Uncovering the impact of UV radiation on mitochondria in dermal cells: a STED nanoscopy study.

Mitochondria are essential organelles in cellular energy metabolism and other cellular functions. Mitochondrial dysfunction is closely linked to cellular damage and can potentially contribute to the aging process. The purpose of this study was to investigate the subcellular structure of mitochondria and their activities in various cellular environments using super-resolution stimulated emission depletion (STED) nanoscopy. We examined the morphological dispersion of mitochondria below the diffraction limit in sub-cultured human primary skin fibroblasts and mouse skin tissues. Confocal microscopy provides only the overall morphology of the mitochondrial membrane and an indiscerptible location of nucleoids within the diffraction limit. Conversely, super-resolution STED nanoscopy allowed us to resolve the nanoscale distribution of translocase clusters on the mitochondrial outer membrane and accurately quantify the number of nucleoids per cell in each sample. Comparable results were obtained by analyzing the translocase distribution in the mouse tissues. Furthermore, we precisely and quantitatively analyzed biomolecular distribution in nucleoids, such as the mitochondrial transcription factor A (TFAM), using STED nanoscopy. Our findings highlight the efficacy of super-resolution fluorescence imaging in quantifying aging-related changes on the mitochondrial sub-structure in cells and tissues.

Edoxaban for the treatment of hypercoagulability and cerebral thromboembolism associated with cancer: A randomized clinical trial of biomarker targets.

BACKGROUND: This study aimed compare efficacy of edoxaban and enoxaparin upon biomarkers of hypercoagulability in patients with cancer-related embolic stroke of undetermined source (ESUS). METHODS: In this open-label, randomized, pilot trial, patients with cancer-related ESUS within 30 days of diagnosis were randomly assigned (1:1) to receive edoxaban (60 mg once daily) or enoxaparin (1 mg/kg twice daily) for 90 days. The primary endpoint was interval change of serum D-dimer level between days 0 and 7. The secondary endpoints were microembolic signals detected by transcranial Doppler at 7 and 90 days, the modified Rankin scale score, and stroke recurrence during 90 days. Safety outcomes included major bleeding and all-cause death at 90 days. RESULTS: Of 303 patients with ischemic stroke and cancer, 40 fully met enrollment criteria and were randomized. Baseline D-dimer levels were numerically higher in the edoxaban group (22.9 ± 15.9 µg/mL vs 16.9 ± 16.9 µg/mL). D-dimer level change (%) between days 0 and 7 was similar in the two groups (53.2 ± 25.7 vs 52.2 ± 52.0; P = 0.11). Microembolic signals were detected in 41.1% and 43.8% at baseline, 41.2% and 42.9% at day 7, and 25.0% and 28.6% at day 90 in the edoxaban and enoxaparin groups, respectively. Non-significantly higher major bleeding (35.0% vs 10.0%, P = 0.06) and 90-day mortality (40.0% vs 25.0%, P = 0.31) were noted in the edoxaban group. CONCLUSION: Edoxaban and enoxaparin were comparable with respect to the biomarkers of hypercoagulability and cerebral thromboembolism. Larger trials are warranted to compare effects of edoxaban and enoxaparin upon recurrent stroke and major bleeding in patients with cancer-related ESUS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT03570281 (https://clinicaltrials.gov/ct2/show/NCT03570281).

Outcome of Atezolizumab Plus Bevacizumab Combination Therapy in High-Risk Patients with Advanced Hepatocellular Carcinoma.

Real-world data regarding treatment with atezolizumab plus bevacizumab in high-risk patients with advanced HCC are lacking. In this multicenter retrospective cohort study, a total of 215 patients with advanced HCC received atezolizumab plus bevacizumab treatment at four tertiary hospitals. High-risk patients were those with grade Vp4 portal vein thrombus, bile duct invasion, or more than 50% liver infiltration. In total, 98 (45.6%) were the high-risk population, 186 (86.5%) were considered to be Child-Pugh class A, and 128 (59.5%) had previously received neoadjuvant or concomitant radiation treatment. Median overall survival (OS) was 11.25 months (95% CI, 9.50-13.10), and the median progression-free survival (PFS) was 8.00 months (95% CI, 6.82-9.18). In the high-risk population, the median OS was 10 months (95% CI, 8.19-11.82) and the median PFS was 6.50 months (95% CI, 3.93-9.08). In the high-risk population, multivariate analysis indicated that radiation therapy and lower ALBI grade were associated with better OS and PFS. A total of 177 (82.3%) patients experienced adverse events of any grade, the most common being proteinuria (23.7%). Atezolizumab plus bevacizumab treatment showed consistent efficacy and tolerability in both the total and high-risk population. Radiation therapy combined with atezolizumab plus bevacizumab treatment might be helpful to improve PFS and OS in high-risk populations.

Understanding the effects of Haemophilus influenzae colonization on bronchiectasis: a retrospective cohort study.

BACKGROUND: Bacterial colonization is an essential aspect of bronchiectasis. Although Haemophilus influenzae is a frequent colonizer in some regions, its clinical impacts are poorly understood. This study aimed to elucidate the impact of H. influenzae colonization in patients with bronchiectasis. METHODS: This retrospective study screened adult patients diagnosed with bronchiectasis at a tertiary referral center between April 1, 2003, and May 16, 2021, in South Korea. Propensity score matching was used to match patients with and without H. influenzae colonization. We assessed the severity of bronchiectasis as per the bronchiectasis severity index, the incidence of exacerbation, differences in lung function, and all-cause mortality. RESULTS: Out of the 4,453 patients with bronchiectasis, 79 (1.8%) were colonized by H. influenzae. After 1:2 propensity score matching, 78 and 154 patients were selected from the H. influenzae colonizer and non-colonizer groups, respectively. Although there were no significant differences between the groups regarding baseline demographics, patients colonized with H. influenzae had a higher bronchiectasis severity index (median 6 [interquartile range 4-8] vs. 4 [2-7], p = 0.002), associated with extensive radiographic involvement (52.2% vs. 37.2%, p = 0.045) and mild exacerbation without hospitalization (adjusted incidence rate ratio 0.15; 95% confidence interval 0.12-0.24). Lung function and mortality rates did not reveal significant differences, regardless of H. influenzae colonization. CONCLUSION: H. influenzae colonization in bronchiectasis was associated with more severe disease and greater incidence of mild exacerbation, but not lung function and mortality. Attention should be paid to patients with bronchiectasis with H. influenzae colonization.

Identification and characterization of novel ERBB4 variant associated with sporadic amyotrophic lateral sclerosis (ALS).

Amyotrophic Lateral Sclerosis (ALS) is the most common type of motor neuron disease characterized by progressive motor neuron degeneration in brain and spinal cord. Most cases are sporadic in ALS and 5-10% of cases are familiar. >50 genes are known to be associated with ALS and one of them is ERBB4. In this paper, we report the case of a 53-year-old ALS patient with progressive muscle weakness and fasciculation, but he had no cognitive decline. We performed the next generation sequencing (NGS) and in silico analysis, it predicted a highly pathogenic variant, c.2116 A > G, p.Asn706Asp (N706D) in the ERBB4 gene. The amino acid residue is highly conserved among species. ERBB4 is a member of the ERBB family of receptor tyrosine kinases. ERBB4 has multiple tyrosine phosphorylation sites, including an autophosphorylation site at tyrosine 1284 residue. Autophosphorylation of ERBB4 promotes biological activity and it associated with NRG-1/ERBB4 pathway. It is already known that tyrosine 128 phosphorylation of ERBB4 is decreased in patients who have ALS-associated ERBB4 mutations. We generated ERBB4 N706D construct using site-directed mutagenesis and checked the phosphorylation level of ERBB4 N706D in NSC-34 cells. We found that the phosphorylation of ERBB4 N706D was decreased compared to ERBB4 wild-type, indicating a loss of function mutation in ERBB4. We report a novel variant in ERBB4 gene leading to ALS through dysfunction of ERBB4.

Lung Organoid on a Chip: A New Ensemble Model for Preclinical Studies.

The lung is a complex organ comprising a branched airway that connects the large airway and millions of terminal gas-exchange units. Traditional pulmonary biomedical research by using cell line model system have limitations such as lack of cellular heterogeneity, animal models also have limitations including ethical concern, race-to-race variations, and physiological differences found in vivo. Organoids and on-a-chip models offer viable solutions for these issues. Organoids are three-dimensional, self-organized construct composed of numerous cells derived from stem cells cultured with growth factors required for the maintenance of stem cells. On-a-chip models are biomimetic microsystems which are able to customize to use microfluidic systems to simulate blood flow in blood channels or vacuum to simulate human breathing. This review summarizes the key components and previous biomedical studies conducted on lung organoids and lung-on-a-chip models, and introduces potential future applications. Considering the importance and benefits of these model systems, we believe that the system will offer better platform to biomedical researchers on pulmonary diseases, such as emerging viral infection, progressive fibrotic pulmonary diseases, or primary or metastatic lung cancer.

A case of nearly complete response in hepatocellular carcinoma with disseminated lung metastasis by combination therapy of nivolumab and ipilimumab after treatment failure of atezolizumab plus bevacizumab.

Recently, the efficacy of immuno-oncologic agents for advanced hepatocellular carcinoma (HCC) has been proven in several trials. In particular, atezolizumab with bevacizumab (AteBeva), as a first-line therapy for advanced HCC, has shown tremendous advances in the IMBrave150 study. However, second or third-line therapy after treatment failure with AteBeva has not been firmly established. Moreover, clinicians have continued their attempts at multidisciplinary treatment that includes other systemic therapy and radiotherapy (RT). Here, we report a case that showed a near complete response (CR) of lung metastasis to nivolumab with ipilimumab therapy after achieving a near CR of intrahepatic tumor using sorafenib and RT in a patient with advanced HCC who had experienced treatment failure of AteBeva.

The association between Adenosine A2A receptor gene polymorphisms and attention deficit hyperactivity disorder in Korean children.

Attention deficit hyperactivity disorder (ADHD) is a common and heritable neurodevelopmental disorder. Particularly, ADHD is known to be related to the dopaminergic system. ADHD symptoms can appear when the dopamine binding affinity diminishes due to dopamine receptor abnormalities, such as the dopamine D2 receptor (D2R). This receptor interacts with the adenosine A2A receptor (A2AR). The A2AR acts as an antagonist of D2R, that is, the increased binding of adenosine with A2AR inhibits the D2R activity. Furthermore, it is found that the single nucleotide polymorphisms of the adenosine A2A receptor gene (ADORA2A) revealed a significant relationship with ADHD in various populations. Therefore, we examined the genetic relationship between ADORA2A polymorphisms (rs2297838, rs5751876, and rs4822492) and Korean ADHD children. A case-control study was performed for 150 cases and 322 controls. Genotyping of ADORA2A polymorphisms was conducted by PCR-RFLP. The results demonstrated that the rs5751876 TC genotype was associated with children with ADHD (p = 0.018). The rs2298383 CC genotype was significantly associated with children with ADHD/HI (p = 0.026). However, when Bonferroni correction was used, the significance vanished (padjusted = 0.054 and padjusted = 0.078, respectively). Haplotype analysis showed that TTC, TCC, and CTG demonstrated a significant difference between ADHD/C children and control groups (padjusted = 0.006, padjusted = 0.011, and padjusted = 0.028, respectively). In conclusion, we propose a possible association between ADORA2A polymorphisms with Korean children having ADHD.

Comparison of electromagnetic navigation bronchoscopy and transthoracic needle biopsy for diagnosing bronchus sign-positive pulmonary lesions.

OBJECTIVES: Electromagnetic navigation bronchoscopy (ENB) is an advanced technique for diagnosing peripheral pulmonary lesions, and the bronchus sign is a well-established factor for improving the diagnostic performance. However, ENB is a novel technology compared to the commonly adopted transthoracic needle biopsy (TTNB). There are limited data on the comparison of these techniques for diagnosing bronchus sign-positive lesions. Therefore, we aimed to compare the diagnostic yield and complication rates of ENB and TTNB for diagnosing lung cancer in bronchus sign-positive pulmonary lesions. MATERIALS AND METHODS: We assessed 2,258 individuals who underwent either of the techniques for initial biopsy between September 2016 and May 2022 at a tertiary center in South Korea and analyzed 1,248 participants (153 ENB and 1,095 TTNB cases) with a positive bronchus sign. We performed multivariable logistic regression analyses to evaluate the factors associated with the diagnostic yield, sensitivity for malignancy, and procedure-related complications. In addition, the outcomes were compared between the two techniques after a 1:2 propensity score-matching to control for pre-procedural factors. RESULTS: After adjustments for clinical/radiological factors, performing TTNB over ENB was not significantly associated with a higher diagnostic yield but with a higher risk of pneumothorax (OR = 9.69, 95% CI = 4.15-22.59). Propensity score-matching resulted in 459 participants (153 ENB and 306 TTNB cases) with balanced pre-procedural characteristics. The overall diagnostic yield did not differ significantly between ENB and TTNB (85.0% vs. 89.9%, p = 0.124). The diagnostic yield (86.7% vs. 90.3%, p = 0.280) and sensitivity for malignancy (85.3% vs. 88.8%, p = 0.361) were comparable among patients with a class 2 bronchus sign. However, TTNB demonstrated a significantly higher complication rate of pneumothorax (28.8% vs. 3.9%, p < 0.001) and pneumothorax requiring tube drainage (6.5% vs. 2.0%, p = 0.034) than ENB. CONCLUSION: ENB demonstrated a diagnostic yield comparable with that of TTNB for diagnosing bronchus sign-positive peripheral pulmonary lesions with significantly lower complication rates.

Electromagnetic Navigation Bronchoscopy Versus Radial Endobronchial Ultrasound for Diagnosing Lung Cancer: A Propensity Score-Matched Analysis.

INTRODUCTION: Electromagnetic navigation bronchoscopy (ENB) and radial endobronchial ultrasound (R-EBUS) are advanced imaging-guided bronchoscopy techniques for diagnosing pulmonary lesions. This study aimed to determine the comparative diagnostic yield of sole ENB and R-EBUS under moderate sedation. METHODS: We investigated 288 patients who underwent sole ENB (n=157) or sole R-EBUS (n=131) under moderate sedation for pulmonary lesion biopsy between January 2017 and April 2022. After a 1:1 propensity score-matching to control for pre-procedural factors, the diagnostic yield, sensitivity for malignancy, and procedure-related complications between both techniques were compared. RESULTS: The matching resulted in 105 pairs/procedure for analyses with balanced clinical and radiological characteristics. The overall diagnostic yield was significantly higher for ENB than for R-EBUS (83.8% vs. 70.5%, p=0.021). ENB demonstrated a significantly higher diagnostic yield than R-EBUS among those with lesions>20mm in size (85.2% vs. 72.3%, p=0.034), radiologically solid lesions (86.7% vs. 72.7%, p=0.015), and lesions with a class 2 bronchus sign (91.2% vs. 72.3%, p=0.002), respectively. The sensitivity for malignancy was also higher for ENB than for R-EBUS (81.3% vs. 55.1%, p<0.001). After adjusting for clinical/radiological factors in the unmatched cohort, using ENB over R-EBUS was significantly associated with a higher diagnostic yield (odd ratio=3.45, 95% confidence interval=1.75-6.82). Complication rates for pneumothorax did not significantly differ between ENB and R-EBUS. CONCLUSION: ENB demonstrated a higher diagnostic yield than R-EBUS under moderate sedation for diagnosing pulmonary lesions, with similar and generally low complication rates. Our data indicate the superiority of ENB over R-EBUS in a least-invasive setting.

Correlation of monocyte counts with clinical outcomes in idiopathic nonspecific interstitial pneumonia.

Higher blood monocyte counts are related to worse survival in idiopathic pulmonary fibrosis. However, studies evaluating the association between blood monocyte counts and clinical outcomes of idiopathic nonspecific interstitial pneumonia (iNSIP) are lacking. We evaluated the impact of monocyte counts on iNSIP prognosis. iNSIP patients (n = 126; median age, 60 years; female, n = 64 [50.8%]) diagnosed by surgical lung biopsy were enrolled and categorized into low (monocyte < 600/µL) and high (monocyte ≥ 600/µL) monocyte groups. The median follow-up duration was 53.0 months. After adjusting for age, sex, and smoking history, the annual decline in forced vital capacity (FVC) showed differences between the monocyte groups (Pinteraction = 0.006) (low vs. high; - 28.49 mL/year vs. - 65.76 mL/year). The high-monocyte group showed a worse survival rate (P = 0.01) compared to low monocyte group. The 5-year survival rates were 83% and 72% in the low- and high-monocyte groups, respectively. In the Cox-proportional hazard analysis, older age, male sex, low baseline FVC, and diffusing capacity of the lung for carbon monoxide were independent risk factors for mortality. However, monocyte count (Hazard ratio 1.61, P = 0.126) was not an independent prognostic factor. Although high monocyte count might be associated with faster lung function decline, it could not independently predict survival in iNSIP.

Robot-assisted radial forearm free flap harvesting: a propensity score-matched case-control study.

Although some surgeons prefer anterolateral thigh and latissimus dorsi flap for soft tissue reconstruction in the head and neck area because it minimizes donor site complications, the radial forearm flap remains the workhorse for soft tissue reconstruction due to its reliability. To reduce donor site morbidity, the authors developed a novel technique for radial forearm flap harvesting using a robotic device. 42 radial forearm free flap reconstruction cases were studied, consisting of 31 conventional and 11 robot-assisted cases. 1:1 propensity score matching was done according to age, sex, previous and postoperative radiation therapy history and method used for vein anastomosis. There was no significant difference in flap outcome, which was 100% vitality in the robot-assisted group and 90.9% vitality in the conventional group. The robot-assisted group showed significantly longer mean harvesting time than did the conventional group, being 107.2 min and 67.0 min, respectively. Robot-assisted radial forearm flap harvesting can reduce donor site complications by minimizing incision. When more surgical experience is gained under appropriate case selection, we expect our robot-assisted method will yield a harvesting time similar to that of the conventional method and thus become more reliable and feasible.

Comparing Free-Flap Reconstruction After Robot-Assisted Neck Dissection via a Retroauricular Approach and a Traditional Transcervical Approach: Single-Surgeon Experiences of 90 Consecutive Cases.

BACKGROUND: Predominant traditional approaches for most patients who have advanced-stage oral cancer with transcervical incision lines left irreversible scars. To address this, surgeons have continuously refined minimally invasive surgery (MIS) techniques, including robot-assisted neck surgeries. This article introduces and discusses the feasibility, versatility, and availability of free-flap reconstruction via the retroauricular approach (RA), considered difficult to date. METHODS: This study retrospectively analyzed 90 consecutive patients who had free-flap reconstruction performed by a single surgeon (D.K.) in the Department of Oral and Maxillofacial Surgery, Yonsei University, from March 2021 to April 2022. The type of defects and flaps, hospitalization days, total operation time, and type of vessels and anastomoses were compared statistically. RESULTS: The type of vessels used did not differ between the RA and the transcervical approach (TA) groups, nor in duration of hospital stays. Likewise, the total reconstruction time did not differ significantly between the TA group (240 min) and the RA group (245 min) (p = 0.756). However, the total operation time was about 1 h less in the TA group, a statistically significant difference (TA group [593 ± 152 min] vs. RA group [655 ± 117 min]; p = 0.044). All flaps were successful in the RA group, whereas one flap in the TA group led to a total loss (TA group [98.3%] vs. RA group [100.0%]; p = 1.000). CONCLUSIONS: Even for patients with advanced oral cancer who require massive tumor ablation, it is feasible to obtain an aesthetic and functional surgical outcome by performing free-flap reconstruction via the retroauricular approach.

Peroxiredoxin 5 is involved in cancer cell invasion and tumor growth of oral squamous cell carcinoma.

OBJECTIVES: Peroxiredoxins (Prxs) are antioxidant enzymes that can coordinate cell signal transduction via reactive species scavenging or by acting as redox sensors. The mechanism by which Prxs promote cancer invasion and progression is not yet fully understood. This study aims to elucidate the precise mechanism through which Prx type 5 (Prx5) promotes cancer invasion and tumor growth. MATERIALS AND METHODS: We analyzed the Prx5 expression in oral squamous cell carcinoma (OSCC) by using microarray analysis for gene expression profiling. To identify Prx5 function in cancer, lentiviral short hairpin RNA was used for Prx5 depletion, and invasion assay and mouse xenograft were performed. RESULTS: In microarray data obtained from OSCC patients, Prx5 showed higher expression at the tumor margin (TM) compared to the tumor center (TC) of the collective invasion. The depletion of Prx5 in OSCC cells (Prx5dep ) led to decreased invasion activity. In orthotopic xenograft models, Prx5dep cells harbored delimited tumorigenicity compared to wild-type cells as well as the suppression of lymph node metastasis. Prx5dep cells showed growth retardation and increased cellular reactive oxygen species (ROS) levels. The growth retardation of Prx5dep cells resulted in G1 phase arrest. CONCLUSIONS: This study provides evidence that Prx5 removes excess ROS, especially in the TM, contributing to cancer invasion and tumor progression.

The Effect of 13 Weeks Long-Distance Bicycle Riding on Inflammatory Response Indicators Related to Joint Cartilage and Muscle Damage.

This study was to investigate the effects of 13 weeks of long-distance cycling on biomarkers of joint cartilage, muscle damage and inflammation. All subjects in this study were seven participants of the "One Korea New-Eurasia Peace Cycle Expedition", in which they rode cycles from Berlin, Germany to Seoul, Korea for thirteen weeks. The total course of the expedition was divided into three sub-courses: course 1 (from Berlin to Moscow), course 2 (from Moscow to Ulaanbaatar) and course 3 (from Ulaanbaatar to Seoul). All the selected participants rode 87.4 km/day (course 1), 70.4 km/day (course 2) and 57.6 km/day (course 3) on average, respectively. We collected their blood samples before the expedition in Seoul (S1), after course 1 in Moscow (M), after course 2 in Ulaanbaatar (U) and after the expedition in Seoul (S2), to analyze biomarkers of joint cartilage damage (Cartilage Oligomeric Matrix Protein; COMP), muscle damage (Creatine Phosphokinase; CPK, Lactate Dehydrogenase; LDH, Myoglobin), inflammation (Interleukin-6; IL-6, Interleukin-1ß; IL-1ß, Tumor Necrosis Factor-α; TNF-α, C-Reactive Protein; CRP) and stress hormone (Cortisol). According to this result, COMP (S1; 188.37 ± 46.68 ng/mL) showed a significant increase after the expedition course 1 (M; 246.69 ± 51.69 ng/mL, p = 0.012) and course 2 (U; 237.09 ± 62.57 ng/mL, p = 0.047), and recovered to the stable state after expedition course 3 (S2; 218.46 ± 34.78. p = 0.047). Biomarkers of muscle damage (CPK, LDH and Myoglobin) and inflammation (IL-6, IL-1ß, TNF-α and CRP) were not significantly changed in all courses, but CRP (S1; 1.07 ± 0.76 ng/mL) showed a tendency to decrease after the expedition course 1 (M; 0.3 ± 0.1 mg/mL, p = 0.044). Lastly, the Cortisol level significantly increased in all courses (per p < 0.05), but the Cortisol level after expedition course 3 (S2; 21.00 ± 3.65 mg/mL) was lower than that of after the expedition course 1 (M; 24.23 ± 2.47 mg/mL, p = 0.028). In summary, it seems that repetitive and continuous 50−90 km/day of cycling can increase joint cartilage damage risk and stress hormone temporarily. However, this result suggests that the appropriate intensity of cycling for thirteen weeks does not increase physical damage, and rather enhances the human body to adapt to exercise training.

Comparison of detection performance of soft tissue calcifications using artificial intelligence in panoramic radiography.

Artificial intelligence (AI) is limited to teeth and periodontal disease in the dental field, and is used for diagnosis assistance or data analysis, and there has been no research conducted in actual clinical situations. So, we created an environment similar to actual clinical practice and conducted research by selecting three of the soft tissue diseases (carotid artery calcification, lymph node calcification, and sialolith) that are difficult for general dentists to see. Therefore, in this study, the accuracy and reading time are evaluated using panoramic images and AI. A total of 20,000 panoramic images including three diseases were used to develop and train a fast R-CNN model. To compare the performance of the developed model, two oral and maxillofacial radiologists (OMRs) and two general dentists (GDs) read 352 images, excluding the panoramic images used in development for soft tissue calcification diagnosis. On the first visit, the observers read images without AI; on the second visit, the same observers used AI to read the same image. The diagnostic accuracy and specificity for soft tissue calcification of AI were high from 0.727 to 0.926 and from 0.171 to 1.000, whereas the sensitivity for lymph node calcification and sialolith were low at 0.250 and 0.188, respectively. The reading time of AI increased in the GD group (619 to 1049) and decreased in the OMR group (1347 to 1372). In addition, reading scores increased in both groups (GD from 11.4 to 39.8 and OMR from 3.4 to 10.8). Using AI, although the detection sensitivity of sialolith and lymph node calcification was lower than that of carotid artery calcification, the total reading time of the OMR specialists was reduced and the GDs reading accuracy was improved. The AI used in this study helped to improve the diagnostic accuracy of the GD group, who were not familiar with the soft tissue calcification diagnosis, but more data sets are needed to improve the detection performance of the two diseases with low sensitivity of AI.

Impact of body weight change on clinical outcomes in patients with idiopathic pulmonary fibrosis receiving pirfenidone.

There have been limited studies on the association between prognosis and body weight change in patients with idiopathic pulmonary fibrosis (IPF). This single-center retrospective observational study evaluated the impact of weight loss on outcomes in Korean patients with IPF receiving pirfenidone at a tertiary medical institution. We analyzed 215 IPF patients prescribed pirfenidone from January 1st, 2015 to December 31st, 2019. The patients were categorized into maintained weight (MW; weight gain or loss < 5%/year) and reduced weight (RW; weight loss ≥ 5%/year) groups. The mean age was 71.8 years and 175 (81.4%) were male. There were 54 (25.1%) patients in the RW group. All patients showed a decrease in body weight (baseline vs. after 1 year; 64.1 kg vs. 62.8 kg, P < 0.001). Although baseline lung function showed a difference, there was no difference in the rate of change (forced vital capacity [% of predicted]; P = 0.221, diffusing capacity of the lung for carbon monoxide [% of predicted]; P = 0.973). The MW group had a lower risk of all-cause mortality (P < 0.001). Weight loss appeared to be a significant risk factor for mortality in patients with IPF. Not only disease control with antifibrotic agents, but also efforts to prevent weight loss may be necessary.

The significance of elevated tumor markers among patients with interstitial lung diseases.

The clinical implication of using serum tumor markers in patients with interstitial lung disease (ILD) is inconclusive. In this retrospective study, we analyzed the data of 1176 subjects (294 with ILDs and 882 healthy controls). Eligible patients were who had at least one or more available tumor marker results [carbohydrate antigen (CA) 19-9, CA 125, and carcinoembryonic antigen (CEA)] with no evidence of malignancies or other benign diseases that could be related to the increasing concentration of the values. The healthy controls selected from a health screening program were also screened for the presence of active cancer, and matched at a ratio of 1:3 with age and sex. The proportion of patients with abnormal values in the ILD group (121, idiopathic pulmonary fibrosis (IPF); 173, non-IPF-ILDs) was higher than in the matched control group (CEA, 21.5% vs. 5.5%; CA 19-9, 27.9% vs. 4.0%; CA 125, 36.4% vs. 2.0%). In the multivariable analysis, higher CEA levels were associated with shorter survival after adjusting for age, sex, lung function, and ILD subtypes (hazard ratio: 2.323, 95% confidence interval: 1.271-4.248, P = 0.006). In subgroup analysis, CEA remained a prognostic factor in patients with non-IPF-ILDs, but not in those with IPF.