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Hye-Rin Kang,1,* So Jeong Kim,2,* Ju Gang Nam,3 Young Sik Park,4 Chang-Hoon Lee4 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Veteran Health Service Medical Center, Seoul, 05368, Republic of Korea; 2Division of Pulmonology and Allergy, Hallym University Dongtan Sacred Heart Hospital, Gyeonggi-do, 18450, Republic of Korea; 3Department of Radiology, Seoul National University Hospital, Seoul, 03080, Republic of Korea; 4Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, Seoul, 03080, Republic of Korea*These authors contributed equally to this workCorrespondence: Chang-Hoon Lee, Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-Ro Jongno-Gu, Seoul, 03080, Republic of Korea, Tel +82-2-2072-4743, Fax +82-2-762-9662, Email kauri670@empal.comIntroduction: Mortality differences in chronic obstructive pulmonary disease (COPD) between nonsmokers and smokers remain unclear. We compared the risk of death associated with smoking and COPD on mortality.Methods: The study included participants aged ≥ 40 years who visited pulmonary clinics and were categorised into COPD or non-COPD and smoker or nonsmoker on the basis of spirometry results and cigarette consumption. Mortality rates were compared between groups using statistical analysis for all-cause mortality, respiratory disease-related mortality, and cardiocerebrovascular disease-related mortality.Results: Among 5811 participants, smokers with COPD had a higher risk of all-cause (adjusted hazard ratio (aHR), 1.69; 95% confidence interval (CI), 1.23– 2.33) and respiratory disease-related mortality (aHR, 2.14; 95% CI, 1.20– 3.79) than nonsmokers with COPD. Non-smokers with and without COPD had comparable risks of all-cause mortality (aHR, 1.39; 95% CI, 0.98– 1.97) and respiratory disease-related mortality (aHR, 1.77; 95% CI, 0.85– 3.68). However, nonsmokers with COPD had a higher risk of cardiocerebrovascular disease-related mortality than nonsmokers without COPD (aHR, 2.25; 95% CI, 1.15– 4.40).Conclusion: The study found that smokers with COPD had higher risks of all-cause mortality and respiratory disease-related mortality compared to nonsmokers with and without COPD. Meanwhile, nonsmokers with COPD showed comparable risks of all-cause and respiratory mortality but had a higher risk of cardiocerebrovascular disease-related mortality compared to nonsmokers without COPD.Keywords: pulmonary disease, chronic obstructive, smokers, nonsmokers, cigarette smoking, comorbidity

This study investigated the impact of temporal light modulation (TLM) generated by light-emitting diode lighting on visual task performance. Five lighting conditions were used in this study. One was a direct current, and the other four used pulse-width modulation with 60 Hz, 100 Hz, 400 Hz and 1000 Hz modulation frequencies, respectively. The study assessed participants' performance in various visual tasks involving eye movements, including arithmetic problem-solving, linking numbers tasks and the CamBlobs™ Contrast Sensitivity test. The experimental results showed that the response time of visual tasks related to typical daily eye movements, such as the arithmetic problem-solving task and the CamBlobs™ Contrast Sensitivity task, were in proportion to the PstLM, which showed the influence of flicker. In contrast, the linking numbers task, which required more extensive eye movements and object movements, was more relevant to the stroboscopic visibility measure than P st LM , which showed a higher influence of stroboscopic effect than flicker. These findings underscore the significance of considering TLM parameters when designing lighting systems for environments where visual tasks are crucial. This research contributes to our understanding of how light modulation affects human performance in visually demanding settings and has implications for optimising lighting design to enhance task performance. [ABSTRACT FROM AUTHOR]

A phantom array can be observed when there are saccadic eye movements across a time-modulated light source. In this study, the highest frequency limit of the phantom array effect that can be observed was investigated using an LED light source by estimating the participant's threshold frequency for the visibility of the phantom array effect using the weighted up-down method. A high luminance, narrow slit, warm white LED, and long saccadic eye movement range were used as the experimental stimuli and conditions. The mean threshold frequency for young adults was approximately 10 kHz under the proposed experimental conditions. The phantom array effect was observed even above 15 kHz in the high threshold frequency group when we divided participants into three groups according to the threshold frequency. In addition, the high threshold frequency group showed a higher eye movement speed than the other groups. [ABSTRACT FROM AUTHOR]

LEDs are widely used for both general and automotive lighting since their brightness can be easily regulated by controlling their on/off time using methods such as pulse width modulation (PWM). However, lighting control using PWM can cause temporal light artefacts, such as the phantom array effect, which affect human visual perception. In this study, we determined the influence of different colour temperatures on the visibility of the phantom array effect using five LEDs with different spectral distributions (red, green, blue, warm white and cool white) and frequencies of temporal modulation ranging from 1 kHz to 11 kHz. The threshold of the warm white LED was between that of the green and red LEDs, and threshold of the cool white LED was between that of the red and blue LEDs. The experimental results revealed a difference in the threshold frequency of the visibility of the phantom array effect, in accordance with the spectral distribution and the colour temperature of the light source. [ABSTRACT FROM AUTHOR]

Light-emitting diode-based lighting systems are now applied in both general lighting and automotive lighting. Time-modulated control methods such as pulse width modulation are frequently applied as a dimming method. This paper presents the characteristics of the visibility of the phantom array effect according to luminance, chromaticity and angular field of view. The threshold frequency of the visibility of the phantom array increases in proportion to the logarithm of the luminance of the light source. As the angular field of view of the light source increases, the threshold frequency of the visibility of the array decreases exponentially over a range from 0.125° to 4° in our experimental conditions. The threshold frequency at which the array is visible depends on chromaticity at high light source modulation frequencies. When designing time-modulated light sources, our findings can be applied so as to minimize the phantom array effect. [ABSTRACT FROM AUTHOR]

De novo variants in the Cytoplasmic FMR1-interacting protein 2 (CYFIP2) have been repeatedly associated with neurodevelopmental disorders and epilepsy, underscoring its critical role in brain development and function. While CYFIP2's role in regulating actin polymerization as part of the WAVE regulatory complex (WRC) is well-established, its additional molecular functions remain relatively unexplored. In this study, we performed unbiased quantitative proteomic analysis, revealing 278 differentially expressed proteins (DEPs) in the forebrain of Cyfip2 knock-out embryonic mice compared to wild-type mice. Unexpectedly, these DEPs, in conjunction with previously identified CYFIP2 brain interactors, included not only other WRC components but also numerous proteins associated with membraneless organelles (MLOs) involved in mRNA processing and translation within cells, including the nucleolus, stress granules, and processing bodies. Additionally, single-cell transcriptomic analysis of the Cyfip2 knock-out forebrain revealed gene expression changes linked to cellular stress responses and MLOs. We also observed morphological changes in MLOs in Cyfip2 knock-out brains and CYFIP2 knock-down cells under basal and stress conditions. Lastly, we demonstrated that CYFIP2 knock-down in cells, potentially through WRC-dependent actin regulation, suppressed the phosphorylation levels of the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), thereby enhancing protein synthesis. These results suggest a physical and functional connection between CYFIP2 and various MLO proteins and also extend CYFIP2's role within the WRC from actin regulation to influencing eIF2α phosphorylation and protein synthesis. With these dual functions, CYFIP2 may fine-tune the balance between MLO formation/dynamics and protein synthesis, a crucial aspect of proper mRNA processing and translation., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

The emerging field of gut-lung axis research has revealed a complex interplay between the gut microbiota and respiratory health, particularly in asthma. This review comprehensively explored the intricate relationship between these two systems, focusing on their influence on immune responses, inflammation, and the pathogenesis of respiratory diseases. Recent studies have demonstrated that gut microbiota dysbiosis can contribute to asthma onset and exacerbation, prompting investigations into therapeutic strategies to correct this imbalance. Probiotics and prebiotics, known for their ability to modulate gut microbial compositions, were discussed as potential interventions to restore immune homeostasis. The impact of antibiotics and metabolites, including short-chain fatty acids produced by the gut microbiota, on immune regulation was examined. Fecal microbiota transplantation has shown promise in various diseases, but its role in respiratory disorders is not established. Innovative approaches, including mucus transplants, inhaled probiotics, and microencapsulation strategies, have been proposed as novel therapeutic avenues. Despite challenges, including the sophisticated adaptability of microbial communities and the need for mechanistic clarity, the potential for microbiota-based interventions is considerable. Collaboration between researchers, clinicians, and other experts is essential to unravel the complexities of the gut-lung axis, paving a way for innovative strategies that could transform the management of respiratory diseases.

Background: Abemaciclib was newly approved for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) high-risk early breast cancer (EBC). Clinical guidelines recommended abemaciclib as the first-line treatment for HR+/ HER2- EBC (early use) or HR+/ HER2- metastatic breast cancer (MBC) (delayed use)., Objective: To compare the cost-effectiveness of early vs delayed use of abemaciclib for treatment of HR+/HER2- high-risk EBC. Early use was defined as combined abemaciclib and endocrine therapy as first-line therapy for EBC, followed by treatment with fulvestrant for MBC. Delayed use was defined as endocrine therapy for EBC, followed by combined abemaciclib and fulvestrant therapy for MBC., Methods: A 5-state model was developed to estimate lifetime costs, life-years (LYs), and quality-adjusted life-years (QALYs) of hypothetical patients with HR+/ HER2- EBC from a third-party US payer's perspective. Key clinical and safety data were derived from the monarchE and MONARCH 2 clinical trials. Costs, utilities, and disutility values of adverse events were obtained from the literature. We calculated the incremental cost-effectiveness ratio (ICER) of early vs delayed abemaciclib use and compared it with a willingness-to-pay (WTP) threshold of $100,000 per LY or QALY. Deterministic and probabilistic sensitivity analyses (PSAs) were performed to test the robustness of the base-case model., Results: Base-case analysis showed early use yielded 21.08 LYs and 17.93 QALYs for $586,213 and delayed use yielded 11.14 LYs and 9.38 QALYs for $157,576. The ICER of early vs delayed use was $43,136/LY and $50,104/QALY, which was cost-effective at the WTP threshold of $100,000. The PSA result indicated that a 94.6% likelihood of early use (vs delayed use) was cost-effective at the WTP threshold of $100,000 per QALY., Conclusions: This study suggests that giving abemaciclib in the early stage rather than waiting until patients develop metastatic disease (current standard of care in MBC) is a cost-effective strategy.

Background: Pseudomonas aeruginosa isolation in bronchiectasis is associated with a poor prognosis, including increased hospital admissions, exacerbation, and mortality. In this study, we aimed to evaluate the clinical characteristics and outcomes of P. aeruginosa isolation from patients with bronchiectasis in South Korea. Methods: This multicenter prospective cohort study analyzed 936 patients with bronchiectasis. We examined the prevalence of P. aeruginosa isolates and other microbiological characteristics. Additionally, the clinical characteristics related to disease severity and 1-year prognosis were compared between patients with and without P. aeruginosa isolation. Propensity score matching was used to mitigate confounding biases. Results: Of the 936 patients with bronchiectasis, P. aeruginosa was isolated from 89. A total of 445 matched patients-356 patients without (non- Pseudomonas group) and 89 with ( Pseudomonas group) P. aeruginosa isolation-were analyzed. The Pseudomonas group showed poorer lung function, greater involvement of radiographic bronchiectasis, and a higher proportion of cystic bronchiectasis than the non- Pseudomonas group. After one year, more patients in the Pseudomonas group were admitted for bronchiectasis than in the non- Pseudomonas group. Moreover, the Bronchiectasis Health Questionnaire scores were significantly lower in the Pseudomonas group than in the non- Pseudomonas group. Conclusions: The isolation of P. aeruginosa was independently associated with increased disease severity and poor clinical outcomes in Korean patients with bronchiectasis.

The cytoplasmic FMR1-interacting protein 2 (CYFIP2) have diverse molecular functions in neurons, including the regulation of actin polymerization, mRNA translation, and mitochondrial morphology and function. Mutations in the CYFIP2 gene are associated with early-onset epilepsy and neurodevelopmental disorders, while decreases in its protein levels are linked to Alzheimer's disease (AD). Notably, previous research has revealed AD-like phenotypes, such as dendritic spine loss, in the hippocampal CA1 pyramidal neurons of 12-month-old Cyfip2 heterozygous mice but not of age-matched CA1 pyramidal neuron-specific Cyfip2 conditional knock-out (cKO) mice. This study aims to investigate whether dendritic spine loss in Cyfip2 cKO mice is merely delayed compared to Cyfip2 heterozygous mice, and to explore further neuronal phenotypes regulated by CYFIP2 in aged mice. We characterized dendrite and dendritic protrusion morphologies, along with excitatory/inhibitory synapse densities in CA1 pyramidal neurons of 17-month-old Cyfip2 cKO mice. Overall dendritic branching was normal, with a reduction in the length of basal, not apical, dendrites in CA1 pyramidal neurons of Cyfip2 cKO mice. Furthermore, while dendritic protrusion density remained normal, alterations were observed in the length of mushroom spines and the head volume of stubby spines in basal, not apical, dendrites of Cyfip2 cKO mice. Although excitatory synapse density remained unchanged, inhibitory synapse density increased in apical, not basal, dendrites of Cyfip2 cKO mice. Consequently, a cell-autonomous reduction of CYFIP2 appears insufficient to induce dendritic spine loss in CA1 pyramidal neurons of aged mice. However, CYFIP2 is required to maintain normal dendritic length, dendritic protrusion morphology, and inhibitory synapse density., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Although several studies deal with breakthrough reactions (BTRs) in patients with contrast media (CM) hypersensitivity reactions, the phenomenon is still unclear. Therefore, this study aimed to analyse in depth patients with BTR in two countries., Methods: We retrospectively analysed the electronic medical records of in- and outpatients (random sample enrolment) from two academic hospitals of tertiary care (Seoul/South Korea, with a special monitoring system exclusively for CM hypersensitivity, and Bern/Switzerland, manually operated) with respect to basic epidemiological data, number of BTRs per patient, and severity grades of severity in follow-up analyses. The study period lasted from 2013 (2000 Bern) to 2017., Results: We identified 445 BTR-patients (91.5% from Seoul) with 691 BTRs (94.5% from Seoul). Most reactions were mild, 11% moderate and 3.9% severe. In Seoul, we found patients with up to 10 BTRs, and in Bern, there were only patients with one BTR. Fatal reactions or deaths did not occur. In most cases, the severity of the BTRs and of the index reactions were identical (80.8%). Mild index reactions remained constant in 90.6%. In contrast, in moderate index reactions the severity decreased/remained identically in 86.8% and increased in 13.2%. In severe index reactions, 55.6% of BTR reactions were severe again, in 44.4% the severity decreased. In 158 BTRs (22.9%) the culprit iodinated contrast medium (ICM) of the index reaction induced the BTR. In the other 482 BTRs (69.8%) the culprit ICM was changed to another non-culprit ICM., Conclusions: To the best of our knowledge, this is the largest study on patients with BTRs, and the first study showing BTRs in two centers in two countries of two continents. The main differences between the two centers result from the different hospital size, the number of patients, and the different documentation [manual (Bern) vs. electronical screening (Seoul)]. BTRs are no contraindications for further ICM-application. We recommend performing an allergy skin test as basis for the decision-making process of the next contrast-enhanced image-guided examination., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-912/coif). The authors have no conflicts of interest to declare., (2024 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Competing Interests: The authors declare that they have no relevant conflicts of interest.

While most NOD-like receptors (NLRs) are predominately expressed by innate immune cells, NLRC3, an inhibitory NLR of immune signaling, exhibits the highest expression in lymphocytes. The role of NLRC3 or any NLRs in B lymphocytes is completely unknown. Gammaherpesviruses, including human Epstein-Barr virus (EBV) and murine gammaherpesvirus 68 (MHV-68), establish latent infection in B lymphocytes, which requires elevated NF-κB. This study shows that during latent EBV infection of human B cells, viral-encoded latent membrane protein 1 (LMP1) decreases NLRC3 transcript. LMP1-induced-NF-κB activation suppresses the promoter activity of NLRC3 via p65 binding to the promoter. Conversely, NLRC3 inhibits NF-κB activation by promoting the degradation of LMP1 in a proteasome-dependent manner. In vivo, MHV-68 infection reduces Nlrc3 transcripts in splenocytes, and Nlrc3-deficient mice show greater viral latency than controls. These results reveal a bidirectional regulatory circuit in B lymphocytes, where viral latent protein LMP1 reduces NLRC3 expression, while NLRC3 disrupts gammaherpesvirus latency, which is an important step for tumorigenesis., (© 2024 Wiley Periodicals LLC.)

Foot-and-mouth disease (FMD) is an economically important disease, and the FMD virus (FMDV) can spread rapidly in susceptible animals. FMD is usually controlled through vaccination. However, commercial FMD vaccines are only effective 4-7 days after vaccination. Furthermore, FMDV comprises seven serotypes and various topotypes, and these aspects should be considered when selecting a vaccine. Antiviral agents could provide rapid and broad protection against FMDV. Therefore, this study aimed to develop a fusion protein of consensus porcine interferon-α and Fc portion of porcine antibody IgG (poIFN-α-Fc) using a baculovirus expression system to develop a novel antiviral agent against FMDV. We measured the antiviral effects of the poIFN-α-Fc protein against FMDV and the enhanced duration in vitro and in vivo. The broad-spectrum antiviral effects were tested against seven FMDV serotypes, porcine reproductive and respiratory syndrome virus (PRRSV), and bovine enterovirus (BEV). Furthermore, the early protective effects and neutralizing antibody levels were tested by co-injecting poIFN-α-Fc and an FMD-inactivated vaccine into mice or pigs. Sustained antiviral effects in pig sera and mice were observed, and pigs injected with a combination of the poIFN-α-Fc and an inactivated FMD vaccine were protected against FMDV in a dose-dependent manner at 2- and 4-days post-vaccination. In addition, combined with the inactivated FMD vaccine, poIFN-α-Fc increased the neutralizing antibody levels in mice. Therefore, poIFN-α-Fc is a potential broad-spectrum antiviral and adjuvant candidate that can be used with inactivated FMD vaccines to protect pigs against FMDV., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Steroids are the standard treatment for allergic airway inflammation in asthma, but steroid-refractory asthma poses a challenge. Group 2 innate lymphoid cells (ILC2s), such as T helper 2 (T H 2) cells, produce key asthma-related type 2 cytokines. Recent insights from mouse and human studies indicate a potential connection between ILC2s and steroid-resistant asthma. Here, we highlight that lung ILC2s, rather than T H 2 cells, can develop steroid resistance, allowing them to persist and maintain their disease-driving activity even during steroid treatment. The emergence of multipotent IL-5 + IL-13 + IL-17A + ILC2s is associated with steroid-resistant ILC2s. The Janus kinase 3 (JAK3)/signal transducer and activator of transcription (STAT) 3, 5, and 6 pathways contribute to the acquisition of steroid-resistant ILC2s. The JAK3 inhibitor reduces ILC2 survival, proliferation, and cytokine production in vitro and ameliorates ILC2-driven Alternaria -induced asthma. Furthermore, combining a JAK3 inhibitor with steroids results in the inhibition of steroid-resistant asthma. These findings suggest a potential therapeutic approach for addressing this challenging condition in chronic asthma.

Background: Allergy to penicillin is commonly reported in many countries and is an overwhelming global public health concern. Penicillin allergy labels can lead to the use of less effective antibiotics and can be associated with antimicrobial resistance. Appropriate assessment of suspected penicillin allergy (often including skin testing, followed by drug provocation testing [DPT] performed by allergists) can prevent the unnecessary restriction of penicillin or delabelling. Many countries in the Asia Pacific (AP) have very limited access to allergy services, and there are significant disparities in the methods of evaluating penicillin allergy. Therefore, a clinical pathway for the management of penicillin allergy is essential., Objectives: To develop a risk-stratified clinical pathway for delabeling penicillin allergy, taking into account the distinct epidemiology, patient/sensitization profiles, and disparities of allergy services or facilities within the AP., Methods: A risk-stratified penicillin allergy delabeling clinical pathway was formulated by the Drug Allergy Committee of the Asia Pacific Association of Allergy, Asthma and Clinical Immunology. and members of the Penicillin Allergy Disparities survey in AP each representing one country/region of the AP. The clinical pathway was tested based on a database of anonymized patients who were sequentially referred for and completed penicillin allergy evaluation in Hong Kong., Results: The clinical pathway was piloted employing a "hub-and-spoke" approach to foster multidisciplinary collaboration between allergists and nonallergists. A simulation run of the algorithm on a retrospective Hong Kong cohort of 439 patients was performed. Overall, 367 (84%) of patients were suitable for direct DPT and reduced the need for skin testing or specialist's care for 357 (97%) skin test-negative individuals. Out of the skin test-negative patients, 345 (94%) patients had a negative DPT., Conclusions: This risk-stratification strategy for direct oral DPT can reduce the need for unnecessary skin testing in patients with low-risk penicillin allergy histories. The hub and spoke model of care may be considered for further piloting and validation in other AP populations that lack adequately trained allergists., Competing Interests: The authors have no financial conflict of interest., (Copyright © 2023. Asia Pacific Association of Allergy, Asthma and Clinical Immunology.)

Background: Little is known about anticoagulation medication nonadherence patterns impacting effectiveness and safety outcomes in clinical practice., Objective: We identified adherence trajectories of extended therapy with direct-acting oral anticoagulants (DOACs) and warfarin after 6 months initial anticoagulant therapy among Medicare beneficiaries with venous thromboembolism (VTE). We further assessed the associated recurrent VTE and major bleeding risks., Methods: Using group-based trajectory models, this retrospective cohort study identified distinct beneficiary subgroups with similar adherence patterns of extended-phase anticoagulant treatment (DOACs or warfarin) for patients with VTE who completed 6 months of initial anticoagulant treatment. We examined associations between adherence trajectories and risks of recurrent VTE and major bleeding using inverse probability treatment weighted Cox proportional hazards models., Results: Compared with no extended treatment, consistently high DOAC adherence was associated with decreased recurrent VTE risk (hazard ratio [HR] = 0.33, 95% confidence interval [CI] = 0.21-0.51) without increased major bleeding risk, and consistently high warfarin adherence was associated with decreased recurrent VTE risk (HR = 0.62, 95% CI = 0.40-0.95) and increased major bleeding risk (HR = 1.64, 95% CI = 1.12-2.41). Gradually declining adherence to DOACs (HR = 1.80, 95% CI = 1.07-3.03) or warfarin (HR = 2.34, 95% CI = 1.57-3.47) was associated with increased bleeding risk with no change in recurrent VTE risk., Conclusion and Relevance: This real-world evidence suggests persistently adhering to extended DOAC therapy is associated with lower recurrent VTE risk without increasing major bleeding among Medicare beneficiaries with VTE. Persistently adhering to extended warfarin therapy was associated with lower recurrent VTE risk but higher major bleeding risk., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: W-H L-C reported receiving research funding from Merck Sharp & Dohme Corp. E.D. reported receiving honorarium for training and education from Bristol Myers Squibb/Pfizer. C.D. is an employee of Sanofi S.A. and a stockholder of Portola Pharmaceuticals and reported receiving personal fees for being on the advisory board of Bristol Myers Squibb. This work was conducted when C.D. was affiliated with the University of Florida. No other disclosures were reported.

Regdanvimab is a novel neutralizing antibody agent used for the treatment of coronavirus disease 2019 (COVID-19). However, the effectiveness of regdanvimab in delta-variant patients has rarely been investigated. We examined the clinical outcomes and adverse events in COVID 19 patients treated with regdanvimab in the delta-variant era. Data were collected from laboratory-confirmed COVID-19 hospitalized patients who received regdanvimab in 2021 and categorized into pre-delta and delta variant groups. The primary outcome was the need for oxygen therapy. Rescue therapy, clinical improvement, and adverse events were analyzed. Among 101 patients treated with regdanvimab, 31 (30.7%) were delta patients and 49 (48.5) were pre-delta patients. 64.4% were male, the mean age was 60.3 years, and 70 patients (69%) had at least one underlying disease. The median interval from symptom onset to injection was 4 days. Twenty-three patients (23%) needed oxygen therapy, including 9 (29%) in the delta and 8 (16.3%) in the pre-delta group. (P = .176) The risk of early oxygen supplement was higher in the delta group (adjusted hazard ratio (aHR), 6.75; 95% confidence interval(CI), 1.53-29.8). The in-hospital survival rate was 100%, and no patients were admitted to the intensive care unit. Adverse events occurred in 43% of patients:13 (42%) delta patients and 23 (47%) pre-delta patients had any adverse events (P = .661). Patients treated with regdanvimab 4 days after symptom onset showed a favorable prognosis (aHR, 0.26; 95% CI, 0.26-0.91). We found that the high-risk mild to moderate COVID-19 patients treated with regdanvimab showed similar disease progression in delta-variant patients and pre-delta variants; however, we need to be more closely observed delta-variant patients than those in the pre-delta group despite regdanvimab treatment due to rapid disease aggravation., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

BACKGROUND: Little is known about medication adherence patterns and their association with effectiveness and safety among patients with venous thromboembolism (VTE) receiving direct oral anticoagulant (DOAC) therapy beyond 3-6 months of initial treatment. OBJECTIVE: To examine the associations between adherence trajectories of extended treatment with DOAC and the risks of recurrent VTE and major bleeding among patients with VTE. METHODS: We conducted a retrospective cohort study of patients with incident VTE who completed 6 months of initial anticoagulant treatment and received either DOAC extended therapy or no extended therapy using MarketScan Commercial and Medicare Supplemental databases (2013-2019). We used group-based trajectory models to identify distinct adherence patterns during extended treatment. Using inverse probability treatment weighted Cox proportional hazards models, we examined the association between the adherence trajectories and the risks of recurrent VTE and major bleeding. RESULTS: Among 10,960 patients with extended treatment with DOACs (rivaroxaban, apixaban, dabigatran, edoxaban) and 5,133 patients with no extended treatment, we identified 4 distinct trajectories (consistently high, gradually declining, rapidly declining, and no extended treatment). Compared with the no extended treatment group, the groups with consistently high adherence (hazard ratio = 0.09, 95% CI = 0.05-0.17) and with gradually declining adherence (0.13, 0.03-0.53) showed decreased recurrent VTE risk without increased major bleeding risk (consistently high adherence 1.19, 0.71-1.99; gradually declining adherence 1.96, 0.81-4.70). There was no difference in the risk of recurrent VTE (0.34, 0.10-1.16) for the group with rapidly declining adherence, but this group was associated with increased major bleeding risk (2.65, 1.01-6.92). CONCLUSIONS: Our findings underscore the clinical importance of continuing and remaining adherent to extended DOAC treatment without increased major bleeding risk for patients with VTE. DISCLOSURES: This research was supported by the BMS/Pfizer Alliance American Thrombosis Investigator Initiated Research Program. The funding source had no role in the design, collection, analysis, or interpretation of the data or the decision to submit the article for publication. Dr Lo-Ciganic reported receiving research funding from Merck Sharp & Dohme Corp. Dr Dietrich reported receiving honorarium for training and education from BMS/Pfizer. Dr DeRemer is a stockholder of Portola Pharmaceuticals and reported receiving personal fees for advisory board meeting from BMS. No other disclosures were reported.

Background: Neuromuscular blocking agents (NMBAs) are one of the most common causes of perioperative anaphylaxis. Although skin test positivity may help identify reactive NMBAs, it is unclear whether skin test negativity can guarantee the safety of systemically administered NMBAs., Objective: This study aimed to evaluate the real-world safety of alternative NMBAs screened using skin tests in patients with suspected NMBA-induced anaphylaxis., Methods: A retrospective cohort of suspected NMBA-induced anaphylaxis were recruited among patients at Seoul National University Hospital from June 2009 to May 2021, and their characteristics and outcomes were assessed., Results: A total of 47 cases (0.017%) of suspected anaphylaxis occurred in 282,707 patients who received NMBAs. Cardiovascular manifestations were observed in 95.7%, whereas cutaneous findings were observed in 59.6%. Whereas 83% had a history of undergoing general anesthesia, 17% had no history of NMBA use. In skin tests, the overall positivity to any NMBA was 94.6% (81.1% to culprit NMBAs) and the cross-reactivity was 75.7%, which is related to the chemical structural similarity among NMBAs; the cross-reactivity and chemical structure similarity of rocuronium were 85.3% and 0.814, respectively, with vecuronium; this is in contrast to 50% and 0.015 with cisatracurium and 12.5% and 0.208 with succinylcholine. There were 15 patients who underwent subsequent surgery with a skin test-negative NMBA; whereas 80.0% (12/15) safely completed surgery, 20.0% (3/15) experienced hypotension., Conclusion: Similarities in chemical structure may contribute to the cross-reactivity of NMBAs in skin tests. Despite the high negative predictability of skin tests for suspected NMBA-induced anaphylaxis, the potential risk of recurrent anaphylaxis has not been eliminated., (Copyright © 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: The older population is at high risk of lung cancer (LC). However, the importance of lung cancer screening (LCS) in this population is rarely investigated. Herein, we evaluated the effect of LCS with low-dose computed tomography (LDCT) in the older population., Methods: This retrospective cohort study was conducted in a single center and included patients aged 70-80 years who had undergone LCS with LDCT. They were categorized into the early 70s (70-74 years) and late 70s (75-80 years) groups based on their age. Using propensity score matching, the control group included patients with non-screening-detected LC from an LC cohort. LC detection, characteristics, and treatment were compared between the early and late 70s groups and between screening-detected LC and non-screening-detected LC., Results: The study included 1,281 participants who underwent LDCT for LCS, of whom 1,020 were in their early 70s and 261 in their late 70s. Among the screening groups, 87.7% of the patients were ever-smokers. The overall LC detection rate was 2.8%. Interestingly, the LC detection rate in the late 70s group was similar to that in the early 70s group (3.4% vs. 2.7%, P=0.485). Furthermore, the incidence of LC was 6.1 cases and 8.3 cases per 1,000 person-years in the early 70s and late 70s groups, respectively (P=0.428). When comparing LC characteristics, patients with screening-detected LC showed a higher proportion of stage I LC (52.8% vs. 30.6%, P=0.010) and a lower proportion of stage IV LC (19.4% vs. 42.2%, P=0.010) than those with non-screening-detected LC. Moreover, 80.6% of patients with screening-detected LC received appropriate tumor reduction treatment based on the cancer stage., Conclusions: In the older population, LCS using LDCT showed remarkable detection of LC, with a higher proportion of cases detected at an early stage., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form. HRK received research grants from VHS Medical Center for this study and another project. JHS received a research grant from VHS Medical Center unrelated to this study. KBC received a consultant fee from KOLON PHARMA and honoraria for lectures from GSK and Hanmi Pharmaceutical. The other authors have no conflicts of interest to declare., (2023 Translational Lung Cancer Research. All rights reserved.)

Recently, carboxymethyl chitosan (CMCS) has proved to be an intrinsically fluorescent material with aggregation-induced emission characteristic. In order to elucidate the influence of CMCS's chemical structure and solution behavior on its fluorescent intensity, two series of CMCS with different degrees of carboxymethylation (DCM) are synthesized by adjusting the mass ratio of monochloroacetic acid and sodium hydroxide to chitosan at various reaction temperature and time, and then characterized using Fourier-transform infrared spectroscopy and nuclear magnetic resonance. Their solution behaviors at different pH values are studied via zeta potential and ultraviolet-visible measurements. The data reveal that the isoelectronic point (IEP) of a CMCS decreases with increasing DCM, and all the CMCSs have good water solubility at pH range below their IEPs. Fluorescence spectra indicate that a CMCS shows the highest fluorescent intensity in a slightly acidic environment next to its IEP, and the photoluminescence of a CMCS solution increases significantly after heat treatment above T = 70 °C. Furthermore, we compare for the first time the use of heated CMCS solutions for the fluorescence turn-on detection of cadmium ion in pure and tap water, respectively. The limit of detection is found to be ca. 1 μM for the Cd 2+ in pure water., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)