Intraprocedural O-arm computed tomography-guided navigation with ventilatory strategy for atelectasis electromagnetic navigation bronchoscopic biopsy of peripheral lung lesions: an IDEAL stage 2a study

Introduction

Electromagnetic navigation bronchoscopy (ENB) has been utilized for pulmonary nodule diagnosis since 2000, gaining attention due to its theoretical capacity for whole-lung accessibility (1). However, its diagnostic yield remains suboptimal, with the largest multicenter prospective studies reporting rates of only about 77% for peripheral pulmonary lesions (2).

The primary limitation of ENB accuracy is computed tomography (CT) to body divergence (CTBD)—the discrepancy between preprocedural CT imaging and intraprocedural lung architecture (3). This arises from two key factors: atelectasis and CT data mismatch (4).

Atelectasis occurs frequently during ENB procedures, with the I-LOCATE trial demonstrating an 89% incidence in anesthetized patients undergoing tracheoscopy, resulting in deviation in the location of the target lesion (5). Although ventilation strategy modifications have been attempted to eliminate CTBD (6,7), the improvement in accuracy was relatively limited.

Importantly, the entire spectrum of current ENB technologies - encompassing the latest robotic platforms (Ion^TM and Monarch^TM) - relies exclusively on preprocedural CT data collected while patients are awake and in a state of deep inspiration. This creates an inherent mismatch with the anesthetized, mechanically ventilated state during actual ENB procedures, inevitably leading to deviation of nodule location.

To address these limitations, we developed intraprocedural CT-guided navigation with ventilatory strategy for atelectasis (ICNVA)-ENB. This innovative approach: (I) uses real-time intraprocedural CT (acquired post-intubation under anesthesia) for navigation planning; and (II) incorporates an optimized ventilation protocol to minimize atelectasis. Theoretically, ICNVA-ENB should significantly improve ENB accuracy. Therefore, we decided to explore the value of ICNVA-ENB.

The evaluation of innovative surgical techniques poses unique methodological challenges distinct from those encountered in assessing established clinical interventions. These challenges stem primarily from two inherent characteristics of surgical innovation: procedural invasiveness and irreversibility. These features demand (I) comprehensive understanding of disease pathophysiology; (II) advanced technical proficiency; and (III) systematic management of the learning curve associated with new technologies. Currently, standardized evidence requirements for evaluating surgical innovations remain undefined.

To address this gap, the IDEAL Collaboration (Idea, Development, Exploration, Assessment, Long-term follow-up) has established a structured framework to guide surgical innovation (8,9). The IDEAL framework specifically advocates for development studies to document early-phase investigations, ensuring methodological transparency and comprehensive reporting—particularly crucial for techniques undergoing rapid iterative refinement. Such development studies require sequential outcome reporting and explicit documentation of all technical modifications during the investigation (Table 1). Our center’s preliminary studies have established the safety profile and initial efficacy of the ICNVA strategy, corresponding to IDEAL stage 1 (4,10). This specific study represents the first IDEAL stage 2a (developmental phase) investigation, implementing the ICNVA-ENB strategy in a human cohort to evaluate its application in ENB. We present this article in accordance with the TREND reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1312/rc).

Methods

Ethics statement

This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of The First Affiliated Hospital, Jiangxi Medical College, Nanchang University (approval No. 2022008). Written informed consent was obtained from patients and/or their immediate family members.

Preparation and prior experience

This single-center prospective cohort study was conducted according to IDEAL framework stage 2a (developmental phase) guidelines. After training supplied by Medtronic^TM, our institution authorized one doctor to use the SuperDimension navigation system (version 7.0, Medtronic, Minneapolis, MN, USA) for ENB biopsy of peripheral lung lesions beginning in September 2018. This operator subsequently maintained an annual volume of approximately 50 ENB procedures, establishing procedural competency prior to implementing the ICNVA-ENB technique.

The initial ICNVA-ENB procedure was successfully performed in March 2022, marking the beginning of an ongoing process of technical optimization. As illustrated in Figure 1, the evolutionary timeline of ICNVA-ENB refinement included: (I) including positive end-expiratory pressure (PEEP) reduction in June 2022; (II) the use of an endobronchial ultrasonography (EBUS) needle to establish puncture tunnels in August 2022; (III) the use of Wang’s needle to establish puncture tunnels in September 2022; and (IV) the adjustment of the CT scanning area in January 2023.

Figure 1 Modifications to the ICNVA-ENB strategy over time. CT, computed tomography; EBUS, endobronchial ultrasonography; ENB, electromagnetic navigation bronchoscopy; ICNVA, intraprocedural computed tomography-guided navigation with ventilatory strategy for atelectasis; PEEP, positive end-expiratory pressure.

Inclusion and exclusion criteria

Prior to the procedure, all patients underwent a chest CT scan, which revealed that their pulmonary lesions were located in the outer third of the lungs. All lesions had undergone more than 1 year of follow-up, and the lesions had increased in size or solid components. After multidisciplinary treatment, both radiologists, oncologists, and thoracic surgeons agreed that the lesion was malignant.

The evaluation results revealed that the patient could tolerate surgical resection of pulmonary nodules. The patients agreed to undergo pulmonary lesion ICNVA-ENB biopsy before surgery.

Patients with lesion diameters ≤6 mm or >3 cm, patients with more than one lesion that needed ENB biopsy, pregnant patients, those with a history of bronchial asthma, severe pneumothorax, rib fractures, severe abdominal or thoracic aortic aneurysm, pleural effusions, ascites, or diaphragmatic paralysis were excluded from the study.

Research design and changes

In accordance with the recommendation of IDEAL, we recorded the main outcomes of each patient sequentially. When we changed surgical techniques or indications, we annotated where the changes occurred.

For all patients, general characteristics and ENB-related data were collected. The ENB-related data included procedure-related complications, ENB operation time, radiation dose, probe-lesion distance in CT, successful probe arrival rate in CT, correct diagnosis rate, ENB detection rate, and CTBD.

The data were subjected to statistical analysis in this study using the statistical software package Statistical Package for the Social Sciences (SPSS) (version 25.0). All normally distributed continuous variables were presented as mean ± standard deviation (SD). Categorical variables were presented as frequencies (%).

ICNVA-ENB procedure

After general anesthesia and bronchoscope implantation, we used the lung navigation ventilation protocol (LNVP) (11) to eliminate atelectasis (Figure 2). Subsequently, O-arm CT (Siemens Somatom Confidence 64 sliding gantry, Siemens Healthcare, Forchheim, Germany) was used to scan the lungs, and the Digital Imaging and Communications in Medicine (DICOM) format file was exported to the SuperDimension navigation system for navigation path planning (Figure 3). By following the preset navigation path, we completed the ENB operation when the navigation probe reached the target lesions in the SuperDimension navigation system. CT was reviewed to confirm the location of the navigation probe and whether there were any complications (pneumothorax, bleeding, etc.).

Figure 2 Flow charts demonstrating the LNVP (left), VESPA (middle), and ICNVA (right) ventilation strategies. FiO₂, fraction of inspired oxygen; IBW, ideal body weight; ICNVA, intraprocedural computed tomography-guided navigation with ventilatory strategy for atelectasis; LNVP, lung navigation ventilation protocol; PC-VG, pressure control volume guaranteed; PCV, pressure-controlled ventilation; PEEP, positive end-expiratory pressure; VCV, volume-controlled ventilation; VESPA, ventilatory strategy to prevent atelectasis; Vt, tidal volume.

Figure 3 Schematic diagram of ICNVA-ENB machine placement. (A) Bronchoscopy station. (B) Anesthesia station. (C) O-arm CT image. (D) ENB operation station. (E) Slide of O-arm CT. CT, computed tomography; ENB, electromagnetic navigation bronchoscopy; ICNVA, intraprocedural computed tomography-guided navigation with ventilatory strategy for atelectasis.

Then, we aligned the navigation catheter and inserted and advanced a biopsy tool toward the targeted lesion. To ensure accurate positioning, a CT scan was performed on the patient to confirm the visibility of the biopsy tool within the lesion. Following the CT scan, we utilized rapid on-site evaluation (ROSE) (Figure 4).

Figure 4 Flow charts demonstrating the ENB and biopsy procedures. APL, adjustable pressure-limiting; CT, computed tomography; DICOM, Digital Imaging and Communications in Medicine; ENB, electromagnetic navigation bronchoscopy; PCV, pressure-controlled ventilation.

After the ENB operation and ROSE, we informed the patients’ immediate family members of ROSE results, and all of them signed and agreed to the nodule resection surgery. Thus, in the end, we localized pulmonary lesions by injecting indocyanine green under the guidance of ENB and resected the lesions under the fluorescence thoracoscopy.

Statistical analysis

Statistical analysis was performed using SPSS software (version 27.0; IBM Corp., Armonk, NY, USA). Continuous variables are presented as mean values with their corresponding SDs. Categorical variables are presented as counts and percentages.

Results

Fifty consecutive participants were included in this study from March 2022 onward. 32 males and 18 females, aged 25–82 years, underwent ICNVA-ENB. Among them, 2 (4%) patients developed pneumothorax, and 2 (4%) patients experienced bleeding. These patients all recovered well after conservative treatment without surgical intervention. Table 2 provides information on the characteristics of all patients.

The evolution of the ICNVA-ENB procedure

For the entire series, we made four modifications to the ICNVA-ENB strategy through experience. All the ENB data of the patients and the pathological diagnoses are shown in Tables 3,4.

First modification

Initially, we used the LNVP (11) to eliminate atelectasis (Figure 2). However, we found that the first three patients all developed procedure-related hypotension during ENB operation, requiring vasoactive drugs to maintain blood pressure. In the LNVP strategy, the PEEP recruitment maneuvers were hand-delivered by bagging with 30 cmH₂O over 30 seconds or 40 cmH₂O over 40 seconds (6). Excessive airway pressure can eliminate atelectasis completely; however, it also increases the risk of intraoperative hypotension (13).

In this study, we used CT data obtained after general anesthesia and bronchoscope implantation for ENB path planning, which was consistent with the patient’s state during the ENB operation. In other words, the position of the nodules in the navigation preset was the same as the actual position during the operation process. Therefore, for most target nodules, mild atelectasis is permissible.

After case 7, milder modified recruitment maneuver mode was applied (increment-decrement recruitment maneuver) (Figure 2). We selected the pressure-controlled ventilation (PCV) mode. Meanwhile, we set inspiratory pressure at 10–15 cmH₂O and PEEP at 5 cmH₂O. Then we increased the PEEP by 5 cmH₂O each time until it reached 35 cmH₂O, and then decreased the PEEP by 5 cmH₂O each time until it reached 5 cmH₂O. Every PEEP changing sustained for five complete respiratory processes.

In order to maintain pulmonary in inflation state while following the principle of lung ventilation protection (13). We set inspiratory pressure to maintain the end expiratory carbon dioxide pressure at 35–45 mmHg (usually 10–15 cmH₂O) and peak airway pressure to 30 cmH₂O.

And previous study on another ventilatory strategy to prevent atelectasis (VESPA) has shown that the dorsal and posterior basal segments often have a higher incidence of atelectasis (7). Considering the impact of excessively high PEEP on the circulatory system, excessive PEEP settings in LNVP were abandoned. Referring to LNVP and VESPA, we modified the ventilation strategy by reducing the PEEP level. For pulmonary nodules within 1 cm of the subpleura in the dorsal and posterior basal segments, the PEEP was set at 10–15 cmH₂O. For other pulmonary nodules, the PEEP was set at 5–8 cmH₂O. The lowest PEEP levels were selected as long as atelectasis did not affect the identification of pulmonary nodules in the intraoperative CT data. Figure 5 shows the comparison of atelectasis under the LNVP and modified ventilation protocol.

Figure 5 Comparison of atelectasis under the LNVP and modified ventilation protocol. (A) Chest CT image showed mGGO (red arrow) in the right upper lobe. (B) According to the LNVP, atelectasis was almost completely eliminated in the reviewed CT image. (C) According to our modified ventilation protocol, the CT image revealed mild lower lobe atelectasis, but atelectasis did not affect the identification of upper lobe nodules in the CT data. CT, computed tomography; mGGO, mixed ground glass opacity; LNVP, lung navigation ventilation protocol.

After this gentler ventilation strategy was used, the accuracy data (probe-lesion distance in CT, successful probe arrival rate in CT, correct diagnosis rate, ENB detection rate, and CTBD did not decrease significantly, while the incidence of intraoperative hypotension decreased significantly.

Second modification

Beginning with Case 18, for nodules lacking direct bronchial connections, we employed an EBUS puncture needle (NA-201SX-4021, Olympus, Tokyo, Japan) to create a working tunnel at the opening of segmental bronchi. This approach facilitated access to the targets while minimizing vascular interference.

We observed that, particularly for pulmonary nodules without direct bronchial communication, the ENB probe frequently displaced adjacent lung tissue toward the nodule, resulting in discrepancies between the target nodule’s location in postoperative CT scans and its position in intraoperative CT data (acquired after general anesthesia intubation). By utilizing the EBUS puncture needle, we reduced the degree of target nodule shifting. The CTBD decreased from 8.72±1.42 to 7.15±0.96 mm, while accuracy data—including probe-lesion distance on CT, successful probe arrival rate, diagnostic yield, and ENB detection rate—all improved.

Figure 6 illustrates the comparative reduction in nodule displacement before and after implementing the puncture needle technique to establish a working channel.

Figure 6 Comparison of the degree of nodule shifting before and after using a puncture needle to establish a working channel. (A) Before establishing working channel. (B) After establishing working channel. The shift in (A) was greater than that in (B). The physical three-dimensional motion of the lesion by using the main carina as a common point of translation (red, green and blue dots represent the positions of the target lesion in pre-ENB CT, anesthesia CT and post-ENB CT, respectively). Please refer to the Appendix 1 for a more detailed description. CT, computed tomography; ENB, electromagnetic navigation bronchoscopy.

Third modifications

Beginning with Case 22, we substituted the EBUS puncture needle with Wang’s needle (MW-319) to establish working tunnels for nodules lacking direct bronchial connections. The EBUS needle’s limited flexibility restricted puncture tunnel creation to second-level bronchial openings, often complicating vascular avoidance—particularly for challenging locations (e.g., posterior segment lesions). In two cases, this limitation prevented the probe from reaching within 1 cm of the target nodule.

The MW-319 needle’s superior bending amplitude resolved this issue (14). Post-implementation, both the average probe-to-lesion distance and CTBD significantly decreased compared to EBUS needle results (6.77±1.78 vs. 4.98±2.25 mm and 7.15±0.96 vs. 5.25±1.28 mm, respectively), indicating enhanced ENB accuracy.

Fourth modifications

Through these modifications, the probe achieved precise access to the target area, eliminating the need for full pulmonary CT scans. Beginning with Case 30, to verify probe positioning, we performed limited O-arm CT scans centered on the target nodules, acquiring 30 contiguous 1-mm slices above and below each lesion. This refined approach significantly reduced patient radiation exposure while maintaining diagnostic accuracy for nodule identification.

Discussion

Guided bronchoscopy comprises a range of minimally invasive endoscopic techniques for diagnosing indeterminate pulmonary nodules. Current guidance modalities include ENB (12,15) and robotic-assisted bronchoscopy (RAB) (16,17), among others. Compared to transthoracic biopsy, guided bronchoscopy demonstrates a superior safety profile (2,18) and is particularly valuable for accessing small peripheral lesions beyond the reach of conventional bronchoscopy (19). However, the diagnostic accuracy of both ENB and RAB remains constrained by CTBD.

CTBD arises from multiple procedural and preprocedural factors. Procedural contributors include anesthesia-induced atelectasis, while preprocedural factors encompass variations in lung volume, as well as differences in CT scan timing and acquisition parameters.

Previous studies indicated that atelectasis develops in 87–100% of healthy adults within minutes of general anesthesia induction (5,20,21). This phenomenon compromises the fidelity of virtual navigation maps, leading to a deviation in the location of the target lesion and reducing lesion visibility on intraprocedural imaging (3). While several studies have investigated ventilation strategies to eliminate atelectasis (6,7), the improvement in ENB accuracy was modest.

Bhadra et al. (6) demonstrated that compared to conventional ventilation, LNVP significantly reduced atelectasis and improved ENB accuracy to 92%. While these results appeared promising, our initial experience implementing LNVP-ENB for lung nodule biopsies yielded unsatisfied results. We attribute these unsatisfactory results primarily to CT data mismatch issues.

Existing ENB studies, including both LNVP strategy (6) and RAB investigations (22,23), universally utilize preoperative CT scans acquired during end-inspiratory breath-hold at near-total lung capacity (TLC) for navigation planning (3,6,7,11,12,24). While this approach optimizes small airway visualization (22), it creates a fundamental physiological discrepancy: ENB procedures are performed under general anesthesia with mechanical ventilation, representing a substantially different pulmonary state from the preoperative CT acquisition. Consequently, positional deviation of target nodules becomes inevitable. In other words, after determining navigation path planning, the operator must still navigate to a virtual lung lesion that may be in a different location than the preprocedural CT (3).

To address these limitations, we implemented a modified approach utilizing intraprocedural CT data (acquired after general anesthesia induction and bronchoscope placement) for ENB navigation planning, combined with the LNVP strategy to minimize atelectasis. This innovation established the foundational framework of our ICNVA-ENB technique, which synergistically integrates real-time CT guidance with optimized ventilation management. Having established this protocol, we decided to explore its value and make further improvements.

During our initial experience with ICNVA-ENB prior to technical modifications, we observed a concerning incidence of intraoperative hypotension, with some cases requiring vasopressor support. Our study data revealed that the first three consecutive patients all experienced significant intraprocedural blood pressure reductions. In the LNVP strategy, recruitment maneuvers were performed with a tidal volume of 10–12 cc/kg ideal body weight. Differential PEEP was applied for upper/middle lobe lesions (10–15 cmH₂O) and lower lobe lesions (15–20 cmH₂O). The airway pressure was then maintained at 40 cmH₂O for 40 seconds (25). While these parameters effectively reduced atelectasis, we recognized that the elevated airway pressures likely contributed to hemodynamic compromise through decreased venous return (13).

These observations prompted us to re-evaluate the necessity of maintaining high airway pressures. The original rationale for implementing elevated airway pressure and PEEP in the LNVP protocol was to minimize CTBD resulting from post-intubation atelectasis. In previous studies, navigation path planning CT data used for navigation path planning were obtained without atelectasis (25). Consequently, complete elimination of atelectasis is essential to ensure precise correlation between the intraoperative target nodule position and its virtual representation in the navigation map.

In our ICNVA-ENB approach, we utilized intraprocedural CT data acquired after anesthesia induction and bronchoscope placement for navigation planning, ensuring consistency between the imaging state and actual procedural conditions. This fundamental alignment meant that nodule positions in the virtual navigation map precisely matched their real-time anatomical locations during the procedure. Consequently, we determined that mild atelectasis could be tolerated for most target nodules, provided it did not compromise nodule identification.

This paradigm shift allowed us to modify our ventilation strategy in two key aspects:

• Pressure management: we abandoned the goal of complete atelectasis reversal and instead maintained consistent lung volumes using the adjustable pressure-limiting (APL) valve—a flow control valve that regulates circuit pressure during breath-holding maneuvers (11).
• Recruitment technique: we replaced the aggressive LNVP protocol (40 cmH₂O for 40 seconds) with a gradual incremental-decremental approach based on lung-protective ventilation principles, employing lower pressure thresholds [detailed in our prior publication (4)].

This optimized ventilation strategy maintained diagnostic accuracy while significantly reducing the incidence of intraoperative hypotension.

With accumulating case experience, we identified particular challenges in accessing nodules lacking direct bronchial communication, especially those oriented perpendicular to the airways. These lesions required multiple CTBD adjustments for accurate probe placement. Our procedural analysis suggested this limitation was primarily equipment-related. The SuperDimension navigation system’s relatively large probe diameter necessitates longer advancement to reach the pulmonary nodules at the distal end of the natural trachea. During this process, it is inevitable that lung tissue will be squeezed toward the nodules, resulting in positional deviation between the intended and actual probe placement.

To address this, we initially employed an EBUS puncture needle to establish vascular-sparing puncture tunnel at secondary-level protrusion, and send the probe from the puncture tunnel to the nodules. However, the needle’s rigidity proved particularly limiting for apical upper lobe nodules, often preventing optimal angulation. After encountering this limitation in four cases, we implemented a further technical modification by switching to the more flexible MW-319 needle.

By using MW-319 puncture needle, we can achieve a larger puncture angle and establish a tunnel at the level of the third-level protrusion or even further away. Through these improvements, we found that the probe-lesion distance was reduced compared with that before without increasing complication rates.

In the final optimization phase, we implemented a reduced-range CT scanning protocol to minimize patient radiation exposure while maintaining procedural safety and diagnostic efficacy. This modified imaging approach achieved significant dose reduction without compromising nodule identification capability.

Previous research on bronchoscopy revealed various techniques and improvements to increase accuracy, including the use of more advanced platforms, real-time advanced imaging technology (radial endobronchial ultrasound, cone-beam CT, augmented and fused fluoroscopy), and modified ventilator strategies, and etc. (3,22,26,27).

Since 2018, RAB has emerged, including the Food and Drug Administration-approved Monarch^TM Platform by Auris Health (Redwood City, CA, USA) and the Ion^TM endoluminal robotic bronchoscopy platform by Intuitive Surgical (Sunnyvale, CA, USA). Additionally, the Galaxy System (Noah Medical, San Jose, CA, USA) is still in the clinical research stage (23). The Monarch^TM platform uses electromagnetic navigation (EMN) in conjunction with the insertion distance and image/airway recognition for guidance. On the other hand, the Ion^TM platform employs shape sensing (SS) technology integrated with an embedded fiber optic sensor that continuously measures the shape of the catheter multiple times per minute. Combining navigational bronchoscopy with real-time advanced imaging technology to increase diagnostic accuracy is a common solution strategy.

Despite technological advancements in bronchoscopic navigation systems—including SS, EMN, and other modalities—CTBD remains a persistent clinical challenge. The underlying etiology stems from a fundamental discordance between preoperative CT imaging data utilized for navigation planning and the dynamic anatomical positioning of pulmonary structures during the actual procedure. Consequently, current approaches primarily enhance diagnostic yield through real-time error detection and compensatory adjustments, rather than addressing the root pathophysiology of CTBD (14).

This study introduces a novel application of intraprocedural CT data for ENB path planning in our ICNVA-ENB protocol, representing the first reported approach to fundamentally address CTBD. Our methodology incorporated two key innovations: (I) real-time CT-guided navigation to eliminate positional discrepancies; and (II) an optimized ventilation strategy that balanced atelectasis reduction with hemodynamic stability. Conducted in accordance with IDEAL stage 2a recommendations, this work provides a comprehensive, sequentially documented account of our technical evolution, offering valuable insights for subsequent research while minimizing redundant efforts.

Preliminary investigations demonstrated the high accuracy of ICNVA-ENB, as previously reported (4,10). This IDEAL stage 2a study further establishes the procedural feasibility and safety profile of this approach. However, there are several limitations in this study. First, the mandatory intraoperative CT imaging increases radiation exposure despite our dose-reduction protocols. While we prioritize targeting accuracy given current technical constraints, we are developing an AI-based predictive algorithm using preoperative CT data to potentially eliminate intraoperative scanning. Second, this study was conducted via an ENB platform rather than a more precise RAB platform. Third, in this study, all the procedures were completed by the same operator. The widespread applicability of this technology is currently insufficient. Finally, this was a single-center study with a small sample size, and further research is needed for validation. To address these limitations, we have initiated a registered clinical trial (Chinese Clinical Trial Registry: ChiCTR2400090784; registered October 13, 2024) to evaluate ICNVA-ENB safety and accuracy in larger populations using RAB platforms.

Conclusions

ICNVA-ENB combines intraprocedural CT data for ENB path planning and a milder ventilation strategy for the first time, which fundamentally eliminates CTBD and ensures safety. This IDEAL stage 2a study showed significant improvement in accuracy without significant complications. ICNVA-ENB may be a safe and effective strategy for the diagnosis and treatment of pulmonary lesions.

Acknowledgments

We sincerely thank Prof. Zhou An (The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China) for providing technical guidance.

Footnote

Reporting Checklist: The authors have completed the TREND reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1312/rc

Data Sharing Statement: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1312/dss

Peer Review File: Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1312/prf

Funding: This work was supported by grants from the National Key Research and Development Program of China (No. 2023YFC25086), Clinical Research Cultivation Project of the First Affiliated Hospital of Nanchang University (No. YFYLCYJPY202430), and the Key Project of Science and Technology Innovation of Jiangxi Provincial Health and Wellness Commission (No. 2024ZD004).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1312/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of The First Affiliated Hospital of Nanchang University (approval No. 2022008). Written informed consent was obtained from patients and/or their immediate family members.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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