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.

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.

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.

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.

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.

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.

Comparison of ramosetron's and ondansetron's preventive anti-emetic effects in highly susceptible patients undergoing abdominal hysterectomy.

BACKGROUND: This study compared the preventive effects of ramosetron and ondansetron on postoperative nausea and vomiting (PONV) in highly susceptible patients undergoing abdominal hysterectomy. METHODS: In a prospective, randomized, double-blinded study, a total of 120 highly susceptible women (nonsmokers, those receiving opioid-based IV patient-controlled analgesia [PCA]) undergoing abdominal hysterectomy were included in the study. Patients were divided into 2 groups and each group received either 0.3 mg of ramosetron or 4 mg of ondansetron, IV. All patients received fentanyl-based IV PCA during the 48 h postoperative periods. The incidences of PONV and side effects of 5-HT(3) antagonists (headache and dizziness) were assessed at 3 intervals (<2 h, 2-24 h and 24-48 h) postoperatively. RESULTS: Patients in the ramosetron group showed a significantly higher ratio of complete response and lower incidence of nausea during the 24-48 h interval after surgery compared with those the ondansetron group. CONCLUSIONS: Ramosetron (0.3 mg) is more effective in preventing delayed PONV in highly susceptible women undergoing abdominal hysterectomy compared with ondansetron (4 mg).

Effects of preoxygenation with the three minutes tidal volume breathing technique in the elderly.

BACKGROUND: Preoxygenation with tidal volume breathing for 3 min is commonly used technique. An end tidal expiratory oxygen concentration greater than 90% is considerd to be adequate for preoxygenation. The aim of this study was to check the effects of preoxygenation on elderly patients through the comparison with young patients during the 3 min tidal volume breathing technique. METHODS: Sixty patients from ASA class I or II who were scheduled for elective orthopedic general surgery were divided into an elderly (>65 yr) group and a control (25-65 yr) group. Patients were instructed in the technique of preoxygenation. Preoxygenation was accomplished with an appropriately sized face mask connected to an anesthesia machine with 100% oxygen during 3 min with patients in both groups. Expired O(2), CO(2) concentration and oxygen saturation were recorded simultaneously for 3 min. RESULTS: The elderly group showed significantly lower end tidal oxygen concentration than the control group from 50 sec to the end of study (180 sec) with the 3 min tidal volume breathing technique (P < 0.05). In 180 sec, the control group had over 90% (91.5%) end tidal oxygen concentration, but in the elderly group end tidal oxygen concentration could not reach 90% (86.2%). In oxygen saturation, the elderly group showed a significantly lower level until 40 sec from the start of study, and then two groups showed a similar levels of oxygen saturation until the end of study. CONCLUSIONS: End tidal oxygen concentration did not reach 90% in 180 sec in the elderly group during preoxygenation with the 3 min tidal volume breathing technique.

The optimal preemptive dose of gabapentin following gynecologic surgery.

BACKGROUND: Gabapentin decreases acute nociceptive pain in animal and human studies when given before surgical incision. Various doses of gabapentin have been used (300-1,200 mg) to measure this preemptive effect. Here, we evaluated the optimal dose of gabapentin for reducing fentanyl consumption and the adverse effects of gabapentin following gynecologic surgery. METHODS: We recruited 100 patients who underwent laparotomy for gynecologic surgery. Patients were randomly divided into 4 groups and received a placebo (control), gabapentin 300 mg (G 300), gabapentin 600 mg (G 600), or gabapentin 1,200 mg (G 1200) 2 h before surgery. Postoperatively, patients received fentanyl via an intravenous patient controlled analgesia device. The cumulative fentanyl doses were recorded 2, 6, 12, 24 h, and 48 h postoperatively, and the sedation scale was recorded in the post anesthetic care unit (PACU). RESULTS: The postoperative fentanyl requirement was lower with gabapentin treatment, but there was no significant differences for the different doses. PACU sedation scores were not different in any group. CONCLUSIONS: Gabapentin has a preemptive effect in gynecologic surgery, but there were no additional fentanyl-sparing benefits at doses above 300 mg. Thus, 300 mg is an optimal dose for decreasing fentanyl consumption following gynecologic surgery.

Common peroneal nerve palsy after robotic assisted laparoscopic colectomy: A case report.

Common peroneal nerve palsy after surgery with lithotomy position has been widely reported, but it is an unexpected complication after surgery with supine position. We report a patient who developed common peroneal nerve palsy after surgery with supine position. A 55-year old man is planed for robotic assisted laparoscopic right hemicolectomy because of colon cancer. The patient was placed supine with Trendelenburg position at an angle about 5 degrees and tilted left about 15 degrees. The operation is uneventful, but he developed common peroneal nerve palsy on the first postoperative day. The patient was fully recovered with conservative treatment after 2 months. We consider that nerve palsy as a result of compression of common peroneal nerve related to patient positioning. So we should be careful not to develop common peroneal nerve palsy even if the patient was placed in the supine position during robotic assisted surgery.