Radiation Principles, Protection, and Reporting for Interventional Pulmonology: A World Association of Bronchology and Interventional Pulmonology White Paper.

The use and availability of diverse advanced X-ray based imaging and guidance systems in the field of interventional pulmonology are rapidly growing. This popularity links inextricably to an increase in ionizing radiation use. Knowing ionizing radiation is hazardous, knowledge and competent use of X-ray imaging and guidance systems are important. The globally implemented As Low As Reasonably Achievable (ALARA) principle demands careful attention to minimize radiation exposure while achieving the precise goals of the intervention and imaging therein. To allow careful and targeted weighing of risk against reward while using X-ray based equipment, proper background knowledge of physics as well as imaging system aspects are needed. This white paper summarizes the principles of ionizing radiation which are crucial to enhance awareness and interpretation of dosimetric quantities. Consecutively, a consensus on standards for reporting radiation exposure in interventional pulmonology procedures is indicated to facilitate comparisons between different systems, approaches and results. Last but not least, it provides a list of practical measures, considerations and tips to optimize procedural imaging as well as reduce radiation dose to patients and staff.

A Multicenter, Single-Arm, Prospective Trial Assessing the Diagnostic Yield of Electromagnetic Bronchoscopic and Transthoracic Navigation for Peripheral Pulmonary Nodules.

Rationale: Strict adherence to procedural protocols and diagnostic definitions is critical to understand the efficacy of new technologies. Electromagnetic navigational bronchoscopy (ENB) for lung nodule biopsy has been used for decades without a solid understanding of its efficacy, but offers the opportunity for simultaneous tissue acquisition via electromagnetic navigational transthoracic biopsy (EMN-TTNA) and staging via endobronchial ultrasound (EBUS). Objective: To evaluate the diagnostic yield of EBUS, ENB, and EMN-TTNA during a single procedure using a strict a priori definition of diagnostic yield with central pathology adjudication. Methods: A prospective, single-arm trial was conducted at eight centers enrolling participants with pulmonary nodules (<3 cm; without computed tomography [CT]- and/or positron emission tomography-positive mediastinal lymph nodes) who underwent a staged procedure with same-day CT, EBUS, ENB, and EMN-TTNA. The procedure was staged such that, when a diagnosis had been achieved via rapid on-site pathologic evaluation, the procedure was ended and subsequent biopsy modalities were not attempted. A study finding was diagnostic if an independent pathology core laboratory confirmed malignancy or a definitive benign finding. The primary endpoint was the diagnostic yield of the combination of CT, EBUS, ENB, and EMN-TTNA. Measurements and Main Results: A total of 160 participants at 8 centers with a mean nodule size of 18 ± 6 mm were enrolled. The diagnostic yield of the combined procedure was 59% (94 of 160; 95% confidence interval [CI], 51-66%). Nodule regression was found on same-day CT in 2.5% of cases (4 of 160; 95% CI, 0.69-6.3%), and EBUS confirmed malignancy in 7.1% of cases (11 of 156; 95% CI, 3.6-12%). The yield of ENB alone was 49% (74 of 150; 95% CI, 41-58%), that of EMN-TTNA alone was 27% (8 of 30; 95% CI, 12-46%), and that of ENB plus EMN-TTNA was 53% (79 of 150; 95% CI, 44-61%). Complications included a pneumothorax rate of 10% and a 2% bleeding rate. When EMN-TTNA was performed, the pneumothorax rate was 30%. Conclusions: The diagnostic yield for ENB is 49%, which increases to 59% with the addition of same-day CT, EBUS, and EMN-TTNA, lower than in prior reports in the literature. The high complication rate and low diagnostic yield of EMN-TTNA does not support its routine use. Clinical trial registered with www.clinicaltrials.gov (NCT03338049).

Ocular surface and meibomian gland evaluation in euthyroid Graves' ophthalmopathy.

PURPOSE: Euthyroid Graves' ophthalmology (EGO) refers to the subgroup of thyroid eye disease patients with distinct clinical presentations. This study evaluated the ocular surface and meibomian gland changes in EGO patients. METHODS: A cross-sectional study was conducted at The Chinese University of Hong Kong including 34 EGO patients and 34 age-and sex- matched healthy controls. Outcome measures include anterior segment examination, keratographic and meibographic imaging. RESULTS: Between 34 EGO patients and 34 age and sex-matched healthy controls, EGO was associated with a higher ocular surface disease index (P < 0.01), higher severity of meibomian gland dropout (upper: P < 0.001, lower: P < 0.00001) and higher percentage of partial blinking (P = 0.0036). The worse affected eyes of the EGO patients were associated with corneal staining (P = 0.0019), eyelid telangiectasia (P = 0.0009), eyelid thickening (P = 0.0013), eyelid irregularity (P = 0.0054), meibomian gland plugging (P < 0.00001), expressibility (P < 0.00001), and meibum quality (P < 0.00001). When the two eyes of the same EGO patient were compared, the degree of meibomian gland dropout was higher among the worse affected eyes (upper: P < 0.00001, and lower: P < 0.00001). Tear meniscus height, lipid layer thickness, and noninvasive break-up time were comparable between the two eyes of EGO patients and also between EGO patients and healthy controls. TMH was positively correlated with the degree of exophthalmos (r = 0.383, P < 0.05). CONCLUSION: EGO patients have more ocular surface complications and meibomian gland dropouts than healthy controls. Almost 60% of them had dry eye symptoms, but aqueous deficiency was not apparent. Further studies are warranted to clarify the mechanism of dry eye in EGO. (249 words).

Bronchoscopic Evaluation of a Steerable Needle for Simulated Tumor Targets in the Lung Periphery: A Feasibility Study (Bullseye).

BACKGROUND: Peripheral bronchoscopy is often performed to biopsy peripheral pulmonary lesions. Despite technological advancements to improve reach and access to the lung periphery, the diagnostic yield of peripheral bronchoscopy has been inconsistent, and challenging, particularly for lesions that are adjacent to peripheral bronchi. Current biopsy instruments are reliant on the catheter or scope to align properly with targeted lesions. OBJECTIVES: This study evaluates the feasibility of using a steerable biopsy needle to gain access to peripheral tumor targets in a cadaveric model. METHODS: Simulated tumor targets 10-30 mm in axial diameter were placed into human cadavers. Bronchoscopy was performed using a 4.2 mm OD flexible bronchoscope, CT-anatomic correlation, and multi-planar fluoroscopy for lesion localization. Once at the targeted location, a steerable needle was deployed and the needle position was determined to be in the central zone, peripheral zone, or outside of the lesion by cone beam CT imaging. If the needle position was within the lesion, a fiducial marker was deployed to mark the needle position, and the needle was articulated and/or rotated in an attempt to place another fiducial marker into a different location within the same lesion. If the needle was outside of the lesion, the bronchoscopist was provided with two additional attempts to gain access to the lesion. RESULTS: Fifteen tumor targets were placed with a mean lesion size of 20.4 mm. The majority of lesions were located in the upper lobes. One fiducial marker was placed in 93.3% of lesions and a second fiducial marker was successfully placed in 80% of lesions. A fiducial marker was placed within the central zone in 60% of lesions. CONCLUSION: The steerable needle was successfully placed within 93% of targeted lesions 10-30 mm in diameter in a cadaveric model, with the ability steer the instrument into another portion of the lesion in 80% of cases. The ability to steer and control needle positioning toward and within peripheral lesions may complement existing catheter and scope technology during peripheral diagnostic procedures.

Minimally invasive delivery of a hydrogel-based exosome patch to prevent heart failure.

Coronary heart disease (CHD) has been the number one killer in the United States for decades and causes millions of deaths each year. Clinical treatment of heart ischemic injury relieves symptoms in the acute stage of CHD; however, patients with an infarcted heart muscle can develop heart failure (HF) due to chronic maladaptive remodeling. Regenerative therapy has been studied as a potential treatment option for myocardial infarction (MI) and HF. Cardiac patches have been designed and tested to increase therapeutic retention and integration. However, the delivery usually requires invasive surgical techniques, including open-chest surgeries and heart manipulation. Those procedures may cause chronic adhesions between the heart anterior wall and the chest wall. This study created and tested an injectable ExoGel by embedding mesenchymal stem cell (MSC) -derived exosomes into a hyaluronic acid (HA) hydrogel. ExoGel was injected into the pericardial cavity of rats with transverse aortic constriction (TAC) induced heart failure. ExoGel therapy reduced LV chamber size and preserved wall thickness. The feasibility and safety of ExoGel injection were further confirmed in a pig model.

Microbial community development during syngas methanation in a trickle bed reactor with various nutrient sources.

Microbial community development within an anaerobic trickle bed reactor (TBR) during methanation of syngas (56% H2, 30% CO, 14% CO2) was investigated using three different nutrient media: defined nutrient medium (241 days), diluted digestate from a thermophilic co-digestion plant operating with food waste (200 days) and reject water from dewatered digested sewage sludge at a wastewater treatment plant (220 days). Different TBR operating periods showed slightly different performance that was not clearly linked to the nutrient medium, as all proved suitable for the methanation process. During operation, maximum syngas load was 5.33 L per L packed bed volume (pbv) & day and methane (CH4) production was 1.26 L CH4/Lpbv/d. Microbial community analysis with Illumina Miseq targeting 16S rDNA revealed high relative abundance (20-40%) of several potential syngas and acetate consumers within the genera Sporomusa, Spirochaetaceae, Rikenellaceae and Acetobacterium during the process. These were the dominant taxa except in a period with high flow rate of digestate from the food waste plant. The dominant methanogen in all periods was a member of the genus Methanobacterium, while Methanosarcina was also observed in the carrier community. As in reactor effluent, the dominant bacterial genus in the carrier was Sporomusa. These results show that syngas methanation in TBR can proceed well with different nutrient sources, including undefined medium of different origins. Moreover, the dominant syngas community remained the same over time even when non-sterilised digestates were used as nutrient medium. KEY POINTS: • Independent of nutrient source, syngas methanation above 1 L/Lpbv/D was achieved. • Methanobacterium and Sporomusa were dominant genera throughout the process. • Acetate conversion proceeded via both methanogenesis and syntrophic acetate oxidation.

Tracheostomy for COVID-19 Respiratory Failure: Multidisciplinary, Multicenter Data on Timing, Technique, and Outcomes.

OBJECTIVE: The aim of this study was to assess the outcomes of tracheostomy in patients with COVID-19 respiratory failure. SUMMARY BACKGROUND DATA: Tracheostomy has an essential role in managing COVID-19 patients with respiratory failure who require prolonged mechanical ventilation. However, limited data are available on how tracheostomy affects COVID-19 outcomes, and uncertainty surrounding risk of infectious transmission has led to divergent recommendations and practices. METHODS: It is a multicenter, retrospective study; data were collected on all tracheostomies performed in COVID-19 patients at 7 hospitals in 5 tertiary academic medical systems from February 1, 2020 to September 4, 2020. RESULT: Tracheotomy was performed in 118 patients with median time from intubation to tracheostomy of 22 days (Q1-Q3: 18-25). All tracheostomies were performed employing measures to minimize aerosol generation, 78.0% by percutaneous technique, and 95.8% at bedside in negative pressure rooms. Seventy-eight (66.1%) patients were weaned from the ventilator and 18 (15.3%) patients died from causes unrelated to tracheostomy. No major procedural complications occurred. Early tracheostomy (≤14 days) was associated with decreased ventilator days; median ventilator days (Q1-Q3) among patients weaned from the ventilator in the early, middle and late groups were 21 (21-31), 34 (26.5-42), and 37 (32-41) days, respectively with P = 0.030. Compared to surgical tracheostomy, percutaneous technique was associated with faster weaning for patients weaned off the ventilator [median (Q1-Q3): 34 (29-39) vs 39 (34-51) days, P = 0.038]; decreased ventilator-associated pneumonia (58.7% vs 80.8%, P = 0.039); and among patients who were discharged, shorter intensive care unit duration [median (Q1-Q3): 33 (27-42) vs 47 (33-64) days, P = 0.009]; and shorter hospital length of stay [median (Q1-Q3): 46 (33-59) vs 59.5 (48-80) days, P = 0.001]. CONCLUSION: Early, percutaneous tracheostomy was associated with improved outcomes compared to surgical tracheostomy in a multi-institutional series of ventilated patients with COVID-19.

Predictive models of aging of the human eye based on ocular anterior segment morphology.

Aging is a major risk factor for various eye diseases, such as cataract, glaucoma, and age-related macular degeneration. Age-related changes are observed in almost all structures of the human eye. Considerable individual variations exist within a group of similarly aged individuals, indicating the need for more informative biomarkers for assessing the aging of the eyes. The morphology of the ocular anterior segment has been reported to vary across age groups, focusing on only a few corneal parameters, such as keratometry and thickness of the cornea, which could not provide accurate estimation of age. Thus, the association between eye aging and the morphology of the anterior segment remains elusive. In this study, we aimed to develop a predictive model of age based on a large number of anterior segment morphology-related features, measured via the high-resolution ocular anterior segment analysis system (Pentacam). This approach allows for an integrated assessment of age-related changes in corneal morphology, and the identification of important morphological features associated with different eye aging patterns. Three machine learning methods (neural networks, Lasso regression and extreme gradient boosting) were employed to build predictive models using 276 anterior segment features of 63,753 participants from 10 ophthalmic centers in 10 different cities of China. The best performing age prediction model achieved a median absolute error of 2.80 years and a mean absolute error of 3.89 years in the validation set. An external cohort of 100 volunteers was used to test the performance of the prediction model. The developed neural network model achieved a median absolute error of 3.03 years and a mean absolute error of 3.40 years in the external cohort. In summary, our study revealed that the anterior segment morphology of the human eye may be an informative and non-invasive indicator of eye aging. This could prompt doctors to focus on age-related medical interventions on ocular health.

Repeatability of pupil size measurements with NIDEK OPD-Scan III in myopic children.

OBJECTIVE: To investigate the repeatability of pupil size measurements, determined from the NIDEK OPD-Scan III, of myopic eyes in children wearing single-vision spectacles (SVS), undergoing orthokeratology (OK) and receiving combined treatment of 0.01% atropine and orthokeratology (AOK). METHODS: A single examiner took two sets of mesopic pupil size measurements from the right eyes of 80 children (SVS:16, OK: 34, AOK: 30) (mesopic 1 and mesopic 2) and two sets of photopic (photopic 1 and photopic 2) pupil size measurements (internal light source) using the NIDEK OPD-Scan III. Each set was taken at a single visit, 15 min apart. Subjects in the OK and AOK groups had undergone treatment for at least 6 months, and the SVS subjects had no previous myopia treatment other than wearing spectacles. Repeatability of measurements was analysed using intraclass correlation coefficient (ICC), Bland-Altman (BA) plot, and coefficient of repeatability (CoR). RESULTS: Mesopic 1 and 2 values were not significantly different among the three groups (p = 0.56, 0.77), hence the data were pooled for each set of measurements (mean [±S.D.] values were 7.09 ± 0.61 and 7.12 ± 0.61 mm, respectively) for further analyses. ICC for repeated mesopic pupil size measurements was 0.98 (95% CI, 0.98-0.99). No significant correlation was found between the means of the mesopic 1 and 2 measurements and their differences (Pearson's r = -0.02, p = 0.83). A BA plot also demonstrated narrow 95% limits of agreement, with a CoR of 0.28 mm. Mean photopic 1 and 2 measurements for the AOK group (3.74 ± 0.46; 3.73 ± 0.43 mm, respectively) were significantly larger (p = 0.01; 0.009) than those of the SVS and OK groups, but no significant difference was found between the latter two groups (p > 0.05). Hence, photopic 1 and 2 measurements for the SVS and OK groups were pooled (SVS-OK) for further analyses. ICC for repeatability of the photopic measurements was 0.98 (95% CI, 0.96 to 0.99) for the SVS-OK and AOK groups. The differences between photopic 1 and 2 measurements were not significantly correlated with their means, either in the AOK group (Pearson's r = -0.25, p = 0.19), or in the pooled SVS-OK group (Pearson's r = -0.04, p = 0.78). BA plots also showed narrow 95% limits of agreement, and CoR was 0.25 mm and 0.23 mm in the AOK and pooled SVS-OK groups, respectively. CONCLUSION: Mesopic and photopic pupil size measurement using the NIDEK OPD-Scan III was highly repeatable and suitable for use on children.

Transepithelial corneal collagen cross-linking using iontophoresis versus the Dresden protocol in progressive keratoconus: A meta-analysis.

BACKGROUND: Standard epithelium-off collagen cross-linking using Dresden protocol (S-CXL) is the standard of care for progressive keratoconus. Despite its efficacy, epithelial debridement is associated with pain, delayed visual rehabilitation, stromal oedema and haze. Minimising these complications while achieving a comparable efficacy remains an unmet need. METHODS: Comparative studies between transepithelial iontophoresis-assisted CXL (I-CXL) and S-CXL reporting the outcomes of visual, refractive, topographic, aberrometry, demarcation line, endothelial cell density, confocal microscopy or complications were identified from databases. Assessments of publication bias, meta-analyses, sensitivity analysis, subgroup analysis, and meta-regressions were performed. RESULTS: In this meta-analysis, 586 eyes from three randomised controlled trials and seven comparative studies were analysed. No differences were found in the change in uncorrected/corrected distance visual acuities, mean/maximum keratometry, central corneal thickness, higher order aberration, spherical aberration, coma, subbasal nerve/anterior stromal keratocyte density and demarcation line depth in both CXL protocols (P ≥ .052). However, I-CXL resulted in less thinning at the minimum pachymetry (standardised mean difference 0.25; 95% confidence interval [CI] 0.06-0.44). More importantly, there was a significant reduction in complications following I-CXL (odds ratio 0.30; 95% CI 0.12-0.75). Meta-regression analyses on demarcation line depth and complication suggested that I-CXL was more effective than S-CXL when baseline maximum keratometry was >55.2 D and the risk of complication was independent of other baseline covariates. CONCLUSION: I-CXL has a more favourable safety profile, as evidenced by the available literature, with less thinning at the minimum pachymetry and reduced risk of complications while achieving comparable effects on visual, refractive, topographic, aberrometry, and morphological outcomes as S-CXL.

One-year results of 0.01% atropine with orthokeratology (AOK) study: a randomised clinical trial.

PURPOSE: To report the 1-year results of an investigation into whether there is an additive effect between 0.01% atropine and orthokeratology (ortho-k), in a single-masked, two-arm, randomised controlled trial: Combined Atropine with Orthokeratology (AOK) for myopia control study (ClinicalTrials.gov number: NCT02955927). METHODS: Chinese children aged between 6 and 11 years with 1.00-4.00 D of myopia, astigmatism <2.50 D, and no more than 1.00 D anisometropia, were randomly assigned either to an AOK group or ortho-k only (OK) group at a 1:1 ratio. Subjects in the AOK group instilled one drop of 0.01% atropine into each eye, 10 min before nightly wear of ortho-k lenses. The primary outcome, axial elongation, was examined at 6-monthly intervals, along with secondary outcomes including best-corrected visual acuity (BCVA), manifest refraction, accommodation, pupil size, and corneal topography. RESULTS: 29 AOK and 30 OK subjects completed the 1-year visit. The overall axial elongation rate was significantly slower in the AOK group than in the OK group (mean (S.D.), 0.07 (0.16) mm vs 0.16 (0.15) mm, respectively; p = 0.03). A significant between-group difference in axial elongation was observed over the first 6-month period only (p < 0.001), but not over the second period (p = 0.818). At the 1-year visit, increases in mean (S.D.) mesopic and photopic pupil sizes in the AOK group were 0.64 (0.48) mm and 0.36 (0.34) mm, respectively, which were significantly higher than 0.10 (0.50) mm and 0.02 (0.28) mm in the OK group (p < 0.001). At the 6-month visit, a significant moderate negative correlation was found between axial elongation and the increase in photopic pupil size (r = -0.42, p = 0.02) in the AOK group. CONCLUSIONS: There is an additive effect between 0.01% atropine and ortho-k over one year, with mean axial elongation in the AOK group 0.09 mm slower than that in the OK group. It appears that the additive effect was only during the first six months; a second-year investigation is warranted to determine whether the effect is sustained over time.

Higher order aberrations and axial elongation in combined 0.01% atropine with orthokeratology for myopia control.

PURPOSE: To compare the changes in higher order aberrations (HOA's) for photopic and mesopic pupil diameters in children undergoing orthokeratology treatment (OK) or combined 0.01% atropine with orthokeratology treatment (AOK), and their association with axial elongation. METHODS: Children aged 6 to <11 years with 1.00-4.00 D of myopia were randomly assigned to each treatment group. Photopic and mesopic pupil diameters were quantified using automated pupillometry and HOA's were measured with a Hartmann-Shack aberrometer and Badal system to control for accommodation. HOA's were rescaled to photopic and mesopic pupil diameters and fitted with a 6th order Zernike polynomial expansion. Axial length was measured using an optical biometer under cycloplegia. RESULTS: Baseline and six-month data from 25 AOK and 28 OK participants were analysed. At the six-month visit, pupil diameter was larger in the AOK group under photopic conditions (3.70 ± 0.42 vs 3.12 ± 0.33 mm, p < 0.001), along with a range of HOA metrics [3rd to 6th order and higher order root mean square error values (HO RMS), all p ≤ 0.003] and individual Zernike terms (primary spherical aberration, and oblique quadrafoil, both p ≤ 0.03). Axial elongation was greater in the OK treatment group (0.05 ± 0.08 vs -0.01 ± 0.12 mm, p = 0.02). In the AOK group, axial elongation was correlated with the increase in photopic pupil diameter (r = -0.45, p = 0.02) and with several HOA metrics; however, these associations were not observed in the OK group. CONCLUSION: AOK treatment resulted in increased photopic pupil size and HOA's, and significantly less axial elongation over a six-month period compared to OK treatment alone. The improved myopia control observed with combination 0.01% atropine and orthokeratology may be a result of an enhanced optical effect due to a larger photopic pupil size.

Effect of corneal curvature on optical zone decentration and its impact on astigmatism and higher-order aberrations in SMILE and LASIK.

PURPOSE: To determine the association between anterior corneal curvature and optical zone centration as well as its impact on aberration profiles in small-incision lenticule extraction (SMILE) and laser in situ keratomileusis (LASIK). METHODS: Seventy-eight eyes of 78 patients treated with SMILE (45 eyes) and LASIK (33 eyes) were included. The centration of the optical zone was evaluated on the instantaneous curvature difference map between the preoperative and 3-month postoperative scans using a superimposed set of concentric circles. The correlation between optical zone decentration and anterior keratometry values was evaluated. The effect of optical zone decentration on vector components of astigmatic correction and induction of higher-order aberrations (HOA) was assessed. RESULTS: The mean decentration distance was 0.21 ± 0.11 mm for SMILE and 0.20 ± 0.09 mm for LASIK (p = 0.808). There was a significant correlation between anterior keratometric astigmatism and decentration distance (r = 0.653, p < 0.001) for SMILE but not for LASIK (r = - 0.264, p = 0.138). Astigmatic correction was performed in 67 eyes. Optical zone decentration and the vector components of astigmatic correction were not correlated (p ≥ 0.420). Significant correlation was demonstrated between the decentration distance and the induced total coma (SMILE: r = 0.384, p = 0.009; LASIK: r = 0.553, p = 0.001) as well as the induced total HOA (SMILE: r = 0.498, p = 0.001; LASIK: r = 0.555, p = 0.001). CONCLUSION: Anterior cornea astigmatism affected the treatment centration in SMILE but not LASIK. Subclinical decentration was associated with the induction of total coma and total HOA, but it did not affect the lower-order astigmatic correction.

Clinical and radiographic predictors of successful therapeutic bronchoscopy for the relief of malignant central airway obstruction.

BACKGROUND: Malignant central airway obstruction (CAO) occurs in approximately 20-30% of patients with lung cancer and is associated with debilitating symptoms and poor prognosis. Multimodality therapeutic bronchoscopy can relieve malignant CAO, though carries risk. Evidence to guide clinicians regarding which patients may benefit from such interventions is sparse. We aimed to assess the clinical and radiographic predictors associated with therapeutic bronchoscopy success in relieving malignant CAO. METHODS: We reviewed all cases of therapeutic bronchoscopy performed for malignant CAO at our institution from January 2010-February 2017. Therapeutic bronchoscopy success was defined as establishing airway patency of > 50%. Patient demographics and baseline characteristics, oncology history, degree of airway obstruction, procedural interventions, and complications were compared between successful and unsuccessful groups. Univariate and multivariate logistic regression identified the significant clinical and radiographic predictors for therapeutic success. The corresponding simple and conditional odds ratio were calculated. A time-to-event analysis with Kaplan-Meier plots was performed to estimate overall survival. RESULTS: During the study period, 301 therapeutic bronchoscopies were performed; 44 (14.6%) were considered unsuccessful. Factors associated with success included never vs current smoking status (OR 5.36, 95% CI:1.45-19.74, p = 0.010), patent distal airway on CT imaging (OR 15.11, 95% CI:2.98-45.83, p < 0.0001) and patent distal airway visualized during bronchoscopy (OR 10.77, 95% CI:3.63-31.95, p < 0.001) in univariate analysis. Along with patent distal airway on CT imaging, increased time from radiographic finding to therapeutic bronchoscopy was associated with lower odds of success in multivariate analysis (OR 0.96, 95% CI:0.92-1.00, p = 0.048). Median survival was longer in the successful group (10.2 months, 95% CI:4.8-20.2) compared to the unsuccessful group (6.1 months, 95% CI:2.1-10.8, log rank p = 0.015). CONCLUSIONS: Predictors associated with successful therapeutic bronchoscopy for malignant CAO include distal patent airway visualized on CT scan and during bronchoscopy. Odds of success are higher in non-smokers, and with decreased time from radiographic finding of CAO to intervention.

Transparent antifouling material for improved operative field visibility in endoscopy.

Camera-guided instruments, such as endoscopes, have become an essential component of contemporary medicine. The 15-20 million endoscopies performed every year in the United States alone demonstrate the tremendous impact of this technology. However, doctors heavily rely on the visual feedback provided by the endoscope camera, which is routinely compromised when body fluids and fogging occlude the lens, requiring lengthy cleaning procedures that include irrigation, tissue rubbing, suction, and even temporary removal of the endoscope for external cleaning. Bronchoscopies are especially affected because they are performed on delicate tissue, in high-humidity environments with exposure to extremely adhesive biological fluids such as mucus and blood. Here, we present a repellent, liquid-infused coating on an endoscope lens capable of preventing vision loss after repeated submersions in blood and mucus. The material properties of the coating, including conformability, mechanical adhesion, transparency, oil type, and biocompatibility, were optimized in comprehensive in vitro and ex vivo studies. Extensive bronchoscopy procedures performed in vivo on porcine lungs showed significantly reduced fouling, resulting in either unnecessary or ∼10-15 times shorter and less intensive lens clearing procedures compared with an untreated endoscope. We believe that the material developed in this study opens up opportunities in the design of next-generation endoscopes that will improve visual field, display unprecedented antibacterial and antifouling properties, reduce the duration of the procedure, and enable visualization of currently unreachable parts of the body, thus offering enormous potential for disease diagnosis and treatment.

Glutaredoxin AtGRXC2 catalyses inhibitory glutathionylation of Arabidopsis BRI1-associated receptor-like kinase 1 (BAK1) in vitro.

Reversible protein phosphorylation, catalysed by protein kinases, is the most widely studied post-translational modification (PTM), whereas the analysis of other modifications such as S-thiolation is in its relative infancy. In a yeast-two-hybrid (Y2H) screen, we identified a number of novel putative brassinosteroid insensitive 1 (BR1)-associated receptor-like kinase 1 (BAK1) interacting proteins including several proteins related to redox regulation. Glutaredoxin (GRX) C2 (AtGRXC2) was among candidate proteins identified in the Y2H screen and its interaction with recombinant Flag-BAK1 cytoplasmic domain was confirmed using an in vitro pull-down approach. We show that BAK1 peptide kinase activity is sensitive to the oxidizing agents H2O2 and diamide in vitro, suggesting that cysteine oxidation might contribute to control of BAK1 activity. Furthermore, BAK1 was glutathionylated and this reaction could occur via a thiolate-dependent reaction with GSSG or a H2O2-dependent reaction with GSH and inhibited kinase activity. Surprisingly, both reactions were catalysed by AtGRXC2 at lower concentrations of GSSG or GSH than reacted non-enzymatically. Using MALDI-TOF MS, we identified Cys353, Cys374 and Cys408 as potential sites of glutathionylation on the BAK1 cytoplasmic domain and directed mutagenesis suggests that Cys353 and Cys408 are major sites of GRXC2-mediated glutathionylation. Collectively, these results highlight the potential for redox control of BAK1 and demonstrate the ability of AtGRXC2 to catalyse protein glutathionylation, a function not previously described for any plant GRX. The present work presents a foundation for future studies of glutathionylation of plant receptor-like protein kinases (RLKs) as well as for the analysis of activities of plant GRXs.

Complete genome sequence of Citroniella saccharovorans DSM 29873, isolated from human fecal sample.

A complete genome was recovered from Citroniella saccharovorans, strain DSM 29873, using Oxford Nanopore Technologies. The genome assembly contains 1,413,868 bp with 30.23% G+C content. The species belongs to the family Peptoniphilaceae and, as of yet, is the only cultivated representative of the genus Citroniella.

COVID-19 Related Tracheal Stenosis Requiring Tracheal Resection: A Case Series.

OBJECTIVE: To characterize the preoperative and intraoperative findings of symptomatic tracheal stenosis associated with COVID-19 related respiratory failure requiring tracheal resection. METHOD: We performed a retrospective review identifying all patients with a history of tracheal stenosis secondary to COVID-19 related respiratory failure who subsequently received a tracheal resection at our institution between January 2020 and June 2023. Clinical, radiological, pathological, and surgical characteristics were recorded to describe and characterize pre-operative and intraoperative findings associated with tracheal stenosis in the setting of a previous COVID-19 infection. RESULTS: We retrospectively reviewed 11 patients with COVID-19 related tracheal stenosis that required open tracheal or cricotracheal resection. The mean age was 54.1. Patients were hospitalized for a mean of 49.5 days related to COVID-19 complications. Tracheotomy was completed in 10 patients (90.9%) during their initial hospitalization with COVID-19 related respiratory failure. Patients were intubated a mean of 18.6 days prior to tracheotomy completion. Ten patients (90.9%) underwent endoscopic operative interventions for their tracheal stenosis prior to open resection. Intraoperatively, the mean stenosis length was 3.33 cm. The mean tracheal resection length was 3.96 cm. Patients were hospitalized for a mean of 8.27 days post operatively with no significant post operative complications. CONCLUSIONS: Symptomatic tracheal stenosis in the setting of prolonged intubation due to COVID-19 is an under-described etiology. This is one of the largest single institution retrospective reviews that identifies 11 patients with prolonged intubation who developed symptomatic tracheal stenosis refractory to conservative management and ultimately requiring tracheal resection.