Abstract Candidemia is associated with substantial mortality in critically ill patients, and early identification of patients at increased risk of death remains challenging. The delta neutrophil index (DNI), an automated hematological parameter reflecting circulating immature granulocytes, has been proposed as a prognostic marker in sepsis, but its role in candidemia remains unclear. This retrospective study included adults who developed candidemia during intensive care unit hospitalization between January 1, 2020, and December 31, 2023; patients with neutropenia, haematological malignancy receiving ongoing chemotherapy, or granulocyte colony-stimulating factor therapy were excluded. Patients were classified as survivors or non-survivors according to 28-day all-cause mortality after blood culture collection. DNI, leukocyte count, C-reactive protein, and procalcitonin were evaluated 24 h before, at the time of, and 24 h after blood culture collection. Multivariable logistic regression identified factors independently associated with mortality, and receiver operating characteristic analysis assessed the prognostic performance of DNI. Among 246 patients, 132 survived and 114 died. Non-survivors had higher APACHE II scores and more frequent acute kidney injury. DNI and procalcitonin levels were significantly higher in non-survivors at all three time points. In the primary multivariable model, acute kidney injury, DNI at blood culture collection, and procalcitonin at blood culture collection were independently associated with mortality; the association of DNI was attenuated and no longer statistically significant after further adjustment for Candida species and antifungal therapy. DNI showed limited discrimination, with area under the curve values ranging from 0.608 to 0.625; the highest value was observed at blood culture collection (0.625), with a cutoff of 2.4, 43.0% sensitivity, and 82.6% specificity. DNI may aid mortality risk stratification in candidemia but should not be used as a standalone prognostic marker.
Abstract Invasive fungal diseases (IFDs) are increasingly recognized in immunocompromised patients, but diagnosis remains challenging because current pathogen-targeted perform variably across heterogeneous immune backgrounds. We investigated whether bronchoalveolar lavage fluid (BALF) immune profiling could identify disease-specific signatures for aspergillosis and Pneumocystis pneumonia. BALF samples from 27 patients were analyzed by shotgun proteomics using a Q Exactive Plus mass spectrometer coupled to an EASY-nLC1200 system. Clinical groups included invasive pulmonary aspergillosis (IPA, n = 7), chronic pulmonary aspergillosis (CPA, n = 4), Pneumocystis pneumonia (PCP, n = 4), Pneumocystis colonization (PCC, n = 4), bacterial infection (BI, n = 4), and controls (n = 4). Overall, 2,278 proteins were identified, with a median of 1,000 proteins per sample (IQR 902-1,384). Within-group pairwise Jaccard similarity was high for controls (median, 0.89), PCP (0.91), PCC (0.87) and BI (0.79), but lower for IPA (0.73) and CPA (0.62), indicating greater heterogeneity in aspergillosis. Hierarchical clustering largely grouped controls, BI, PCC, and PCP according to clinical diagnosis, whereas aspergillosis profiles were more variable. Two IPA clusters emerged: kidney transplant recipients, whose proteomic profiles resembled controls, and non-neutropenic patients with hematological malignancies. Analysis of 77 soluble immune mediators produced broadly similar clustering, suggesting that immune proteins may distinguish clinically relevant disease patterns. In this exploratory analysis, BALF immune proteomic profiles differed according to clinical diagnosis, with the most pronounced heterogeneity observed within aspergillosis. Complement proteins and antimicrobial peptides emerged as candidate biomarkers that warrant validation in larger, independent cohorts before their diagnostic utility can be established.
Abstract Lung cancer survivors may be at increased risk of pulmonary aspergillosis due to structural lung damage and treatment-related immunosuppression, yet population-based data quantifying this risk are limited. Using the Korean National Health Insurance Service database, we conducted a nationwide retrospective cohort study of 37,005 surgically treated lung cancer survivors (2010–2017) and 111,015 age- and sex-matched controls without lung cancer. Incident pulmonary aspergillosis was identified using ICD-10 codes, and its association with lung cancer survivorship was evaluated using multivariable Cox proportional hazards models adjusted for demographic factors and comorbidities, with additional analyses in a health-screening subgroup. Among 148,020 participants followed for 1,126,079 person-years, lung cancer survivors had a significantly higher incidence of pulmonary aspergillosis than age- and sex-matched controls (1.96 vs 0.39 per 1,000 person-years), with an increased adjusted risk (adjusted HR, 4.47; 95% CI, 3.83–5.21). The risk increased in a stepwise manner with treatment intensity and was highest among patients who received combined surgery, chemotherapy, and radiotherapy (adjusted HR, 15.00; 95% CI, 11.91–18.88). This elevated risk was greatest within the first year after diagnosis and remained significant at 5 years. Lung cancer survivors had a significantly increased risk of pulmonary aspergillosis compared with matched controls, particularly during the early post-treatment period and among those receiving multimodal therapy.
Abstract Invasive fusariosis is a rare but often fatal infection in immunocompromised patients. However, data in allogeneic hematopoietic cell transplantation (HCT) are limited. Using a nationwide Japanese transplant registry database, we identified patients who underwent allogeneic HCT between 2008 and 2021 and subsequently developed invasive fusariosis. We conducted questionnaire survey to characterize invasive fusariosis and identify factors associated with early mortality. Thirty-one patients were included. Invasive fusariosis developed at a median of 24 days after HCT. Neutropenia was present in 23 patients (74.2%), and corticosteroids were administered to 23 patients (74.2%). The most commonly involved sites were the bloodstream (71.0%), skin (54.8%), and the respiratory tract (35.5%). Serum (1→3)-β-D-glucan (BDG) was positive in 26 of 31 patients (83.9%) within 2 weeks after diagnosis, whereas BDG positivity preceded the diagnosis in only 15 of 29 evaluable patients (51.7%). Twenty-two (71.0%) died within 30 days after the diagnosis. BDG value normalized to the upper limit of normal (BDG/ULN) within 1 week before diagnosis was significantly lower in 30-day survivors than in non-survivors (median, survivor 0.55 vs. non-survivor 2.94). A pre-diagnostic BDG/ULN of 1.27 predicted 30-day mortality with a sensitivity of 85.7% and a specificity of 81.0%. Among 23 patients who developed invasive fusariosis during neutropenia, all seven 30-day survivors achieved neutrophil recovery, whereas none of the non-survivors did. In conclusion, invasive fusariosis after allogeneic HCT was associated with extremely poor outcomes, particularly in patients with persistent neutropenia. Elevated BDG levels around the time of diagnosis were strongly associated with early mortality.
Abstract Mucormycosis remains a devastating fungal infection. Albumin has been proposed as a host defense mechanism against Mucorales with direct antifungal effects. In both matched and unmatched case-control analyses, serum albumin levels were lower in pediatric cancer patients with mucormycosis (N = 12) compared to children with other infections. Children with mucormycosis that died had significantly lower albumin levels than those who survived, whereas albumin levels were not associated with mortality in children with other infections. In addition, hypoalbuminemia preceded mucormycosis suggesting it may serve as a risk factor and potential therapeutic target.
