Anti-Granulocyte-Macrophage Colony-Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial.

Rationale: GM-CSF (granulocyte-macrophage colony-stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). Objectives: We sought to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. Measurements and Main Results: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [-6 to 17]; P = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. Conclusions: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. Clinical trial registered with www.clinicaltrials.gov (NCT04351243).

Fostamatinib for the Treatment of Hospitalized Adults With Coronavirus Disease 2019: A Randomized Trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) requiring hospitalization is characterized by robust antibody production, dysregulated immune response, and immunothrombosis. Fostamatinib is a novel spleen tyrosine kinase inhibitor that we hypothesize will ameliorate Fc activation and attenuate harmful effects of the anti-COVID-19 immune response. METHODS: We conducted a double-blind, randomized, placebo-controlled trial in hospitalized adults requiring oxygen with COVID-19 where patients receiving standard of care were randomized to receive fostamatinib or placebo. The primary outcome was serious adverse events by day 29. RESULTS: A total of 59 patients underwent randomization (30 to fostamatinib and 29 to placebo). Serious adverse events occurred in 10.5% of patients in the fostamatinib group compared with 22% in placebo (P = .2). Three deaths occurred by day 29, all receiving placebo. The mean change in ordinal score at day 15 was greater in the fostamatinib group (-3.6 ±â€…0.3 vs -2.6 ±â€…0.4, P = .035) and the median length in the intensive care unit was 3 days in the fostamatinib group vs 7 days in placebo (P = .07). Differences in clinical improvement were most evident in patients with severe or critical disease (median days on oxygen, 10 vs 28, P = .027). There were trends toward more rapid reductions in C-reactive protein, D-dimer, fibrinogen, and ferritin levels in the fostamatinib group. CONCLUSION: For COVID-19 requiring hospitalization, the addition of fostamatinib to standard of care was safe and patients were observed to have improved clinical outcomes compared with placebo. These results warrant further validation in larger confirmatory trials. CLINICAL TRIALS REGISTRATION: Clinicaltrials.gov, NCT04579393.

Idiopathic pulmonary fibrosis patients with severe physiologic impairment: characteristics and outcomes.

RESEARCH QUESTION: There is no widely accepted grading system for IPF disease severity, although physiologic impairment based on pulmonary function testing is frequently employed. We sought to describe clinical and functional characteristics as well as outcomes of patients with severe physiologic impairment. PATIENTS AND METHODS: IPF patients with severe physiologic impairment defined by FVC ≤ 50% and/or DLco ≤ 30% predicted evaluated in the Inova Advanced Lung Disease Program between 2011 and 2019 were included. Demographic, physiologic, functional treatment and outcome data were collated. RESULTS: There were 531 patients with IPF evaluated of whom 242 (46%) had severe physiologic impairment. Mean age was 72 ± 8 years; baseline FVC was 53 ± 17% and DLCO 28 ± 9% of predicted. The mean 6 min walks test (6MWT) distance was 304 ± 121 m with 59% of the patients requiring supplemental oxygen ([Formula: see text] group). There was a poor correlation between the 6MWT distance and both FVC% and DLco%. Patients in the 6MWTRA group had a better transplant-free survival than the [Formula: see text] group (p = 0.002). Patients managed before October 2014 and not receiving antifibrotic therapy had worse outcomes with reduced transplant-free survival compared with patients presenting after this date who did receive antifibrotic therapy (n = 113) (log rank p < 0.0001). CONCLUSION: IPF patients often present with severe physiologic impairment which may be poorly correlated with their functional status. Assessment of IPF disease severity should not be based on physiologic impairment alone, but should also encompass functional status as well as need for supplemental oxygen. Antifibrotic therapy in patients with severe physiologic impairment is associated with improved outcomes.

Impaired Myofibroblast Dedifferentiation Contributes to Nonresolving Fibrosis in Aging.

Idiopathic pulmonary fibrosis (IPF) is a fatal age-associated disease with no cure. Although IPF is widely regarded as a disease of aging, the cellular mechanisms that contribute to this age-associated predilection remain elusive. In this study, we sought to evaluate the consequences of senescence on myofibroblast cell fate and fibrotic responses to lung injury in the context of aging. We demonstrated that nonsenescent lung myofibroblasts maintained the capacity for dedifferentiation, whereas senescent/IPF myofibroblasts exhibited an impaired capacity for dedifferentiation. We previously demonstrated that the transcription factor MyoD acts as a critical switch in the differentiation and dedifferentiation of myofibroblasts. Here, we demonstrate that decreased levels of MyoD preceded myofibroblast dedifferentiation and apoptosis susceptibility in nonsenescent cells, whereas MyoD expression remained elevated in senescent/IPF myofibroblasts, which failed to undergo dedifferentiation and demonstrated resistance to apoptosis. Genetic strategies to silence MyoD restored the susceptibility of IPF myofibroblasts to undergo apoptosis and led to a partial reversal of age-associated persistent fibrosis in vivo. The capacity for myofibroblast dedifferentiation and subsequent apoptosis may be critical for normal physiologic responses to tissue injury, whereas restricted dedifferentiation and apoptosis resistance in senescent cells may underlie the progressive nature of age-associated human fibrotic disorders. These studies support the concept that senescence may promote profibrotic effects via impaired myofibroblast dedifferentiation and apoptosis resistance, which contributes to myofibroblast accumulation and ultimately persistent fibrosis in aging.

Single-center experience with use of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) infection is common in thoracic organ transplant recipients. Valganciclovir and ganciclovir are used for both prophylaxis and treatment of this infection, but intolerance and treatment failure are common. Letermovir has been demonstrated to reduce the risk of CMV infection when used for prophylaxis in allogeneic hematopoietic cell transplantation. However, there are no data on its efficacy in thoracic organ transplantation. METHODS: We examined the use of letermovir for either CMV prophylaxis (primary and secondary) or treatment in heart and lung transplant recipients at our institution from February 1, 2018, through December 31, 2018. RESULTS: Nine total patients received letermovir at our institution (8 lung transplant, 1 heart transplant) during the study period. Letermovir was prescribed for CMV prophylaxis in eight patients (primary prophylaxis in two patients and secondary prophylaxis in 6 patients), and for treatment of CMV DNAemia in two cases. One patient received letermovir for both secondary prophylaxis and treatment on separate occasions. Three out of 8 (37.5%) patients receiving letermovir for prophylaxis developed CMV DNAemia during prophylaxis. One patient treated for CMV disease had clinical failure with a sharp rise in serum CMV DNA PCR. The other patient treated for low-grade CMV DNAemia initially had a slight rise in CMV DNA PCR, but has since had a sustained response. No major side effects were experienced, and 2 patients reported minor side effects. CONCLUSION: Letermovir was well tolerated with only minor side effects reported; however, the rate of development of CMV DNAemia on prophylaxis was considerable. Further study of the dosing and efficacy of letermovir for CMV prophylaxis or treatment in thoracic organ transplant recipients is warranted.

Dysregulated Nox4 ubiquitination contributes to redox imbalance and age-related severity of acute lung injury.

Acute respiratory distress syndrome (ARDS) is a devastating critical illness disproportionately affecting the elderly population, with both higher incidence and mortality. The integrity of the lung endothelial cell (EC) monolayer is critical for preservation of lung function. However, mechanisms mediating EC barrier regulation in the context of aging remain unclear. We assessed the severity of acute lung injury (ALI) in young (2 mo) and aged (18 mo) mice using a two-hit preclinical model. Compared with young cohorts, aged mice exhibited increased ALI severity, with greater vascular permeability characterized by elevated albumin influx and levels of bronchoalveolar lavage (BAL) cells (neutrophils) and protein. Aged/injured mice also demonstrated elevated levels of reactive oxygen species (ROS) in the BAL, which was associated with upregulation of the ROS-generating enzyme, Nox4. We evaluated the role of aging in human lung EC barrier regulation utilizing a cellular model of replicative senescence. Senescent EC populations were defined by increases in ß-galactosidase activity and p16 levels. In response to lipopolysaccharide (LPS) challenge, senescent ECs demonstrate exacerbated permeability responses compared with control "young" ECs. LPS challenge led to a rapid induction of Nox4 expression in both control and senescent ECs, which was posttranslationally mediated via the proteasome/ubiquitin system. However, senescent ECs demonstrated deficient Nox4 ubiquitination, resulting in sustained expression of Nox4 and alterations in cellular redox homeostasis. Pharmacological inhibition of Nox4 in senescent ECs reduced LPS-induced alterations in permeability. These studies provide insight into the roles of Nox4/senescence in EC barrier responses and offer a mechanistic link to the increased incidence and mortality of ARDS associated with aging.

Transformation of personal computers and mobile phones into genetic diagnostic systems.

Molecular diagnostics based on the polymerase chain reaction (PCR) offer rapid and sensitive means for detecting infectious disease, but prohibitive costs have impeded their use in resource-limited settings where such diseases are endemic. In this work, we report an innovative method for transforming a desktop computer and a mobile camera phone--devices that have become readily accessible in developing countries--into a highly sensitive DNA detection system. This transformation was achieved by converting a desktop computer into a de facto thermal cycler with software that controls the temperature of the central processing unit (CPU), allowing for highly efficient PCR. Next, we reconfigured the mobile phone into a fluorescence imager by adding a low-cost filter, which enabled us to quantitatively measure the resulting PCR amplicons. Our system is highly sensitive, achieving quantitative detection of as little as 9.6 attograms of target DNA, and we show that its performance is comparable to advanced laboratory instruments at approximately 1/500th of the cost. Finally, in order to demonstrate clinical utility, we have used our platform for the successful detection of genomic DNA from the parasite that causes Chagas disease, Trypanosoma cruzi, directly in whole, unprocessed human blood at concentrations 4-fold below the clinical titer of the parasite.

Selection is more intelligent than design: improving the affinity of a bivalent ligand through directed evolution.

Multivalent molecular interactions can be exploited to dramatically enhance the performance of an affinity reagent. The enhancement in affinity and specificity achieved with a multivalent construct depends critically on the effectiveness of the scaffold that joins the ligands, as this determines their positions and orientations with respect to the target molecule. Currently, no generalizable design rules exist for construction of an optimal multivalent ligand for targets with known structures, and the design challenge remains an insurmountable obstacle for the large number of proteins whose structures are not known. As an alternative to such design-based strategies, we report here a directed evolution-based method for generating optimal bivalent aptamers. To demonstrate this approach, we fused two thrombin aptamers with a randomized DNA sequence and used a microfluidic in vitro selection strategy to isolate scaffolds with exceptionally high affinities. Within five rounds of selection, we generated a bivalent aptamer that binds thrombin with an apparent dissociation constant (K(d)) <10 pM, representing a ∼200-fold improvement in binding affinity over the monomeric aptamers and a ∼15-fold improvement over the best designed bivalent construct. The process described here can be used to produce high-affinity multivalent aptamers and could potentially be adapted to other classes of biomolecules.

Selection strategy to generate aptamer pairs that bind to distinct sites on protein targets.

Many analytical techniques benefit greatly from the use of affinity reagent pairs, wherein each reagent recognizes a discrete binding site on a target. For example, antibody pairs have been widely used to dramatically increase the specificity of enzyme linked immunosorbent assays (ELISA). Nucleic acid-based aptamers offer many advantageous features relative to protein-based affinity reagents, including well-established chemical synthesis, thermostability, and low production cost. However, the generation of suitable aptamer pairs has posed a significant challenge, and few such pairs have been reported to date. To address this important challenge, we present multivalent aptamer isolation systematic evolution of ligands by exponential enrichment (MAI-SELEX), a technique designed for the efficient selection of aptamer pairs. In contrast to conventional selection methods, our method utilizes two selection modules to generate separate aptamer pools that recognize distinct binding sites on a single target. Using MAI-SELEX, we have isolated two groups of 2'-fluoro-modified RNA aptamers that specifically recognize the αV or ß3 subunits of integrin αVß3. These aptamers exhibit low nanomolar affinities for their targets, with minimal cross-reactivity to other closely related integrin homologues. Moreover, we show that these aptamer pairs do not interfere with each other's binding and effectively detect the target even in complex mixtures such as undiluted serum.

Ex Vivo Lung Perfusion: A Review of Current and Future Application in Lung Transplantation.

The number of waitlisted lung transplant candidates exceeds the availability of donor organs. Barriers to utilization of donor lungs include suboptimal lung allograft function, long ischemic times due to geographical distance between donor and recipient, and a wide array of other logistical and medical challenges. Ex vivo lung perfusion (EVLP) is a modality that allows donor lungs to be evaluated in a closed circuit outside of the body and extends lung donor assessment prior to final acceptance for transplantation. EVLP was first utilized successfully in 2001 in Lund, Sweden. Since its initial use, EVLP has facilitated hundreds of lung transplants that would not have otherwise happened. EVLP technology continues to evolve and improve, and currently there are multiple commercially available systems, and more under investigation worldwide. Although barriers to universal utilization of EVLP exist, the possibility for more widespread adaptation of this technology abounds. Not only does EVLP have diagnostic capabilities as an organ monitoring device but also the therapeutic potential to improve lung allograft quality when specific issues are encountered. Expanded treatment potential includes the use of immunomodulatory treatment to reduce primary graft dysfunction, as well as targeted antimicrobial therapy to treat infection. In this review, we will highlight the historical development, the current state of utilization/capability, and the future promise of this technology.

Lung Disease-Related Pulmonary Hypertension.

Patients with advanced lung disease can develop pulmonary hypertension and succumb to right ventricular failure/cor pulmonale. Patients with pulmonary hypertension owing to chronic lung disease, or World Health Organization group 3 pulmonary hypertension, are more limited and carry a high risk of mortality. Adjunctive therapies remain the cornerstones of treatment. Recent evidence suggests that inhaled pulmonary vasodilator therapy can be helpful in patients with pulmonary hypertension owing to interstitial lung disease. Lung transplantation may be the only life-saving option in select patients, whereas palliative care and hospice should be sought for those who are not candidates as the disease progresses.

Improving aptamer selection efficiency through volume dilution, magnetic concentration, and continuous washing in microfluidic channels.

The generation of nucleic acid aptamers with high affinity typically entails a time-consuming, iterative process of binding, separation, and amplification. It would therefore be beneficial to develop an efficient selection strategy that can generate these high-quality aptamers rapidly, economically, and reproducibly. Toward this goal, we have developed a method that efficiently generates DNA aptamers with slow off-rates. This methodology, called VDC-MSELEX, pairs the volume dilution challenge process with microfluidic separation for magnetic bead-assisted aptamer selection. This method offers improved aptamer selection efficiencies through the application of highly stringent selection conditions: it retrieves a small number (<10(6)) of magnetic beads suspended in a large volume (>50 mL) and concentrates them into a microfluidic chamber (8 µL) with minimal loss for continuous washing. We performed three rounds of the VDC-MSELEX using streptavidin (SA) as the target and obtained new DNA aptamer sequences with low nanomolar affinity that specifically bind to the SA proteins.

Inhaled Nitric Oxide via High-Flow Nasal Cannula in Patients with Acute Respiratory Failure Related to COVID-19.

INTRODUCTION: Limited evidence exists regarding use of inhaled nitric oxide (iNO) in spontaneously breathing patients. We evaluated the effectiveness of continuous iNO via high-flow nasal cannula (HFNC) in COVID-19 respiratory failure. METHODS: We performed a multicenter cohort study of patients with respiratory failure from COVID-19 managed with HFNC. Patients were stratified by administration of iNO via HFNC. Regression analysis was used to compare the need for mechanical ventilation and secondary endpoints including hospital mortality, length of stay, acute kidney injury, need for renal replacement therapy, and need for extracorporeal life support. RESULTS: A total of 272 patients were identified and 66 (24.3%) of these patients received iNO via HFNC for a median of 88 h (interquartile range: 44, 135). After 12 h of iNO, supplemental oxygen requirement was unchanged or increased in 52.7% of patients. Twenty-nine (43.9%) patients treated with iNO compared to 79 (38.3%) patients without iNO therapy required endotracheal intubation (P = .47). After multivariable adjustment, there was no difference in need for mechanical ventilation between groups (odds ratio: 1.53; 95% confidence interval [CI]: 0.74-3.17), however, iNO administration was associated with longer hospital length of stay (incidence rate ratio: 1.41; 95% CI: 1.31-1.51). No difference was found for mortality, acute kidney injury, need for renal replacement therapy, or need for extracorporeal life support. CONCLUSION: In patients with COVID-19 respiratory failure, iNO delivered via HFNC did not reduce oxygen requirements in the majority of patients or improve clinical outcomes. Given the observed association with increased length of stay, judicious selection of those likely to benefit from this therapy is warranted.

Incidence and prognostic significance of pleural effusions in pulmonary arterial hypertension.

It has been suggested pleural effusions may develop in right heart failure in the absence of left heart disease. The incidence and prognostic significance of pleural effusions in pulmonary arterial hypertension is uncertain. Patients with pulmonary arterial hypertension followed at our tertiary care center were reviewed. Survival was examined based on the subsequent development of a pleural effusion. A total of 191 patients with pulmonary arterial hypertension met the inclusion criteria. The prevalence of pleural effusions on initial assessment was 7.3%. Among patients without a pleural effusion on initial imaging and at least one follow-up computerized tomography (N = 142), pleural effusion developed in 27.5% (N = 39) of patients. No alternative etiology of the effusion was identified in 19 (48.7%) cases and effusions deemed related to pulmonary arterial hypertension occurred at an incident rate of 38.6 cases per 1000 person-years. Of these, 14 (73.7%) were bilateral, 3 (15.8%) were right-sided, and 2 (10.5%) were left-sided. Effusion size was trace or small in 18 patients (94.7%). Development of a new pleural effusion was associated with attenuated survival in unadjusted survival analysis (HR: 3.80; 95% CI: 1.55-9.31), multivariate analysis (HR: 5.13; 95% CI: 1.86-14.16), and after the multivariate model was adjusted for concomitant pericardial effusion (HR: 4.86; 95% CI: 1.51-15.71). Negative impact on survival remained unchanged when effusions more likely related to an alternative cause were removed from analysis. In conclusion, pleural effusions can complicate pulmonary arterial hypertension in the absence of left heart disease. These effusions are frequently small in size, bilateral in location, and their presence is associated with decreased survival. Attenuated survival appears independent of the risk associated with a new pericardial effusion.

Association Between Anticoagulation and Survival in Interstitial Lung Disease: An Analysis of the Pulmonary Fibrosis Foundation Patient Registry.

BACKGROUND: Aberrations in the coagulation system have been implicated in the pathogenesis of interstitial lung disease (ILD). Anticoagulants have been proposed as a potential therapy in ILD; however, a randomized controlled trial examining warfarin as a treatment for IPF was terminated early due to increased death rates. This has led some to speculate that warfarin specifically may be harmful in ILD, and use of direct oral anticoagulants (DOACs) could result in superior outcomes. RESEARCH QUESTION: The goal of this study was to delineate the relationship between anticoagulation and outcomes in patients with ILD through an analysis of the Pulmonary Fibrosis Foundation Patient Registry. STUDY DESIGN AND METHODS: An analysis of all patients in the Pulmonary Fibrosis Foundation Patient Registry was performed. Patients were stratified into three groups: no anticoagulation, DOAC use, or warfarin use. Survival was analyzed by using both Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Of 1,911 patients included in the analysis, 174 (9.1%) were given anticoagulants; 93 (4.9%) received DOACs, and 81 (4.2%) received warfarin. There was a twofold increased risk of death or transplant for patients receiving DOACS; for warfarin, the risk was over two and half times greater. DOACs were not associated with an increased risk of mortality following adjustment for confounding variables. However, even after adjustment, patients given the anticoagulant warfarin remained at increased risk of mortality. In patients with IPF, warfarin was associated with reduced transplant-free survival, but DOACs were not. There was no statistically significant difference in survival between those receiving warfarin and those receiving a DOAC. INTERPRETATION: The need for anticoagulation is associated with an increased risk for death or transplant in patients with ILD, in both the IPF and non-IPF population. Further research is required to determine if warfarin and DOACs present varying safety profiles in patients with ILD.

Surgical Lung Biopsy for Interstitial Lung Disease. Safety and Feasibility at a Tertiary Referral Center.

Rationale: Video-assisted thoracoscopic surgery (VATS) remains the gold standard for interstitial lung disease (ILD) characterization when histology is deemed necessary. There is diminishing use of VATS owing to increased reliance on high-resolution computed tomographic patterns, as well as concerns regarding the potential morbidity and mortality of the procedure.Objectives: The goal of this study was to evaluate the safety and tolerability of VATS among a broad group of patients with ILD referred to a tertiary care center.Methods: Data for all patients with ILD who underwent VATS lung biopsies at Inova Fairfax hospital for the period from December 2012 to September 2019 were collected. Clinical, physiologic, and functional parameters as well as postoperative outcomes including any complications, hospital length of stay, and mortality were collated.Results: There were 268 diagnostic VATS biopsies performed during the period. The mean age of the cohort was 63 ± 13 years, 54% were male, and 25% were ultimately diagnosed with idiopathic pulmonary fibrosis. Two hundred twenty-nine patients were scheduled (85%, Elective VATS group) whereas 39 were inpatients (15%). In the elective group, the 1-month complication rate was 8%, whereas 4% had a severe complication, and there were no deaths. The only mortalities were in the group who were hospitalized before the VATS (4/39 = 10%). Complications were less frequent when VATS was requested by the tertiary referral ILD team. Of the elective group, 87% patients were discharged the same day.Conclusions: This report demonstrates the safety, tolerability, and feasibility of VATS lung biopsy as a same-day procedure in the modern era, especially if patients are first vetted by a team with expertise in the field of ILD. These results support a lower threshold to pursue a VATS biopsy when histology is required for an ILD diagnosis.

Development and Validation of a Clinical Diagnostic Scoring System for the Diagnosis of Idiopathic Pulmonary Fibrosis.

Rationale: Interpreting the radiologic data in conjunction with an objective clinical score could help to harmonize idiopathic pulmonary fibrosis (IPF) diagnosis and improve accuracy. Objectives: We sought to establish and validate a multivariable objective scoring model based on clinical parameters by stratifying the risk of patients having IPF diagnosed versus having other forms of interstitial lung disease (ILD) diagnosis. Methods: A clinical score was derived from review of patients evaluated at the Inova Fairfax ILD Program and validated in three distinct cohorts. On the basis of known IPF clinical characteristics, a multivariable model was created and assessed by using receiver operating characteristic curves. Results: There were 844 patients with ILD with either IPF (n = 347, 41%) or non-IPF ILD (n = 497, 59%) diagnosis. On the basis of calculated odds ratios, a score was assigned to each of the following clinical parameters: age, sex, smoking history, race or ethnicity, ILD family history, exposures, presence of connective tissue disease signs or symptoms, and velcro crackles. The final Fairfax IPF Clinical Score (FICS) ranged from 1 to 25. The clinical diagnostic score system was accurate in predicting IPF, as measured by the area under the curve (0.88) in the derivation cohort, with similar areas under the curve of 0.91, 0.81, and 0.71 being demonstrated in the respective validation cohorts. Conclusions: The FICS appears to be an accurate tool for estimating the pretest probability of IPF in patients with ILD. How the FICS performs in conjunction with the various high-resolution computed tomographic patterns remains to be determined. This model could ultimately be useful for increasing the degree of confidence in the final diagnosis and could help to obviate the need for lung biopsy in cases with non-usual interstitial pneumonia patterns on high-resolution computed tomographic images.

Use of Pheno Room, Augmented Reality, and 3-Rod Technique for 3-Dimensional Correction of Adolescent Idiopathic Scoliosis.

This is a surgical video that showcases the surgical repair of a young male patient with idiopathic scoliosis in a hybrid operating room with the utilization of a new imaging modality Advanced Radar Target Identification System (ARTIS) PHENO (Siemens Medical Solutions, Pennsylvania, USA) and augmented reality (Video 1). A 17-year-old male patient with idiopathic scoliosis underwent scoliosis repair in a hybrid operating room with segment reality surgical planning. The use of augmented reality helped in visualization of proper screw trajectory, and the use of ARTIS PHENO helped in identification of correct screw placement and rod fixation. Intraoperative use of new imaging modalities as augmented reality imaging and ARTIS PHENO can decrease surgical complication and time.

HRCT evaluation of patients with interstitial lung disease: comparison of the 2018 and 2011 diagnostic guidelines.

BACKGROUND AND AIMS: Chest high-resolution computed tomography (HRCT) is the central diagnostic tool in discerning idiopathic pulmonary fibrosis (IPF) from other interstitial lung disease (ILDs). In 2018, new guidelines were published and the nomenclature for HRCT interpretation was changed. We sought to evaluate how clinicians' interpretation would change based on reading HRCTs under the framework of the old versus new categorization. MATERIALS AND METHODS: We collated HRCTs from 50 random cases evaluated in the Inova Fairfax ILD clinic. Six ILD experts were provided the deidentified HRCTs. They were all instructed to independently provide two reads of each HRCT, based on the old and the new guidelines. RESULTS: The kappa statistic for concordance for HRCT reads under old guidelines was 0.5, while for the new guidelines it was 0.38. Under the framework of the old guidelines, there were 22 HRCTs with unanimous consensus reads, while only 15 with the new guidelines. There were 12 HRCTs read unanimously as usual interstitial pneumonia (UIP) pattern based on both the old and the new guidelines. Ten HRCTs were read as a possible UIP pattern based on the old guidelines and were classified in nine cases as probable UIP and one indeterminate based on the new guidelines. Of the 28 inconsistent UIP HRCTs (old guidelines), 25 were read as alternative diagnosis suggested, two were read as indeterminate and one as probable UIP. CONCLUSION: Implementation of the new guidelines to categorize HRCTs in ILD patients appears to be associated with greater inter-interpreter variability. How or whether new guidelines improve the care and management of ILD patients remains unclear.The reviews of this paper are available via the supplemental material section.