Novel score for predicting early emergency endovascular therapy in trauma care using logistic LASSO regression.

Aim: To support decision-making for early interventional radiology, this study aimed to derive and validate a novel and simple scoring system for predicting the necessity of interventional radiology therapies in trauma patients. Methods: This retrospective study used data derived from the medical records of patients with severe traumatic injuries treated at a tertiary-level emergency institution. The score was derived from 168 patients treated between April 2015 and October 2016 and validated using data from 68 patients treated between November 2016 and July 2017. Logistic "least absolute shrinkage and selection operator (LASSO)" regression was used to select predictors. In order to compose the score, odds ratios derived from the logistic model were simplified to integer score coefficients. The score was evaluated using the area under the receiver operating characteristic curve. The best cut-off point for the score was determined using Youden's index, and sensitivity and specificity were calculated. Results: The derived score comprised three predictors (systolic blood pressure, positive findings in abdominal ultrasound assessment, and pelvic fracture) and ranged from 0 to 30. On validation, the area under the receiver operating characteristic curve for the score was 0.86 (95% confidence interval, 0.64-1.00). The sensitivity and specificity were 80% and 89%, respectively, with a cut-off point of 3. Conclusion: This simple score, requiring variables obtainable immediately after hospital arrival, could aid in facilitating early interventional radiology team activation.

Effects of temperature alteration on viscosity, polymerization, and in-vivo arterial distribution of N-butyl cyanoacrylate-iodized oil mixtures.

PURPOSE: Temperature alteration can modify the polymerization of n-butyl cyanoacrylate (NBCA)-iodized oil mixtures during vascular embolization; its effects on viscosity, polymerization time, and intra-arterial distribution of the NBCA-iodized oil mixture were investigated. MATERIALS AND METHODS: In vitro, the viscosities of NBCA, iodized oil, and NBCA-iodized oil mixtures (ratio, 1:1-8) were measured at 4-60 ºC using a rotational rheometer. The polymerization times (from contact with blood plasma to stasis) were recorded at 0-60 ºC using a high-speed video camera. In vivo, the 1:2 mixture was injected into rabbit renal arteries at 0, 20, and 60 ºC; intra-arterial distribution of the mixture was pathologically evaluated. RESULTS: The mixtures' viscosities decreased as temperature increased; those at 60 ºC were almost four to five times lower than those at 4 ºC. The polymerization time of NBCA and the 1:1-4 mixtures increased as temperature decreased in the 0-30 ºC range; the degree of time prolongation increased as the percentage of iodized oil decreased. The 0 ºC group demonstrated distributions of the mixture within more peripheral arterial branches than the 20 and 60 ºC groups. CONCLUSION: Warming reduces the mixture's viscosity; cooling prolongs polymerization. Both can be potential factors to improve the handling of NBCA-iodized oil mixtures for lesions requiring peripheral delivery. Temperature alteration influences the polymerization time, viscosity, and intra-arterial distribution of NBCA-iodized oil mixtures. Warming reduces the viscosity of the mixture, while cooling prolongs polymerization.

Hybrid emergency room system improves timeliness of angioembolization for pelvic fracture.

BACKGROUND: Timely angioembolization (AE) is known to improve outcomes of patients with hemorrhage resulting from pelvic fracture. The hybrid emergency room system (HERS) is a novel trauma resuscitation room equipped with a computed tomography scanner, fluoroscopy equipment, and an operating room setup. We hypothesized that the HERS would improve the timeliness of AE for pelvic fracture. METHODS: A retrospective medical record review of patients who underwent AE for pelvic fracture at our institution from April 2015 to December 2018 was conducted. Patients' demographics, location of AE, Injury Severity Score, Revised Trauma Score, probability of survival by the trauma and injury severity score (TRISS Ps) method, presence of interventional radiologists (IRs) upon patient arrival, time from arrival to AE, and in-hospital mortality were analyzed. These data were compared between patients who underwent AE in the HERS (HERS group) and in the regular angio suite (non-HERS group). RESULTS: Ninety-six patients met the inclusion criteria. The HERS group comprised 24 patients, and the non-HERS group, 72 patients. Interventional radiologists were more frequently present upon patient arrival in the HERS than non-HERS group (IRs, 79% vs. 22%, p < 0.01). The time from arrival to AE was shorter in the HERS than non-HERS group (median [range], 46 [5-75] minutes vs. 103 [2-690] minutes, p < 0.01). There were no differences in the rate of in-hospital mortality (13% vs. 15%, p = 0.52) between the two groups. Survivors in the HERS group had a lower probability of survival by the trauma and injury severity score (median [range], 61% [1%-98%] vs. 93% [1%-99%], p < 0.01) than survivors in the non-HERS group. CONCLUSION: The HERS improved the timeliness of AE for pelvic fracture. More severely injured patients were able to survive in the HERS. The new team building involving the addition of IRs to the traditional trauma resuscitation team will enhance the benefit of the HERS. LEVEL OF EVIDENCE: Therapeutic, level IV.

Efficacy of Automated Supplying Artery Tracking Software Using Multidetector-Row Computed Tomography Images for Emergent Transcatheter Arterial Embolization.

PURPOSE: To assess the reliability of a prototype automated supplying artery tracking software (ASATS) using multidetector-row CT (MDCT) images in emergent TAE. MATERIALS AND METHODS: Consecutive 53 patients underwent 57 sessions of emergent TAE during 7 months. Twenty-one cases were excluded due to a lack of CT data (n = 12) or negative angiographic findings (n = 9). Remaining 34 sessions of TAE and MDCT images in 32 patients (mean age 62.9 years; age range 37-92 years) were enrolled. ASATS was retrospectively conducted for the identification of supplying arteries which were confirmed with angiography (automated method). Manual modification was added as needed (semi-automated method). Two observers independently reviewed the MDCT images to detect supplying arteries (manual method). Detectability of supplying artery and time to analysis were compared among the automated, semi-automated, and manual methods by both observers. RESULTS: A total of 64 bleeding sites were demonstrated on angiography. The detectability was 28 (43.8%) for automated method, 53 (82.8%) for semi-automated method, 55 (85.9%) for observer 1, and 58 (90.6%) for observer 2. Detectability of semi-automated method was significantly better than of automated method (P = 0.000) and comparable with manual method by both observers (P = 0.193 and 0.081). Average time to analysis was 185.4 s for automated method, 297.2 s for semi-automated method, 186.2 s for observer 1, and 243.7 s for observer 2. CONCLUSION: ASATS has a sufficient ability to identify supplying arteries of bleeding by adding manual modification as needed and can be used for emergent TAE. LEVEL OF EVIDENCE: Level 4, Case Control Study.

Unilateral cardiogenic pulmonary edema associated with acute mitral regurgitation.

Case: Two cases of cardiogenic unilateral pulmonary edema are reported. Both patients presented to the emergency department with dyspnea, and chest radiography revealed unilateral infiltration, which mimics pulmonary disease. However, the patients were diagnosed with cardiogenic pulmonary edema, because echocardiography showed severe mitral regurgitation with an eccentric jet. Outcome: The patients underwent mitral valve replacement and were discharged without complications. Conclusion: Unilateral cardiogenic pulmonary edema is rare, and early diagnosis and treatment are difficult. Delayed treatment leads to high mortality. The major cause of unilateral pulmonary edema is acute mitral regurgitation, and the direction of the jet is suggested as a mechanism of laterality.

Predictors of Delirium in Corticosteroid-Treated Patients with Advanced Cancer: An Exploratory, Multicenter, Prospective, Observational Study.

BACKGROUND: Corticosteroids are often used to treat fatigue and anorexia, but occasionally produce delirium. Information on the predictors of delirium in corticosteroid-treated cancer patients remains limited. OBJECTIVE: To identify potential factors predicting the development of delirium in corticosteroid-treated cancer patients. DESIGN: An exploratory, multicenter, prospective, observational study. SETTING/SUBJECTS: Inclusion criteria for this study were patients who had metastatic or locally advanced cancer and a fatigue or anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale. MEASUREMENT: Univariate and multivariable analyses were performed to identify the predictors of delirium diagnosed by the Confusion Assessment Method (CAM) within three days of initiation of corticosteroids. RESULTS: Among 207 patients administered corticosteroids, 35 (17%; 95% confidence interval [CI] 12%-23%) developed at least one episode of delirium diagnosed by the CAM. Factors predictive of the development of delirium were as follows: Palliative Performance Scale ≤20, Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 4, the Support Team Assessment Schedule (STAS) score of drowsiness >1, concurrent opioid use, parenteral hydration volume ≤500 mL, and the absence of lung metastasis. A multivariable analysis identified the independent factors predicting responses as ECOG PS = 4 (odds ratio [OR] 4.0; 95% CI 1.7-9.3), STAS score of drowsiness >1 (OR 3.4; 95% CI 1.4-8.2), and concurrent opioid use (OR 3.7; 95% CI 1.0-13). CONCLUSION: Delirium in corticosteroid-treated advanced cancer patients may be predicted by PS, drowsiness, and concurrent opioid use. Larger prospective studies are needed to confirm these results.

Predictors of responses to corticosteroids for anorexia in advanced cancer patients: a multicenter prospective observational study.

PURPOSE: Although corticosteroids are widely used to relieve anorexia, information regarding the factors predicting responses to corticosteroids remains limited. The purpose of the study is to identify potential factors predicting responses to corticosteroids for anorexia in advanced cancer patients. METHODS: Inclusion criteria for this multicenter prospective observational study were patients who had metastatic or locally advanced cancer and had an anorexia intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting ≥2-point reduction in NRS on day 3. RESULTS: Among 180 patients who received corticosteroids, 99 (55 %; 95 % confidence interval [CI], 47-62 %) had a response with ≥2-point reduction. Factors that significantly predicted responses were Palliative Performance Scale (PPS) > 40 and absence of drowsiness. In addition, factors that tended to be associated with ≥2-point reduction in NRS included PS 0-3, absence of diabetes mellitus, absence of peripheral edema, presence of lung metastasis, absence of peritoneal metastasis, baseline anorexia NRS of >6, presence of pain, and presence of constipation. A multivariate analysis showed that the independent factors predicting responses were PPS of >40 (odds ratio = 2.7 [95 % CI = 1.4-5.2]), absence of drowsiness (2.6 [1.3-5.0]), and baseline NRS of >6 (2.4 [1.1-4.8]). CONCLUSIONS: Treatment responses to corticosteroids for anorexia may be predicted by PPS, drowsiness, and baseline symptom intensity. Larger prospective studies are needed to confirm these results.

Predictors of Responses to Corticosteroids for Cancer-Related Fatigue in Advanced Cancer Patients: A Multicenter, Prospective, Observational Study.

CONTEXT: Although corticosteroids are widely used to relieve cancer-related fatigue (CRF), information regarding the factors predicting responses to corticosteroids remains limited. OBJECTIVES: The aim of this study was to identify potential factors predicting responses to corticosteroids for CRF in advanced cancer patients. METHODS: Inclusion criteria for this multicenter, prospective, observational study were patients who had metastatic or locally advanced cancer and had a fatigue intensity score of 4 or more on a 0-10 Numerical Rating Scale (NRS). Univariate and multivariate analyses were conducted to identify the factors predicting two-point reduction or more in NRS on day 3. RESULTS: Among 179 patients who received corticosteroids, 86 (48%; 95% CI 41%-56%) had a response with two-point reduction or more. Factors that significantly predicted responses were performance status score of 3 or more, Palliative Performance Scale score more than 40, absence of ascites, absence of drowsiness, absence of depression, serum albumin level greater than 3 mg/dL, serum sodium level greater than 135 mEq/L, and baseline NRS score greater than 5. A multivariate analysis showed that the independent factors predicting responses were baseline NRS score greater than 5 (odds ratio [OR] 6.6, 95% CI 2.8-15.4), Palliative Performance Scale score more than 40 (OR 4.4, 95% CI 2.1-9.3), absence of drowsiness (OR 3.4, 95% CI 1.7-6.9), absence of ascites (OR 2.3, 95% CI 1.1-4.7), and absence of pleural effusion (OR 2.2, 95% CI 1.0-5.0). CONCLUSION: Treatment responses to corticosteroids for CRF may be predicted by baseline symptom intensity, performance status, drowsiness, and severity of fluid retention symptoms. Larger prospective studies are needed to confirm these results.

A clinical pharmacokinetic microdosing study of docetaxel with Japanese patients with cancer.

PURPOSE: Whether microdosing studies can be used to evaluate the human pharmacokinetics of new anticancer drugs remains unclear. The disposition of docetaxel in cancer patients is linear in terms of dose proportionality. We examined whether the pharmacokinetics of docetaxel in a clinically relevant therapeutic dose could be predicted from the pharmacokinetics of a microdose of docetaxel in Japanese patients with cancer. METHODS: A microdose of docetaxel (100 µg/patient) was given by 5-min intravenous infusion on day 1, followed by a therapeutic dose of docetaxel (60-75 mg m(-2)), given by 1-h intravenous infusion on day 8. Plasma docetaxel was analyzed by liquid chromatography-tandem mass spectrometry. A two-compartment pharmacokinetic model was used to calculate the area under the plasma concentration-time curve from time 0 to infinity (AUC0-inf). RESULTS: Nine patients received both a microdose and therapeutic dose of docetaxel. The AUC0-inf after microdosing was 3640 ± 1150 ng h L(-1), while that after therapeutic dosing adjusted to 100 mg/patient was 2230 ± 757 µg h L(-1). The ratio of docetaxel clearance in therapeutic dose to that in microdose was 1.8 (P = 0.0041). Plasma α1-acid glycoprotein concentrations negatively correlated with docetaxel clearance at therapeutic dose, whereas the trend was weak at microdose. CONCLUSION: Docetaxel clearance showed marginal nonlinearity between microdose and therapeutic dose, presumably because of saturation of plasma protein binding; however, the magnitude was within twofold, allowing practically acceptable extrapolation.

Phase 1 study of pazopanib alone or combined with lapatinib in Japanese patients with solid tumors.

PURPOSE: A phase 1 study of pazopanib alone or in combination with lapatinib was conducted to assess the safety, tolerability, and pharmacokinetics of these oral tyrosine kinase inhibitors in Japanese patients with solid tumors. METHODS: In part A (monotherapy), 7 patients initially received pazopanib 800 mg/day, the recommended dose for non-Japanese patients. Then, 3 patients received pazopanib 400 mg/day on day 1 followed by 800 mg/day from day 2 onward. Three other patients received pazopanib 1,000 mg/day. In part B (combination therapy), 17 patients received pazopanib plus lapatinib (pazopanib/lapatinib) at once-daily doses of 400/1,000 mg (4 patients), 800/1,000 mg (3 patients), 400/1,500 mg (3 patients), and then 600/1,250 mg (7 patients). RESULTS: There was no dose-limiting toxicity during the study. In part A, most drug-related adverse events were grade 2 or lower, including neutropenia/neutrophil count decreased, thrombocytopenia/platelet count decreased, diarrhea, hypertension, aspartate aminotransferase increased, and lipase increased. In part B, rash, decreased appetite, and serum thyroid-stimulating hormone increased also occurred. In all dose groups, the plasma concentrations after multiple doses of pazopanib exceeded the target trough concentration for inhibition of vascular endothelial growth factor receptor-2 activity (20 µg/mL). CONCLUSIONS: The pharmacokinetic profiles of pazopanib and lapatinib in Japanese patients were not apparently different from those reported in non-Japanese patients. There were no consistent trends in pharmacokinetic drug interactions between pazopanib and lapatinib. Pazopanib monotherapy at 800 and 1,000 mg once daily and pazopanib plus lapatinib once daily at any doses studied were well tolerated in Japanese patients.

Methylation of ASC/TMS1, a proapoptotic gene responsible for activating procaspase-1, in human colorectal cancer.

ASC/TMS1, a proapoptotic activator of procaspase-1, was reported to be aberrantly methylated in human breast cancer. We found that ASC was methylated in three of five human colon cancer cell lines lacking ASC protein expression. Demethylation treatment of these cell lines lacking ASC with 5-aza-2'-deoxycytidine partially restored ASC expression. Methylated ASC was also detected in six of ten colorectal cancer tissues. Although clear down-regulation of ASC in the whole region of a tumor tissue was hardly observed by immunostaining with anti-ASC mAb, complete suppression of ASC was identified in a minor population of the colorectal tumor cells. The biological significance of ASC methylation inducible ASC suppression in colorectal cancer will be discussed.

ASC/TMS1, a caspase-1 activating adaptor, is downregulated by aberrant methylation in human melanoma.

ASC/TMS1 is an adaptor protein activating caspase-1 that stimulates processing of proIL-1beta and proIL-18. ASC was reported to be aberrantly methylated and silenced in human breast cancers. In our present study, ASC expression was examined in 12 melanoma cell lines by Western blot analysis and in 18 benign melanocytic nevi and 32 melanoma tissues by immunohistochemical staining. ASC expression was absent or reduced in 7 of 12 (58.3%) cell lines and in 20 of 32 (62.5%) melanoma tissues, whereas all 18 benign melanocytic nevi showed intensive ASC expression. To investigate whether ASC silencing in melanoma is involved in aberrant methylation, methylation specific PCR was carried out. Five of ten (50%) melanoma tissues exhibited methylation in CpG island of ASC companied with reduced ASC expression. Six of twelve (50%) melanoma cell lines showed aberrant methylation in the ASC gene, and 4 of the 6 (66.7%) methylation positive cell lines exhibited reduced ASC expression. We characterized methylation patterns in melanoma cell lines by using bisulfite genomic sequencing, and found that the degree of aberrant methylation correlated with the level of reductive ASC expression. Treatment with demethylating agent 5-aza-2'-deoxycytidine resulted in both demethylation of the ASC gene and the upregulation of ASC expression in the methylation positive melanoma cell lines. Our study shows that ASC is downregulated in melanoma, and that its suppression is partially mediated by aberrant methylation.