated with patient prognosis., Results: The number of patients admitted through the ED before and after COVID-19 was 5,333 and 4,625, respectively. The mean ED length of stay before and after COVID-19 was 401 and 442 minutes, respectively (P<0.001). The number of in-hospital deaths before and after COVID-19 were 269 (5.0%) and 322 (7.0%), respectively (P<0.001). Multivariable logistic regression analysis showed that the COVID-19 period was significantly associated with higher in-hospital mortality (adjusted odds ratio, 1.37; 95% confidence interval, 1.12-1.67; P=0.002)., Conclusion: In the COVID-19 period, in-hospital mortality increased compared to that before COVID-19 among hospitalized ED patients.

Since the high configurational entropy-driven structural stability of multicomponent oxide system was proposed Rost et al. in 2015, many experiments and simulations have been done to develop new multicomponent oxides. Although many notable findings have shown unique physical and chemical properties, high configurational entropy oxide systems that have more than 3 distinct cation sites are yet to be developed. By utilizing atomic-scale direct imaging with scanning transmission electron microscopy and AC-impedance spectroscopy analysis, we demonstrated for the first time that a multicomponent equimolar proton-conducting quadruple hexagonal perovskite-related Ba 5 RE 2 Al 2 ZrO 13 (RE = rare earth elements) oxide system can be synthesized even when adding eight different rare earth elements. In particular, as the number of added elements was increased, i.e. , as the configurational entropy was increased, we confirmed that the chemical stability toward CO 2 was improved without a significant decrement of the proton conductivity. The findings in this work broaden the use of the crystal structure to which the multicomponent model can be applied, and a systematic study on the correlation between the configurational entropy and proton conductivity and/or chemical stability is noteworthy.

Welding defects are common during the production of large welded structures. However, few studies have explored methods of compensating for clear welding defects without resorting to re-welding. Here, an ultrasonic peening method to compensate for the deteriorated mechanical properties of overlap weld defects without repair welding was studied. We experimentally investigated changes in the mechanical properties of defective welds before and after ultrasonic peening. The weld specimen with an overlap defect contained a large cavity-type defect inside the weld bead, which significantly reduced the fatigue life. When the surface of the defective test piece was peened, the fatigue life of the weld plate was restored, resulting in an equivalent or higher number of cycles to failure, compared to a specimen with a normal weld. The recovery of mechanical properties was attributed to the effect of surface work hardening by ultrasonic peening and the change in stress distribution. Thus, ultrasonic peening could compensate for the deterioration of mechanical properties such as tensile strength, fatigue life, and elongation due to overlap defects, without resorting to repair welding.

Background: Occupational hand eczema (OHE) is common among healthcare workers (HCWs), especially during the coronavirus disease 2019 (COVID-19) pandemic., Aims: Our study aimed to determine the prevalence of OHE among HCWs and to identify its associated risk factors., Methods: We conducted a cross-sectional study. A self-administered questionnaire study was done. It was followed by a clinical assessment of subjects with skin changes on their hands to determine the likely cause and its severity. Descriptive analysis and inferential analysis were performed to determine the prevalence of OHE and its associated risk factors., Results: A total of 1004 HCWs with a mean age of 34.58 years old were recruited. Of these, 50.1% were nurses, another 24.6% were doctors. A 1-year prevalence of 42.3% and a point prevalence of 16.5% were reported. Dry skin ( n = 368, 86.6%) and itching ( n = 274, 64.5%) were the common symptoms. Risk factors that were significantly associated with OHE were atopic eczema, allergic rhinitis, frequent hand washing and caring for children under four years old, whereas HCWs who frequently use alcoholic disinfectant and moisturizer hand cream showed lower odds of OHE. No significant association was found between age, gender, profession, involvement in COVID-19 care, number or duration of glove usage and occurrence of hand eczema., Conclusions: We report a high prevalence of OHE among HCWs during the current COVID-19 pandemic. Education and effective preventive measures are paramount to prevent and improve occupational dermatosis., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Indian Journal of Dermatology.)

A reliable prognostic score for minimizing futile treatments in advanced cancer patients with septic shock is rare. A machine learning (ML) model to classify the risk of advanced cancer patients with septic shock is proposed and compared with the existing scoring systems. A multi-center, retrospective, observational study of the septic shock registry in patients with stage 4 cancer was divided into a training set and a test set in a 7:3 ratio. The primary outcome was 28-day mortality. The best ML model was determined using a stratified 10-fold cross-validation in the training set. A total of 897 patients were included, and the 28-day mortality was 26.4%. The best ML model in the training set was balanced random forest (BRF), with an area under the curve (AUC) of 0.821 to predict 28-day mortality. The AUC of the BRF to predict the 28-day mortality in the test set was 0.859. The AUC of the BRF was significantly higher than those of the Sequential Organ Failure Assessment score and the Acute Physiology and Chronic Health Evaluation II score (both p < 0.001). The ML model outperformed the existing scores for predicting 28-day mortality in stage 4 cancer patients with septic shock. However, further studies are needed to improve the prediction algorithm and to validate it in various countries. This model might support clinicians in real-time to adopt appropriate levels of care.

Background & Aims: RNA interference therapy has been shown to reduce hepatitis B surface antigen (HBsAg) levels in preclinical models, which could confer functional cure in patients with chronic hepatitis B. This phase IIa trial (ClinicalTrials.gov Identifier: NCT03365947) assessed the safety and efficacy of the small-interfering RNA JNJ-73763989 (JNJ-3989) plus a nucleos(t)ide analogue (NA), with/without the capsid assembly modulator JNJ-56136379 (JNJ-6379) in patients with chronic hepatitis B., Methods: Treatment-naïve and NA-suppressed patients received 3 subcutaneous JNJ-3989 doses every week (QW; 100, 200, or 300 mg), 2 weeks (Q2W; 100 mg) or 4 weeks (Q4W; 25, 50, 100, 200, 300, or 400 mg), or JNJ-3989 Q4W (200 mg) plus oral JNJ-6379 250 mg daily for 12 weeks. Patients received NAs throughout., Results: Eighty-four patients were recruited. All treatments were well tolerated, with all 5 serious adverse events considered unrelated to study drugs. JNJ-3989 100 to 400 mg Q4W resulted in HBsAg reductions ≥1 log 10 IU/ml from baseline in 39/40 (97.5%) patients at the nadir. All patients receiving the triple combination (n = 12) had HBsAg reductions ≥1 log 10 IU/ml from baseline at the nadir. HBsAg reductions were similar for HBeAg-positive (n = 21) and HBeAg-negative (n = 47) patients in all JNJ-3989 Q4W treatment arms, including the triple combination (n = 68). Smaller HBsAg reductions were seen with 25 mg (n = 8) and 50 mg (n = 8) than with 100 to 400 mg (n = 40). Shorter dosing intervals (QW [n = 12] and Q2W [n = 4]) did not improve response vs. Q4W dosing. HBsAg reductions ≥1 log 10 IU/ml from baseline persisted in 38% of patients 336 days after the last JNJ-3989 dose., Conclusions: JNJ-3989 plus an NA, with/without JNJ-6379, was well tolerated and resulted in HBsAg reductions up to 336 days after the last JNJ-3989 Q4W dose., Clinical Trial Number: NCT03365947., Lay Summary: Hepatitis B virus affects people's livers and produces particles called hepatitis B surface antigen (HBsAg) that damage a person's liver and can help the virus infect a person for a long time, known as chronic hepatitis B (CHB). In this study, a new treatment called JNJ-3989 was assessed (in combination with normal treatment known as nucleos(t)ide analogues), for its safety and effectiveness in reducing the number of HBsAg particles in people with CHB. The results of this study showed that treatment with JNJ-3989 could be safe for people with CHB, lowered their HBsAg levels, and kept HBsAg levels lowered for 336 days in 38% of patients after receiving their last dose of JNJ-3989., Competing Interests: Conflicts of interest MFY serves as advisor/consultant for AbbVie, Arbutus Biopharma, Allovir International, Aligos Therapeutics, Clear B Therapeutics, Dicerna Pharmaceuticals, Finch Therapeutics, GlaxoSmithKline, Gilead Sciences, Janssen, Merck Sharp and Dohme, and Roche and received grant/research support from Assembly Biosciences, Arrowhead Pharmaceuticals, Dicerna Pharmaceuticals, Gilead Sciences, Merck Sharp and Dohme, Roche, and Vir Biotechnology. SS received honoraria for advisory boards or speaker fees from AbbVie, AstraZeneca, Bayer, BMS, Chiesi, CSL Behring, Dr Falk, Eisai, Gilead, Ipsen, MSD, Pfizer, and Roche Products. WS received payments from Janssen for providing a clinical site for the current study. AJT served on advisory boards for Janssen, Gilead, AbbVie, Merck, BMS, Roche, Bayer, Eisai, Roche Diagnostics, and Assembly Biosciences; received speaker fees from Gilead, AbbVie, Merck, Roche, and BMS; received institutional research grants from NHMRC/MRFF, Gilead Sciences, and Roche Diagnostics; and serves as a board member and director of the Gastroenterological Society of Australia. BG, TS, and JH are current or former employees of Arrowhead and may be Arrowhead shareholders. MB, RK, MB, OL, and FDR are current or former employees of Janssen Pharmaceuticals and may be Johnson & Johnson stockholders. GC is an Abbott employee and shareholder. KJ receives funding from SpringBank Pharmaceuticals. CLL discloses sponsored lectures for Gilead Sciences. RGG is/has been a consultant and/or advisor to Abbot, AbbVie, Access Biologicals, Alexion, Antios, Arrowhead, Bayer AG, Bristol Myers Squibb, Eiger, Eisai, Enyo, eStudySite, Forty-Seven Inc, Gilead Sciences, HepaTX, HepQuant, Intercept, Ionis Pharmaceuticals, Janssen, Laboratory for Advanced Medicine, Lilly, Merck, Salix, Shionogi, and Trimaran and Viking Therapeutics; provides consulting for ADMA Biologics, AEC Partners, Arena Pharmaceuticals Inc, Arterys Inc, Cirina, Consumer Health Products Assoc, DRG Abacus, Intellia, Iqvia, KannaLife, Labyrinth Holdings, Organovo, Patient Connect and Spring Bank; is on scientific or clinical advisory boards for Abbott, AbbVie, Merck, Arrowhead, Bayer, Dova Pharmaceuticals, Eiger, Enyo, Hatch Biofund, HepQuant, Intercept, Janssen, and Medimmune; is an advisory consultant for Biocollections, Fujifilm/Wako, and Quest; is chair of the clinical advisory board for Prodigy, is on the data safety monitoring board for Altimmune, Arrowhead, CymaBay Therapeutics, and Durect; has speaker contracts with AbbVie, Bayer, Bristol Myers Squibb, Dova Pharmaceuticals, Eisai, Genentech, Gilead, Intercept, Salix, and Shionogi; is a minor stock shareholder in Athenex, Cocrystal, RiboSciences, and Triact; and holds stock options in Athenex, Eiger, HepaTx, and HepQuant; over 80% of income from Pharma received by RGG is directed to research, education, public policy, and/or donated to charities. EG has been an advisor and/or speaker for AbbVie, Arrowhead, Assembly, Gilead, GSK, Janssen, Merck, Novartis, Roche, and Vir Biotechnology. SL, THL, WC, CS, and DKHW have no disclosures to report. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: To evaluate the predictors of complete polypoidal lesion regression (CPREG) in polypoidal choroidal vasculopathy., Methods: Post hoc analysis of EVEREST II-a 24-month, multicenter, randomized, controlled clinical trial of 322 patients with polypoidal choroidal vasculopathy, randomized to receive ranibizumab with or without photodynamic therapy. Images of indocyanine green angiography (ICGA) were graded by a central reading center. Multiple logistic regression analysis with significant baseline predictors then was conducted to assess adjusted odds ratios for CPREG at month (M) 12., Results: Baseline ICGA characteristics were comparable between the treatment groups. Patients treated with combination therapy had higher odds of achieving CPREG at M12 (adjusted odds ratio = 4.64; 95% confidence interval, 2.85-7.55; P < 0.001) compared with those in the monotherapy group. Absence of polypoidal lesion pulsation on ICGA was also associated with CPREG at M12 (adjusted odds ratio = 2.62; 95% confidence interval, 1.32-5.21; P = 0.006). The presence of CPREG at M3 had higher odds of maintaining CPREG at M12 (adjusted odds ratio = 6.60; 95% confidence interval, 3.77-11.57; P < 0.001) compared with those with persistent polypoidal lesions., Conclusion: At M12, treatment with combination therapy was associated with higher probability of achieving CPREG than with ranibizumab monotherapy. The results contribute to the further understanding of the response of polypoidal lesions to treatment.

We aimed to evaluate early phase serum albumin levels in and outcomes of resuscitated patients after cardiac arrest. Medline, EMBASE, and the Cochrane Library were systematically searched until 4 July 2022, for studies on post-cardiac arrest patients and involving measurement of early phase albumin levels and assessment of in-hospital mortality or neurologic outcomes. Two reviewers independently assessed the methodological quality of the included studies using the Quality in Prognosis Studies tool. We included 3837 patients from seven observational studies in this systematic review and meta-analysis. The serum albumin level was significantly higher in survivors than in non-survivors, showing a positive association with an overall standardized mean difference (SMD) [(mean value of non-survivors—mean value of survivors)/pooled standard deviation] of 0.55 (95% confidence interval [CI], 0.48−0.62; I2 = 0%; p < 0.001). Additionally, the serum albumin level was significantly higher in the good neurologic outcome group than in the poor neurologic outcome group (four studies; SMD = 1.01, 95% CI = 0.49−1.52, I2 = 87%; p < 0.001). Relatively low serum albumin levels in the early phase may be associated with in-hospital mortality of resuscitated patients after cardiac arrest. However, we could not evaluate the association between albumin level and neurologic outcome because of limited included studies and unresolved high heterogeneity.

Adverse drug events are significant causes of emergency department visits. Systematic evaluation of adverse drug events leading to emergency department visits by age is lacking. This multicenter retrospective observational study evaluated the prevalence and features of adverse drug event-related emergency department visits across ages. We reviewed emergency department medical records obtained from three university hospitals between July 2014 and December 2014. The proportion of adverse drug events among total emergency department visits was calculated. The cause, severity, preventability, and causative drug(s) of each adverse drug event were analyzed and compared between age groups (children/adolescents [<18 years], adults [18-64 years], and the elderly [≥65 years]). Of 59,428 emergency department visits, 2,104 (3.5%) were adverse drug event-related. Adverse drug event-related emergency department visits were more likely to be female and older. Multivariate logistic regression analysis revealed that compared to non- adverse drug event-related cases, adverse drug event-related emergency department visitors were more likely to be female (60.6% vs. 53.6%, p<0.001, OR 1.285, 95% CI 1.025-1.603) and older (50.8 ± 24.6 years vs. 37.7 ± 24.4 years, p<0.001, OR 1.892, 95% CI: 1.397-2.297). Comorbidities such as diabetes, chronic kidney disease, chronic liver disease, and malignancies were also significantly associated with adverse drug event-related emergency department visits. Side effects were the most common type of adverse drug events across age groups, although main types differed substantially depending on age. Serious adverse drug events, hospitalizations, and adverse drug event-related deaths occurred more frequently in the elderly than in adults or children/adolescents. The proportion of adverse drug event-related emergency department visits that were preventable was 15.3%. Causative drugs of adverse drug events varied considerably depending on age group. Adverse drug event features differ substantially according to age group. The findings suggest that an age-specific approach should be adopted in the preventive strategies to reduce adverse drug events., Competing Interests: The authors have declared that no competing interests exist.

Background: The Sepsis-3 criteria introduced the system that uses the Sequential Organ-Failure Assessment (SOFA) score to define sepsis. The cardiovascular SOFA (CV SOFA) scoring system needs modification due to the change in guideline-recommended vasopressors. In this study, we aimed to develop and to validate the modified CV SOFA score., Methods: We developed, internally validated, and externally validated the modified CV SOFA score using the suspected infection cohort, sepsis cohort, and septic shock cohort. The primary outcome was 28-day mortality. The modified CV SOFA score system was constructed with consideration of the recently recommended use of the vasopressor norepinephrine with or without lactate level. The predictive validity of the modified SOFA score was evaluated by the discrimination for the primary outcome. Discrimination was assessed using the area under the receiver operating characteristics curve (AUC). Calibration was assessed using the calibration curve. We compared the prognostic performance of the original CV/total SOFA score and the modified CV/total SOFA score to detect mortality in patients with suspected infection, sepsis, or septic shock., Results: We identified 7,393 patients in the suspected cohort, 4038 patients in the sepsis cohort, and 3,107 patients in the septic shock cohort in seven Korean emergency departments (EDs). The 28-day mortality rates were 7.9%, 21.4%, and 20.5%, respectively, in the suspected infection, sepsis, and septic shock cohorts. The model performance is higher when vasopressor and lactate were used in combination than the vasopressor only used model. The modified CV/total SOFA score was well-developed and internally and externally validated in terms of discrimination and calibration. Predictive validity of the modified CV SOFA was significantly higher than that of the original CV SOFA in the development set (0.682 vs 0.624, p < 0.001), test set (0.716 vs 0.638), and all other cohorts (0.648 vs 0.557, 0.674 vs 0.589). Calibration was modest. In the suspected infection cohort, the modified model classified more patients to sepsis (66.0 vs 62.5%) and identified more patients at risk of septic mortality than the SOFA score (92.6 vs 89.5%)., Conclusions: Among ED patients with suspected infection, sepsis, and septic shock, the newly-developed modified CV/total SOFA score had higher predictive validity and identified more patients at risk of septic mortality., (© 2022. The Author(s).)

This paper proposes a 5G glass antenna that can be printed on the thick window glass of a vehicle. The proposed antenna consists of a coplanar waveguide (CPW), a printed monopole radiator, parasitic elements, a linearly arrayed patch director, and a grid-slotted patch reflector. The linearly arrayed patch director and grid-slotted patch reflector are applied to improve the bore-sight gain of the antenna. To verify the performance improvement and feasibility, the proposed antenna is fabricated, and a reflection coefficient and a radiation pattern are measured and compared with the simulation results. The measured reflection coefficient shows broadband characteristics of less than -10 dB from 24.1 GHz to 31.0 GHz (fractional bandwidth of 24.6%), which agrees well with the simulation results. The reflection coefficients are -33.1 dB by measurement and -25.7 dB by simulation, and the maximum gains are 6.2 dBi and 5.5 dBi at 28 GHz, respectively. These results demonstrate that the proposed antenna has high-gain characteristics being suitable for 5G wireless communications.

Background: Antenatal antiviral therapy (AVT) is effective in preventing mother-to-child transmission (MTCT) in chronic hepatitis B (CHB); tenofovir disoproxil fumarate (TDF) is the preferred agent. Tenofovir alafenamide (TAF) is a prodrug of tenofovir (TFV) similar to TDF, with improved bone and renal safety. There are no data on TAF breast milk pharmacokinetics and exposure to breastfeeding infants in CHB., Aim: To assess the pharmacokinetics of TAF/TFV in breastfeeding women with CHB on TAF monotherapy., Methods: Pregnant women with CHB requiring AVT commenced TAF 25 mg daily at third trimester or postpartum. Sample collection occurred while breastfeeding and taking TAF for minimum 4 weeks. Maternal blood, breast milk and infant urine samples were collected. Drug concentrations were measured by LCMS/MS analyses using validated methods. Non-compartmental analyses were performed to quantify the pharmacokinetic parameters., Results: Eight women provided samples. In breast milk and plasma, median TAF half-life was 0.81 and 0.94 h, respectively, and C max 1.69 and 120.5 ng/ml, respectively. Median maternal breast milk to plasma (M/P) ratio of TAF was 0.029; for and TFV it was 2.809. The relative infant dose of TAF was 0.005% of maternal dose, well below safety threshold of 5-10%. TFV was detectable in three out of seven infant urine samples with median steady-state concentration of 5 ng/ml being 300-2500 times less than reported adult steady-state urine concentrations in those taking TAF and TDF, respectively., Conclusions: In this first pharmacokinetic study of TAF monotherapy in breastfeeding women with CHB, concentrations of TAF and TFV were low in breast milk with negligible infant exposure, supporting the use of TAF to prevent MTCT., (© 2022 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

The rapid antigen test (RAT) has been adopted as a screening tool for SARS-CoV-2 infection in many emergency departments (EDs). We aimed to investigate the diagnostic value of the accuracy of the SARS-CoV-2 RAT as a screening tool in the ED. This retrospective observational study included patients who underwent both RAT and RT−PCR and visited the ED from 1 December 2021 to 15 March 2022. RAT and RT−PCR were performed by appropriately trained physicians. We performed detailed analyses using the E gene cyclic threshold (Ct) values of RT−PCR. Out of a total of 1875 patients, 348 (18.6%) had positive and 1527 (81.4%) had negative RT−PCR results. The overall sensitivity, specificity, positive predictive value, and negative predictive value of the RAT were 67.8%, 99.9%, 99.6%, and 93.2%, respectively. The E gene Ct value was significantly lower in the RAT-positive patients than in the RAT-negative patients (18.5 vs. 25.3, p < 0.001). When the E gene Ct cutoff was 30.0, 25.0, 20.0, and 15.0, the sensitivity of the RAT was 71.9%, 80.3%, 93.0%, and 97.8%, respectively. The sensitivity of the RAT could be considered high in patients with a high viral load, and the RAT could be used as a screening tool in the ED.

Background: Acne vulgaris is a common skin condition that affects adolescents and young adults. Its psychosocial impact can be significant. The primary objective of this study was to determine the prevalence of acne vulgaris and its psychosocial impact among high school and university students in Kuching, Sarawak. In addition, the clinical characteristics of acne and its potential predisposing factors were assessed., Methods: This cross-sectional study was conducted among high school and university students in Kuching, Sarawak. A team of dermatology-trained doctors examined a representative sample of high school and university students aged 16 to 25 years to identify acne vulgaris. The Dermatology Life Quality Index (DLQI) was used to assess the psychosocial impact of acne on affected individuals. The Global Acne Grading System (GAGS) was used to determine the severity of acne. Demographic data and clinical characteristics of acne were recorded., Results: A total of 582 students aged 16 to 25 years were recruited. The overall prevalence of acne vulgaris was 75.8% (n=441). The prevalence of acne was highest (85.5%) in the age group of 16-18 years. There was a significantly higher tendency for male students to have moderate to severe acne (p=0.010). A significantly higher proportion of female students had impaired quality of life (p<0.001) compared to male students. In comparison to male students, the mean DLQI scores were significantly higher in female students in the domains of 'Work and school' and 'Personal relationship' (p<0.05). There were 41 students who had a very large impact on the quality of life with a DLQI score of 11-20 and 34 (82.9%) of them had mild acne. There was a significantly higher proportion of students who had frequent insomnia in the group of students with acne compared to those without acne (11.6% vs. 4.3%, p=0.011). There was no significant association of acne vulgaris with dietary intakes, such as chocolates, sweets, potato chips, yoghurt, milk, fried chicken, ice cream, nuts and carbonated drinks (p>0.05). Of the 441 students with acne, 247 (56%) had not sought any medical attention., Conclusion: Acne vulgaris impacts the quality of life similarly to psoriasis, atopic eczema, and chronic urticaria. In mild acne cases, the quality of life may be significantly affected. Therefore, acne education is required in high schools and colleges to ensure that students understand their disease and are aware of available treatments.

Background and objectives : This study aims to evaluate the usefulness of the quantitative pupillary light reflex as a prognostic tool for neurological outcomes in post-cardiac arrest patients treated with targeted temperature management (TTM). Material and Methods : We systematically searched MEDLINE, EMBASE, and the Cochrane Library (search date: 9 July 2021) for studies on post-cardiac arrest patients treated with TTM that had measured the percent constriction of pupillary light reflex (%PLR) with quantitative pupillometry as well as assessed the neurological outcome. For an assessment of the methodological quality of the included studies, two authors utilized the prognosis study tool independently. Results : A total of 618 patients from four studies were included in this study. Standardized mean differences (SMDs) were calculated to compare patients with good or poor neurological outcomes. A higher %PLR measured at 0-24 h after hospital admission was related to good neurological outcomes at 3 months in post-cardiac arrest patients treated with TTM (SMD 0.87; 95% confidence interval 0.70-1.05; I 2 = 0%). A higher %PLR amplitude measured at 24-48 h after hospital admission was also associated with a good neurological outcome at 3 months in post-cardiac arrest patients treated with TTM, but with high heterogeneity (standardized mean difference 0.86; 95% confidence interval 0.40-1.32; I 2 = 70%). The evidence supporting these findings was of poor quality. For poor neurological outcome, the prognosis accuracy of %PLR was 9.19 (pooled diagnostic odds ratio, I 2 = 0%) and 0.75 (area under the curve). Conclusions : The present meta-analysis could not reveal that change of %PLR was an effective tool in predicting neurological outcomes for post-cardiac arrest patients treated with TTM owing to a paucity of included studies and the poor quality of the evidence.

The study aimed to evaluate the impact of the updated 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on Human Epidermal Growth Factor Receptor 2 (HER2) testing in invasive breast cancer compared with previous 2013 guidelines. Between Jan 2014 and May 2020, 3364 consecutive invasive breast carcinomas with concurrent HER2 immunohistochemistry (IHC) and fluorescence in-situ hybridization (FISH) results were retrospectively reviewed for HER2 status. Both 2013 and 2018 testing criteria were applied to establish the HER2 status. The testing algorithms involved testing of invasive breast carcinomas by IHC, with equivocal results being reflexed to FISH assays. Concordance rate improved from 92.7% to 94.1% in the non-equivocal IHC cases with the 2018 guidelines. Comparing 2013 versus 2018 criteria, HER2 non-amplified cases increased significantly from 73.7% (n = 2478) to 76.8% (n = 2585), HER2 amplified cases remained similar from 23.4% (n = 789) to 23.2% (n = 779) while equivocal cases decreased from 2.9% (n = 97) to 0% with the new guidelines. Thus, 107 cases (3.2%) were reclassified from HER2 equivocal (n = 97) and amplified (n = 10) to non-amplified with the updated 2018 guidelines. Under the 2018 criteria, a total of 259 cases (7.7%) belonged to the uncommon categories (groups 2 to 4), with group 3 being the most frequent (4.6%), followed by group 4 (2.9%) and group 2 (0.2%). Implementation of 2018 guidelines resulted in a significant increase in HER2 non-amplified cases, mainly due to the abolishment of the equivocal FISH group. This has helped resolve the clinical practice dilemma by providing a more definitive HER2 gene status., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Longitudinal evidence on retinal microvasculature and subsequent systemic inflammatory alteration is lacking. We investigated the association between retinal microvasculature and immune response among patients with HIV/AIDS over a 9-month antiretroviral therapy., Methods: We conducted a prospective cohort study on patients with HIV/AIDS at Singapore Communicable Disease Centre since June 2011. We recruited all eligible patients and then reviewed them every 3 months over a 9-month follow-up, including performing blood tests (CD4+/CD8+ T-cell counts and HIV viral load), blood pressure, anthropometry measurements, and retinal photography at each visit. We assessed retinal vascular indexes using a semiautomated computer-based program. Finally, we applied a linear mixed model to analyze associations between baseline retinal vascular indexes and 9-month changes of CD4+/CD8+ T-cell counts and HIV viral load throughout study observation, after adjusting for major confounders., Results: We found that narrower arteriolar caliber (per 10 μm decrease), wider venular caliber (per 10 μm increase), and larger arteriolar branching angle (per 10° increase) in the retina assessed at baseline were significantly associated with 9-month reductions in CD4+ T-cell count by 52.97 cells/μL (P = 0.006), 33.55 cells/μL (P = 0.01), and 39.09 cells/μL (P = 0.008), accordingly., Conclusion: Patients with HIV/AIDS with a suboptimal retinal microvascular morphology tended to fail immune restoration undertaking a 9-month antiretroviral therapy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To examine the association of inferior vena cava (IVC) diameter ratio measured using computed tomography with outcomes in patients with gastrointestinal bleeding (GIB)., Methods: A single-center retrospective observational study was conducted on consecutive patients with GIB who presented to the emergency department. The IVC diameter ratio was calculated by dividing the maximum transverse and anteroposterior diameters perpendicular to it. The association of the IVC diameter ratio with outcomes was examined using multivariable logistic regression analysis. The primary outcome was in-hospital mortality. The area under the receiver operator characteristic curve (AUC) of the IVC diameter ratio was calculated, and the sensitivity and specificity, including the cutoff values, were computed., Results: In total, 585 patients were included in the final analysis. The in-hospital mortality rate was 4.6% (n=27). The IVC diameter ratio was significantly associated with higher in-hospital mortality in multivariable logistic regression analysis (odds ratio, 1.793; 95% confidence interval [CI], 1.239-2.597; P=0.002). The AUC of the IVC diameter ratio for in-hospital mortality was 0.616 (95% CI, 0.498-0.735). With a cutoff of the IVC diameter ratio (≥2.1), the sensitivity and specificity for predicting in-hospital mortality were 44% (95% CI, 26%-65%) and 71% (95% CI, 67%-75%), respectively., Conclusion: The IVC diameter ratio was independently associated with in-hospital mortality in patients with GIB. However, the AUC of the IVC diameter ratio for in-hospital mortality was low.