Impact of Environmental Exposures on Lung Cancer in Patients Who Never Smoked.

BACKGROUND: Despite the rising incidence of lung cancer in patients who never smoked, environmental risk factors such as ambient air pollution in this group are poorly described. Our objective was to identify the relationship of environmental exposures with lung cancer in patients who never smoked. METHODS: A prospectively collected database was reviewed for all patients with non-small cell lung carcinoma (NSCLC) who underwent resection from 2006 to 2021. Environmental exposures were estimated using the geocoded home address of patients. Logistic regression was used to determine the association of clinical and environmental variables with smoking status. Kaplan-Meier and Cox proportional hazards analyses were used to assess survival. RESULTS: A total of 665 patients underwent resection for NSCLC, of which 67 (10.1%) were patients who never smoked and 598 (89.9%) were current/former smokers. Patients who never smoked were more likely of white race (p = 0.001) and had well-differentiated tumors with carcinoid or adenocarcinoma histology (p < 0.001). Environmental exposures were similar between groups, but patients who never smoked had less community material deprivation (p = 0.002) measured by household income, education, health insurance, and vacancies. They had improved overall survival (p = 0.012) but equivalent cancer recurrence (p = 0.818) as those who smoked. In univariable Cox analyses, fine particulate matter (HR: 1.447 [95% CI 1.197-1.750], p < 0.001), distance to nearest major roadway (HR: 1.067 [1.024-1.111], p = 0.002), and greenspace (HR: 0.253 [0.087-0.737], p = 0.012) were associated with overall survival in patients who never smoked. CONCLUSIONS: Lung cancer patients who never smoked have unique clinical and pathologic characteristics, including higher socioeconomic status. Interventions to reduce environmental exposures may improve lung cancer survival in this population.

Brain microstructural antecedents of visual difficulties in infants born very preterm.

Infants born very preterm (VPT) are at risk of later visual problems. Although neonatal screening can identify ophthalmologic abnormalities, subtle perinatal brain injury and/or delayed brain maturation may be significant contributors to complex visual-behavioral problems. Our aim was to assess the micro and macrostructural antecedents of early visual-behavioral difficulties in VPT infants by using diffusion MRI (dMRI) at term-equivalent age. We prospectively recruited a cohort of 262 VPT infants (≤32 weeks gestational age [GA]) from five neonatal intensive care units. We obtained structural and diffusion MRI at term-equivalent age and administered the Preverbal Visual Assessment (PreViAs) questionnaire to parents at 3-4 months corrected age. We used constrained spherical deconvolution to reconstruct nine white matter tracts of the visual pathways with high reliability and performed fixel-based analysis to derive fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC). In multiple logistic regression analyses, we related these tract metrics to visual-behavioral function. Of 262 infants, 191 had both high-quality dMRI and completed PreViAs, constituting the final cohort: mean (SD) GA was 29.3 (2.4) weeks, 90 (47.1%) were males, and postmenstrual age (PMA) at MRI was 42.8 (1.3) weeks. FD and FC of several tracts were altered in infants with (N = 59) versus those without retinopathy of prematurity (N = 132). FDC of the left posterior thalamic radiations (PTR), left inferior longitudinal fasciculus (ILF), right superior longitudinal fasciculus (SLF), and left inferior fronto-occipital fasciculus (IFOF) were significantly associated with visual attention scores, prior to adjusting for confounders. After adjustment for PMA at MRI, GA, severe retinopathy of prematurity, and total brain volume, FDC of the left PTR, left ILF, and left IFOF remained significantly associated with visual attention. Early visual-behavioral difficulties in VPT infants are preceded by micro and macrostructural abnormalities in several major visual pathways at term-equivalent age.

Early micro- and macrostructure of sensorimotor tracts and development of cerebral palsy in high risk infants.

Infants born very preterm (VPT) are at high risk of motor impairments such as cerebral palsy (CP), and diagnosis can take 2 years. Identifying in vivo determinants of CP could facilitate presymptomatic detection and targeted intervention. Our objectives were to derive micro- and macrostructural measures of sensorimotor white matter tract integrity from diffusion MRI at term-equivalent age, and determine their association with early diagnosis of CP. We enrolled 263 VPT infants (≤32 weeks gestational age) as part of a large prospective cohort study. Diffusion and structural MRI were acquired at term. Following consensus guidelines, we defined early diagnosis of CP based on abnormal structural MRI at term and abnormal neuromotor exam at 3-4 months corrected age. Using Constrained Spherical Deconvolution, we derived a white matter fiber orientation distribution (fOD) for subjects, performed probabilistic whole-brain tractography, and segmented nine sensorimotor tracts of interest. We used the recently developed fixel-based (FB) analysis to compute fiber density (FD), fiber-bundle cross-section (FC), and combined fiber density and cross-section (FDC) for each tract. Of 223 VPT infants with high-quality diffusion MRI data, 14 (6.3%) received an early diagnosis of CP. The cohort's mean (SD) gestational age was 29.4 (2.4) weeks and postmenstrual age at MRI scan was 42.8 (1.3) weeks. FD, FC, and FDC for each sensorimotor tract were significantly associated with early CP diagnosis, with and without adjustment for confounders. Measures of sensorimotor tract integrity enhance our understanding of white matter changes that antecede and potentially contribute to the development of CP in VPT infants.

Near-infrared laser thermal conjunctivoplasty.

Conjunctivochalasis is a common cause of tear dysfunction due to the conjunctiva becoming loose and wrinkly with age. The current solutions to this disease include either surgical excision in the operating room, or thermoreduction of the loose tissue with hot wire in the clinic. We developed a near-infrared laser thermal conjunctivoplasty system. The system utilizes a 1460-nm programmable laser diode system as the light source. At this wavelength, a water absorption peak exists and the blood absorption is minimal, so the heating of redundant conjunctiva is even and there is no bleeding. A miniaturized handheld probe delivers the laser light and reshapes the laser into a 10 × 1 mm2 line on the working plane. A foot pedal is used to deliver a preset number of calibrated laser pulses. A fold of loose conjunctiva is grasped by a pair of forceps. The NIR laser light is delivered through an optical fiber and a laser line is aimed exactly on the conjunctival fold by a cylindrical lens. Ex vivo experiments using porcine eye was performed to investigate the induced shrinkage of conjunctiva and decide the optimal laser parameters. It was found that up to 45% of conjunctiva shrinkage could be achieved.

Polarization-multiplexed, dual-beam swept source optical coherence tomography angiography.

A polarization-multiplexed, dual-beam setup is proposed to expand the field of view (FOV) for a swept source optical coherence tomography angiography (OCTA) system. This method used a Wollaston prism to split sample path light into 2 orthogonal-polarized beams. This allowed 2 beams to shine on the cornea at an angle separation of ~14°, which led to a separation of ~4.2 mm on the retina. A 3-mm glass plate was inserted into one of the beam paths to set a constant path length difference between the 2 polarized beams so the interferogram from the 2 beams are coded at different frequency bands. The resulting OCTA images from the 2 beams were coded with a depth separation of ~2 mm. A total of 5 × 5 mm2 angiograms from the 2 beams were obtained simultaneously in 4 seconds. The 2 angiograms then were montaged to get a wider FOV of ~5 × 9.2 mm2 .

Calibration of optical coherence tomography angiography with a microfluidic chip.

A microfluidic chip with microchannels ranging from 8 to 96 µm was used to mimic blood vessels down to the capillary level. Blood flow within the microfluidic channels was analyzed with split-spectrum amplitude-decorrelation angiography (SSADA)-based optical coherence tomography (OCT) angiography. It was found that the SSADA decorrelation value was related to both blood flow speed and channel width. SSADA could differentiate nonflowing blood inside the microfluidic channels from static paper. The SSADA decorrelation value was approximately linear with blood flow velocity up to a threshold Vsat of 5.83±1.33 mm/s (mean±standard deviation over the range of channel widths). Beyond this threshold, it approached a saturation value Dsat. Dsat was higher for wider channels, and approached a maximum value Dsm as the channel width became much larger than the beam focal spot diameter. These results indicate that decorrelation values (flow signal) in capillary networks would be proportional to both flow velocity and vessel caliber but would be capped at a saturation value in larger blood vessels. These findings are useful for interpretation and quantification of clinical OCT angiography results.

Split-spectrum phase-gradient optical coherence tomography angiography.

A phase gradient angiography (PGA) method is proposed for optical coherence tomography (OCT). This method allows the use of phase information to map the microvasculature in tissue without the correction of bulk motion and laser trigger jitter induced phase artifacts. PGA can also be combined with the amplitude/intensity to improve the performance. Split-spectrum technique can further increase the signal to noise ratio by more than two times. In-vivo imaging of human retinal circulation is shown with a 70 kHz, 840 nm spectral domain OCT system and a 200 kHz, 1050 nm swept source OCT system. Four different OCT angiography methods are compared. The best performance was achieved with split-spectrum amplitude and phase-gradient angiography.