Introduction: Diagnosis of peripheral lung nodules and masses can be achieved through various techniques, including bronchoscopy, CT-guided needle biopsy, and video-assisted thoracoscopic surgery. Advances in bronchoscopy, such as radial endobronchial ultrasound (r-EBUS), have enhanced the appeal of transbronchial biopsy (TBBx) approaches. Reported diagnostic yields (DY) for flexible bronchoscopy combined with r-EBUS in clinical trials range from 46% to 88%. New navigation platforms, including shape-sensing robotic-assisted bronchoscopy (ssRAB), have emerged, offering different DYs. The addition of cone-beam computed tomography (CBCT) has been shown to improve DY by enabling real-time confirmation of biopsy tool positions. However, comparative studies of conventional bronchoscopy and these newer technologies are limited. This study aimed to compare the diagnostic yield of flexible bronchoscopy with r-EBUS and cryobiopsy to that of ssRAB with CBCT, r-EBUS, and cryobiopsy for sampling pulmonary lesions. Methods: A retrospective comparative study was conducted, involving patients who underwent RB/FB/r-EBUS/cryobiopsy at a center in Mexico and those who underwent ssRAB/CBCT/r-EBUS/cryobiopsy at two centers in the USA. Diagnostic yield was assessed through the detection of malignancy or specific benign histological findings at bronchoscopy and follow-up for cases with non-specific benign results. Results: FB/r-EBUS/cryobiopsy (Group 1) was used to biopsy 224 nodules, while ssRAB/CBCT/r-EBUS (Group 2) cryobiopsy was used for 239 nodules. The median lesion size in Group 1 was 34 mm, compared to 13 mm (IQR) for Group 2 (P < 0.001). The proportion of nodules <2 cm was significantly higher in the Group 2 (89.1%) versus the Group 1 (37.1%) (P < 0.001). Diagnostic yield with follow-up was 71% for Group 1 and 91% for Grouo 2 (P < 0.001). For nodules ≤2 cm, DY was 45% for Group 1 and 91% for Group 2 (P < 0.001). For nodules >2 cm, DY was 74% for Group 1 and 84% for Group 2 (P < 0.001). Sensitivity and diagnostic accuracy were higher for Group 2 (87% and 91%) compared to Group 1 (58% and 71%) (P < 0.001). Adverse events, particularly bleeding, were more frequent in Group 1 (18.8%, P < 0.001), while the incidence of pneumothorax remained low (<3%) in both groups. Conclusion: The ssRAB/CBCT/r-EBUS/cryobiopsy approach demonstrated a higher diagnostic yield than the conventional FB/r-EBUS/cryobiopsy approach, particularly in nodules smaller than 2 cm. The addition of CBCT and robotic assistance improved procedural outcomes and reduced the incidence of bleeding, without increasing other adverse events. Prospective studies are warranted to further validate these findings.

RATIONALE Bronchoscopic treatment of malignant lung nodules may offer unique advantages, however this area of research remains in an early phase. Treat and resect study is warranted to optimize safety and efficacy. METHODS We report initial results of a single-center phase one study of bronchoscopic microwave ablation followed by standard of care surgical resection in patients with peripheral lung malignancy (≤30 mm in diameter and >5 mm from the pleura). Following evaluation by a multi-disciplinary team, bronchoscopy was performed for mediastinal staging and target nodule sampling via shape-sensing robotic assisted bronchoscopy with cone beam CT imaging and intraoperative pathologic analysis. If stage 1A lung cancer was confirmed, bronchoscopic microwave ablation was performed using the AveCure® microwave probe (MedWaves Inc., San Diego, CA). Settings for ablation used manufacturer guidelines based on preclinical and percutaneous ablation data. CT imaging was obtained intraoperatively ten minutes post-ablation and in follow-up 2 weeks post-ablation. Surgical resection was performed 2-4 weeks post-ablation. RESULTS Five patients underwent bronchoscopic microwave ablation followed by surgical resection. Histologic subtype of lung cancer, total energy applied, ablation zone size, and percentage of viable tumor is summarized in table 1. Microwave ablation was performed at 80°C for 10 minutes in four cases with one case (patient 5) receiving bracketed ablation for two treatments at 80°C for 10 minutes. Two patients underwent wedge resection while three patients required lobectomy. Two of five patients were noted to have extensive hilar scarring at the time of resection. There were no adverse events across the first four patients. The fifth patient who underwent a bracketed ablation had trace pneumothorax and mild post-ablation syndrome. Upon resection, an abscess in the ablation zone was encountered which ruptured into the pleural space during surgery, however the resection was completed without complication and the patient was discharged the next day. All five patients were well upon routine follow-up. CONCLUSIONS Our single-center experience with bronchoscopic microwave ablation shows promising safety, feasibility, and preliminary efficacy. Following our initial experience, we conclude: i) Further preclinical study is needed to safely implement bracketed ablation. ii) Recruitment of patients who require non-anatomic resection may mitigate surgical resection complexity and risk of complications. iii) Further optimization is needed to ensure complete ablation of tumor, improve understanding of association of post-ablation imaging and pathology, and to gather further safety data. This trial will soon expand to multicenter with four additional study sites.

Epstein-Barr virus (EBV) is a ubiquitous human gammaherpesvirus implicated in a wide spectrum of inflammatory and malignant diseases. Although EBV toggles between latent and lytic states, the host cues that control this switch remain incompletely defined. Interleukin-17A (IL-17A; hereafter IL-17), a signature Th17 cytokine, is abundant in EBV-associated tissues, and EBV products can augment IL-17 responses. Whether IL-17 directly modulates the EBV life cycle has remained unknown. Here we show that IL-17 alone is sufficient to induce EBV lytic reactivation in latently infected human B cells. Across RT-qPCR, immunoblotting, and RNA-seq, IL-17 increased the immediate-early regulator BZLF1 (Zta) and upregulated downstream early and late viral genes, consistent with activation of a transcriptome-wide lytic program. Culture supernatants from IL-17-treated cells contained elevated DNase-resistant extracellular EBV DNA, indicating productive replication with encapsidated genomes. Transcriptomic pathway analyses confirmed engagement of IL-17-linked signaling and highlighted inflammatory modules, including NF-κB and JAK-STAT. Gene Ontology analysis further enriched for regulation of B-cell receptor signaling and B-cell activation, situating IL-17 within B-cell inflammatory circuitry. Together, these findings identify IL-17 as a cytokine cue for EBV lytic entry and provide a mechanistic link between Th17-skewed inflammation and episodic EBV reactivation. This cytokine-driven pathway complements existing models centered on B-cell receptor signaling, hypoxia/HIF-1α, COX-2/PGE₂, and TGF-β and motivates testing whether modulation of the IL-17/IL-17R axis can alter EBV reactivation in IL-17-rich settings. To our knowledge, this is the first demonstration that IL-17 alone directly triggers EBV lytic reactivation in human cells. IMPORTANCE:Epstein-Barr virus (EBV) persists for life by maintaining latency with intermittent lytic reactivation, yet the physiological cues that initiate the latency-lytic switch remain poorly defined. Here we identify the Th17 cytokine interleukin-17A (IL-17) as a direct host trigger of EBV lytic reactivation in latently infected human B cells. IL-17 alone induced the immediate-early transactivator Zta, activated a transcriptome-wide lytic program, and promoted release of DNase-resistant extracellular EBV DNA consistent with encapsidated virions. Transcriptomic analyses confirmed engagement of IL-17-linked inflammatory modules and implicated convergence on signaling nodes shared with canonical B-cell receptor pathways. These findings establish a mechanistic link between Th17-skewed inflammation and EBV reactivation burden, providing a framework to interrogate how IL-17-rich microenvironments influence EBV dissemination and immunopathology and to evaluate whether targeting the IL-17/IL-17R axis can modulate EBV reactivation in disease settings.

Successful procedural training is a universal concern for pulmonary and critical care medicine (PCCM) program directors. Bootcamps may provide a unique and often first opportunity for intense, immersive procedural learning without exposing patients to harm. New trainees must otherwise learn on the job while acclimating to unfamiliar environments and responsibilities. Our goal was to create a structured regional educational event conducted early in fellowship. We aspired to optimize familiarity with procedures and equipment, allay stress among trainees, and create a collaborative learning environment through sharing of simulation equipment and faculty among programs. This article outlines the design, implementation, and lessons learned from this 1-day, multidisciplinary PCCM and critical care medicine procedural bootcamp in the southwest region of the United States. The bootcamp program was designed as learner centered, with educational and experiential goals and feasibility in mind, using a flipped classroom model and testing to maximize time for psychomotor skills building. A multidisciplinary approach enriched the learning environment, modeled team-based procedural care, and fostered interprofessional collaboration. Assessments measured pre-knowledge and post-knowledge acquisition as well as gauged learner performance using checklists and small group interaction. Evaluation of feedback from learners, faculty, and participating programs allowed for yearly iterative improvements. We share these lessons learned as a model for other scalable and impactful medical education initiatives.

Microwave ablation is a well-established therapeutic option for percutaneous treatment of lung tumors, however transbronchial microwave ablation remains under investigation. Our study aims to evaluate the safety and feasibility of transbronchial microwave ablation for lung cancer using state of the art bronchoscopy and imaging platforms and a microwave ablation system featuring tumor permittivity feedback control. This study is an investigator initiated multicenter prospective diagnose-stage-treat, then resect, trial designed to evaluate the safety and feasibility of bronchoscopic microwave ablation. Patients with surgically resectable, treatment-naïve primary lung cancer tumors ≤ 3.0 cm will undergo shape sensing robotic assisted bronchoscopy (ssRAB) with cone-beam CT imaging for diagnostic sampling. Following intraoperative pathologic verification of malignancy, transbronchial microwave ablation will be performed. Cone-beam CT imaging will be used for verification of microwave probe position and for evaluation of ablation zone. Dedicated CT chest will be performed two weeks post-ablation. Two to four weeks following ablation patients will undergo standard of care surgical resection. Post-resection histopathologic analysis will evaluate treatment effect. Enrollment began March 2024 as a single-center study. The study will transition to multi-center to increase recruitment and improve generalizability. This study will be a first of its kind using shape sensing robotic assisted bronchoscopy and cone-beam CT for transbronchial microwave ablation. Our treat and resect design will provide short-term clinical safety data and vital treatment effect data. This trial is registered at ClinicalTrials.gov (Identifier: NCT05281237 ). This study was prospectively registered on March 15, 2022.

Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease characterized by progressive, irreversible lung scarring. Immune dysfunction contributes to IPF pathogenesis, although the role of adaptive immunity is not well understood. In this study, we explored the transcriptional landscape of immune cells in bronchoalveolar lavage (BAL) from IPF patients. Methods: BAL from human subjects with IPF (n = 8) and non-IPF lung diseases (n = 8) were collected under the Tulane University Biomedical IRB (2021-713). The cellular component of BAL was subjected to single cell RNA sequencing (scRNA-seq); approximately one million cells with minimum 70% viability from each subject were fixed prior to scRNA-seq analyses. Single cell capturing and subsequent library construction were carried out using the chromium fixed RNA profiling reagent kits from 10x Genomics (CG000527). The constructed library was sequenced on the Illumina platform supported by the NextGen Sequencing Core at Tulane University. Subsequent analyses were conducted using Seurat and R packages. Results: We identified 13 distinct cell clusters in BAL cells, including T and NK cells, epithelial cells, stromal cells, mast cells, plasmacytoid dendritic cells, conventional dendritic cells, neutrophils, three types of alveolar macrophages (AM1, AM2, AM3), monocyte-derived macrophages and monocytes. GSEA analysis of differentially expressed genes indicated that the IPF cohort was enriched for the following pathways” inflammatory response, KRas signaling, glycolysis, IL6-JAK-STAT3 signaling, and interferon-γ response. Furthermore, within the CD8 T cell cluster, we found an upregulation of several exhaustion markers, including PRDM1, LAG3, and CTLA4. We also observed considerable heterogeneity in the expression of these exhaustion markers across different CD8+ T cell subtypes, notably ZNF683+/CXCR6+ CD8 Trm, CD8 Trm/Temra, GZMK+ CD8 Tem, STAT1+ISG15 CXCR6+ CD8 T cells, and ZNF683+CXCR6- CD8 Trm. Conclusion: This study of BAL immune cells from patients with IPF, non-IPF chronic lung disease and a limited number of control subjects reveal notable heterogeneity of immune cell (sub)populations. Interestingly, we noted variable expression of exhaustion markers in CD8+ T cells, both across different samples and within distinct CD8+ T cell subsets. While this exploratory study of the BAL cell transcriptome may be influenced by multiple factors such as age, co-morbidities, smoking history, exposome, and other metabolic variables, our study suggests CD8+ T cell exhaustion and immune dysfunction within the IPF alveolar microenvironment.

Background:Accurate preoperative identification of invasiveness in pulmonary part-solid nodules (PSNs) is critical to guide extent of resection and operative timing, yet reliable, automated imaging markers are limited. This study aimed to evaluate the predictive value of volumetric proportion and mean computed tomography (CT) value of solid components for the invasiveness of pulmonary PSNs using computer-aided detection (CAD). Methods:This retrospective study included 313 patients with 324 PSNs who underwent thin-section CT (TSCT) before surgery and had postoperative pathologic diagnoses of atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), or invasive adenocarcinoma (IA). The proportion of solid components at CT values of -300 Hounsfield units (HU) and -400 HU and the mean CT values of the solid components were automatically computed. The diagnostic accuracy was evaluated with the area under the receiver operating characteristic curve (AUC). The tumor size was stratified, and the optimal predictive indicators within each stratum were evaluated. Results:Among 313 patients (324 PSNs; median age 58 years), 4 AAH, 88 AIS, 69 MIA, and 163 IA were identified. The mean CT value of the solid component had an AUC of 0.795 (threshold -144.5 HU), with sensitivity 0.799, and specificity 0.696. Tumor size had an AUC of 0.784 (threshold 1.65 cm, sensitivity 0.595, specificity 0.826), and solid component size had an AUC of 0.759 (threshold 0.95 cm, sensitivity 0.804, specificity 0.509). Analysis of solid component proportion demonstrated AUCs of 0.795 and 0.783 at -300 and -400 HU, respectively, with corresponding optimal thresholds of 16.2% (sensitivity 0.706, specificity 0.814) and 31.3% (sensitivity 0.687, specificity 0.807). In the stratified analysis, the mean CT value and solid component proportion showed high AUCs in all tumor size strata. Conclusions:CAD-derived volumetric solid proportion and mean CT attenuation show promise for predicting PSN invasiveness in this single-center retrospective cohort; prospective multicenter validation with standardized protocols is warranted.

Background:Video-assisted thoracoscopic surgery (VATS) is more effective for diagnosing and treating solitary pulmonary nodules (SPNs). It is sometimes difficult to localize through use of minimally invasive techniques. We evaluated the feasibility, effectiveness, and safety of a novel localization method for SPNs. Here, we describe our technical process, perioperative results, and accumulated experience over the years. Methods:Between February 2018 and April 2023, a retrospective study of a novel claw-suture localization technique was conducted in a single center. A total of 490 patients participating in the localization of preoperative SPNs were enrolled. An anchor claw device with four hooks and three-colored sutures was used for localizing nodules under computed tomography (CT). We then evaluated the localization process and the outcomes of the operative procedure (success rate, safety, feasibility, and patient comfort). Results:A total of 510 SPNs were localized before surgery, and the median size of the nodules was 0.70 cm (range, 0.4-2.0 cm). Additionally, 97.1% of these nodules (495 of 510) were localized successfully without dislodgment or device fracture. Types of failures included not meeting the target value of the distance between the claw and lesion (n=12, 2.4%) and displacement of the device (n=3, 0.6%). Pneumothorax (n=63, 12.4%), parenchymal hemorrhage (n=46, 9.0%), and hemothorax (n=1, 0.2%) were the most common complications that did not require further medical treatment. Pleural reactions were reported in 2 patients (0.4%). A notable correlation was also found between the depth of the pulmonary nodules and the incidence of parenchymal hemorrhage (P<0.001). The median length for the entire process was 12 minutes (7-25 minutes). No patients reported significant pain during the localization process, and the device was retrieved with a 100% survival rate after VATS resection. Conclusions:This method of claw-suture localization is safe, effective, and feasible and can be used to localize SPNs that are challenging to locate before operation.

Background:Electromagnetic navigation bronchoscopy (ENB) and shape-sensing robotic-assisted bronchoscopy (ssRAB) are minimally invasive technologies for the diagnosis of pulmonary nodules. Cone-beam computed tomography (CBCT) has shown to increase diagnostic yield by allowing real-time confirmation of position of lesion and biopsy tool. There is a lack of comparative studies of such platforms using CBCT guidance to overcome computed tomography to body divergence. The aim of this study was to compare the diagnostic yield of ENB- and ssRAB-guided CBCT for biopsy of pulmonary nodules. Methods:We conducted a retrospective comparative study of consecutive patients undergoing ENB-CBCT and ssRAB-CBCT. Navigational success was defined as biopsy tool within lesion confirmed during CBCT. Diagnostic yield was assessed using two methods: (I) presence of malignancy or benign histological findings that lead to a specific diagnosis at the time of bronchoscopy, and (II) longitudinal follow-up of patients with nonspecific benign finding during bronchoscopy. Results:ENB-CBCT was used to biopsy 97 nodules and ssRAB-CBCT was used to biopsy 111 nodules. Median size of the lesion for the ENB-CBCT group was 16.5 mm [interquartile range (IQR), 12-22 mm] as compared to 12 mm (IQR, 9-16 mm) in the ssRAB-CBCT group (P<0.001). Navigational success was 70.1% in ENB-CBCT arm as compared to 83% in ssRAB-CBCT arm respectively (P=0.03). Diagnostic yield was 66% for ENB-CBCT and 89.2% for ssRAB-CBCT (P<0.001) following bronchoscopy; 79.4% for ENB-CBCT and 95.4% for ssRAB-CBCT (P<0.001) with longitudinal follow-up data respectively. Following multivariate regression analysis adjusting for the size of the lesion, distance from the pleura, presence of bronchus sign, number of CBCT spins, and number of nodules, the odds ratio for the diagnostic yield was 4.72 [95% confidence interval (CI): 2.05-10.85; P<0.001] in the ssRAB-CBCT group as compared with ENB-CBCT. The overall rate of adverse events was similar in both groups (P=0.77). Conclusions:ssRAB-CBCT showed increased navigational success and diagnostic yield as compared to ENB-CBCT for pulmonary nodule biopsies.

Background:Interstitial lung diseases (ILDs) are a group of pulmonary disorders affecting the lung's structure. Acute exacerbation of ILD (AE-ILD) following medical procedures is a significant clinical concern. Lung cryoprobe transbronchial biopsy (cryobiopsy) is a relatively new diagnostic technique for ILD, but data on AE-ILD post-cryobiopsy is limited. This study aims to fill this gap by examining the prevalence, risk factors, and outcomes of AE-ILD following cryobiopsy. Methods:This multicenter retrospective study analyzed data from patients who underwent cryobiopsy for ILD diagnosis at three U.S. institutions between January 2014 and August 2022. The study included patients over 18 years with confirmed or suspected ILD, categorized into those who experienced AE-ILD post-cryobiopsy and those who did not. Results:Out of 111 patients, 3.6% experienced AE-ILD, with a 50% mortality rate in these cases. The study cohort was predominantly white, with a median age of 69.0 years. Common comorbidities included tobacco use and hypertension. Patients who developed AE-ILD had an increased median number of biopsies. The overall 30-day mortality was 1.8%. Overall complication rate was 32%, including pneumonia, pneumothorax, AE-ILD, and bleeding requiring intervention. The study findings suggest that bronchoscopic cryobiopsy may be associated with lower overall mortality, particularly in patients with compromised lung function. Conclusions:This study provides significant insights into AE-ILD following cryobiopsy, underscoring the need for careful patient selection and procedural assessment. While cryobiopsy may offer a safer alternative to surgical lung biopsy in specific patient cohorts, the elevated risk of AE-ILD necessitates further research to optimize patient outcomes and procedural safety.

Spindle cell lesions span from benign to aggressively malignant, the most concerning being the carcinoma, sarcoma, and melanoma species. While spindle cell carcinoma is the most common spindle cell lesion found along the upper aerodigestive tract (UADT), it only accounts for <0.5% of pulmonary malignancies 1, 2. We present an adult male admitted for chest pain, who was found to have a malignant left upper lobe (LUL) spindle cell neoplasm. Three pathology departments preformed immunohistochemical analysis on various tissue specimens, searching for a speciated diagnosis, highlighting the importance of advanced immunostains for the diagnosis and subsequent treatment of these difficult lesions.

Introduction: Lung nodules are commonly encountered in clinical practice. Technological advances in navigational bronchoscopy and imaging modalities have led to paradigm shift from nodule screening or follow-up to early lung cancer detection. This is due to improved nodule localization and biopsy confirmation with combined modalities of navigational platforms and imaging tools. To conduct this article, relevant literature was reviewed via PubMed from January 2014 until January 2024. Areas covered: This article highlights the literature on different imaging modalities combined with commonly used navigational platforms for diagnosis of peripheral lung nodules. Current limitations and future perspectives of imaging modalities will be discussed. Expert opinion: The development of navigational platforms improved localization of targets. However, published diagnostic yield remains lower compared to percutaneous-guided biopsy. The discordance between the actual location of lung nodule during the procedure and preprocedural CT chest is the main factor impacting accurate biopsies. The utilization of advanced imaging tools with navigation-based bronchoscopy has been shown to assist with localizing targets in real-time and improving biopsy success. However, it is important for interventional bronchoscopists to understand the strengths and limitations of these advanced imaging technologies.

Introduction: Pheochromocytomas are neuroendocrine tumors that cause release of excess catecholamines. This release causes commonly known signs and symptoms of hypertension, tachycardia, headache, flushing, and palpitations. Less commonly seen is abdominal pain with transaminitis. Description: A 47-year-old woman with no medical history presented with one day of severe abdominal pain, nausea, vomiting, palpitations, and symptoms of feeling flushed. Initial evaluation found the patient to be hypertensive, tachycardic, and tachypneic. On CT imaging, the patient was found to have a 6.5cm ovoid adrenal mass and lab work showed elevated 24-hour urine and plasma metanephrines, consistent with pheochromocytoma. The patient’s course was complicated by the development of transaminitis (had been normal on initial lab work), with elevation to AST 4882 U/L, ALT 4183 U/L, with normal alkaline phosphatase and bilirubin. Both ultrasound and CT imaging showed intrinsic fatty liver disease with patent vasculature, though no underlying pathology in the setting of no personal history of alcohol abuse, IV drug use, and non-reactive hepatitis panel. Hepatology consulted, and etiology thought to be in the setting of poor perfusion due to catecholamine storm. With medical treatment of the pheochromocytoma, AST and ALT significantly down-trended (75% within one week), and had normalized by the patient’s adrenalectomy and have remained normal in the post-operative period. Discussion: Pheochromocytoma is a rare neuroendocrine tumor, which has varying symptomatology on presentation, though commonly includes severe hypertension with headache, sweating, and palpitations related to catecholamine surge. A less common, though still reported presenting symptom, is abdominal pain. There have been cases in the literature wherein patients with pheochromocytoma present with abdominal pain and transaminitis, though not to the degree that has been seen in our patient. The pathogenesis of this in the setting of pheochromocytoma is not completely understood, though is thought to be related to increased vascular resistance due to catecholamine release, leading to decreased blood flow and oxygenation. With medical and ultimate surgical management of pheochromocytoma, liver function tests can be expected to return to baseline values.