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.
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.
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.
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。.
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.
Sporothrix brasiliensis is the principal etiological agent responsible for cat-transmitted zoonotic sporotrichosis, which is currently the most prevalent mycosis in South America-especially in Brazil-and is increasingly being reported in other regions. While itraconazole is the standard treatment, its use is limited by hepatotoxicity, high cost, and emerging reports of reduced susceptibility. Complexes of 1,10-phenanthroline-5,6-dione (phendione) with transition metals have previously shown promise as antifungal agents against bacteria, parasites, yeasts and filamentous fungi. This study investigates the in vitro and in vivo antifungal properties of [Cu(phendione)3](ClO4)2.4H2O (Cu-phendione) and [Ag(phendione)2]ClO4 (Ag-phendione) against S. brasiliensis isolates from domestic felines in endemic regions. Six clinical isolates of S. brasiliensis obtained from cutaneous lesions in six felines with laboratory-confirmed sporotrichosis from hyperendemic regions in the state of Rio de Janeiro, Brazil, were investigated. Selection was made according to in vitro Minimum Inhibitory Concentration (MIC) response criteria for itraconazole ("wild type" WT = MIC ≤ 2 µg/mL; "non-wild type" NWT = MIC ≥ 4 µg/mL). The American Type Culture Collection (ATCC) S. brasiliensis MYA 4823 was included. The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of phendione, its metal complexes, and simple silver and copper salts were evaluated against S. brasiliensis saprophytic and parasitic phases. Additionally, in vivo antifungal efficacy was assessed using Galleria mellonella larvae as a model. Both metal complexes exhibited low MIC (0.3-5 µM) and MFC (0.3-10 µM) values against conidia and yeast forms of both WT ("sensitive") and NWT ("resistant") S. brasiliensis clinical isolates. Notably, MFC values were equal to or at most twice the MICs, indicating a fungicidal profile, even against itraconazole-resistant strains. Galleria mellonella treated groups exhibited higher values than the S. brasiliensis group (6.0 days) while all compounds provided larvae mean survival higher than the itraconazole treated group (p > 0.05). Cu-phendione was the compound that conferred the highest median survival (8.0 days). Silver(I) and Copper(II) complexes of 1,10-phenanthroline-5,6-dione demonstrated both inhibitory and fungicidal activity against itraconazole-resistant S. brasiliensis isolates from diseased cats residing in the Brazilian hyperendemic region, highlighting their promise as novel antifungal agents. This finding is notable because drugs currently used for sporotrichosis treatment are characterized as fungistatic. This study provides data on alternative molecules that may be considered for future control of sporotrichosis, a zoonosis currently spreading throughout Latin America.
Influenza is a major concern, but it has been affected by the COVID-19 pandemic worldwide. The objective of this study was to clarify the differences in the clinical manifestations of severely ill patients infected with influenza in Japan among the pre-, during, and post-COVID-19 pandemic periods. The clinical data of patients who were severely ill with influenza and required hospitalization were gathered and analyzed between September 2019 and August 2025 (6 influenza seasons) using an internet-based data-capture system, and the pre-(2019 season), during (2020, 2021, and 2022 seasons), and post- (2023 and 2024 seasons) COVID-19 pandemic periods were compared. A total of 490 patients were enrolled and analyzed, with 87 (17.8%), 21 (4.29%), and 382 (78.5%) patients in the pre-, during, and post-COVID-19 pandemic periods, with mortality of 2.3%, 0%, and 7.9%, respectively. Age, male/female ratio, underlying diseases, pneumonia rates, oxygen use, isolated bacteria, including Streptococcus pneumoniae, and anti-influenza agents were similar among the three groups. However, intrafamilial transmission was decreased, although the influenza vaccination rate and antibiotic use were decreased in the post-COVID-19 period. Influenza infection might be a greater issue after the COVID-19 pandemic because of the decreased vaccination rate and worse prognosis in the post-COVID-19 period. Although intrafamilial transmission and antibiotic use were decreased in the post-COVID-19 period, continuous nationwide surveillance and promotion of vaccination will be required to inhibit the increase of hospitalized and/or severe influenza patients.
Tuberculosis (TB) remains a major global public health problem, emphasizing the necessity of identifying attenuation targets in Mycobacterium tuberculosis (Mtb) for the development of novel control strategies. In this context, plasma membrane transporters are critical determinants of Mtb virulence, including CtpF, a Ca2+ P-type ATPase, and MmpL7, a translocator of phthiocerol dimycocerosate (PDIM). In this study, we characterized in vitro the microbiological features of the MtbH37RvΔctpF and MtbH37RvΔmmpL7 strains. Both mutants displayed reduced colony roughness and hydrophobicity compared to MtbH37Rv, suggesting alterations in the composition of cell wall lipids. Chromatographic analyses confirmed changes in the lipid profiles; MtbH37RvΔctpF exhibited altered phosphatidylinositol mannosides and trehalose dimycolates profiles, whereas MtbH37RvΔmmpL7 showed accumulated PDIM intracellularly. Moreover, transcriptional analyses revealed the downregulation of PDIM biosynthesis and transport genes in both mutants. However, both strains retained the ability to secrete early secreted antigenic target-6 (ESAT-6) and culture filtrate protein-10 (CFP-10), indicating that their immunostimulatory potential was preserved. These findings provide in vitro evidence that deletions of ctpF and mmpL7 alter envelope-associated traits commonly linked to mycobacterial virulence.
Introduction. Vulvovaginal candidiasis (VVC) is a common fungal infection that has a significant impact on global public health. Although studies associate VVC with male infertility, its influence on the female reproductive system, particularly uterine involvement, remains unknown.Gap statement. While recent animal studies propose that Candida albicans migration from the vaginal tract to the uterus in VVC could lead to infertility, the underlying histopathological alterations that support this connection are not well understood.Aim. To investigate possible changes in the uterine tissue of BALB/c mice infected experimentally with C. albicans, by analysing the progression and effects of infection on the uterus.Methodology. Female BALB/c mice were divided into two groups (infected and control). Vaginal infection was induced by C. albicans, and vaginal and uterine tissues were collected at different intervals (1, 3, 5, 7 and 10 days). Analyses included fungal burden (c.f.u. g-1), histopathology stained with Grocott-Gomori and macroscopic and microscopic evaluation (haematoxylin-eosin staining) of uterine tissue.Results. Vaginal infection was confirmed by a consistent presence of yeast in vaginal tissue. C. albicans migration was observed in the uterus, with a significant increase in fungal burden on day 3, followed by macroscopic alterations such as oedema and hyperaemia. Histologically, inflammatory infiltrates, epithelial necrosis and progressive degeneration were identified until day 7, with signs of resolution by day 10.Conclusion. The results demonstrate that vaginal infection by C. albicans was able to cause significant uterine alterations with self-limiting progression. These findings suggest that VVC may have direct implications for female fertility, warranting future investigations into its influence on infertility cases.
Metamizole is an analgesic drug with moderate cytochrome P450 (CYP) inductive properties. The antifungal triazoles are metabolized by several CYP enzymes, but the interaction with metamizole remains poorly described. We investigated the influence of metamizole on the exposure of voriconazole, isavuconazole, and posaconazole. Patients from UZ Leuven (Belgium) and Ljubljana University Medical Centre (Slovenia) receiving voriconazole, isavuconazole, or posaconazole concomitantly with metamizole were included in the study. Routine therapeutic drug monitoring (TDM) measurements collected between January 2019 and December 2024 were retrieved retrospectively. TDM concentrations outside of concomitant therapy were collected as controls. The influence of metamizole and other clinically relevant covariates was analysed using generalized estimating equations (GEE). A total of 126 distinct treatments with a triazole from 115 patients, accounting for 392 measurements, were included in the study. GEE analysis revealed a significant negative association between the 7-day cumulative metamizole dose and lower voriconazole and posaconazole concentrations. Additionally, C-reactive protein had a positive association with voriconazole concentrations. Only ICU admission and patient characteristics, that is, sex and weight, had a significant influence on isavuconazole concentrations. Concomitant therapy with metamizole led to lower voriconazole and posaconazole concentrations, presumably through induction of CYP enzymes and possibly UDP-glucuronyltransferase. We recommend avoiding concomitant use of metamizole with the antifungal triazoles to prevent underexposure and treatment failure or frequent TDM if the combination cannot be avoided. Further studies are needed to confirm our findings and investigate the influence of metamizole on other triazoles.
Crystal dumplings are susceptible to quality deterioration during frozen storage, exhibiting textural hardening, loss of springiness, and reduced water retention due to starch retrogradation and ice crystal damage. This study aimed to systematically investigate the effects of hydroxypropyl distarch phosphate (HPDSP), trehalose (TRE), guar gum (GG), and composite phosphate (CP) on the quality and structural properties of frozen crystal dumpling wrappers (FCDW) during long-term frozen storage (-18 °C, 60 days) and elucidate potential mechanisms. The results demonstrated that the additives delayed the increase in hardness (reduced from 38,339.26 g to 31,408.86 g on day 60) and the decrease in springiness of FCDW. The additives reduced the freezable water content of FCDW. Notably, HPDSP and GG decreased the proportion of free water, thereby significantly improving the freezing stability of FCDW. Additionally, additives suppressed the continuous increase in contact angle and delayed starch retrogradation. Additives reduced the gelatinization enthalpy of FCDW and inhibited the increase in particle size to some extent. Multiple analytical techniques (SEM, FTIR, XRD) indicated that additives reduced the short-range ordered structure and relative crystallinity of FCDW, with HPDSP exhibiting the most pronounced effect. In conclusion, additives improved the quality deterioration of FCDW by reducing water migration, providing freeze protection, and delaying starch retrogradation.
Drought-induced senescence is a major cause of maize yield loss. While biostimulant priming improves stress tolerance, its molecular basis is unclear. Here we demonstrate that priming maize with the plant-derived biostimulant AgriPrime Stimulus (APS) delays drought-induced leaf senescence at reproductive-stage, resulting in improved cob weight and yield. Integrated physiological, transcriptomic, metabolomic, and phytohormone analyses revealed that APS priming preserves source leaf functionality by maintaining key metabolic processes. APS-primed drought-stressed leaves showed enrichment of photosynthesis-related genes and elevated levels of tricarboxylic acid cycle intermediates, indicating maintained carbon metabolism. APS priming also strengthened cell wall through the induction of genes involved in cellulose, hemicellulose, pectin, cutin, and wax biosynthesis, with increased structural metabolites such as xylose, mannose, and galactonic acid. Delayed senescence was further supported by enhanced redox homeostasis, with upregulation of antioxidant-related genes including superoxide dismutase (SOD3), peroxidases (PRXs), glutathione S-transferases (GSTs), and ascorbate-associated genes (BX13), together with increased levels of protective metabolites such as proline, trehalose, and myo-inositol. In parallel, APS priming suppressed proteolysis and senescence-associated genes (NYC1, NYE1, SAG39, NAC042). Integration of phytohormone and transcriptomic data further revealed maintained growth-promoting hormones alongside reduced abscisic acid and ethylene biosynthesis. Consistent with this reduced catabolic state, APS-primed leaves accumulated amino acids linked to growth, while unprimed drought-stressed leaves accumulated amino acids related to protein degradation. Collectively, these findings show that APS priming preserves source-sink relationships during drought by maintaining leaf longevity, and strengthening sink support, which improves cob weight under water deficit.
Storage of biological materials underpins medical, research, and biotechnological applications. Although cold-chain preservation is effective, it is costly, infrastructure-dependent, and vulnerable to disruption. Room-temperature dry storage, inspired by desiccation-tolerant organisms, offers an alternative by stabilizing biomolecules in vitrified matrices that limit molecular motion and degradation. Trehalose is widely used as a vitrifying agent, but its protective capacity depends on glassy properties shaped by drying conditions, environment, storage duration, and biomolecule type. However, systematic links between these factors and stability remain poorly defined. Here, we examine how drying conditions and storage duration influence the stability of DNA, RNA, and enzymes in trehalose-based vitrified systems. DNA remained stable across all conditions, independent of trehalose or drying parameters, reflecting intrinsic resistance to desiccation damage. RNA exhibited moderate sensitivity to drying without trehalose but was stabilized in its presence, although RNA integrity did not consistently correlate with measured glassy properties. In contrast, enzymes were highly sensitive to drying in the absence of trehalose and strongly protected under conditions that promoted favorable vitrified properties. Short-term enzyme protection (30 min) positively correlated with higher glass transition temperature (Tg). However, during prolonged dry storage, higher Tg was inversely correlated with enzyme stability and instead tracked detrimental physical aging of the vitrified matrix. These findings demonstrate that optimal glass properties depend on both biomolecule class and timescale, providing a framework for rationally designing room-temperature preservation strategies.
The incidence and mortality of severe influenza complicated by invasive pulmonary aspergillosis (IPA) have risen markedly in recent years. This study aimed to evaluate the diagnostic performance of metagenomic next-generation sequencing (mNGS) for detecting IPA in patients with severe influenza. Severe influenza patients with suspected of having IPA admitted to Xinxiang Central Hospital, Henan Province, China, from March 2020 to September 2025 were retrospectively enrolled. Bronchoalveolar lavage fluid (BALF) and blood were collected for fungal culture, galactomannan (GM) assay, and mNGS. Final classification into IPA and non-IPA groups was based on composite clinical and microbiological criteria. Sensitivity, specificity, and receiver operating characteristic curves were used to compare the diagnostic performance of the three methods. Comparison with traditional fungal culture and GM testing, mNGS provided significantly faster results. Among 189 patients suspected of severe influenza-associated IPA, mNGS demonstrated a sensitivity of 72.1% and a specificity of 80.2%. Its sensitivity was higher than that of fungal culture (28.6%), serum GM testing (37.6%), and BALF GM testing (44.1%); however, its specificity was slightly lower than that of fungal culture (89.5%), serum GM testing (84.3%), and BALF GM testing (81.3%). The area under the ROC curve (AUC) for mNGS was 0.76, which is higher than that for BALF GM testing (0.63), serum GM testing (0.61), and fungal culture (0.59). The combined diagnostic approach yielded an AUC of 0.83. mNGS offers a rapid, sensitive and accurate solution for invasive pulmonary aspergillosis in severe influenza patients. It outperforms conventional fungal culture and galactomannan assays. Integrating mNGS with traditional diagnostic methods could substantially improve early detection and overall yield of IPA.
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.
Anti-interferon-γ autoantibodies (AIGAs) are an established cause of adult-onset immunodeficiency (AOID), predisposing individuals to disseminated intracellular infections such as Talaromyces marneffei (TM). However, their role in promoting persistent immune dysregulation and subsequent lymphomagenesis remains poorly understood. A 63-year-old Chinese female with high-titer AIGAs (1:2500) initially presented with disseminated TM. Despite antifungal therapy, her clinical course was complicated by recurrent opportunistic infections-including Varicella-zoster virus (VZV) and Mycobacterium persicum (M. persicum), and steroid-dependent inflammatory episodes. Approximately two years after the initial presentation, she developed an Epstein-Barr virus (EBV)-positive aggressive B-cell lymphoma, confirmed by mass biopsy and PET/CT. Despite treatment with rituximab and broad-spectrum antimicrobials, she died of Gram-negative septic shock. Whole-exome sequencing (WES) revealed a CREBBP p.Q278P mutation, providing a genetic perspective on her disease susceptibility. This case illustrates a rare progression from AIGAs-associated immunodeficiency to EBV-driven lymphoma, suggesting a "triple-hit" pathogenic model that warrants further investigation, comprising: (1) AIGAs-associated AOID; (2) chronic antigenic stimulation from persistent infections that may exacerbate immune dysregulation; and (3) a CREBBP mutation that may act as a genetic contributor to malignant transformation. This case underscores the necessity for rigorous tumor surveillance and individualized treatment in patients with AIGAs-associated immunodeficiency.
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.
This study aimed to investigate the microorganisms isolated, antimicrobial resistance patterns, clinical profiles, and therapeutic approaches in adult acute dacryocystitis cases requiring multidisciplinary management, and to present epidemiological data from Turkey. We retrospectively analyzed adult patients referred from a tertiary ophthalmology hospital to the infectious diseases (ID) specialist between January 2022 and April 2025. Clinical and microbiological data were obtained from electronic medical records. Pathogen identification and susceptibility testing were performed using routine microbiological methods, and the results were interpreted according to applicable standard criteria. Sixty-eight patients were included (mean age: 54.9 years; 79.4% female). Of the 68 included patients, 49 underwent microbiological sampling when indicated and sufficient material was available; 38 (77.6%) had positive cultures, yielding 49 isolates. Staphylococcus aureus (n = 12) was the most frequent isolate. Pseudomonas aeruginosa and Enterobacteriaceae were the leading Gram-negative pathogens. All tested Gram-positive isolates were susceptible to vancomycin. Susceptibility to other antibiotics varied across pathogen groups. All fungal isolates were Candida species. Prior antibiotic exposure was not associated with lower culture positivity in this sample. In adult acute dacryocystitis, culture-based therapy is essential, particularly for complex or nonresponsive cases. This study presents local epidemiological data and may help guide empirical therapy and support individualized antimicrobial management.
Trichophyton indotineae is an emerging dermatophytic pathogen causing severe infections that are frequently resistant to standard antifungals. Since 2015, this species has spread intercontinentally. To highlight the clinical characteristics and challenges in managing T. indotineae infections in the United States and to introduce the utility of rapid real-time PCR (qPCR) diagnosis. Records from a molecular diagnostics laboratory (Bako Diagnostics, GA, USA) were retrospectively reviewed for T. indotineae detections between May 2025 and January 2026. Cases were identified using a novel single-plex qPCR assay and confirmed by sequencing of the internal transcribed spacer region. The squalene epoxidase gene (SQLE) was sequenced to assess terbinafine resistance. A survey was distributed to treating physicians to collect information on recent international travel, household transmission, clinical features, immunosuppressive medications or conditions, and treatment history. All patients (median age: 54; 3 males and 2 females) reported recent travel to India or Nepal, except one, who was the spouse of a patient who had traveled to India. Two different SQLE substitutions were detected, F397L (N = 2) and L393F (N = 1), which are common among terbinafine-resistant T. indotineae isolates found globally. Potential gaps in clinical management - attributed to treatment initiation prior to confirmatory diagnosis of T. indotineae - were identified. These gaps include the use of topical corticosteroids, lack of itraconazole use (100-200 mg/day for 6-8 weeks or longer) as first-line treatment, and prescribing fixed, short treatment durations. In T. indotineae cases, these practices may increase the risk of disease recurrence and domestic spread. Current clinical recommendations are summarized herein, highlighting the utility of this novel qPCR assay for real-time treatment decision-making.