Evaluation of the Dynamiker Quantitative Anti-Aspergillus Fumigatus Specific Detection for the Diagnosis of Different Kinds of Chronic Pulmonary Aspergillosis.

Background: Aspergillus-specific IgG antibody test is considered to be the most reliable method for diagnosing chronic pulmonary aspergillosis (CPA), while its diagnostic roles in different kinds of CPA are still uncertain and it is a challenge of having a threshold to interpret the IgG levels. Purpose: This study aimed to evaluate the diagnostic value of the Dynamiker quantitative Aspergillus fumigatus-specific IgG antibody in different types of CPA with the aim of providing a reference for clinical work. Methods: This prospective study collected the clinical data of patients with suspected CPA admitted to the hospital from January 2020 to December 2022 and divided them into two groups: CPA and non-CPA. The study analyzed clinical characteristics and Aspergillus-specific IgG antibody test's diagnostic value, and a receiver operating characteristic (ROC) curve was used to evaluate diagnostic efficacy. Results: We enrolled 54 CPA patients and 132 non-CPA patients. The average admission age of the CPA group was 61.0 (43.8, 70.0) years, and the sex ratio was 32/22 (male/female). The level of Aspergillus fumigatus-specific IgG antibody in the CPA group was significantly higher than the non-CPA group (95.2 (31.3, 213.3) vs 47.5 (34.0, 80.3) AU/mL, p = 0.001). The area under the ROC curve was 0.653 (95% confidence interval [CI]: 0.580-0.721, p = 0.003). The cutoff with the best diagnostic efficacy was 87 AU/mL, and the sensitivity and specificity were 57.4% and 77.3%, respectively. There was no significant difference in the level of specific IgG antibody among the five CPA types (p = 0.543); however, it was relatively higher in chronic cavitary pulmonary aspergillosis (CCPA). Conclusion: Aspergillus-specific IgG antibody is valuable diagnostic marker for CPA, while its value in differential diagnosis among different types of CPA is limited.

Value Evaluation of Quantitative Aspergillus fumigatus-Specific IgG Antibody Test in the Diagnosis of Non-neutropenic Invasive Pulmonary Aspergillosis.

Background: The role of Aspergillus-specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited. Purpose: This study aims to evaluate the quantitative test value of Aspergillus fumigatus-specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis. Methods: This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of Aspergillus-specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy. Results: The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2±9.6 (33-79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, P=0.027; 33.9% vs 14.7%, P =0.011, respectively). The level of Aspergillus fumigatus-specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1±167.0 vs 62.6±58.0, P<0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 P<0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL. Conclusion: Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and Aspergillus-specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.

Analysis of clinical characteristics and prognosis of talaromycosis (with or without human immunodeficiency virus) from a non-endemic area: a retrospective study.

PURPOSE: Talaromyces marneffei (TM) is a pathogenic fungus endemic in Southeast Asia and human immunodeficiency virus (HIV)-positive populations, but studies related to non-endemic areas and HIV-negative populations are still limited. Therefore, this study aims to provide more additional evidence for clinical work of talaromycosis. METHODS: To collect clinical information of patients with talaromycosis admitted to hospitals in Zhejiang Province, China from January 1, 2010 to May 31, 2020, retrospectively analyzed clinical characteristics and prognosis, COX multivariate regression analysis was used for survival analysis. RESULTS: A total of 92 patients were enrolled, including 76 males, 73 HIV-positive patients, with an average age of 40.1 ± 13.0. Compared to HIV-positive group, the negative group had higher admission age (47.7 ± 14.6 vs 38.1 ± 11.9, p = 0.003) and lower proportion of male (89.0% vs 57.9%, p = 0.004), there was no significant difference in imaging of lungs. There were significantly more HIV-positive patients in those with pleural effusion (100% vs 69.4%, p = 0.001). COX multivariate regression analysis suggested pleural effusion (HR = 3.220; 95% CI 1.117-9.287; p = 0.030) and HIV infection (HR = 0.057; 95% CI 0.009-0.370; p = 0.003) which were independent predictors of prognosis in patients with talaromycosis. CONCLUSIONS: In non-endemic areas, clinical symptoms, signs, and laboratory tests of patients with talaromycosis are similar to those in endemic areas. Patients with pleural effusion have lower survival rate, HIV-infected people are less likely to relapse, and there is no significant correlation between extent of lung involvement and survival of infected patients.

Diagnosis and treatment of primary pulmonary enteric adenocarcinoma: Report of Six cases.

BACKGROUND: Primary pulmonary enteric adenocarcinoma (PEAC) is a very rare subtype of invasive adenocarcinoma, and there have been no large studies on PEAC to date. Therefore, it is necessary to obtain much more information about the clinical and pathological features, diagnosis, differential diagnosis, and treatment of PEAC. CASE SUMMARY: All clinical data of six patients with confirmed PEAC from 2013 to 2018 were collected, and data on diagnosis, differential diagnosis, and treatment of PEAC are discussed combined with all the associated literature. The mean age of six patients was 64.0 ± 5.6 (59-73) years old. Their clinical manifestations were heterogeneous, and during their disease course, there were no gastrointestinal symptoms. There was no evidence from colonoscopy or imaging studies to suggest digestive tract tumors or new metastases. The most commonly mutated gene was KRAS (50.0%), and the pathological features of the six cases were similar to those of colorectal cancer. CDX2 (83.3%) and CK7 (66.7%) had the highest positive rates upon immunohistochemical examination. In the associated literature, 252 cases were identified, and the most commonly mutated gene was KRAS (42.9%). Additionally, CDX2 (68.3%) and CK7 (85.8%) had the highest positive rates. Patients mainly received surgery, chemotherapy, and radiotherapy, immunotherapy was not included. CONCLUSION: Positive results for CDX2 and CK7 play an important role in the diagnosis and differential diagnosis of PEAC, and immunotherapy or targeted therapy focused on KRAS needs to be further studied for the treatment of PEAC.

Case Report: Transformation From Non-Small Cell Lung Cancer to Small Cell Lung Cancer During Anti-PD-1 Therapy: A Report of Two Cases.

BACKGROUND: Histological transformation of lung cancer to small cell lung cancer (SCLC) is uncommon. It is a small subset of the possible resistance mechanisms, even in epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors. Reports on programmed cell death-1 (PD-1) inhibitors are rare. We report two cases of lung squamous carcinomas that transformed to SCLC during anti-PD-1 therapy, and present a detailed description of histological examination of the pre-and post-transformation tissues, hitherto absent from reports on the topic. CASE PRESENTATION: Case 1: A 69-year-old man was diagnosed with stage IVa squamous cell carcinoma of the lung. He had a programmed cell death-ligand 1 tumor proportion score ≥50%. He achieved partial response after four cycles of sintilimab as first-line treatment. However, sintilimab was discontinued because of severe decrease in hemoglobin levels and platelet counts. Moreover, the occurrence of pleural effusion favored disease progression. Interestingly, bone marrow puncture and biopsy showed transformation to SCLC. Case 2: A 71-year-old man diagnosed with stage IIIa lung squamous cell carcinoma received neoadjuvant chemotherapy, underwent radical surgery, and finally received adjuvant chemotherapy. Five months later, he presented with tumor recurrence. He was treated with nivolumab, though disease progression was observed after four cycles. Notably, a subsequent computed tomography-guided biopsy showed SCLC. CONCLUSION: Phenotypic transformation to SCLC is a potential mechanism of resistance to immunotherapy in squamous cell carcinomas of the lung. Disease progression should prompt re-biopsy to diagnose potential histological changes to assess the requirement for change in treatment.

HIV-negative case of Talaromyces marneffei pulmonary infection with a TSC2 mutation.

Talaromyces marneffei is a rare dimorphic pathogenic fungus that can induce severe infections in human immunodeficiency virus (HIV)-infected patients. However, such infections have also been reported in non-HIV hosts. This current case report describes a very rare case of a T. marneffei pulmonary infection in an HIV-negative patient with a mutation in the tuberous sclerosis complex subunit 2 (TSC2) gene. A 24-year-old male patient presented with cough and expectoration for 6 months. Computed tomography showed multiple ground-glass opacities and cystic and cavitated lesions in both lungs. Next generation sequencing (NGS) of the bronchoalveolar lavage fluid was performed to confirm T. marneffei pulmonary infection. The results were further verified using bronchoscopy specimen cultures. This was an HIV-negative patient without a travel history to endemic zones and his blood exon sequencing results showed a mutation in the TSC2 gene. To date, he has recovered well with voriconazole therapy. In summary, patients with TSC2 mutations that induce bronchopulmonary dysplasia may be potential hosts for T. marneffei. Early and timely diagnosis is important for improving prognosis. NGS plays a critical role in the diagnosis of T. marneffei pulmonary infection.

Efficacy of different antifungal drugs as initial treatment for patients with talaromycosis: A systematic review and meta-analysis.

There are no standard choices on antifungal drugs for talaromycosis due to various factors, and related studies are also limited. This study summarizes and analyzes efficacy of different antifungal drugs for patients with talaromycosis, which can provide more reference evidence for drugs' choices in practice. We conducted a meta-analysis on prognostic impacts of different antifungal drugs against talaromycosis, and primary outcome was all-cause mortality. A total of 975 patients from 8 studies were included. One of the 8 studies was a randomized controlled trial and the others were retrospective studies. Among these patients, 582 cases were initiated with amphotericin B, 31 cases died (9.28%). The other 393 cases were initiated with itraconazole, and 54 cases died (14.00%). The initial use of amphotericin B for talaromycosis significantly reduced mortality compared with itraconazole (risk ratio (RR): 0.61; 95% confidence interval (CI): 0.41-0.90; P=0.01; I2=4%). Initial treatment with amphotericin B for talaromycosis in different regions (internal and external) and studies (sample size<100) had no obvious prognostic advantages over itraconazole (RR: 0.60, 95% CI: 0.32-1.13; P=0.11; I2=44%; RR: 0.61, 95% CI: 0.37- 1.00; P=0.05; I2=0%; RR: 0.71, 95% CI: 0.39-1.29; P=0.26; I2=0%, respectively). However, when study's sample size was ≥ 100, the mortality of amphotericin B group was significantly reduced (RR: 0.54, 95% CI: 0.32- 0.92; P=0.02; I2=46%). In conclusion, amphotericin B is a better choice as initial therapeutic drug for talaromycosis.