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.

Affordable Care Act Medicaid Expansion is Associated With Increased Utilization of Minimally Invasive Lung Resection for Early Stage Lung Cancer.

OBJECTIVE: Minimally invasive lung resection (MILR) is underutilized in the United States. Under the Affordable Care Act (ACA), 39 states adopted Medicaid expansion, while 12 did not. Although Medicaid expansion has been associated with improved access to cancer care, its effect on utilization of MILR is unclear. We hypothesize that MILR would increase in Medicaid expansion states. METHODS: The National Cancer Database was queried for adult patients from 2010 to 2018 with cT1/2N0M0 non-small cell lung cancer who received surgical resection by wedge, segmentectomy, or lobectomy. Patients were grouped by whether they received care in a state without Medicaid expansion vs expansion in January 2014. The outcome of interest was MILR (defined as video-assisted or robotic-assisted thoracoscopy) relative to open. Multivariable difference in differences (DID) cross-sectional analysis was used to estimate the average treatment effect (ATE) of Medicaid expansion. RESULTS: There were 41,439 patients who met inclusion criteria: 20,446 (49.3%) in expansion states and 20,993 (50.7%) in non-expansion states. Multivariable DID analysis showed that Medicaid expansion was associated with an increase in Medicaid insurance type with an ATE of 7.4% (95% CI 7.1-7.7%, P = .002). Medicaid expansion was also associated with increased MILR utilization in unadjusted analysis (10,278/20,446 (50.3%) vs 9,953/20,993 (47.4%), p < .001) and in multivariable DID analysis (ATE 0.6%, 95% CI 0.3-0.8%, P = .008). CONCLUSIONS: Although Medicaid expansion was associated with increased utilization of MILR for early stage lung cancer, the treatment effect was modest. This suggests that barriers in access to MILR are larger than simply access to care.

Reversed Neurovascular Coupling on Optical Coherence Tomography Angiography Is the Earliest Detectable Abnormality before Clinical Diabetic Retinopathy.

Diabetic retinopathy (DR) has traditionally been viewed as either a microvasculopathy or a neuropathy, though neurovascular coupling deficits have also been reported and could potentially be the earliest derangement in DR. To better understand neurovascular coupling in the diabetic retina, we investigated retinal hemodynamics by optical coherence tomography angiography (OCTA) in individuals with diabetes mellitus (DM) but without DR (DM no DR) and mild non-proliferative DR (mild NPDR) compared to healthy eyes. Using an experimental design to monitor the capillary responses during transition from dark adaptation to light, we examined 19 healthy, 14 DM no DR and 11 mild NPDR individuals. We found that the only structural vascular abnormality in the DM no DR group was increased superficial capillary plexus (SCP) vessel density (VD) compared to healthy eyes, while mild NPDR eyes showed significant vessel loss in the SCP at baseline. There was no significant difference in inner retinal thickness between the groups. During dark adaptation, the deep capillary plexus (DCP) VD was lower in mild NPDR individuals compared to the other two groups, which may leave the photoreceptors more susceptible to ischemia in the dark. When transitioning from dark to ambient light, both diabetic groups showed a qualitative reversal of VD trends in the SCP and middle capillary plexus (MCP), with significantly decreased SCP at 5 min and increased MCP VD at 50 s compared to healthy eyes, which may impede metabolic supply to the inner retina during light adaptation. Mild NPDR eyes also demonstrated DCP dilation at 50 s and 5 min and decreased adjusted flow index at 5 min in light. Our results show altered neurovascular responses in all three macular vascular plexuses in diabetic subjects in the absence of structural neuronal changes on high resolution imaging, suggesting that neurovascular uncoupling may be a key mechanism in the early pathogenesis of DR, well before the clinical appearance of vascular or neuronal loss.

Detection of Mg2+-dependent, coaxial stacking rearrangements in a bulged three-way DNA junction by single-molecule FRET.

Three-way helical junctions (3WJs) arise in genetic processing, and they have architectural and functional roles in structured nucleic acids. An internal bulge at the junction core allows the helical domains to become oriented into two possible, coaxially stacked conformers. Here, the helical stacking arrangements for a series of bulged, DNA 3WJs were examined using ensemble fluorescence resonance energy transfer (FRET) and single-molecule FRET (smFRET) approaches. The 3WJs varied according to the GC content and sequence of the junction core as well as the pyrimidine content of the internal bulge. Mg2+ titration experiments by ensemble FRET show that both stacking conformations have similar Mg2+ requirements for folding. Strikingly, smFRET experiments reveal that a specific junction sequence can populate both conformers and that this junction undergoes continual interconversion between the two stacked conformers. These findings will support the development of folding principles for the rational design of functional DNA nanostructures.