Treatment Patterns and Clinical Outcomes Among Patients with Metastatic Non-small Cell Lung Cancer Without Actionable Genomic Alterations Previously Treated with Platinum-Based Chemotherapy and Immunotherapy.

BACKGROUND: For patients with metastatic non-small cell lung cancer, timely molecular testing is essential to determine the appropriate course of therapy. Initial treatment with platinum chemotherapy and/or an immune checkpoint inhibitor (ICI) is the standard of care for patients without actionable genomic alterations. OBJECTIVE: We aimed to assess treatment patterns and clinical outcomes among patients with metastatic non-small cell lung cancer, no actionable genomic alterations, and with prior ICI and platinum-based chemotherapy in a community oncology setting. METHODS: This retrospective observational study examined electronic health records from adult patients with an initial metastatic non-small cell lung cancer diagnosis without actionable genomic alterations from 2017 to 2019. Patients had received a subsequent line of therapy (LOT) [index] after discontinuing platinum-based chemotherapy plus an ICI in the previous one or two LOTs. Patient demographics and clinical characteristics were analyzed descriptively. Clinical outcomes were evaluated using Kaplan-Meier analyses. RESULTS: Among the study population (n = 961), the most common index LOT regimens were non-platinum-based chemotherapies (57.3%), platinum-based chemotherapies (12.9%), ICI-based chemotherapies (12.7%), platinum + ICI-based chemotherapies (9.4%), and other (7.7%). The most common post-index LOT regimens were non-platinum based (61.2%), ICI based (15.3%), platinum based (10.7%), platinum + ICI based (3.2%), and other (2.5%). Median time to treatment discontinuation, time to next treatment, and overall survival were numerically longest with index LOT ICI-based regimens (6.5, 9.9, and 18.9 months, respectively) and shortest with platinum-based regimens (2.8, 5.3, and 8.0 months, respectively) and non-platinum-based regimens (2.6, 5.0, and 7.8 months, respectively). CONCLUSIONS: Among patients with metastatic non-small cell lung cancer without actionable genomic alterations previously treated with platinum + ICIs, non-platinum chemotherapy agents were most commonly prescribed in the index LOT. Clinical outcomes including time to treatment discontinuation, time to next treatment, and overall survival were short, highlighting the unmet need for more effective later-line treatments.

Health care services utilization in patients with ovarian cancer receiving PARP inhibitor maintenance treatment in a US community oncology setting.

OBJECTIVES: The objective of this study was to describe healthcare resource use (HCRU) in addition to treatment patterns and discontinuations, in patients with ovarian cancer (OC) initiating PARP inhibitor (PARPi) maintenance treatment in a US community oncology setting. METHODS: This was a retrospective study of patients with OC initiating PARPi monotherapy maintenance during 01/01/2017 to 06/30/2019 (followed until 12/31/2019). Patients aged ≥18 years at first diagnosis of OC with ≥2 visits within The US Oncology Network were included. Structured and chart review data as well as claims data were used to describe treatment patterns and HCRU. RESULTS: Of the 162 charts reviewed, the median age of patients was 66 years and 80% had stage III or IV disease at diagnosis. In the niraparib, rucaparib and olaparib groups, proportions of patients experiencing dose interruptions were 51%, 50%, and 28%, and discontinuations due to toxicity were 37%, 17% and 15%, respectively. Within the first 6 months, mean numbers of total claims were 43.5, 56.4, and 36.0 in the niraparib, rucaparib, and olaparib groups, and laboratory claims were 13.9, 19.4, and 15.6, respectively. Proportions of patients with hospitalizations (niraparib 40%, rucaparib 32%, olaparib 19%; p = 0.03), also differed as did emergency department visits (niraparib 37%, rucaparib 23%, olaparib 16%; p = 0.02). CONCLUSION: Despite patients initiating niraparib having higher rates of dose management events and toxicity-related discontinuations, outpatient and laboratory utilization were similar across all three PARPi. Adequate monitoring of these medications, with differing toxicities, should be emphasized to potentially decrease dose reductions and toxicities.

Real-world study of patients with locally advanced HNSCC in the community oncology setting.

Introduction: There is a need to understand the current treatment landscape for LA HNSCC in the real-world setting. Methods: This retrospective study assessed real-world outcomes and treatment patterns of 1,158 adult patients diagnosed with locally advanced (stage III-IVB) HNSCC initiating chemoradiotherapy (CRT) within the period January 2015 to December 2017 in a large network of US community oncology practices. Structured data were abstracted from electronic health records. Demographic, clinical and treatment characteristics were analyzed descriptively overall and stratified by index treatment (cisplatin + radiotherapy [RT], cisplatin + other chemotherapy + RT, or cetuximab + RT). Time to next treatment (TTNT) and overall survival (OS) were measured using the Kaplan-Meier method, and median duration of treatment was assessed. OS was compared across treatment cohorts using multinomial logistic regression with inverse probability treatment weighting. To identify covariates associated with OS, a multivariable adjusted Cox proportional hazard model was used. Results: This study examined 22,782 records, of which 2124 had stage III to stage IVB and no other cancers, and 1158 met all eligibility criteria. Among the treatment cohorts analyzed (cisplatin + RT, cisplatin + other chemotherapy + RT, or cetuximab + RT), cisplatin + RT was the most common concurrent chemotherapy (65.8%). Among 1158 patients, 838 (72.4%) did not initiate subsequent treatment and 139 (12.0%) died. The median TTNT and median OS were only reached by the cetuximab + RT cohort. Among patients with oropharynx primary tumor location, patients with human papilloma virus (HPV) positive status had the longest time on treatment and highest survival at 60 months. Covariates associated with improved survival were never/former tobacco use, HPV positive status, and overweight or obese body mass index. Covariates associated with poorer survival were age of 60+ years, primary tumor location of hypopharynx or oral cavity and Eastern Cooperative Oncology Group performance status score of 2+. Conclusion: These data describe real-world treatment patterns in locally advanced head and neck squamous cell cancer and sets the baseline to assess outcomes for future studies on the community oncology population.

The multi-factor analysis of computer-based test scores in objective structured clinical examination of clerkship in school of dentistry, National Taiwan University.

Background/purpose: The objective structured clinical examination (OSCE) is a test designed to test technical, clinical, and practical competency in medicine teaching. This study tried to evaluate the influencing factors of the computer-based tests (CBT) results for dental students. Materials and methods: The 32 5th-year dental students of the dental school of National Taiwan University (NTU) joined preclinical CBT. The contents of CBT included clinical knowledge and practical skills of nine dental specialties. Twenty single-choice questions were played with the PowerPoint 2016 on a desktop, and the playing time for each question was 30 s. Several factors including the gender, age, and dental student admission ways (with or without the skill tests) were evaluated. Also, the comparison between the clerk's grade and CBT scores of nine dental specialties was performed. The students also filled the feedback questionnaire about the examination questions and suggestions for the CBT. Results: There were no significant differences in the mean CBT scores between male and female dental students, between two groups of dental students with or without the skill tests in the admission process, and among three different age groups of dental students. The clerk's scores were not directly related to the CBT scores. Conclusion: The CBT has been well-intentioned in dental education since 2022 in Taiwan. The CBT results revealed that the conjunction of knowledge from the textbook and clinical observation should be enhanced. The guideline should be established to integrate CBT into preclinical education and promote the performance of clinical work of dental students.

The analysis and feedback from the performance of pre-clinical operation skills tests for clerkship in School of Dentistry, National Taiwan University in 2022.

Background/purpose: The simulated pre-clinical operation skill test (PCOST) is part of the objective structured clinical examination (OSCE) and designed for clinical practice using manikins, physical typodonts, and instruments in the laboratory. This study tried to evaluate the influencing factors of the PCOST results for dental students. Materials and methods: The 32 5th-year dental students of the dental school of National Taiwan University (NTU) joined the PCOST. The contents of PCOST included two specialties: operative dentistry (OD) and prosthodontics (PS). The examination content of OD was tooth 36 mesio-occluso-distal (MOD) cavity preparation, and that of PS was crown preparation and temporary crown fabrication of tooth 11. Several factors including the gender, age, and dental student admission ways (with or without the skill tests) were evaluated. Each scoring item was calculated. The students also filled the feedback questionnaire about the examination questions and suggestions for the PCOST. Results: For both OD and PS, there were no significant differences in the mean PCOST scores between male and female dental students, between two groups of dental students with or without the skill tests in the admission process, and among three different age groups of dental students. According to the feedback questionnaire from the participated dental students, they were satisfied with the PCOST. Conclusion: The PCOST is a good simulated examination in clinical practice. However, we still need to collect more PCOST data and feedback to revise the guideline of the PCOST, and to promote the performance of clinical works of dental students.

The influence on surface characteristic and biocompatibility of nano-SnO2-modified titanium implant material using atomic layer deposition technique.

BACKGROUND/PURPOSE: To investigate the surface characteristics of titanium (Ti) implant materials, which were coated with different thicknesses of nanoscale tin oxide (SnO2) using the atomic layer deposition technique, and evaluated its biological performance on human embryonic palatal mesenchyme (HEPM) cells. METHODS: The thickness of the coating layer on Ti was 0 (Ti0), 20 nm (Ti20), 50 nm (Ti50), and 100 nm (Ti100), respectively. The surface morphology was observed with an SEM and AFM. The root mean square roughness of micron-scale (mRq) and nanoroughness (nRq) of Ti discs' surface were measured. The Alamar blue (AB) assay and F-actin fluorescence staining were used to evaluate the biocompatibility, and the osteocalcin (OCN) was measured to clarify the differentiation of HEPM cells on materials. RESULTS: In the coating groups, the mRq was decreased, but the nRq was increased. The spreading and polygonal morphology of HEPMs was apparent in coating groups. On Day 4, the survival rate of HEPM cells on Ti0 was higher than on Ti20 and Ti50. There was no significant difference on Day 7, Day 10, and Day 14. The OCN was significantly higher on Day 14 in all the coating groups than Ti0. CONCLUSION: The results showed that the cell growth was intensified with rough surfaces. However, the OCN and morphology change was prominent when the nanoroughness was increased, which meant the increased nanoroughness might enhance OCN production and improve the tendency of osseointegration. The nanoscale SnO2 coating could increase the ability of bone formation but not cell growth.

Research Trends in Artificial Intelligence-Associated Nursing Activities Based on a Review of Academic Studies Published From 2001 to 2020.

The present study referred to the technology-based learning model to conduct a systematic review of the dimensions of nursing activities, research samples, research methods, roles of artificial intelligence, applied artificial intelligence algorithms, evaluation measure of algorithms, and research foci. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedure, this study obtained and analyzed a total of 102 high-quality artificial intelligence-associated nursing activities studies published from 2001 to 2020 in the Web of Science database. The results showed: (1) In terms of nursing activities, nursing management was explored the most, followed by nursing assessment; (2) quantitative methods were most frequently adopted in artificial intelligence-associated nursing activities studies to investigate issues related to patients, followed by nursing staff; (3) the most adopted roles of artificial intelligence in artificial intelligence-associated nursing activities studies were profiling and prediction, followed by assessment and evaluation; (4) artificial intelligence-associated nursing activities studies frequently mixed applied artificial intelligence algorithms and evaluation measure of algorithms; (5) in the dimension of research foci, most studies mainly paid attention to the design or evaluation of the artificial intelligence systems/instruments, followed by investigating the correlation and affect issues. Based on the findings, several recommendations are raised as a reference for future researchers, educators, and policy makers.

Treatment patterns and outcomes in metastatic synovial sarcoma: a real-world study in the US oncology network.

Aim: To examine and understand patient characteristics, treatment patterns and outcomes for patients with metastatic synovial sarcoma (mSS) treated in a US community setting. Materials & methods: Retrospective observational study in adults with mSS in The US Oncology Network (diagnosed January 2012-December 2018). Results: Of 202 patients diagnosed with synovial sarcoma (SS), 71 had mSS. Of 39 patients with mSS who received first-line (1L) systemic treatment, 25 and 16 continued to 2L and 3L+ treatment, respectively. With each subsequent treatment line, time-to-treatment-discontinuation (1L-3L: 3.9-2.7 months) and time-to-next-treatment (1L-3L: 9.3-4.6 months) decreased. At 1L, median overall survival was 24.5 months. Conclusion: This study highlights the ongoing need for effective therapies for mSS.

Synovial sarcoma (SS) is a rare and aggressive type of soft tissue sarcoma (STS), a group of rare cancers that start in the soft tissues, such as muscle, tendons, fat, lymph and blood vessels and nerves. Usually STS presents in one location, and frequently spreads to other locations, referred to as metastatic SS (mSS). Many studies have explored the characteristics, treatments and outcomes of people with STS. Yet, a limited number of studies have been performed specifically for people with mSS. This study aims to describe characteristics, treatment patterns and clinical outcomes of people with mSS treated in a US community setting. The study showed that more than a third of people diagnosed with SS had disease that spread, mostly to the lung. Of the 71 people with mSS included in the analysis, 39 people received chemotherapy. Of these, 25 people with mSS needed second-line chemotherapy and a further 16 people with mSS required third-line treatment. People with mSS who did not respond well to chemotherapy received a variability of treatments in the US community setting. More lines of treatment were associated with shorter time-to-next-treatment and reduced survival time. Together, these findings highlight the burden of illness and the need for more effective treatments for people with this rare disease. Investigating the characteristics, treatment patterns and clinical outcomes of people with mSS can help to understand the unmet need in this population and pave the way to improving future treatment approaches.

Er:YAG laser irradiation enhances bacterial and lipopolysaccharide clearance and human gingival fibroblast adhesion on titanium discs.

To investigate the effect of Er:YAG laser treatment on lipopolysaccharide (LPS) clearance and fibroblast adhesion on titanium disks. Grade IV titanium discs (n = 216) were used and allocated to 6 groups. Group 1 was the negative control without Porphyromonas gingivalis inoculation. Discs in Groups 2-6 were incubated with P. gingivalis to form a biofilm. Group 3 received 0.12% chlorhexidine irrigation and Group 4 received titanium curettage to remove the biofilm. Group 5 was treated with Er:YAG laser irradiation and Group 6 was treated with titanium curettage plus Er:YAG laser irradiation. The contact angle and surface roughness were measured after the various treatments. The surface microstructure and residual bacteria were examined using scanning electron microscopy and confocal laser scanning microscopy, respectively. Residual LPS was examined using a limulus amoebocyte lysate assay and human gingival fibroblast adhesion was quantified using fluorescent microscopy. Curettage plus Er:YAG laser irradiation was the most effective method for removing bacteria and LPS. No significant difference in the amount of fibroblast adhesion was found between the control and Group 6. Combined use of Er:YAG laser irradiation and curettage optimizes LPS clearance and fibroblast adhesion on titanium discs.

Understanding Contemporary Molecular Biomarker Testing Rates and Trends for Metastatic NSCLC Among Community Oncologists.

INTRODUCTION: Although guidelines recommend testing for actionable biomarkers for patients with advanced or metastatic non-small cell lung cancer (NSCLC), testing rates have varied. This study aimed to assess molecular testing patterns in a large network of US community-based oncology practices. METHODS: This retrospective observational study examined adult patients with newly diagnosed stage IV NSCLC with ≥ 2 visits in The US Oncology Network from July 1, 2016 to September 30, 2019. Testing patterns were examined using electronic health record structured fields and chart review. Structured data were analyzed for the overall study population (cohort A), and structured and unstructured data were analyzed for a select cohort of 300 patients (cohort B). RESULTS: In cohort A (n = 3337), programmed death ligand 1 (37%) was the most frequently tested biomarker documented in structured data, followed by epidermal growth factor receptor (36%), anaplastic lymphoma kinase (35%), ROS1 (20%), and BRAF (16%). According to unstructured data in cohort B (n = 300), epidermal growth factor receptor (80%) was the most frequently tested biomarker, followed by anaplastic lymphoma kinase (79%), programmed death ligand 1 (72%), ROS1 (71%), and BRAF (56%). The proportion of tests ordered prior to first-line (1L) treatment increased from 2016 to 2018 for all biomarkers, as did the proportion of test results available prior to 1L treatment. However, some of the test results became available after 1L or later lines of treatment were in progress. CONCLUSION: Our study found increased testing rates over time and decreases in testing turnaround times. However, rates of testing for all biomarkers still need to improve, as does completion of testing prior to initiation of therapy.

The effects of low-dose 2-hydroxyethyl methacrylate on apoptosis and survival in human dental pulp cells.

BACKGROUND/PURPOSE: 2-hydroxyethyl methacrylate (HEMA) is one of the most major components in dentin bonding systems. Uncured HEMA is eluted through the dentin and harmful to pulp cells. The study aimed to investigate the death pattern, morphological change and factors of human dental pulp cells (HDPCs) cultured with low-dose HEMA. METHODS: HDPCs were cultured with low-dose concentration of HEMA at 0 mM (control), 0.125 mM, 0.25 mM, 1 mM, 2 mM and 4 mM on Day 3 and 5. The cell morphology was observed with F-actin immunocytochemical staining. The flow cytometry was used to analyze the death pattern. NF-κB and Trx-1 were measured using ELISA kits. RESULTS: The major death pattern was early apoptosis and late apoptosis. The morphological characteristics of apoptosis were observed clearly at 4 mM on Day 3 and Day 5. The phosphorylated NF-κB normalized to total NF-κB protein was significantly higher at 2 mM and 4 mM on Day 5. There was no difference of Trx-1 on Day 3, but significantly higher at 0.25 mM and 1 mM on Day 5. The trend line of phosphorylated NF-κB and Trx-1 showed highly positive correlations with HEMA concentration. CONCLUSION: The significant cellular morphology characteristics of apoptosis can be observed at higher dose and longer period after exposed to uncured HEMA. The expression of NF-κB was following the ratio of late apoptosis at longer exposure period. Clinically, the remaining dentin thickness should be enough to decrease HEMA concentration and thus to protect pulp cells free from harm.

7-Ketocholesterol induces ATM/ATR, Chk1/Chk2, PI3K/Akt signalings, cytotoxicity and IL-8 production in endothelial cells.

Cardiovascular diseases (atherosclerosis, stroke, myocardiac infarction etc.) are the major systemic diseases of elder peoples in the world. This is possibly due to increased levels of oxidized low-density lipoproteins (oxLDLs) such as 7-ketocholesterol (7-KC) and lysophosphatidylcholine (LPC) that damage vascular endothelial cells, induce inflammatory responses, to elevate the risk of cardiovascular diseases, Alzheimer's disease, and age-related macular degeneration. However the toxic effects of 7-KC on endothelial cells are not known. In this study, 7-KC showed cytotoxicity to endothelial cells at concentrations higher than 10 µg/ml. 7-KC stimulated ATM/Chk2, ATR-Chk1 and p53 signaling pathways in endothelial cells. 7-KC also induced G0/G1 cell cycle arrest and apoptosis with an inhibition of Cyclin dependent kinase 1 (Cdk1) and cyclin B1 expression. Secretion and expression of IL-8 in endothelial cells were stimulated by 7-KC. 7-KC further induced intracellular ROS production as shown by increase in DCF fluorescence and Akt phosphorylation. LY294002 attenuated the 7-KC-induced apoptosis and IL-8 mRNA expression of endothelial cells. These results indicate that oxLDLs such as 7-KC may contribute to the pathogenesis of atherosclerosis, thrombosis and cardiovascular diseases by induction of endothelial damage, apoptosis and inflammatory responses. These events are associated with ROS production, activation of ATM/Chk2, ATR/Chk1, p53 and PI3K/Akt signaling pathways.

Economic impact of disease progression following front-line therapy in classical Hodgkin lymphoma.

The current study aimed to assess the economic burden of progressive disease among patients with Hodgkin lymphoma (HL) receiving second- or third-line therapy in a large US network of community-based practices. This retrospective, observational cohort analysis used electronic health records to examine adult patients with classical HL who received chemotherapy between 2007 and 2011. Of 291 observations, 112 had non-progressive disease (received only one line of therapy; LOT1), 114 received second-line therapy (LOT2), and 65 received third-line therapy (LOT3). In LOT2, 49 patients (43%) underwent transplant. In LOT3, 13 patients (20%) underwent transplant. The mean total cost per line of therapy was $21 956 in LOT1, $77 219 in LOT2, and $59 442 in LOT3. When transplant was required, the mean total cost per line of therapy increased 7- to 8-fold when compared with the cost of LOT1 (approximately $154 000 for LOT2 and $193 000 for LOT3). Future therapies that intervene as early as possible in the treatment algorithm to prevent or significantly delay relapse will likely result in significant cost savings.

Effect of dentin bonding agent diffusing through dentin slices on the reactive oxygen species production and apoptosis of pulpal cells.

BACKGROUND/PURPOSE: Dentin bonding agents (DBAs) are cytotoxic to dental pulp cells. This study aimed to evaluate the effects of three DBAs (Optibond Solo Plus, Op; Clearfil SE Bond, SE; and Xeno III, Xe) after diffusion through 0.2-mm or 0.5-mm dentin slices on reactive oxygen species (ROS) production and apoptosis in dental pulp cells. METHODS: The amounts of DBAs diffusing through 0.2-mm or 0.5-mm dentin slices were quantified using a UV-Vis spectrophotometer. The effects of diffused DBAs on ROS production and viability of dental pulp cells were investigated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay on Days 1 and 2. Flow cytometric analysis and double staining of treated dental pulp cells with Annexin V-fluorescein isothiocyanate (V-FITC) and propidium iodide (PI) were performed on Day 2. RESULTS: Xe showed greatest diffusion through dentin slices after 8-hour period, followed by SE and Op. Dental pulp cells produced a lesser amount of ROS, when treated with DBAs diffusing through a 0.5-mm dentin slice than through a 0.2-mm dentin slice for the same period of time. A small proportion of cells were TUNEL-positive after treatment with any of the three diffused DBAs. Annexin V-FITC/PI staining identified apoptotic cells; cell survival was higher in those cells treated with DBAs diffusing through a 0.5-mm dentin slice than through a 0.2-mm dentin slice. CONCLUSION: The three DBAs after diffusion through 0.2- or 0.5-mm dentin slice still exhibit cytotoxicity to dental pulp cells. However, the 0.5-mm dentin slice is found to be a better barrier than the 0.2-mm dentin slice to protect dental pulp cells from DBA-induced cytotoxicity.

p-Cresol affects reactive oxygen species generation, cell cycle arrest, cytotoxicity and inflammation/atherosclerosis-related modulators production in endothelial cells and mononuclear cells.

AIMS: Cresols are present in antiseptics, coal tar, some resins, pesticides, and industrial solvents. Cresol intoxication leads to hepatic injury due to coagulopathy as well as disturbance of hepatic circulation in fatal cases. Patients with uremia suffer from cardiovascular complications, such as atherosclerosis, thrombosis, hemolysis, and bleeding, which may be partly due to p-cresol toxicity and its effects on vascular endothelial and mononuclear cells. Given the role of reactive oxygen species (ROS) and inflammation in vascular thrombosis, the objective of this study was to evaluate the effect of p-cresol on endothelial and mononuclear cells. METHODS: EA.hy926 (EAHY) endothelial cells and U937 cells were exposed to different concentrations of p-cresol. Cytotoxicity was evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5 -diphenyltetrazolium bromide (MTT) assay and trypan blue dye exclusion technique, respectively. Cell cycle distribution was analyzed by propidium iodide flow cytometry. Endothelial cell migration was studied by wound closure assay. ROS level was measured by 2',7'-dichlorofluorescein diacetate (DCF) fluorescence flow cytometry. Prostaglandin F2α (PGF2α), plasminogen activator inhibitor-1 (PAI-1), soluble urokinase plasminogen activator receptor (suPAR), and uPA production were determined by Enzyme-linked immunosorbant assay (ELISA). RESULTS: Exposure to 100-500 µM p-cresol decreased EAHY cell number by 30-61%. P-cresol also decreased the viability of U937 mononuclear cells. The inhibition of EAHY and U937 cell growth by p-cresol was related to induction of S-phase cell cycle arrest. Closure of endothelial wounds was inhibited by p-cresol (>100 µM). P-cresol (>50 µM) also stimulated ROS production in U937 cells and EAHY cells but to a lesser extent. Moreover, p-cresol markedly stimulated PAI-1 and suPAR, but not PGF2α, and uPA production in EAHY cells. CONCLUSIONS: p-Cresol may contribute to atherosclerosis and thrombosis in patients with uremia and cresol intoxication possibly due to induction of ROS, endothelial/mononuclear cell damage and production of inflammation/atherosclerosis-related molecules.

Biocompatibility and cytotoxicity of two novel low-shrinkage dental resin matrices.

BACKGROUND/PURPOSE: To reduce the polymerization shrinkage of dental composite resin, we used two different ratios of toluene 2,4-diisocyanate (TDI) or 1,6-hexamethylene diisocyanate (HDI) as functional side chains of bisphenol A-glycidyl methacrylate (bis-GMA) to synthesize two series of new dental resin matrices. This study evaluated the biocompatibility and cytotoxicity of these two series of new resin matrices. METHODS: Two series of new dental resin matrices with the ratios of TDI or HDI functional side chain to bis-GMA (defined as B group) being 1:4, 1:2, 1:1 and 3:2 (defined as T1/4, T1/2, T1, T3/2, and H1/4, H1/2, H1, H3/2 groups, respectively) were synthesized. Each resin sample was light cured and immersed in the culture medium for 24 hours to make the extract solution. Then, human gingival fibroblasts were cultured in different extract solutions for 72 hours. The cytotoxicities of different resins were evaluated by microtitertetrazolium (MTT) assay, the levels of cell-produced reactive oxygen species (ROS) induced by different extract solutions was measured. RESULTS: Resins of the T1/4 and B groups revealed significantly higher cytotoxicity than resins of other groups. However, resins of the T1 and T3/2 groups exhibited less cytotoxicity. In general, resins of the TDI-modified groups showed equal or less cytotoxicity and induced equal or lower levels of ROS than the corresponding resins of the HDI-modified and B groups. CONCLUSION: Our results showed that the TDI-modified resin matrices containing more functional side chains were less cytotoxic than the corresponding HDI-modified resin matrices. When the ratio of functional side chain to bis-GMA is increased, the stereo hindrance of resin structure is increased, more toxic resin monomers are trapped in the complicated resin structure, and thus the resin matrix reveals less cytotoxicity. The TDI-modified resin matrices exhibit higher stereo hindrance of resin structure and thus show less cytotoxicity than the corresponding HDI-modified resin matrices.

Epidemiology, treatment patterns, and outcomes of metastatic soft tissue sarcoma in a community-based oncology network.

Purpose. To assess epidemiology, treatment patterns, and outcomes of metastatic soft tissue sarcoma (mSTS) patients in USA community oncology practices. Methods. This retrospective, descriptive study used US Oncology's iKnowMed electronic health records database. Adults (≥18 years) with mSTS and at least two visits between July 2007 and June 2010 were included. Key outcomes were practice patterns, overall survival (OS), and progression-free survival (PFS). Results. 363 mSTS patients (174 treated and 189 untreated) met the prespecified exclusion/inclusion criteria. The most common subtypes were leiomyosarcoma (n = 104; 29%), liposarcoma (n = 40; 11%), and synovial sarcoma (n = 12; 3%); the remainder (n = 207; 57%) comprised 27 histologic subtypes. Treated patients were younger and had lower ECOG scores; 75% and 25% received first-line combination or monotherapy, respectively. Median OS of treated and untreated patients was 22 and 17 months, respectively, and 29 months in patients with the three most common subtypes. Before controlling for effects of covariates, younger age and lower ECOG scores were associated with better OS and PFS. Conclusion. This study provides insights into mSTS epidemiology, treatment patterns, and outcomes in a large community-based oncology network. These results warrant further studies with larger cohorts.

Conjugation of diisocyanate side chains to dimethacrylate reduces polymerization shrinkage and increases the hardness of composite resins.

BACKGROUND/PURPOSE: Polymerization shrinkage is one of the main causes of dental restoration failure. This study tried to conjugate two diisocyanate side chains to dimethacrylate resins in order to reduce polymerization shrinkage and increase the hardness of composite resins. METHODS: Diisocyanate, 2-hydroxyethyl methacrylate, and bisphenol A dimethacrylate were reacted in different ratios to form urethane-modified new resin matrices, and then mixed with 50 wt.% silica fillers. The viscosities of matrices, polymerization shrinkage, surface hardness, and degrees of conversion of experimental composite resins were then evaluated and compared with a non-modified control group. RESULTS: The viscosities of resin matrices increased with increasing diisocyanate side chain density. Polymerization shrinkage and degree of conversion, however, decreased with increasing diisocyanate side chain density. The surface hardness of all diisocyanate-modified groups was equal to or significantly higher than that of the control group. CONCLUSION: Conjugation of diisocyanate side chains to dimethacrylate represents an effective means of reducing polymerization shrinkage and increasing the surface hardness of dental composite resins.

Evaluating use characteristics for the oncotype dx 21-gene recurrence score and concordance with chemotherapy use in early-stage breast cancer.

PURPOSE: Oncotype Dx 21-gene assay recurrence score (RS) predicts recurrence of early-stage breast cancer (ESBC). We investigated whether patient, tumor, or practice characteristics drive its use and explored Oncotype DX RS and chemotherapy use in subgroups. METHODS: Patients with ESBC with documented estrogen receptor-positive, lymph node-negative, human epidermal growth factor receptor 2-negative tumors registered within McKesson Specialty Health's iKnowMed electronic health record were included. Patient and practice characteristics by region and size were analyzed. The association between Oncotype DX RS value and use of chemotherapy were assessed. RESULTS: The study included 6,229 patients. Of these, 1,822 (29%) had an Oncotype DX RS result. Test use was 36%, 38%, 34%, 25%, and 6%, respectively, in patients age ≤ 45, 46-55, 56-65, 66-75, and ≥ 76 years; 33%, 25%, and 9% in patients with Eastern Cooperative Oncology Group performance status of 0, 1, and ≥ 2; 7%, 9%, 25%, 38%, 27%, and 10% in T1mic, T1a, T1b, T1c, T2, and T3 tumors; and 26%, 32%, and 33% for grades 1, 2, and 3 tumors. Of the 1,822 patients with available Oncotype DX RS, adjuvant chemotherapy use was 6%, 42%, and 84% in the low-, intermediate-, and high-risk groups. CONCLUSION: Patients who were younger, had better ECOG performance status, or had higher grade tumors were more likely to undergo RS testing. It appears that the RS test may have influenced the decision about whether to administer adjuvant chemotherapy: a low RS score was associated with lower chemotherapy use and a high RS score was associated with higher chemotherapy use.