Bexotegrast in Patients with Idiopathic Pulmonary Fibrosis: The INTEGRIS-IPF Study.

RATIONALE: Idiopathic pulmonary fibrosis (IPF) is a rare and progressive disease, which causes progressive cough, exertional dyspnea, impaired quality of life and death. OBJECTIVES: Bexotegrast (PLN 74809) is an oral, once-daily, investigational drug in development for the treatment of IPF. METHODS: This Phase 2a, multicenter, clinical trial, randomized participants with IPF to receive oral, once daily bexotegrast 40 mg, 80 mg, 160 mg, 320 mg, or placebo, with or without background IPF therapy (pirfenidone or nintedanib), in an approximately 3:1 ratio in each bexotegrast dose cohort, for at least 12 weeks. The primary endpoint was incidence of treatment-emergent adverse events (TEAEs). Exploratory efficacy endpoints included change from baseline in forced vital capacity (FVC); quantitative lung fibrosis (QLF) extent (%) and changes from baseline in fibrosis-related biomarkers. MEASUREMENTS AND MAIN RESULTS: Bexotegrast was well tolerated with similar rates of TEAEs in the pooled bexotegrast and placebo groups (62/89 [69.7%] and 21/31 [67.7%], respectively). Diarrhea was the most common TEAE; most participants with diarrhea also received nintedanib. Bexotegrast treated participants experienced a reduction in FVC decline over 12 weeks vs. placebo, with or without background therapy. A dose-dependent antifibrotic effect of bexotegrast was observed with QLF imaging and a decrease in fibrosis-associated biomarkers was observed with bexotegrast vs. placebo. CONCLUSIONS: Bexotegrast demonstrated a favorable safety and tolerability profile, up to 12 weeks for the doses studied. Exploratory analyses suggest an antifibrotic effect according to FVC, QLF imaging, and circulating levels of fibrosis biomarkers. Clinical trial registration available at www. CLINICALTRIALS: gov, ID: NCT04396756. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Quantifying lung fissure integrity using a three-dimensional patch-based convolutional neural network on CT images for emphysema treatment planning.

Purpose: Evaluation of lung fissure integrity is required to determine whether emphysema patients have complete fissures and are candidates for endobronchial valve (EBV) therapy. We propose a deep learning (DL) approach to segment fissures using a three-dimensional patch-based convolutional neural network (CNN) and quantitatively assess fissure integrity on CT to evaluate it in subjects with severe emphysema. Approach: From an anonymized image database of patients with severe emphysema, 129 CT scans were used. Lung lobe segmentations were performed to identify lobar regions, and the boundaries among these regions were used to construct approximate interlobar regions of interest (ROIs). The interlobar ROIs were annotated by expert image analysts to identify voxels where the fissure was present and create a reference ROI that excluded non-fissure voxels (where the fissure is incomplete). A CNN configured by nnU-Net was trained using 86 CT scans and their corresponding reference ROIs to segment the ROIs of left oblique fissure (LOF), right oblique fissure (ROF), and right horizontal fissure (RHF). For an independent test set of 43 cases, fissure integrity was quantified by mapping the segmented fissure ROI along the interlobar ROI. A fissure integrity score (FIS) was then calculated as the percentage of labeled fissure voxels divided by total voxels in the interlobar ROI. Predicted FIS (p-FIS) was quantified from the CNN output, and statistical analyses were performed comparing p-FIS and reference FIS (r-FIS). Results: The absolute percent error mean (±SD) between r-FIS and p-FIS for the test set was 4.0% (±4.1%), 6.0% (±9.3%), and 12.2% (±12.5%) for the LOF, ROF, and RHF, respectively. Conclusions: A DL approach was developed to segment lung fissures on CT images and accurately quantify FIS. It has potential to assist in the identification of emphysema patients who would benefit from EBV treatment.

Assessing variability in non-contrast CT for the evaluation of stroke: The effect of CT image reconstruction conditions on AI-based CAD measurements of ASPECTS value and hypodense volume.

Purpose: To rule out hemorrhage, non-contrast CT (NCCT) scans are used for early evaluation of patients with suspected stroke. Recently, artificial intelligence tools have been developed to assist with determining eligibility for reperfusion therapies by automating measurement of the Alberta Stroke Program Early CT Score (ASPECTS), a 10-point scale with > 7 or ≤ 7 being a threshold for change in functional outcome prediction and higher chance of symptomatic hemorrhage, and hypodense volume. The purpose of this work was to investigate the effects of CT reconstruction kernel and slice thickness on ASPECTS and hypodense volume. Methods: The NCCT series image data of 87 patients imaged with a CT stroke protocol at our institution were reconstructed with 3 kernels (H10s-smooth, H40s-medium, H70h-sharp) and 2 slice thicknesses (1.5mm and 5mm) to create a reference condition (H40s/5mm) and 5 non-reference conditions. Each reconstruction for each patient was analyzed with the Brainomix e-Stroke software (Brainomix, Oxford, England) which yields an ASPECTS value and measure of total hypodense volume (mL). Results: An ASPECTS value was returned for 74 of 87 cases in the reference condition (13 failures). ASPECTS in non-reference conditions changed from that measured in the reference condition for 59 cases, 7 of which changed above or below the clinical threshold of 7 for 3 non-reference conditions. ANOVA tests were performed to compare the differences in protocols, Dunnett's post-hoc tests were performed after ANOVA, and a significance level of p < 0.05 was defined. There was no significant effect of kernel (p = 0.91), a significant effect of slice thickness (p < 0.01) and no significant interaction between these factors (p = 0.91). Post-hoc tests indicated no significant difference between ASPECTS estimated in the reference and any non-reference conditions. There was a significant effect of kernel (p < 0.01) and slice thickness (p < 0.01) on hypodense volume, however there was no significant interaction between these factors (p = 0.79). Post-hoc tests indicated significantly different hypodense volume measurements for H10s/1.5mm (p = 0.03), H40s/1.5mm (p < 0.01), H70h/5mm (p < 0.01). No significant difference was found in hypodense volume measured in the H10s/5mm condition (p = 0.96). Conclusion: Automated ASPECTS and hypodense volume measurements can be significantly impacted by reconstruction kernel and slice thickness.

ChatGPT in radiology: A systematic review of performance, pitfalls, and future perspectives.

PURPOSE: The purpose of this study was to systematically review the reported performances of ChatGPT, identify potential limitations, and explore future directions for its integration, optimization, and ethical considerations in radiology applications. MATERIALS AND METHODS: After a comprehensive review of PubMed, Web of Science, Embase, and Google Scholar databases, a cohort of published studies was identified up to January 1, 2024, utilizing ChatGPT for clinical radiology applications. RESULTS: Out of 861 studies derived, 44 studies evaluated the performance of ChatGPT; among these, 37 (37/44; 84.1%) demonstrated high performance, and seven (7/44; 15.9%) indicated it had a lower performance in providing information on diagnosis and clinical decision support (6/44; 13.6%) and patient communication and educational content (1/44; 2.3%). Twenty-four (24/44; 54.5%) studies reported the proportion of ChatGPT's performance. Among these, 19 (19/24; 79.2%) studies recorded a median accuracy of 70.5%, and in five (5/24; 20.8%) studies, there was a median agreement of 83.6% between ChatGPT outcomes and reference standards [radiologists' decision or guidelines], generally confirming ChatGPT's high accuracy in these studies. Eleven studies compared two recent ChatGPT versions, and in ten (10/11; 90.9%), ChatGPTv4 outperformed v3.5, showing notable enhancements in addressing higher-order thinking questions, better comprehension of radiology terms, and improved accuracy in describing images. Risks and concerns about using ChatGPT included biased responses, limited originality, and the potential for inaccurate information leading to misinformation, hallucinations, improper citations and fake references, cybersecurity vulnerabilities, and patient privacy risks. CONCLUSION: Although ChatGPT's effectiveness has been shown in 84.1% of radiology studies, there are still multiple pitfalls and limitations to address. It is too soon to confirm its complete proficiency and accuracy, and more extensive multicenter studies utilizing diverse datasets and pre-training techniques are required to verify ChatGPT's role in radiology.

Comparison of Old and New Systemic Treatments for Moderate to Severe Atopic Dermatitis.

PURPOSE OF REVIEW: Historically, systemic treatments for atopic dermatitis (AD) primarily consisted of immunosuppressive agents such as corticosteroids and Disease Modifying Antirheumatic Drugs (DMARDS), which provided symptomatic relief but often had long-term adverse effects. Newer treatments have shown significant efficacy with less side effects in clinical trials. This review discusses and compares conventional and newer systemic treatments for AD. RECENT FINDINGS: Newer medications for AD including dupilumab, tralokinumab, lebrikizumab, and oral JAK inhibitors have been shown to be safe and efficacious. High dose cyclosporine and dupilumab were more effective than methotrexate and azathioprine in improving clinical signs of AD. High-dose upadacitinib was shown in another meta-analysis to be most effective in the measured outcomes but had the highest frequency of adverse events. Targeted biologic treatments are increasingly favored over traditional immunosuppressive treatments of AD. Treatment can be individualized based on potency, adverse side effects, mechanism of action, and administration preference. Ongoing research continues to expand treatment options for AD.

Automated abdominal adipose tissue segmentation and volume quantification on longitudinal MRI using 3D convolutional neural networks with multi-contrast inputs.

OBJECTIVE: Increased subcutaneous and visceral adipose tissue (SAT/VAT) volume is associated with risk for cardiometabolic diseases. This work aimed to develop and evaluate automated abdominal SAT/VAT segmentation on longitudinal MRI in adults with overweight/obesity using attention-based competitive dense (ACD) 3D U-Net and 3D nnU-Net with full field-of-view volumetric multi-contrast inputs. MATERIALS AND METHODS: 920 adults with overweight/obesity were scanned twice at multiple 3 T MRI scanners and institutions. The first scan was divided into training/validation/testing sets (n = 646/92/182). The second scan from the subjects in the testing set was used to evaluate the generalizability for longitudinal analysis. Segmentation performance was assessed by measuring Dice scores (DICE-SAT, DICE-VAT), false negatives (FN), and false positives (FP). Volume agreement was assessed using the intraclass correlation coefficient (ICC). RESULTS: ACD 3D U-Net achieved rapid (< 4.8 s/subject) segmentation with high DICE-SAT (median ≥ 0.994) and DICE-VAT (median ≥ 0.976), small FN (median ≤ 0.7%), and FP (median ≤ 1.1%). 3D nnU-Net yielded rapid (< 2.5 s/subject) segmentation with similar DICE-SAT (median ≥ 0.992), DICE-VAT (median ≥ 0.979), FN (median ≤ 1.1%) and FP (median ≤ 1.2%). Both models yielded excellent agreement in SAT/VAT volume versus reference measurements (ICC > 0.997) in longitudinal analysis. DISCUSSION: ACD 3D U-Net and 3D nnU-Net can be automated tools to quantify abdominal SAT/VAT volume rapidly, accurately, and longitudinally in adults with overweight/obesity.

Enzymatic upcycling of wild-simulated ginseng leaves for enhancing biological activities and compound K.

Compound K (CK), a ginsenoside with high bioavailability, is present at low levels in wild-simulated ginseng leaves (WSGL). WSGL contains the CK precursors, Rd and F2, in amounts up to 26.4 ± 0.4 and 24.1 ± 1.9 mg/g extract, respectively. In this study, CK production in WGSL reached 25.9 ± 1.0 mg/g extract following treatment with Viscozyme, Celluclast 1.5 L, Pectinex Ultra SP-L, and their combination. The antioxidant activities indicated by oxygen radical absorbance capacity, ferric reducing antioxidant power, and ABTS- and DPPH radical scavenging activity of enzyme-treated WSGL were enhanced 1.69-, 2.51-, 2.88-, and 1.80-fold, respectively, compared to non-treated WSGL. Furthermore, the CK-enriched WSGL demonstrated a 1.94-fold decrease in SA-ß-galactosidase expression in human dermal fibroblasts and a 3.8-fold enhancement of inhibition of nitric oxide release in lipopolysaccharide-induced RAW 264.7 cells relative to non-treated WSGL. Consequently, WSGL subjected to enzymatic upcycling has potential as a functional material in the food and pharmaceutical industries.

Interstitial lung abnormality evaluated by an automated quantification system: prevalence and progression rate.

BACKGROUND: Despite the importance of recognizing interstitial lung abnormalities, screening methods using computer-based quantitative analysis are not well developed, and studies on the subject with an Asian population are rare. We aimed to identify the prevalence and progression rate of interstitial lung abnormality evaluated by an automated quantification system in the Korean population. METHODS: A total of 2,890 healthy participants in a health screening program (mean age: 49 years, men: 79.5%) with serial chest computed tomography images obtained at least 5 years apart were included. Quantitative lung fibrosis scores were measured on the chest images by an automated quantification system. Interstitial lung abnormalities were defined as a score ≥ 3, and progression as any score increased above baseline. RESULTS: Interstitial lung abnormalities were identified in 251 participants (8.6%), who were older and had a higher body mass index. The prevalence increased with age. Quantification of the follow-up images (median interval: 6.5 years) showed that 23.5% (59/251) of participants initially diagnosed with interstitial lung abnormality exhibited progression, and 11% had developed abnormalities (290/2639). Older age, higher body mass index, and higher erythrocyte sedimentation rate were independent risk factors for progression or development. The interstitial lung abnormality group had worse survival on follow-up (5-year mortality: 3.4% vs. 1.5%; P = 0.010). CONCLUSIONS: Interstitial lung abnormality could be identified in one-tenth of the participants, and a quarter of them showed progression. Older age, higher body mass index and higher erythrocyte sedimentation rate increased the risk of development or progression of interstitial lung abnormality.

Quantitative Computed Tomography Lung COVID Scores with Laboratory Markers: Utilization to Predict Rapid Progression and Monitor Longitudinal Changes in Patients with Coronavirus 2019 (COVID-19) Pneumonia.

Coronavirus disease 2019 (COVID-19), is an ongoing issue in certain populations, presenting rapidly worsening pneumonia and persistent symptoms. This study aimed to test the predictability of rapid progression using radiographic scores and laboratory markers and present longitudinal changes. This retrospective study included 218 COVID-19 pneumonia patients admitted at the Chungnam National University Hospital. Rapid progression was defined as respiratory failure requiring mechanical ventilation within one week of hospitalization. Quantitative COVID (QCOVID) scores were derived from high-resolution computed tomography (CT) analyses: (1) ground glass opacity (QGGO), (2) mixed diseases (QMD), and (3) consolidation (QCON), and the sum, quantitative total lung diseases (QTLD). Laboratory data, including inflammatory markers, were obtained from electronic medical records. Rapid progression was observed in 9.6% of patients. All QCOVID scores predicted rapid progression, with QMD showing the best predictability (AUC = 0.813). In multivariate analyses, the QMD score and interleukin(IL)-6 level were important predictors for rapid progression (AUC = 0.864). With >2 months follow-up CT, remained lung lesions were observed in 21 subjects, even after several weeks of negative reverse transcription polymerase chain reaction test. AI-driven quantitative CT scores in conjugation with laboratory markers can be useful in predicting the rapid progression and monitoring of COVID-19.

Pulmonary Fibrosis Stakeholder Summit: A Joint NHLBI, Three Lakes Foundation, and Pulmonary Fibrosis Foundation Workshop Report.

Despite progress in elucidation of disease mechanisms, identification of risk factors, biomarker discovery, and the approval of two medications to slow lung function decline in idiopathic pulmonary fibrosis and one medication to slow lung function decline in progressive pulmonary fibrosis, pulmonary fibrosis remains a disease with a high morbidity and mortality. In recognition of the need to catalyze ongoing advances and collaboration in the field of pulmonary fibrosis, the NHLBI, the Three Lakes Foundation, and the Pulmonary Fibrosis Foundation hosted the Pulmonary Fibrosis Stakeholder Summit on November 8-9, 2022. This workshop was held virtually and was organized into three topic areas: 1) novel models and research tools to better study pulmonary fibrosis and uncover new therapies, 2) early disease risk factors and methods to improve diagnosis, and 3) innovative approaches toward clinical trial design for pulmonary fibrosis. In this workshop report, we summarize the content of the presentations and discussions, enumerating research opportunities for advancing our understanding of the pathogenesis, treatment, and outcomes of pulmonary fibrosis.

One-year clinical and radiologic outcomes of Surpass Evolve flow diverter for large unruptured intracranial aneurysms.

BACKGROUND: Surpass Evolve Flow Diverter (SE-FD; Stryker Neurovascular, Kalamazoo, MI, USA) was launched in 2019 as a new generation FD of Surpass Streamline. The aim of this study was to report the effectiveness and safety of SE-FD insertion for unruptured intracranial aneurysm at one-year follow-up. METHODS: Between November 2019 and October 2021, a total of 106 patients with 108 aneurysms were treated with FD in single institution. Of these, SE-FD insertion was performed in 40 patients with 41 aneurysms. At one-year follow-up, clinical and angiographic outcomes were retrospectively evaluated from electronic medical record and aneurysm database. RESULTS: There were 12 male and 28 female patients (mean age 59.1 years, 95% CI: 55.3-62.9). Fusiform aneurysm dissection was 46.3% (19/41). Mean maximum aneurysm diameter was 13.2 mm (SD 5.53), and 34.1% (14/41) of aneurysms were 15 mm or bigger. Among 41 aneurysms, complex aneurysm (recurred, thrombosed, or branch artery-incorporated) was accounted for 41.5% (17/41). All procedures were successfully conducted with 7.3% (3/41) of procedure-related complications. At one-year follow-up (N.=40), neurologic morbidity was noted in 2 cases (5.0%; both with modified Rankin Scale [mRS] 1) without any mortality. At one-year follow-up (N.=41), radiologic outcomes were adequate occlusion in 33 (80.5%) and complete occlusion in 29 (70.7%). There was no retreatment in our cohort. CONCLUSIONS: Surpass Evolve Flow Diverter seemed to be safe and effective for the treatment of dissecting/fusiform or complex aneurysms at one-year follow-up. However, further study is needed to evaluate long term results.

Comparison of Pirfenidone and Nintedanib: Post Hoc Analysis of the CleanUP-IPF Study.

BACKGROUND: Antifibrotics are effective in slowing FVC decline in idiopathic pulmonary fibrosis (IPF). However, whether antifibrotic type is differentially associated with FVC decline remains inconclusive. RESEARCH QUESTION: Are there significant differences in 12-month FVC decline between pirfenidone and nintedanib? STUDY DESIGN AND METHODS: A post hoc analysis was performed using the Clinical Efficacy of Antimicrobial Therapy Strategy Using Pragmatic Design in IPF (CleanUP-IPF) trial (No. NCT02759120). Participants who reported using pirfenidone or nintedanib on enrollment into the trial were in the primary analysis. Spirometry was scheduled at baseline and the 12- and 24-month study visits. Linear mixed-effects models with random intercept and slope were used to examine changes in FVC over time. Models were adjusted for age, sex, smoking history, coronary artery disease history, baseline FVC, and 12-month spline term. Survival and nonelective respiratory hospitalization by antifibrotic type were determined using Cox regression models with adjustment for age, sex, smoking history, coronary artery disease history, and baseline FVC and diffusing capacity for carbon monoxide. RESULTS: Out of the 513 participants with IPF randomized in the CleanUP-IPF trial, 407 reported using pirfenidone (n = 264, 65%) or nintedanib (n = 143, 35%). The pirfenidone group had more participants with a history of coronary artery disease than the nintedanib group (34.1% vs 20.3%, respectively). Patients treated with nintedanib had a higher 12-month visit FVC than patients treated with pirfenidone (mean difference, 106 mL; 95% CI, 34-178). This difference was attenuated at the 24-month study visit. There were no significant differences in overall survival and nonelective respiratory hospitalization between the pirfenidone- and nintedanib-treated groups. INTERPRETATION: Patients with IPF who used nintedanib had a slower 12-month FVC decline than pirfenidone in a post hoc analysis of a clinical trial.

Effects of the multi-channeled oral irrigation (MCOI) unit in preventing dental plaque formation and gingivitis: A randomized controlled trial.

PURPOSE: To evaluate the efficacy of COMORAL a new multi-channeled oral irrigation (MCOI) unit with pulsating water jet, in plaque score reduction and gingivitis. METHODS: This was a single-blinded clinical randomized controlled trial (NCT05031260). Forty-two healthy subjects between 18 to 35 years old were initially recruited, and the control group (n = 20) and the intervention group (n = 17) were randomly assigned. Both groups were asked to brush their teeth one or two times a day without any supplementary oral hygiene products while the intervention group used COMORAL 3 times a day, 5 days a week. Clinical indices including gingival index (GI), plaque index (PI), bleeding on probing (BOP), pocket depth (PD), gingival recession (GR), and clinical attachment loss (CAL) were obtained at the baseline (D0), day 14 (D14), and day 28 (D28). Saliva was collected to examine the presence of periodontal pathogens. The repeated measures analysis of variance or generalized estimating equation was used to compare the interaction between groups and time points. The independent t-test or Mann-Whitney test were used for intergroup differences at each time point. RESULTS: At V0, PI, GI, BOP, and PD scores showed no differences between the two groups. At V1 and V2, these scores showed significant difference between two groups (P < 0.05) such that the intervention group showed gradual decreases while the control group showed no change. There were no differences in GR, CAL, and periodontal pathogens between the two groups. COMORAL showed improvement in reducing gingival inflammation and dental plaque formation adjuvant to routine toothbrushing in healthy adults. CLINICAL SIGNIFICANCE: The results of this study can be useful to clinicians when selecting oral hygiene devices that can help improve patients' routine oral hygiene practice and their overall oral health.

RECIST 1.1 Target Lesion Categorical Response in Metastatic Renal Cell Carcinoma: A Comparison of Conventional versus Volumetric Assessment.

Purpose To investigate Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) approximations of target lesion tumor burden by comparing categorical treatment response according to conventional RECIST versus actual tumor volume measurements of RECIST target lesions. Materials and Methods This is a retrospective cohort study of individuals with metastatic renal cell carcinoma enrolled in a clinical trial (from 2003 to 2017) and includes individuals who underwent baseline and at least one follow-up chest, abdominal, and pelvic CT study and with at least one target lesion. Target lesion volume was assessed by (a) Vmodel, a spherical model of conventional RECIST 1.1, which was extrapolated from RECIST diameter, and (b) Vactual, manually contoured volume. Volumetric responses were determined by the sum of target lesion volumes (Vmodel-sum TL and Vactual-sum TL, respectively). Categorical volumetric thresholds were extrapolated from RECIST. McNemar tests were used to compare categorical volume responses. Results Target lesions were assessed at baseline (638 participants), week 9 (593 participants), and week 17 (508 participants). Vmodel-sum TL classified more participants as having progressive disease (PD), compared with Vactual-sum TL at week 9 (52 vs 31 participants) and week 17 (57 vs 39 participants), with significant overall response discordance (P < .001). At week 9, 25 (48%) of 52 participants labeled with PD by Vmodel-sum TL were classified as having stable disease by Vactual-sum TL. Conclusion A model of RECIST 1.1 based on a single diameter measurement more frequently classified PD compared with response assessment by actual measured tumor volume. Keywords: Urinary, Kidney, Metastases, Oncology, Tumor Response, Volume Analysis, Outcomes Analysis ClinicalTrials.gov registration no. NCT01865747 © RSNA, 2023 Supplemental material is available for this article.

Combining Clinical and Biological Data to Predict Progressive Pulmonary Fibrosis in Patients With Systemic Sclerosis Despite Immunomodulatory Therapy.

OBJECTIVE: Progressive pulmonary fibrosis (PPF) is the leading cause of death in systemic sclerosis (SSc). This study aimed to develop a clinical prediction nomogram using clinical and biological data to assess risk of PPF among patients receiving treatment of SSc-related interstitial lung disease (SSc-ILD). METHODS: Patients with SSc-ILD who participated in the Scleroderma Lung Study II (SLS II) were randomized to treatment with either mycophenolate mofetil (MMF) or cyclophosphamide (CYC). Clinical and biological parameters were analyzed using univariable and multivariable logistic regression, and a nomogram was created to assess the risk of PPF and validated by bootstrap resampling. RESULTS: Among 112 participants with follow-up data, 22 (19.6%) met criteria for PPF between 12 and 24 months. An equal proportion of patients randomized to CYC (n = 11 of 56) and mycophenolate mofetil (n = 11 of 56) developed PPF. The baseline severity of ILD was similar for patients who did, compared to those who did not, experience PPF in terms of their baseline forced vital capacity percent predicted, diffusing capacity for carbon monoxide percent predicted, and quantitative radiological extent of ILD. Predictors in the nomogram included sex, baseline CXCL4 level, and baseline gastrointestinal reflux score. The nomogram demonstrated moderate discrimination in estimating the risk of PPF, with a C-index of 0.72 (95% confidence interval 0.60-0.84). CONCLUSION: The SLS II data set provided a unique opportunity to investigate predictors of PPF and develop a nomogram to help clinicians identify patients with SSc-ILD who require closer monitoring while on therapy and potentially an alternative treatment approach. This nomogram warrants external validation in other SSc-ILD cohorts to confirm its predictive power.

Recent advances in immunomodulators for atopic dermatitis.

PURPOSE OF REVIEW: Conventional treatments of atopic dermatitis have been inadequate, especially in patients with moderate-to-severe disease. RECENT FINDINGS: In the past 5 years, four immunomodulators have been approved for the treatment of atopic dermatitis in children. These include dupilumab, ruxolitinib, upadacitinib, and abrocitinib. The review summarizes the pivotal phase 3 trials of these medications. SUMMARY: The newer immunomodulators have transformed the treatment of atopic dermatitis, particularly in patients with moderate-to-severe disease. Dupilumab targets IL-4 and IL-13, which are the main causes of allergic inflammation, resulting in great efficacy and few side effects. Upadacitinib and abrocitinib are alternative systemic medications for adolescents who have failed or are unable to tolerate dupilumab. Ruxolitinib cream is the latest addition to the current topical therapy. It is indicated for children 12 years and older with mild-to-moderate atopic dermatitis. Further studies are needed to confirm its safety and efficacy for younger children and for patients with more severe disease.

How AI Responds to Common Lung Cancer Questions: ChatGPT vs Google Bard.

Background The recent release of large language models (LLMs) for public use, such as ChatGPT and Google Bard, has opened up a multitude of potential benefits as well as challenges. Purpose To evaluate and compare the accuracy and consistency of responses generated by publicly available ChatGPT-3.5 and Google Bard to non-expert questions related to lung cancer prevention, screening, and terminology commonly used in radiology reports based on the recommendation of Lung Imaging Reporting and Data System (Lung-RADS) v2022 from American College of Radiology and Fleischner society. Materials and Methods Forty of the exact same questions were created and presented to ChatGPT-3.5 and Google Bard experimental version as well as Bing and Google search engines by three different authors of this paper. Each answer was reviewed by two radiologists for accuracy. Responses were scored as correct, partially correct, incorrect, or unanswered. Consistency was also evaluated among the answers. Here, consistency was defined as the agreement between the three answers provided by ChatGPT-3.5, Google Bard experimental version, Bing, and Google search engines regardless of whether the concept conveyed was correct or incorrect. The accuracy among different tools were evaluated using Stata. Results ChatGPT-3.5 answered 120 questions with 85 (70.8%) correct, 14 (11.7%) partially correct, and 21 (17.5%) incorrect. Google Bard did not answer 23 (19.1%) questions. Among the 97 questions answered by Google Bard, 62 (51.7%) were correct, 11 (9.2%) were partially correct, and 24 (20%) were incorrect. Bing answered 120 questions with 74 (61.7%) correct, 13 (10.8%) partially correct, and 33 (27.5%) incorrect. Google search engine answered 120 questions with 66 (55%) correct, 27 (22.5%) partially correct, and 27 (22.5%) incorrect. The ChatGPT-3.5 is more likely to provide correct or partially answer than Google Bard, approximately by 1.5 folds (OR = 1.55, P = 0.004). ChatGPT-3.5 and Google search engine were more likely to be consistent than Google Bard by approximately 7 and 29 folds (OR = 6.65, P = 0.002 for ChatGPT and OR = 28.83, P = 0.002 for Google search engine, respectively). Conclusion Although ChatGPT-3.5 had a higher accuracy in comparison with the other tools, neither ChatGPT nor Google Bard, Bing and Google search engines answered all questions correctly and with 100% consistency.

The Experience of Testing for Coronavirus Disease (COVID-19) at a Single Diagnostic Center in Paraguay before the Introduction of Vaccination.

Soon after the declaration of the COVID-19 pandemic, the Institute for Health Sciences Research (IICS) of the National University of Asunción, Paraguay became a testing laboratory (COVID-Lab) for SARS-CoV-2. The COVID-Lab testing performance was assessed from 1 April 2020 to 12 May 2021. The effect of the pandemic on the IICS and how the COVID-Lab contributed to the academic and research activities of the institute were also assessed. IICS researchers and staff adjusted their work schedules to support the COVID-Lab. Of the 13,082 nasopharyngeal/oropharyngeal swabs processed, 2704 (20.7%) tested positive for SARS-CoV-2 by RT-PCR. Of the individuals testing positive, 55.4% were female and 48.3% were aged 21-40 years. Challenges faced by the COVID-Lab were unstable reagent access and insufficient staff; shifting obligations regarding research, academic instruction, and grantsmanship; and the continuous demands from the public for information on COVID-19. The IICS provided essential testing and reported on the progress of the pandemic. IICS researchers gained better laboratory equipment and expertise in molecular SARS-CoV-2 testing but struggled to manage their conflicting educational and additional research obligations during the pandemic, which affected their productivity. Therefore, policies protecting the time and resources of the faculty and staff engaged in pandemic-related work or research are necessary components of healthcare emergency preparedness.

Dual receptor T cells mediate effective antitumor immune responses via increased recognition of tumor antigens.

BACKGROUND: Discovery that ~16% of T cells naturally co-express two T-cell receptor (TCR) clonotypes prompts examining the role of dual TCR cells in immune functions. METHODS: Using TCRα-reporter transgenic mice, enabling unambiguous identification of single-TCR and dual-TCR cells, we tested the role of dual TCR cells in antitumor immune responses against immune-responsive syngeneic 6727 sarcoma and immune-resistant B16F10 melanoma. RESULTS: Dual TCR cells were specifically increased among tumor-infiltrating lymphocytes (TILs) in both models, indicating selective advantage in antitumor responses. Phenotype and single-cell gene expression analyses identified dual TCR are predominant during the effective antitumor response, demonstrating selectively increased activation in the TIL compartment and skewing toward an effector memory phenotype. Absence of dual TCR cells impaired immune response to B16F10 but not 6727, suggesting that dual TCR cells may be more influential in responses against poorly immunogenic tumors. Dual TCR cells demonstrated an advantage in recognition of B16F10-derived neoantigens in vitro, providing a mechanistic basis for their antitumor reactivity. CONCLUSIONS: These results discover an unrecognized role for dual TCR cells in protective immune function and identify these cells and their TCRs as a potential resource for antitumor immunotherapy.