Survey on Value Elements Provided by Artificial Intelligence and Their Eligibility for Insurance Coverage With an Emphasis on Patient-Centered Outcomes.

OBJECTIVE: This study aims to explore the opinions on the insurance coverage of artificial intelligence (AI), as categorized based on the distinct value elements offered by AI, with a specific focus on patient-centered outcomes (PCOs). PCOs are distinguished from traditional clinical outcomes and focus on patient-reported experiences and values such as quality of life, functionality, well-being, physical or emotional status, and convenience. MATERIALS AND METHODS: We classified the value elements provided by AI into four dimensions: clinical outcomes, economic aspects, organizational aspects, and non-clinical PCOs. The survey comprised three sections: 1) experiences with PCOs in evaluating AI, 2) opinions on the coverage of AI by the National Health Insurance of the Republic of Korea when AI demonstrated benefits across the four value elements, and 3) respondent characteristics. The opinions regarding AI insurance coverage were assessed dichotomously and semi-quantitatively: non-approval (0) vs. approval (on a 1-10 weight scale, with 10 indicating the strongest approval). The survey was conducted from July 4 to 26, 2023, using a web-based method. Responses to PCOs and other value elements were compared. RESULTS: Among 200 respondents, 44 (22%) were patients/patient representatives, 64 (32%) were industry/developers, 60 (30%) were medical practitioners/doctors, and 32 (16%) were government health personnel. The level of experience with PCOs regarding AI was low, with only 7% (14/200) having direct experience and 10% (20/200) having any experience (either direct or indirect). The approval rate for insurance coverage for PCOs was 74% (148/200), significantly lower than the corresponding rates for other value elements (82.5%-93.5%; P ≤ 0.034). The approval strength was significantly lower for PCOs, with a mean weight ± standard deviation of 5.1 ± 3.5, compared to other value elements (P ≤ 0.036). CONCLUSION: There is currently limited demand for insurance coverage for AI that demonstrates benefits in terms of non-clinical PCOs.

Bufotalin Suppresses Proliferation and Metastasis of Triple-Negative Breast Cancer Cells by Promoting Apoptosis and Inhibiting the STAT3/EMT Axis.

Triple-negative breast cancer (TNBC) is a highly aggressive type of breast cancer and has a poor prognosis. As standardized TNBC treatment regimens cause drug resistance and tumor recurrence, the development of new TNBC treatment strategies is urgently required. Bufotalin is a bufadienolide isolated from the skin and parotid venom glands of the toad Bufo gargarizan, and has several pharmacological properties, including antiviral, anti-inflammatory, and anticancer activities. However, the anticancer effect and underlying molecular mechanisms of action of bufotalin in TNBC have not been fully studied. In the current study, we investigated the effects of bufotalin on the growth and metastasis of MDA-MB-231 and HCC1937 TNBC cells. Bufotalin potently inhibited the proliferation of both TNBC cell lines by promoting cell cycle arrest and caspase-mediated apoptosis. Furthermore, bufotalin effectively suppressed the migration and invasion of both TNBC cell lines by regulating the expression of key epithelial-mesenchymal transition (EMT) biomarkers, matrix metalloproteinases (MMPs), and integrin α6. Notably, the anticancer effect of bufotalin in TNBC cells was associated with the downregulation of the signal transducer and activator of the transcription 3 (STAT3) signaling pathway. Collectively, our results suggest that the natural compound bufotalin may exert antiproliferative and antimetastatic activities in TNBC cells by modulating the apoptotic pathway and the STAT3/EMT axis.

Bioconversion of Mixed Alkanes to Polyhydroxyalkanoate by Pseudomonas resinovornas: Upcycling of Pyrolysis Oil from Waste-Plastic.

Polyhydroxyalkanoate (PHA) is a biodegradable plastic that can be used to replace petroleum-based plastic. In addition, as a medium-chain-length PHA (mcl-PHA), it can be used to provide elastomeric properties in specific applications. Because of these characteristics, recently, there has been much research on mcl-PHA production using inexpensive biomass materials as substrates. In this study, mcl-PHA producers were screened using alkanes (n-octane, n-decane, and n-dodecane) as sources of carbon. The amount of PHA produced by Pseudomonas resinovorans using sole n-octane, n-decane, or n-dodecane was 0.48 g/L, 0.27 g/L, or 0.07 g/L, respectively, while that produced using mixed alkane was 0.74 g/L. As a larger amount of PHA was produced using mixed alkane compared with sole alkane, a statistical mixture analysis was used to determine the optimal ratio of alkanes in the mixture. The optimal ratio predicted by the analysis was a medium with 9.15% n-octane, 6.44% n-decane, and 4.29% n-dodecane. In addition, through several concentration-specific experiments, the optimum concentrations of nitrogen and phosphorus for cell growth and maximum PHA production were determined as 0.05% and 1.0%, respectively. Finally, under the determined optimal conditions, 2.1 g/L of mcl-PHA and 60% PHA content were obtained using P. resinovorans in a 7 L fermenter.

Development and evaluation of smartphone usage management system for preventing problematic smartphone use.

Objective: The increased use of smartphones has led to several problems, including excessive smartphone use and the decreased self-ability to control smartphone use. To prevent these problems, the MindsCare app was developed as a method of self-management and intervention based on an evaluation of smartphone usage. We designed the MindsCare app to manage smartphone usage and prevent problematic smartphone use by providing personalized interventions. Methods: We recruited 342 Korean participants over the age of 20 and asked them to use MindsCare for 13 weeks. Subsequently, we evaluated the changes in average smartphone usage time and the usability of the app. We designed a usability evaluation questionnaire based on the Technology Acceptance Model and conducted factor and reliability analyses on the participants' responses. In the eighth week of the study, participants responded to a survey on the usability of the app. We ultimately collected data from 190 participants. Results: The average score for the usability of the system was 3.61 on a five-point Likert scale, and approximately 58% of the participants responded positively to the evaluation items. In addition, our analysis of MindsCare data revealed a significant reduction in average smartphone use time in the eighth week compared to the baseline (t = 3.47, p = 0.001). Structural equation model analysis revealed that effort expectancy and performance expectancy had a positive relation with behavior intention for the app. Conclusions: Through this study, we confirmed the MindsCare app's smartphone usage time reduction effect and proved its good usability. As a result, MindsCare may contribute to achieving users' goals of reducing problematic smartphone use.

Deep Learning Model Based on 3D Optical Coherence Tomography Images for the Automated Detection of Pathologic Myopia.

Pathologic myopia causes vision impairment and blindness, and therefore, necessitates a prompt diagnosis. However, there is no standardized definition of pathologic myopia, and its interpretation by 3D optical coherence tomography images is subjective, requiring considerable time and money. Therefore, there is a need for a diagnostic tool that can automatically and quickly diagnose pathologic myopia in patients. This study aimed to develop an algorithm that uses 3D optical coherence tomography volumetric images (C-scan) to automatically diagnose patients with pathologic myopia. The study was conducted using 367 eyes of patients who underwent optical coherence tomography tests at the Ophthalmology Department of Incheon St. Mary's Hospital and Seoul St. Mary's Hospital from January 2012 to May 2020. To automatically diagnose pathologic myopia, a deep learning model was developed using 3D optical coherence tomography images. The model was developed using transfer learning based on four pre-trained convolutional neural networks (ResNet18, ResNext50, EfficientNetB0, EfficientNetB4). Grad-CAM was used to visualize features affecting the detection of pathologic myopia. The performance of each model was evaluated and compared based on accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC). The model based on EfficientNetB4 showed the best performance (95% accuracy, 93% sensitivity, 96% specificity, and 98% AUROC) in identifying pathologic myopia.

Factors associated with different levels of daytime sleepiness among Korean construction drivers: a cross-sectional study.

BACKGROUND: Commercial vehicle accidents are the leading cause of occupational fatalities and an increased risk of traffic accidents is associated with excessive fatigue, other health problems as well as poor sleep during work. This study explores individual and occupational factors associated with different levels of daytime sleepiness and identifies their association with driving risk among occupational drivers working at construction sites. METHODS: This cross-sectional and correlational study adopted a self-reported questionnaire of Korean construction drivers (N = 492). The data were collected from October 2018 to February 2019 using a battery of six validated instruments about participants' sociodemographic, health-related, and occupational characteristics. One-way ANOVA and multinomial logistic regression were conducted using IBM SPSS WIN/VER 25.0, with a two-tailed alpha of .05. RESULTS: Based on the Epworth Sleepiness Scale, "moderate" (31.7%) and "severe" (10.2%) daytime sleepiness groups were identified. There were significant differences in break time, driving fatigue, depressive symptom, subjective sleep quality, physical and mental health, and driving risk among the three groups (all p-values < .001). Driving fatigue (Adjusted Odds Ratio [aOR] = 1.08, 1.17), depressive symptoms (aOR = 0.91, 0.98), subjective sleep quality (aOR = 1.18 in moderate only), and driving over the speed limit (aOR = 1.43, 2.25) were significant factors for determining "moderate" and "severe" daytime sleepiness groups, respectively. CONCLUSION: A significant number of construction drivers experience excessive daytime sleepiness; thus it is important to reduce the negative impact of driving fatigue and other factors on daytime sleepiness. Our study findings suggest that occupational health care providers should pay attention to development and implementation of health management interventions to reduce driving fatigue that incorporate the drivers' physical, mental, and occupational factors. Professional organizations need to establish internal regulations and public policies to promote health and safety among occupational drivers who specifically work at construction sites.

Machine learning prediction of dropping out of outpatients with alcohol use disorders.

BACKGROUND: Alcohol use disorder (AUD) is a chronic disease with a higher recurrence rate than that of other mental illnesses. Moreover, it requires continuous outpatient treatment for the patient to maintain abstinence. However, with a low probability of these patients to continue outpatient treatment, predicting and managing patients who might discontinue treatment becomes necessary. Accordingly, we developed a machine learning (ML) algorithm to predict which the risk of patients dropping out of outpatient treatment schemes. METHODS: A total of 839 patients were selected out of 2,206 patients admitted for AUD in three hospitals under the Catholic Central Medical Center in Korea. We implemented six ML models-logistic regression, support vector machine, k-nearest neighbor, random forest, neural network, and AdaBoost-and compared the prediction performances thereof. RESULTS: Among the six models, AdaBoost was selected as the final model for recommended use owing to its area under the receiver operating characteristic curve (AUROC) of 0.72. The four variables affecting the prediction based on feature importance were the length of hospitalization, age, residential area, and diabetes. CONCLUSION: An ML algorithm was developed herein to predict the risk of patients with AUD in Korea discontinuing outpatient treatment. By testing and validating various machine learning models, we determined the best performing model, AdaBoost, as the final model for recommended use. Using this model, clinicians can manage patients with high risks of discontinuing treatment and establish patient-specific treatment strategies. Therefore, our model can potentially enable patients with AUD to successfully complete their treatments by identifying them before they can drop out.

Machine learning prediction of pathologic myopia using tomographic elevation of the posterior sclera.

Qualitative analysis of fundus photographs enables straightforward pattern recognition of advanced pathologic myopia. However, it has limitations in defining the classification of the degree or extent of early disease, such that it may be biased by subjective interpretation. In this study, we used the fovea, optic disc, and deepest point of the eye (DPE) as the three major markers (i.e., key indicators) of the posterior globe to quantify the relative tomographic elevation of the posterior sclera (TEPS). Using this quantitative index from eyes of 860 myopic patients, support vector machine based machine learning classifier predicted pathologic myopia an AUROC of 0.828, with 77.5% sensitivity and 88.07% specificity. Axial length and choroidal thickness, the existing quantitative indicator of pathologic myopia only reached an AUROC of 0.758, with 75.0% sensitivity and 76.61% specificity. When all six indices were applied (four TEPS, AxL, and SCT), the discriminative ability of the SVM model was excellent, demonstrating an AUROC of 0.868, with 80.0% sensitivity and 93.58% specificity. Our model provides an accurate modality for identification of patients with pathologic myopia and may help prioritize these patients for further treatment.

Machine Learning Approach to Predict the Probability of Recurrence of Renal Cell Carcinoma After Surgery: Prediction Model Development Study.

BACKGROUND: Renal cell carcinoma (RCC) has a high recurrence rate of 20% to 30% after nephrectomy for clinically localized disease, and more than 40% of patients eventually die of the disease, making regular monitoring and constant management of utmost importance. OBJECTIVE: The objective of this study was to develop an algorithm that predicts the probability of recurrence of RCC within 5 and 10 years of surgery. METHODS: Data from 6849 Korean patients with RCC were collected from eight tertiary care hospitals listed in the KOrean Renal Cell Carcinoma (KORCC) web-based database. To predict RCC recurrence, analytical data from 2814 patients were extracted from the database. Eight machine learning algorithms were used to predict the probability of RCC recurrence, and the results were compared. RESULTS: Within 5 years of surgery, the highest area under the receiver operating characteristic curve (AUROC) was obtained from the naïve Bayes (NB) model, with a value of 0.836. Within 10 years of surgery, the highest AUROC was obtained from the NB model, with a value of 0.784. CONCLUSIONS: An algorithm was developed that predicts the probability of RCC recurrence within 5 and 10 years using the KORCC database, a large-scale RCC cohort in Korea. It is expected that the developed algorithm will help clinicians manage prognosis and establish customized treatment strategies for patients with RCC after surgery.

Multidisciplinary team approach in acute myocardial infarction patients undergoing veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Limited data are available on the impact of a specialized extracorporeal membrane oxygenation (ECMO) team on clinical outcomes in patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS). This study evaluated whether specialized ECMO team is associated with improved in-hospital mortality in AMI patients undergoing veno-arterial (VA) ECMO. METHODS: A total of 255 AMI patients who underwent VA-ECMO were included. In January 2014, a multidisciplinary ECMO team was founded at our institution. Eligible patients were classified into a pre-ECMO team group (n = 131) and a post-ECMO team group (n = 124). The primary outcome was in-hospital mortality. RESULTS: In-hospital mortality (pre-ECMO team vs. post-ECMO team, 54.2% vs. 33.9%; p = 0.002) and cardiac intensive care unit mortality (pre-ECMO team vs. post-ECMO team, 51.9% vs. 30.6%; p = 0.001) were significantly lower after the implementation of a multidisciplinary ECMO team. On multivariable logistic regression model, implementation of the multidisciplinary ECMO team was associated with reduction of in-hospital mortality [odds ratio: 0.37, 95% confidence interval (CI) 0.20-0.67; p = 0.001]. Incidence of all-cause mortality [58.3% vs. 35.2%; hazard ratio (HR): 0.49, 95% CI 0.34-0.72; p < 0.001) and readmission due to heart failure (28.2% vs. 6.4%; HR: 0.21, 95% CI 0.08-0.58; p = 0.003) at 6 months of follow-up were also significantly lower in the post-ECMO team group than in the pre-ECMO team group. CONCLUSIONS: Implementation of a multidisciplinary ECMO team was associated with improved clinical outcomes in AMI patients complicated by CS. Our data support that a specialized ECMO team is indispensable for improving outcomes in patients with AMI complicated by CS.

Cs desorption behavior during hydrothermal treatment of illite with oxalic acid.

The desorption of radioactive cesium (Cs) in soil is influenced by the clay mineral type, adsorption site, and concentration of Cs. In this study, experiments to detect desorption of non-radioactive and radioactive Cs from illite using oxalic acid were performed for 2 days at 70 °C in hydrothermal conditions. The results showed that the 133Cs removal efficiency by oxalic acid and inorganic acid treatment was similar at high concentration (22.86 mmol/kg) of non-radioactive 133Cs. In the radioactive 137Cs experiment, the removal efficiency by oxalic acid was higher than that by inorganic acid at low concentration (0.79 × 10-6 mmol/kg) of radioactive 137Cs. Based on the illite hypothetical frayed edge site (FES) concentration of 0.612 mmol/kg, the results suggested that 137Cs was preferentially adsorbed to FES on illite. The 137Cs at low concentration was difficult to remove because it was irreversible adsorption to FES, while the non-radioactive Cs at high concentration was mainly adsorbed to planar sites, and so was easy to desorb by ion exchange. Based on the results of NMR, FTIR, and XPS analyses, we concluded that the higher efficiency of 137Cs removal at low concentration by oxalic acid treatment than by treatment with inorganic acid was because of chelation effects associated with the complexation of oxalic acid (ligands) and metal ions in irreversible site (FES).

Drain placement in thyroidectomy is associated with longer hospital stay without preventing hematoma.

OBJECTIVE: To analyze the effect of drain placement on postoperative hematoma formation and other associated outcomes post-thyroid surgery in a large national cohort. METHODS: This was a retrospective study that analyzed data from the 2016-2017 National Surgical Quality Improvement Program (NSQIP) public use files. Baseline characteristics and perioperative outcomes were compared between drain and no drain cohorts. RESULTS: A total of 11,626 patients were included; 3281 had a drain placed intraoperatively and 8345 did not. Otolaryngologists were 6.98 times more likely to place a drain after thyroidectomy than general surgeons (P < .001), and patients undergoing subtotal or total thyroidectomy were 2.17 times more likely to have a drain placed than if undergoing partial thyroidectomy (P < .001). Drain placement did not reduce hematoma formation on both univariate and multivariate analyses (adjusted OR = 0.93, P = .696). A slightly larger proportion of patients underwent unplanned intubation postoperatively among those who had a drain placed (0.76% vs. 0.29%, P < .001). Patients who received a drain were on average 4.63 times as likely to remain in the hospital for 2 or more days compared to those who did not receive a drain. CONCLUSION: Drain placement did not significantly affect postoperative hematoma formation following thyroidectomy. Drain placement should not be routinely employed in these patients. However, surgeon judgement and intraoperative considerations should be taken into account, as to when to place a drain. LEVEL OF EVIDENCE: N/A Laryngoscope, 130:1349-1356, 2020.

Factors Affecting Smartphone Usage Self-Report Levels.

For the treatment of smartphone addiction, it is important to understand users' smartphone usage patterns. Most of the studies are based on self-report surveys. However, there are differences between self-reported usage and real usage. For a better understanding of usage patterns, this study identified demographic and social factors that affect smartphone usage self-report levels. Also, it was confirmed that the influencing factors differ depending on the smartphone usage content by application category.

Cisplatin and oxaliplatin induce similar immunogenic changes in preclinical models of head and neck cancer.

OBJECTIVES: Prior studies suggest that oxaliplatin is unique among platinum chemotherapy drugs in its ability to enhance anti-tumor immunity, but the immune mechanisms of different platinum chemotherapy drugs have not been previously compared in preclinical models of head and neck squamous cell carcinoma (HNSCC). MATERIALS AND METHODS: Human HNSCC cell lines were treated with cisplatin or oxaliplatin, then assessed for markers associated with immunogenic cell death (ICD) and antigen processing. A syngeneic mouse model of oral cancer was then used to compare the effects of cisplatin vs. oxaliplatin, alone or in combination with anti-PD-1 immunotherapy, on tumor growth and survival. A subset of spleens and tumors were analyzed for ICD markers and immune cell infiltrates by flow cytometry. RESULTS: Cisplatin and oxaliplatin both increased cell surface levels of calreticulin, HSP70, MHC class I and PD-L1 in multiple cell lines. Inoculation of immunocompetent mice with cells killed in vitro by either drug resulted in failure of subsequently-injected live tumor cells to establish and grow in a small proportion of animals. Systemic cisplatin and oxaliplatin induced similar tumor growth delay when combined with anti-PD-1 therapy. CONCLUSIONS: Treatment of HNSCC cells with platinum chemotherapy appears to induce some features of anti-tumor immunity, which may be enhanced by anti-PD-1 therapy. Cisplatin, the standard drug for HNSCC, appears to affect anti-tumor immunity in a similar fashion to oxaliplatin in these preclinical models.

Association of statin therapy with clinical outcomes in patients with vasospastic angina: Data from Korean health insurance review and assessment service.

There is conflicting evidence for the clinical benefit of statin therapy in patients with vasospastic angina (VSA). We investigated the association of statin therapy with clinical outcomes in relatively large populations with clinically suspected VSA from a nationwide population-based database. Data were collected from the Health Insurance Review and Assessment database records of 4,099 patients that were in an intensive care unit with VSA between January 1, 2008 and May 31, 2015. We divided the patients into a statin group (n = 1,795) and a non-statin group (n = 2,304). The primary outcome was a composite of cardiac arrest and acute myocardial infarction (AMI). The median follow-up duration was 3.8 years (interquartile range: 2.2 to 5.8 years). Cardiac arrest or AMI occurred in 120 patients (5.2%) in the statin group, and 97 patients (5.4%) in the non-statin group (P = 0.976). With inverse probability of treatment weighting, there was no significant difference in the rate of cardiac arrest or AMI between the two groups (adjusted hazard ratio [HR], 0.99; 95% confidence interval [CI], 0.76-1.30; P = 0.937), or even between the non-statin group and high-intensity statin group (adjusted HR, 1.08; 95% CI, 0.69-1.70; P = 0.75). The beneficial association of statin use with the primary outcome was consistently lacking across the various comorbidity types. Statin therapy was not associated with reduced cardiac arrest or AMI in patients with VSA, regardless of statin intensity. Prospective, randomized trials will be needed to confirm our findings.

Antagonist of cIAP1/2 and XIAP enhances anti-tumor immunity when combined with radiation and PD-1 blockade in a syngeneic model of head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) frequently harbor genomic mutations in cell death pathways. Nearly 30% of HNSCCs overexpress Fas-Associated Death Domain (FADD), with or without BIRC2/3 genes encoding cellular Inhibitor of Apoptosis Proteins 1/2 (cIAP1/2), critical components of the Tumor Necrosis Factor (TNF) Receptor signaling pathways. ASTX660 is a novel non-peptidomimetic antagonist of cIAP1/2 and XIAP under evaluation in a clinical trial for advanced solid tumors and lymphomas. Herein, we show that ASTX660, at nanomolar concentrations, sensitized Murine Oral Cancer (MOC1) cells to TNFα. Using syngeneic mouse models, ASTX660 showed additive anti-tumor activity with radiation therapy (XRT), cisplatin chemotherapy, and PD-1 blockade to significantly delay or eradicate MOC1 tumors. These combinations significantly increased CD8 + T cells and dendritic cells, as well as T cell activity. ASTX660 stimulated cytotoxic T lymphocyte (CTL) killing of MOC1 cells expressing ovalbumin. Early stages of CTL killing were predominantly mediated by perforin/granzyme B, whereas later stages were mediated by death ligands TNFα, TRAIL, and FasL. Correspondingly, depletion of CD8 + T cells and NK cells in vivo revealed both types of immune cells to be important components of the complete anti-tumor response enhanced by ASTX660+XRT. These findings serve to inform future studies of IAP inhibitors and support the potential for future clinical trials investigating ASTX660 with XRT and immunotherapies like PD-1/PD-L1 blockade in HNSCC.

Differential prognosis of vasospastic angina according to presentation with sudden cardiac arrest or not: Analysis of the Korean Health Insurance Review and Assessment Service.

BACKGROUND: The long-term prognosis of vasospastic angina (VSA) patients presenting with aborted sudden cardiac death (ASCD) is still unknown. We sought to compare the long-term clinical outcomes between VSA patients presenting with and without ASCD by retrospective analysis of a nationwide population-based database. METHODS: A total of 6972 patients in the Health Insurance Review and Assessment database who were hospitalized in the intensive care unit with VSA between July 1, 2007 and May 31, 2015 were enrolled. Primary outcome was the composite of cardiac arrest and acute myocardial infarction after discharge. RESULTS: Five hundred ninety-eight (8.6%) VSA patients presented with ASCD. On inverse probability of treatment weighting, ASCD patients had a significantly increased risk of the composite of cardiac arrest and acute myocardial infarction (adjusted hazard ratio, 2.52; 95% confidence interval, 1.72-3.67; p < 0.001) during the median follow-up duration of 4 years. The association of ASCD presentation with a worse outcome in terms of primary outcome was consistent across various subgroups, including comorbidity type and use of vasodilators (all p-values for interaction: non-significant). ASCD patients treated with an implantable cardioverter defibrillator (ICD) had a lower incidence of the composite of cardiac arrest and acute myocardial infarction during follow-up than those without an ICD (p = 0.009). CONCLUSIONS: VSA patients that present with ASCD are at increased risk of cardiac arrest or myocardial infarction during long-term follow-up despite adequate vasodilator therapy. An ICD is a potential therapeutic option for secondary prevention.

Evaluation of risk factors for vancomycin-induced nephrotoxicity.

Background Vancomycin is a glycopeptide antibiotic of choice for the treatment of serious infections caused by multi-resistant Gram-positive bacteria. However, vancomycin-associated nephrotoxicity (VAN) often limits its use. Previous data suggested a few risk factors of VAN, including higher mean vancomycin trough level, higher daily doses, old age, long duration of vancomycin therapy, and concomitant nephrotoxins. Objective To evaluate the incidence and risk factors of VAN and determine whether higher vancomycin trough concentrations were associated with a greater risk for VAN. Settings A retrospective, observational, single-center study at the 1960-bed university-affiliated tertiary care hospital (Samsung Medical Center), Seoul, Korea. Method A retrospective analysis of adult patients who received vancomycin parenterally in a tertiary care medical center from March 1, 2013 to June 30, 2013 was performed. We excluded patients with a baseline serum creatinine level > 2 mg/dL and those who had a history of end-stage renal disease and dialysis at baseline. The clinical characteristics were compared between patients with nephrotoxicity and those without nephrotoxicity to identify the risk factors associated with VAN. Main outcome measure Incidence of VAN and VAN-associated risk factors were analyzed. Results Of the 315 vancomycin-treated patients, nephrotoxicity occurred in 15.2% of the patients. In multivariate analysis, higher vancomycin trough concentrations of > 20 mg∕L (OR 9.57, 95% CI 2.49-36.83, p < 0.01) and intensive care unit (ICU) residence (OR 2.86, 95% CI 1.41-5.82, p < 0.01) were independently associated with VAN. Conclusion Our findings suggest that higher vancomycin trough levels and ICU residence might be associated with a greater risk for VAN. More careful monitoring of vancomycin serum trough levels and patient status might facilitate the timely prevention of VAN.

Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC) has been treated for decades with cisplatin chemotherapy, and anti-PD-1 immunotherapy has recently been approved for the treatment of this disease. However, preclinical studies of how antitumor immunity in HNSCC is affected by cisplatin alone or in combination with immunotherapies are lacking. Here, we show that sublethal doses of cisplatin may enhance antigen presentation and T-cell killing in vitro, though cisplatin also upregulates tumor cell expression of PD-L1 and may impair T-cell function at higher doses. In a syngeneic mouse model of HNSCC, concurrent use of cisplatin and anti-PD-L1/PD-1 delayed tumor growth and enhanced survival without significantly reducing the number or function of tumor-infiltrating immune cells or increasing cisplatin-induced toxicities. These results suggest that moderate doses of cisplatin may enhance antitumor immunity by mechanisms other than direct tumor cell killing, which may be further enhanced by anti-PD-L1/PD-1 therapy. Cancer Immunol Res; 5(12); 1141-51. ©2017 AACR.

Trough Concentrations of Vancomycin in Patients Undergoing Extracorporeal Membrane Oxygenation.

To investigate the appropriateness of the current vancomycin dosing strategy in adult patients with extracorporeal membrane oxygenation (ECMO), between March 2013 and November 2013, patients who were treated with vancomycin while on ECMO were enrolled. Control group consisted of 60 patients on vancomycin without ECMO, stayed in medical intensive care unit during the same study period and with the same exclusion criteria. Early trough levels were obtained within the fourth dosing, and maintenance levels were measured at steady state. A total of 20 patients were included in the analysis in ECMO group. Sixteen patients received an initial intravenous dose of 1.0 g vancomycin followed by 1.0 g every 12 hours. The non-steady state trough level of vancomycin after starting administration was subtherapeutic in 19 patients (95.00%) in ECMO group as compared with 40 patients (66.67%) in the control group (p = 0.013). Vancomycin clearance was 1.27±0.51 mL/min/kg, vancomycin clearance/creatinine clearance ratio was 0.90 ± 0.37, and elimination rate constant was 0.12 ± 0.04 h-1. Vancomycin dosingfrequency and total daily dose were significantly increased after clinical pharmacokinetic services of the pharmacist based on calculated pharmacokinetic parameters (from 2.10 ± 0.72 to 2.90 ± 0.97 times/day, p = 0.002 and from 32.54 ± 8.43 to 42.24 ± 14.62mg/kg, p = 0.014) in ECMO group in contrast with those (from 2.11 ± 0.69 to 2.37 ± 0.86 times/day, p = 0.071 and from 33.91 ± 11.85 to 31.61 ± 17.50 mg/kg, p = 0.350) in the control group.Although the elimination rate for vancomycin was similar with population parameter of non ECMO patients, the current dosing strategy of our institution for vancomycinin our ICU was not sufficient to achieve the target trough in the initial period in most patients receiving ECMO.