Cryptococcosis is a life-threatening fungal infection with global public health impact, affecting both immunocompromised individuals and the general population. Accurate clinical management requires differentiation of Cryptococcus species and detection of subclinical infections. However, current diagnostic methods suffer from limited sensitivity and, notably, selectivity. Here, we report a highly sensitive and selective electrochemical immunosensor for rapid and simple serological diagnosis of cryptococcosis. The sensor employs novel multi-epitope chimeric proteins (A, B, C, and D) directly anchored onto a molybdenum disulfide (MoS2)-functionalized gold electrode, enabling simplified construction and stable bioreceptor immobilization without chemical cross-linkers. Comprehensive physicochemical characterization by SPR, AFM, EDS, SEM, Raman spectroscopy, and electrochemical techniques provided essential structural information governing the synergistic integration of MoS2 and chimeric proteins. Using Square Wave Voltammetry (SWV), a comparative evaluation against human serum samples identified Protein D as the main bioreceptor, providing the highest discrimination between positive and negative groups. The optimized MoS2/Protein D immunosensor achieved an outstanding limit of detection (LOD) of 0.124 fmol L-1 and a wide linear range spanning from fmol L-1 to nmol L-1. Clinical validation via ROC curve analysis demonstrated excellent diagnostic performance, with 100% sensitivity, 87.5% specificity, and an area under the curve (AUC) of 0.987. Furthermore, the sensor exhibited high selectivity against a panel of five other systemic mycoses (aspergillosis, histoplasmosis, sporotrichosis, coccidioidomycosis, and paracoccidioidomycosis), overcoming the specificity gaps of routine assays. These results represent a significant advance for clinical practice and highlight the potential of simple electrochemical approaches to resolve complex diagnostic problems.
Trichophyton rubrum is a highly prevalent dermatophyte re for superficial mycoses affecting keratinized tissues such as skin, hair and nails. Its ability to colonize these tissues is attributed to its keratolytic activity and adaptability to different environmental conditions. This retrospective study included cases of dermatophytosis caused by Trichophyton rubrum diagnosed at the Parasitology-Mycology Laboratory of the Mohammed VI University Hospital in Oujda over a period of four and a half years, from January 7, 2020, to July 7, 2024. Each sample was examined by direct microscopy after clarification with 30 % KOH and cultured on Sabouraud media at 25 °C. This study aims to investigate the epidemiological and mycological characteristics of patients diagnosed with Trichophyton rubrum dermatophytosis. Trichophyton rubrum dermatophytosis was mycologically confirmed in 287 of the 1328 samples received during the study period. The mean age of our patients was 52 years, with extremes ranging from 7 to 98 years. Our series was characterized by a M/F sex ratio of 1. Onychomycosis represented 67.8 % of all collected samples. Among the affected patients, 168 cases (58.74 %) involved onychomycosis of the feet, while 25 cases (8.74 %) involved onychomycosis of the hands. Additionally, 71 patients (24.83 %) presented with scales, and 22 patients (7.69 %) exhibited intertrigo. Among all collected samples, 68.64 % were positive on direct examination after clarification with KOH 30 %. Trichophyton rubrum is the most widespread dermatophyte worldwide. Direct examination and mycological culture are complementary techniques for accurate diagnosis. Further epidemiological studies across Morocco are needed for meaningful comparisons.
Pneumocystis jiroveci pneumonia (PJP) is a common but serious opportunistic infection after allogeneic hematopoietic cell transplantation (HCT). The preferred regimen for PJP prophylaxis is trimethoprim-sulfamethoxazole (TMP-SMX), but TMP-SMX can delay engraftment and has some toxicities. This study retrospectively analyzed the efficacy and safety of aerosolized pentamidine (AP) as an alternative to TMP-SMX for PJP prophylaxis after allogeneic HCT. One hundred and fifty-five patients received AP and 86 patients received TMP-SMX. Pentamidine isethionate 300 mg was nebulized every 4 weeks and double-strength TMP-SMX was administrated once-daily and 2 days per week. Incidences of suspicious PJP and confirmed PJP were not statistically different between two groups (suspicious PJP, 4.5% vs. 3.5%, P = 1.000; confirmed PJP, 0.6% vs. 0.0%, P = 1.000). There were fewer adverse reaction in AP group than TMP-SMX group (10.3% vs. 26.7%, P < 0.001). Only 1 patient (0.6%) discontinued prophylaxis due to adverse reaction in AP group, while 17 patients (19.8%) in TMP-SMX group discontinued prophylaxis due to adverse reaction (P < 0.001). There was more incidence of graft failure in TMP-SMX group and the incidence of prolonged thrombocytopenia was significantly higher in TMP-SMX group. There was no deterioration of lung function in patients received AP prophylaxis. In conclusion, AP is well tolerated without severe adverse events and effective in preventing PJP after allogeneic HCT.
Oral candidiasis (OC) is the most frequent fungal infection among users of dental prosthetic devices, immunocompromised patients, and those who underwent chemotherapy treatment and had a complication of long-term antibiotic therapy. About 150 species of Candida fungi have been described, whereas over 80% of oral fungal infections are attributed to the opportunistic pathogen Candida albicans. Pain, dryness of oral mucosa, pathological lesions, and intermittent mucosal bleeding are the main symptoms that worsen the daily functioning of the abovementioned fungal-infected patients. A promising adjunctive strategy may involve the use of probiotic bacteria to attenuate fungal colonization in the oral cavity in order to reduce the need for conventional treatment, which carries a risk of antifungal drug resistance-a significant problem worldwide. Probiotic formulations mostly incorporate commensal bacteria that naturally inhabit oral ecosystems such as Lactobacillus spp., Bifidobacterium spp., Bacillus spp., and others. Probiotic organisms may contribute to the restoration of oral microbiome homeostasis through numerous mechanisms, such as competitive control of Candida species numbers, better adhesion to oral mucosa and production of bioactive compounds and antimicrobial metabolites. Despite many studies, the current evidence base remains heterogeneous. Well-designed studies across diverse populations are required to determine whether probiotic-based interventions can be an effective and clinically useful alternative or adjunct to standard antifungal therapy of OC.
Invasive aspergillosis (IA) is a major cause of morbidity and mortality in immunocompromised children. Pediatric data are limited, and treatment guidelines often rely on adult studies. This study aimed to assess clinical characteristics and treatment outcomes of pediatric IA. We conducted a retrospective cohort study of pediatric patients (0-18 years) diagnosed with IA at a tertiary center in Türkiye between 2010 and 2022. Data on demographics, underlying conditions, Aspergillus species, antifungal susceptibility, treatment regimens, and outcomes were analyzed. Survival analysis was performed using Kaplan-Meier curves. Fifty-five children met criteria for proven (69%) or probable (31%) IA after excluding 22 possible cases. Median age was 8.6 years; mortality did not differ significantly by age, sex, or underlying condition. Hematologic malignancies were the most common comorbidity (35%). Aspergillus fumigatus was the predominant species (57%), and no antifungal resistance was detected. Classical risk factors; central venous catheter use (53%), neutropenia (51%), and recent chemotherapy (35%) were frequent but showed no association with mortality. Lung involvement was the most common presentation (71%), followed by sinus (31%) and central nervous system involvement (13%). Thirty-day mortality was 11%, 12-week mortality was 20% (11/55), and overall mortality reached 29%. Pediatric IA remains associated with substantial morbidity and mortality, although outcomes in this cohort were more favorable than those reported in many prior pediatric series. No single clinical, microbiological, or radiological factor reliably predicted mortality, underscoring the complexity of risk stratification. Early diagnosis and timely antifungal therapy remain essential, and multicenter prospective studies are needed to optimize treatment approaches.
Increasing incidence of candidiasis and emergence of antifungal resistance necessitate the development of alternative antifungal strategies. In this context, the antifungal activity of the crude extract of Punica granatum L. peel (PGPE) and its chitosan nanoparticle-coated formulation (PGPE-CSNPs) was investigated against Candida albicans (ATCC 10231), Candida glabrata (ATCC 66032), Candida kefyr (ATCC 46764), Candida parapsilosis (ATCC 22019), and Candida tropicalis (ATCC 13803). Although the individual antimicrobial activities of PGPE and CSNPs have been investigated, their combined application against Candida spp. remains unexplored in the literature. The antifungal efficacy was evaluated using agar well diffusion, disk diffusion, minimum inhibitory concentration (MIC), and minimum fungicidal concentration (MFC) testing, and compared with fluconazole and amphotericin B. The morphological characterization of PGPE-CSNPs was performed using scanning electron microscopy (SEM), which confirmed successful encapsulation and revealed a smoother surface with uniformly distributed nanometric pore structures and reduced aggregation compared to uncoated CSNPs. PGPE-CSNPs showed greater inhibition zones than amphotericin B, except against C. albicans. The CSNPs formulation reduced the MIC from 8 µg/mL to 4 µg/mL and the MFC from 16 µg/mL to 8 µg/mL, representing a two-fold enhancement against C. albicans. No enhancement in activity was observed against C. glabrata, whereas for C. kefyr, only MFC values decreased from 8 µg/mL to 4 µg/mL. For both C. parapsilosis and C. tropicalis, MIC values reduced from 16 µg/mL to 8 µg/mL, and MFC values reduced from 32 µg/mL to 16 µg/mL for both species. PGPE-CSNPs exhibited significantly lower MIC and MFC values than the crude extract alone (p < 0.05). These findings suggest that chitosan-based nanocarriers may enhance the antifungal efficacy of plant-derived bioactive compounds, highlighting their potential as a promising alternative antifungal strategy, a combinatorial approach not previously reported in the literature.
Objective: To investigate the bronchoscopic features of invasive pulmonary aspergillosis (IPA) and to summarize the clinical efficacy of comprehensive bronchoscopic interventional therapy. Methods: A retrospective analysis was conducted on the clinical data of 11 patients with IPA who received comprehensive bronchoscopic interventional therapy at Beijing Tsinghua Changgung Hospital between December 2018 and December 2024. The therapeutic efficacy and safety were evaluated. Results: Among the 11 patients, 7 were male and 4 were female, with an age range of 14 to 69 years (mean 45.8±17.6 years). Underlying diseases included diabetes mellitus (4 cases), hematological malignancies (2 cases), solid tumors (2 cases), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (1 case), high IgE recurrent infection syndrome (1 case) and allergic bronchopulmonary aspergillosis (1 case). Chest CT findings showed multi-lobar involvement in nine cases and single-lobar involvement in two cases. Bronchoscopy revealed obstructive white necrotic material within the airways in four cases, purulent secretions in four cases, and bronchopulmonary cavity fistula in three cases. Pathological examination of the necrotic material confirmed the presence of abundant Aspergillus hyphae. All patients received systemic antifungal therapy. Local treatments included aerosolized amphotericin B deoxycholate inhalation in nine cases and bronchoscopic local drug perfusion in all 11 cases. Bronchoscopic interventional procedures included forceps removal of lesions in four cases, with one case experiencing grade Ⅲ hemorrhage. No severe complications such as pneumothorax occurred. Following treatment, clinical cure was achieved in six cases (54.5%) and significant improvement in five cases (45.5%), with no deaths. During the one-year follow-up, no recurrence was observed in 10 cases. Conclusions: IPA commonly occurs in immunocompromised hosts, with bronchoscopic findings often revealing airway obstruction caused by whitish necrotic material and/or secretions. An integrated therapeutic strategy combining systemic and local antifungal therapy with bronchoscopic interventional treatment can significantly enhance clinical efficacy and demonstrate a favorable safety profile. 目的： 探讨侵袭性肺曲霉病（IPA）的支气管镜下特征，总结支气管镜介入综合治疗的临床效果。 方法： 回顾性分析2018年12月至2024年12月北京清华长庚医院收治的11例接受支气管镜介入综合治疗的IPA患者临床资料，评估其疗效与安全性。 结果： 11例患者中男性7例、女性4例，年龄14~69（45.8±17.6）岁。基础疾病包括糖尿病4例、白血病2例、肝癌2例、抗中性粒细胞胞浆抗体（ANCA）相关性血管炎1例、高IgE反复感染综合征1例、变应性支气管肺曲霉病1例。胸部CT显示多肺叶受累9例，单肺叶受累2例。支气管镜下主要表现为气道内白色坏死物阻塞（4例），其次为脓性分泌物（4例）和支气管肺空洞瘘（3例）；坏死物病理检查均见大量曲霉菌丝。所有患者均接受全身抗真菌治疗，局部药物治疗包括两性霉素B脱氧胆酸盐雾化吸入治疗9例，支气管镜下局部灌注治疗11例。支气管镜介入治疗包括钳除病灶（4例），其中1例发生Ⅲ级出血，无气胸等严重并发症。治疗后临床治愈6例（54.5%），疗效显著5例（45.5%），无死亡病例；随访1年，10例未见复发。 结论： IPA好发于免疫抑制宿主，支气管镜下常见白色坏死物和（或）脓性分泌物堵塞气道；全身、局部药物治疗联合支气管镜介入治疗的综合策略，可显著提高临床疗效，安全性良好。.
Off-flavor compounds often bind to proteins during extraction from animal byproducts and compromise protein applicability. This study proposed the integration of ultra-high pressure (UHP) pretreatment with propylene glycol and trehalose addition (UNPA) to facilitate off-flavor dissociation during duck liver protein (DLvP) extraction. UHP treatment at 350 MPa for 10 min induced a molten globule-like state with loosened tertiary packing and increased hydrophobic exposure, whereas propylene glycol and trehalose helped maintain the pressure-modulated conformation and limit aggregation. UNPA decreased the total peak area of headspace volatiles by approximately 50.8%, and reduced trimethylamine, dimethylamine, histamine, and formaldehyde by 28.78%, 32.19%, 12.21%, and 44.00%, respectively (p < 0.05). Water-holding capacity and emulsifying activity were improved by 13.6% and 60.1%, respectively (p < 0.05). These findings indicate that controlled UHP-induced unfolding, assisted by conformational stabilization, can promote off-flavor release while improving selected functional properties of DLvP.
Coccidioidomycosis, or Valley fever, is a climate-driven fungal disease. Dogs are valuable sentinels for human disease. We sought to evaluate veterinarian-reported clinical encounters with coccidioidomycosis in dogs and the relative awareness of coccidioidomycosis by veterinarians in endemic versus nonendemic states. Survey responses were solicited from 45,240 veterinarians subscribing to the Veterinary Information Network in June/July 2024. For US-based veterinarians, data were gathered on the number of coccidioidomycosis cases evaluated, recall of education on coccidioidomycosis, and respondent knowledge of diagnostic tests, epidemiology, causative agents, and human exposure. Knowledge responses were averaged to yield an awareness score. Reported case data and continuing education hours were normalized with publicly available population data. For a subset of cases reported from nonendemic states, medical records were reviewed for travel history. Responses were received from 640 veterinarians (365 endemic, 275 nonendemic [response rate, 1.4%]). Median case encounters reported per 100,000 households was 230-fold higher for veterinarians working in endemic states compared to those in nonendemic states. Median awareness scores were low (≤ 50%) in both groups. Most education occurred during veterinary school. There was no difference in practitioner-reported median continuing education hours for endemic versus nonendemic states. All cases for which medical records were reviewed had travel history to endemic regions. Awareness of coccidioidomycosis amongst veterinarians using the Veterinary Information Network was low, especially among nonendemic states. Educational and reporting initiatives are needed to improve disease awareness and recognition by veterinarians, with implications for early recognition of human disease in nonendemic regions.
Allergic bronchopulmonary aspergillosis (ABPA) is defined as a type I hypersensitivity reaction against allergens derived from Aspergillus spp., ubiquitous fungi present in various environments. Annually, the disease contributes a significant proportion to global morbidity and mortality, relative to other fungal diseases. Although known to affect populations worldwide, the exact pathogenesis of the disease from environmental to clinically-pertinent isolates and the basis for the emergence of antifungal resistance, a known by-product of unregulated prescription and use of drugs targeted at specific factors involved in forming fungal structural elements (i.e., ergosterol, chitin) and mediating survival mechanisms (i.e., fungal metabolism, DNA/RNA synthesis), remains poorly understood. Here, we focus on the role of the one health approach in combating the environment-host transition and mitigating the emergence of antifungal resistance. This includes the synthesis of current literature relevant to the subsequent insights on strategies to control the spread of the disease. From the findings of the present review, novel approaches to manage the incidence of ABPA and reduce the overall disease burden can be developed on a global scale. Perspectives utilizing the One Health approach has emerged as a prominent future direction for health programs worldwide, geared towards reducing the incidence and overall burden of fungal respiratory infections, such as ABPA.
An outbreak of endogenous fungal endophthalmitis (EFE) caused by contaminated intravenous infusion was identified in immunocompetent individuals. We aimed to describe its clinical characteristics and outcomes. This retrospective case series included all patients referred with EFE and had a history of intravenous infusions at the same rural clinic, between May 1st, 2024 and November 30th, 2024, to Ophthalmology Department of Ningde Municipal Hospital. Demographic and clinical data were collected. Whole-genome sequencing (WGS) and SNP-based phylogenetic analysis were performed on 7 culture-positive Candida albicans vitreous isolates. The inclusion criteria were met in 26 eyes of 17 patients. All were healthy and immunocompetent. On average, patients presented after 24.3 days of symptoms. Presenting best corrected visual acuity (BCVA) ranged from 20/25 to no light perception (NLP). All patients were initially treated with pars plana vitrectomy (PPV) and intravitreal voriconazole injection followed by systemic voriconazole therapy. Vitreous cultures obtained during PPV were positive in 19 eyes, all showing growth of Candida albicans. Three months after treatment, patients' BCVA improved significantly from a mean of 20/100 to 20/50 (p = 0.00011). All sequenced isolates clustered tightly in SNP-based phylogenetic analysis, supporting a clonal outbreak. Two patients with a final BCVA of NLP were initially misdiagnosed with noninfectious uveitis and treated with an intravitreal steroid injection at other hospitals. Since the closure of the rural clinic, no new cases have been reported. Primary PPV followed by systemic and intravitreal antifungal therapy and an epidemiological investigation could be effective in finding the infectious source of an EFE outbreak and achieving favorable visual outcomes. Misuse of intravitreal steroids due to incorrect diagnosis could lead to severe vision loss in individuals with EFE.
To evaluate the clinical utility of a pragmatic, off-label multiplex PCR strategy using FilmArray® panels on corneal swabs in suspected infectious keratitis, with emphasis on diagnostic yield, turnaround time, and early therapeutic impact in routine care. This prospective, single-center observational study was conducted over 24 months (January 2024-December 2025) at a tertiary referral center. In episodes of clinically suspected infectious keratitis, corneal swabs were immersed in brain-heart infusion medium. A FilmArray® Meningitis/Encephalitis (ME) panel was used as first-line testing, with selective FilmArray® Blood Culture Identification 2 (BCID2) panel use when clinically indicated. Conventional bacterial and fungal cultures were systematically performed. Outcomes included diagnostic yield of the PCR algorithm, turnaround time (TAT), concordance patterns with culture, and early treatment changes after PCR results. Fifty episodes were included. The multiplex PCR algorithm (ME ± BCID2) detected at least one pathogen in 50% of cases, with viral detections, mainly herpes simplex virus type 1, accounting for a substantial proportion of PCR-positive results. Conventional culture was positive in 32% of cases and identified bacterial and/or fungal pathogens. Median TAT was 6.5 h for PCR versus 79 h for culture, corresponding to a median reduction of 72.5 h. PCR findings were associated with treatment modification within 24 h in 32% of cases, with additional changes after 48 h in 6%, predominantly antiviral initiation or targeted antimicrobial adjustment. In this real-world exploratory study, the main advantage of the pragmatic FilmArray® strategy was the marked reduction in turnaround time compared with culture, providing microbiological information within hours rather than days. Because PCR and culture differ fundamentally in detectable pathogen classes, particularly due to viral detection by PCR, these findings should not be interpreted as evidence of diagnostic superiority. FilmArray® testing may serve as a complementary approach in selected severe, atypical, pretreated, or culture-negative keratitis cases when rapid therapeutic decisions are needed.
High altitudes pose extreme survival challenges for organisms, yet the origins and molecular strategies underlying their resilience remain poorly understood. Here, we report the molecular and evolutionary mechanisms underlying stress resilience in Apourosomoida sp. LHA081A01, a ciliate isolated from a high-altitude Tibetan salt lake that endures high salinity, low temperature, and hypoxia. We identified TreT glycosyltransferases, acquired through horizontal gene transfer from an anaerobic and halophilic Desulfobacteraceae bacterium, to be involved in the synthesis of α,α-trehalose-a universal protein stabilizer absent in most other ciliates but essential for counteracting multiple environmental stressors. Additional strategies include β-carotene accumulation to mitigate oxidative stress from hypoxia, along with numerous others common to many eukaryotes. Extensive gene family expansions and rapid divergence of stress‑responsive genes underscore their evolutionary significance and critical role in surviving harsh habitats. Intolerance to low salinity may render this ciliate, and other protists, vulnerable to climate‑driven salinity declines in Tibetan salt lakes. Together, these extraordinary features-shaped by horizontal gene transfer, natural selection, and regulatory plasticity-position high-altitude microbial eukaryotes as powerful extremophile models for uncovering the molecular mechanisms of stress resilience and adaptive evolution across life.
In vitro co-culture models of human cells and microbial pathogens offer a controlled system to study host-pathogen interactions. This chapter details the methods to establish such co-culture models for a fungal and an amoebic infection using two different human cell lines. Employing this experimental system allows the researcher to evaluate MIF's contribution to infection-driven host cell death and pro-inflammatory gene expression.
Co-infection with Aspergillus and Mucorales in the intensive care unit (ICU) represents a devastating syndrome with high mortality that is frequently clinically occult. Clinically distinguishing this co-infection from invasive pulmonary aspergillosis (IPA) is challenging but critical for tailoring precise antifungal strategies. We conducted a single-center, retrospective observational study involving 93 critically ill patients (75 with Aspergillus infection and 18 with co-infection) admitted between 2017 and 2025. We compared clinical characteristics, inflammatory markers, and immunophenotypes between groups. A three-stage variable selection strategy integrating univariable regression pre-screening, multi-algorithm importance ranking (LASSO, Ridge, and Random Forest), and clinical applicability filtering was employed to identify predictors for a multivariable logistic regression nomogram. The co-infection group exhibited substantially higher ICU mortality than the sole Aspergillus group, although the difference did not reach statistical significance (72.2% vs. 53.3%, p = 0.24).Kaplan-Meier analysis demonstrated that initiation of amphotericin B within <7 days of diagnosis or strong clinical suspicion was significantly associated with improved survival (log-rank p < 0.0001). A three-stage variable selection strategy integrating univariable regression, multi-algorithm importance ranking (LASSO, Ridge, and Random Forest), and clinical applicability filtering identified four key predictors. The resulting multivariable logistic regression nomogram - incorporating NK cell count, C-reactive protein, corticosteroid use history, and Gram-positive bacterial co-infection - demonstrated robust discrimination (AUC = 0.878, 95% CI: 0.789-0.967), with good calibration (Hosmer-Lemeshow p = 0.849) and stability on internal validation (cross-validated AUC = 0.860). Aspergillus and Mucorales co-infection constitutes a distinct, high-mortality clinical entity in the ICU. The developed nomogram, integrating clinical, immunological, and inflammatory features, may facilitate the early identification of high-risk patients and guide timely initiation of Mucorales-active therapy to improve prognosis.
Our aim was to record current susceptibility results of genital yeast isolates and to compare the results to the previous report covering the period 2001-2015. Genital yeast isolates had their antifungal susceptibility determined by disc diffusion or minimum inhibitory concentration following standard methods. Sequential isolates from the same person had their initial and last susceptibility results compared. Disc testing was performed on 1,307 initial isolates; 17 (1.3%) were from males. The most frequent isolates were Candida albicans (64%), Nakaseomyces glabratus complex (17%) and Candida parapsilosis complex (7%). While 94% of isolates were susceptible to clotrimazole, susceptibility for other azoles ranged from 62% to 84%. All isolates were susceptible to nystatin. Isolates non-susceptible to one topical azole were often resistant to all azoles tested. For fluconazole, itraconazole and miconazole fewer isolates were susceptible than in the previous time period. The susceptibility to clotrimazole did not change. One hundred and eight women had sequential isolates, range 2-5, collected 1 week to 75 months apart, median 6 months. Four pairs (4%) had a change from susceptible to resistant, all for miconazole, suggesting increased resistance. All latter isolates were susceptible to at least two other azoles and nystatin. There appears to have been an increase in antifungal resistance to several topical agents used for genital yeast infections. However, in a previously susceptible isolate, treatment failure seldom indicates a change to antifungal resistance. Women with recurrent vulvovaginal yeast infection can be reasonably treated empirically while identification and susceptibility results are awaited.
Aspergillus species are opportunistic fungi that can cause severe, potentially life - threatening infections, particularly in immunocompromised individuals. Invasive aspergillosis most commonly affects the lungs (70 % -90 % ) but may also involve other organs, including the central nervous system (10 % -25 % ), heart (5 % -10 % ), kidneys (5 % -10 % ), liver and spleen (5 % -8 % ), and gastrointestinal tract (2 % -5 % ). The incidence of aspergillosis is markedly increased among solid-organ transplant recipients due to prolonged immunosuppression. Thyroid involvement is extremely rare ( <1 % ) and is most often reported in autopsy studies. Infection of the thyroid gland may occur through hematogenous dissemination, direct extension from adjacent structures, or iatrogenic routes. Herein, we describe a liver transplant recipient who developed thyroid aspergillosis, emphasizing the importance of considering fungal infections in the differential diagnosis of thyroid lesions in immunosuppressed patients.
Immune reconstitution inflammatory syndrome (IRIS) refers to an exaggerated inflammatory response to existing infections or latent pathogens that occurs during rapid immune recovery in immunocompromised hosts, paradoxically leading to clinical deterioration despite appropriate treatment. IRIS is commonly observed in patients with human immunodeficiency virus (HIV)-associated tuberculosis and cryptococcal meningitis after starting antiretroviral therapy. However, it can also occur in immunocompromised individuals without HIV, which remains relatively under-recognized, particularly following neutrophil recovery after chemotherapy for acute leukemia or hematopoietic stem cell transplantation, during the post-operative phase of anti-rejection therapy following solid organ transplantation, or after the rapid reduction or withdrawal of corticosteroids or immunosuppressants, etc. This article summarizes the definition, clinical characteristics, diagnosis, treatment, and prevention of IRIS associated with invasive pulmonary fungal diseases. Clinical management requires accurate identification and careful evaluation to guide optimal and prompt intervention. Appropriate timing of antifungal treatment, initiation of antiretroviral therapy, and adjustment of immunosuppressive agents are crucial to reduce the risk of IRIS and prevent related morbidity and mortality. 免疫重建炎症反应综合征（IRIS）好发于HIV相关结核病、隐球菌脑膜炎患者ART治疗期，但近年来发现，IRIS同样好发于非HIV真菌感染患者免疫功能快速恢复期，如急性白血病化疗或造血干细胞移植患者粒细胞缺乏恢复期、实体器官移植术后抗排异治疗期、糖皮质激素等免疫抑制剂的快速减量或停用时，但临床对其认识相对不足。本文聚焦于侵袭性肺真菌病相关IRIS的定义、临床特征、诊断标准、治疗和预防，旨在为该病的早期识别和规范管理提供参考。.
Voriconazole (VRCZ) is a first-line agent for treating invasive fungal infections, but its pharmacokinetics vary widely, necessitating therapeutic drug monitoring (TDM) to maintain trough concentrations within the therapeutic range (1.0-4.0 µg/mL). C-reactive protein (CRP) is an inflammatory marker reportedly associated with VRCZ concentrations. However, its precise impact in machine learning models remains unclear because of missing values in previous studies. Thus, this study aimed to identify factors associated with supratherapeutic VRCZ concentrations using a classification and regression tree (CART) model incorporating CRP in Japanese patients. We retrospectively analyzed 121 patients who received VRCZ (2-4 mg/kg/dose) and underwent TDM. The patients were classified into a therapeutic range group (1.0-4.0 µg/mL; n=51) and a supratherapeutic group (>4.0 µg/mL; n=70). We excluded outpatients to ensure strict sampling timing, patients whose maintenance doses were changed before the first TDM, and patients with missing laboratory data immediately prior to administration. The CART analysis identified dose (threshold: 2.7 mg/kg/dose) as the primary predictor, followed by CRP (threshold: 5.0 mg/dL) and age (threshold: 74 years). The model demonstrated moderate performance in predicting the therapeutic range group, with an area under the curve of 0.770 [95% confidence interval (CI): 0.689-0.851], sensitivity of 78.4%, and specificity of 71.4%. Dose, CRP, and age were significant factors associated with supratherapeutic VRCZ concentrations. Our findings suggest that a decision-tree-based approach incorporating inflammatory status and age could provide valuable clinical insights for optimizing initial VRCZ dosing.
Background: Edible and medicinal mushrooms have attracted growing attention as functional foods due to their rich content of bioactive compounds and their potential to modulate host physiology through microbiota-mediated mechanisms. Methods: This narrative review was conducted through a comprehensive literature search across major scientific databases, including PubMed, Scopus, ScienceDirect, Web of Science, and Google Scholar, selecting studies focused on mushroom-derived compounds, gut microbiota, short-chain fatty acids (SCFAs), and the gut-brain axis (GBA). Results: Current evidence indicates that mushroom-derived polysaccharides, particularly β-glucans, along with polyphenols, trehalose, and chitin, resist digestion and are fermented by intestinal microorganisms, promoting SCFA production. These metabolites contribute to intestinal barrier integrity, immune regulation, and metabolic homeostasis and may also influence neuroinflammation and neurotransmitter pathways via the GBA. However, significant variability in mushroom preparations and the limited availability of well-designed human clinical trials remain important limitations. Conclusions: Edible and medicinal mushrooms represent a promising source of novel prebiotic compounds with potential systemic health benefits, although further standardized studies and robust clinical trials are needed to confirm their efficacy and mechanisms of action.