Ana Margarita Rodriguez Garcia

Background and Objectives: Krebs von den Lungen-6 (KL-6) is a promising biomarker of interstitial lung disease (ILD), but data in immune-mediated ILD remain limited. We aimed to evaluate the clinical, functional, and radiological correlates of serum KL-6 levels in a real-world cohort of patients with immune-mediated ILD. Materials and Methods: We conducted a retrospective, cross-sectional, single-center study including adults with multidisciplinary follow-up for immune-mediated ILD and at least one serum KL-6 determination between January 2023 and September 2025. Clinical, laboratory, radiological, and pulmonary function data closest to the index KL-6 measurement were collected. KL-6 was analyzed as both a continuous variable and a categorical variable using a predefined cutoff of 500 U/mL. Correlation analyses and multivariable logistic regression were performed to identify factors independently associated with elevated KL-6 levels. Results: A total of 112 patients were included; 72.3% were women, with a median age of 70 years (IQR 63–77). The most frequent underlying diseases were systemic sclerosis (30.4%), rheumatoid arthritis (25.9%), and inflammatory myopathy (14.3%). Median KL-6 concentration was 770.5 U/mL (IQR 437.3–1148.5). Patients with FVC < 80% predicted and DLCO < 60% predicted had significantly higher KL-6 levels than those with better lung function (p = 0.001 and p = 0.004, respectively). KL-6 levels correlated inversely with DLCO (% predicted) (ρ = −0.388, p < 0.001) and FVC (% predicted) (ρ = −0.328, p < 0.001) but not with the presence of radiological fibrosis. In the multivariable analysis, lower DLCO (% predicted) (OR 0.919, 95% CI 0.884–0.955; p < 0.001) and older age (OR 1.063, 95% CI 1.014–1.115; p = 0.012) were independently associated with elevated KL-6 levels. Conclusions: Elevated serum KL-6 concentrations were associated with impaired gas transfer as measured by DLCO % predicted in this cross-sectional cohort. Longitudinal studies are required to determine whether KL-6 can predict functional decline, disease progression, or clinical outcomes.

Background/Objectives: Accurate diagnosis of lymph node pathology is essential for the management of both malignant and benign diseases. This study compares the diagnostic performance of endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in a real-world cohort. Methods: A single-center retrospective observational study was conducted, including 91 patients who underwent both cryobiopsy and EBUS-TBNA for lymph node evaluation. EBUS-TBNA was performed with a 19-G needle and cryobiopsy with a 1.1 mm flexible cryoprobe. Clinical characteristics, positron emission tomography–computed tomography (PET–CT) findings, ultrasonographic characteristics of the lymph nodes, diagnostic yield, and procedure-related complications were analyzed. Diagnostic accuracy, sensitivity, specificity, and factors associated with correct diagnosis were assessed. Results: The median age of the cohort was 65 years [interquartile range-IQR-56–74], 63.7% were male, and 74.7% were former or current smokers. Malignant disease was ultimately diagnosed in 60 patients (65.9%), of whom 78.3% had non-lymphoproliferative tumours and 21.7% had lymphoproliferative malignancies. The diagnostic accuracy of cryobiopsy was 89%, compared with 82.4% for EBUS-TBNA. The paired comparison between the two techniques did not reach statistical significance. After exclusion of non-diagnostic samples, sensitivity was numerically higher for cryobiopsy (96.4%, 95% CI 90.7–100) than for EBUS-TBNA (88.9%, 95% CI 79.6–98.2). Factors associated with correct diagnosis included chronic obstructive pulmonary disease for cryobiopsy, cardiovascular comorbidities, and maximum SUV for EBUS-TBNA. In malignant lesions, cryobiopsy showed higher diagnostic accuracy than EBUS-TBNA (90% vs. 80% accuracy), particularly in lymphoproliferative diseases. In benign lesions, both techniques agreed in 17 (54%) of cases, with cryobiopsy showing a higher yield for sarcoidosis and contributing to the diagnosis of tuberculosis. Complications were infrequent and minor, with no major adverse events reported. Conclusions: Cryobiopsy showed numerically higher diagnostic accuracy and sensitivity compared with EBUS-TBNA, particularly in malignant and lymphoproliferative disorders, with a favorable safety profile. These findings support its role as a valuable complement—or alternative—to conventional EBUS-TBNA in the assessment of mediastinal lymph nodes.

Introduction: Following up on treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions poses a challenge. Cervical cytology often has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing, though sensitive, lacks specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) is proposed as an indicator of viral integration, which is crucial for identifying severe lesions. Additionally, HPV vaccination could reduce recurrence rates in patients treated for high-grade cervical intraepithelial neoplasia. Objective: Our study aimed to assess the clinical utility of E6/E7 mRNA determination in the follow-up of HPV-immunized patients who were treated for HSIL/CIN. Methods: We conducted a retrospective observational study including 407 patients treated for HSIL/CIN. The recurrence rate and the validity parameters of E6/E7 mRNA testing were analyzed. Results: The recurrence rate for high-grade lesions was 1.7%. This low percentage might be related to the vaccination of patients who were not immunized before treatment. The sensitivity of the E6/E7 mRNA test was 88% at the first clinical visit, reaching 100% in the second and third reviews. Specificity was 91% at the first visit, 92% at the second, and 85% at the third. Regarding predictive values, the positive predictive value was 18% at the first visit, 10% at the second, and 14% at the third, while the negative predictive value was 100% across all follow-up visits. Conclusions: The E6/E7 mRNA test appears to be an effective tool for ruling out recurrence after treatment for HSIL/CIN lesions in HPV-immunized patients.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by its poor prognosis. The current challenge remains the absence of predictive biomarkers. Cytokines are crucial factors in the pathogenesis and prognosis of PDAC. Furthermore, there is growing interest in differentiating between molecular subtypes of PDAC. The aim of our study is to evaluate the association between the analyzed cytokines and the molecular subtypes of PDAC and to determine their prognostic value. Cytokine levels were measured in 73 patients, and molecular subtypes were analyzed in 34 of these patients. Transforming Growth Factor Beta 2 (TGF-β2) levels were independently associated with the basal-like and null subtypes. In patients with locally advanced and metastatic PDAC, elevated levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-9, and IL-15 were associated with a higher risk of progression during first-line treatment, and increased levels of IL-1β, IL-6, IL-8, IL-9, and IL-15 were related to increased mortality. Furthermore, a significant association was observed between higher percentiles of IL-6 and IL-8 and shorter progression-free survival (PFS) during first-line treatment, and between higher percentiles of IL-8 and shorter overall survival (OS). In the multivariate analysis, only elevated levels of IL-8 were independently associated with a higher risk of progression during first-line treatment and mortality. In conclusion, the results of our study suggest that cytokine expression varies according to the molecular subtype of PDAC and that cytokines also play a relevant role in patient prognosis.

In the follow-up of treated high-grade cervical intraepithelial neoplasia (HSIL/CIN) lesions, cer-vical cytology has a high false-negative rate, while high-risk human papillomavirus (HR-HPV) DNA testing showed high sensitivity and lower specificity. The detection of messenger RNA of the HR-HPV E6 and E7 oncoproteins (E6/E7 mRNA) seems to be an indicator of viral integration and it allows the identification of severe lesions. Our objective was to assess the clinical utility of E6/E7 mRNA determination in the follow-up of patients treated for HSIL/CIN. A retrospective obser-vational study including 407 patients treated for HSIL/CIN was performed. The recurrence rate and the validity of E6/E7 mRNA testing were evaluated. The recurrence rate of high-grade lesions was 1.7%. The sensitivity of the test was 88% in the first clinical revision and 100% in the second and third revisions. Specificity was 91% in the first revision, 92% in the second revision, and 85% in the third revision. The positive predictive value was 18% in the first medical revision, 10% in the second and 14% in the third. The negative predictive value was 100% in all follow-up visits. In conclusion, the E6/E7 mRNA test seems to be effective in ruling out recurrence after treatment for HSIL/CIN lesions.