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Invasive fungal disease (IFD) has high morbidity and mortality, the spectrum of pathogenic fungi and high-risk groups have also changed. Fewer literature focus on the overall incidence of IFD in various departments of general hospitals. Among the adult inpatients in four Chinese tertiary hospitals located in Beijing, Shanghai, Nanning and Nanchang, proven or probable cases of IFD were included prospectively in this study between May 1, 2021 and May 1, 2022. The clinical data were collected and analyzed. A total of 330 patients (342 episodes) with 278 of proven and 64 of probable IFDs were included, including invasive candidiasis (IC) (132, 40.0%), cryptococcosis (64, 19.4%), invasive aspergillosis (IA) (54, 16.4%), Talaromyces marneffei ( TsM ) infection (43, 13.0%), Pneumocystis pneumonia (PCP) (16, 4.8%), mixed fungal infection (10, 3.0%), other mold or yeast infection. 37.9% occurred in elderly patients (age ≥ 65 years). Nosocomial infection accounted for 44.5%, the proportion of nosocomial infection was highest in patients with IC (81.8%). Diabetes (19.7%) was the most common underlying disease. 83.9% of the 342 episodes of IFD had evidence of fungal culture, while the proportion of microscopic examination and histopathology as mycological evidence was 26.9% and 3.5%, respectively. The cumulative all-cause mortality at 180 days after diagnosis of IFD was 38.5%. Age ≥ 65 years old (HR = 1.670, P  = 0.009), ICU (HR = 2.002, P  = 0.001), nosocomial infection (HR = 1.630, P  = 0.016) and diabetes (HR = 1.679, P  = 0.013) were associated with increased death in IFD patients. The prognosis of IFD patients was poor. Doctors should pay attention to nosocomial fungal infection especially in old and diabetes.

Chronic mucocutaneous or invasive fungal infections are generally the result of primary or secondary immune dysfunction. Patients with autosomal recessive CARD9 mutations are also predisposed to recurrent mucocutaneous and invasive fungal infections with Candida spp . , dermatophytes (e.g. Trichophyton spp.) and phaeohyphomycetes ( Exophiala spp., Phialophora verrucosa ). We study a consanguineous family of Turkish origin in which three members present with distinct clinical phenotypes of chronic mucocutaneous and invasive fungal infections, ranging from chronic mucocutaneous candidiasis (CMC) in one patient, treatment-resistant cutaneous dermatophytosis and deep dermatophytosis in a second patient, to CMC with Candida encephalitis and endocrinopathy in a third patient. Two patients consented to genetic testing and were found to have a previously reported homozygous R70W CARD9 mutation. Circulating IL-17 and IL-22 producing T cells were decreased as was IL-6 and granulocyte/macrophage colony–stimulating factor (GM-CSF) secretion upon stimulation with Candida albicans . Patients with recurrent fungal infections in the absence of known immunodeficiencies should be analyzed for CARD9 gene mutations as the cause of fungal infection predisposition.

Background Ruxolitinib is a highly potent janus kinase inhibitor that places its users at risk for various bacterial infections and viral reactivation. However new reports are also emerging that suggest greater immunosuppression and risk for fungal disease. Case presentation We report the case of a 51 year-old veteran from Guam, treated with ruxolitinib for polycythemia vera, who developed disseminated histoplasmosis and concurrent cryptococcal meningitis. Conclusion This case draws attention to the degree of immunosuppression that may be seen with this drug and the need for heightened vigilance for opportunistic infections in those treated with inhibitors of janus kinase/signal transducers and activators of transcription (JAK/STAT) such as ruxolitinib.

Background Invasive fungal rhinosinusitis (IRFS) is a rare but highly fatal disease. The two primary groups of pathogens, Mucorales and Aspergillus , require different treatments and have distinct prognoses. Purpose This study aimed to analyze the histopathological features of IFRS. Methods We conducted a retrospective study involving 57 IFRS cases. Demographic and comorbid characteristics were obtained from clinical records. Two pathologists independently examined the histopathological features using H&E, PAS, and GMS-stained slides. Fungal groups were identified with PCR under the guidance of histopathology. Results The mean age of IFRS was 58.9 ± 13.4. The male-to-female ratio was 1.4:1. 100% of cases had diabetes comorbidity. Mucorales , Aspergillus , and other fungi were found in 61.4%, 33.3%, and 5.3% of cases, respectively. No Aspergillus and Mucorales co-infections were detected. Histopathology and PCR results were strongly concordant in classifying pathogens (Cohen’s kappa = 84.2%, 95% CI 60.1% – 100%, p  < 0.001). Mucormycosis exhibited higher rates of extensive necrosis and vascular invasion, and lower rates of pigment and spore presence than the non-Mucormycosis group ( p  < 0.001, p  = 0.01, p  = 0.02, p  = 0.03, respectively). Extensive necrosis and vascular invasion were statistically significantly correlative (OR = 13.03, 95% CI 2.62–64.75, p  = 0.002). Conclusions IFRS predominantly affects older adults and males. Histopathology is a reliable method for differentiating between Mucorales and Aspergillus . When extensive necrosis is detected, it is critical to investigate for vascular invasion carefully. The vascular invasion, degree of necrosis, pigments, and spores are valuable factors for distinguishing fungal agents of IFRS.

Invasive fungal infections pose a significant health threat. Yarrowia lipolytica (formerly known as Candida lipolytica ) is an opportunistic yeast with pathogenic potential, but its virulence and impact on the host remain poorly understood. This study aimed to investigate the infection characteristics associated with this relatively unknown pathogen by establishing reliable animal models. We developed intravenous challenge models in immunocompetent and immunosuppressed BALB/c mice by injecting fungal cells directly into the bloodstream. In immunocompetent mice, Y. lipolytica was effectively cleared even at the highest challenge dose of 1 × 10⁸ cells, resulting in minimal mortality. However, this clearance was accompanied by a significant elevation in peripheral blood cytokine levels. Three days post-infection, the fungal burden was highest in the lungs ( P  < 0.0001), followed by the spleen, kidneys, liver, and brain. In immunosuppressed mice, the mortality rate following Y. lipolytica infection significantly increased ( P  < 0.001), with the highest fungal burden consistently observed in the lungs. In the immunosuppressed model, clinical isolates exhibited a greater lung fungal burden compared to industrial isolate. In conclusion, Y. lipolytica is a low-virulence fungus that is challenging to establish as a fatal infection in immunocompetent hosts but exhibits a marked tropism for the lungs, where lung fungal burden serves as an effective indicator of virulence. This model may also provide critical insights for studying fungal pulmonary infection pathogenesis and the infection dynamics of Y. lipolytica , especially for immunocompromised patients.

Post-transplant thoracic air-leak syndrome (ALS) is rare but potentially life-threatening in patients receiving allogeneic haematopoietic stem cell transplantation (HSCT). Nevertheless, papers on thoracic ALS are limited, and this complication remains largely unknown. We reviewed 423 adult patients undergoing allogeneic HSCT from 2003 to 2014. Risk factors, clinical features and survival for thoracic ALS were collected and analysed. Thirteen out of 423 patients (3.1%) developed post-transplant thoracic ALS, including two ALS patients in the early phase. The median age at HSCT was 33 years among 13 patients with thoracic ALS. Male patients were predominant (69%). The median onset time was 253 days (range: 40–2680) after HSCT. Multivariate analysis revealed that grade III–IV acute graft-versus-host disease (GVHD) ( p  = 0.017), extensive chronic GVHD (cGVHD) ( p  = 0.019) and prior history of pulmonary invasive fungal infection ( p  = 0.007) were significant risk factors for thoracic ALS. In patients with cGVHD, those with thoracic ALS had a significantly worse survival than those without thoracic ALS ( p  = 0.04). Currently, published data analysing and exploring post-transplant thoracic ALS are limited. Our study employed a large patient cohort and determined the risk factors and clinical features for post-transplant thoracic ALS.

Background Patients with hematological malignancies and allogeneic hematopoietic stem-cell transplant recipients carry a high risk of rare (non- Aspergillus  molds and non- Candida yeasts) invasive fungal infections (IFI). Methods We retrospectively evaluated and described the patient profile, clinical manifestations, isolated species, treatment and outcome of patients with hematological malignancies diagnosed with these rare IFIs during 15 years in a large single hemato-oncology center. Results Eighty-seven patients with hematological malignancies treated in our center had at least one positive culture or molecular identification of a rare fungus. Ninety-three isolates were considered the etiological agents of the infection. The most common underlying hematological malignancy was acute myeloid leukemia, 36 patients (41.4%). Eighty patients (91%) received chemotherapy less than 30 days prior to IFI diagnosis. The most frequent site of infection was the respiratory tract: 34 patients (39%) had pulmonary and 19 patients (22%) had a sinusal or nasopharyngeal infections. Disseminated infection, defined as positive blood cultures or parallel infection in multiple organ systems, was documented in 20 patients (23%). The most common fungal species were Fusarium (35%) and Zygomycetes (25%). Coinfection with more than one fungus was noted in 20 patients (23%). Forty-seven of 87 patients (54%) in this study died within 90 days of IFI diagnosis. Conclusions Rare IFIs in patients with hematological malignancy become increasingly frequent. Early identification with traditional and molecular methods is important in management of these patients.

Hormographiella is a rare fungal pathogen in humans; however, case reports have described disseminated infection in immunocompromised hosts. This pathogen has been described to yield poor prognosis in patients who harbor it. Herein, we present a case report of autopsy-proven disseminated Hormographiella aspergillata infection, confirmed by DNA sequencing, in a patient experiencing a relapse of leukemia. This 54-year-old Caucasian man with chronic myelogenous leukemia (CML) that had been diagnosed in 1989, after having received a hematopoietic cell allotransplant from a compatible sibling donor, had B-cell lymphoid-blast phase of CML in April of 2013, with multiple relapses. His most recent relapse was in September of 2016, when bone marrow biopsy showed 90% blasts. The results of bronchoalveolar lavage (BAL) cultures were positive for filamentous fungus infection. The patient developed encephalopathy and worsening respiratory statusand tachycardia with flutter and hypotension, which resulted in his death. At autopsy, bilateral pleural effusions, multiple right pleural nodules, and subarachnoid hemorrhage were noted. Angioinvasive hyphal fungi were found in the right frontal lobe of the brain and the right upper lobe of the lung. Morphologically, the fungi had multiseptate, branching hyphae. The bronchoalveolar lavage specimen grew a fungus for which the colony morphologic characteristics and microscopic features were compatible with a Hormographiella species. H. aspergillata from the bronchoalveolar lavage was further identified by sequencing the D2 hypervariable region of the large-subunit (LSU) ribosomal DNA gene and the full internal transcribed spacer (ITS) regions.

Invasive aspergillosis (IA) is the most common invasive fungal infection following a hematopoietic cell transplant, with emerging cryptic species exhibiting resistance to commonly used antifungals such as azoles. These species have been increasingly found after the introduction of anti-mold prophylaxis. We report a case of a 56-year-old female with primary myelofibrosis whose allogeneic hematopoietic cell transplant was complicated by disseminated fungal infection (skin, lung) due to Aspergillus calidoustus , a cryptic specie. Treatment of Aspergillus species remains challenging as these cryptic species are usually resistant to azoles including voriconazole which is the first line of treatment of IA. Infection was successfully treated with surgical excision and combination antifungal therapy based on in vitro susceptibility and synergy testing. Therapy included isavuconazole, a drug that has been shown to be non-inferior to voriconazole in the treatment of invasive mold infections.