Texture preserving low dose CT image denoising using Pearson divergence.

OBJECTIVE: The mean squared error (MSE), also known as $L_2$ loss, has been widely used as a loss function to optimize image denoising models due to its strong performance as a mean estimator of the Gaussian noise model. Recently, various low-dose computed tomography (LDCT) image denoising methods using deep learning combined with the MSE loss have been developed; however, this approach has been observed to suffer from the regression-to-the-mean problem, leading to over-smoothed edges and degradation of texture in the image. Approach: To overcome this issue, we propose a stochastic function in the loss function to improve the texture of the denoised CT images, rather than relying on complicated networks or feature space losses. The proposed loss function includes the MSE loss to learn the mean distribution and the Pearson divergence loss to learn feature textures. Specifically, the Pearson divergence loss is computed in an image space to measure the distance between two intensity measures of denoised low-dose and normal-dose CT images. The evaluation of the proposed model employs a novel approach of multi-metric quantitative analysis utilizing relative texture feature distance. Results: Our experimental results show that the proposed Pearson divergence loss leads to a significant improvement in texture compared to the conventional MSE loss and generative adversarial network (GAN), both qualitatively and quantitatively. Significance: Achieving consistent texture preservation in LDCT is a challenge in conventional GAN-type methods due to adversarial aspects aimed at minimizing noise while preserving texture. By incorporating the Pearson regularizer in the loss function, we can easily achieve a balance between two conflicting properties. Consistent high-quality CT images can significantly help clinicians in diagnoses and supporting researchers in the development of AI-diagnostic models.

Remnant cholesterol is an independent risk factor for the incidence of chronic kidney disease in newly-diagnosed type 2 diabetes: A nationwide population-based study.

AIMS: To evaluate the impact of remnant cholesterol (remnant-C) on chronic kidney disease (CKD) incidence in newly-diagnosed type 2 diabetes. METHODS: This retrospective cohort study used Korean National Health Insurance Service data on 212,836 patients with newly-diagnosed type 2 diabetes between 2009 and 2014. We conducted cox regression analysis to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for developing CKD according to remnant-C tertile. RESULTS: During a median follow-up duration of 5.23 years, 6,850 CKD cases developed. In the fully adjusted model, HRs and 95 % CIs for incident CKD increased in the highest tertile of baseline remnant-C compared to the lowest (HR [95 % CI]; 1.234 [1.159-1.314]). This association was more prominent in patients with hypertension or low-income status (P for interaction < 0.05). Increased HRs in the highest tertile of remnant-C was sustained in type 2 diabetes patients within target range of conventional lipid profile such as low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL and < 70 mg/dL (1.165 [1.041-1.304] and 1.308 [1.063-1.609]), high-density lipoprotein cholesterol (HDL-C) (1.243 [1.155-1.338]) and triglyceride (1.168 [1.076-1.268]), respectively. CONCLUSIONS: In newly-diagnosed type 2 diabetes patients, higher remnant-C is independently associated with CKD incidence, even when conventional lipid values are well-controlled.

Independent effect of Aß burden on cognitive impairment in patients with small subcortical infarction.

BACKGROUND: The effect of amyloid-ß (Aß) on cognitive impairment in patients with small subcortical infarction remains controversial, although a growing body of evidence shows a substantial overlap between Alzheimer's disease (AD) and subcortical ischemic vascular dementia, another form of cerebral small vessel disease (cSVD). Therefore, we investigated the relationships between Aß positivity and the development of post-stroke cognitive impairment (PSCI) in patients with small subcortical infarction. METHODS: We prospectively recruited 37 patients aged ≥ 50 years, with first-ever small subcortical infarction, who underwent amyloid positron emission tomography, 3 months after stroke at Korea University Guro Hospital. We also enrolled CU participants matched for age and sex with stroke patients for comparison of Aß positivity. Patients were followed up at 3 and 12 months after the stroke to assess cognitive decline. Logistic and linear mixed-effect regression analyses were performed to identify the effect of Aß positivity on PSCI development and long-term cognitive trajectories. RESULTS: At 3 months after stroke, 12/37 (32.4%) patients developed PSCI, and 11/37 (29.7%) patients had Aß deposition. Aß positivity (odds ratio [OR] = 72.2, p = 0.024) was predictive of PSCI development regardless of cSVD burden. Aß positivity (ß = 0.846, p = 0.014) was also associated with poor cognitive trajectory, assessed by the Clinical Dementia Rating-Sum of Box, for 1 year after stroke. CONCLUSIONS: Our findings highlight that Aß positivity is an important predictor for PSCI development and cognitive decline over 1 year. Furthermore, our results provide evidence that anti-AD medications may be a strategy for preventing cognitive decline in patients with small subcortical infarctions.

Cullin7 induces docetaxel resistance by regulating the protein level of the antiapoptotic protein Survivin in lung adenocarcinoma cells.

Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC). Chemotherapy resistance is the main cause of chemotherapy failure. Cullin7 (Cul7) is highly expressed in LUAD and is associated with poor prognosis. Moreover, Cul7 is abnormally overexpressed in docetaxel-resistant LUAD cells. Therefore, further exploration of the role and molecular mechanism of Cul7 in LUAD docetaxel resistance is necessary. Methods: We established docetaxel-resistant cell lines (A549DTX and H358DTX cell lines) by exposing cells to gradually increasing concentrations of docetaxel. Cell (A549, A549DTX, H358, and H358DTX cell lines) sensitivity to docetaxel was determined via a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymmethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay. And then quantitative polymerase chain reaction (qPCR) and Western blotting were performed to measure the expression of Cul7 and Survivin in A549, A549DTX, H358, and H358DTX cell lines. Subsequently, we knocked down Cul7 in docetaxel-resistant cells and overexpressed Cul7 in parental cells via lentiviral transduction to further validate the correlation between Cul7 and docetaxel resistance, while exploring the molecular mechanism of docetaxel resistance it caused. Immunofluorescence and immunohistochemical (IHC) staining were also used to evaluate the expression and cellular localization of Cul7. To confirm the effect of Cul7 expression on cell apoptosis, we used flow cytometry to detect the apoptosis rate of A549 and A549DTX cells with the same drug concentration. Results: Cul7 was highly expressed in A549DTX and H358DTX cells. However, when Cul7 expression was knocked down in A549DTX and H358DTX cells, cell sensitivity to docetaxel was significantly increased. In addition, we found that Cul7 was coexpressed with Survivin. Silencing Survivin reversed the docetaxel insensitivity caused by Cul7 overexpression. High expression of Cul7 and Survivin in docetaxel-resistant LUAD cells inhibited the intrinsic apoptosis pathway and promoted cell proliferation. Therefore, the Cul7/Survivin axis may play a role in inducing LUAD docetaxel chemoresistance. Conclusions: Cul7 and Survivin were both highly expressed in docetaxel-resistant LUAD cells. Our results suggest that Cul7 may inhibit apoptosis and promote the proliferation of LUAD cells by increasing the Survivin protein level, which in turn contributes to docetaxel chemoresistance in LUAD.

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids.

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.

CT-based three-dimensional invasiveness analysis of adenocarcinoma presenting as pure ground-glass nodules.

Background: We invest computed tomography (CT) image differences between non-invasive adenocarcinomas (NIAs) and invasive adenocarcinomas (IAs) presenting as pure ground glass nodules (GGNs). Methods: From 2013 to 2019, 48 pure GGNs were surgically resected in 45 patients. Of these, 40 were pathologically diagnosed as non-small cell lung cancers (NSCLCs). We assessed them using the Synapse Vincent (Fujifilm Co., Ltd., Tokyo, Japan) three-dimensional (3D) analysis system; we drew histograms of the CT densities. We calculated the maximum, minimum, means, and standard deviations of the densities. The proportions of GGNs of high CT density were compared between the two groups. The diagnostic performance was investigated via receiver operating curve (ROC) analysis. Results: Of the 40 pure GGNs, 20 were NIAs (4 adenocarcinomas in situ and 16 minimally IAs) and 20 IAs. Significant correlations were evident between histological invasiveness and the maximum and mean CT densities and the standard deviation. Neither the nodule volume nor the minimum CT density significantly predicted invasiveness. A CT volume density proportion >-300 Hounsfield units optimally predicted the invasiveness of pure GGNs; the cutoff was 5.41% with a sensitivity of 85% and a specificity of 95%. Conclusions: CT density reflected the invasiveness of pure GGNs. A CT volume proportion density >-300 Hounsfield units may significantly predict histological invasiveness.

Comparison between costotransverse foramen block and thoracic paravertebral block for VATS pulmonary resection: A randomized noninferiority trial.

STUDY OBJECTIVE: The present study assessed whether costotransverse foramen block (CTFB) is noninferior to thoracic paravertebral block (TPVB) for postoperative analgesia in video-assisted thoracoscopic surgery (VATS) pulmonary resection. DESIGN: Single-center, double-blinded, randomized, non-inferiority trial. SETTING: Operating room and intensive care unit or ward in a tertiary hospital. PATIENTS: Patients aged 20 to 80 years with American Society of Anesthesiology physical status 1 to 3 scheduled for elective VATS pulmonary resection. INTERVENTIONS: Sixty patients were randomly allocated 1:1 to receive CTFB or TPVB using 15 mL aliquots of 0.5% ropivacaine at the T4-5 and T6-7 intercostal levels immediately after the induction of general anesthesia. MEASUREMENTS: The primary outcome was the area under the curve (AUC) of numeric rating scale (NRS, 0 to 10) during 24 h postoperatively (noninferiority limit was 24; NRS 1 per hour). The secondary outcomes included postoperative opioid consumption, rescue analgesic use, postoperative nausea and vomiting, pulmonary function, dermatomal spread of the blockade, and quality of recovery. MAIN RESULTS: Forty-seven patients were included for final analysis. The difference between the mean 24-h AUCs of NRS in the CTFB (34.25 ± 16.30, n = 24) and TPVB (39.52 ± 17.13, n = 23) groups was -5.27 (95% confidence interval [CI], -15.09 to 4.55), with the upper limit of 95% CI being far below the predefined noninferiority margin of 24. There was no significant difference in the dermatomal spread of the blockades between the groups, as both reached the upper and lower most levels of T3 and T7 (median). Additionally, there were no significant differences in other secondary outcomes between the two groups. CONCLUSIONS: The analgesic effect of CTFB was noninferior to that of TPVB during 24 h postoperatively in VATS pulmonary resection. Moreover, CTFB may offer potential safety benefits by keeping the tip of the needle far from the pleura and vascular structure.

Incidence of Parkinson's disease and modifiable risk factors in Korean population: A longitudinal follow-up study of a nationwide cohort.

Introduction: We aimed to investigate the incidence of Parkinson's disease (PD) by age and year for each sex as well as the modifiable risk factors for PD. Using data from the Korean National Health Insurance Service, 938,635 PD and dementia-free participants aged ≥40 years who underwent general health examinations were followed to December 2019. Methods: We analyzed the PD incidence rates according to age, year and sex. To investigate the modifiable risk factors for PD, we used the Cox regression model. Additionally, we calculated the population-attributable fraction to measure the impact of the risk factors on PD. Results: During follow-up, 9,924 of the 938,635 (1.1%) participants developed PD. The incidence of PD increased continuously from 2007 to 2018, reaching 1.34 per 1,000 person-years in 2018. The incidence of PD also increases with age, up to 80 y. Presence of hypertension (SHR = 1.09, 95% CI 1.05 to 1.14), diabetes (SHR = 1.24, 95% CI 1.17 to 1.31), dyslipidemia (SHR = 1.12, 95% CI 1.07 to 1.18), ischemic stroke (SHR = 1.26, 95% CI 1.17 to 1.36), hemorrhagic stroke (SHR = 1.26, 95% CI 1.08 to 1.47), ischemic heart disease (SHR = 1.09, 95% CI 1.02 to 1.17), depression (SHR = 1.61, 95% CI 1.53 to 1.69), osteoporosis (SHR = 1.24, 95% CI 1.18 to 1.30), and obesity (SHR = 1.06, 95% CI 1.01 to 1.10) were independently associated with a higher risk for PD. Discussion: Our results highlight the effect of modifiable risk factors for PD in the Korean population, which will help establish health care policies to prevent the development of PD.

Graphical user interface design to improve understanding of the patient-reported outcome symptom response.

BACKGROUND: Symptom monitoring application (SMA) has clinical benefits to cancer patients but patients experience difficulties in using it. Few studies have identified which types of graphical user interface (GUI) are preferred by cancer patients for using the SMA. METHODS: This is a cross-sectional study aimed to identify preferred GUI among cancer patients to use SMA. Total of 199 patients were asked to evaluate 8 types of GUIs combining text, icon, illustration, and colors using mixed-methods. Subgroup analyses were performed according to age and gender. RESULTS: The mean age of the patients was 57 and 42.5% was male. The most preferred GUI was "Text + Icon + Color" (mean = 4.43), followed by "Text + Icon" (mean = 4.39). Older patients (≥ 60 years) preferred "Text + Icon" than younger patients (p for interaction < 0.01). Simple and intuitive text and icons were the most useful GUI for cancer patients to use the SMA. CONCLUSION: Simple and intuitive text and icons were the most useful GUI for cancer patients to use the SMA. Researchers need to be careful when applying realistic face drawings to cancer symptom monitoring applications because they can recall negative images of cancer.

Improving the efficiency of identifying malignant pulmonary nodules before surgery via a combination of artificial intelligence CT image recognition and serum autoantibodies.

OBJECTIVE: To construct a new pulmonary nodule diagnostic model with high diagnostic efficiency, non-invasive and simple to measure. METHODS: This study included 424 patients with radioactive pulmonary nodules who underwent preoperative 7-autoantibody (7-AAB) panel testing, CT-based AI diagnosis, and pathological diagnosis by surgical resection. The patients were randomly divided into a training set (n = 212) and a validation set (n = 212). The nomogram was developed through forward stepwise logistic regression based on the predictive factors identified by univariate and multivariate analyses in the training set and was verified internally in the verification set. RESULTS: A diagnostic nomogram was constructed based on the statistically significant variables of age as well as CT-based AI diagnostic, 7-AAB panel, and CEA test results. In the validation set, the sensitivity, specificity, positive predictive value, and AUC were 82.29%, 90.48%, 97.24%, and 0.899 (95%[CI], 0.851-0.936), respectively. The nomogram showed significantly higher sensitivity than the 7-AAB panel test result (82.29% vs. 35.88%, p < 0.001) and CEA (82.29% vs. 18.82%, p < 0.001); it also had a significantly higher specificity than AI diagnosis (90.48% vs. 69.04%, p = 0.022). For lesions with a diameter of ≤ 2 cm, the specificity of the Nomogram was higher than that of the AI diagnostic system (90.00% vs. 67.50%, p = 0.022). CONCLUSIONS: Based on the combination of a 7-AAB panel, an AI diagnostic system, and other clinical features, our Nomogram demonstrated good diagnostic performance in distinguishing lung nodules, especially those with ≤ 2 cm diameters. KEY POINTS: • A novel diagnostic model of lung nodules was constructed by combining high-specific tumor markers with a high-sensitivity artificial intelligence diagnostic system. • The diagnostic model has good diagnostic performance in distinguishing malignant and benign pulmonary nodules, especially for nodules smaller than 2 cm. • The diagnostic model can assist the clinical decision-making of pulmonary nodules, with the advantages of high diagnostic efficiency, noninvasive, and simple measurement.

Moderate-Intensity Statins Plus Ezetimibe vs. High-Intensity Statins After Coronary Revascularization: A Cohort Study.

PURPOSE: Whether moderate-intensity statins plus ezetimibe could be an alternative to high-intensity statins in patients with atherosclerotic cardiovascular disease is unclear. We compared the risk of adverse cardiovascular events in patients receiving moderate-intensity statins plus ezetimibe vs. high-intensity statins after a coronary revascularization procedure using data from a large cohort study. METHOD: Population-based cohort study using nationwide medical insurance data from Korea. Study participants (n = 20,070) underwent percutaneous coronary intervention or coronary artery bypass graft surgery between January 1, 2015, and December 31, 2016, and received moderate-intensity statins (atorvastatin 10-20 mg or rosuvastatin 5-10 mg) plus ezetimibe (n = 922) or high-intensity statins (atorvastatin 40-80 mg or rosuvastatin 20 mg; n = 19,148). The primary outcome was a composite of cardiovascular mortality, hospitalization for myocardial infarction (MI), hospitalization for stroke, or revascularization. RESULTS: At 12 months, the incidence rates of the primary outcome were 138.0 vs. 154.0 per 1000 person-years in the moderate-intensity stains plus ezetimibe and the high-intensity statins group, respectively. The fully adjusted hazard ratio [HR] for the primary outcome was 1.11 (95% confidence interval [CI] 0.86-1.42; p = 0.43). The multivariable-adjusted HR for a composite of cardiovascular mortality, hospitalization for MI, or hospitalization for stroke was 1.05 (95% CI 0.74-1.47; p = 0.80). During follow-up, the proportion of patients maintaining their initial lipid-lowering therapy was significantly higher in the moderate-intensity statins plus ezetimibe group than in the high-intensity statins group. CONCLUSIONS: Patients undergoing a coronary revascularization procedure who received moderate-intensity statins plus ezetimibe showed similar rates of major adverse cardiovascular events as patients who received high-intensity statins.

Associations between aided speech audiometry and subjective assessment of hearing aid outcomes.

OBJECTIVE: This study aimed to analyse outcomes with hearing aid (HA) use and to determine whether common audiological tests, including pure-tone audiometry or word recognition test, correlate with HA wearers' subjective benefit. DESIGN: A retrospective chart review. STUDY SAMPLE: A total of 129 patients who adopted new HAs between January 2011 and December 2018 were enrolled. Outcome measures including pure tone thresholds, word recognition score (WRS), and self-reported questionnaires were obtained 1, 4, and 12 months post fit. RESULTS: The mean aided threshold and WRS at each post-fit visit significantly improved from the unaided condition. Self-reported outcomes confirmed by the Hearing Handicap Inventory for the Elderly (HHIE) scores significantly improved compared to the unaided condition at 1- and 4-month follow-up. Results of the regression analysis indicated that the aided WRS score is a significant factor at all post-fit visits that explains less than 10% of the variance in HHIE scores. CONCLUSIONS: Aided WRS is the factor most associated with subjectively reported HA outcomes, both in the short- and long term. Therefore, aided WRS should be considered as a useful tool for evaluating HA benefits, even after the prolonged use of HAs.

Impact of nationwide hepatocellular carcinoma surveillance on the prognosis in patients with chronic liver disease.

BACKGROUND/AIMS: This study aimed to investigate the effect of hepatocellular carcinoma (HCC) surveillance using the Korea National Liver Cancer Screening Program on the receipt of curative treatment for HCC and mortality in patients with chronic liver disease. METHODS: This population-based cohort study from the Korean National Health Insurance Service included 2003 to 2015 claims data collected from 1,209,825 patients aged ≥40 years with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis. Patients were divided according to HCC surveillance using ultrasonography and serum alpha-fetoprotein every 6-12 months. The study outcomes were the receipt of curative treatment (surgical resection, radiofrequency ablation, or liver transplantation) and all-cause mortality. RESULTS: The study population consisted of 1,209,825 patients with chronic hepatitis B, chronic hepatitis C, and liver cirrhosis (median age, 52.0 years; interquartile range, 46-55 years; 683,902 men [56.5%]). The proportion of participants who underwent HCC surveillance was 52.7% (n=657,889). During 10,522,940 person-years of follow-up, 74,433 HCC cases developed, including 36,006 patients who underwent curative treatment. The surveillance group had a significantly higher proportion of curative treatment for HCC than the non-surveillance group after adjusting for confounding factors (adjusted hazard ratio [HR], 5.64; 95% confidence interval [CI], 5.48-5.81). The surveillance group had a significantly lower mortality rate than the non-surveillance group (adjusted HR, 0.56; 95% CI, 0.55-0.56). CONCLUSION: HCC surveillance using the national screening program in patients with chronic viral hepatitis or liver cirrhosis provides better opportunity for curative treatment for HCC and improves overall survival.

NIR fluorescence imaging and treatment for cancer immunotherapy.

Cancer immunotherapy has emerged as one of the most powerful anticancer therapies. However, the details on the interaction between tumors and the immune system are complicated and still poorly understood. Optical fluorescence imaging is a technique that allows for the visualization of fluorescence-labeled immune cells and monitoring of the immune response during immunotherapy. To this end, near-infrared (NIR) light has been adapted for optical fluorescence imaging because it is relatively safe and simple without hazardous ionizing radiation and has relatively deeper tissue penetration into living organisms than visible fluorescence light. In this review, we discuss state-of-the-art NIR optical imaging techniques in cancer immunotherapy to observe the dynamics, efficacy, and responses of the immune components in living organisms. The use of bioimaging labeling techniques will give us an understanding of how the immune system is primed and ultimately developed.

Temporal patterns of chronic disease incidence after breast cancer: a nationwide population-based cohort study.

We conducted a retrospective cohort study to evaluate the temporal pattern of incidence of chronic conditions after developing breast cancer using a population-based national registry. We selected 84,969 women with newly diagnosed breast cancer between 2002 and 2016 and a 1:10 sample of age-matched non-breast cancer controls (N = 1,057,674). The main study exposure was incident breast cancer, considered as a time-varying exposure. The outcomes were incident cases of leukemia, endometrial cancer, myeloma, cardiomyopathy, osteoporosis, end stage renal disease (ESRD), pulmonary fibrosis, hypothyroidism, type 2 diabetes, hypertension and hyperlipidemia. The development of breast cancer was associated with a significantly increased risk of all outcomes analyzed except for ESRD and hypertension. The fully-adjusted risks of leukemia (HR 3.09; 95% CI 2.11-4.51), cardiomyopathy (HR 2.65; 95% CI 1.90-3.68), endometrial cancer (HR 3.53; 95% CI 2.76-4.53), hypothyroidism (HR 1.29; 95% CI 1.19-1.40), pulmonary fibrosis (HR 1.84; 95% CI 1.12-3.02), and hyperlipidemia (HR 1.24; 95% CI 1.20-1.28) remained significantly elevated after more than 5 years since diagnosis. Optimal care for breast cancer survivors requires close collaboration between oncologists and allied health care professionals to identify and manage the long-term morbidity and mortality associated with these chronic conditions.

Fast and Durable Intraoperative Near-infrared Imaging of Ovarian Cancer Using Ultrabright Squaraine Fluorophores.

The residual tumor after surgery is the most significant prognostic factor of patients with epithelial ovarian cancer. Near-infrared (NIR) fluorescence-guided surgery is actively utilized for tumor localization and complete resection during surgery. However, currently available contrast-enhancing agents display low on-target binding, unfavorable pharmacokinetics, and toxicity, thus not ideal for clinical use. Here we report ultrabright and stable squaraine fluorophores with optimal pharmacokinetics by introducing an asymmetric molecular conformation and surface charges for rapid transporter-mediated cellular uptake. Among the tested, OCTL14 shows low serum binding and rapid distribution into cancer tissue via organic cation transporters (OCTs). Additionally, the charged squaraine fluorophores are retained in lysosomes, providing durable intraoperative imaging in a preclinical murine model of ovarian cancer up to 24 h post-injection. OCTL14 represents a significant departure from the current bioconjugation approach of using a non-targeted fluorophore and would provide surgeons with an indispensable tool to achieve optimal resection.

Comprehensive risk assessment for hospital-acquired pneumonia: sociodemographic, clinical, and hospital environmental factors associated with the incidence of hospital-acquired pneumonia.

BACKGROUND: Social and hospital environmental factors that may be associated with hospital-acquired pneumonia (HAP) have not been evaluated. Comprehensive risk assessment for the incidence of HAP including sociodemographic, clinical, and hospital environmental factors was conducted using national health insurance claims data. METHODS: This is a population-based retrospective cohort study of adult patients who were hospitalized for more than 3 days from the Health Insurance Review and Assessment Service-National Inpatient Sample data between January 1, 2016 and December 31, 2018 in South Korea. Multivariable logistic regression analyses were conducted to identify the factors associated with the incidence of HAP. RESULTS: Among the 512,278 hospitalizations, we identified 25,369 (5.0%) HAP cases. In multivariable analysis, well-known risk factors associated with HAP such as older age (over 70 vs. 20-29; adjusted odds ratio [aOR], 3.66; 95% confidence interval [CI] 3.36-3.99), male sex (aOR, 1.35; 95% CI 1.32-1.39), pre-existing lung diseases (asthma [aOR, 1.73; 95% CI 1.66-1.80]; chronic obstructive pulmonary disease [aOR, 1.62; 95% CI 1.53-1.71]; chronic lower airway disease [aOR, 1.79; 95% CI 1.73-1.85]), tube feeding (aOR, 3.32; 95% CI 3.16-3.50), suctioning (aOR, 2.34; 95% CI 2.23-2.47), positioning (aOR, 1.63; 95% CI 1.55-1.72), use of mechanical ventilation (aOR, 2.31; 95% CI 2.15-2.47), and intensive care unit admission (aOR, 1.29; 95% CI 1.22-1.36) were associated with the incidence of HAP. In addition, poverty (aOR, 1.08; 95% CI 1.04-1.13), general hospitals (aOR, 1.54; 95% CI 1.39-1.70), higher bed-to-nurse ratio (Grade ≥ 5; aOR, 1.45; 95% CI 1.32-1.59), higher number of beds per hospital room (6 beds; aOR, 3.08; 95% CI 2.77-3.42), and ward with caregiver (aOR, 1.19; 95% CI 1.12-1.26) were related to the incidence of HAP. CONCLUSIONS: The incidence of HAP was associated with various sociodemographic, clinical, and hospital environmental factors. Thus, taking a comprehensive approach to prevent and treat HAP is important.

Changes in the Plasma Apurinic/Apyrimidinic Endonuclease 1/Redox Factor-1(APE1/Ref-1) Level during Cancer Surgery: An Observational Study.

Background and Objectives: Propofol-based total intravenous anesthesia (TIVA) is presumed to have more favorable effects on the prognosis of patients with cancer compared with volatile inhaled anesthesia (VIA). We hypothesized that these anesthetics target plasma apurinic apyrimidinic endonuclease/redox effector factor-1 (APE1/Ref-1) as a possible mechanism of action. Materials and Methods: The plasma APE1/Ref-1 level was evaluated three times during surgery for cancer, i.e., before anesthesia, immediately after cancer resection, and finally, in the recovery room. Blood (3 cc) was drawn from the radial artery catheter, and plasma APE1/Ref-1 levels were compared according to measurement time and between the two groups. Spearman's Rho correlation analysis was performed to determine relationships among body mass index, American Society of Anesthesiologists classification, age, sex, cancer type, and tumor-node-metastasis (TNM) stage. A total of 166 patients (VIA: 129; TIVA: 37) were enrolled. Results: Plasma APE1/Ref-1 level increased significantly (p = 0.028) after cancer resection compared with before surgery, but no significant difference was observed between anesthetics (p = 0.134). The post-resection plasma APE1/Ref-1 level showed a positive correlation with the NM stages, but not the T stage. Conclusions: The plasma APE1/Ref-1 level increased during surgery with more severe lymph node invasion, but there were no significant differences according to the anesthetics used.

Circulating Tumor Cell Detection in Lung Cancer Animal Model.

BACKGROUND: Metastasis and recurrence of primary cancer are the main causes of cancer mortality. Disseminated tumor cells refer to cancer cells that cause metastasis from primary cancer to other organs. Several recent studies have suggested that circulating tumor cells (CTCs) are associated with the clinical stage, cancer recurrence, cancer metastasis, and prognosis. There are several methods of isolating CTCs from whole blood; in particular, using a membrane filtration system is advantageous due to its cost-effectiveness and availability in clinical settings. In this study, an animal model of lung cancer was established in nude mice using the human large cell lung cancer cell line H460. METHODS: Six-week-old nude mice were used. The H460 lung cancer cell line was injected subcutaneously into the nude mice. Blood samples were obtained from the orbital area before cell line injection, 2 weeks after injection, and 2 weeks after tumor excision. Blood samples were filtered using a polycarbonate 12-well Transwell membrane (Corning Inc., Corning, NY, USA). An indirect immunofluorescence assay was performed with the epithelial cell adhesion molecule antibody. The number of stained cells was counted using fluorescence microscopy. RESULTS: The average size of the tumor masses was 35.83 mm. The stained cells were counted before inoculation, 2 weeks after inoculation, and 2 weeks after tumor excision. Cancer cells generally increased after inoculation and decreased after tumor resection. CONCLUSION: The CTC detection method using the commercial polycarbonate 12-well Transwell (Corning Inc.) membrane is advantageous in terms of cost-effectiveness and convenience.

Developing a Dementia Platform Databank Using Multiple Existing Cohorts.

This study was conducted as a pilot project to evaluate the feasibility of building an integrate dementia platform converging preexisting dementia cohorts from several variable levels. The following four cohorts were used to develop this pilot platform: 1) Clinical Research Center for Dementia of South Korea (CREDOS), 2) Korean Brain Aging Study for Early Diagnosis and Prediction of Alzheimer's disease (K-BASE), 3) Environmental Pollution-induced Neurological Effects (EPINEF) study, and 4) a prospective registry in Dementia Platform Korea project (DPKR). A total of 29916 patients were included in the platform with 348 integrated variables. Among participants, 13.9%, 31.5%, and 44.2% of patients had normal cognition, mild cognitive impairment, and dementia, respectively. The mean age was 72.4 years. Females accounted for 65.7% of all patients. Those with college or higher education and those without problems in reading or writing accounted for 12.3% and 46.8%, respectively. Marital status, cohabitation, family history of Parkinson's disease, smoking and drinking status, physical activity, sleep status, and nutrition status had rates of missing information of 50% or more. Although individual cohorts were of the same domain and of high quality, we found there were several barriers to integrating individual cohorts, including variability in study variables and measurements. Although many researchers are trying to combine pre-existing cohorts, the process of integrating past data has not been easy. Therefore, it is necessary to establish a protocol with considerations for data integration at the cohort establishment stage.