Evolution and Spread of Highly Pathogenic Avian Influenza A(H5N1) Clade 2.3.4.4b Virus in Wild Birds, South Korea, 2022-2023.

During October 2022-March 2023, highly pathogenic avian influenza (HPAI) A(H5N1) clade 2.3.4.4b virus caused outbreaks in South Korea, including 174 cases in wild birds. To understand the origin and role of wild birds in the evolution and spread of HPAI viruses, we sequenced 113 HPAI isolates from wild birds and performed phylogenetic analysis. We identified 16 different genotypes, indicating extensive genetic reassortment with viruses in wild birds. Phylodynamic analysis showed that the viruses were most likely introduced to the southern Gyeonggi-do/northern Chungcheongnam-do area through whooper swans (Cygnus cygnus) and spread southward. Cross-species transmission occurred between various wild bird species, including waterfowl and raptors, resulting in the persistence of HPAI in wild bird populations and further geographic spread as these birds migrated throughout South Korea. Enhanced genomic surveillance was an integral part of the HPAI outbreak response, aiding in timely understanding of the origin, evolution, and spread of the virus.

Characteristics and outcomes of patients with do-not-resuscitate and physician orders for life-sustaining treatment in a medical intensive care unit: a retrospective cohort study.

BACKGROUND: In the intensive care unit (ICU), we may encounter patients who have completed a Do-Not-Resuscitate (DNR) or a Physician Orders to Stop Life-Sustaining Treatment (POLST) document. However, the characteristics of ICU patients who choose DNR/POLST are not well understood. METHODS: We retrospectively analyzed the electronic medical records of 577 patients admitted to a medical ICU from October 2019 to November 2020, focusing on the characteristics of patients according to whether they completed DNR/POLST documents. Patients were categorized into DNR/POLST group and no DNR/POLST group according to whether they completed DNR/POLST documents, and logistic regression analysis was used to evaluate factors influencing DNR/POLST document completion. RESULTS: A total of 577 patients were admitted to the ICU. Of these, 211 patients (36.6%) had DNR or POLST records. DNR and/or POLST were completed prior to ICU admission in 48 (22.7%) patients. The DNR/POLST group was older (72.9 ± 13.5 vs. 67.6 ± 13.8 years, p < 0.001) and had higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (26.1 ± 9.2 vs. 20.3 ± 7.7, p < 0.001) and clinical frailty scale (5.1 ± 1.4 vs. 4.4 ± 1.4, p < 0.001) than the other groups. Solid tumors, hematologic malignancies, and chronic lung disease were the most common comorbidities in the DNR/POLST groups. The DNR/POLST group had higher ICU and in-hospital mortality and more invasive treatments (arterial line, central line, renal replacement therapy, invasive mechanical ventilation) than the other groups. Body mass index, APAHCE II score, hematologic malignancy, DNR/POLST were factors associated with in-hospital mortality. CONCLUSIONS: Among ICU patients, 36.6% had DNR or POLST orders and received more invasive treatments. This is contrary to the common belief that DNR/POLST patients would receive less invasive treatment and underscores the need to better understand and include end-of-life care as an important ongoing aspect of patient care, along with communication with patients and families.

Risk Factors for the Mortality of Patients With Coronavirus Disease 2019 Requiring Extracorporeal Membrane Oxygenation in a Non-Centralized Setting: A Nationwide Study.

BACKGROUND: Limited data are available on the mortality rates of patients receiving extracorporeal membrane oxygenation (ECMO) support for coronavirus disease 2019 (COVID-19). We aimed to analyze the relationship between COVID-19 and clinical outcomes for patients receiving ECMO. METHODS: We retrospectively investigated patients with COVID-19 pneumonia requiring ECMO in 19 hospitals across Korea from January 1, 2020 to August 31, 2021. The primary outcome was the 90-day mortality after ECMO initiation. We performed multivariate analysis using a logistic regression model to estimate the odds ratio (OR) of 90-day mortality. Survival differences were analyzed using the Kaplan-Meier (KM) method. RESULTS: Of 127 patients with COVID-19 pneumonia who received ECMO, 70 patients (55.1%) died within 90 days of ECMO initiation. The median age was 64 years, and 63% of patients were male. The incidence of ECMO was increased with age but was decreased after 70 years of age. However, the survival rate was decreased linearly with age. In multivariate analysis, age (OR, 1.048; 95% confidence interval [CI], 1.010-1.089; P = 0.014) and receipt of continuous renal replacement therapy (CRRT) (OR, 3.069; 95% CI, 1.312-7.180; P = 0.010) were significantly associated with an increased risk of 90-day mortality. KM curves showed significant differences in survival between groups according to age (65 years) (log-rank P = 0.021) and receipt of CRRT (log-rank P = 0.004). CONCLUSION: Older age and receipt of CRRT were associated with higher mortality rates among patients with COVID-19 who received ECMO.

Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. METHODS: This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. RESULTS: The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). CONCLUSION: Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

Factors and Outcomes of Intensive Care Unit Readmission in Elderly Patients.

INTRODUCTION: An increase in age has been observed among patients admitted to the intensive care unit (ICU). Age is a well-known risk factor for ICU readmission and mortality. However, clinical characteristics and risk factors of ICU readmission of elderly patients (≥65 years) have not been studied. METHODS: This retrospective single-center cohort study was conducted in a total of 122-bed ICU of a tertiary care hospital in Seoul, Korea. A total of 85,413 patients were enrolled in this hospital between January 1, 2007, and December 31, 2017. The odds ratio of readmission and in-hospital mortality was calculated by logistic regression analysis. RESULTS: Totally, 29,503 patients were included in the study group, of which 2,711 (9.2%) had ICU readmissions. Of the 2,711 readmitted patients, 472 patients were readmitted more than once (readmitted 2 or more times to the ICU, 17.4%). In the readmitted patient group, there were more males, higher sequential organ failure assessment (SOFA) scores, and hospitalized for medical reasons. Length of stay (LOS) in ICU and in-hospital were longer, and 28-day and in-hospital mortality was higher in readmitted patients than in nonreadmitted patients. Risk factors of ICU readmission included the ICU admission due to medical reason, SOFA score, presence of chronic heart disease, diabetes mellitus, chronic kidney disease, transplantation, use of mechanical ventilation, and initial ICU LOS. ICU readmission and age (over 85 years) were independent predictors of in-hospital mortality on multivariable analysis. The delayed ICU readmission group (>72 h) had higher in-hospital mortality than the early readmission group (≤72 h) (20.6 vs. 16.2%, p = 0.005). CONCLUSIONS: ICU readmissions occurred in 9.2% of elderly patients and were associated with poor prognosis and higher mortality.

Characteristics and outcomes of patients screened by rapid response team who transferred to the intensive care unit.

BACKGROUND: The utilization of a rapid response team (RRT) has influenced the clinical outcomes of patients in the general ward. However, the characteristics of RRT-screened patients who are transferred to the intensive care unit (ICU) are unknown. Therefore, the present study aimed to evaluate these factors. METHODS: We conducted a retrospective study using patient data from a tertiary medical center in Republic of Korea between January 2016 and December 2017. Multivariate logistic regression analyses were performed to assess the factors associated with the risk of in-hospital mortality. RESULTS: A total of 1,096 patients were included: 389 patients were transferred to the ICU, and 707 patients stayed in the ward. Patients in the ICU group were more likely to be admitted for medical reasons, hepatobiliary disease, and high heart rate. More interventions were performed, hospital stays were longer, and the 28-day and in-hospital mortality rates were higher in the ICU group than in the ward group. Multivariate logistic regression analyses showed that risk factors affecting ICU admission were higher Sequential Organ Failure Assessment (SOFA) score, National Early Warning Score (NEWS), platelet count, and lactate level. ICU transfer was not associated with in-hospital mortality. CONCLUSIONS: Among RRT-screened patients, those with higher SOFA score, NEWS, and lactate level were more likely to be transferred to the ICU. Therefore, these patients should be closely monitored and considered for ICU transfer.

Usefulness of ICU criteria for diagnosis of invasive pulmonary aspergillosis in nonhematologic critically ill patients.

Invasive pulmonary aspergillosis (IPA) is a life-threatening disease in the intensive care unit (ICU). The ICU criteria were proposed to diagnose IPA in critically ill patients. This study aims to evaluate the usefulness of ICU criteria for diagnosis and treatment of IPA in nonhematologic patients in the ICU. We retrospectively reviewed 103 ICU patients with positive galactomannan test in blood and respiratory tract from January 1, 2016, to May 31, 2017. We excluded patients with hematologic malignancy. We divided the treatment and non-treatment groups according to the IPA treatment. We compared the baseline characteristics and outcomes between two groups and the agreement with ICU criteria. There were 49 patients in treatment groups and 54 patients in non-treatment groups. There were more cases of solid organ transplantation (P = .003), immunosuppressive therapy (P < .001) and bacterial viral coinfection (P = .048) in the treatment group compared to nontreatment group. There was no statistically significant difference in mortality, the use of ventilator, and septic shock between the two groups. The agreement rate between the putative group and treatment was low (59.2%). There was no statistically significant difference in outcome between the putative and colonization groups according to the ICU criteria in each group. The treatment of IPA based on the symptom, radiologic finding and galactomannan test did not showed the better outcome. Also, the treatment based on the ICU criteria didn't show the difference of outcome. The new criteria for diagnosis of IPA in critically ill patients are needed.

Pleuroparenchymal fibroelastosis in patients with idiopathic pulmonary fibrosis.

BACKGROUND AND OBJECTIVE: PPFE is characterized by fibrosis in the pleura and subpleural lung parenchyma in the upper lobes, while other types of ILD, mainly UIP, can be observed in about half of the patients in their lower lobes. The aim of this study was to evaluate the clinical significance of the radiologically defined PPFE in patients with IPF. METHODS: Clinical data and chest CT images were retrospectively analysed in 445 patients with IPF (biopsy-proven cases, n = 165). The radiological criteria of PPFE were defined as follows: (i) bilateral subpleural dense fibrosis with or without pleural thickening in the upper lobes, (ii) evidence of disease progression and (iii) no clinical evidence of identifiable aetiologies. RESULTS: The median follow-up period was 43.0 months. The mean age of the patients was 66.4 years and 76.4% were male. PPFE was identified in 28 patients (6.3%). The PPFE group showed lower BMI and lung function (FVC and TLC) at baseline, more frequent pneumothorax and pneumomediastinum, higher decline rates in lung function and poorer prognosis during follow-up than the no-PPFE group. PPFE was an independent risk factor (HR = 2.953, 95% CI: 1.350-6.460, P = 0.007) for pneumothorax or pneumomediastinum, but not for mortality in patients with IPF. CONCLUSION: Among patients with IPF, the PPFE group, when compared to the no-PPFE group, showed lower BMI and lung function and showed more frequent complications and poorer survival during follow-up.

Calcification following tongue necrosis induced by vasopressor use in a nonintubated patient with septic shock: a case report.

BACKGROUND: Tongue necrosis is a rare and relatively uncommon condition, usually caused by vasculitis, thrombosis, severe hypotension due to septic or cardiogenic shock, vasopressor use, or intubation. Following damage such as necrosis, dystrophic calcification, a type of soft tissue calcification, can occur. CASE PRESENTATION: Herein, we present a unique case of bilateral tongue necrosis in a patient with nonintubated septic shock. A 70-year-old East Asian man with no significant medical history presented to the emergency department with postprandial epigastric pain. The patient was admitted to the intensive care unit with hypotension due to septic shock and disseminated intravascular coagulation. After a short course of vasopressors, the patient developed tongue discoloration and swelling without limb ischemia. Computed tomography was performed to observe the tongue necrosis, and calcification of the tongue was found. The patient was successfully treated by wiping the area with a hexamidine-soaked gauze. CONCLUSION: Tongue necrosis remains a rare finding, and its occurrence as a complication of vasopressor use is even rarer. Therefore, even with relatively short courses of vasopressors in the intensive care unit, daily visualization of the tongue to check for discoloration, along with daily inspection and pulse checks of the limbs, can help identify vasospasms. These measures allow for prompt intervention, minimizing permanent damage and shortening the recovery time.

Spontaneous regression of recurrent pulmonary large cell neuroendocrine carcinoma with alteration of PD-L1 expression after surgical resection: A case report.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of non-small cell lung cancer with a poor prognosis. Spontaneous regression, that is, partial or complete disappearance of a malignancy without medical intervention, is extremely rare in LCNEC. Herein, we present a case of spontaneous complete regression in a 71-year-old male patient with recurrent LCNEC after surgical resection. The patient was diagnosed with stage IB LCNEC and underwent surgical resection. At 1-year follow-up, chest computed tomography revealed a recurrent lesion next to the stump site and enlargement of lymph nodes 4R and 7; recurrent LCNEC was confirmed. The patient declined chemoradiation therapy. One year after recurrence, the patient experienced severe multifocal necrotizing pneumonia and was treated with antibiotics, resulting in a gradual decrease in the size of the recurrent lesion. Five years after the initial diagnosis, positron emission tomography/computed tomography revealed no hypermetabolic lesions, indicating the spontaneous complete regression of LCNEC.

Clinical Manifestations and Outcomes of Older Patients with COVID-19: A Comprehensive Review.

The consequences of coronavirus disease 2019 (COVID-19) are particularly severe in older adults with a disproportionate number of severe and fatal outcomes. Therefore, this integrative review aimed to provide a comprehensive overview of the clinical characteristics, management approaches, and prognosis of older patients diagnosed with COVID-19. Common clinical presentations in older patients include fever, cough, and dyspnea. Additionally, preexisting comorbidities, especially diabetes and pulmonary and cardiovascular diseases, were frequently observed and associated with adverse outcomes. Management strategies varied, however, early diagnosis, vigilant monitoring, and multidisciplinary care were identified as key factors for enhancing patient outcomes. Nonetheless, the prognosis remains guarded for older patients, with increased rates of hospitalization, mechanical ventilation, and mortality. However, timely therapeutic interventions, especially antiviral and supportive treatments, have demonstrated some efficacy in mitigating the severe consequences in this age group. In conclusion, while older adults remain highly susceptible to severe outcomes from COVID-19, early intervention, rigorous monitoring, and comprehensive care can play a pivotal role in improving their clinical outcomes.

Age Distribution and Clinical Results of Critically Ill Patients above 65-Year-Old in an Aging Society: A Retrospective Cohort Study.

BACKGROUND: Increasing age has been observed among patients admitted to the intensive care unit (ICU). Age traditionally considered a risk factor for ICU mortality. We investigated how the epidemiology and clinical outcomes of older ICU patients have changed over a decade. METHODS: We analyzed patients admitted to the ICU at a university hospital in Seoul, South Korea. We defined patients aged 65 and older as older patients. Changes in age groups and mortality risk factors over the study period were analyzed. RESULTS: A total of 32,322 patients were enrolled who aged ≥65 years admitted to the ICUs between January 1, 2007, and December 31, 2017. Patients aged ≥65 years accounted for 35% and of these, the older (O, 65 to 74 years) comprised 19,630 (66.5%), very older (VO, 75 to 84 years) group 8,573 (29.1%), and very very older (VVO, ≥85 years) group 1,300 (4.4%). The mean age of ICU patients over the study period increased (71.9±5.6 years in 2007 vs. 73.2±6.1 years in 2017) and the proportions of the VO and VVO group both increased. Over the period, the proportion of female increased (37.9% in 2007 vs. 43.3% in 2017), and increased ICU admissions for medical reasons (39.7% in 2007 vs. 40.2% in 2017). In-hospital mortality declined across all older age groups, from 10.3% in 2007 to 7.6% in 2017. Hospital length of stay (LOS) decreased in all groups, but ICU LOS decreased only in the O and VO groups. CONCLUSION: The study indicates a changing demographic in ICUs with an increase in older patients, and suggests a need for customized ICU treatment strategies and resources.

Cathepsin C regulates tumor progression via the Yes-associated protein signaling pathway in non-small cell lung cancer.

Cathepsin C (CTSC), also known as dipeptidyl peptidase I, is a cathepsin with lysosomal exocysteine protease activity and a central coordinator for the activation of neutrophil-derived serine proteases in the lysosomes of neutrophils. Although the role of CTSC in various cancers, including liver and breast cancers, has recently been reported, its role in non-small cell lung cancer (NSCLC) is largely unknown. This study aimed to investigate the functional role of CTSC in NSCLC and the molecular mechanisms underlying CTSC involvement in disease progression. CTSC overexpression markedly enhanced the growth, motility, and invasiveness of NSCLC cells in vitro and in vivo. CTSC knockdown using shRNA in NSCLC cells reversed the migratory and invasive behavior of NSCLC cells. CTSC also induced epithelial-mesenchymal transition through the Yes-associated protein signaling pathway. In addition, our analyses of clinical samples confirmed that high CTSC expression was associated with lymph node metastasis and recurrence in lung adenocarcinoma. In conclusion, CTSC plays an important role in the progression of NSCLC. Thus, targeting CTSC may be a promising treatment option for patients with NSCLC.

Prognostic and predictive significance of soluble programmed death ligand 1 in bronchoalveolar lavage fluid in stage IV non-small cell lung cancer.

Background: Patients with non-small cell lung cancer (NSCLC) have been shown to exhibit elevated levels of soluble programmed death-ligand 1 (sPD-L1) in the blood, associated with poor survival in NSCLC. The bronchoalveolar lavage fluid (BALF) composition reflects the tumor microenvironment of lung cancer. In this study, we investigated sPD-L1 levels in BALF and its role as a prognostic and predictive marker in patients with stage IV NSCLC. Methods: We prospectively obtained BALF from lung cancer patients who underwent bronchoscopy between January 2020 and September 2022 at Chungnam National University Hospital (CNUH). Finally, 94 NSCLC stage IV patients were included in this study. Soluble PD-L1 levels in BALF were measured using a human PD-L1 Quantikine ELISA kit. Results: The correlation between PD-L1 expression in tumor cells and sPD-L1 in BALF was weakly positive (rho =0.314, P=0.002). The median overall survival (OS) of the low sPD-L1 in BALF group was 16.47 months [95% confidence interval (CI): 11.15-21.79 months], which is significantly longer than 8.87 months (95% CI: 0.0-19.88 months, P=0.001) in the high sPD-L1 in BALF group. In 64 patients treated with or without immune checkpoint inhibitors (ICIs), sPD-L1 in BALF was significantly associated with progression-free survival (PFS) and OS. In the subgroup analysis of 31 patients treated with ICI, the objective response rate (ORR) in the low sPD-L1 BALF group was significantly higher than in high sPD-L1 in BALF group (ORR: 60.9% vs. 12.5%, P=0.02). Conclusions: Soluble PD-L1 in BALF is a potential prognostic indicator for patients with stage IV NSCLC and a predictive marker for ICI treatment response.

Clinical characteristics and prognosis of patients with COVID-19 on mechanical ventilation undergoing continuous renal replacement therapy.

BACKGROUND: The coronavirus disease (COVID-19) pandemic has significantly strained global healthcare, particularly in the management of patients requiring mechanical ventilation (MV) and continuous renal replacement therapy (CRRT). This study investigated the characteristics and prognoses of these patients. METHODS: This multicenter retrospective cohort study gathered data from patients with COVID-19 across 26 medical centers. Logistic analysis was used to identify the factors associated with CRRT implementation. RESULTS: Of the 640 patients with COVID-19 who required MV, 123 (19.2%) underwent CRRT. Compared to the non-CRRT group, the CRRT group was older and exhibited higher sequential organ failure assessment scores. The incidence of hypertension, diabetes, cardiovascular disease, chronic neurological disease, and chronic kidney disease was also higher in the CRRT group. Moreover, the CRRT group had higher intensive care unit (ICU) (75.6% vs. 26.9%, p < 0.001) and in-hospital (79.7% vs. 29.6%, p < 0.001) mortality rates. CRRT implementation was identified as an independent risk factor for both ICU mortality (hazard ratio [HR]:1.833, 95% confidence interval [CI]:1.342-2.505, p < 0.001) and in-hospital mortality (HR: 2.228, 95% CI: 1.648-3.014, p < 0.001). Refractory respiratory failure (n = 99, 19.1%) was the most common cause of death in the non-CRRT death group, and shock with multi-organ failure (n = 50, 40.7%) was the most common cause of death in the CRRT death group. Shock with multi-organ failure and cardiac death were significantly more common in the CRRT death group, compared to non-CRRT death group. CONCLUSION: This study indicates that CRRT is associated with higher ICU and in-hospital mortality rates in patients with COVID-19 who require MV. Notably, the primary cause of death in the CRRT group was shock with multi-organ failure, emphasizing the severe clinical course for these patients, while refractory respiratory failure was most common in non-CRRT patients.

Clinical Characteristics and Prognosis of Older Patients with Coronavirus Disease 2019 Requiring Mechanical Ventilation.

An older age is associated with severe progression and poor prognosis in coronavirus disease 2019 (COVID-19), and mechanical ventilation is often required. The specific characteristics of older patients undergoing mechanical ventilation and their prognostic factors are largely unknown. We aimed to identify potential prognostic factors in this group to inform treatment decisions. This retrospective cohort study collected data from patients with COVID-19 at 22 medical centers. Univariate and multivariate Cox regression analyses were performed to assess factors that influence mortality. We allocated 434 patients in geriatric (≥80 years) and elderly (65-79 years) groups. The former group scored significantly higher than the elderly group in the clinical frailty scale and sequential organ failure assessment, indicating more severe organ dysfunction. Significantly lower administration rates of tocilizumab and extracorporeal membrane oxygenation and higher intensive care unit (ICU) and in-hospital mortality were noted in the geriatric group. The factors associated with ICU and in-hospital mortality included high creatinine levels, the use of continuous renal replacement therapy, prone positioning, and the administration of life-sustaining treatments. These results highlight significant age-related differences in the management and prognosis of critically ill older patients with COVID-19. Increased mortality rates and organ dysfunction in geriatric patients undergoing mechanical ventilation necessitate age-appropriate treatment strategies to improve their prognoses.

The Matrix Stiffness Coordinates the Cell Proliferation and PD-L1 Expression via YAP in Lung Adenocarcinoma.

The extracellular matrix (ECM) exerts physiological activity, facilitates cell-to-cell communication, promotes cell proliferation and metastasis, and provides mechanical support for tumor cells. The development of solid tumors is often associated with increased stiffness. A stiff ECM promotes mechanotransduction, and the predominant transcription factors implicated in this phenomenon are YAP/TAZ, ß-catenin, and NF-κB. In this study, we aimed to investigate whether YAP is a critical mediator linking matrix stiffness and PD-L1 in lung adenocarcinoma. We confirmed that YAP, PD-L1, and Ki-67, a marker of cell proliferation, increase as the matrix stiffness increases in vitro using the lung adenocarcinoma cell lines PC9 and HCC827 cells. The knockdown of YAP decreased the expression of PD-L1 and Ki-67, and conversely, the overexpression of YAP increased the expression of PD-L1 and K-67 in a stiff-matrix environment (20.0 kPa). Additionally, lung cancer cells were cultured in a 3D environment, which provides a more physiologically relevant setting, and compared to the results obtained from 2D culture. Similar to the findings in 2D culture, it was confirmed that YAP influenced the expression of PD-L1 and K-67 in the 3D culture experiment. Our results suggest that matrix stiffness controls PD-L1 expression via YAP activation, ultimately contributing to cell proliferation.

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.

Evolution of the Stethoscope: Advances with the Adoption of Machine Learning and Development of Wearable Devices.

The stethoscope has long been used for the examination of patients, but the importance of auscultation has declined due to its several limitations and the development of other diagnostic tools. However, auscultation is still recognized as a primary diagnostic device because it is non-invasive and provides valuable information in real-time. To supplement the limitations of existing stethoscopes, digital stethoscopes with machine learning (ML) algorithms have been developed. Thus, now we can record and share respiratory sounds and artificial intelligence (AI)-assisted auscultation using ML algorithms distinguishes the type of sounds. Recently, the demands for remote care and non-face-to-face treatment diseases requiring isolation such as coronavirus disease 2019 (COVID-19) infection increased. To address these problems, wireless and wearable stethoscopes are being developed with the advances in battery technology and integrated sensors. This review provides the history of the stethoscope and classification of respiratory sounds, describes ML algorithms, and introduces new auscultation methods based on AI-assisted analysis and wireless or wearable stethoscopes.