Flexible bronchoscopy in pediatric lung transplantation.

Pediatric lung transplantation represents a treatment option for children with advanced lung disease or pulmonary vascular disorders who are deemed an appropriate candidate. Pediatric flexible bronchoscopy is an important and evolving field that is highly relevant in the pediatric lung transplant population. It is thus important to advance our knowledge to better understand how care for children after lung transplant can be maximally optimized using pediatric bronchoscopy. Our goals are to continually improve procedural skills when performing bronchoscopy and to decrease the complication rate while acquiring adequate samples for diagnostic evaluation. Attainment of these goals is critical since allograft assessment by bronchoscopic biopsy is required for histological diagnosis of acute cellular rejection and is an important contributor to establishing chronic lung allograft dysfunction, a common complication after lung transplant. Flexible bronchoscopy with bronchoalveolar lavage and transbronchial lung biopsy plays a key role in lung transplant graft assessment. In this article, we discuss the application of bronchoscopy in pediatric lung transplant evaluation including historical approaches, our experience, and future directions not only in bronchoscopy but also in the evolving pediatric lung transplantation field. Pediatric flexible bronchoscopy has become a vital modality for diagnosing lung transplant complications in children as well as assessing therapeutic responses. Herein, we review the value of flexible bronchoscopy in the management of children after lung transplant and discuss the application of novel techniques to improve care for this complex pediatric patient population and we provide a brief update about new diagnostic techniques applied in the growing lung transplantation field.

Is Minimally Invasive Resection of Large Thymoma Appropriate?

BACKGROUND: Current practice patterns suggest open rather than minimally invasive (MIS) approaches for thymomas >4 cm. We hypothesized there would be similar perioperative outcomes and overall survival between open and MIS approaches for large (>4 cm) thymoma resection. METHODS: The National Cancer Database was queried for patients who underwent thymectomy from 2010 to 2020. Surgical approach was characterized as either open or MIS. The primary outcome was overall survival and secondary outcomes were margin status, and length of stay (LOS). Differences between approach cohorts were compared after a 1:1 propensity match. RESULTS: Among 4121 thymectomies, 2474 (60%) were open and 1647 (40%) were MIS. Patients undergoing MIS were older, had fewer comorbidities, and had smaller tumors (median; 4.6 vs 6 cm, P < .001). In the unmatched cohort, MIS and open had similar 90-day mortality (1.1% vs 1.8%, P = .158) and rate of positive margin (25.1% vs 27.9%, P = .109). MIS thymectomy was associated with shorter LOS (2 (1-4) vs 4 (3-6) days, P < .001). Propensity matching reduced the bias between the groups. In this cohort, overall survival was similar between the groups by log-rank test (P = .462) and multivariate cox hazard analysis (HR .882, P = .472). Multivariable regression showed shorter LOS with MIS approach (Coef -1.139, P < .001), and similar odds of positive margin (OR 1.130, P = .150). DISCUSSION: MIS has equivalent oncologic benefit to open resection for large thymomas, but is associated with shorter LOS. When clinically appropriate, MIS thymectomy may be considered a safe alternative to open resection for large thymomas.

The Society of Thoracic Surgeons Database Analysis: Comparing Sublobar Techniques in Stage IA Lung Cancer.

BACKGROUND: This study compares sublobar resections-wedge resection and segmentectomy-in clinical stage IA lung cancers. It tests the hypothesis that overall survival after wedge resection is similar to segmentectomy. METHODS: Adults undergoing wedge resection or segmentectomy for clinical stage IA lung cancer were identified from The Society of Thoracic Surgeons General Thoracic Surgery Database. Eligible patients were linked to the Centers for Medicare and Medicaid Services database using a matching algorithm. The primary outcome was long-term overall survival. Propensity scores overlap weighting (PSOW) adjustment of wedge resection using validated covariates was used for group difference mitigation. Kaplan-Meier and Cox regression models analyzed survival. All-cause first readmission, and morbidity and mortality were examined using PSOW regression models. RESULTS: Of 9756 patients, 6141 met inclusion criteria, comprising 2154 segmentectomies and 3987 wedge resections. PSOW reduced differences between the groups. Unadjusted perioperative mortality was comparable, but wedge resection showed lower major morbidity rates. Weighted regression analysis indicated reduced mortality and major morbidity risks in wedge resection. Kaplan-Meier analysis revealed no mortality difference between groups, which was confirmed by PSOW Cox regression models. The cumulative risk of readmission was also comparable for both groups, with Cox Fine-Gray models showing no difference in rehospitalization risks. CONCLUSIONS: In clinical stage IA lung cancer, relative to segmentectomy, wedge resection has comparable overall survival and lower perioperative morbidity, suggesting it is an equally effective option for the broader population of patients with clinical stage IA lung cancer, not only those at highest risk of complications.

Frailty is associated with 90-day mortality in urgent thoracic surgery conditions.

Objective: In patients undergoing elective thoracic surgery, frailty is associated with worse outcomes. However, the magnitude by which frailty influences outcomes of urgent thoracic surgery (UTS) is unknown. Methods: We identified patients admitted with a UTS condition from January to September 2017 in the National Readmissions Database. UTS conditions were classified as esophageal perforation, hemo/pneumothorax, rib fracture, and obstructed hiatal hernia. Outcome of interest was mortality within 90 days of index admission. Frailty score was calculated using a deficit accumulation method. Cox proportional hazard modeling was used to calculate a hazard ratio for each combination of UTS disease type and frailty score, adjusted for sex, insurance payor, hospital size, and hospital and patient location, and was compared with the effect of frailty on elective lung lobectomy. Results: We identified 107,487 patients with a UTS condition. Among UTS conditions overall, increasing frailty elements were associated with increased mortality (hazard ratio, 2270; 95% CI, 1463-3523; P < .001). Compared with patients without frailty undergoing elective lobectomy, increasing frailty demonstrated trending toward increased mortality in all diagnoses. The magnitude of the effect of frailty on 90-day mortality differed depending on the disease and level of frailty. Conclusions: The effect of frailty on 90-day mortality after admission for urgent thoracic surgery conditions varies by disease type and level of frailty. Among UTS disease types, increasing frailty was associated with a higher 90-day risk of mortality. These findings suggest a valuable role for frailty evaluation in both clinical settings and administrative data for risk assessment.

Early Repair of Rib Fractures Is Associated with Superior Length of Stay and Total Hospital Cost: A Propensity Matched Analysis of the National Inpatient Sample.

Background and Objectives: Previous studies have suggested that early scheduling of the surgical stabilization of rib fractures (SSRF) is associated with superior outcomes. It is unclear if these data are reproducible at other institutions. We hypothesized that early SSRF would be associated with decreased morbidity, length of stay, and total charges. Materials and Methods: Adult patients who underwent SSRF for multiple rib fractures or flail chest were identified in the National Inpatient Sample (NIS) by ICD-10 code from the fourth quarter of 2015 to 2016. Patients were excluded for traumatic brain injury and missing study variables. Procedures occurring after hospital day 10 were excluded to remove possible confounding. Early fixation was defined as procedures which occurred on hospital day 0 or 1, and late fixation was defined as procedures which occurred on hospital days 2 through 10. The primary outcome was a composite outcome of death, pneumonia, tracheostomy, or discharge to a short-term hospital, as determined by NIS coding. Secondary outcomes were length of hospitalization (LOS) and total cost. Chi-square and Wilcoxon rank-sum testing were performed to determine differences in outcomes between the groups. One-to-one propensity matching was performed using covariates known to affect the outcome of rib fractures. Stuart-Maxwell marginal homogeneity and Wilcoxon signed rank matched pair testing was performed on the propensity-matched cohort. Results: Of the 474 patients who met the inclusion criteria, 148 (31.2%) received early repair and 326 (68.8%) received late repair. In unmatched analysis, the composite adverse outcome was lower among early fixation (16.2% vs. 40.2%, p < 0.001), total hospital cost was less (USD114k vs. USD215k, p < 0.001), and length of stay was shorter (6 days vs. 12 days) among early SSRF patients. Propensity matching identified 131 matched pairs of early and late SSRF. Composite adverse outcomes were less common among early SSRF (18.3% vs. 32.8%, p = 0.011). The LOS was shorter among early SSRF (6 days vs. 10 days, p < 0.001), and total hospital cost was also lower among early SSRF patients (USD118k vs. USD183k late, p = 0.001). Conclusion: In a large administrative database, early SSRF was associated with reduced adverse outcomes, as well as improved hospital length of stay and total cost. These data corroborate other research and suggest that early SSRF is preferred. Studies of outcomes after SSRF should stratify analyses by timing of procedure.

Pretreatment and Posttreatment Tumor Metabolic Activity Assessed by FDG-PET/CT as Predictors of Tumor Recurrence and Survival Outcomes in Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Body Radiation Therapy.

Purpose: Stereotactic body radiation therapy (SBRT) is considered the standard of care for medically inoperable early-stage non-small cell lung cancer. There is mixed evidence on the prognostic significance of tumor metabolic activity assessed by positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG). The objectives of this study were to evaluate the maximum standardized uptake value (SUVmax) pretreatment and at 3 and 6 months after SBRT for prediction of tumor control and survival outcomes. Methods and Materials: Consecutive patients from a single institution with T12N0M0 non-small cell lung cancer receiving primary treatment with SBRT with pretreatment FDG-PET/CT (n = 163) and follow-up FDG-PET/CT at 3 or 6 months (n = 71) were included. Receiver operator characteristic analysis was performed to dichotomize variables for Kaplan-Meier survival analysis. Multivariate analysis was performed with Cox proportional hazards regression. Results: Median follow-up was 19 months. For the whole cohort, 1-year and 2-year local control, progression-free survival (PFS), and overall survival (OS) were 95.0% and 80.3%, 87.1% and 75.4%, and 67.0% and 49.6% respectively. The following pre-SBRT SUVmax cutoffs were significant: SUV > 4.0 for distant failure-free survival (adjusted hazard ratio [aHR], 3.33, P = .006), >12.3 for PFS (aHR, 2.80, P = .011), and >12.6 for OS (aHR, 3.00, P = .003). SUVmax decreases of at least 45% at 3 months (aHR, 0.15, P = .018), and 53% at 6 months (aHR, 0.12, P = .046) were associated with improved local failure-free survival. Conclusions: Pre-SBRT SUVmax cutoffs can predict distant failure, PFS, and OS. At both 3 and 6 months after SBRT, cutoffs for percentage change in SUVmax can potentially stratify risk of local recurrence.

Outcomes of Trauma "Walk-Ins" in the American College of Surgeons Trauma Quality Program Database.

BACKGROUND: Outcomes of trauma "walk-in" patients (using private vehicles or on foot) are understudied. We compared outcomes of ground ambulance vs walk-ins, hypothesizing that delayed resuscitation and uncoordinated care may worsen walk-in outcomes. METHODS: A retrospective analysis 2020 American College of Surgeons Trauma Quality Programs (ACS-TQP) databases compared outcomes between ambulance vs "walk-ins." The primary outcome was in-hospital mortality, excluding external facility transfers and air transports. Data was analyzed with descriptive statistics, bivariate, multivariable logistic regression, including an Inverse Probability Weighted Regression Adjustment with adjustments for injury severity and vital signs. The primary outcome for the 2019 (pre-COVID-19 pandemic) data was similarly analyzed. RESULTS: In 2020, 707,899 patients were analyzed, 556,361 (78.59%) used ambulance, and 151,538 (21.41%) were walk-ins. We observed differences in demographics, hospital attributes, medical comorbidities, and injury mechanism. Ambulance patients had more chronic conditions and severe injuries. Walk-ins had lower in-hospital mortality (850 (.56%) vs 23,131 (4.16%)) and arrived with better vital signs. Multivariable logistic regression models (inverse probability weighting for regression adjustment), adjusting for injury severity, demographics, injury mechanism, and vital signs, confirmed that walk-in status had lower odds of mortality. For the 2019 (pre-COVID-19 pandemic) database, walk-ins also had lower in-hospital mortality. DISCUSSION: Our results demonstrate better survival rates for walk-ins before and during COVID-19 pandemic. Despite limitations of patient selection bias, this study highlights the need for further research into transportation modes, geographic and socioeconomic factors affecting patient transport, and tailoring management strategies based on their mode of arrival.

Risk Factors for Chronic Atrial Fibrillation Following Lung Lobectomy.

INTRODUCTION: Postoperative atrial fibrillation (POAF) is a common complication following lung lobectomy and is associated with increased risk of stroke, mortality, and prolonged hospital length of stay. The purpose of this study was to define the risk factors for POAF after lobectomy, hypothesizing that operative approach would be associated with risk of chronic POAF. METHODS: The TriNetX database was used to identify adult patients with no history of arrythmia receiving elective lung lobectomy for cancer from 7/6/2003-7/6/2023. Patients were categorized by approach: video-assisted thoracoscopic surgery (VATS) or open. The outcome of interest was the presence of POAF occurring at 1-3 months ("early") and 12-24 months postop ("chronic"). Propensity matching was performed to reduce bias between cohorts. RESULTS: We identified 22,998 patients: 8472 (36.8%) who received open and 14,526 (63.2%) VATS lobectomy. The rate of early POAF was 3.7% of VATS and 5.3% of open patients. The rate of chronic POAF was 5.5 % of VATS patients and 6.2% of open lobectomy patients. Propensity matching decreased bias between the approach groups, creating 7942 pairs for analysis. After matching, the risk of early POAF was greater in the open approach (5.5% open vs 3.4% VATS, risk ratio 1.607 (95% confidence interval 1.385-1.865), P < 0.001). Chronic POAF was (also) higher in the open approach (6.3% open vs 5.2% VATS, Risk Ratio 1.211 (95%CI 1.067-1.374), P = 0.003). CONCLUSIONS: Postoperative atrial fibrillation (POAF) occurs more commonly after open lobectomy, both acutely and chronically. Providers should counsel patients about the risk of chronic arrythmia after lung resection.

Disease Course, Treatments, and Outcomes of Children With Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease.

OBJECTIVE: Systemic juvenile idiopathic arthritis-associated lung disease (SJIA-LD) is a life-threatening disease complication. Key questions remain regarding clinical course and optimal treatment approaches. The objectives of the study were to detail management strategies after SJIA-LD detection, characterize overall disease courses, and measure long-term outcomes. METHODS: This was a prospective cohort study. Clinical data were abstracted from the electronic medical record, including current clinical status and changes since diagnosis. Serum biomarkers were determined and correlated with presence of LD. RESULTS: We enrolled 41 patients with SJIA-LD, 85% with at least one episode of macrophage activation syndrome and 41% with adverse reactions to a biologic. Although 93% of patients were alive at last follow-up (median 2.9 years), 37% progressed to requiring chronic oxygen or other ventilator support, and 65% of patients had abnormal overnight oximetry studies, which changed over time. Eighty-four percent of patients carried the HLA-DRB1*15 haplotype, significantly more than patients without LD. Patients with SJIA-LD also showed markedly elevated serum interleukin-18 (IL-18), variable C-X-C motif chemokine ligand 9 (CXCL9), and significantly elevated matrix metalloproteinase 7. Treatment strategies showed variable use of anti-IL-1/6 biologics and addition of other immunomodulatory treatments and lung-directed therapies. We found a broad range of current clinical status independent of time from diagnosis or continued biologic treatment. Multidomain measures of change showed imaging features were the least likely to improve with time. CONCLUSION: Patients with SJIA-LD had highly varied courses, with lower mortality than previously reported but frequent hypoxia and requirement for respiratory support. Treatment strategies were highly varied, highlighting an urgent need for focused clinical trials.

The Society of Thoracic Surgeons General Thoracic Surgery Database: 2023 Update on Outcomes and Research.

The Society of Thoracic Surgeons General Thoracic Surgery Database (GTSD) continues its trajectory of growth and enhancement, solidifying its stature as a premier global thoracic surgical database. The past year witnessed a notable expansion with the inclusion of 10 additional participating sites, now totaling 287, augmenting the database's repository to more than 800,000 procedures. A significant stride was made in refining the data audit process, thereby elevating the accuracy and completeness metrics, a testament to the relentless pursuit of data integrity. The GTSD further broadened its research apparatus, with 15 scholarly publications, a 50% uptick from the preceding year. These publications underscore the database's instrumental role in advancing thoracic surgical knowledge. In a concerted effort to alleviate data entry exigencies, the GTSD Task Force also instituted streamlined data submission protocols, a move lauded by participant sites. This report delineates the recent advancements, volume trajectories, and outcome metrics and encapsulates the prolific research output emanating from the GTSD, reflecting a year of substantial progress and academic fecundity.

Speed kills? Quantifying the association between police traffic stops, types of stops, and motor vehicle collisions.

BACKGROUND: Motor vehicle crashes (MVCs) are a leading cause of traumatic death and injury. Police traffic stops (PTS) are a common approach to enforcing motor vehicle laws intended to prevent MVCs. However, it is unclear which types of PTS are most effective. This study examined the relationship of PTS subtypes among municipal police patrols on non-interstate roads and MVCs and MVC-related deaths. METHODS: PTS subtype data were characterized from six North Carolina cities: Charlotte, Durham, Fayetteville, Greensboro, Raleigh, and Winston-Salem. The primary outcomes of this study were yearly non-interstate MVC and MVC-related death rates per 100 population. The data were analyzed as balanced time-series cross-sectional data. The statistical analysis accounted for time-dependent and city-dependent confounding. We used a two-way fixed effects model to analyze the relationship between PTS and MVC or MVC-related deaths. We also utilized the difference in difference (DID) analysis to analyze if the reduction of PTS following a 2012 policing administrative change in Fayetteville had an association with MVC or MVC-related deaths. RESULTS: We found no significant overall association between non-interstate PTS and MVCs (Coeff: -0.00006; p = 0.43) or MVC-related deaths (Coeff: -0.00011; p = 0.15). Panel regression suggested no significant relationship between MVCs and MVC-related deaths and PTS related to driving while impaired (p = 0.36), safe movement violation (p = 0.43), or seatbelt violations (p = 0.17). However, speed limit violations (Coeff: -0.00025; p = 0.032) and stop-light/sign violations (Coeff: -0.00147; p = 0.017) related to PTS significantly reduced MVC-related deaths. The DID regression showed no significant impact on MVCs (p = 0.924) or MVC-related deaths (0.706) before and after the police reform period. CONCLUSIONS: The evidence regarding the absence of an overall association and any association with most PTS subtypes suggest that PTS are not effective for MVC death prevention. Policymakers may proceed with exploring modifications to policing efforts without detriments to public safety as defined by MVC and MVC-related deaths. LEVEL OF EVIDENCE: Retrospective epidemiological study, level IV.

National enrollment of lung cancer clinical trials is disproportionate based on race and health care access.

OBJECTIVE: Despite declining lung cancer mortality in the United States, survival differences remain among racial and ethnic minorities in addition to those with limited health care access. Improvements in lung cancer treatment can be obtained through clinical trials, yet there are disparities in clinical trial enrollment of other cancer types. This study aims to evaluate disparities in lung cancer clinical trial enrollment to inform future enrollment initiatives. METHODS: We analyzed patients with non-small cell lung cancer from the National Cancer Database (2004-2018), categorizing them as enrolled or not enrolled in clinical trials based on "rx_summ_other" data element. Clinical, demographic, and institutional factors associated with trial enrollment were assessed using bivariate and multivariate analysis, adjusting for institutional-level clustering. RESULTS: A total of 1924 (0.12%) patients with lung cancer were enrolled in clinical trials. Enrolled patients were predominantly non-Hispanic White (82%), with greater socioeconomic status, treated at academic programs (67%), and had private insurance (42%) or Medicare (44%). They also traveled further for treatment compared with unenrolled patients (56 vs 27 miles, P < .001). After adjusting for demographic and clinical factors, lung cancer trial enrollment was significantly less likely among Black (odds ratio, 0.55; 95% confidence interval, 0.5-0.7, P < .001) and Hispanic (0.66; 95% confidence interval, 0.5-0.9, P = .01) patients. Patients with Medicaid or uninsured, in the lowest socioeconomic status group, and those treated at community-based cancer programs were the least likely to enroll. CONCLUSIONS: Enrollment in lung cancer trials disproportionally excludes minority patients, those in the lowest socioeconomic status, community cancer programs, and the underinsured. These disparities in demographic and access for trial participation show a need for improved enrollment strategies.

Motor Vehicle Protective Device Usage Associated with Decreased Rate of Flail Chest: A Retrospective Database Analysis.

Background and Objectives: Protective equipment, including seatbelts and airbags, have dramatically reduced the morbidity and mortality rates associated with motor vehicle collisions (MVCs). While generally associated with a reduced rate of injury, the effect of motor vehicle protective equipment on patterns of chest wall trauma is unknown. We hypothesized that protective equipment would affect the rate of flail chest after an MVC. Materials and Methods: This study was a retrospective analysis of the 2019 iteration of the American College of Surgeons Trauma Quality Program (ACS-TQIP) database. Rib fracture types were categorized as non-flail chest rib fractures and flail chest using ICD-10 diagnosis coding. The primary outcome was the occurrence of flail chests after motor vehicle collisions. The protective equipment evaluated were seatbelts and airbags. We performed bivariate and multivariate logistic regression to determine the association of flail chest with the utilization of vehicle protective equipment. Results: We identified 25,101 patients with rib fractures after motor vehicle collisions. In bivariate analysis, the severity of the rib fractures was associated with seatbelt type, airbag status, smoking history, and history of cerebrovascular accident (CVA). In multivariate analysis, seatbelt use and airbag deployment (OR 0.76 CI 0.65-0.89) were independently associated with a decreased rate of flail chest. In an interaction analysis, flail chest was only reduced when a lap belt was used in combination with the deployed airbag (OR 0.59 CI 0.43-0.80) when a shoulder belt was used without airbag deployment (0.69 CI 0.49-0.97), or when a shoulder belt was used with airbag deployment (0.57 CI 0.46-0.70). Conclusions: Although motor vehicle protective equipment is associated with a decreased rate of flail chest after a motor vehicle collision, the benefit is only observed when lap belts and airbags are used simultaneously or when a shoulder belt is used. These data highlight the importance of occupant seatbelt compliance and suggest the effect of motor vehicle restraint systems in reducing severe chest wall injuries.

Validation of the PREDICT Prognostication Tool in US Patients With Breast Cancer.

BACKGROUND: PREDICT is an online prognostication tool derived from breast cancer registry information on approximately 6,000 women treated in the United Kingdom that estimates the postsurgical treatment benefit of surgery alone, chemotherapy, trastuzumab, endocrine therapy, and/or adjuvant bisphosphonates in early-stage breast cancer. Our aim was to validate the PREDICT algorithm in predicting 5- and 10-year overall survival (OS) probabilities using real-world outcomes among US patients with breast cancer. METHODS: A retrospective study was performed including women diagnosed with unilateral breast cancer in 2004 through 2012. Women with primary unilateral invasive breast cancer were included. Patients with bilateral or metastatic breast cancer, no breast surgery, or missing critical clinical information were excluded. Prognostic scores from PREDICT were calculated and external validity was approached by assessing statistical discrimination through area under time-dependent receiver-operator curves (AUC) and comparing the predicted survival to the observed OS in relevant subgroups. RESULTS: We included 708,652 women, with a median age of 58 years. Most patients were White (85.4%), non-Hispanic (88.4%), and diagnosed with estrogen receptor-positive breast cancer (79.6%). Approximately 50% of patients received adjuvant chemotherapy, 67% received adjuvant endocrine therapy, 60% underwent a partial mastectomy, and 59% had 1 to 5 axillary sentinel nodes removed. Median follow-up time was 97.7 months. The population's 5- and 10-year OS were 89.7% and 78.7%, respectively. Estimated 5- and 10-year median survival with PREDICT were 88.3% and 73.8%, and an AUC of 0.77 and 0.76, respectively. PREDICT performed most poorly in patients with high Charlson-Deyo comorbidity scores (2-3), where PREDICT overestimated OS. Sensitivity analysis by year of diagnosis and HER2 status showed similar results. CONCLUSIONS: In this prognostic study utilizing the National Cancer Database, the PREDICT tool accurately predicted 5- and 10-year OS in a contemporary and diverse population of US patients with nonmetastatic breast cancer.

Diagnosis and Management of the Systemic Juvenile Idiopathic Arthritis Patient with Emerging Lung Disease.

Chronic lung disease in children with systemic juvenile idiopathic arthritis (SJIA-LD) is an emerging and potentially life-threatening disease complication. Despite recent descriptions of its clinical spectrum, preliminary immunologic characterization, and proposed hypotheses regaarding etiology, optimal approaches to diagnosis and management remain unclear. Here, we review the current clinical understanding of SJIA-LD, including the potential role of biologic therapy in disease pathogenesis, as well as the possibility of drug reactions with eosinophilia and systemic symptoms (DRESS). We discuss approaches to evaluation of children with suspected SJIA-LD, including a proposed algorithm to risk-stratify all SJIA patients for screening to detect LD early. We review potential pharmacologic and non-pharmacologic treatment approaches that have been reported for SJIA-LD or utilized in interstitial lung diseases associated with other rheumatic diseases. This includes lymphocyte-targeting therapies, JAK inhibitors, and emerging therapies against IL-18 and IFNγ. Finally, we consider urgent unmet needs in this area including in basic discovery of disease mechanisms and clinical research to improve disease detection and patient outcomes.

Estimating the overall survival benefit of adjuvant chemo-endocrine therapy in women over age 50 with pT1-2N0 early stage breast cancer and 21-gene recurrence score ≥26: A National Cancer Database analysis.

BACKGROUND: Validation studies of the 21-gene recurrence score (RS) previously demonstrated that adjuvant chemotherapy plus endocrine therapy (CET) was associated with a significant survival benefit in women with node negative breast cancer (BC) and RS >31. However, the TAILORx trial, did not quantify the benefit of adjuvant CET in older women with node negative hormone receptor positive (HR+) BC with RS ≥26. We hypothesized that CET would be associated with improved overall survival (OS) compared to endocrine therapy (ET) in women >50 with HR+/HER2-node negative BC and RS ≥26. METHODS: The National Cancer Database (NCDB) was queried to identify women >50 with RS ≥26 ER+/HER2-BC pT1-2N0M0. Chi-square and logistic regression analysis determined the difference between ET and CET. OS was analyzed using a multivariable Cox model. RESULTS: We included 16,745 women-4740 (28.3%) received ET and 12,005 (71.7%) received CET. Women who received CET had: moderately (OR = 1.853, p < 0.001) or poorly/undifferentiated tumors (OR = 3.875, p < 0.001), pT2 (OR = 1.356, p < 0.001), or lymph-vascular invasion (OR = 1.206, p = 0.001). After accounting for demographic and oncologic factors, 5-year OS rates were significantly superior in women receiving CET vs. ET alone (95.4% vs. 92.0%, Hazard Ratio = 0.680, p < 0.001). CONCLUSIONS: We observed that CET was associated with a clinically and statistically significant higher OS compared to ET alone in women >50 years of age with RS ≥26 pT1 and pT2 N0M0 HR+/HER2-breast cancer, and which suggests that cytotoxic chemotherapy has an impact on reducing mortality that is independent of induction of premature ovarian failure.

Computational risk model for predicting 2-year malignancy of pulmonary nodules using demographic and radiographic characteristics.

OBJECTIVES: To determine whether discriminatory performance of a computational risk model in classifying pulmonary lesion malignancy using demographic, radiographic, and clinical characteristics is superior to the opinion of experienced providers. We hypothesized that computational risk models would outperform providers. METHODS: Outcome of malignancy was obtained from selected patients enrolled in the NAVIGATE trial (NCT02410837). Five predictive risk models were developed using an 80:20 train-test split: univariable logistic regression model based solely on provider opinion, multivariable logistic regression model, random forest classifier, extreme gradient boosting model, and artificial neural network. Area under the receiver operating characteristic curve achieved during testing of the predictive models was compared to that of prebiopsy provider opinion baseline using the DeLong test with 10,000 bootstrapped iterations. RESULTS: The cohort included 984 patients, 735 (74.7%) of which were diagnosed with malignancy. Factors associated with malignancy from multivariable logistic regression included age, history of cancer, largest lesion size, lung zone, and positron-emission tomography positivity. Testing area under the receiver operating characteristic curve were 0.830 for provider opinion baseline, 0.770 for provider opinion univariable logistic regression, 0.659 for multivariable logistic regression model, 0.743 for random forest classifier, 0.740 for extreme gradient boosting, and 0.679 for artificial neural network. Provider opinion baseline was determined to be the best predictive classification system. CONCLUSIONS: Computational models predicting malignancy of pulmonary lesions using clinical, demographic, and radiographic characteristics are inferior to provider opinion. This study questions the ability of these models to provide additional insight into patient care. Expert clinician evaluation of pulmonary lesion malignancy is paramount.

Lung Cancer in Young Patients is Associated With More Advanced Disease but Better Overall Survival.

INTRODUCTION: It is unclear whether nonsmall cell lung cancer (NSCLC) is associated with more aggressive disease and worse overall survival (OS) among younger patients. The aim of this study is to evaluate outcomes in young patients. We hypothesize that young age is associated with more advanced disease upon presentation, but better OS. METHODS: We identified patients with NSCLC from 2004 to 2018 in the National Cancer Database. Patients were categorized in 3 groups: age≤50, 51-84, and ≥85 y. The outcomes were OS, stage IV NSCLC and clinical nodal metastasis. OS was analyzed using multivariate cox and Kaplan-Meier analysis accounting for stage, comorbidities, and other factors. The association of age, presentation with stage IV NSCLC and node positivity was analyzed using multivariate logistic regression. RESULTS: In total 1,651,744 patients were identified: 92,506 (5.57%) age ≤50, 1,477,723 (88.90%) age 51-84, and 91,964 (5.53%) age ≥85. Multivariate model showed stage IV NSCLC was associated with age ≤50 (OR 1.17 (1.15-1.20) P < 0.001) and ≥85 (odds ratio (OR) 1.03 (1.02-1.04) P < 0.001). Clinical lymph node positivity was associated with age ≤50 (OR 1.27 (1.23-1.30) P < 0.001). Relative to patients 51-84, the ≤50 group was associated with better survival in Stage I (hazard ratio (HR) 0.61 versus 1.00), stage II (HR 1.12 versus 1.50), stage III (HR 2.12 versus 2.53), and stage IV (HR 6.65 versus 7.53). CONCLUSIONS: Patients ≤50-y-old present with more advanced NSCLC, but better OS compared to patients 51-84. These findings suggest the need for increased awareness regarding NSCLC among age groups seen as low risk.

Evaluating the Optimal Time Between Diagnosis and Surgical Intervention for Early-Stage Lung Cancer.

INTRODUCTION: There is no consensus on the optimal timing for lung cancer surgery. We aim to evaluate the impact of timing of surgical intervention. We hypothesize delay in intervention is associated with worse overall survival and higher pathologic upstaging in early-stage lung cancer. METHODS: We identified patients with cT1/2N0M0 nonsmall cell lung cancer in the National Cancer Database from 2004 to 2018. Patients were categorized by time to surgery groups: early (<26 d), average (26-60 d), and delayed (61-365 d). Primary outcome was overall survival and secondary outcome was pathologic upstaging. Multivariate models and survival analyses were used to determine factors associated with time from diagnosis to surgery, pathologic upstaging, and overall survival. RESULTS: In multivariate model, advanced age, non-Hispanic Black patients, nonprivate insurance, low median income and education, and treatment at low-volume facilities were less likely to undergo early intervention and compared to the average group were more likely to receive delayed intervention. Pathologic upstaging was more likely in the delayed group (odds ratio 1.11, 1.07-1.14) compared to early group (odds ratio 0.96, 0.93-0.99). Early intervention was associated with improved overall survival (hazard ratio 0.93, 0.91-0.95), while delayed intervention was associated with inferior survival (hazard ratio 1.11, 1.09-1.14). CONCLUSIONS: Expeditious surgical intervention is associated with lower rates of pathologic upstaging and improved overall survival in early-stage lung cancer. Delays in surgery are associated with social and economic factors, suggesting disparities in access to surgery. Lung cancer surgery should be performed as quickly as possible to maximize oncologic outcomes.

Improved donor lung size matching by estimation of lung volumes based on chest X-ray measurements.

RATIONALE: Organ size matching is an important determinant of successful allocation and outcomes in lung transplantation. While computed tomography (CT) is the gold standard, it is rarely used in an organ-donor context, and chest X-ray (CXR) may offer a practical and accurate solution in estimating lung volumes for donor and recipient size matching. We compared CXR lung measurements to CT-measured lung volumes and traditional estimates of lung volume in the same subjects. METHODS: Our retrospective study analyzed clinically obtained CXR and CT lung images of 250 subjects without evidence of lung disease (mean age 9.9 ± 7.8 years; 129 M/121F). From CT, each lung was semi-automatically segmented and total lung volumes were quantified. From anterior-posterior CXR view, each lung was manually segmented and areas were measured. Lung lengths from the apices to the mid-basal regions of each lung were measured from CXR. Quantified CT lung volumes were compared to the corresponding CXR lung lengths, CXR lung areas, height, weight, and predicted total lung capacity (pTLC). RESULTS: There are strong and significant correlations between CT volumes and CXR lung areas in the right lung (R2 = .89, p < .0001), left lung (R2 = .87, p < .0001), and combined lungs (R2 = .89, p < .0001). Similar correlations were seen between CT volumes and CXR measured lung lengths in the right lung (R2 = .79, p < .0001) and left lung (R2 = .81, p < .0001). This correlation between anatomical lung volume (CT) and CXR was stronger than lung-volume correlation to height (R2 = .66, p < .0001), weight (R2 = .43, p < .0001), or pTLC (R2 = .66, p < .0001). CONCLUSION: CXR measures correlate much more strongly with true lung volumes than height, weight, or pTLC. The ability to obtain efficient and more accurate lung volume via CXR has the potential to change our current listing practices of using height as a surrogate for lung size, with a case example provided.