Pathological features of connective tissue disease-associated interstitial lung disease in transbronchial cryobiopsies.

AIM: Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies. METHODS: We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP. RESULTS: A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent. CONCLUSIONS: In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

Pathologic Criteria for the Diagnosis of Usual Interstitial Pneumonia vs Fibrotic Hypersensitivity Pneumonitis in Transbronchial Cryobiopsies.

Transbronchial cryobiopsy (TBCB) is increasingly used for the diagnosis of fibrosing interstitial pneumonias, but there are few detailed descriptions of the pathologic findings in such cases. It has been proposed that a combination of patchy fibrosis and fibroblast foci with an absence of alternative features is diagnostic of usual interstitial pneumonia (UIP; ie, idiopathic pulmonary fibrosis [IPF]) in TBCB. In this study, we reviewed 121 TBCB in which a diagnosis of fibrotic hypersensitivity pneumonitis (FHP; n = 83) or IPF (n = 38) was made by multidisciplinary discussion and evaluated a range of pathologic features. Patchy fibrosis was found in 65 of 83 (78%) biopsies from FHP and 32of 38 (84%) biopsies from UIP/IPF cases. Fibroblast foci were present in 47 of 83 (57%) FHP and 27 of 38 (71%) UIP/IPF cases. Fibroblast foci/patchy fibrosis combined did not favor either diagnosis. Architectural distortion was seen in 54 of 83 (65%) FHP and 32 of 38 (84%) UIP/IPF cases (odds ratio [OR] for FHP, 0.35; P = .036) and honeycombing in 18 of 83 (22%) and 17 of 38 (45%), respectively (OR, 0.37; P = .014). Airspace giant cells/granulomas were present in 13 of 83 (20%) FHP and 1 of 38 (2.6%) UIP/IPF cases (OR for FHP, 6.87; P = .068), and interstitial giant cells/granulomas in 20 of 83 (24%) FHP and 0 of 38 (0%) UIP/IPF (OR, 6.7 x 106; P = .000). We conclude that patchy fibrosis plus fibroblast foci can be found in TBCB from both FHP and UIP/IPF. The complete absence of architectural distortion/honeycombing favors a diagnosis of FHP, as does the presence of airspace or interstitial giant cells/granulomas, but these measures are insensitive, and many cases of FHP cannot be separated from UIP/IPF on TBCB.

Traumatic Brain Injury Practice Guidelines: Variability in U.K. PICUs.

OBJECTIVES: Traumatic brain injury in children is a leading cause of morbidity and mortality. Lack of high-quality evidence may lead to variation in management within and between PICUs. We examined U.K. pediatric traumatic brain injury management guidelines for extent of variability. DESIGN: Analysis of U.K. PICU traumatic brain injury guidelines for areas of consistency and variation among each other and against the second edition of Brain Trauma Foundation pediatric traumatic brain injury guidelines. SETTING: Not applicable. SUBJECTS: Not applicable. INTERVENTIONS: Textual analysis of U.K. PICU guidelines. MEASUREMENTS AND MAIN RESULTS: Twelve key clinical topics in three traumatic brain injury management domains were identified. We performed textual analysis of recommendations from anonymized local guidelines and compared them against each other and the Brain Trauma Foundation pediatric traumatic brain injury guidelines. Fifteen guidelines used by 16 of the 20 U.K. PICUs that manage traumatic brain injury were analyzed. Relatively better consistency was observed for intracranial pressure treatment thresholds (10/15), avoiding prophylactic hyperventilation (15/15), cerebrospinal fluid drainage (13/15), barbiturate (14/15), and decompressive craniectomy (12/15) for intracranial hypertension. There was less consistency in indications for intracranial pressure monitoring (3/15), cerebral perfusion pressure targets (2/15), target osmolarities (7/15), and hyperventilation for intracranial hypertension (2/15). Variability in choice and hierarchy of the interventions for intracranial hypertension were observed, albeit with some points of consistency. CONCLUSIONS: Significant variability in pediatric traumatic brain injury management guidelines exists. Despite the heterogeneity, we have highlighted a few points of consistency within the key topic areas of pediatric traumatic brain injury management. We anticipate that this provides impetus for further work around standardization.

Efficacy of the Spiration Valve System in Patients with Severe Heterogeneous Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Spiration Valve System (SVS) is an alternative for patients with severe heterogeneous emphysema; however, data about efficacy from randomized controlled trials (RCT) are unclear. OBJECTIVES: To explore both efficacy and safety of SVS in patients with severe emphysema and hyperinflation. METHODS: We included PubMed, EMBASE, Coch-rane database. All searches were performed until August 2019. Only RCTs were included for analysis. Risk of bias was assessed using Cochrane risk of bias tool. A meta-analysis evaluated change in forced expiratory volume in 1 s (FEV1), 6-min walking test (6MWT), residual volume, modified medical research council (mMRC) and Saint George respiratory questionnaire (SGRQ), all-cause mortality, risk of pneumothorax, and risk of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Quality of the evidence was rated using GRADE approach. RESULTS: Four RCTs including 629 subjects were included. SVS showed an overall change of 0.03 L (-0.07 to 0.13, I2 = 90%) in the in FEV1 (L) and a 2.03% (-2.50 to 6.57, I2 = 96%) in the predicted FEV1 (%) compared to baseline; however, studies without collateral ventilation (CV) showed an improvement of 0.12 L (95% CI 0.09-0.015, I2 = 0%), This subgroup also reported better results in SGRQ -12.27 points (95% CI -15.84 to -8.70, I2 = 0%) and mMRC -0.54 (95% CI -0.74 to -0.33, I2 = 0%). We found no benefit in 6MWT mean difference = 4.56 m (95% CI -21.88 to 31.00, I2 = 73%). Relative risk of mortality was 2.54 (95% CI 0.81-7.96, I2 = 0%), for pneumothorax 3.3 (95% CI 0.61-18.12, I2 = 0%) and AECOPD 1.68 (95% CI 1.04-2.70, I2 = 0%). CONCLUSION: In patients with severe heterogeneous emphysema and hyperinflation without CV, SVS is an alternative that showed an improvement in pulmonary function, quality of life, and dyspnea score with an acceptable risk profile.

Single-center In-hospital Cardiac Arrest Outcomes.

BACKGROUND: This study was designed to evaluate the patient characteristics and outcomes of in-hospital cardiac arrest (IHCA). MATERIALS AND METHODS: We carried out a single-center, 5-year, retrospective chart review and analysis of resuscitation data for age, gender, body mass index (BMI), length of stay (LOS) until cardiac arrest, survival of initial IHCA, survival to hospital discharge, primary medical service, and determination of the etiology of cardiac arrest. RESULTS: A total of 500 cases occurred with a mean LOS of 8.5 days until the initial IHCA. Overall, 79.5% survived the initial IHCA and 32.4% survived to discharge. As LOS increased, there was an increase in the proportion of pulmonary and metabolic etiologies. Logistic regression analysis adjusting for BMI, gender, age, LOS, and primary medical service were on a surgical service significant for survival to discharge (p = 0.0007) and LOS <9 days significant for survival of IHCA (p = 0.018). CONCLUSION: There are a number of causes of IHCA, and the incidence of death and respiratory related IHCA etiologies increase with LOS. Length of stay carries the highest weight when predicting survival of IHCA. Also, there is a higher rate of survival to discharge when on a primary surgical service. HOW TO CITE THIS ARTICLE: Riley LE, Mehta HJ, Lascano J. Single-center In-hospital Cardiac Arrest Outcomes. Indian J Crit Care Med 2020;24(1):44-48.

Bronchoscopic Lung Volume Reduction with Endobronchial Zephyr Valves for Severe Emphysema: A Systematic Review and Meta-Analysis.

BACKGROUND: Endoscopic lung volume reduction using Zephyr® valves has been recently adopted as a treatment option for patients with severe emphysema without collateral ventilation (CV). OBJECTIVES: To assess the efficacy and safety of Zephyr valves in such a population. METHODS: Studies were identified from MEDLINE and EMBASE databases. All searches were current until June 2018. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of Zephyr. We defined as outcome: change in forced expiratory volume in 1 s (FEV1), in the 6-min walking test (6MWT), in the St George's Respiratory Questionnaire (SGRQ), and in residual volume (RV). Safety analysis included relative risk (RR) of pneumothorax. We assessed the quality of the evidence using GRADE. RESULTS: 7 RCTs reported on Zephyr valves and 5 RCTs included only patients without CV. Zephyr improved FEV1 with a mean difference (MD) of 17.36% (CI, 9.28-25.45, I2 = 78%). Subgroup analysis showed significant FEV1 improvement following Zephyr placement in patients with heterogeneous distribution: MD = 21.78% (CI, 8.70-34.86, I2 = 89%) and 16.27% (CI, 8.78-23.76, I2 = 0%) in patients with homogeneous emphysema. Studies with a follow-up of 3 months reported FEV1 MD = 17.19% (CI, 3.16-31.22, I2 = 89%) compared to studies with a follow-up of 6-12 months, which showed a consistent improvement of FEV1 MD = 17.90% (CI, 11.47-24.33, I2 = 0%). Zephyr also showed improvement of SGRQ, 6MWT, and RV. RR of pneumothorax was 6.32 (CI, 3.74-10.67, I2 = 0%). CONCLUSION: In this population, Zephyr valves provided significant and clinically meaningful short-term improvements in either homogeneous or heterogeneous emphysema without CV but with an increase in adverse events.

Association between inflammatory bowel disease and chronic obstructive pulmonary disease: a systematic review and meta-analysis.

INTRODUCTION: There is evidence of an association between inflammatory bowel disease (IBD) and lung conditions such as chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis explored the risk of new onset IBD in patients with COPD and new onset COPD in IBD patients. METHODS: We performed a systematic review of observational studies exploring the risk of both associations. Two independent reviewers explored the EMBASE, MEDLINE, LILACS and DOAJ databases, and the risk of bias was evaluated using the ROBBINS-I tool. Data from included studies was pooled in a random effect meta-analysis following a DerSimonian-Laird method. The quality of the evidence was ranked using GRADE criteria. RESULTS: Four studies including a pooled population of 1355 new cases were included. We found association between new onset IBD in COPD population. The risk of bias was low in most of them. Only one study reported tobacco exposure as a potential confounding factor. The pooled risk ratio (RR) for a new diagnosis of IBD in COPD patients was 2.02 (CI, 1.56 to 2.63), I2 = 72% (GRADE: low). The subgroup analyses for Crohn's disease and ulcerative colitis yielded RRs of 2.29 (CI, 1.51 to 3.48; I2 = 62%), and 1.79 (CI, 1.39 to 2.29; I2 = 19%.), respectively. DISCUSSION: According to our findings, the risk of new onset IBD was higher in populations with COPD compared to the general population without this condition. Based on our analysis, we suggest a potential association between IBD and COPD; however, further research exploring the potential effect of confounding variables, especially cigarette smoking, is still needed. REVIEW REGISTER: (PROSPERO: CRD42018096624).

[Airway tridimensional printing]. / Aplicaciones de la impresión 3D en la vía aérea central.

Tridimensional printing is becoming relevant in medicine, specially in surgical and interventional specialties. We review the technical aspects and clinical application of airway tridimensional printing. Using this technique, simulation models for bronchoscopy and models for diagnostic and therapeutic procedures such as stent design, tracheal reconstruction and airway models can be created.

Chronic obstructive pulmonary disease and lung cancer: inter-relationships.

PURPOSE OF REVIEW: Chronic obstructive pulmonary disease (COPD) is a well established risk factor for lung cancer. Newer studies reveal a myriad of other mechanisms, some proven and some putative, which may contribute to their association. RECENT FINDINGS: There is an ever-growing bundle of evidence that suggests a close association between persistent chronic inflammation and lung cancer. A few potential targets of genetic susceptibility locus for COPD and lung cancer have been suggested. Better characterization of immune dysregulation and identification of signaling pathways may assist the development of strategies to reduce risk of developing lung cancer in patients with COPD. Current lung cancer screening strategies may exclude some patients at high risk of having lung cancer. Prospective studies indicate that a screening criterion that includes variables reflecting the severity of COPD may increase the sensitivity of the screening program and reduce 'over-diagnosis bias' of indolent lung cancers. Examples of such variables include the emphysema score generated from computed tomography scans and diffusion capacity for carbon monoxide derived from lung function tests. SUMMARY: A better understanding of the inter-relationship between lung cancer pathogenesis and COPD has been described recently. Improving lung cancer screening strategies by incorporating markers of COPD severity has recently been proposed.

[Endoscopic lung volume reduction in advanced pulmonary emphysema: initial experience in Chile]. / Reducción de volumen pulmonar endoscópica en enfisema pulmonar avanzado: Casos clínicos.

Chronic obstructive pulmonary disease (COPD) has no curative treatment, and in moderate to advanced stages, functional parameters and quality of life are affected. Lung volume reduction improves respiratory parameters and quality of life of these patients. Endoscopic lung volume reduction is a minimally invasive procedure that uses endobronchial valves or coils. Valves are unidirectional, blocking the air from entering the target lobe during inspiration, allowing the exit of air and secretions during expiration. Complete fissure and absence of collateral ventilation are needed for an adequate functioning of endobronchial valves. Endobronchial coils cause mechanical retraction of the lung parenchyma. We report two patients who underwent endoscopic lung volume reduction by endobronchial valves. One patient was on continuous positive pressure non-invasive ventilation due to his severe emphysema.

Management of Intrapleural Sepsis with Once Daily Use of Tissue Plasminogen Activator and Deoxyribonuclease.

BACKGROUND: Pleural infection remains a significant cause of morbidity, mortality, prolonged hospital stay, and increased healthcare costs, despite advances in therapy. Twice daily intrapleural tissue plasminogen activator (tPA)/deoxyribonuclease (DNase) initiated at the time of diagnosis has been shown to significantly improve radiological outcomes and decrease the need for surgery. OBJECTIVES: To analyze our experience with once daily tPA/DNase for intrapleural sepsis. METHODS: Data derived from consecutive patients with empyema and complicated parapneumonic effusion who received once daily intrapleural tPA/DNase between January 2012 and August 2014 were reviewed. Measured outcomes included treatment success at 30 days, volume of pleural fluid drained, improvement in radiographic pleural opacity, length of hospital stay, need for surgery, and adverse events. RESULTS: 55 consecutive patients (33 male; mean age ± SD, 54.6 ± 16.1 years) were treated with once daily intrapleural tPA/DNase for 3 days. The majority of the patients (n = 51; 92.7%) were successfully managed without the need for surgical intervention. The mean change in pleural opacity measured on chest radiograph at day 7 was -28.8 ±17.6%. The median amount of fluid drained was 2,195 ml. No serious adverse events requiring discontinuation of intrapleural medications were observed. The most common complication was pain requiring escalating doses of analgesics (n = 8; 15%). Compliance with the protocol was excellent. CONCLUSION: Early administration of once daily intrapleural tPA/DNase for 3 days is safe, effective, and represents a viable option for the management of empyema and complicated parapneumonic effusion.

Induction of cyclooxygenase-2 signaling by Stomatococcus mucilaginosus highlights the pathogenic potential of an oral commensal.

Stomatococcus mucilaginosus is an oral commensal that has been occasionally reported to cause severe infections in immunocompromised patients. There is no information about the pathogenic role of S. mucilaginosus in airway infections. In a cohort of 182 subjects with bronchiectasis, we found that 9% were colonized with S. mucilaginosus in their lower airways by culture growth from bronchoalveolar lavage. To address the pathogenic potential of S.mucilaginosus, we developed a murine model of S. mucilaginosus lung infection. Intratracheal injection of S. mucilaginosus in C57BL/6 mice resulted in a neutrophilic influx with production of proinflammatory cytokines, chemokines, and lipid mediators, mainly PGE2 with induction of cyclooxygenase-2 (COX-2) in the lungs. Presence of TLR2 was necessary for induction of COX-2 and production of PGE2 by S. mucilaginosus. TLR2-deficient mice showed an enhanced clearance of S. mucilaginosus compared with wild-type mice. Administration of PGE2 to TLR2(-/-) mice resulted in impaired clearance of S. mucilaginosus, suggesting a key role for COX-2-induced PGE2 production in immune response to S. mucilaginosus. Mechanistically, induction of COX-2 in macrophages was dependent on the p38-ERK/MAPK signaling pathway. Furthermore, mice treated with S. mucilaginosus and Pseudomonas aeruginosa showed an increased mortality compared with mice treated with PA103 or S. mucilaginosus alone. Inhibition of COX-2 significantly improved survival in mice infected with PA103 and S. mucilaginosus. These data provide novel insights into the bacteriology and personalized microbiome in patients with bronchiectasis and suggest a pathogenic role for S. mucilaginosus in patients with bronchiectasis.

Correlation of end tidal and arterial carbon dioxide levels in critically Ill neonates and children.

AIM OF THE STUDY: End tidal carbon dioxide (EtCO2) monitoring is considered to reflect real-time estimation of partial pressure of carbon dioxide in arterial blood (PaCO2) noninvasively. However, knowledge about its relationship with PaCO2 in critically ill pediatric and neonatal patients is limited. The primary objective was to evaluate predictive capability of end tidal carbon dioxide monitoring and secondary objective was to determine the influence of severity of lung disease on EtCO2 and PaCO2 relationship. MATERIALS AND METHODS: This was a prospective, nonrandomized, consecutive enrollment study carried out in neonatal and pediatric intensive care units of a tertiary care children hospital. It was conducted in 66 neonates and 35 children receiving mechanical ventilation. Severity of lung disease was estimated by ventilation index and PaO2/FiO2 (P/F) ratio. Simultaneous recording of EtCO2 and PaCO2 levels was done and data were analyzed for correlation and agreement. RESULTS: In neonates, 150 EtCO2 and PaCO2 pairs were recorded. The mean weight ± SD of patients was 2.1 ± 0.63 kg. PaCO2 had a positive correlation with EtCO2 (r = 0.836, 95% CI = 0.78-0.88). P/F ratio <200 adversely affected relationship. In infants and children, 96 pairs were recorded. Mean age ± SD of patients was 4.20 ± 4.92 years and mean weight ± SD was 13.1 ± 9.49 kg. PaCO2 had an excellent correlation with EtCO2 (r = 0.914, 95% CI = 0.87 and 0.94). P/F ratio <200 adversely affected relationship. CONCLUSION: EtCO2 monitoring displayed a good validity to predict PaCO2. Correlation was affected by low P/F ratio (<200); hence, it is recommended that blood gases be measured in these patients until such time that a good relation can be established between end tidal and arterial CO2 values.

Real-World Effectiveness of Lung Cancer Screening Using Deep Learning-Based Counterfactual Prediction.

The benefits and harms of lung cancer screening (LCS) for patients in the real-world clinical setting have been argued. Recently, discriminative prediction modeling of lung cancer with stratified risk factors has been developed to investigate the real-world effectiveness of LCS from observational data. However, most of these studies were conducted at the population level that only measured the difference in the average outcome between groups. In this study, we built counterfactual prediction models for lung cancer risk and mortality and examined for individual patients whether LCS as a hypothetical intervention reduces lung cancer risk and subsequent mortality. We investigated traditional and deep learning (DL)-based causal methods that provide individualized treatment effect (ITE) at the patient level and evaluated them with a cohort from the OneFlorida+ Clinical Research Consortium. We further discussed and demonstrated that the ITE estimation model can be used to personalize clinical decision support for a broader population.

Extracting Pulmonary Nodules and Nodule Characteristics from Radiology Reports of Lung Cancer Screening Patients Using Transformer Models.

 Pulmonary nodules and nodule characteristics are important indicators of lung nodule malignancy. However, nodule information is often documented as free text in clinical narratives such as radiology reports in electronic health record systems. Natural language processing (NLP) is the key technology to extract and standardize patient information from radiology reports into structured data elements. This study aimed to develop an NLP system using state-of-the-art transformer models to extract pulmonary nodules and associated nodule characteristics from radiology reports. We identified a cohort of 3080 patients who underwent LDCT at the University of Florida health system and collected their radiology reports. We manually annotated 394 reports as the gold standard. We explored eight pretrained transformer models from three transformer architectures including bidirectional encoder representations from transformers (BERT), robustly optimized BERT approach (RoBERTa), and A Lite BERT (ALBERT), for clinical concept extraction, relation identification, and negation detection. We examined general transformer models pretrained using general English corpora, transformer models fine-tuned using a clinical corpus, and a large clinical transformer model, GatorTron, which was trained from scratch using 90 billion words of clinical text. We compared transformer models with two baseline models including a recurrent neural network implemented using bidirectional long short-term memory with a conditional random fields layer and support vector machines. RoBERTa-mimic achieved the best F1-score of 0.9279 for nodule concept and nodule characteristics extraction. ALBERT-base and GatorTron achieved the best F1-score of 0.9737 in linking nodule characteristics to pulmonary nodules. Seven out of eight transformers achieved the best F1-score of 1.0000 for negation detection. Our end-to-end system achieved an overall F1-score of 0.8869. This study demonstrated the advantage of state-of-the-art transformer models for pulmonary nodule information extraction from radiology reports. Supplementary Information: The online version contains supplementary material available at 10.1007/s41666-024-00166-5.

Acute exacerbation of interstitial lung diseases and mortality post-cryobiopsy: a multicenter cohort study.

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.