Aspergillus Infection Research Articles

Fatal invasive Aspergillus infection in an elderly patient with hepatitis E: A case report and literature review.

Elderly patients with acute liver failure are highly susceptible to severe complications, such as invasive fungal infections, due to weakened immune systems and altered gut microbiota. A thorough understanding of liver failure and opportunistic infections is crucial for effective management. An 84-year-old male with acute liver failure from hepatitis E experienced worsening jaundice despite standard treatments. He also developed respiratory symptoms, including blood-streaked sputum, raising concerns about a potential fungal infection. The patient was diagnosed with acute liver failure secondary to hepatitis E and an invasive fungal infection caused by Aspergillus fumigatus. Initial treatments included artificial liver plasma exchange and antifungal prophylaxis. Further diagnostics, including bronchoscopy and next-generation sequencing of alveolar lavage fluid, confirmed the Aspergillus infection. Elderly liver failure patients are particularly prone to opportunistic infections, underscoring the need for vigilant monitoring and early intervention. Despite aggressive treatments, including antifungal therapy and artificial liver support, prognosis remains poor, highlighting the importance of prompt diagnosis and comprehensive management to enhance patient outcomes.

Healthcare Costs of Hospitalizations Due to Aspergillosis and 25-Year Trends in Spain, 1997–2021

In the last 40 years, a significant increase in the incidence of lung infections by Aspergillus has been reported. The scarcity of studies that describe the costs of aspergillosis indicates that the economic impact of aspergillosis in the hospital environment is greater than that of other fungal infections. The objective of the study was to evaluate the direct healthcare costs associated with aspergillosis in the Spanish National Health System from 1997 to 2021. A retrospective nationwide longitudinal descriptive study was designed to review hospital records from the Minimum Basic Data Set of patients admitted to hospitals of the National Health System from 1997 to 2021, with a diagnosis of aspergillosis. A total of 44,586 patients were admitted for aspergillosis in the Spanish National Health System. There was a progressive increase in the average annual cost from 1997 to 2012, which reached a maximum peak, EUR 1,395,154.21 (±2,155,192.87). It decreased between 2014 and 2019, but increased again in 2020 and 2021, EUR 28,675.79 (±30,384.12). The Pearson correlation coefficient revealed a weak negative correlation between age and hospital costs and a moderate positive correlation between average length of stay and hospital costs. Our data show that the economic impact of hospitalizations for aspergillosis is significant and increasing at a rate proportionally higher than that of other prevalent diseases. Costs related to Aspergillus infection are associated mainly with respiratory diseases. The results of this economic evaluation may be useful for health authorities to develop a future economic strategy for managing this fungal infection.

Invasive fungal disease in patients with cancer in a tertiary care pediatric hospital

Abstract Background In the last two decades, the raise in invasive fungal diseases (IFD) has been associated with increased morbidity and mortality in immunosuppressed hosts. Its incidence varies between 2 to 21% and depends on the host´s underlying disease, the intensity of immunosuppressive treatment and the presence of comorbidities. The aim of this study is to describe the epidemiological, clinical and microbiological characteristics of IFD in patients with hematology-oncology disease. Methods Retrospective, descriptive study. Patients under 18 years of age with acute leukemias, lymphomas and solid tumors with a diagnosis of proven IFD (according to EORTC-MSG 2019 criteria) were included during the period from January 2020 to November 2023 in a tertiary care pediatric hospital. Results During the study period, 304 patients were under follow-up. 14 episodes of proven IFD were identified in 13 patients.The median age was 120 months. Male sex predominated (69.2%). The recognized factors associated were neutropenia (69.2%), use of corticosteroids in the last 3 months (61.5%) and use of previous antibiotics (92.3%). The most common underlying disease was Acute Lymphoblastic Leukemia (ALL) in 11 cases (78.5%), of which 3 were in relapse. The 21.4% of the episodes occurred in solid tumors (1 osteosarcoma of the tibia, 1 abdominal germ cell tumor, 1 neuroblastoma). Patients receiving primary prophylaxis for filamentous fungi were 3/14 (21.4%), according to the European Conference on Infections in Leukemia (ECIL-8). All received voriconazole. The fungal isolates identified were: 1 Rhizopus spp. (eye biopsy, paranasal sinuses) 1 Penicillum spp. (lung biopsy), 1 Exserohilum rostratum (skin biopsy), 1 Trichophyton asahii (blood cultures), 1 Purpuracillum lilacinus (skin biopsy), 1 Aspergillus fumigatus (Bronchoalveolar lavage, BAL),: 3 Candida parapsilosis (blood cultures), 1 Candida tropicalis (blood cultures), 1 Candida spp (blood cultures), 1 Malassezia (BAL). The patients with invasive molds infections were six, all of them with pathological chest tomography. Galactomannans (GM) were positive in 66% (4/6). BAL with positive GM was performed in 2 of them. The primary focus were: cutaneous (3/6), pulmonary (2/6) and orbital-rhinosinusal (1/6). Regarding IFD due to yeast fungi: all Candida infections were associated with central venous catheters fungemia. Malassezia infection presented with pulmonary involvement. Fungal co-infection was observed in 1 patient with documentation of Aspergillus fumigatus in BAL and Candida tropicalis in blood and urine cultures. Empirical antifungal therapy was liposomal amphotericin in 76.9 % of the patients. Two patients died (15.4%) at 30 days of follow-up. Conclusion Early diagnosis and timely antifungal therapy represent the main strategies to increase the survival of patients with IFD. Antifungal prophylaxis is postulated as an effective prevention measure and its indication should be defined according to the patient’s characteristics and the incidence of IFD at the treating center. We consider that patients with suspected IFD and clinical focus should undergo the corresponding tissue biopsy for culture, histological evaluation, and molecular biology, to direct the appropriate treatment. Candida species represent the most frequent isolates, however, Aspergillus and Rhizopus infections are associated with higher morbidity and mortality.

Bilateral chronic cavitary pulmonary aspergillomas in an adult patient with recurrent tuberculosis: a case report and literature review

BackgroundAspergillomas are globular growths of Aspergillus fumigatus, a benign aspergillosis of the lungs. It usually affects patients who are immunocompromised and have anatomically defective lung structures. The majority of aspergilloma cases are asymptomatic, despite the fact that 10% of cases spontaneously resolve. Most patients do not have any symptoms from their lesions. Direct serological or microbiological evidence of an Aspergillus species along with radiologic evidence is required for the diagnosis of an aspergilloma.CaseWe describe a 35-year-old adult Oromo male patient who had been experiencing night sweats, an intermittent productive cough with sparse whitish sputum, loss of appetite, and easy fatigability for 3 months. At 5 years prior, he received treatment for pulmonary tuberculosis that was smear-positive and was subsequently certified healed. Objectively, he was tachypneic and had intercostal, subcostal, and supraclavicular retractions with symmetric chest movement. A high-resolution computed tomography scan revealed bilateral apical cavitary lesions with core soft tissue attenuating spherical masses and an air crescentic sign suggestive of aspergillomas, which were confirmed by sputum light microscopic examination. The patient was managed with antibiotics and antifungals.ConclusionAspergilloma is a symptom of chronic pulmonary aspergillosis, a category of lung disorders caused by a persistent Aspergillus infection. Primary aspergillomas are uncommon and frequently occur in people with compromised immune systems. A prolonged cough, fever, chest pain, and hemoptysis are all symptoms of pulmonary aspergillomas. The majority of the time, pulmonary aspergillosis is difficult to identify. Despite high mortality and morbidity rates, surgery is still the most effective treatment for pulmonary aspergilloma.

The Real-World Effectiveness of Antifungals in People with Cystic Fibrosis and Aspergillus-Positive Cultures.

The pathogenicity of Aspergillus in the cystic fibrosis (CF) airway is debated, leading to unclear clinical benefit of antifungal therapy for Aspergillus infection. To determine the real-world effectiveness of antifungal use in people with CF (PwCF) with Aspergillus species in the United States. We conducted a retrospective cohort study evaluating the association of antifungal use and respiratory outcomes in PwCF and Aspergillus positive cultures using the Cystic Fibrosis Foundation patient registry. Marginal structural models using inverse-probability treatment weighted estimators were used to test if antifungal exposure was associated with forced expiratory volume in one second percent predicted (FEV1pp) and pulmonary exacerbation rate, while controlling for fixed and time-varying confounders. We conducted sensitivity analyses on individuals with persistent Aspergillus and without concomitant allergic bronchopulmonary aspergillosis (ABPA). A total of 14,754 individuals with Aspergillus positive cultures between 2006 and 2019 were identified. Antifungals were prescribed to 3,575 (24.2%) unique PwCF during the study period. Antifungal use was not associated with FEV1pp (adjusted estimate -0.96 percentage points, 95% CI -2.21,0.29). Antifungal use was associated with 29% increased rate of pulmonary exacerbations requiring intravenous (IV) antibiotics (adjusted IRR=1.29, 95% CI 1.22, 1.37). In sensitivity analyses limited to individuals without ABPA< antifungals were associated with 1.88 lower FEV1pp (95% CI -3.35, -0.41) and an increased rate of pulmonary exacerbations (adjusted IRR= 1.30, 95% CI 1.21,1.40). Whereas, in patients with persistent Aspergillus and persistent Aspergillus without concomitant ABPA, antifungals were not associated with FEV1pp. Antifungal therapy in PwCF and Aspergillus positive cultures was not associated with improvements in FEV>1pp. While antifungal therapy was associated with increased risk for pulmonary exacerbations, this could reflect confounding by severity of disease. Randomized clinical trials examining the clinical efficacy of antifungals in Aspergillus infections are warranted.

Glucocorticoids Suppress NF-κB-Mediated Neutrophil Control of Aspergillus fumigatus Hyphal Growth.

Glucocorticoids are a major class of therapeutic anti-inflammatory and immunosuppressive drugs prescribed to patients with inflammatory diseases, to avoid transplant rejection, and as part of cancer chemotherapy. However, exposure to these drugs increases the risk of opportunistic infections such as with the fungus Aspergillus fumigatus, which causes mortality in >50% of infected patients. The mechanisms by which glucocorticoids increase susceptibility to A. fumigatus are poorly understood. In this article, we used a zebrafish larva Aspergillus infection model to identify innate immune mechanisms altered by glucocorticoid treatment. Infected larvae exposed to dexamethasone succumb to infection at a significantly higher rate than control larvae. However, both macrophages and neutrophils are still recruited to the site of infection, and dexamethasone treatment does not significantly affect fungal spore killing. Instead, the primary effect of dexamethasone manifests later in infection with treated larvae exhibiting increased invasive hyphal growth. In line with this, dexamethasone predominantly inhibits neutrophil function rather than macrophage function. Dexamethasone-induced mortality also depends on the glucocorticoid receptor. Dexamethasone partially suppresses NF-κB activation at the infection site by inducing the transcription of IκB via the glucocorticoid receptor. Independent CRISPR/Cas9 targeting of IKKγ to prevent NF-κB activation also increases invasive A. fumigatus growth and larval mortality. However, dexamethasone treatment of IKKγ crispant larvae further increases invasive hyphal growth and host mortality, suggesting that dexamethasone may suppress other pathways in addition to NF-κB to promote host susceptibility. Collectively, we find that dexamethasone acts through the glucocorticoid receptor to suppress NF-κB-mediated neutrophil control of A. fumigatus hyphae in zebrafish larvae.

Relationship between SARS-CoV-2 infection and ICU-acquired candidemia in critically ill medical patients: a multicenter prospective cohort study

BackgroundWhile SARS-CoV2 infection has been shown to be a significant risk-factor for several secondary bacterial, viral and Aspergillus infections, its impact on intensive care unit (ICU)-acquired candidemia (ICAC) remains poorly explored.MethodUsing the REA-REZO network (French surveillance network of ICU-acquired infections), we included all adult patients hospitalized for a medical reason of admission in participating ICUs for at least 48 h from January 2020 to January 2023. To account for confounders, a non-parsimonious propensity score matching was performed. Rates of ICAC according to SARS-CoV2 status were compared in matched patients. Factors associated with ICAC in COVID-19 patients were also assessed using a Fine-Gray model.ResultsA total of 55,268 patients hospitalized at least 48 h for a medical reason in 101 ICUs were included along the study period. Of those, 13,472 were tested positive for a SARS-CoV2 infection while 284 patients developed an ICAC. ICAC rate was higher in COVID-19 patients in both the overall population and the matched patients’ cohort (0.8% (107/13,472) versus 0.4% (173/41,796); p < 0.001 and 0.8% (93/12,241) versus 0.5% (57/12,241); p = 0.004, respectively). ICAC incidence rate was also higher in those patients (incidence rate 0.51 per 1000 patients-days in COVID-19 patients versus 0.32 per 1000 patients-days; incidence rate ratio: 1.58 [95% CI:1.08–2.35]; p = 0.018). Finally, patients with ICAC had a higher ICU mortality rate (49.6% versus 20.2%; p < 0.001).ConclusionIn this large multicenter cohort of ICU patients, although remaining low, the rate of ICAC was higher among COVID-19 patients.

Reassessment of the role of combination antifungal therapy in the current era.

Given the high mortality and morbidity associated with invasive fungal diseases (IFDs), the use of combination antifungal therapies is often considered despite the dearth of data. This review aims to summarize the current state of literature of combination antifungal therapies, discussing the potential roles of newer antifungal combinations and key considerations for their clinical use. In infections other than cryptococcal meningitis or in the setting of empirical treatment for suspected azole-resistant Aspergillus infections, the utility of the combination antifungal approaches remains controversial given the paucity of well designed randomized controlled trials. Data on potential combined antifungal treatments have been primarily limited to in-vitro studies, animal models, case reports and/or observational studies. With availability of novel antifungal agents (e.g. ibrexafungerp, fosmanogepix), combination therapy to treat mould infections should be re-visited. A phase 2 clinical trial of ibrexafungerp combined with voriconazole to treat invasive pulmonary aspergillosis is on-going. There is a need to investigate the use of combination antifungal agents. This includes delineating the indication of these combined antifungal therapies and determining how to use them most appropriately in the clinical setting.

Successful treatment of mixed pulmonary Aspergillus and Mucor infection using intrabronchial amphotericin B infusion: a case report and literature review

BackgroundReports of pulmonary aspergillosis and mucormycosis co-infections are rare; thus, limited guidance is available on early diagnosis and treatment. We present a case of mixed pulmonary Aspergillus and Mucor infection and review the literature regarding this co-infection. The diagnosis and treatment methods are summarized to improve clinicians’ understanding of the disease and to facilitate early diagnosis and treatment.Case presentationA 60-year-old male farmer with poorly controlled diabetes mellitus was admitted to hospital with a fever of unknown origin that had been present for 15 days and pulmonary aspergillosis complicated by Mucor spp. infection. Because multiple lobes were involved, the infection worsened despite surgical resection and antifungal therapy. Finally, we treated this patient with a bronchoscopic infusion of amphotericin B. After four courses of bronchoscopic amphotericin B infusion, we observed rapid clinical improvement and subsequent resolution of pulmonary infiltrates.ConclusionOur case highlights the use of bronchoscopy in the successful clinical treatment of invasive fungal diseases of the lung.

Clinical analysis of progressive destroyed lung after lung cancer surgery.

"Progressive destroyed lung (PDL)" refers to a state in which the normal structure and function of the lung are permanently disrupted owing to repeated inflammation. After lung cancer surgery, the remaining lung tissue can experience progressive destruction; however, the exact cause remains unclear. In this study, we retrospectively analyzed cases in which the remaining lung deteriorated after lung cancer surgery and investigated the associated risk factors. A case-control study was conducted on 31 cases of PDL and 247 cases of non-PDL among 1,234 patients who underwent surgery for primary lung cancer from 2006 to 2021. The following factors were analyzed: age, sex, medical history, smoking status, surgical procedure, lung cancer histology, surgical approach, postoperative complications, chemotherapy, radiation therapy, and lung cancer recurrence. Patients were matched 1:1 based on preoperative factors, and postoperative risk factors were evaluated using multivariate logistic regression analysis. A higher proportion of men and higher prevalence of chronic lung diseases, smokers, squamous cell carcinoma (SCC), postoperative acute pneumonia, chronic pneumonia, air leak, and history of radiation therapy were noted in the PDL group than in the non-PDL group. In the analysis following propensity score matching, chronic pneumonia [odds ratio (OR): 10.1, 95% confidence interval (CI): 2.9 to 35.8] was identified as an independent risk factor for PDL. In this study, PDL after lung cancer surgery was associated with postoperative chronic pneumonia, including Aspergillus infection and aspiration pneumonia.

Comparative evaluation of Sensititre YeastOne and CLSI M38-Ed3 reference method for determining echinocandin minimum effective concentrations against Aspergillus isolates.

The minimum inhibitory concentration (MIC) of echinocandins against Aspergillus spp. does not represent the actual inhibition threshold of echinocandins. Therefore, the recommended method to evaluate their activity is determining the minimum effective concentration (MEC) in broth microdilution, a method that is less common in clinical settings. This study aimed to assess a user-friendly commercial method, Sensititre YeastOne (SYO), to determine the effectiveness of echinocandins (caspofungin, anidulafungin and micafungin) against Aspergillus spp. Echinocandins MEC was determined against 23 isolates of Aspergillus spp. using SYO and the reference Clinical and Laboratory Standards Institute (CLSI) method. MECs were read with an inverted microscope and a reading mirror. Essential agreement (EA) between the tested methods was defined as a ±twofold dilution difference. There was a high EA (91%-100%) between the reference method and SYO in determining echinocandins MEC against Aspergillus isolates using inverted microscopy. A high EA was also observed between SYO MEC determined by inverted microscopy and a reading mirror, but different incubation times were required. SYO is a reliable, simple method for determining the MEC of echinocandins against Aspergillus isolates, preferably with an inverted microscope, and can be easily used in clinical laboratories when echinocandin susceptibility testing is required.IMPORTANCEUsing a commercial method such as Sensititre YeastOne (SYO) to determine the minimum effective concentration (MEC) of echinocandins against Aspergillus spp. has been shown to be a reliable alternative to the Clinical and Laboratory Standards Institute (CLSI) reference method. This makes it more suitable for high-volume clinical laboratories. SYO provides accurate results comparable to the standard method and could potentially improve patient care by guiding more optimal antifungal treatment choices for patients with Aspergillus infections.

Value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in acute exacerbation of fibrosing interstitial lung disease: an individualized treatment protocol based on microbiological evidence

BackgroundAcute exacerbation of fibrosing interstitial lung diseases (AE-ILD) is a serious life-threatening event per year. Methylprednisolone and/or immunosuppressive agents (ISA) are a mainstay in any regimen, under the premise that pulmonary infection has been promptly identified and controlled. We investigated the value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) on the treatment adjustment of AE-ILD.MethodsWe conducted a cross-sectional observational study. All data were collected prospectively and retrospectively analyzed. We included fifty-six patients with AE-ILD and nineteen stable ILD who underwent BALF mNGS at the beginning of admission.ResultsPatients with a variety of ILD classification were included. Connective–tissue disease related ILD (CTD-ILD) occupy the most common underlying non-idiopathic pulmonary fibrosis (non-IPF). The infection-triggered AE accounted for 39.29%, with the majority of cases being mixed infections. The microorganisms load in the AE-ILD group was significantly higher. After adjusted by mNGS, the therapy coverage number of pathogens was significantly higher compared to the initial treatment (p < 0.001). After treatment, the GGO score and the consolidation score were significantly lower during follow up in survivors (1.57 ± 0.53 vs. 2.38 ± 0.83 with p < 0.001, 1.11 ± 0.24 vs. 1.49 ± 0.47 with p < 0.001, respectively). Some detected microorganisms, such as Tropheryma whipplei, Mycobacterium, Aspergillus, and mixed infections were difficult to be fully covered by empirical medication. BALF mNGS was also very helpful for excluding infections and early administration of methylprednisolone and/or ISA.ConclusionsmNGS has been shown to be a useful tool to determine pathogens in patients with AE-ILD, the results should be fully analyzed. The comprehensive treatment protocol based on mNGS has been shown crucial in AE-ILD patients.

Diagnosis of peripheral cavitary squamous cell lung carcinoma with Aspergillus infection using LungPro navigation system: a case report

Virtual bronchoscopic navigation (VBN) is increasingly being used to diagnose peripheral lung lesions, allowing precise guidance of the bronchoscope to the target lesions, thereby improving diagnostic accuracy. This paper reported a patient admitted due to hemoptysis, with an initial clinical diagnosis of squamous cell lung carcinoma with brain and bone metastases. Previous attempts had failed to obtain tissue samples from the lung lesions. Upon admission, the LungPro navigation system was used to perform a bronchoscopic transparenchymal nodule access (BTPNA). Pathological examination of the lung tissue and microbiological analysis of bronchoalveolar lavage fluid confirmed the diagnosis of peripheral cavitary squamous cell lung carcinoma with Aspergillus infection. Following antifungal and antineoplastic treatment, the patient's symptoms improved markedly and she was subsequently discharged.

Urinary Tract Aspergillosis in a Child with Pelviureteric Junction Obstruction

Abstract Aspergillus spp. are fungi which are mostly nonpathogenic, but some species such as Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger can cause aspergillosis in humans. Aspergillosis can manifest as pulmonary or extrapulmonary infections, with respiratory involvement being common but infections in other body parts being rare. Urinary aspergillosis, an uncommon manifestation of Aspergillus infection, presents unique challenges in diagnosis and management due to its rarity and varied clinical presentations. It is seen in immunocompromised individuals, patients with underlying structural urinary tract abnormalities, or those undergoing invasive procedures. Here, we present a case of an 8-month-old child who presented with intermittent fever and increased urination since birth. The child underwent bilateral open pyeloplasty with double-J (DJ) stenting. A month later, the child returned with anuria, fever, and abdominal mass, leading to infected DJ stent removal and bilateral percutaneous nephrostomy. Despite antibiotic treatment, fever persisted. A fungal culture was done which showed growth of A. flavus. Liposomal amphotericin B was started for the patient after which he became afebrile, and all the fungal cultures done, thereafter, were negative. Urinary tract aspergillosis is rare, particularly among individuals with a strong immune system. Persistence of urinary tract symptoms despite antibiotic and medical therapy may raise the possibility of fungal infection such as urinary tract aspergillosis.

Retrospective Comparison of Two Aspergillus IgG Enzyme Immunoassays for Diagnosing Pulmonary Aspergillosis.

Aspergillus-specific antibodies are diagnostic indicators of allergic bronchopulmonary aspergillosis (ABPA) and chronic pulmonary aspergillosis (CPA). Tests for detecting Aspergillus-specific antibodies were not used clinically in Japan, and the production of the Aspergillus precipitin test was discontinued. Thus, alternative tests for diagnosing aspergillosis are urgently needed. We retrospectively evaluated 64 patients with suspected ABPA and CPA who underwent precipitin antibody testing. Serum Aspergillus IgG levels were measured and compared using the Bordier Aspergillus fumigatus ELISA and the Platelia Aspergillus IgG (Bio-Rad) kits. Of the participants, 18 were diagnosed with CPA, and 8 were diagnosed with ABPA. Both the Bordier and Bio-Rad kits showed high sensitivity and specificity for CPA and ABPA. The area under the receiver operating characteristic curves for the Bordier and Bio-Rad kits were 0.97 and 0.95, respectively, for CPA, and 0.89 and 0.91, respectively, for ABPA. In contrast to the Bordier kit, the Bio-Rad kit showed relatively low anti-Aspergillus IgG levels and lower sensitivity to non-fumigatus Aspergillus infections. The Aspergillus-specific IgG ELISA tests showed sufficient diagnostic accuracy. Therefore, these assays are recommended as alternatives to the precipitin kit for diagnosing aspergillosis in clinical settings in Japan.

Chest computed tomography manifestations in neonates with chronic granulomatous disease

To study chest computed tomography (CT) manifestations in neonates with chronic granulomatous disease (CGD) to provide clues for early diagnosis of this disease. A retrospective analysis was conducted on the clinical data and chest CT scan results of neonates diagnosed with CGD from January 2015 to December 2022 at Anhui Provincial Children's Hospital. Nine neonates with CGD were included, with eight presenting respiratory symptoms as the initial sign. Chest CT findings included: consolidation in all 9 cases; nodules in all 9 cases, characterized by multiple, variably sized scattered nodules in both lungs; masses in 4 cases; cavities in 3 cases; abscesses in 6 cases; bronchial stenosis in 2 cases; pleural effusion, interstitial changes, and mediastinal lymphadenopathy each in 1 case. CT enhancement scans showed nodules and masses with uneven or ring-shaped enhancement; no signs of pulmonary emphysema, lung calcification, halo signs, crescent signs, bronchiectasis, or scar lesions were observed. There was no evidence of rib or vertebral bone destruction. Fungal infections were present in 8 of the 9 cases, including 6 with Aspergillus infections; three of these involved mixed infections with Aspergillus, with masses most commonly associated with mixed Aspergillus infections (3/4). The primary manifestations of neonatal CGD on chest CT are consolidation, nodules, and/or masses, with Aspergillus as a common pathogen. These features can serve as early diagnostic clues for neonatal CGD.

Research advances on the mechanism of immune regulation of interferon in Aspergillus infection

Pulmonary aspergillosis is a serious pulmonary fungal infectious disease. It is difficult to manage and has limited treatment options. Existing anti-aspergillus medications have high rates of treatment failure and increased drug resistance, making it difficult to meet the clinical requirements. Therefore, the development of new, effective treatment programs is critical. According to research, interferons play an important role in the body's immune response to bacterial and viral infectious diseases. Inadequate interferon expression or dysfunction can put the body at risk for certain infectious diseases. Interferon has been used in clinical trials to prevent or treat infectious diseases. In recent years, researchers have focused on the immunological role of interferon in Aspergillus infections and its potential for clinical application. This review summarized the most recent advances in the immunoregulatory mechanisms of interferon and its clinical application in Aspergillus infections.

Ruxolitinib in treatment-naive or corticosteroid-refractory paediatric patients with chronic graft-versus-host disease (REACH5): interim analysis of a single-arm, multicentre, phase 2 study

Chronic graft-versus-host disease (GVHD) is a debilitating, and sometimes life threatening, complication of allogeneic haematopoietic stem-cell transplantation (HSCT). We aimed to investigate the activity, pharmacokinetics, and safety of ruxolitinib added to corticosteroids in paediatric patients (ie, <18 years) with moderate-to-severe chronic GVHD. In this single-arm, phase 2 study, patients were recruited at 21 hospitals or clinics across 14 countries in Asia, Europe, and Canada. Eligible patients were aged 28 days to younger than 18 years, had undergone allogenic HSCT, and had been diagnosed with treatment-naive or corticosteroid-refractory moderate-to-severe chronic GVHD, per 2014 National Institutes of Health consensus criteria. Patients received oral ruxolitinib dosing on the basis of their age at the start of treatment: those aged 12 years to younger than 18 years received 10 mg twice daily (age ≥12 to <18 years group), those aged 6 years to younger than 12 years (age ≥6 to <12 years group) received 5 mg twice daily, and those aged 2 years to younger than 6 years received 4 mg/m2 twice daily (age ≥2 to <6 years group). Treatment was to be administered in 28-day cycles for approximately 36 months, alongside supportive treatment per institutional guidelines. The primary activity endpoint was overall response rate at cycle 7 day 1. Activity and safety analyses are reported in the full analysis set, which included all patients who received at least one dose of ruxolitinib. Here we report the prespecified interim analysis, scheduled to occur after all patients had completed 1 year of treatment or discontinued treatment, and the results for the primary endpoint evaluation reported here is to be considered final. This study is registered with ClinicalTrials.gov, NCT03774082, enrolment is complete, and the study is ongoing. Between May 20, 2020, and Sept 17, 2021, 48 patients were screened, of whom 45 were enrolled and received at least one dose of study drug (median age was 11·0 years [IQR 7·2-14·3], 16 [36%] were female, 29 [64%] were male, 21 [47%] were White, one [2%] was Black or African American, 23 [51%] were Asian, 17 [38%] were treatment-naive, 28 [62%] were corticosteroid-refractory). As of data cutoff (Oct 19, 2022), after a median ruxolitinib exposure of 55·1 weeks (IQR 13·1-75·3), the overall response rate at cycle 7 day 1 was 40·0% (18 of 45; 90% CI 27·7-53·3), with responses seen in seven (41%) of 17 treatment-naive patients and 11 (39%) of 28 corticosteroid-refractory patients. The most common treatment-related adverse events of grade 3 or worse were neutropenia (eight [18%] of 45) and thrombocytopenia (six [13%]). Seven (16%) patients had grade 3 or worse serious treatment-related adverse events; the most common was hyponatraemia (two [4%] of 45). Three (7%) patients died while on-treatment (within 30 days of treatment discontinuation), one due to Aspergillus infection, one due to septic shock, and one due to acute respiratory distress syndrome; none were considered to be related to study drug. Pending final analysis, this study suggests that ruxolitinib is active and well tolerated in both treatment-naive and corticosteroid-refractory patients aged 2 years to younger than 18 years with chronic GVHD, thereby supporting its use in this patient population. The safety profile of ruxolitinib in this patient population is consistent with that of adults. Final analysis of this study will provide further information on the long-term benefits of ruxolitinib in children with chronic GVHD. Novartis.

Antifungal prophylaxis against invasive Candida and Aspergillus infection in adult heart transplant recipients: protocol for a systematic review and meta-analysis

IntroductionInvasive fungal infections (IFI) can contribute to increased mortality and morbidity rates after heart transplant in adults. The most common causes are Aspergillus and Candida species. There is uncertainty on...

Fully Automated Cassette-Based Synthesis of 2-Deoxy-2-[18F]Fluorocellobiose Using Trasis AllInOne Module.

Due to the continuous rise in global incidence and severity of invasive fungal infections (IFIs), particularly among immunocompromised and immunodeficient patients, there is an urgent demand for swift and accurate fungal pathogen diagnosis. Therefore, the need for fungal-specific positron emission tomography (PET) imaging agents that can detect the infection in the early stages is increasing. Cellobiose, a disaccharide, is readily metabolized by fungal pathogens such as Aspergillus species. Recently, our group reported fluorine-18 labeled cellobiose, 2-deoxy-2-[18F]fluorocellobiose ([18F]FCB), for specific imaging of Aspergillus infection. The positive imaging findings with very low background signal on delayed imaging make this ligand a promising fungal-specific imaging ligand. Inspired by this result, the decision was made to automate the radiolabeling procedure for better reproducibility and to facilitate clinical translation. A Trasis AllInOne (Trasis AIO) automated module was used for this purpose. The reagent vials contain commercially available 2-deoxy-2-[18F]fluoroglucose ([18F]FDG), glucose-1-phosphate, and enzyme (cellobiose phosphorylase). A Sep-Pak cartridge was used to purify the tracer. The overall radiochemical yield was 50%-70% (n = 6, decay corrected) in 75-min synthesis time with a radiochemical purity of > 98%. This is a highly reliable protocol to produce current good manufacturing practice (cGMP)-compliant [18F]FCB for clinical PET imaging.