Journal of Infection and Chemotherapy

Aims: To estimate the preventable pneumococcal disease burden by 21-valent pneumococcal conjugate vaccine (PCV21) compared to PCV20 for the national immunization program for adults aged 65 years or older in Japan. Methods: Serotype distribution among isolates and the annual incidence of invasive pneumococcal disease (IPD) in adults were monitored. The numbers of IPD or pneumococcal community-acquired pneumonia (pCAP) cases preventable by immunization with PCV20 or PCV21 were estimated according to reported vaccine efficacy and duration of protection in older adults. Data from our nationwide study of adult IPD surveillance and a multicenter study of pCAP were used. Results: The mean annual incidence of adult patients with IPD caused by all serotypes among adults aged [≥]65 years, which declined during the COVID-19 pandemic period, recovered to 89% of the pre-pandemic level in 2025. During 2023-2025, the proportion of PCV20-non-PCV21 serotypes was 8.5% for adults aged [≥]65 years. At the current vaccination coverage rate of 40%, the numbers of preventable IPD cases (per person per year) by PCV20 and PCV21 were 36 and 53, respectively. The preventable numbers of pCAP cases by PCV20 and PCV21 were 2,821 and 4,765, respectively. The estimated number of preventable pCAP cases was approximately 80-90 times higher than that of preventable IPD cases. Conclusion: Our data indicate that PCV21 could prevent 1.5-1.7 times as many pneumococcal disease cases as PCV20 among adults aged [≥] 65 years in Japan. However, PCV20 should be considered if the incidence of adult IPD cases caused by PCV20-non-PCV21 serotypes increases.

Background: Alpha-mannosidosis (AM) is a debilitating lysosomal storage disorder (LSD) caused by insufficient activity of alpha-mannosidase, an enzyme responsible for cleavage of alpha-linked mannose residues from N-glycan-type oligosaccharides during their degradation. As a result, specific oligosaccharides accumulate in tissues and are also detectable in body fluids. AM is a progressive multi-organ disease for which hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT) are therapeutic options, however, treatment results depend considerably on early diagnosis. Therefore, inclusion of AM into newborn screening panels would significantly contribute to improving therapeutic outcome. Methods: A rapid and fully quantitative method for the specific AM oligosaccharide biomarker Man2GlcNAc in dried blood spots (DBS) using ultra-performance liquid chromatography coupled to tandem-mass spectrometry was developed. DBS from 420 controls, 27 AM patients (including five newborn screening samples), and 35 patients with other LSDs were analyzed. Results: A distinct separation in biomarker concentrations was observed between unaffected individuals and untreated AM patients (0.1 - 0.8 vs 3.2 - 11.3 mol Man2GlcNAc/L, p<0.0001). Furthermore, Man2GlcNAc concentrations significantly differed between untreated patients and those on ERT (n = 17, p<0.0001) or after HSCT (n = 15, p<0.0001), and between both treatment groups (p<0.0001). Moreover, we demonstrated that this method is appropriate for monitoring treatment efficacy by analysis of samples from individual patients before and after initiation of therapy. We retrospectively analyzed residual samples of dried blood spots (DBS) from routine newborn screening that had been stored from patients with later-confirmed AM, which resulted in clear separation from the concentrations observed in a newborn screening control cohort (7.7 - 11.3 vs 0.1 - 0.8 mol Man2GlcNAc/L, p=0.0001). Conclusion: We present a simple and rapid method for quantitative analysis of the specific AM oligosaccharide biomarker Man2GlcNAc, which is remarkably stable compared to enzymatic assays. Thus, the method is useful for selective screening in suspected cases as well as for monitoring the response to different forms of treatment. Furthermore, Man2GlcNAc has the potential to serve as a useful biomarker for newborn screening offering the prospect of earlier treatment initiation, improved therapeutic outcome and higher quality of life for AM patients.

Background: COVID-19 vaccination uptake is influenced by various sociodemographic and psychological factors. Previous studies have suggested that the relationship between personality traits and vaccination is context-dependent. However, this association has not been investigated in Japan, a unique sociocultural context characterized by historically low vaccine confidence but exceptionally high COVID-19 vaccine uptake. We examined the association between the Big Five personality traits and completion of the primary COVID-19 vaccination series, exploring potential gender-personality interactions. Methods: A web-based, cross-sectional survey was conducted among 7,210 Japanese adults (aged 20-85 years) in December 2021. Personality was assessed using the Japanese version of the Ten-Item Personality Inventory. Multivariable Poisson generalized estimating equations were used to calculate adjusted prevalence ratios (PRs) and assess gender-personality interactions. Results: Higher extraversion and lower openness were significantly associated with vaccination completion across genders. A significant gender-agreeableness interaction was observed: agreeableness (PR = 1.016, 95% CI: 1.008-1.024) was positively associated with vaccination completion among men but not women. A similar, though only marginally significant, interaction pattern was observed for neuroticism (PR = 1.011, 95% CI: 1.004-1.019 among men). Conclusions: Personality traits act as modest but meaningful, gender-specific psychological modifiers of vaccination behavior in Japan. Public health campaigns should transition from traditional "one-size-fits-all" messages to personality-tailored and gender-responsive communication strategies to optimize vaccine uptake and bolster psychological resilience in future pandemics.

BACKGROUND Diagnosis of Tuberculosis (TB) from stool specimen using the Xpert MTB/RIF Ultra assay (Xpert-Ultra assay) is important to confirm diagnosis for presumptive TB patients who are unable to produce sputum. We evaluated diagnostic performance of the Xpert-Ultra assay in stool specimen among adult migrant population living in generalized HIV epidemic situation. METHODS A prospective, cross-sectional study was conducted at outpatient and inpatient departments of the Shoklo Malaria Research Unit (SMRU) clinics and Mae Tao Clinic (MTC) located in Thailand-Myanmar border area. Presumptive TB patients of any age who were registered between November 14, 2022, and May 23, 2023, were eligible for inclusion based on reported signs and symptoms and/or radiological findings. Using liquid MTB culture in sputum as reference standard, evaluation of diagnostic performance of the Xpert-Ultra assay in stool was performed, and it was also compared with performance of smear microscopy and Xpert-Ultra assay in sputum specimen. RESULTS Total 113 participants were included in the analysis; 9 (7.96 %) had human immunodeficiency virus (HIV) infection, and 31 (27.43%) had confirmed TB on culture results. Among these culture-confirmed TB cases, the sensitivity of Xpert-Ultra assay in stool specimen was 90.32 % (95% confidence interval [CI], 74.25% to 97.96%). Although the absolute difference in sensitivity of Xpert-Ultra assay in stool was 3.23 % lower than sputum (95% CI: -9.46 % to 3.00 %), there was no statistically significant difference between the two sample types. The specificity of Xpert-Ultra assay in stool specimen was 98.78% (95% CI, 93.39% to 99.97%) against culture-negative TB cases, giving an absolute difference of 1.22 % (95% CI, -1.16% to 3.59%) compared to sputum Xpert-Ultra assay. This method demonstrated that diagnostic performance was consistent with World Health Organization (WHO) target product profiles on low-complexity assays for detecting Mycobacterium tuberculosis (MTB). CONCLUSIONS The Xpert-Ultra assay in stool specimen can be considered as a potential, alternative method in diagnosis of presumptive pulmonary TB in adults when respiratory sample is difficult to collect.

Seasonal influenza remains a major cause of morbidity and mortality worldwide. Although neuraminidase inhibitors improve outcomes, influenza-related deaths persist. We evaluated the impact of early aspirin (ASA) and non-aspirin nonsteroidal anti-inflammatory drug (NSAID) use on outcomes in adults hospitalized with influenza. This retrospective study included adults admitted to the University of Minnesota Medical Center from 2016 to 2018. Continuous variables were summarized as medians with interquartile ranges (IQRs) and categorical variables as counts and percentages. Group comparisons used Wilcoxon rank-sum, Chi-square, or Fishers exact tests. Analyses included case-control comparisons, assessments by vaccination status, and subgroup analyses by early ASA or NSAID use. Among 2,816 patients, 320 had laboratory-confirmed influenza, with vaccination less common among cases. Unvaccinated patients had higher rates of intensive care unit (ICU) admission (23.6% vs. 11.1%; P = 0.003) and ventilatory support (15.0% vs. 6.1%; P = 0.009). In vaccinated patients, early ASA use was associated with older age and higher in-hospital mortality, whereas early NSAID use was associated with no in-hospital deaths, better one- and three-year survival (P < 0.001), and fewer, though not statistically significant, cardiovascular complications. In unvaccinated patients, ASA use was associated with lower three-year survival (59.1% vs. 79.2%; P = 0.013), while NSAID use was associated with fewer ICU admissions and no cardiovascular or renal complications. In both vaccinated and unvaccinated adults hospitalized with influenza, early NSAID use was associated with improved survival and fewer complications, whereas ASA use was associated with worse outcomes.

Importance: Recurrence rates in head and neck squamous cell carcinoma (HNSCC) remain high, yet current post-treatment surveillance relies primarily on clinical examination and imaging with known limitations. Circulating tumor DNA (ctDNA) has shown promise for recurrence detection in HPV-positive HNSCC, but less is known about its role in non-virally associated disease. Objective: To evaluate the diagnostic performance of a methylation-based ctDNA assay for detecting recurrence during post-treatment surveillance of non-virally associated HNSCC and to assess its prognostic association with survival outcomes. Design, Setting, and Participants: This retrospective single-institution cohort study included patients with non-metastatic non-virally associated HNSCC who underwent definitive therapy and had at least one Guardant360 ctDNA test during post-treatment surveillance between January 2024 and October 2025. Guardant360 identifies tumor-specific DNA methylation patterns via next-generation sequencing of plasma cell-free DNA. A positive result was defined by a methylation signal of 0.05% or greater. Main Outcomes and Measures: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Results: Fifty patients were included; most had larynx (38%) or oral cavity (36%) primaries, AJCC stage IVA-IVB disease (72%), T3-T4 tumors (69%), and N2-N3 nodal classification (48%). Treatment was chemoradiation (54%) or surgery (46%). At a median follow-up of 18.0 months, 13 patients recurred, and 12 had positive ctDNA results. Sensitivity, specificity, PPV, and NPV were 76.9%, 94.6%, 83.3%, and 92.1%, respectively (AUC, .858; 95% CI, .733-.982). Positive ctDNA was associated with worse PFS (1-year: 25.0% vs 96.4%; P < .001) and OS (1-year: 75.0% vs 100%; P < .001). Among 10 patients with recurrence and positive ctDNA, ctDNA preceded clinical detection in 6 (60%) by a median of 131 days. An exploratory analysis identified TP53, SETD2, and ROBO2 mutations as associated with recurrence. Conclusions and Relevance: A methylation-based ctDNA assay demonstrated high sensitivity and specificity for detecting disease recurrence in non-virally associated HNSCC. Positive post-treatment ctDNA was associated with inferior survival and preceded clinical detection in most cases, supporting ctDNA integration into surveillance strategies, though prospective validation is warranted.

Background Otitis media is a leading cause of childhood morbidity and presents a significant healthcare burden worldwide. Streptococcus pneumoniae is a major aetiological agent of OM, and the introduction of pneumococcal conjugate vaccines into the Malaysian National Immunisation Programme in 2020 would have altered pneumococcal carriage and serotype distribution. This study aimed to determine pneumococcal carriage, serotype distribution, and associated risk factors among children with OM in the early post-PCV era in Peninsular Malaysia. Methods and Findings A total of 360 children with OM were recruited from hospitals on the east and west coasts of Peninsular Malaysia between 2023 and 2025. Nasopharyngeal and middle ear fluid samples were collected for Spn isolation by culture, followed by serotyping using multiplex PCR. Sociodemographic, environmental, and medical history data were analysed for associations with pneumococcal carriage using chi-square, Fishers exact tests, and logistic regression. Pneumococcal carriage was detected in 26.7% of children in either NP or MEF samples, with carriage rates of 25.6% and 1.9% in NP and MEF samples, respectively. The most prevalent serotypes were 23A, 15B/15C, non-typable strains, 19F, and 11A/11D. Daycare attendance (p = 0.012, aOR [95% CI]: 2.177 [1.186 - 3.995] and residence in rural areas (p = 0.019, aOR [95% CI]: 2.476 [1.159 - 5.292] were significantly associated with pneumococcal carriage. The main limitation of the study was the reliance on self-reported questionnaire data, which may have introduced recall bias and reporting errors. Conclusions The predominance of non-vaccine serotypes and non-typable Spn indicates ongoing serotype replacement and the emergence of phase-variant strains in the early post-PCV era. Continued surveillance is essential to monitor these changes and inform the development of next-generation pneumococcal vaccines. This study was registered under clinical trial registration number NCT05429541.

Background: Non-medically attended (NMA) and outpatient medically attended (MA) influenza illnesses contribute substantially to influenza disease burden in the United States. We leveraged a household study to estimate out-of-pocket and lost productivity costs of NMA and MA influenza illness. Methods: The Respiratory Virus Transmission Network for Influenza was a 2024-2025 case-ascertained household study at 3 U.S. sites. Influenza-positive index patients and household contacts self-reported daily symptoms, over-the-counter (OTC) medication use, medical care-seeking, time missed from work or activities, and self-collected nasal swabs for PCR testing. We included participants with PCR-confirmed influenza infection and influenza-like-illness symptoms who ever (MA) or never (NMA) sought medical care during follow-up. We obtained costs of OTC medications from retail websites and productivity costs from published values. We calculated OTC medication and lost productivity costs in 2025 USD for MA and NMA influenza separately and household-level lost productivity costs among caregivers for MA and NMA household members. Results: Median out-of-pocket OTC medication costs were $6.38 (interquartile range [IQR] $2.92-$11.60) among 594 MA and $3.72 (IQR $1.50-$7.05) among 153 NMA influenza illnesses. Among participants [&ge;]15 years of age, median lost productivity was $315 ($149-$743) for MA and $248 ($0-$624) for NMA illnesses. Median household-level lost productivity for caregiving was $148 (households with 1 ill child), $379 (multiple ill children), and $0 ([&ge;]1 ill adult). Conclusions: Influenza causes substantial lost productivity costs within households. These estimates can inform future economic burden and cost effectiveness analyses.

Background: Papillary thyroid microcarcinoma (PTMC, equal to or smaller than 1 cm) is increasingly diagnosed, and a subset behaves aggressively. Preoperative ultrasound (US) and fine needle aspiration (FNA) accuracy in this size range, particularly with multinodular disease, is poorly defined outside East Asian screening cohorts. Materials and Methods: We retrospectively analyzed 180 consecutive PTMC cases (2017 to 2026) with preoperative US and FNA and compared them with 191 benign thyroidectomy controls. ROC analysis identified an optimal size cutoff. We compared sensitivity, specificity, PPV, NPV, and accuracy across tumor-size subgroups, before/after 2023, and with/without dominant nodules (DNs) equal to or larger than 2 cm. Results: ROC analysis identified 5 mm as the optimal cutoff (AUC 0.80). FNA sensitivity was 44.4% overall, falling to 14.1% for tumors <5 mm versus 61.2% for [&ge;]5 mm, with specificity uniformly high (94.8%). US showed a similar pattern (sensitivity 23.4% vs. 64.7%) but lower specificity (69.6%), driven largely by calcification and Hashimoto's-related hypoechogenicity. Combined FNA+US improved sensitivity to 59.4%. DNs equal to or larger than 2 cm markedly reduced FNA true-positive rates (67.9% vs. 10.8%; OR 17.4). Excluding DN cases raised FNA sensitivity to 67%, NPV to 84.2%, and accuracy to 85.2%. Post-2023 experience significantly improved all metrics (sensitivity 34.4% to 54.4%). Conclusion: FNA and US sensitivity for PTMC decline sharply below 5 mm and in multinodular glands with dominant nodules, while specificity/PPV remain high. A 5 mm threshold, operator experience, and selective avoidance of FNA in dominant-nodule bearing multinodular goiters (favoring direct surgical referral) can meaningfully improve diagnostic performance and guide management.

Low pathogenic avian influenza A(H7N7) virus detected in a poultry worker in Taiwan, 2026 was related to viruses circulating in Asian wild birds and possessed PB2 E627K, a mammalian adaptation marker. Enhanced surveillance for H7 viruses in poultry and rapid characterization of human cases are essential to assess pandemic potential.

Background: Cancer patients face a significantly elevated risk of severe COVID-19 outcomes. Although vaccination is a cornerstone of prevention, data on vaccination coverage and association with survival among Russian cancer patients remain scarce. We assessed COVID-19 vaccination coverage and its association with overall survival in a population-based cohort of cancer patients in Northwest Russia. Methods: This retrospective registry-based cohort study integrated data from the Population-Based Cancer Registry (PBCR) of the Arkhangelsk Region and the Nenets Autonomous Okrug, regional vaccination records, and an artificial intelligence (AI)-based analysis of chest computed tomography (CT) scans. The cohort consisted of 1,144 cancer patients who underwent CT between August 2020 and April 2021. Vaccination status was ascertained via data linkage. Overall survival (OS) was compared between vaccinated and unvaccinated patients using Kaplan-Meier analysis and multivariable Cox proportional hazards regression, adjusted for demographic, clinical, and AI-derived CT biomarkers. To mitigate immortal time bias, the primary analysis used a landmark approach restricted to patients alive on March1, 2021 (N=1,136). A sensitivity analysis used a November1, 2021 landmark (N=894). Vaccination status was defined as receipt of at least one dose before the landmark date. Results: Only 6.6% (n=76) of patients received at least one dose of a COVID-19 vaccine (Sputnik V or Sputnik Light). Vaccinated patients were more likely to have earlier-stage cancer and were less likely to be receiving active treatment. In the primary landmark analysis, vaccination was associated with a significantly higher 3-year OS (80.3% vs. 45.7%, p<0.001). In multivariable analysis, vaccination was independently associated with a 60% lower hazard of all-cause mortality (adjusted HR 0.40, 95% CI 0.25-0.64). AI-detected COVID-19 pneumonia on baseline CT was also an independent predictor of poorer survival (adjusted HR 1.32, 95% CI 1.09-1.59). In the sensitivity analysis (November1, 2021 landmark), the adjusted HR for vaccination was 0.56 (95% CI 0.34-0.92), showing a consistent but attenuated association. Conclusion: This study reveals critically low COVID-19 vaccination coverage among cancer patients in Northwest Russia. Nevertheless, vaccination was strongly associated with a substantial survival benefit, underscoring its importance as a potentially lifesaving intervention for this vulnerable population.

Background: Cervical cancer (CC), mostly associated with high-risk human papillomaviruses (hrHPV) infection, is the most common cancer that disproportionately affects women in developing countries, including Ethiopia. Early detection of CC and initiation of treatment are key to positive health outcomes. Identifying factors associated with delayed CC diagnosis is essential for effective prevention and control efforts. This study assessed the stage at diagnosis and examined associated clinical and sociodemographic factors. Methods: An institution-based cross-sectional study was conducted among 284 women newly diagnosed with CC who attended Tibebe Ghion Specialized Hospital (TGSH) between 1st January 2021 and 31st December 2022. A structured questionnaire was used to collect data on the participants' demographic, reproductive, and gynaecologic history, and clinical profiles. The CC stage at diagnosis was categorised as early (stage I-IIA) or late (stage IIB-IV). Logistic regression models (unadjusted and adjusted) were used to examine associations of sociodemographic or clinical factors with stage at CC diagnosis. Results: The mean age ({+/-}standard deviation) at presentation was 53.2 {+/-} 11.3 years, with an age range of 18 - 80 years. Most of the patients (73.6%) were from rural areas, and three-fifths (58.1%) had no medical insurance. Among participants, 74.6% (95% CI: 69.4, 79.6%) had late-stage CC. The odds of late-stage CC diagnosis were higher for women from rural areas (AOR: 2.21; 95% CI:1.18, 4.12; p<0.013), and those with anaemia (defined as <12 mg/dl haemoglobin) (AOR: 3.42; 95% CI: 1.88, 6.23; p<0.001). On the other hand, the odds of late-stage CC diagnosis were lower in HIV positive women (AOR:0.41; 95%CI:0.19, 0.88; p<0.021). Conclusion: The proportion of late-stage diagnosis among CC patients was high. Residential area, anaemia status, and HIV serostatus were factors associated with stage at CC diagnosis. These findings can inform screening efforts of CC and call for expanding of the screening services to the rural setting in order to reduce the burden of late-stage CC diagnosis.

Background: Treponema pallidum quantitative polymerase chain reaction (qPCR) positivity and cycle threshold (Ct) by rapid plasma reagin (RPR), disease stage, and other characteristics are poorly characterized in routine-care specimens, leaving it unclear when qPCR of such specimens is informative for diagnosis. Methods: This Japanese multicenter cross-sectional study explored qPCR positivity and Ct by these characteristics. Nonblood specimens collected during routine care underwent qPCR at a central laboratory for this study. Bayesian logistic and normal regressions modeled positivity and mean Ct of TP0574 and polA with stage-specific continuous automated RPR terms, patient characteristics, collection site, and facility random intercepts. Estimates were standardized over the analyzed specimens. Population-group predictions were instead averaged within each group. Results: Among 154 nonblood specimens from 145 patients (71.7% non-MSM men and women) at 14 facilities, 109 (70.8%) were qPCR positive. At RPR 1, adjusted positivity was 72.2% (95% credible interval, 60.9%--82.9%) in primary and 43.8% (16.7%--69.9%) in secondary syphilis. Positivity showed a modest downward trend with RPR in primary but increased in secondary syphilis, reflecting a stage-by-RPR interaction (secondary-to-primary ratio of odds ratios, 1.78; 1.25--2.65). Predicted positivity showed an upward trend with RPR values among MSM; adjusted positivity was relatively high for genital/urethral/urinary and anal/perianal/rectal specimens. Adjusted mean Ct increased with RPR in primary and followed an inverted-U pattern in secondary syphilis. Conclusions: In primary syphilis, nonblood qPCR positivity was high even at low RPR. When serologic findings remain inconclusive in this stage, qPCR is highly recommended for securing an early diagnosis.

Background: Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) shows higher prevalence of lymph node metastases than HPV-negative OPSCC. It remains unclear whether HPV-positive and HPV-negative OPSCC differ in occult metastasis risk, which is relevant to personalize elective nodal treatment volumes. Methods: We performed a retrospective analysis of 780 untreated OPSCC patients from four European centers. Patterns of lymph node level involvement (LNLs I, II, III, IV, V, VII) were assessed using a consensus diagnosis integrating imaging (CT, MRI, PET) and pathological findings from surgically treated patients. Occult metastases were assessed in 288 surgical patients with paired clinical and pathological information. Results: HPV-positive patients more frequently presented with ipsilateral LNL II involvement, particularly in early T-stage disease (80.6% [75.6-84.8] vs. 54.8% [47.2-62.2]). However, the probability of downstream involvement in LNLs III and IV conditioned on upstream LNL involvement was similar between HPV-positive and HPV-negative patients. Similarly, contralateral involvement conditioned on midline extension of the primary tumor was similar. The overall proportion of occult metastases, defined as clinically false-negative LNLs divided by pathologically positive LNLs, was lower in HPV-positive patients (24.7% [19.7-30.1] vs. 48.7% [39.7-57.8]). Conclusions: HPV-positive OPSCC showed higher prevalence of LNL involvement, especially in ipsilateral LNL II and early T-stage tumors. The data to directly compare occult metastasis risk has important limitations and does not allow definitive conclusions. However, the presented data suggests that higher prevalence likely does not translate into higher risk of occult metastases for the most common clinical diagnoses and therefore does not support larger elective nodal treatment volumes compared with HPV-negative tumors.

Background: Serum proteomic signatures may reflect tumor- and host-related biology and serve as prognostic biomarkers in patients receiving immune checkpoint inhibitors (ICIs). We evaluated the association of the VeriStrat serum proteomic classification with survival outcomes and immune-related adverse events (irAEs) in patients with non-small cell lung cancer (NSCLC) treated with ICIs. Methods: We retrospectively reviewed patients with NSCLC who received ICI-containing therapy and underwent VeriStrat testing at Northwestern Memorial Hospital from October 2015 through June 2023. Patients were classified as proteomic signature Good (PS-Good) or Poor (PS-Poor). Progression-free survival (PFS) and overall survival (OS) were assessed among patients receiving palliative-intent ICI therapy. First any-grade and grade 3 or higher irAEs were evaluated in all ICI-treated patients using cumulative incidence functions and Fine-Gray competing-risk regression. Results: Among 162 ICI-treated patients included in the toxicity analysis, 129 received palliative-intent therapy and were included in the survival analysis; 91 (71%) were PS-Good and 38 (29%) were PS-Poor. PS-Good status was associated with longer PFS (median, 6 vs 3 months; hazard ratio [HR], 0.50; 95% CI, 0.33-0.77; P<0.01) and OS (median, 20 vs 8 months; HR, 0.59; 95% CI, 0.39-0.91; P=0.02). These associations remained significant after multivariable adjustment for PFS (adjusted HR, 0.46; 95% CI, 0.26-0.82; P<0.01) and OS (adjusted HR, 0.50; 95% CI, 0.28-0.87; P=0.01). Any-grade irAEs showed a nonsignificant trend toward a higher cumulative incidence in PS-Good patients. At 12 months, the cumulative incidence was 32.6% for PS-Good versus 22.5% for PS-Poor (subdistribution HR, 1.53; 95% CI, 0.77-3.02; P=0.23). The cumulative incidence of grade 3 or higher irAEs was similar between groups (16.3% vs 15.0%; subdistribution HR, 1.12; 95% CI, 0.48-2.62; P=0.79). Conclusions: PS-Good classification was independently associated with improved survival in patients with NSCLC receiving ICI-containing therapy. Although any-grade irAEs were numerically more frequent among PS-Good patients, proteomic classification was not significantly associated with any-grade or high-grade irAE risk. Prospective validation is warranted.

Background The COVID-19 pandemic substantially altered respiratory pathogen circulation worldwide. However, longitudinal analyses of changes in respiratory pathogen ecology across the pandemic and post-pandemic periods remain limited. Methods We analyzed 19,968 respiratory samples tested with the BioFire(R) FilmArray(R) Respiratory Panel at a hospital in Tokyo, Japan, between January 2020 and March 2026. We evaluated temporal changes in pathogen circulation, age-specific epidemiology, co-detection patterns, pairwise pathogen associations, and clinical parameters. Results At least one respiratory pathogen was detected in 27.8% of tests. Respiratory pathogens resurged asynchronously following the relaxation of COVID-19-related public health measures. Influenza virus circulation remained markedly suppressed until late 2022 before re-emerging in successive large seasonal epidemics, whereas other pathogens, including RSV, human metapneumovirus, and Mycoplasma pneumoniae, exhibited distinct resurgence patterns. Pathogen distributions also varied by age. Human rhinovirus/enterovirus remained predominant among young children, whereas SARS-CoV-2 predominated among older adults. Co-detection occurred in 14.0% of positive specimens and was significantly more frequent in younger patients. Pairwise analysis identified both positive and negative pathogen associations; however, the patterns varied across age groups and study periods. Conclusions Respiratory pathogen circulation changed substantially during the transition from the COVID-19 pandemic to the post-pandemic period, with pathogen-specific, age- and period-dependent patterns. Continued surveillance is warranted to determine how respiratory pathogen circulation will evolve and to inform infection control strategies in the post-pandemic era.

Non-muscle invasive bladder cancer (NMIBC) exhibits high recurrence, necessitating frequent invasive surveillance. Urine DNA methylation profiling represents a promising non-invasive biomarker approach for early detection and monitoring. This pilot study aimed to investigate urine DNA methylation patterns in NMIBC among Thai patients. Five patients with high-grade NMIBC and three healthy volunteers were enrolled, and midstream urine and blood samples were collected prior to transurethral resection of bladder tumor (TUR-BT). Urine cell-free DNA (cfDNA) was extracted, mechanically sheared from an atypical peak of approximately 400 bp to an optimal target length of 150-200 bp, and analyzed using cell-free methylated DNA immunoprecipitation followed by high-throughput sequencing (cfMeDIP-seq). Differentially methylated regions (DMRs) were identified between NMIBC and controls, and principal component analysis (PCA) was performed. A total of 82 DMRs were identified (adjusted P < 0.001), including 76 hypermethylated and 6 hypomethylated regions, with IRX4, TBX5, and MIR124-3 representing the top hypermethylated genes. To account for cohort heterogeneity, a refined subset analysis excluding two outlier samples (UC2 and UC3) was performed, revealing 476 significant DMRs (449 hypermethylated). PCA demonstrated clear, robust segregation between NMIBC and controls, highlighting MIR124-3, IRX4, and LHX1-DT as the most significantly hypermethylated targets. Our findings demonstrate that urine cfDNA methylation profiling can robustly distinguish NMIBC from healthy controls, highlighting MIR124-3, IRX4, and LHX1-DT as highly promising, demographic-specific biomarkers. This non-invasive approach successfully bypasses the degradative limits of traditional bisulfite conversion and establishes a technically validated foundation for clinical surveillance and diagnostics

Objective To identify optimal initiation ages and screening intervals for low-dose computed tomography (LDCT) screening among never-smoking Asian women using an integrated polygenic risk score (PRS)-environmental tobacco smoke (ETS) risk model, and to evaluate the cost-effectiveness of alternative screening strategies at these optimized ages. Design Integrated PRS-ETS microsimulation modelling. Setting Japan. Participants Never-smoking women stratified into eight risk groups defined by combinations of PRS levels and ETS exposure. Interventions LDCT screening at intervals of 1 to 10 years, annual chest radiography (CXR), or no screening. Main outcome measures Costs, quality-adjusted life years (QALYs), incremental cost-effectiveness ratios (ICERs), net monetary benefits, lung adenocarcinoma incidence and mortality, and optimal LDCT initiation ages. Sensitivity analyses used a willingness-to-pay threshold of US$50,000 per QALY gained. Results Optimal initiation ages ranged from 40 to 55 years across the eight PRS-ETS risk groups, with higher PRS-ETS risk associated with younger optimal initiation ages. Annual LDCT was the most cost-effective strategy across all PRS-ETS risk strata, yielding an ICER of US$40,471 per QALY in the lowest risk stratum and becoming cost-saving in higher risk strata. Over a lifetime, annual LDCT averted 8,534 lung adenocarcinoma deaths compared with annual CXR and 14,940 deaths compared with no screening. Conclusions Tailoring LDCT initiation age across integrated PRS-ETS risk groups maximizes mortality reduction achievable with cost-effective annual LDCT screening among never-smoking Asian women. These findings highlight an urgent limitation of global lung cancer screening guidelines that rely exclusively on smoking history and provide policy-ready evidence supporting the integration of PRS and ETS into future recommendations for precision LDCT screening for never-smoking populations.

In primary healthcare centers lacking advanced imaging, community-based active tuberculosis (TB) case finding often relies on basic symptom screening. This approach often misses cases and leads to the inefficient allocation of rapid molecular testing (RMT). We aimed to develop and internally validate a simple clinical triage scorecard to improve TB detection and guide RMT use in resource-constrained settings. We conducted a retrospective cross-sectional study of 15,137 adults ([&ge;]18 years) evaluated within the Zero TB Yogyakarta program (2020-2025). Participants with complete clinical assessments and confirmatory GeneXpert results were included. Using multivariable logistic regression, we identified independent clinical predictors, which were subsequently transformed into an integer-based point scorecard. Model performance was evaluated via discrimination and calibration, utilizing bootstrap resampling (1,000 iterations) for internal validation. Among the 15,137 participants, 251 (1.7%) were GeneXpert-positive. The final multivariable model identified eight independent predictors: age, male sex, body mass index, prolonged cough, hemoptysis, unexplained weight loss, TB contact history, and diabetes mellitus. The model demonstrated strong predictive accuracy, with an optimism-adjusted AUROC of 0.836 and good calibration. When translated to the integer scorecard and compared directly to standard national symptom screening, the scorecard performed (AUROC 0.81 vs. 0.73; p<0.001). At a high sensitivity cut off score of [&ge;] 0, the tool achieved 93.63% sensitivity and 41.33% specificity. This point-of-care clinical scorecard provides higher diagnostic accuracy than standard symptom screening algorithms. By offering flexible operational thresholds, it empowers local health programs to dynamically balance the urgency of case detection with available diagnostic capacity, optimizing GeneXpert allocation where advanced radiological imaging is unavailable.

Background/Aims: In medical practice, the rising prevalence of infections in kidney transplant recipients (KTRs) is a notable concern. However, understanding the incidence and risk factors associated with infections in KTRs remains limited. This study aims to assess the incidence and factors associated infection among KTRs. Additionally, we also investigate the median time of each infection among KTRs. Methods: A retrospective cohort study was conducted from 1 January 2018- 31 December 2022 at Thailand's tertiary hospital. We performed univariable and multivariable logistic regression analyses to identify potential risk factors related infection and investigated for the incidence and median time of each infection among KTRs. Results: A total of 179 participants were included in this study. Our findings reveal the kidney from living donor was protective factor for infection among KTRs (aOR 0.063, 95% CI 0.005-0.792; p = 0.032). Urinary tract infections (UTIs)showed as the predominant pathogenic manifestation among KTRs (43%). The median time of UTIs, cytomegalovirus (CMV) infection and pneumocystis pneumonia (PCP) were 16, 57 and 94.5 days, respectively. Conclusions: Our study establishes that receiving a kidney from a living donor is a protective factor against post-kidney transplant infections. Particularly urinary tract infections were most common of infection. Monitoring urinary tract infections post-transplantation is recommended. Moreover, awareness of UTI, CMV infection and PCP should be concerned during 2-3 months after transplantation. However, due to a small sample size; we recommend to increase the number of particular participants in further investigations.