Satoshi Kakiuchi

An aspergilloma is a fungus ball that forms within a preexisting cavity, most commonly in the lungs but also in the paranasal sinuses. It represents a chronic inflammatory disorder that can persist for months and cause life-threatening hemoptysis. In this study, we hypothesized that the fungus ball is predominantly composed of non-viable hyphae and that chronic inflammation is maintained primarily by host responses to these non-viable elements rather than by ongoing fungal proliferation. To investigate this, we created a murine fungus ball model by implanting heat-killed Aspergillus fumigatus fungus balls, allowing for ≥16 weeks of longitudinal assessment. The model recapitulated key pathological features of the human disease, including progressive fibrosis and sustained angiogenesis, coinciding with elevated vascular endothelial growth factor (VEGF). A distinct immune response was observed where neutrophils infiltrated the fungus ball core, while macrophages accumulated at the periphery. Strikingly, these macrophages surrounding the lesion progressively became lipid-laden foam-like cells with an M1-skewed profile, a phenomenon reproduced in vitro by exposure to non-viable hyphae alone. Thus, the fungal material itself can sustain chronic inflammation and vascular remodeling, implicating macrophage lipid accumulation as a process potentially contributing to the chronic host response. These findings highlight lipid dysregulation and failed fungal clearance as key features of the host-response disorder associated with the fungus ball and establish a tractable platform for evaluating host-directed therapies. IMPORTANCE: Aspergilloma, a fungus ball that forms in preexisting cavities of the lung or paranasal sinuses, can cause chronic symptoms and life-threatening bleeding. Current fungicidal treatments, including antifungals, are often ineffective, and surgery to remove the fungal ball is risky. To better understand why these lesions can persist even when active fungal growth is limited, we developed a murine subcutaneous fungus ball model using non-viable Aspergillus fumigatus . In this model, a fungal mass composed largely of non-viable hyphae was associated with chronic inflammation, neovascularization, fibrosis, and the accumulation of lipid-laden, foam cell-like macrophages around the fungus ball. These findings support the concept that persistent non-viable fungal material can sustain key features of aspergilloma-like pathology through dysregulated host responses. They provide a conceptual rationale for future studies of host-directed strategies that modulate inflammatory and lipid-handling pathways in addition to conventional antifungal approaches.

As azole-resistant Aspergillus fumigatus emerges globally, healthcare facilities face mounting challenges in managing invasive aspergillosis. This review synthesizes worldwide azole resistance data to reveal profound regional variability, demonstrating that findings from other regions cannot be directly extrapolated to local settings. Consequently, hospital-level environmental surveillance is crucial for tailoring interventions to local epidemiology and detecting resistant strains in real-time. We outline practical approaches—encompassing sampling site prioritization, diagnostic workflows (culture-based and molecular), and PDCA-driven continuous improvement—so that even resource-limited facilities can manage resistant isolates more effectively. By linking real-time surveillance findings with clinical decisions, hospitals can tailor antifungal stewardship programs and swiftly adjust prophylaxis or treatment regimens. Our approach aims to enable accurate, ongoing evaluations of emerging resistance patterns, ensuring that institutions maintain efficient and adaptive programs. Ultimately, we advocate for sustained, collaborative efforts worldwide, where facilities adapt protocols to local conditions, share data through international networks, and contribute to a global knowledge base on resistance mechanisms. Through consistent application of these recommendations, healthcare systems can better preserve azole efficacy, safeguard immunocompromised populations, and refine infection control practices in the face of evolving challenges.

Background: Non–AIDS-defining cancers (NADCs) in patients infected with HIV have recently attracted attention because of the improved survival of this patient population. To obtain accurate data, a longitudinal study is warranted for the nationwide surveillance of the current status and national trend of NADCs in patients infected with HIV in Japan. Setting: An annual nationwide surveillance of NADCs in patients infected with HIV-1 in Japan from 1999 to 2021. Methods: An annual questionnaire was sent to 378 HIV/AIDS referral hospitals across Japan to collect data (clusters of differentiation 4-positive lymphocytes, time of onset, outcomes, and antiretroviral therapy status) of patients diagnosed with any of the NADCs between 1999 and 2021. Results: The response and case-capture rates for the questionnaires in 2021 were 37.8% and 81.2%, respectively. The number of reported NADC cases subsequently increased since the beginning of this study. Evaluation of the case counts of NADCs demonstrated a high incidence of lung, colorectal, gastric, and liver cancers as the top 4 cancers. Pancreatic cancer (0.63), lung cancer (0.49), and leukemia (0.49) had the highest mortality rates among the NADCs. Trends of NADCs regarding transmission routes were maintained over the years in male individuals who have sex with male individuals compared with heterosexual male individuals and female individuals. Conclusions: We demonstrated an increasing trend in the incidence of NADCs over a period of 23 years in Japan. The current data highlighted the importance of raising awareness regarding cancer management for patients infected with HIV in Japan.

The direct impact of a combined vaccination strategy pneumococcal 13-valent conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPSV23) for adults in preventing pneumococcal infections has yet to be thoroughly investigated. We aimed to estimate the comparative effectiveness of preventing the most severe form of pneumococcal infections, invasive pneumococcal disease (IPD), by comparing the risk of IPD stratified by the use of PCV13, PPSV23, and their combinations. We included all patients who were 65 years or older, had established primary care within the Veterans Health Administration (VHA) between 2005 and 2021, and had not received any prior pneumococcal vaccination. We measured time-to-event from cohort enrollment to the onset of culture-proven IPD, considering death a competing risk event, and constructed a Cox regression model to estimate cause-specific hazards. PCV13 only, PPSV23 only, and PCV13 + PPSV23 were incorporated into the model as a time-dependent exposure variable, and we estimated hazard ratios (HRs) associated with them. We also considered a waning effect by incorporating time-by-vaccine interaction terms in the model to estimate continuously changing time-dependent hazards. In this large cohort study at the VHA, neither vaccine by itself appeared to lower the risk of IPD, but the combination of PCV13 and PPSV23 was associated with a significantly lower risk. In addition, we did not observe evidence of a waning effect to prevent IPD. Further studies are needed to evaluate the effect of newer pneumococcal vaccines. Michihiko Goto, MD MSCI, Merck & Co.: Grant/Research Support

The optimal metric for outpatient antimicrobial stewardship has not been well defined. The number of antibiotic prescriptions per clinic visit does not account for the therapeutic duration. We found only moderate association between prescription-based metrics and days-supplied–based metrics. Outpatient antibiotic consumption metrics should incorporate the duration of therapy.