Journal of Infection and Chemotherapy

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: 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/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.

Background: This systematic review and meta-analysis evaluated the prognostic value of Hippo signaling pathway biomarkers in oral squamous cell carcinoma. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, electronic database searches identified 17 eligible studies involving 1,194 patients. Associations between the immunohistochemical expression of Hippo pathway effectors, primarily YAP and TAZ, and clinicopathological characteristics were assessed. Meta-analyses using random-effects models estimated pooled hazard ratios for overall survival. Results: Predominantly nuclear expression of YAP and TAZ was consistently associated with adverse clinicopathological features, including advanced clinical stage, lymph node metastasis, and poorer histological differentiation. Meta-analysis demonstrated that YAP overexpression was associated with worse overall survival (hazard ratio, 1.918; 95% confidence interval, 1.036 to 3.549; p = 0.038). TAZ overexpression was similarly associated with poorer overall survival (hazard ratio, 2.845; 95% confidence interval, 1.682 to 4.811; p < 0.001). Although substantial between-study heterogeneity was observed, the direction of the prognostic association remained consistent across studies. Conclusions: Increased nuclear expression of YAP and TAZ is consistently associated with more aggressive disease and poorer overall survival in oral squamous cell carcinoma. These findings support the prognostic value of Hippo pathway biomarkers, although methodological heterogeneity warrants cautious interpretation.

Objectives: To evaluate the epidemiological evolution of unique pneumococcal serotypes covered by either PCV20 or PCV21, common serotypes by both vaccines and non-vaccine serotypes in adults. Methods: We characterized all national IPD clinical isolates from January 2009 to June 2026. Results: The highest burden of IPD was caused by serotypes shared between PCV20 and PCV21 with serotypes 3 and 8 the most prevalent in adults of all ages. During the pre-pandemic period, IPD caused by unique-PCV20 serotypes declined probably due to herd protection by paediatric vaccination with PCVs. In contrast, unique-PCV21 serotypes increased in incidence accounting for more cases than unique-PCV20 serotypes. However, after the COVID-19 pandemic, a different pattern was observed with unique-PCV20 serotypes increasing in incidence due a marked rise in IPD caused by serotypes 4 and 14 that has progressively reduced the gap in disease coverage. In adults aged 18-64 years, the fraction of disease that could be prevented with PCV20/PCV21 changed from 5% in favour of PCV21 (years 2022/2023) to 15% in favour of PCV20 (year 2026) whereas in adults [&ge;]65 years the vaccine contribution declined from 20% in favour of PCV21 (year 2022) to 8% in 2026. Conclusions: IPD trends in adults have changed after the COVID-19 pandemic, especially in recent years. Our study emphasizes the rapid re-emergence of infections caused by traditional PCV7 serotypes especially serotypes 4 and 14 and reinforce the idea that the use of broader PCVs must be accompanied by an increase in the uptake rates in adults of all ages.

This was a cohort study of 1,663 subjects (1196 women, 467 men; median age 48 years, IQR 37-57) with thyroid nodules recruited from 2020 to 2025 in five tertiary medical centers. Cytological/histopathological diagnoses were established by an independent review committee, and preoperative serum thyroid hormone metabolites (THMs) were tested using liquid chromatography tandem mass spectrometry. A diagnostic model on this serum THM test to distinguish between differentiated thyroid cancer (DTC) and benign thyroid nodule (BTN) was trained on 872 retrospective subjects (454 DTC and 418 BTN), followed, prospectively, by model validation on 392 subjects (195 DTC and 197 BTN) and a second validation on 399 subjects (300 DTC and 99 BTN). Following successful diagnostic model training, the model validation demonstrated a diagnostic specificity of 99.5% (196/197), sensitivity of 92.3% (180/195), positive predictive value (PPV) of 99.4%, negative predictive value (NPV) of 92.9%, and diagnostic accuracy of 95.9% (95% CI, 90.8 to 100.0%) for DTC. Combination of the two validation cohorts showed a diagnostic specificity of 99.7% (295/296), sensitivity of 92.1% (456/495), PPV of 99.8%, NPV of 88.3%, and diagnostic accuracy of 94.9% (95% CI, 91.5 to 98.0%) for DTC. The test on indeterminate Bethesda categories III-IV (139 DTC, 87 BTN) showed a diagnostic specificity of 100.0% (87/87), sensitivity of 93.5% (130/139), PPV of 100.0%, NPV of 90.6%, and diagnostic accuracy of 96.0% (95% CI, 89.2 to 100.0%) for DTC. This study develops a novel molecular blood test of serum THMs for preoperative diagnostic evaluation of thyroid nodules, which displays a high PPV and decent NPV with an excellent overall diagnostic accuracy for DTC.

Objectives To evaluate the impact of COVID-19 vaccination on the prevention of long COVID (LC) in the Omicron era through an updated systematic review and meta-analysis. Methods We performed an update of our previously published systematic review and meta-analysis of vaccination and LC risk (searches between 1 January 2022 and 1 March 2024). Databases (Embase, MEDLINE, PubMed, Europe PMC, LILACS, Cochrane COVID-19 Study Register) were searched for studies published between 1 March 2024 and 13 July 2026. Observational studies assessing the impact of vaccination on the risk of LC four or more weeks after SARS-CoV-2 infection were included. Vaccines were restricted to those centrally authorised in the European Union. Random-effects meta-analyses, restricted to adults, were performed to calculate pooled odds ratios (OR) of LC in three comparisons: vaccinated (any dose) versus unvaccinated; booster vaccination versus unvaccinated; and booster vaccination versus primary course vaccination only. Results Nineteen new studies were identified, of which ten were included in the updated meta-analyses alongside eight studies from the original review. The pooled OR of LC in vaccinated adults (any dose) versus unvaccinated was 0.75 (95% confidence interval [CI] 0.67-0.84; 13 studies). ORs were also lower for booster vaccination versus unvaccinated (0.73; 95% CI 0.65-0.82; 6 studies), and booster vaccination versus primary course vaccination (0.63; 95% CI 0.53-0.75; 6 studies). Significant associations between vaccination and lower LC odds were observed in subgroup analyses of mRNA-only vaccination and LC outcomes three or more months after infection. Conclusions This updated review and meta-analysis reinforces our previous finding that vaccination may reduce the burden of LC in the Omicron era, with booster doses potentially providing additional protection. Although evidence in high-risk groups now prioritised for vaccination in most countries remains limited, these findings clearly demonstrate the benefits of vaccination and support current seasonal vaccination strategies.

Background: Pertussis has resurged in the post-COVID-19 era, yet diagnostic delay remains a barrier to timely treatment and transmission interruption, particularly among adults. Methods: Retrospective observational cohort study of 787 patients with confirmed pertussis from January 2016 through March 2026 across two South Carolina health systems. Electronic health record data from the 60 days preceding confirmation were used to characterize diagnostic timing (same-day vs. delayed), delay duration, and respiratory pathogen testing patterns including pertussis test modality. Results: Adults accounted for 48.4% of cases (median age 16 years [IQR 4-52]; 61.6% female). Same-day diagnosis was highest among children aged 1-4 years (75.4%) and lowest among adults aged 50 and older (approximately 50%). Among the 305 patients (38.8%) with delayed diagnosis, median delay ranged from 7-12 days in children to 22.5-26.5 days in adults aged 50 and older. Delay did not vary significantly by COVID-19 period, race, ethnicity, or insurance type. Testing breadth was greater in inpatient and emergency settings than outpatient. Pertussis testing was predominantly PCR-based in children but serologic in adults, potentially reflecting later clinical presentation relative to illness onset; however, the near-absence of PCR testing in older adults may contribute to missed diagnoses during the early illness window when PCR sensitivity is highest. Conclusions: Older adults experienced markedly delayed pertussis diagnoses compared with children. Earlier consideration of pertussis in adults with prolonged cough, including PCR testing early in illness before serologic conversion, may reduce diagnostic delay and facilitate timelier treatment and contact tracing.

Background: The Central Brain Tumor Registry of the United States (CBTRUS) uses a histology grouping model based on the World Health Organization (WHO) to classify cancer registry records for clinically relevant statistical reporting. Methods: CBTRUS, together with its consulting neuropathologists, reviewed and aligned its histology groupings with the 2021 WHO Classification update. Obsolete histology nomenclature along with their International Classification of Diseases for Oncology 3rd edition (ICD-O-3) codes were identified, currently included histologies were reclassified as appropriate, and new codes found in 2021 WHO were incorporated. An evaluation was conducted of the frequency of histology codes affected in the reclassification process, as well as incidence and survival pre- and post- reclassification of CBTRUS Tumor Type Groupings. Results: After review of the CBTRUS grouping scheme, 205 codes were reclassified and 2 new codes were incorporated. Tumor type groups most affected were those classified as glioma. Reclassification resulted in 167,038 of 491,804 (34%) cases having a grouping reclassification or reporting change, indicating that the 2021 revision of the WHO Classification has significantly impacted the collection and reporting of primary b CNS tumors. Conclusion: This work demonstrates the need to be responsive to changes in classification and coding for statistics to reflect real-world clinical use. This will require collaboration from all parties to have the ability to reconcile clinical practices and surveillance requirements.

Background: The C-reactive protein-albumin-lymphocyte (CALLY) index integrates systemic inflammation, nutritional status, and immune function. We evaluated its association with survival in primary lung malignancies. Methods: Embase, PubMed, Scopus, and Web of Science were searched from inception to 18 September 2026. Risk of bias was assessed using the Quality In Prognosis Studies tool. Hazard ratios (HRs) were synthesized using random-effects models with restricted maximum likelihood estimation and Hartung-Knapp adjustment. Sensitivity analyses, subgroup analyses, and meta-regression examined robustness and heterogeneity. Results: Eleven studies contributed 13 cohorts to the overall survival (OS) analysis and 8 cohorts from seven studies to a combined recurrence/progression-free survival (RFS/PFS) analysis. Lower CALLY was associated with poorer OS (HR 1.78, 95% CI 1.49-2.12; I2=71.6%) and poorer RFS/PFS (HR 1.60, 95% CI 1.40-1.84; I2=0%). Associations persisted in leave-one-out analyses. No statistically significant subgroup differences were detected. Funnel-plot asymmetry suggested small-study effects for OS and RFS/PFS. Seven studies had moderate and four had high overall risk of bias. The certainty of evidence was rated as low for both OS and RFS/PFS, primarily due to risk of bias, heterogeneity, and endpoint indirectness. Conclusion: Lower CALLY was associated with adverse survival outcomes in the current synthesis. Methodological limitations and variation in biomarker measurement and endpoint definitions restrict interpretation. Prospective validation using standardized measurements and clinically coherent outcomes is needed to establish incremental prognostic value and clinical utility. Keywords: CALLY index; lung cancer; prognosis; overall survival; systematic review; meta-analysis

Orientia tsutsugamushi is the causative agent of scrub typhus infection in humans. This pathogen is transmitted into mammalian hosts including humans through Leptotrombidium mites. Till date, detection of O. tsutsugamushi in human was performed using PCR assay with 56kDa type specific antigen (TSA56), 47kDa outer membrane protein (47kDa-OMP) and groEL chaperonin gene. To understand the efficiency of different genes for the detection of O. tsutsugamushi in Leptotrombidium mites, we performed a comparative PCR assay with various universal primers targeting different genes including TSA56, 47kDa-OMP and groEL gene. We have collected 500 Leptotrombidium mites from Vellore, Tamil Nadu and, the mites were segregated into 50 pools with 10 mites in each pool were used for DNA extraction. The molecular detection of O. tsutsugamushi was performed using PCR assays (including conventional, nested and duplex PCR). The comparative PCR analysis showed nested PCR of groEL gene has high efficiency in detecting the presence of O. tsutsugamushi in chigger samples compared to other genes. Interestingly, groEL target demonstrated high efficiency for detection of O. tsutsugamushi in chigger samples and, when used with nested primers, can facilitate differentiation of O. tsutsugamushi from other rickettsial pathogens. Thus, we conclude groEL gene nested PCR assay can be used routinely to detect O. tsutsugamushi in trombiculid mites.

Background: Prostate cancer (PCa) is the most common urological malignancy globally and remains a major cause of cancer mortality among men. In Hong Kong, a comprehensive evaluation of disease burden, real-world treatment patterns, and outcomes across clinically relevant PCa subgroups is essential for identifying unmet needs and optimising care delivery. Objectives: This study aims to characterise the burden of PCa and patterns of care in Hong Kong by (1) estimating annual patient load (2) describing treatment patterns, and (3) evaluating real-world outcomes among patients receiving systemic therapy (chemotherapy or novel hormonal agents [NHA]) and novel agents (immunotherapy, poly ADP-ribose polymerase [PARP] inhibitors, radiation therapy). Methods: We conducted a population-based retrospective cohort study using electronic medical records from the Hong Kong Hospital Authority (HA). The cohort included patients diagnosed with PCa between January 1, 2012 and December 31, 2024. Subgroup analyses included patients with metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) and were further stratified by the treatment received. Descriptive analyses summarised annual patient load and treatment patterns over 2018 to 2022. We evaluated treatment outcomes from 2012 to 2024, including overall survival, progression-free survival, number of hospitalisations, and main adverse events. Results: From 2018 to 2022, prevalence increased for prostate cancer (12,014 to15,610), mHSPC (1,188 to 1,779), and mCRPC (167 to 290), while annual mCRPC incidence rose from 125 to 274. There was an increasing number of prevalent and new users of the investigated novel treatment, including first-/second-/third-line therapy for mCRPC. Compared with patients treated with NHAs, chemotherapy showed a numerically higher rate of hospitalisations, bone treatment initiation and higher hematologic toxicity. Conclusions: This population-based retrospective study provides Hong Kong-specific evidence on PCa burden, real-world management, and outcomes across key subgroups, thereby supporting policy planning, formulary evaluation, and targeted strategies to address unmet clinical needs. Funding: This work was supported by a grant from Novartis.

Purpose Tarlatamab, a bispecific T-cell engager, has generated favorable response and survival outcomes in relapsed small cell lung cancer (SCLC). Factors influencing tarlatamab-associated treatment outcomes and toxicity have yet to be established. We performed a multivariate analysis to identify biomarkers associated with cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS) and integrated these variables into a novel risk stratification tool to identify patients at high risk of clinically significant toxicity. Patients and Methods Logistic and ordinal regression analyses evaluated the predictive value of variables contributing to the presence and severity, respectively, of CRS and ICANS in 115 patients with ES-SCLC receiving tarlatamab. Selected variables were then tuned using 5-fold cross-validation and incorporated into novel elastic net-based prediction models. Results Rates of observed CRS, ICANS, and dysgeusia were 46%, 28%, and 47%, respectively. ORR (overall response rate) and DCR (disease control rate) were 44% and 58.2%, while 6-month PFS (progression free survival) and OS (overall survival) rates were 30.4% and 54.9%, respectively. Excluding patients on tarlatamab <30 days, presence of dysgeusia was associated with a lower rate of disease progression (HR 0.44, p=0.00691) and death (HR 0.34, p=0.0145). The presence of, increased size and number of extracranial metastases as well as elevated baseline LDH were significantly associated with increased likelihood of CRS. Increased ECOG performance status, increased volume of brain metastases, development of CRS, and elevated baseline LDH were all associated with increased risk of developing ICANS. Our cross-validated risk model successfully predicted CRS grade [&ge;]2 and ICANS events with 90.9% and 75% sensitivity, respectively. Conclusions This exploratory analysis identified several predictive biomarkers of toxicity that successfully stratified low and high-risk populations as part of an internally validated novel risk scoring tool.

Objective: Current guidelines recommend different adjuvant treatment strategies for women with endometrioid early stage endometrial cancer exhibiting a p53 abnormal pattern. We aimed to evaluate recurrence patterns and explore the clinical implications for adjuvant therapy in this population. Materials and methods: This multicenter retrospective study included 86 patients with endometrioid, p53 abnormal, FIGO stage I, II endometrial cancer treated between 2013 and 2023 at six hospitals in the Republic of Korea. Clinicopathologic data were collected through medical record review. Progression free survival (PFS) was estimated using the Kaplan Meier method, and prognostic factors were analyzed using Cox proportional hazards regression models. Results: The 12, 24, and 36 month PFS rates were 91%, 78%, and 76%, respectively. Among the 16 patients who experienced recurrence, 12 (75%) had distant metastases. Adjuvant chemotherapy showed a trend toward improved PFS compared with adjuvant radiation therapy with or without chemotherapy (p=0.10). In multivariable analysis, the p53 overexpression pattern was independently associated with worse PFS compared with the p53 null pattern (HR 8.59, 95% CI 1.61 to 45.79, p=0.01). Conclusion: Given the poor PFS, the predominance of distant recurrence and the observed trend toward improved PFS with chemotherapy, adjuvant chemotherapy may be considered in women with endometrioid early stage endometrial cancer exhibiting a p53 abnormal pattern. Further studies are warranted to clarify the prognostic impact of p53 abnormality subtypes.