Extreme ultraviolet ( EUV) lithography has become essential for advanced semiconductor manufacturing. However, the development and evaluation of high-performance EUV photoresists remain challenging due to sensitivity limitations, stochastic variations, and secondary-electron-driven reactions, which ultimately limit resolution and increase line-edge roughness. To address the need for reproducible actinic evaluation, we developed a laboratory-scale EUV photoresist sensitivity measurement (EPSM) platform based on a femtosecond high-harmonic generation (HHG) EUV source at 13.5 nm. This platform enables systematic and manufacturing-relevant screening of commercial photoresists using reproducible evaluation protocols. The EPSM system addresses the inherently low flux of tabletop EUV sources by integrating beam focusing with precise scanning control, enabling stable areal exposure and consistent evaluation. Areal exposure is achieved using a scanning EUV beam by controlling the scan distance ( SD) and scan speed (SS). Using hydrogen silsesquioxane (HSQ) as a negative-tone resist, we confirmed the resulting surface roughness using atomic force microscopy (AFM). In addition, contrast curve analysis of HSQ films with varying thicknesses demonstrates the system's capability for quantitative sensitivity evaluation. This compact and flexible platform provides a reliable pathway for systematic screening of next-generation EUV photoresists. Beyond sensitivity measurements, its expandability to time-resolved and stochastic studies will further advance the understanding and optimization of photoresist performance for future high-volume manufacturing and advanced EUV lithography.

PURPOSE:To investigate the risk factors and clinical characteristics of immune recovery uveitis (IRU) in patients with cytomegalovirus (CMV) retinitis after hematopoietic stem cell transplantation (HSCT). METHODS:Clinical variables-including age, sex, type of hematologic disease, survival status, absolute neutrophil count, involved eye, visual acuity, number of intravitreal antiviral injections, recurrence of CMV retinitis, CMV titers in blood and aqueous humor, extent and location of retinal involvement, donor human leukocyte antigen matching, donor relationship, and systemic CMV treatment-were evaluated in patients with CMV retinitis following HSCT. RESULTS:The IRU group included 26 eyes from 20 patients, and the non-IRU group included 114 eyes from 79 patients. The IRU group had worse visual acuity than the non-IRU group at both the time of CMV retinitis diagnosis and the final visit (p = 0.036 and p < 0.001). IRU was more likely to develop in eyes with posterior pole involvement, larger retinal lesion areas, and a shorter interval between HSCT and CMV retinitis diagnosis (p = 0.032, p = 0.025, and p = 0.012, respectively). Among patients with IRU, those with extensive retinal involvement, cystoid macular edema, and recurrent IRU had poorer visual outcomes (p = 0.019, p = 0.016, and p = 0.027, respectively). CONCLUSION:Retinal involvement near the posterior pole, larger affected areas, and a shorter interval between HSCT and CMV retinitis diagnosis are significant risk factors for developing IRU in patients with CMV retinitis after HSCT. Careful monitoring for IRU remains essential even after resolution of CMV retinitis.

In this prospective study (N = 12), autologous virus-specific T cells (auto-VSTs) were successfully manufactured in 10 patients (83.3%). Three received VSTs, achieving viral clearance and symptom resolution without severe adverse events. Auto-VST therapy appears feasible and effective for managing persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection; however, manufacturing and timing challenges remain.

We investigated a KPC-2-producing Enterobacterales (KPC-2 CPE) outbreak in a Korean hospital from July to September 2019, which subsided following enhanced surveillance and strict infection control. The study aimed to elucidate transmission dynamics using epidemiological and genomic methods. The study period covered the outbreak and a 9-month post-outbreak observation. Investigations included a matched case-control study and whole-genome sequencing (WGS) of isolates, including long-read sequencing for two isolates. Single nucleotide polymorphism (SNP) analysis (≤ 6 SNPs for clonality, ≤ 15 for relatedness) was used to construct transmission networks. A total of 42 KPC-2 CPE cases were identified: 34 Klebsiella pneumoniae, 4 Escherichia coli, 1 Enterobacter asburiae, and 3 cases co-colonized with K. pneumoniae and E. coli. Among these, 33 were hospital-linked and 9 were imported. Retrospective tracing indicated that covert transmission began a month before the outbreak, and 13 hospital wards were identified as potential acquisition sites. Genomic analysis revealed all but one K. pneumoniae belonged to ST307, cgMLST 439, which grouped into three clades. Clade 1 was linked to a specific hospital ward, supported by the case-control study (adjusted odds ratio, 3.63; 95

Abstract Background We explored the efficacy of AS01 E -adjuvanted respiratory syncytial virus prefusion F protein-based vaccine (adjuvanted RSVPreF3) in subpopulations of participants with underlying medical conditions in the multi-country, phase 3 AReSVi-006 trial (conducted May/2021-May/2024). Methods Medically stable ≥60-year-olds were 1:1-randomised to receive one adjuvanted RSVPreF3 or placebo dose pre-RSV season 1. In exploratory post-hoc analyses in subgroups of participants with underlying conditions (including COPD, asthma, diabetes, obesity [BMI≥30 kg/m 2 ]), we evaluated efficacy of one vaccine dose against RSV-related lower respiratory tract disease (RSV-LRTD), acute respiratory illness (RSV-ARI), and RSV-ARI-related complications (e.g., pneumonia, COPD/asthma exacerbation, cardiovascular events). We also evaluated (post-hoc) RSV-ARI-related systemic corticosteroid and antibiotics use in participants with COPD or asthma. Results The efficacy analyses comprised 12,468 vaccine and 12,498 placebo recipients. Efficacy against RSV-LRTD over three RSV seasons was similar among participants with COPD (75.1%, 95% CI: 40.2-91.4), asthma (65.8%, 31.0-84.7), diabetes (69.8%, 37.5-87.1), and obesity (74.1%, 56.4-85.5) as in the overall study population (62.9%, 97.5% CI: 46.7-74.8). Efficacy was also observed against RSV-ARI in these subgroups. Efficacy against RSV-ARI-related complications was 74.4% (95% CI: 11.2-95.2) in participants with COPD and 60.8% (−9.9-88.7) in those with asthma. Among participants with COPD, 15.4% (1.9-45.4) of RSV-ARI episodes in vaccine vs 22.4% (12.5-35.3) in placebo recipients were treated with systemic corticosteroids, and 46.2% (19.2-74.9) vs 56.9% (43.2-69.8) with antibiotics. Conclusions Post-hoc analyses of the AReSVi-006 trial suggest that adjuvanted RSVPreF3 may help prevent RSV-ARI, RSV-LRTD, and RSV-related complications in medically stable older adults with underlying medical conditions like COPD and asthma. Trial registration ClinicalTrials.gov : NCT04886596 Summary Post-hoc analyses of the AReSVi-006 trial suggest that 1 dose of adjuvanted RSVPreF3 may help prevent RSV-related illness and complications over 3 consecutive RSV seasons in subgroups of ≥60-year-olds with chronic medical conditions, e.g., COPD and asthma.

Background: Candida auris is an emerging pathogenic yeast of increasing global concern. This study aimed to explore recent epidemiological trends in C. auris at a single center and evaluate its impact on otologic surgery outcomes. Methods: An epidemiological review was conducted for patients with positive fungal culture results at Seoul St. Mary's Hospital between January 2018 and December 2023. Medical records of patients with C. auris were retrospectively analyzed, focusing on surgical outcomes and comparing them with those of patients infected with other fungi. Results: Of 3,430 fungal cultures from ear discharge, C. auris was identified in 104 cases (3.0%). Among 89 patients with C. auris isolated from ear discharge, 53 (59.6%) had mixed infections, with Staphylococcus species being the most common co-pathogen. Of 207 patients with fungal infections who underwent otologic surgery, 39 had C. auris. The postoperative complication rate was significantly higher in the C. auris group (34.2%) compared to that with other fungal infections (16.1%) (P = 0.011). Conclusion: C. auris is widely distributed in the community and is particularly prevalent in patients requiring surgical treatment. Its presence in otologic surgery cases is linked to a higher risk of postoperative complications. Enhanced vigilance and proactive management by otolaryngologists are crucial to minimize nosocomial transmission and improving surgical outcomes.

Background Antivirals remain an important treatment strategy for persons who experience severe and life-threatening COVID-19. Ensitrelvir is an oral 3CL protease inhibitor with potent antiviral activity. Methods We conducted an international randomized, placebo-controlled trial of ensitrelvir with standard of care (SOC) among adults hospitalized for COVID-19. The primary outcome was clinical recovery assessed by the days to recovery scale through day 60 (DRS-60), analyzed using a Van Elteren test. Results From 2023 to 2025, 589 participants received blinded study treatment (293 ensitrelvir and 296 placebo). Median age was 69 years, 49% were female, 68% were White, and SOC commonly included corticosteroids (61% and 54%) and remdesivir (62% and 60%) in ensitrelvir and placebo groups, respectively. Median DRS-60 category was 6 (IQR: 3-15) in the ensitrelvir and 5.5 (IQR: 3-12) in the placebo group (P = .19), and the OR was 0.82 (95% CI: 0.62-1.09) for a better DRS-60 category with ensitrelvir. Ensitrelvir participants had lower detectable viral antigen in plasma at Day 5 (13.4% vs 25.1%; P < .001). There was no difference in secondary clinical outcomes or prespecified safety outcomes, though the mortality rate was 6.1% vs 4.4% and the frequency of hemorrhagic events was 3.4% vs 0.3% among ensitrelvir and placebo groups, respectively. Conclusions Ensitrelvir treatment did not improve clinical recovery in addition to SOC for adults hospitalized for COVID-19. The lower illness severity in the Omicron era compared with earlier periods in the COVID-19 pandemic and high use of remdesivir and corticosteroids, may have contributed to the lack of clinical benefit.

PURPOSE:This study evaluated the bioequivalence of a newly developed liposomal amphotericin B (LAmB) formulation (DKF-5122, Amphosom™) relative to AmBisomeⓇ and mechanistically characterized the pharmacokinetic property. METHODS:The two-period crossover trial included a patient cohort receiving once-daily infusions for 5 days per period and a healthy-adult cohort receiving a single dose per period. Both cohorts received 3 mg/kg intravenously, and plasma concentrations of LAmB and free drug (fAmB) were analyzed. Bioequivalence in healthy adults was evaluated using conventional criteria. A joint population model was developed based on healthy-adult data, linking LAmB and fAmB through first-order liposomal release and linear disposition. Model adequacy was assessed by goodness-of-fit diagnostics, prediction-corrected visual predictive checks, and bootstrap analysis. RESULTS:Thirty-one participants contributed to the dataset (six patients and twenty-five healthy adults). In healthy adults, Test-to-Reference geometric mean ratios (90% confidence intervals) were 1.08 (1.04-1.12) for the maximum concentration of LAmB and 1.01 (0.94-1.08) for the area under the curve; for fAmB, the corresponding values were 1.00 (0.91-1.10) and 1.01 (0.95-1.07), meeting conventional bioequivalence criteria. Both LAmB and fAmB were well described by 3-compartment models, and the only formulation-related difference was a statistically significant reduction in the central compartment volume of LAmB for the Test formulation. However, this difference was not of a magnitude that would meaningfully affect the BE outcome. Covariate effects were not clinically relevant. CONCLUSIONS:Amphosom™ achieved pharmacokinetic bioequivalence to AmBisomeⓇ, and the joint model explained the observed similarity by quantifying liposomal release and systemic disposition of LAmB and fAmB. CLINICALTRIALS:gov identifier: NCT05749380.

Respiratory virus (RV) infections cause significant morbidity in patients with hematologic malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients. However, predictors of progression from upper respiratory tract infection (URTI) to lower respiratory tract infection (LRTI) in the nosocomial setting remain poorly characterized, particularly beyond HCT-only cohorts. The effectiveness of URTI-stage antiviral therapy is also unclear, and nosocomial seasonal patterns in hematology settings have not been well described. This study aimed to identify risk factors for URTI-to-LRTI progression across influenza virus (IFV), respiratory syncytial virus (RSV), and parainfluenza virus (PIV) in hospitalized patients with HM. Secondary objectives included evaluation of URTI-stage antiviral therapy and characterization of nosocomial seasonal patterns. This multicenter retrospective study (South Korea, 2016 to 2024) included hospitalized adults with HM and laboratory-confirmed nosocomial IFV, RSV, or PIV detection >48 hours after admission, excluding community-acquired episodes and pre-existing pneumonia. URTI-to-LRTI progression within 30 days was analyzed using Fine-Gray subdistribution hazard models with death as a competing event. Antiviral effects were evaluated via propensity-weighted landmark analyses. Seasonality was assessed using Poisson harmonic regression. Of 473 eligible episodes, 359 presenting as URTI were analyzed; 99 (27.6%) progressed to LRTI. Systemic glucocorticoid exposure (≥20 mg/d prednisolone equivalent; subdistribution hazard ratio [sHR], 2.41; 95% confidence interval [CI], 1.22 to 4.74) and neutropenia (<0.5 × 10⁹ cells/L; sHR, 1.69; 95% CI, 1.11 to 2.59) were independently associated with progression. The 30-day cumulative incidence increased stepwise with 0, 1, and 2 risk factors (13.8%, 35.7%, and 59.8%, respectively; Gray test, P < .001), consistently across all three viruses. In antiviral analyses, propensity-weighted landmark models showed no significant ribavirin effect in RSV; in PIV, a protective association that did not reach statistical significance was observed (adjusted sHR, 0.15; 95% CI, 0.02 to 1.06; P = .057). Nosocomial detection patterns broadly mirrored community circulation across all three viruses (Poisson harmonic regression, all P < .01). Two readily assessable risk factors-systemic glucocorticoid exposure and neutropenia-independently predict LRTI progression across IFV, RSV, and PIV and inform bedside risk stratification. URTI-stage ribavirin therapy for PIV warrants further investigation in adequately powered prospective studies. Nosocomial seasonality aligned with community trends, supporting seasonal infection control strategies.

BACKGROUND:Healthcare-associated infections (HAIs) pose a significant threat to patient safety, particularly for vulnerable populations such as critically ill patients, the elderly, and individuals with multiple comorbidities. Hospital surfaces often act as reservoirs for pathogens, including multidrug-resistant strains, yet conventional disinfectants frequently lack sustained activity. We evaluated the real-world effectiveness of a novel disinfectant wipe combining low-concentration didecyldimethylammonium chloride (DDAC) and organosilane quaternary ammonium compound (Si-QAC) for its immediate and persistent antimicrobial properties across multiple hospitals. MATERIALS AND METHODS:A multi-center, paired-design study was conducted at five university-affiliated hospitals between March and April 2025. Eight high-touch surfaces were categorized into dry zones (e.g., bed rails, nurse station desks) and wet zones (e.g., ward sinks, toilet lids). We compared the disinfection effectiveness of DDAC+Si-QAC wipes (experimental group) against each hospital's standard disinfection protocol (control group). Microbial samples were collected at baseline and at 1, 6, and 24 hours post-disinfection. Effectiveness was measured by the change in microbial load (Δ colony-forming unit/mL) from baseline. RESULTS:A total of 640 specimens were analyzed from 160 surfaces. To ensure rigorous analysis, pairs containing "zero-point" baseline surfaces were excluded, resulting in 39 pairs (78 surfaces) for final evaluation. The experimental group showed significant reductions from baseline at 1, 6, and 24 hours (P<0.001), whereas the control group failed to exhibit significant changes. In comparative analysis, the experimental group demonstrated superior effectiveness over the control group at 1 hour (P=0.041) and 6 hours (P=0.042). Although the difference at 24 hours (P=0.276) was not statistically significant, the experimental group maintained a lower median microbial load. Sub-group analysis revealed that the experimental group's potency was most pronounced in wet zones at 1 hour (P=0.004), where the bioburden was highest. CONCLUSION:The DDAC+Si-QAC wipe provides superior and sustained antimicrobial activity compared to standard hospital protocols, particularly in challenging high-bioburden wet environments. While the statistical advantage diminished at 24 hours, the persistent coating effect of Si-QAC offers a robust alternative to conventional point-in-time disinfection. Integrating these wipes into routine environmental management may help prevent the formation of microbial reservoirs and contribute to reducing HAIs.

Background: Tuberculosis (TB) reactivation is a serious complication after allogeneic haematopoietic cell transplantation (allo-HCT). Nonetheless, evidence for isoniazid (INH) prophylaxis in this population remains limited, and critical uncertainties persist regarding prophylactic effectiveness, optimal duration, and pharmacogenetic predictors of toxicity. We evaluated the effectiveness, optimal duration, and safety of INH prophylaxis for latent TB infection (LTBI) among allo-HCT recipients in a TB-endemic setting. Methods: This retrospective cohort study involved 765 consecutive adult allo-HCT recipients with LTBI at a single centre in Republic of Korea between 2008 and 2023. The primary outcome was active TB incidence according to INH prophylaxis completion (≥180 days). Time-dependent confounding was addressed using inverse probability of treatment weighting (IPTW) with Fine–Gray competing-risk regression accounting for death. Landmark analyses at 1 and 3 months eliminated immortal time bias and defined duration-dependent effects. NAT2-based pharmacogenetic analyses were performed in 357 patients (46·6%). Findings: Of the 765 patients, 294 (38·4%) completed the INH prophylaxis. Active TB occurred in 0·7% and 4·2% completers and non-completers, respectively. In IPTW-adjusted Fine-Gray regression, TB risk was markedly lower with INH completion (adjusted subdistribution hazard ratio [SHR] 0·14, 95% confidence interval [CI] 0·06–0·37, P<0·001). A duration-dependent benefit was observed: prophylaxis ≥3 months conferred significant protection (SHR 0·18, 95% CI 0·09–0·38), with the maximal effect at 6 months (SHR 0·14). With full-course prophylaxis, the number needed to treat to prevent one TB case was 28·0 (95% CI 11·9–44·2). Age ≥60 years and chronic graft-versus-host disease (cGvHD) were independent risk factors for active TB. INH-related adverse events led to discontinuation in 17·8% of patients. NAT2 slow acetylators had approximately a threefold higher toxicity risk (adjusted SHR 2·94, 95% CI 0·95–9·08), suggesting a clinically meaningful pharmacogenetic signal warranting prospective evaluation. Interpretation: In this 15-year cohort from a TB-endemic country, INH prophylaxis markedly reduced TB risk in allo-HCT recipients, lowering the incidence to levels comparable to those of the general population. These findings provide the strongest evidence to date supporting INH prophylaxis in this setting and directly address the uncertainties highlighted in recent international guidelines. Tailored strategies, including extended prophylaxis for older patients and those with cGvHD, and pharmacogenetic-guided risk stratification for NAT2 slow acetylators, warrant prospective evaluation.

Importance:Antimicrobial resistance (AMR) poses an urgent global health challenge, undermining treatment efficacy and threatening patient safety. Antimicrobial stewardship (AMS) programs are recognized as essential interventions to optimize antibiotic use, but implementation has often been fragmented and underresourced. The Republic of Korea (ROK), facing high antibiotic consumption and increasing multidrug resistance, launched a national pilot program for AMS as part of its Second National Action Plan on AMR (2021-2025). This program represents the first government-coordinated effort to establish a standardized framework for hospital-based stewardship nationwide. Observations:The pilot program, initiated in November 2024, was developed by the Korea Disease Control and Prevention Agency with academic and clinical partners. It set explicit eligibility criteria, requiring hospitals with at least 300 beds to form multidisciplinary AMS teams with minimum physician and pharmacist staffing. Core program components include leadership commitment, workforce development, guideline implementation, real-time audit and feedback, surveillance, reporting, and education. Institutions undergo annual evaluation based on both foundational and advanced criteria, with operational funding linked to performance grades. Depending on size and evaluation outcomes, hospitals may receive financial support from the government annually. Early implementation highlights both progress and challenges. The program has enabled the establishment of dedicated AMS teams, integration of stewardship into hospital governance, and initiation of national monitoring systems. However, persistent workforce shortages, uneven institutional readiness, limited awareness of AMS among clinicians and the public, and disparities between tertiary and smaller hospitals pose significant barriers. Sustained progress will require workforce expansion, awareness-building, stable long-term financing, and integration of stewardship into broader quality and safety frameworks. Conclusions and Relevance:The ROK's national AMS pilot illustrates how government-led policy, financing, and accountability mechanisms can motivate large-scale stewardship implementation. The initiative provides a replicable model for embedding stewardship into health systems while aligning public health priorities with clinical practice. Lessons from the Korean experience are relevant for countries seeking to strengthen national AMR strategies, particularly in resource-limited settings. By institutionalizing stewardship at the policy level, the program offers critical insights for sustaining progress against AMR and advancing global health security.

Abstract Background In a phase 3 study, the approved RSVPreF3 OA vaccine, administered as a single dose in adults aged ≥ 60 years, has demonstrated high efficacy against RSV disease and was well tolerated with a favorable safety profile. Here we present immunogenicity results in older adults of different age and frailty status from the same study. Methods This phase 3, placebo-controlled, observer-blind, multi-country study (NCT04886596) enrolled adults aged ≥ 60 years who were randomized (1:1) to receive a dose of RSVPreF3 OA or placebo, before the RSV season. Blood samples were collected at pre-vaccination (day 1) and 1 month post-vaccination (day 31). Humoral immune responses were assessed in a subset of participants, and outcomes included RSV-A and RSV-B neutralization titers by age category and frailty status. Results Of the 24,966 participants who received RSVPreF3 OA or placebo at day 1, 1,702 were included in the per-protocol set for immunogenicity. Demographic characteristics in the immunogenicity subset were well balanced between groups (Table 1). The mean age was 70.3 (± 6.8) years. At day 1, all tested participants had detectable RSV-A and RSV-B neutralization titers due to previous exposure to RSV. At day 31, 1 month post-vaccination, neutralization titers were between 9.4–11.3-fold (RSV-A) and between 8.0–9.0-fold (RSV-B) higher than pre-vaccination levels across the different age categories (Figure 1). In pre-frail and frail adults, neutralization titers increased 10.0- and 13.7-fold (RSV-A), and 8.8- and 9.2-fold (RSV-B) between day 1 and 1 month post-vaccination (Figure 1). Conclusion For both RSV subtypes, RSVPreF3 OA induced a large increase in neutralization titers across the different age categories, including a robust immune response even in adults aged ≥80 years, known to have immunosenescence. A robust immune response was also observed in pre-frail and frail adults, however the results for frail adults should be considered with caution as the number of frail adults in the study was low. Funding: GSK Disclosures Isabel Leroux-Roels, PhD MD, Curevac: Grant/Research Support|GSK: Grant/Research Support|Icosavax: Grant/Research Support|Janseen Vaccines: Advisor/Consultant|Janseen Vaccines: Board Member|Janseen Vaccines: Grant/Research Support|Moderna: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|OSE Immunotherapeutics: Grant/Research Support|Osivax: Grant/Research Support Robert G. Feldman, MD, GSK: Payment to attend congress and speaking events, travel expenses for these events Raffaele Antonelli-Incalzi, MD, GSK: Grant/Research Support Alberto Papi, MD, Agenzia Italiana del farmaco (AIFA): Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Board Member|AstraZeneca: Grant/Research Support|AstraZeneca: Honoraria|Avillion: Advisor/Consultant|Avillion: Board Member|Avillion: Honoraria|CHIESI: Advisor/Consultant|CHIESI: Board Member|CHIESI: Grant/Research Support|CHIESI: Honoraria|Edmond Pharma: Advisor/Consultant|Edmond Pharma: Honoraria|Elpen Pharmaceutica: Advisor/Consultant|Elpen Pharmaceutica: Board Member|Elpen Pharmaceutica: Honoraria|GSK: Advisor/Consultant|GSK: Board Member|GSK: Grant/Research Support|GSK: Honoraria|IQVIA: Board Member|IQVIA: Honoraria|Menarini: Honoraria|Mundipharma: Honoraria|Novartis: Advisor/Consultant|Novartis: Board Member|Novartis: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Board Member|Sanofi: Grant/Research Support|Sanofi: Honoraria|Zambon: Advisor/Consultant|Zambon: Honoraria Michael G. Ison, MD MS, Adagio: Advisor/Consultant|Adamis: Advisor/Consultant|Adamis: Board Member|ADMA Biologics: Advisor/Consultant|AlloVir: Advisor/Consultant|AlloVir: Board Member|Cidara: Advisor/Consultant|CSL Behring: Board Member|Genentech: Advisor/Consultant|GSK: Grant/Research Support|ISIRV AVG: Chair|Janssen: Advisor/Consultant|Janssen: Board Member|Merck: Board Member|NIH: Board Member|Roche: Advisor/Consultant|Sequiris: Board Member|Shinogi: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Board Member|Talaris: Advisor/Consultant|Talaris: Board Member|Transplant Infectious Disease: Editor-in-Chief|UpToDate: Royalties Marie-Pierre David, Master in Statistics, GSK: As GSK employee, I’m part of a patent application|GSK: Salary as GSK employee with stock options|GSK: Stocks/Bonds (Public Company) Carline Vanden Abeele, MS, GSK: Salary as GSK employee with stock options|GSK: Stocks/Bonds (Public Company) Magali de Heusch, PhD, GSK: Salary as GSK employee with stock options|GSK: Stocks/Bonds (Public Company) Nathalie De Schrevel, PhD, GSK: Magali De Heusch|GSK: Stocks/Bonds (Public Company) Catherine Gerard, PhD, GSK: Salary as GSK employee with stock options|GSK: Stocks/Bonds (Public Company) Aurélie Olivier, PhD, GSK: As GSK employee, I’m part of a patent application|GSK: employee|GSK: Stocks/Bonds (Public Company) Marie Van Der Wielen, MD, GSK: As GSK employee, I’m part of a patent application|GSK: Salary as GSK employee with stock options|GSK: Stocks/Bonds (Public Company) Veronica Hulstrøm, MD, PhD, GSK: Salary as GSK employee with stock options|GSK: Stocks/Bonds (Public Company)

PURPOSE:Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a multifactorial pathophysiology. Although AD has been characterized by a T helper type 2 cell response, the role of the myeloid populations in the pathogenesis of AD remains unclear. METHODS:Peripheral blood mononuclear cells from 48 AD patients and 48 healthy controls were profiled using mass cytometry, primarily focusing on dendritic cells (DCs) and monocytes. Further analysis of a public single-cell RNA sequencing (scRNA-seq) dataset and immunofluorescence staining of lesional skin in AD were conducted for further validation. RESULTS:The frequency of circulating cDC1 was significantly decreased in AD compared with healthy controls. The frequency of cDC1 was negatively correlated with disease severity scores and serum immunoglobulin E levels. The expression of FcεRIa was significantly increased in the DC populations, including cDC1, cDC2, plasmacytoid DC, and Axl+ DC. CD163, a marker of the inflammatory DC subset DC3, was increased in AD patients, suggesting an increased DC3 signature in AD patients. Analysis of a public scRNA-seq dataset further corroborated the decreased frequency of cDC1. The expression of cutaneous lymphocyte antigen was increased in cDC1 of AD compared with HC, suggesting increased migration of cDC1 to the skin. Aligned with this hypothesis, the frequency of cDC1 was shown to be increased in AD lesional skin using immunofluorescence staining. CONCLUSIONS:These results provide insight into the potential role of DC and monocyte populations in AD. We report decreased circulating cDC1 frequency and increased DC3 signature. The corresponding increased frequency of cDC1 in AD lesional skin implies their role in modulating AD pathophysiology.

This study developed a pharmacokinetic model and web-based tool to distinguish true invasive aspergillosis from false positives caused by contaminated fluids. By analyzing galactomannan kinetics, false positives were identified within 24 hours, improving diagnostic accuracy and aiding clinicians in early decision making while minimizing unnecessary interventions.

The transmission pathways and risks of COVID-19-associated pulmonary aspergillosis (CAPA) remain unclear. This study investigated the genetic relationships of Aspergillus fumigatus isolates from patients with and without COVID-19 and environmental air samples to suggest possible transmission patterns. We conducted a prospective study from March 2020 to December 2022, collecting clinical and environmental isolates from a tertiary hospital. Isolates from patients with and without COVID-19 were compared with those from air samples at four hospital locations. The genetic analysis included internal transcribed spacer and β-tubulin A sequencing, with azole resistance assessed via cyp51A gene analysis. Multiple locus variable-number tandem repeat analysis was performed to elucidate genetic relationships. A total of 155 isolates (19 from COVID-19 patients, 104 from non-COVID-19 patients, and 32 from environmental samples) were identified and genotyped, revealing 131 sequence types (Simpson Diversity Index 0.9972). Four CAPA clinical strains genetically related to environmental strains were isolated from the COVID-19 intensive care unit (ICU), while two CAPA clinical strains sharing multiple locus variable-number tandem repeat sequence types and azole-resistant mutations were isolated in the same COVID-19 ICU 4 months apart. All but one of these strains were isolated from patients requiring mechanical ventilation. The observed genetic similarities between strains from critically ill patients with COVID-19 and those from the environment, as well as within the same ICU, raise the possibility of nosocomial acquisition via contaminated air or environmental sources. These findings highlight the risks of CAPA associated with negative pressure rooms and the need for enhanced environmental infection control measures.IMPORTANCEThis study reveals genetic links between Aspergillus fumigatus in patients with COVID-19 and environmental sources, suggesting nosocomial transmission and urging a reevaluation of universal negative pressure isolation practices in hospitals, especially for critically ill patients.

Cytomegalovirus (CMV) is a significant concern for patients with allogeneic hematopoietic cell transplantation (allo-HCT). CMV management differs between institutions due to the lack of local guidelines. Here, we describe a case of refractory/resistant CMV infection treated using our institution's CMV management protocol. A 59-year-old woman who underwent allo-HCT was treated for CMV reactivation. Despite 3 months of valganciclovir administration, serum CMV level surged. CMV gene mutation test revealed a ganciclovir-resistant A594V mutation in the UL97 gene. Treatment was switched to foscarnet until the drug became unavailable nationwide. During the foscarnet shortage, cidofovir was used, leading to a decline in CMV levels when foscarnet was reintroduced and used for 2 months. Following allo-HCT, CMV prophylaxis with letermovir is crucial to prevent reactivation in seropositive recipients. CMV titers should be monitored frequently after allo-HCT. The cutoff value for preemptive therapy varies across institutions, with ganciclovir/valganciclovir usually administered as first-line therapy. Maribavir is an option in cases of ganciclovir/valganciclovir resistance or intolerance. CMV gene mutations should be examined in patients with suspected resistance after 2 weeks of appropriate treatment. This case was discussed at the Clinical Grand Round of the Annual Conference of the Korean Society of Infectious Diseases on November 2, 2023.

Background: Coronavirus disease 2019 (COVID-19) has led to the expansion of the spectrum of invasive fungal infections beyond traditional immunocompromised populations. Although COVID-19-associated pulmonary aspergillosis is increasingly being recognised, COVID-19-associated mucormycosis remains rare, particularly in non-endemic regions. Concurrent COVID-19-associated invasive tracheobronchial aspergillosis and pulmonary mucormycosis with histopathological confirmation is exceedingly uncommon and poses significant diagnostic and therapeutic challenges. Case presentation: We report the case of a 57-year-old female with myelodysplastic syndrome who underwent haploidentical allogeneic haematopoietic stem cell transplantation. During post-transplant recovery, she developed COVID-19 pneumonia, complicated by respiratory deterioration and radiological findings, including a reverse halo sign. Bronchoscopy revealed multiple whitish plaques in the right main bronchus. Despite negative serum and bronchoalveolar lavage fluid galactomannan assay results, cytopathological examination revealed septate hyphae and Aspergillus fumigatus was subsequently identified. Given the patient’s risk factors and clinical features, liposomal amphotericin B therapy was initiated. Subsequent surgical resection and histopathological analysis confirmed the presence of Rhizopus microsporus. Following antifungal therapy and surgical intervention, the patient recovered and was discharged in stable condition. Conclusions: This case highlights the critical need for heightened clinical suspicion of combined invasive fungal infections in severely immunocompromised patients with COVID-19, even in non-endemic regions for mucormycosis. Early tissue-based diagnostic interventions and prompt initiation of optimal antifungal therapy are essential for obtaining ideal outcomes when co-infection is suspected.