Medicine and Pharmacology

Abstract: Background: Chikungunya virus (CHIKV) has circulated in the Philippines for more than six decades. Reviewing the evidence accumulated over this period provides an oppor-tunity to summarize its epidemiology and describe patterns of transmission over time. We systematically reviewed the epidemiology of CHIKV in the Philippines, integrating evidence on transmission, seroprevalence, diagnostics and molecular lineages. Methods: We followed PRISMA 2020 and searched PubMed and Embase to March 2026 for original studies reporting incidence, prevalence, seroprevalence, outbreak characteristics, or surveillance findings in human populations in the Philippines. Grey literature from the Department of Health (DOH) Epidemiology Bureau (2018–March 2026) was included separately. Findings were synthesized narratively because of substantial heterogeneity. Results: Sixteen studies and one national surveillance dataset were included. Serological reconstruction and prospective cohorts indicate approximately four major transmission waves over six decades, separated by intervals of about 17 years. Each wave infected an estimated 23% (16–37%) of remaining susceptible, while more than half remained sus-ceptible thereafter. In Cebu, incidence declined from 12.32 to 2.84 infections per 100 person-years as neutralizing-antibody prevalence increased from 28% to 42%; only about one in five infections was symptomatic. National surveillance recorded 12,662 cases from 2018 to early 2026, including 722 laboratory-confirmed; three deaths. The Asian genotype predominated during the 2011–2013 epidemic, while the Indian Ocean lineage viruses were detected in southern Mindanao. Conclusions: Transmission of CHIKV in the Phil-ippines appears to follow a periodic, recurrent pattern, with outbreaks occurring as population susceptibility accumulates following periods of low-level transmission. Pe-riodic arboviral serosurveys and testing of acute febrile illness are needed to better characterize CHIKV epidemiology in the Philippines.

Abstract: Background and Aim: HDV infection represents one of the most severe forms of chronic viral hepatitis, characterized by rapid fibrosis progression and poor long-term outcomes, and is associated with a markedly increased likelihood of developing liver cirrhosis, hepatocellular carcinoma (HCC), and hepatic decompensation. Metabolic dysfunction-associated steatotic liver disease (MASLD), now recognized as the most common chronic liver disorder globally, has been proposed to amplify hepatic injury through overlapping metabolic and inflammatory mechanisms when concurrent with viral hepatitis. To date, however, systematic data on the co-occurrence of MASLD and metabolic dysfunction-associated steatohepatitis (MASH) in the setting of chronic HDV infection are remarkably scarce. Accordingly, the present study aimed to characterize the prevalence and severity of MASLD and MASH, as assessed by transient elastography (FibroScan), in a cohort of patients with chronic HDV infection. Methods: A total of 125 anti-HDV seropositive patients were enrolled in this cross-sectional study . HDV-RNA quantification was performed in all participants. Liver stiffness measurement (LSM, kPa) and controlled attenuation parameter (CAP, dB/m) were obtained via FibroScan. Results: The mean patient age was 39.0 years; 74.4% of participants were male (n=93). Of all the patients, 68% (n=85) had received pegylated interferon-alpha (peg-IFN-alpha) therapy for at least 12 months; however, sustained virological response (SVR) was achieved in only 14.1% (n=12). The overall mean LSM was 9.1 kPa, while the mean CAP was 228 dB/m. Liver cirrhosis was identified in 36.8% of patients (n=46; mean LSM 16.2 kPa), with 17.4% of cirrhotic patients (n=8) classified as decompensated and referred for liver transplantation evaluation. HCC was detected in 1.6% (n=2). MASLD was present in 24.0% of patients (n=30; mean CAP 289 dB/m) and MASH in 8.8% (n=11). LSM values were significantly higher in the cirrhotic group compared with non-cirrhotic patients (p< 0.001). No statistically significant difference in CAP was observed between cirrhotic and non-cirrhotic groups (p=0.121). Conclusion: Chronic HDV infection carries a heavy burden of cirrhosis and HCC, further compounded by markedly limited therapeutic efficacy. The presence of MASLD in approximately one in four patients, and MASH in nearly one in ten, underscores the necessity of routine FibroScan-based metabolic liver assessment in this high-risk population.

Abstract: Community-acquired pneumonia carries high mortality in very old adults with multimorbidity, yet preventable medication-related harm is often under-recognised. This case report describes a woman in her late 80s with stage G3a chronic kidney disease who presented with community‑acquired pneumonia to a large multidisciplinary centre. Empiric meropenem was initiated shortly after admission and the dose was increased on day 8 despite persistent renal impairment. Amikacin 1 g once daily was then added. On the same day, the patient received furosemide, intravenous potassium chloride, and glucose infusions as metabolic abnormalities emerged. After temporary stabilisation in the intensive care unit, amikacin was discontinued, linezolid was started, and the patient was transferred to a general ward, where she died four days later. On her final day, life-threatening hyperkalaemia was documented, yet additional potassium was administered, precipitating cardiac arrest. This case illustrates how routine interventions—broad-spectrum antibiotics, aminoglycosides, diuretics, and potassium supplementation—can become iatrogenic in frail older adults when dosing and monitoring are not adjusted for age and kidney function. It underscores the need for strict renal dose adjustment, cautious potassium management, and early geriatric assessment in hospitalised multimorbid older patients.

Abstract: Background: Severe varicella in previously healthy adults is uncommon, and underlying genetic susceptibility is increasingly recognized as a contributing factor in such cases. However, the coexistence of heterozygous variants affecting distinct immunological pathways has rarely been documented. Case presentation: We report a 39-year-old previously healthy Chinese male who presented with a 2-day history of fever and a 1-day history of a generalized vesicular rash after exposure to a patient with herpes zoster. The patient rapidly developed severe pneumonia, acute liver injury (ALT 617.9 U/L, AST 1055.2 U/L), acute myocardial injury (troponin T 17.91 pg/mL), acute kidney injury (creatinine 121.4 μmol/L), and severe thrombocytopenia (36×10⁹/L) with coagulopathy. Lymphocyte subset analysis obtained during acute illness revealed decreased CD4⁺ T cells (373.6/μL), elevated CD8⁺ T cells (1450.3/μL), and an inverted CD4⁺/CD8⁺ ratio, likely reflecting infection-induced perturbations. Whole-exome sequencing identified a heterozygous missense variant in FOXN1 (NM_003593.3) (c.163G>A, p.G55S) and a heterozygous missense variant in PIK3CD (NM_005026.4) (c.1487G>A, p.R496Q), both classified as variants of uncertain significance without functional validation. The patient received high-flow nasal cannula oxygen therapy, intravenous acyclovir, intravenous immunoglobulin, and multiorgan supportive care, and achieved full recovery without sequelae. Conclusions: This case represents the first report of coexisting FOXN1 and PIK3CD concurrent heterozygous variants in an adult presenting with severe varicella and multiorgan dysfunction. As both variants are VUS and lack functional characterization, any attribution of functional impact remains speculative. It is hypothesized that the FOXN1 variant, if pathogenic, might reduce thymic T-cell output, and the PIK3CD variant, if gain-of-function, could cause T- and B-cell dysregulation, potentially impairing antiviral responses. Causality has not been established, and functional studies are required to determine the significance of these variants. This case underscores the importance of genetic evaluation in previously healthy adults who develop unusually severe infections and suggests that concurrent heterozygous variants of uncertain significance may contribute to a "hidden immunodeficiency" phenotype, wherein a baseline vulnerability only becomes clinically apparent upon a potent viral trigger.

Abstract: Clostridioides difficile infection (CDI) has evolved from a sporadic, antibiotic-associated illness into a leading European healthcare-associated infection (HAI). Romania is an instructive case: hypervirulent ribotype 027 (RT027) has dominated locally since 2011–2012, and national surveillance traces four phases — emergence, consolidation, pandemic-era distortion, and recent resurgence. This review synthesises 102 Romanian and pan-European sources (ECDC, ECDIS-Net, COMBACTE-CDI, ESCMID/IDSA-SHEA guidance) to characterise CDI’s epidemiology, molecular typing, and clinical outcomes in Romania relative to Europe. Romanian RT027 prevalence (68–82.6% of typed isolates) far exceeds the 2008 pan-European baseline (5%); national confirmed cases rose from 5,845 in 2015 to a pre-pandemic peak of 12,068 in 2019, fell during the pandemic despite persistently elevated calculated incidence, and resurged to 11,651 in 2022; hospital incidence more than tripled between 2020 and 2023 at one tertiary centre; a 2026 multicentre analysis found CDI caused over half of reported HAIs, amid high antibiotic consumption despite low official HAI rates; and treatment access remains constrained, with limited fidaxomicin reimbursement data and just 31 active faecal microbiota transplantation centres continent-wide. Romania exemplifies a surveillance-bias-masked endemic pattern in which true CDI burden is likely underestimated; priorities include mandatory notification, systematic ribotyping, disciplined antimicrobial stewardship, and equitable access to guideline-recommended therapy.

Abstract: The global emergence of coronavirus disease 2019 (COVID-19) was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The clinical manifestations of COVID-19 in patients range from asymptomatic disease to severe multiorgan dysfunction and even death. Moreover, the growing population of clinically immunodeficient patients and the use of single clinical antifungal agents have gradually increased the incidence of Aspergillus fumigatus infections, the complex clinical manifestations of which are yet to be fully clarified. The mortality rate among COVID-19 patients coinfected with A. fumigatus has risen significantly. Therefore, a comprehensive understanding of the diagnosis and treatment of A. fumigatus infections, SARS-CoV-2 infections, and their coinfections is crucial. In this review, we first provide a comprehensive description of the life cycle of A. fumigatus, together with an in-depth analysis of its characteristics, diagnosis, and treatment strategies for associated diseases. Then the basic structure of SARS-CoV-2, the evolution of variant strains, and key aspects of its prevention and control was discussed. Finally, the symptoms, diagnosis, and treatment of COVID-19 coinfection with A. fumigatus are summarized. In this paper, we provide methodological references and data to support the clinical prevention and treatment of A. fumigatus and SARS-CoV-2 infections.

Abstract: Background: Gastrointestinal infections remain a major cause of morbidity, mortality, and healthcare utilization worldwide. Although most episodes are self-limiting and require supportive care, antibiotics are essential in selected severe, invasive, or high-risk infections. Inappropriate prescribing contributes to adverse events, microbiome disruption, Clostridioides difficile infection, and antimicrobial resistance. Methods: This narrative review examined evidence on antibiotic use in gastrointestinal infections, emphasizing clinical indications, pathogen-directed therapy, stewardship, resistance, and emerging treatments. PubMed, Scopus, and Google Scholar were searched primarily for publications from 2014 to 2026. Relevant international guidelines and landmark earlier studies were also included. Evidence was selected according to clinical relevance and methodological quality. Results: Antibiotic decisions should be guided by disease severity, host factors, epidemiological exposures, microbiological findings, and local susceptibility patterns. Routine treatment is generally unnecessary for uncomplicated non-typhoidal salmonellosis and campylobacteriosis but may benefit patients with severe disease or increased risk of invasive infection. Treatment is indicated for selected shigellosis, cholera, travelers’ diarrhea, and Clostridioides difficile infection, whereas antibiotics should be avoided in Shiga toxin-producing Escherichia coli infection because of the potential risk of hemolytic uremic syndrome. Rapid molecular diagnostics improve pathogen detection but require careful interpretation and do not replace culture or susceptibility testing. Fidaxomicin, microbiota-based therapies, vaccines, and clinical decision-support systems may further improve outcomes. Conclusion: Effective management requires selective, evidence-based prescribing integrated with prompt rehydration, diagnostic stewardship, and resistance surveillance. Preserving antimicrobial effectiveness and intestinal microbial integrity will require coordinated clinical, public-health, and One Health strategies, alongside equitable access to diagnostics, effective treatments, sanitation, vaccination, and continuing professional education.

Abstract: Background: Clostridioides difficile infection (CDI) is an important healthcare-associated infection associated with substantial morbidity and mortality. This study aimed to characterize the clinical and epidemiological profile of hospitalized CDI patients and identify independent predictors of 90-day all-cause mortality. Methods: We conducted a retrospective observational study of adult patients with CDI admitted to a regional infectious diseases’ hospital in Galați, Romania, during 2024. CDI was defined according to ECDC criteria and diagnosed using a two-step laboratory algorithm. Clinical, epidemiological, and laboratory data were collected. Predictors of 90-day mortality were assessed using multivariable logistic regression. Results: Among 170 patients (median age, 70 years), 74.3% had an age-adjusted Charlson Comorbidity Index >5, and 49.4% had previous antibiotic exposure. Three patients died during hospitalization, while an additional 52 deaths occurred among 167 patients discharged alive. An ATLAS score >4 (adjusted OR, 3.96; 95% CI, 1.78–8.81; p = 0.001) and indwelling urinary catheter use (adjusted OR, 2.89; 95% CI, 1.13–7.35; p = 0.026) were independently associated with 90-day mortality. Conclusions: Ninety-day all-cause mortality was substantial. An ATLAS score >4 and indwelling urinary catheter use were independently associated with mortality, supporting early risk stratification and closer follow-up of high-risk patients.

Abstract: Background: Bromhexine hydrochloride (BRH) has been proposed to functionally inhibit the host serine protease TMPRSS2, a key mediator of viral entry for SARS-CoV-2, influenza A and B viruses, and other respiratory viruses that depend on TMPRSS2-mediated proteolytic activation. Emerging evidence suggests that the antiviral activity of BRH against SARS-CoV-2 may extend beyond TMPRSS2 inhibition. BRH may interfere with spike–ACE2 interaction through ACE2-targeted mechanisms, while preliminary molecular and computational evidence suggests probable inhibition of the SARS-CoV-2 main protease (Mpro/3CLpro), potentially affecting viral polyprotein processing and replication. Thus, BRH may exert a three-pronged antiviral effect against SARS-CoV-2—interference with spike–ACE2 binding, inhibition of TMPRSS2-dependent viral entry, and probable inhibition of Mpro/3CLpro-dependent viral replication. Rather than completely preventing infection, such multimodal pharmacological attenuation may reduce viral entry and amplification while preserving sufficient antigen exposure for adaptive immune priming. This strategy may be particularly relevant to personalized prevention according to individual susceptibility, comorbidities, exposure risk, and vulnerability to severe respiratory infection. Methods and Clinical Observations: We describe a 72-year-old man who had received no SARS-CoV-2 vaccination 2021 and had been taking BRH prophylactically (8 mg twice daily) for approximately two weeks before an incidentally diagnosed SARS-CoV-2 infection. The infection remained clinically inapparent apart from mild throat irritation. Despite the absence of clinically significant disease, he developed a robust humoral immune response, with an anti-spike antibody concentration of 2,080 BAU/mL three months after infection and persistent anti-spike IgG reactivity nine months later (Vircell anti-S IgG ratio 22.209). A parallel household observation involved his 71-year-old wife, who had multiple established risk factors for severe COVID-19, including chronic obstructive pulmonary disease, previous pancreaticoduodenectomy for pancreatic cancer, severe underweight, and a long history of heavy smoking. Despite continuous BRH prophylaxis and presumed household exposure, she remained clinically asymptomatic while demonstrating measurable anti-spike immune reactivity. Additional real-world observations from individuals receiving prolonged BRH prophylaxis—including elderly patients with multiple comorbidities, heavy smokers, and a child receiving seasonal prophylaxis—were characterized by favorable tolerability and absent or markedly attenuated clinically apparent COVID-19 and influenza. Hypothesis and Conclusions: These observations support the hypothesis of Pharmacologically Attenuated Natural Immunization (PANI), whereby pharmacological attenuation of infection reduces viral entry and subsequent amplification sufficiently to limit tissue injury and clinically significant disease without necessarily producing sterilizing protection, thereby preserving antigen presentation and adaptive immune priming. In SARS-CoV-2 infection, the proposed three-pronged activity of BRH—targeting spike–ACE2 interaction, TMPRSS2-dependent entry, and potentially Mpro/3CLpro-dependent replication—provides a mechanistic framework for such controlled attenuation. For influenza, the principal proposed mechanism remains inhibition of TMPRSS2-dependent hemagglutinin activation. Within a personalized medicine framework, this concept raises the possibility of tailoring host-directed prophylaxis according to individual risk profiles. The observations presented here are hypothesis-generating and do not establish causality. Prospective controlled studies incorporating documented viral exposure, serial quantitative virological assessment, neutralizing antibody measurements, cellular immune profiling, and predefined risk stratification are required to determine whether BRH can reproducibly achieve infection sufficient for immune priming but pharmacologically constrained below the threshold for clinically significant disease.

Abstract: Sepsis-associated renal injury involves interacting oxidative, inflammatory, and microvascular mechanisms. Molsidomine, a nitric oxide donor, may modulate these pathways. We investigated whether molsidomine pretreatment attenuates renal injury in cecal ligation and puncture (CLP)-induced polymicrobial sepsis. Forty male Wistar albino rats were randomized to Sham, molsidomine (MOL), CLP, or MOL+CLP groups. Molsidomine (10 mg/kg/day) was administered orally for 14 days before surgery. At 24 h, renal biochemical, histopathological, and immunohistochemical outcomes were assessed. Seven septic animals died before the endpoint, resulting in outcome-specific numbers of evaluable animals. The primary outcome was total renal histopathological damage score. The total renal histopathological damage score was lower in MOL+CLP than CLP animals [median (IQR), 2 (1–3) vs. 5.5 (5–6); overall p < 0.001], with reductions across all four histopathological components. Renal MDA was lower in MOL+CLP than CLP animals (106.41 ± 9.03 vs. 136.45 ± 20.27 nmol/g), whereas SOD (36.23 ± 4.19 vs. 24.12 ± 2.23 U/g) and GPx (99.43 ± 26.38 vs. 61.54 ± 9.10 U/mg) activities were higher. VEGF and P-selectin H-scores were also markedly lower in MOL+CLP than CLP animals. Conversely, renal NO, GSH, TOS, OSI, and TNF-α and serum creatinine, BUN, and urea did not differ significantly between the two septic groups. Molsidomine pretreatment attenuated renal structural injury, selected redox abnormalities, and VEGF/P-selectin immunoreactivity in experimental polymicrobial sepsis. This renoprotective phenotype was not accompanied by uniform biochemical or renal functional improvement. These proof-of-concept findings warrant evaluation using post-sepsis treatment protocols and longer-term renal outcomes.

Abstract: Invasive fungal diseases (IFD) have become a routine diagnostic and therapeutic challenge in high-acuity hospitals worldwide, and Latin America presents a distinctive scenario in which opportunistic mycoses of tertiary care coexist with endemic dimorphic fungi, heterogeneous diagnostic capacity, and uneven antifungal access. This narrative review organizes a practical, clinically usable pathway for Latin American high-acuity hospitals, from the construction of a “window of suspicion” based on host risk factors, through the diagnostic work-up available in the region (non-culture biomarkers, molecular platforms, imaging, and histopathology), to syndrome-specific clinical pathways for candidemia, invasive aspergillosis, mucormycosis, and cryptococcal meningitis, including antifungal selection, dosing, and stewardship. We highlight where regional diagnostic and therapeutic constraints depart from guidance developed in high-resource settings and where structured clinical suspicion must substitute for advanced biomarkers. We conclude that early, syndrome-directed pathways adapted to local resource availability, rather than uncritical adoption of international algorithms, offer the most realistic route to earlier antifungal therapy and improved outcomes in Latin American high-acuity hospitals.

Abstract: Introduction: Infective endocarditis (IE) remains associated with high mortality, and the optimal timing of surgery in patients without an urgent indication remains uncertain. We evaluated the association between surgical timing, in-hospital mortality, and a study-specific ECHO risk score. Methods: We retrospectively studied 100 adults with definite IE treated at a tertiary care center in Bucharest, Romania. The ECHO score incorporated etiology, blood culture time to positivity, vegetation size, and embolization or surgical indication. Surgical timing was categorized as < 7 days, 7–14 days, or >14 days after hospital admission. The primary outcome was in-hospital mortality. Results: Eighty-two patients had a surgical indication, and 60 underwent surgery. Mortality was lowest after surgery at 7–14 days (23.1%), compared with >14 days (27.3%), no surgery despite indication (36.4%), and < 7 days (56.0%) (p = 0.123). Among patients with a non-urgent surgical indication, intermediate-risk patients had the lowest mortality after surgery at 7–14 days (25%), whereas no deaths occurred among surgically treated high-risk patients. ECHO risk category was not associated with mortality (p = 0.165). Conclusions: Surgery at 7–14 days was associated with the lowest observed mortality. These exploratory findings require confirmation in larger prospective studies.

Abstract: Background: Urinary tract infections (UTI) are a major driver of laboratory testing and antimicrobial prescribing, yet inappropriate urine collection, specimen handling, due to limited patient and nursing engagement can compromise diagnostic accuracy and contribute to unnecessary or inappropriate antibiotic use. This study evaluated knowledge, attitudes, and practices (KAP) related to pre-analytical diagnostic stewardship (DS), infection prevention and control (IPC), and antimicrobial stewardship (AMS) amongst nurses and hospitalized UTI patients. Methods: A cross-sectional study was conducted at two tertiary hospitals in Oman between September 2022 and August 2023. Three structured, internally validated questionnaires assessed pre-analytical DS, IPC, and AMS amongst nurses and patients. A total of 327 nurses participated, including 165 for the pre-analytical DS survey and 162 for the IPC and AMS survey; 77 hospitalized patients with UTI completed the patient questionnaire. KAP domain scores were standardized to a 0–100 scale and summarized as mean ± SD. MANOVA assessed the effects of covariates on combined KAP outcomes. Mann–Whitney U, Kruskal–Wallis tests compared KAP scores across demographic and professional groups. Results: Patients demonstrated strong awareness of importance of correct urine collection (91%); however, only 7.9% reported receiving midstream urine instructions, contrasting with 86.1% of nurses who reported providing them. They demonstrated high IPC engagement with 88.3% willing to prompt hand hygiene/glove use among doctors and nurses, and 74% would question antibiotic necessity. Amongst nurses gaps persisted in inserting new catheter before culture (66.7%) and refrigeration of specimens if delay expected (36.4%). Work experience significantly influenced pre-analytical KAP outcomes (p=0.002). Knowledge amongst nurses was high for hand hygiene, IPC prevention and antibiotic resistance drivers; however, 56.3% incorrectly associated antibiotics with pain/inflammation. Institutional affiliation significantly influenced IPC/AMS practice scores (p=0.004). Overall, findings revealed motivated stakeholders alongside discrete, actionable weaknesses in diagnostic and antimicrobial stewardship workflows. Conclusion: This study identifies a critical but modifiable gap between perceived and patient-experienced pre-analytical DS practices in UTI . Strengthening microbiology and nursing collaborative diagnostic stewardship, standardizing patient instructions, improving specimen-handling infrastructure, and actively engaging patients represent practical, high-impact strategies to enhance diagnostic accuracy, infection prevention, and antimicrobial stewardship in Oman.

Abstract: Background: Antimicrobial resistance (AMR) is a major global health threat, while conventional diagnostic, stewardship, dosing, and drug-development strategies remain limited by diagnostic delays, population-level decision-making, and a shrinking antibiotic pipeline. Artificial intelligence (AI) may help address these gaps by integrating complex clinical, microbiological, genomic, pharmacological, and chemical data. Methods: We conducted a narrative review of English-language publications issued between January 2010 and March 2026. PubMed/MEDLINE, Scopus, and Web of Science were searched using terms related to AI, machine learning, AMR, antimicrobial stewardship, diagnosis, susceptibility prediction, antibiotic dosing, pharmacokinetics, pharmacodynamics, and antibiotic discovery. ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and ISRCTN were additionally searched on 27 August 2026 for prospective interventional studies registered or publicly available by 31 March 2026. Results: AI-based systems demonstrated promising performance in differentiating bacterial from viral infections, predicting bacteremia and sepsis, enhancing matrix-assisted laser desorption/ionization time-of-flight interpretation, estimating antimicrobial susceptibility, supporting individualized empirical therapy, optimizing antibiotic dosing, and accelerating compound discovery. However, external and temporal validation frequently produced substantially poorer performance than internal validation. In representative resistance-prediction studies, AUROC declined from 0.94 internally to 0.55 during temporally independent external validation and by 0.10–0.25 over 18 months. Moreover, only six eligible prospective interventional studies were identified across the four domains examined: two concerning AI-assisted diagnosis or antibiotic-use decisions, three concerning resistance prediction or stewardship, one concerning model-informed precision dosing, and none concerning AI-assisted antibiotic discovery. Conclusions: Current evidence demonstrates that AI can generate technically promising predictions, but it does not yet establish consistent clinical or economic benefit. Discrimination alone is insufficient to demonstrate clinical usefulness. Prospective multicenter trials, clinically meaningful outcome measures, external validation, continuous monitoring for model drift, and formal implementation and cost-effectiveness evaluations are required before widespread adoption.

Abstract: Background: Favorable attitudes toward human papillomavirus (HPV) vaccination do not necessarily translate into vaccine uptake, particularly among young adults who were too old to benefit from recently expanded adolescent programs. We assessed the gap between attitudes and self-reported HPV vaccination and examined sociodemographic and psychosocial correlates of uptake among young adults in Poland. Methods: An anonymous cross-sectional online survey was conducted from 12 January 2025 to 14 August 2026. The analysis included 334 complete responses from adults aged 18–45 years recruited through social media. The 42-item questionnaire assessed sociodemographic characteristics, HPV knowledge, vaccine trust, perceived personal threat, social exposure to vaccinated persons, access, and barriers. Group differences were examined using Pearson chi-square tests. Multivariable logistic regression estimated adjusted odds ratios (aORs) for self-reported vaccination; two respondents reporting sex as other/prefer not to say were excluded from the sex-adjusted model (N=332). Results: Overall, 113/334 participants (33.8%) reported HPV vaccination, whereas 300/334 (89.8%) considered vaccination important. Among unvaccinated respondents, the most frequent barriers were lack of a clinician recommendation (83/221; 37.6%) and cost (75/221; 33.9%). In the adjusted model, vaccination was associated with female sex (aOR 2.49, 95% CI 1.10–5.65), greater vaccine trust (aOR 1.70 per scale point, 95% CI 1.17–2.45), and knowing a vaccinated person (aOR 7.73, 95% CI 4.02–14.86). Compared with participants aged < 20 years, those aged 23–25 years (aOR 0.33, 95% CI 0.12–0.86) and >25 years (aOR 0.27, 95% CI 0.09–0.86) had lower odds of vaccination. Objective HPV knowledge, education, urban residence, region, and medical/health-related study or work were not independently associated with uptake. Model AUC was 0.846. Conclusions: In this non-probability sample, the attitude-uptake gap was substantial. Vaccine confidence and social exposure were more strongly associated with HPV vaccination than objective knowledge, while lack of clinician recommendation and cost remained prominent barriers. Catch-up strategies for young adults should combine clear clinician recommendation, affordable and convenient access, gender-neutral cancer-prevention communication, and social normalization of vaccination.

Abstract: Background: This study was conducted to determine the relationship between microorganisms found in the hands, noses, and throats of music students and bacterial contamination on the wind and string instruments they use, and to evaluate the effect of the cleaning process on instrument contamination. Methods: Swab samples were taken from the hands, noses, and throats of the participants; from the mouthpieces, inner surfaces, and keys of the flutes; and from the fingerboards and bows of the string instruments. The effectiveness of the cleaning process was evaluated by comparing samples taken from the flutes after use and cleaning. The samples were examined using microbiological culture methods, and the isolated microorganisms were identified. In addition, the students’ participation in the orchestra and instrument-cleaning habits were evaluated. Results: There were varying relationships between the hand and upper respiratory tract microbiota of the students and bacterial contamination on the instruments, depending on the instrument type and the sampling area. Significant relationships were found between the upper respiratory tract microbiota and instrument contamination in flute-playing students; pathogen growth was completely eliminated, and flora growth was significantly reduced after cleaning. Furthermore, orchestra participation and less frequent instrument-cleaning habits were associated with pathogen colonization in the upper respiratory tract. Conclusions: These findings suggest that musical instruments may be susceptible to bacterial contamination related to the user’s microbiota, and that regular cleaning practices can play a significant role in reducing this contamination. Accordingly, it is recommended to develop standard practices for instrument hygiene and increase hygiene awareness in music education settings.

Abstract:

Azole resistance in Aspergillus fumigatus is an emerging threat to invasive and chronic aspergillosis management, yet multicenter trend analyses rarely verify whether the composition of surveillance data remained stable over time. We performed a longitudinal, secondary-data analysis of 2,111 Aspergillus isolates registered in the VIVLI AMR platform (ATLAS Antifungals, SENTRY Program) between 2010 and 2020. Because Clinical and Laboratory Standards Institute (CLSI) voriconazole breakpoints are established only for A. fumigatus in this dataset, the susceptibility-trend analysis was restricted to A. fumigatus isolates with a valid interpretation (n = 1,482/1,483). A. fumigatus accounted for 70.3% of all Aspergillus isolates; most originated from Europe (43.9%) and North America (35.2%). Region and clinical specialty differed significantly across the three study periods (both p < 0.0001), while species, age, sex and specimen-source distributions remained stable (p > 0.10). Voriconazole susceptibility in A. fumigatus declined from 97.9% (2010) to 90.4% (2020), with a significant linear downward trend (Cochran-Armitage Z = −3.03, p = 0.002). This decline was statistically robust, but the concurrent shift in participating regions and specialties indicates that compositional changes in surveillance sampling should be considered alongside biological resistance emergence when interpreting multicenter antifungal surveillance trends.

Abstract: Introduction: Following the end of the COVID-19 pandemic, excess mortality rates declined in many countries. However, Japan’s excess mortality rate remained elevated even in 2024. Most countries have stopped administering booster vaccines on a large scale; however, Japan continues to recommend COVID-19 vaccination for elderly individuals, and its booster vaccination per capita rate is the highest in the world. This study attempted to identify the variables related to excess mortality rates during and after the pandemic. Methods: The age-adjusted numbers of deaths and excess mortality rates were calculated for Japan's 47 prefectures from 2020 to 2024. Scatter plots were generated to visualize the relationship between the excess mortality rates and doses of COVID-19 booster vaccine administered. The regression model was subsequently conducted to examine variables associated with excess mortality rates during and after the pandemic across Japan's 47 prefectures. Results: In Japan, age-adjusted excess mortality was not observed in 2020 and 2021; however, it increased to 5.9% in 2022 and 4.9% in 2023. This increase continued even in 2024, when the pandemic ended, reaching 5.7%. During the pandemic period from January to September 2022, when vaccine doses were limited to four, the age-adjusted excess mortality rate showed a negative correlation with the number of vaccine doses (r=-0.55, p<0.01). From June 2023 to September 2024, however, after the pandemic ended and doses 5 to 7 were added, a positive correlation emerged ( r=0.25, p=0.1). A multiple regression analysis showed that excess mortality rates after the pandemic was more strongly associated with the number of booster vaccine doses than with the number of COVID-19 infections and population density of the 47 prefectures. Conclusions: This ecological analysis underscore the importance of continued surveillance of excess mortality in super-aged societies and highlight the need for individual-level and mechanistic studies to elucidate the relative contributions of SARS-CoV-2 infection, demographic factors, healthcare changes, and vaccination.

Abstract: Background: Invasive fungal infections are an important global public health problem, causing morbidity and mortality, particularly among immunocompromised and critically ill patients. Outcomes depend on timely diagnosis, laboratory capacity, and access to effective antifungal therapy. However, national data describing these resources in Chile remain limited. We aimed to characterize gaps in mycological diagnostic and therapeutic access. Methods: We conducted a nationwide survey of physicians, pharmacists, and laboratory professionals representing Chilean hospitals. Multiple responses from the same institution were consolidated. A 15-item diagnostic and therapeutic access score was developed to assess differences between hospitals. Results: 35 hospitals participated. Diagnostic infrastructure varied substantially across institutions. Although all hospitals reported access to direct mycological examination, 65.7% had MALDI-TOF MS and 51.4% had molecular identification methods. The access score differed significantly according to hospital size, with median scores of 53.3% (20.0–80.0), 66.7% (46.7–86.7), and 73.3% (60.0–86.7) in hospitals with 0–300, 301–499, and ≥500 beds, respectively (p=0.003). Conclusions: This nationwide assessment identified size-dependent inequities in mycological capacity in Chile. Larger hospitals had greater diagnostic and therapeutic access, supporting targeted national strategies to strengthen smaller institutions and ensure equitable care.

Abstract: Invasive Fungal Infections (IFIs) represent a significant threat to transplant recipients and patients with non-HIV-related immunosuppression, particularly in low- and middle-income countries (LMICs). While the disease burden in HIV populations is widely recognized, this group faces a critical gap in diagnosis and treatment that perpetuates a cycle of preventable deaths. Advances in medical therapies have revolutionized the management of hematologic malignancies, autoimmune diseases, and solid organ transplantation, increasing the number of severely immunocompromised individuals susceptible to opportunistic pathogens. In the US, IFI incidence rose from 30.2 to 31.8 per 100,000 between 2006 and 2015 [1]. However, epidemiological knowledge in LMICs remains limited due to scarce surveillance, high diagnostic and treatment costs, and low access to diagnostic methods, with disparities between regions and even within centers from the same countries. Current clinical guidelines must be adapted to regional resources to optimize diagnostic strategies and timely treatment. This review aims to analyze the primary gaps in LMICs to identify key intervention nodes for reducing mortality in non-HIV immunocompromised patients in our region.