Microscopic Small Airway Abnormalities Identified in Early Idiopathic Pulmonary Fibrosis In Vivo Using Endobronchial Optical Coherence Tomography.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) affects subpleural lung, but is considered to spare small airways. Micro-CT studies demonstrated small airway reduction in end-stage IPF explanted lungs, raising questions about small airway involvement in early-stage disease. Endobronchial optical coherence tomography (EB-OCT) is a volumetric imaging modality that detects microscopic features from subpleural to proximal airways. We use EB-OCT to evaluate small airways in early IPF and control subjects in vivo. METHODS: EB-OCT was performed in 12 IPF and 5 control subjects (matched by age, sex, smoking-history, height, BMI). IPF subjects had early disease with mild restriction (FVC: 83.5% predicted), diagnosed per current guidelines and confirmed by surgical biopsy. EB-OCT volumetric imaging was acquired bronchoscopically in multiple, distinct, bilateral lung locations (total: 97 sites). IPF imaging sites were classified by severity into affected (all criteria for UIP present) and less affected (some but not all criteria for UIP present) sites. Bronchiole count and small airway stereology metrics were measured for each EB-OCT imaging site. RESULTS: Compared to control subjects (mean: 11.2 bronchioles/cm3; SD: 6.2), there was significant bronchiole reduction in IPF subjects (42% loss; mean: 6.5/cm3; SD: 3.4; p=0.0039), including in IPF affected (48% loss; mean: 5.8/cm3; SD: 2.8; p<0.00001) and IPF less affected (33% loss; mean: 7.5/cm3; SD: 4.1; p=0.024) sites. Stereology metrics showed IPF affected small airways were significantly larger and more distorted/irregular than in IPF less affected sites and control subjects. IPF less affected and control airways were statistically indistinguishable for all stereology parameters (p=0.36-1.0). CONCLUSION: EB-OCT demonstrated marked bronchiolar loss in early IPF (between 30 and 50%), even in areas minimally affected by disease, compared to matched controls. These findings support small airway disease as a feature of early IPF, providing novel insight into pathogenesis and potential therapeutic targets.

Implementation of an Institution-Wide Rules-Based Automated CT Protocoling System.

BACKGROUND. Examination protocoling is a noninterpretive task that increases radiologists' workload and can cause workflow inefficiencies. OBJECTIVE. The purpose of this study was to evaluate effects of an automated CT protocoling system on examination process times and protocol error rates. METHODS. This retrospective study included 317,597 CT examinations (mean age, 61.8 ± 18.1 [SD] years; male, 161,125; female, 156,447; unspecified sex, 25) from July 2020 to June 2022. A rules-based automated protocoling system was implemented institution-wide; the system evaluated all CT orders in the EHR and assigned a protocol or directed the order for manual radiologist protocoling. The study period comprised pilot (July 2020 to December 2020), implementation (January 2021 to December 2021), and postimplementation (January 2022 to June 2022) phases. Proportions of automatically protocoled examinations were summarized. Process times were recorded. Protocol error rates were assessed by counts of quality improvement (QI) reports and examination recalls and comparison with retrospectively assigned protocols in 450 randomly selected examinations. RESULTS. Frequency of automatic protocoling was 19,366/70,780 (27.4%), 68,875/163,068 (42.2%), and 54,045/83,749 (64.5%) in pilot, implementation, and postimplementation phases, respectively (p < .001). Mean (± SD) times from order entry to protocol assignment for automatically and manually protocoled examinations for emergency department examinations were 0.2 ± 18.2 and 2.1 ± 69.7 hours, respectively; mean inpatient examination times were 0.5 ± 50.0 and 3.5 ± 105.5 hours; and mean outpatient examination times were 361.7 ± 1165.5 and 1289.9 ± 2050.9 hours (all p < .001). Mean (± SD) times from order entry to examination completion for automatically and manually protocoled examinations for emergency department examinations were 2.6 ± 38.6 and 4.2 ± 73.0 hours, respectively (p < .001); for inpatient examinations were 6.3 ± 74.6 and 8.7 ± 109.3 hours (p = .001); and for outpatient examinations were 1367.2 ± 1795.8 and 1471.8 ± 2118.3 hours (p < .001). In the three phases, there were three, 19, and 25 QI reports and zero, one, and three recalls, respectively, for automatically protocoled examinations, versus nine, 19, and five QI reports and one, seven, and zero recalls for manually protocoled examinations. Retrospectively assigned protocols were concordant with 212/214 (99.1%) of automatically protocoled versus 233/236 (98.7%) of manually protocoled examinations. CONCLUSION. The automated protocoling system substantially reduced radiologists' protocoling workload and decreased times from order entry to protocol assignment and examination completion; protocol errors and recalls were infrequent. CLINICAL IMPACT. The system represents a solution for reducing radiologists' time spent performing noninterpretive tasks and improving care efficiency.

RadioGraphics Update: The 10 Pillars of Lung Cancer Screening-Rationale and Logistics of a Lung Cancer Screening Program.

Editor's Note.-RadioGraphics Update articles supplement or update information found in full-length articles previously published in RadioGraphics. These updates, written by at least one author of the previous article, provide a brief synopsis that emphasizes important new information such as technological advances, revised imaging protocols, new clinical guidelines involving imaging, or updated classification schemes.

Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole-ß-lactams, biological evaluations, magic chloro effect and molecular docking studies.

A convenient methodology for C-4 indole-ß-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-ß-lactams assigned with respect to C3-H and C4-H. The synthesized novel ß-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuration was further estabilished based on X-ray crystallographic data. Examination of antibacterial properties unveiled that only derivatives 5a and 5b, featuring chloro substitution, exhibited potent activities, underscoring the emergence of the recently coined term "magic chloro effect". Molecular docking analysis provided additional support for the observed in vitro antibacterial activities of compounds 5a-b.

Imaging of Neuroendocrine Neoplasms; Principles of Treatment Strategies. What Referring Clinicians Want to Know.

ABSTRACT: Neuroendocrine neoplasms (NENs) are a diverse group of tumors that express neuroendocrine markers and primarily affect the lungs and digestive system. The incidence of NENs has increased over time due to advancements in imaging and diagnostic techniques. Effective management of NENs requires a multidisciplinary approach, considering factors such as tumor location, grade, stage, symptoms, and imaging findings. Treatment strategies vary depending on the specific subtype of NEN. In this review, we will focus on treatment strategies and therapies including the information relevant to clinicians in order to undertake optimal management and treatment decisions, the implications of different therapies on imaging, and how to ascertain their possible complications and treatment effects.

Interstitial lung disease in ANCA-associated vasculitis: associated factors, radiographic features and mortality.

OBJECTIVE: To evaluate the prevalence, clinical and radiographic features, and long-term outcomes of interstitial lung disease (ILD) in a United States-based ANCA-associated vasculitis (AAV) cohort. METHODS: In this retrospective cohort study, we identified cases of ILD within the 2002-2019 Mass General Brigham AAV Cohort, a consecutive inception cohort of PR3- or MPO-ANCA+ AAV patients. ILD diagnosis and classification as fibrotic or non-fibrotic were confirmed by review of available chest imaging by two board-certified radiologists. Cox proportional hazard models, with age as the time scale, were used to estimate the association of AAV-ILD with all-cause mortality. RESULTS: Of 684 patients in the MGB AAV Cohort, 91 (13%) had ILD which preceded the diagnosis of AAV by a mean of 2.2 years. AAV-ILD patients were older (67 vs 60 years, P < 0.001) than patients without ILD but the distribution of sex and race was similar. AAV-ILD patients were more often MPO-ANCA+ (93% vs 65%, P < 0.001); among MPO-ANCA+ patients (n = 470), 85 (18%) had ILD. The majority of ILD was fibrotic (76%) and UIP was the most common ILD pattern (42%). The baseline forced vital capacity (FVC) % predicted among ILD patients was 81 ± 20%. Fibrotic AAV-ILD was associated with a 58% higher risk of death (aHR 1.58, 95% CI 1.06, 2.37) compared with AAV patients without ILD. CONCLUSION: ILD is a frequent complication of AAV, especially MPO-ANCA+ AAV, often preceding recognition of AAV. Fibrotic AAV-ILD is associated with a higher risk of death than AAV without ILD.

Electronic Health Record Order Entry-Based Interventions in Response to a Global Iodinated Contrast Media Shortage: Impact on Contrast-Enhanced CT Utilization.

BACKGROUND. Radiology informatics systems and clinical decision support tools in the electronic health record (EHR) can be leveraged to help impact ordering patterns in response to the ongoing global iodinated contrast media shortage. OBJECTIVE. The purpose of our study was to assess the impact of EHR order entry-based interventions, implemented as part of a health system's response to the global contrast media shortage, on contrast-enhanced CT utilization. METHODS. This retrospective study included 79,259 patients who underwent CT at a large multisite health system between April 1, 2022, and July 3, 2022. Two EHR-based interventions were implemented as part of the health system's response to the global contrast media shortage. A first EHR-based intervention on May 10, 2022, entailed creating an alert that appeared in a sidebar after any contrast-enhanced body CT orders, indicating the present shortage and recommending alternate imaging modalities. A second EHR-based intervention on May 16, 2022, required referrers to enter detailed clinical information for all contrast-enhanced body CT orders, which radiologists used when protocoling examinations. Data regarding CT orders and examinations performed were extracted from the electronic data warehouse. RESULTS. During the preintervention, first postintervention, and second postintervention periods, the mean number of patients who underwent contrast-enhanced CT per weekday was 726, 689, and 639, respectively (p for preintervention vs second postintervention periods, < .001). During the three periods, the mean number of patients who underwent CT per weekday was 1350, 1323, and 1314 (p < .001). During the three periods, the mean number of patients who underwent contrast-enhanced body CT per weekday was 561, 532, and 492 (p < .001). During the three periods, the mean number of orders for CT with IV contrast media per weekday was 154, 143, and 131 (p < .001). During the three periods, the mean number of orders for CT without IV contrast media per weekday was 196, 202, and 221 (p < .001). CONCLUSION. EHR order entry-based interventions implemented in response to the global contrast media shortage significantly reduced contrast-enhanced CT utilization in a large health system. CLINICAL IMPACT. The findings indicate the ability to rapidly achieve changes in ordering clinician behavior and subsequent clinical practice using systemwide EHR changes.

Identification of Plausible Candidates in Prostate Cancer Using Integrated Machine Learning Approaches.

Background: Currently, prostate-specific antigen (PSA) is commonly used as a prostate cancer (PCa) biomarker. PSA is linked to some factors that frequently lead to erroneous positive results or even needless biopsies of elderly people. Objectives: In this pilot study, we undermined the potential genes and mutations from several databases and checked whether or not any putative prognostic biomarkers are central to the annotation. The aim of the study was to develop a risk prediction model that could help in clinical decision-making. Methods: An extensive literature review was conducted, and clinical parameters for related comorbidities, such as diabetes, obesity, as well as PCa, were collected. Such parameters were chosen with the understanding that variations in their threshold values could hasten the complicated process of carcinogenesis, more particularly PCa. The gathered data was converted to semi-binary data (-1, -0.5, 0, 0.5, and 1), on which machine learning (ML) methods were applied. First, we cross-checked various publicly available datasets, some published RNA-seq datasets, and our whole-exome sequencing data to find common role players in PCa, diabetes, and obesity. To narrow down their common interacting partners, interactome networks were analysed using GeneMANIA and visualised using Cytoscape, and later cBioportal was used (to compare expression level based on Z scored values) wherein various types of mutation w.r.t their expression and mRNA expression (RNA seq FPKM) plots are available. The GEPIA 2 tool was used to compare the expression of resulting similarities between the normal tissue and TCGA databases of PCa. Later, top-ranking genes were chosen to demonstrate striking clustering coefficients using the Cytoscape-cytoHubba module, and GEPIA 2 was applied again to ascertain survival plots. Results: Comparing various publicly available datasets, it was found that BLM is a frequent player in all three diseases, whereas comparing publicly available datasets, GWAS datasets, and published sequencing findings, SPFTPC and PPIMB were found to be the most common. With the assistance of GeneMANIA, TMPO and FOXP1 were found as common interacting partners, and they were also seen participating with BLM. Conclusion: A probabilistic machine learning model was achieved to identify key candidates between diabetes, obesity, and PCa. This, we believe, would herald precision scale modeling for easy prognosis.

Can Application of Pressmud Mediated Plant Nutrient Dynamics Under Lead Contaminated Soils of Indian Vertisol?

Long- term application of marginal quality water accumulated significant amount of pollutant into the soil. It reduces soil health parameters, and crop yield and their quality. In this regards, graded application of pressmud (PM), i.e. 0, 2.5, 5 and 10 g/kg was applied on lead (Pb) contamination level (0, 100, 150, 300 mg/kg) and evaluated interaction effect on plant nutrients uptake by spinach. Analytical data showed that increasing the PM levels enhanced the macro (phosphorus, potassium, sulphur) and micro-nutrient (zinc, copper, manganese, iron) concentration into the soil. Whereas, increasing the level of Pb significantly (p ≤ 0.05) reduced the P, K and S nutrient concentration and uptake pattern by spinach crop. Increasing PM levels (control to 10 g/kg soil) improved P, K and S by 46.99, 98.96 and 76.79%, respectively in soil. This study is useful to formulate management strategies for minimizing Pb contamination in the food chain by the application of PM mostly in peri-urban areas.

Pressmud Subdue Phytoremediation Indices in Lead-Contaminated Soils: A Human Health Perspective.

Direct discharge of waste into water bodies and mining are two major sources of lead contamination in ecosystems. Water scarcity promoted the usage of industrial effluent-contaminated waters for crop production, mainly in peri-urban areas. These wastewaters may contain heavy metals and pollute crop ecosystems. These metals can reach the living cell via contaminated raw foodstuffs that grow under these conditions and cause various ill effects in metabolic activities. In this study, graded levels of pressmud (0, 2.5, 5, 10 g/kg) were applied on lead imposed soil with different contamination levels (0, 100, 150, 300 mg/kg) and metal dynamics was studied in spinach crop. Experimental results showed that the addition of pressmud upto 10 mg/kg had decreased different phytoremediation indices in spinach crop. Whereas, increasing Pb level enhanced the indices' values, indicating accumulation of significant amount of Pb in spinach biomass. However, application of pressmud (upto 10 mg/kg) reduced the bioconcentration factor (BCF) from 0.182 to 0.136, transfer factor (TF) from 0.221 to 0.191, translocation efficiency 66.11-59.34%; whereas, Pb removal enhanced from 0.063 to 0.072 over control treatment. These findings suggest that application of pressmud declined Pb concentration, the BCF and the TF in test crop which lead to less chances of adverse effect in human. These information are very useful for effectively managing wastewater irrigated agricultural crop production systems.

Comparison of expected imaging findings following percutaneous microwave and cryoablation of pulmonary tumors: ablation zones and thoracic lymph nodes.

OBJECTIVE: To compare temporal changes of ablation zones and lymph nodes following lung microwave ablation (MWA) and cryoablation. METHODS: This retrospective cohort study compared lung ablation zones and thoracic lymph nodes following MWA and cryoablation performed 2006-2020. In the ablation zone cohort, ablation zone volumes were measured on serial CT for 12 months. In the lymph node cohort, the sum of bidimensional products of lymph node diameters was measured before (baseline) and up to 6 months following ablation. Cumulative incidence curves estimated the time to 75% ablation zone reduction and linear mixed-effects regression models compared the temporal distribution of ablation zones and lymph node sizes between modalities. RESULTS: Ablation zones of 59 tumors treated in 45 sessions (16 MWA, 29 cryoablation) in 36 patients were evaluated. Differences in the time to 75% volume reduction between modalities were not detected. Following MWA, half of the ablation zones required an estimated time of 340 days to achieve a 75% volume reduction compared to 214 days following cryoablation (p = .30). Thoracic lymph node sizes after 33 sessions (13 MWA, 20 cryoablation) differed between modalities (baseline-32 days, p = .01; 32-123 days, p = .001). Following MWA, lymph nodes increased on average by 38 mm2 (95%CI, 5.0-70.7; p = .02) from baseline to 32 days, followed by an estimated decrease of 50 mm2 (32-123 days; p = .001). Following cryoablation, changes in lymph nodes were not detected (baseline-32 days, p = .33). CONCLUSION: The rate of ablation zone volume reduction did not differ between MWA and cryoablation. Thoracic lymph nodes enlarged transiently after MWA but not after cryoablation. KEY POINTS: • Contrary to current belief, the rate of lung ablation zone volume reduction did not differ between microwave and cryoablation. • Transient enlargement of thoracic lymph nodes after microwave ablation was not associated with regional tumor spread and decreased within six months following ablation. • No significant thoracic lymph node enlargement was observed following cryoablation.

Utility of Patient-Reported Risk Factors for Identifying Advanced Chronic Kidney Disease Before Outpatient CT: Comparison With Recent ACR/NKF Consensus Criteria.

BACKGROUND. Practices vary for screening patients for risk of renal dysfunction before administration of iodinated contrast medium. A 2020 American College of Radiology/National Kidney Foundation (ACR/NKF) consensus statement provided streamlined screening criteria. OBJECTIVE. The purpose of this study was to assess the yield of patient-reported risk factors for identifying estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m2 before outpatient CT. METHODS. This retrospective study was performed at a health system that implemented an electronic screening form for patients to complete before outpatient CT encounters to report undergoing dialysis, taking cancer-treating medications, having kidney disease, undergoing prior kidney surgery, having diabetes mellitus treated with medication, having hypertension treated with medication, or having multiple myeloma. Patients with any risk factor were required to undergo eGFR testing before CT. Of 44,708 patients completing the form from June 1, 2020, through February 28, 2021, 10,256 patients (5315 men, 4941 women; mean age, 66.8 ± 11.9 [SD] years; range, 21-98 years) underwent eGFR testing on the day of CT. Multivariable regression analysis for predicting reduced eGFR was performed. Findings were compared with those from theoretic use of the ACR/NKF criteria. RESULTS. Same-day testing yielded eGFR less than 30 mL/min/1.73 m2 in 1.4% (144/10,256) of patients. The only significant independent predictors of low eGFR were dialysis (odds ratio [OR], 203.30], kidney disease (OR, 12.55), and diabetes mellitus treated with medication (OR, 2.44). If the ACR/NKF criteria (only kidney disease, defined as dialysis, kidney disease, or prior kidney surgery) had been followed as a trigger for eGFR testing, the number of patients needing testing would have decreased 89.7%, from 10,256 to 1059; yield would have increased to 7.2% (76/1059); and 47.2% (68/144) of patients with low eGFR would have been missed. If the ACR/NKF criteria had been followed but diabetes mellitus been considered a required rather than an optional criterion, the number of patients needing testing would have decreased 77.1%, to 2353; yield would have increased to 4.0% (95/2353); and 34.0% (49/144) of patients with low eGFR would have been missed. CONCLUSION. Using patient-reported risk factors resulted in frequent eGFR testing but low yield of low eGFR. Commonly applied risk factors were not independently associated with low eGFR. CLINICAL IMPACT. Application of ACR/NKF criteria would substantially reduce eGFR testing, but patients with renal dysfunction would be missed. The statement should consider omitting kidney surgery as a trigger for eGFR testing and including diabetes mellitus as a required trigger.

High-Resolution Computed Tomography of Fibrotic Interstitial Lung Disease.

While radiography is the first-line imaging technique for evaluation of pulmonary disease, high-resolution computed tomography (HRCT) provides detailed assessment of the lung parenchyma and interstitium, allowing normal anatomy to be differentiated from superimposed abnormal findings. The fibrotic interstitial lung diseases have HRCT features that include reticulation, traction bronchiectasis and bronchiolectasis, honeycombing, architectural distortion, and volume loss. The characterization and distribution of these features result in distinctive CT patterns. The CT pattern and its progression over time can be combined with clinical, serologic, and pathologic data during multidisciplinary discussion to establish a clinical diagnosis. Serial examinations identify progression, treatment response, complications, and can assist in determining prognosis. This article will describe the technique used to perform HRCT, the normal and abnormal appearance of the lung on HRCT, and the CT patterns identified in common fibrotic lung diseases.

Diagnostic Accuracy of Endobronchial Optical Coherence Tomography for the Microscopic Diagnosis of Usual Interstitial Pneumonia.

Rationale: Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. High-resolution computed tomography has limited resolution, and surgical lung biopsy (SLB) carries risks of morbidity and mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis. Objectives: We performed a prospective diagnostic accuracy study of EB-OCT in patients with ILD with a low-confidence diagnosis undergoing SLB. The primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern. Methods: EB-OCT was performed immediately before SLB. The resulting EB-OCT images and histopathology were interpreted by blinded, independent pathologists. Clinical diagnosis was obtained from the treating pulmonologists after SLB, blinded to EB-OCT. Measurements and Main Results: We enrolled 31 patients, and 4 were excluded because of inconclusive histopathology or lack of EB-OCT data. Twenty-seven patients were included in the analysis (16 men, average age: 65.0 yr): 12 were diagnosed with UIP and 15 with non-UIP ILD. Average FVC and DlCO were 75.3% (SD, 18.5) and 53.5% (SD, 16.4), respectively. Sensitivity and specificity of EB-OCT was 100% (95% confidence interval, 75.8-100.0%) and 100% (79.6-100%), respectively, for both histopathologic UIP and clinical diagnosis of IPF. There was high agreement between EB-OCT and histopathology for diagnosis of ILD fibrosis pattern (weighted κ: 0.87 [0.72-1.0]). Conclusions: EB-OCT is a safe, accurate method for microscopic ILD diagnosis, as a complement to high-resolution computed tomography and an alternative to SLB.

Pressmud overcome lead toxicity by improving spinach biomass in lead-contaminated soils.

Lead (Pb) pollution is a severe problem that primarily affects food chain in developing countries. Continuous use of Pb containing effluent for growing food crops builds up measurable concentration of Pb in soils; and adversely affects the soil properties and crop produce quality. To reduce the Pb metal toxicity in contaminated soil, a pot experiment was conducted with graded doses of pressmud (PM) (0, 2.5, 5.0, and 10.0 g/kg) and Pb (0, 100, 150, and 300 mg/kg soil). Various metal dynamics parameters were computed after spinach crop was harvested. Result showed that higher doses of Pb (300 mg/kg) diminished the spinach root and shoot biomass during the study; whereas, application of PM improved the spinach biomass. However, increasing the pressmud reduced the Pb concentration in shoot from 6.16, 5.99, 4.94, and 3.39 µg/g. Maximum reduction was measured in highest PM applied treatment in shoot (44.92%) and root (57.33%). In this experiment, increasing level of Pb significantly uptake was recorded with higher application rate of Pb (150 and 300 mg/kg). However, elevated doses of PM from control initially enhanced the small chunk of Pb and drastically reduced the shoot Pb uptake (0.060 to 0.049 mg/pot) in maximum level of PM applied treatment. This study is very useful to improve the soil health by immobilizing the labile fraction of Pb by addition of PM in Pb-contaminated soils.

Practical application and validation of the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines for the diagnosis of idiopathic pulmonary fibrosis.

BACKGROUND: Accurate diagnosis of idiopathic pulmonary fibrosis (IPF) is essential to inform prognosis and treatment. In 2018, the ATS/ERS/JRS/ALAT and Fleischner Society released new diagnostic guidelines for usual interstitial pneumonitis (UIP)/IPF, adding Probable UIP as a CT category based on prior studies demonstrating this category had relatively high positive predictive value (PPV) for histopathologic UIP/Probable UIP. This study applies the 2018 ATS/ERS/JRS/ALAT and Fleischner Society guidelines to determine test characteristics of CT categories in academic clinical practice. METHODS: CT and histopathology were evaluated by three thoracic radiologists and two thoracic pathologists. Comparison of consensus categorization by the 2018 ATS and Fleischner Society guidelines by CT and histopathology was performed. RESULTS: Of patients with CT UIP, 87% (PPV, 95% CI: 60-98%) had histopathologic UIP with 97% (CI: 90-100%) specificity. Of patients with CT Probable UIP, 38% (PPV, CI: 14-68%) had histopathologic UIP and 46% (PPV, CI: 19-75%) had either histopathologic UIP or Probable UIP, with 88% (CI: 77-95%) specificity. Patients with CT Indeterminate and Alternative Diagnosis had histopathologic UIP in 27% (PPV, CI: 6-61%) and 21% (PPV, CI: 11-33%) of cases with specificities of 90% (CI: 80-96%) and 25% (CI: 16-37%). Interobserver variability (kappa) between radiologists ranged 0.32-0.81. CONCLUSIONS: CT UIP and Probable UIP have high specificity for histopathologic UIP, and CT UIP has high PPV for histopathologic UIP. PPV of CT Probable UIP was 46% for combined histopathologic UIP/Probable UIP. Our results indicate that additional studies are needed to further assess and refine the guideline criteria to improve classification performance.

Comparison of Chest CT Findings of COVID-19, Influenza, and Organizing Pneumonia: A Multireader Study.

BACKGROUND. Previous studies compared CT findings of COVID-19 pneumonia with those of other infections; however, to our knowledge, no studies to date have included noninfectious organizing pneumonia (OP) for comparison. OBJECTIVE. The objectives of this study were to compare chest CT features of COVID-19, influenza, and OP using a multireader design and to assess the performance of radiologists in distinguishing between these conditions. METHODS. This retrospective study included 150 chest CT examinations in 150 patients (mean [± SD] age, 58 ± 16 years) with a diagnosis of COVID-19, influenza, or non-infectious OP (50 randomly selected abnormal CT examinations per diagnosis). Six thoracic radiologists independently assessed CT examinations for 14 individual CT findings and for Radiological Society of North America (RSNA) COVID-19 category and recorded a favored diagnosis. The CT characteristics of the three diagnoses were compared using random-effects models; the diagnostic performance of the readers was assessed. RESULTS. COVID-19 pneumonia was significantly different (p < .05) from influenza pneumonia for seven of 14 chest CT findings, although it was different (p < .05) from OP for four of 14 findings (central or diffuse distribution was seen in 10% and 7% of COVID-19 cases, respectively, vs 20% and 21% of OP cases, respectively; unilateral distribution was seen in 1% of COVID-19 cases vs 7% of OP cases; non-tree-in-bud nodules was seen in 32% of COVID-19 cases vs 53% of OP cases; tree-in-bud nodules were seen in 6% of COVID-19 cases vs 14% of OP cases). A total of 70% of cases of COVID-19, 33% of influenza cases, and 47% of OP cases had typical findings according to RSNA COVID-19 category assessment (p < .001). The mean percentage of correct favored diagnoses compared with actual diagnoses was 44% for COVID-19, 29% for influenza, and 39% for OP. The mean diagnostic accuracy of favored diagnoses was 70% for COVID-19 pneumonia and 68% for both influenza and OP. CONCLUSION. CT findings of COVID-19 substantially overlap with those of influenza and, to a greater extent, those of OP. The diagnostic accuracy of the radiologists was low in a study sample that contained equal proportions of these three types of pneumonia. CLINICAL IMPACT. Recognized challenges in diagnosing COVID-19 by CT are furthered by the strong overlap observed between the appearances of COVID-19 and OP on CT. This challenge may be particularly evident in clinical settings in which there are substantial proportions of patients with potential causes of OP such as ongoing cancer therapy or autoimmune conditions.

Chemogenomic Approaches for Revealing Drug Target Interactions in Drug Discovery.

The drug discovery process has been a crucial and cost-intensive process. This cost is not only monetary but also involves risks, time, and labour that are incurred while introducing a drug in the market. In order to reduce this cost and the risks associated with the drugs that may result in severe side effects, the in silico methods have gained popularity in recent years. These methods have had a significant impact on not only drug discovery but also the related areas such as drug repositioning, drug-target interaction prediction, drug side effect prediction, personalised medicine, etc. Amongst these research areas predicting interactions between drugs and targets forms the basis for drug discovery. The availability of big data in the form of bioinformatics, genetic databases, along with computational methods, have further supported data-driven decision-making. The results obtained through these methods may be further validated using in vitro or in vivo experiments. This validation step can further justify the predictions resulting from in silico approaches, further increasing the accuracy of the overall result in subsequent stages. A variety of approaches are used in predicting drug-target interactions, including ligand-based, molecular docking based and chemogenomic-based approaches. This paper discusses the chemogenomic methods, considering drug target interaction as a classification problem on whether or not an interaction between a particular drug and target would serve as a basis for understanding drug discovery/drug repositioning. We present the advantages and disadvantages associated with their application.