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To evaluate and compare the clinical efficacy of transabdominal ultrasound-guided percutaneous microwave ablation (PMWA) in the treatment of symptomatic focal and nonfocal adenomyosis.Retrospective cohort study.Longyan First Affiliated Hospital of Fujian Medical University.From May 2019 to October 2021, 107 patients with symptomatic adenomyosis who refused hysterectomy received PMWA.Patients were divided into a focal group (n = 47, including 40 focal adenomyosis and 7 adenomyoma cases) and a nonfocal group (n = 60, including 36 diffuse and 24 mixed adenomyosis cases) according to the extent of lesion involvement.We collected and analyzed preoperative baseline data on patient characteristics; postoperative efficacy measures at 3, 6, and 12 months; and intraoperative and postoperative complications. There was a significant post-treatment reduction in the uterine corpus volume and cancer antigen 125 levels, an increase in hemoglobin levels, and an improvement in the Uterine Fibroid Symptom and Health-related Quality of Life scores (consisting of the Symptom Severity Scale and the Health-related Quality of Life scale), dysmenorrhea visual analog scale, and menstrual volume score (MVS) (all p.05). One patient had recurrence. Most adverse events (72.0%) were mild. Although the nonfocal group had significantly greater anemia severity, higher Symptom Severity Scale and MVS, lower Health-related Quality of Life scale, greater extent and severity of myometrial involvement, and larger uterine corpus volume, after treatment, the uterine corpus volume, uterine corpus reduction rate, cancer antigen 125 levels, hemoglobin levels, Uterine Fibroid Symptom and Health-related Quality of Life score, dysmenorrhea visual analog scale, MVS score, and clinical response rate were similar between the groups (p.05).PMWA had good, similar, short-term efficacy for symptomatic focal and nonfocal adenomyosis.

Approximately 15% of patients with non-small cell lung cancer (NSCLC) harbor an epidermal growth factor receptor mutation (EGFRm). Mutation testing (including EGFRm) is recommended for patients with advanced NSCLC (aNSCLC) prior to initiating first-line therapy (L1) or after progression on targeted therapy. To elucidate current and future unmet needs, the present study characterized real-world EGFR testing patterns and treatment patterns in patients with aNSCLC.This retrospective observational cohort study evaluated newly diagnosed adult patients with aNSCLC (stage IIIB or higher) from the Flatiron Health database. Eligible patients received at least L1 during 2015-2020 (testing cohorts) or 2011-2020 (treatment cohorts). Eligible patients for the treatment cohorts had an EGFR mutation.The testing cohort included 22,726 patients, 75.5% had at least one EGFR test and 15.2% of those tested were positive for EGFR mutation. From 2015 to 2020, the median time from sample collection to test results decreased substantially while the proportion of NGS EGFR tests and use of plasma samples increased. The treatment cohort included 3701 patients (95% common mutations [cEGFR], 5.0% exon 20 insertions [ex20ins]). Three or more lines of therapy (LOTs) were observed in approximately 30% of patients. For L1, most cEGFR patients received EGFR tyrosine kinase inhibitors (EGFR-TKI, 68.1%) or platinum-based chemotherapy (PBC, 24.8%); most ex20ins patients received PBC (66.1%) or EGFR-TKI (17.5%). The most common L2 was EGFR-TKI (54.1%) or PBC (22.8%) for cEGFR and immunotherapy (25.9%) or PBC (25.9%) for ex20ins. No predominant L3 was evident in either group.This real-world study, among the largest analyses of testing patterns for patients with aNSCLC, demonstrates a comprehensive view of treatment patterns for patients with EGFR mutations, including ex20ins. Despite recent improvement, increased use of EGFR testing, including advanced methods, is needed to optimize treatment pathways and outcomes. Additionally, the lack of a predominant therapy in later lines indicates a need for new therapies.

This study compared the feasibility and efficacy of transabdominal ultrasound (TAU) and combined transabdominal and transvaginal ultrasound (TA/TV US)-guided percutaneous microwave ablation (PMWA) for uterine myoma (UM).This study enrolled 73 patients with UM who underwent PMWAIn the TA/TV group, the real-time position of the needle tip and the endometrium complete display rate of the same lesions with TVU guidance were significantly higher than those using TAU. TA/TV US guidance significantly improved the complete display rate of each indicator. The intraoperative supplementary ablation rate in the TA/TV group was lower than that in the TA group. Similarly, the postoperative immediate ablation and volume reduction rates of the lesions three months postoperatively were higher than those in the TA group, especially for lesions with a maximum diameter ≥6 cm.TA/TV US is an effective monitoring method that can be used to improve imaging display. Its use is recommended in patients with obesity, poor transabdominal ultrasound image quality and large myoma volumes.

Introduction Nonvalvular atrial fibrillation (NVAF) is associated with a substantial economic burden, particularly in patients with comorbid conditions. This study compared healthcare resource utilization (HRU) and costs of rivaroxaban and warfarin in patients with NVAF, obesity, and diabetes. Methods A de-identified healthcare claims database was used to identify adult patients newly initiating rivaroxaban or warfarin and having at least one medical claim with a diagnosis of AF, obesity determined by validated algorithm, and at least one claim with a diagnosis of diabetes or for antidiabetic medication from December 2011 to March 2020. Propensity score matching was used to balance the treatment cohorts on the basis of demographics and baseline characteristics. All-cause and NVAF-related HRU rates and costs were compared between treatments using rate ratios, and mean cost differences were calculated on a per patient per year (PPPY) basis. Results A total of 9999 matched pairs of patients with NVAF, obesity, and diabetes were identified in the rivaroxaban and warfarin cohorts. Rate ratios of all-cause HRU were significantly reduced with rivaroxaban versus warfarin in all healthcare settings evaluated, except emergency room visits. The greatest impact was on physician office visits followed by hospital outpatient and inpatient visits. NVAF-related HRU was significantly lower for rivaroxaban versus warfarin in all care settings. Consistent with these findings, the length of hospital stay was significantly reduced by approximately 4 days among all patients for both all-cause and NVAF-related hospitalizations in the rivaroxaban cohort compared with the warfarin cohort. Rivaroxaban was associated with reductions in all-cause total healthcare costs by more than $5000 PPPY and NVAF-related medical costs by approximately $1100 PPPY. Conclusion In comparison with warfarin, rivaroxaban reduced HRU and costs, particularly hospital inpatient and outpatient visits and physician office visits, in patients with NVAF and comorbidities of obesity and diabetes. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01161-4., Plain Language Summary People who are overweight or obese are at risk of developing atrial fibrillation (AF) along with other medical conditions, such as diabetes. Standard therapy with oral anticoagulants or blood thinners is recommended to reduce the risk of stroke and systemic embolism in patients with nonvalvular AF (NVAF). In this study, we evaluated healthcare insurance claims for people with NVAF, obesity, and diabetes who started therapy with warfarin or rivaroxaban from 2011 to 2020 to compare the use and cost of healthcare services, such as hospitalizations and doctor visits, using diagnosis and procedure codes. The study included nearly 20,000 patients with similar characteristics. Patients who started treatment with rivaroxaban used fewer healthcare services for any cause and for those related to NVAF than those who started treatment with warfarin. The difference in use of services was largest for hospital outpatient and inpatient visits and doctor office visits; emergency room visits were only different for those related to NVAF. Length of hospital stay was also shorter for patients receiving rivaroxaban versus those receiving warfarin. These differences in healthcare service use translated into lower costs associated with rivaroxaban versus warfarin. The findings of this study suggest that treatment with rivaroxaban reduces the use of healthcare services compared with warfarin. This difference may be related, in part, to the reduced risks of stroke and systemic embolism observed in other real-world studies with rivaroxaban compared to warfarin. In addition, rivaroxaban does not require routine blood testing, which is required with warfarin treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01161-4.

Introduction Multiple myeloma (MM) is a malignancy of plasma cells; most MM patients will eventually relapse or become refractory to treatment. Treating MM patients remains a challenge since patients eventually progress through several lines of therapy (LOTs), requiring the use of multiple MM drug classes. We examined healthcare resource utilization (HCRU) and the costs incurred by MM patients following triple class exposure (TCE; defined as exposure to a proteosome inhibitor, an immunomodulatory agent, and an anti-CD-38 antibody). Methods Adult MM patients were selected from the MarketScan® commercial and Medicare supplemental databases (January 2009–February 2021). From this cohort, patients who had TCE and ≥ 1 subsequent LOT that occurred after January 1, 2017 were included in the study population. The initiation date for the first post-TCE LOT was defined as the index date. All-cause and MM-related HCRU and the associated costs were examined post-index date. Results A total of 85 MM patients with TCE who initiated ≥ 1 subsequent LOT post-TCE and had ≥ 1 year of follow-up post-index date were included in the study population; mean age on index date was 58.8 years, and 60.0% were male. The time from first-observed MM diagnosis until index date averaged 47.5 months. During an average follow-up of 20.9 months post-index date, 64.7% of patients (N = 55) initiated a second LOT and 35.2% (N = 30) received at least 3 LOTs. During follow-up, mean total all-cause healthcare cost per patient was $722,992 (equivalent to $34,578 per patient per month [PPPM]). Approximately 90.7% ($655,524 per patient) of the total all-cause healthcare costs were MM related, 66.0% of which were MM drug/infusion costs. Conclusion In this real-world US study, MM patients with TCE incurred high healthcare costs, with the majority being MM related and primarily attributed to MM drug and infusion costs. Supplementary Information The online version contains supplementary material available at 10.1007/s40487-021-00175-z.

The Brassicaceae is an important plant family. We built a user-friendly, web-based, comparative, and functional genomic database, The Brassicaceae Genome Resource (TBGR, http://www.tbgr.org.cn), based on 82 released genomes from 27 Brassicaceae species. The TBGR database contains a large number of important functional genes, including 4,096 glucosinolate genes, 6,625 auxin genes, 13,805 flowering genes, 36,632 resistance genes, 1,939 anthocyanin genes, and 1,231 m6A genes. A total of 1,174,049 specific guide sequences for clustered regularly interspaced short palindromic repeats and 5,856,479 transposable elements were detected in Brassicaceae. TBGR also provides information on synteny, duplication, and orthologs for 27 Brassicaceae species. The TBGR database contains 1,183,851 gene annotations obtained using the TrEMBL, Swiss-Prot, Nr, GO, and Pfam databases. The BLAST, Synteny, Primer Design, Seq_fetch, and JBrowse tools are provided to help users perform comparative genomic analyses. All the genome assemblies, gene models, annotations, and bioinformatics results can be easily downloaded from the TBGR database. We plan to improve and continuously update the database with newly assembled genomes and comparative genomic studies. We expect the TBGR database to become a key resource for the study of the Brassicaceae.

Objective. To explore the anthropometric indicators suitable for screening for nonalcoholic fatty liver disease (NAFLD) in the elderly population. Methods. This cross-sectional study screened subjects over 65 years, who had undergone a physical examination in 2019. Their height, weight, waist circumference, and fasting blood glucose and triglyceride levels were measured. Body mass index (BMI), waist circumstance (WC), waist-to-height ratio (WHtR), relative fat mass (RFM), ponderal index (PI), conicity index (CI), lipid accumulation product (LAP), and body shape index (ABSI) were calculated. Statistical analyses were performed using the Chi-square test, logistic regression, and receiver operating characteristic (ROC) curve. Subjects. Of a total of 4985 subjects, 1173 diagnosed with NAFLD and 3812 without NAFLD were included. Results. The NAFLD group had increased BMI, WC, WHtR, RFM, PI, CI, and LAP. ABSI was only significantly different in males between the groups. Logistic regression analysis showed that RFM was an effective prognostic factor for males with NAFLD, and LAP, BMI, and WC were effective prognostic factors for females. ROC curve analysis showed that LAP played a significant role in the prediction of NAFLD. Conclusion. LAP is closely related to the occurrence of NAFLD and could be an efficient screening and treatment tool for NAFLD in the elderly people. Lay Summary. We conducted a screening and study of nonalcoholic fatty liver disease in the elderly population by determining the association between obesity indexes and nonalcoholic fatty liver disease. We found that LAP is practical, easy-to-measure tool for screening and studying NAFLD in the high-risk community elderly population, making it a valuable indicator in research.

330 Background: Patients (pts) with localized prostate cancer (LPC) or locally advanced prostate cancer (PC) have several treatment options, including external beam radiation therapy (EBRT) and radical prostatectomy, which can be curative in some pts. However, limited real-world evidence exists on the long-term clinical outcomes of these pts, particularly those with high-risk LPC (HRLPC). This study examines real-world clinical outcomes for HRLPC and low/intermediate risk LPC (LIRLPC) pts treated with EBRT in the US. Methods: A retrospective study using Surveillance, Epidemiology, and End Results (SEER)-Medicare linked registry-claims data from 2012−2019 included LPC pts aged ≥65 treated with EBRT as initial definitive therapy. Baseline demographic and clinical characteristics were summarized for HRLPC and LIRLPC pts. Clinical outcomes of interest (overall survival, metastasis-free survival [MFS] and time to initiation of advanced PC treatment) were compared using Kaplan-Meier (KM) and Cox proportional hazards (PH) models. Results: Of 11,127 LPC pts treated with EBRT within 6 months of LPC diagnosis, ~40% (n=4,414) were HRLPC and ~60% (N=6,713) were LIRLPC. Patient characteristics for both groups appeared similar, with mean age at EBRT initiation >70 years, 86% white, and mean follow-up time >40 months. ADT was used with EBRT in 78% HRLPC and 34% LIRLPC. Median (IQR) duration of ADT therapy (via KM analysis) was 9.9 (5.8, 21.5) months for HRLPC and 7.2 (5.3, 9.8) months for LIRLPC. A higher proportion of HRLPC vs LIRLPC pts experienced metastasis, death, and progression to advanced PC therapies (medians were not reached). Unadjusted Cox PH survival analyses showed higher risk of mortality, metastasis, and advanced PC therapy use for HRLPC vs LIRLPC pts. Conclusions: This real-world study of clinical outcomes in pts with HRLPC and LIRLPC treated with EBRT suggested substantial additional disease burden in pts with HRLPC and highlights the need for additional strategies and treatments to improve clinical outcomes in pts with HRLPC. [Table: see text]

Current evidence suggests that rivaroxaban may be well tolerated and effective in patients with nonvalvular atrial fibrillation (NVAF) and obesity; however, there is limited evidence on the impact of polypharmacy in this population. This study evaluated real-world clinical outcomes with rivaroxaban versus warfarin in patients with NVAF and obesity according to the number of concurrent medications.This retrospective cohort study identified patients with one or more pharmacy claim for rivaroxaban or warfarin from two large claims databases. Patients were required to have an atrial fibrillation diagnosis, body mass index ≥ 30 kg/mA total of 95,875 patients were identified with one or more claim for either rivaroxaban or warfarin. After PSM, patient characteristics were balanced between cohorts (n = 21,547 in each cohort). The overall composite risk of stroke and systemic embolism was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70-0.84; p 0.001). The risks of ischemic stroke, hemorrhagic stroke, and systemic embolism separately were also significantly reduced with rivaroxaban. Major bleeding risk was similar between cohorts (HR 0.93, 95% CI 0.81-1.06; p = 0.2842), and results were consistent across the three polypharmacy groups.In this real-world study of NVAF patients with obesity, rivaroxaban was associated with lower risks of stroke and systemic embolism and similar risk of major bleeding versus warfarin across polypharmacy categories.

Objective: To describe chemotherapy treatments, associated health care use and costs, and survival for women diagnosed with cervical cancer in the United States.Methods: This was a retrospective co...

Expedited reporting of unexpected serious adverse reactions that occur during clinical trials conducted under an IND is a critical component of the clinical trial process designed to protect patients by identifying potential safety issues with new agents. However, in recent years, the US FDA has presented extensive data about the problem of uninformative IND safety reporting. Despite published guidance documents aimed at clarifying requirements for submission of IND safety reports for individual events, there continues to be significant over-reporting of these events by many sponsors. This leads to excessive burden for the sponsors, the investigators who conduct clinical trials, and the FDA reviewers, who must evaluate each individual report submitted by the sponsor. This trend has the potential to endanger patients by obscuring true safety signals. To address this problem, LUNGevity Foundation empaneled a multi-sector working group of its Scientific and Clinical Research Roundtable (SCRT) charged with identifying ways to reduce unnecessary distribution of serious adverse events (SAEs) reports. This paper outlines the working group's activities, including a brief list of serious adverse events "anticipated" to occur within the lung cancer population that are either related to the underlying disease or condition being studied, concomitant or background therapy, or events associated with a demographic parameter such as age. These "anticipated" events, while required to be reported by investigators to sponsors, in general, should not then be individually reported by sponsors to FDA and to individual investigators in an IND safety report because these events require aggregate analysis across the development program to determine if they occur more frequently in treated versus untreated patients. This paper also includes discussion of how the use of background threshold values, generated from real-world data, could serve as one potential tool to guide sponsors in making causality assessments. If sponsors and other key stakeholders within the clinical research ecosystem embrace this type of approach and refrain from reporting "anticipated" events as single IND safety reports to the FDA staff and to each participating investigator, it could significantly reduce the amount of unnecessary reporting and serve as a model for other disease areas.

Most cases of small cell lung cancer (SCLC) are diagnosed at an advanced stage. The objective of this study was to investigate patient characteristics, survival, chemotherapy treatments, and health care use after a diagnosis of advanced SCLC in subjects enrolled in a health system network. This was a retrospective cohort study of patients aged ≥ 18 years who either were diagnosed with stage III/IV SCLC or who progressed to advanced SCLC during the study period (2005–2015). Patients identified from the Indiana State Cancer Registry and the Indiana Network for Patient Care were followed from their advanced diagnosis index date until the earliest date of the last visit, death, or the end of the study period. Patient characteristics, survival, chemotherapy regimens, associated health care visits, and durations of treatment were reported. Time-to-event analyses were performed using the Kaplan-Meier method. A total of 498 patients with advanced SCLC were identified, of whom 429 were newly diagnosed with advanced disease and 69 progressed to advanced disease during the study period. Median survival from the index diagnosis date was 13.2 months. First-line (1L) chemotherapy was received by 464 (93.2%) patients, most commonly carboplatin/etoposide, received by 213 (45.9%) patients, followed by cisplatin/etoposide (20.7%). Ninety-five (20.5%) patients progressed to second-line (2L) chemotherapy, where topotecan monotherapy (20.0%) was the most common regimen, followed by carboplatin/etoposide (14.7%). Median survival was 10.1 months from 1L initiation and 7.7 months from 2L initiation. Patients in a regional health system network diagnosed with advanced SCLC were treated with chemotherapy regimens similar to those in earlier reports based on SEER-Medicare data. Survival of patients with advanced SCLC was poor, illustrating the lack of progress over several decades in the treatment of this lethal disease and highlighting the need for improved treatments.

A homeomorphically irreducible spanning tree (HIST) of a connected graph is a spanning tree without vertices of degree two. The determination of the existence problem of a homeomorphically irreducible spanning tree in a plane cubic graph is NP-complete. A hexangulation of a surface is a cubic graph embedded on a surface such that every face is bounded by a hexagon. It is a problem asked by Hoffmann-Ostenhof and Ozeki that whether there are finitely or infinitely many hexangulations of torus with homeomorphically irreducible spanning trees. In this paper, we show that a family of hexangulations of surfaces, denoted by H ( m , n ) , have a homeomorphically irreducible spanning tree if and only if it has an odd number of faces, which answers the problem of Hoffmann-Ostenhof and Ozeki for hexangulations of surfaces.

Aims To compare clinical outcomes of rivaroxaban and warfarin in patients with nonvalvular atrial fibrillation (NVAF) and concurrent obesity and diabetes. Methods Patients aged ≥18 years were identified from a healthcare claims database with the following criteria: newly initiating rivaroxaban or warfarin, ≥1 medical claim with a diagnosis of AF, obesity determined by validated machine learning algorithm, and ≥1 claim with a diagnosis of diabetes or for antidiabetic medication. Treatment cohorts were matched using propensity scores and were compared for stroke/systemic embolism (SE) and major bleeding using Cox proportional hazards models. Results A total of 9999 matched pairs of NVAF patients with obesity and diabetes who initiated treatment with rivaroxaban or warfarin were included. The composite risk of stroke/SE was significantly lower in the rivaroxaban cohort compared with the warfarin cohort (HR 0.82; 95% CI 0.74–0.90). Risks of ischemic and hemorrhagic strokes were also significantly reduced with rivaroxaban versus warfarin, but not SE. Major bleeding risk was similar between treatment cohorts (HR 0.92; 95% CI 0.78–1.09). Conclusions In NVAF patients with comorbidities of obesity and diabetes, rivaroxaban was associated with lower risks of stroke/SE and similar risk of major bleeding versus warfarin.

e19057 Background: Ibrutinib is an oral, once daily Bruton’s tyrosine kinase inhibitor and is the only targeted treatment that has demonstrated progression-free survival and overall survival in multiple phase 3 trials across age, fitness, and high-risk markers for CLL/SLL. This study examined the trends in genomic testing and compared outcomes of first line (1L) CLL patients treated with ibrutinib or CIT in clinical practice. Methods: The nationwide Flatiron Electronic Health Record-derived de-identified database (03/04/2016-08/31/2021) was used to select patients with CLL/SLL who had ≥2 clinic visits and started 1L therapy with ibrutinib or CIT. Patient baseline characteristics prior to 1L initiation were compared between the two treatment groups. Propensity score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between treatment groups. Kaplan-Meier (KM) analysis was used to evaluate time to next treatment (TTNT) from 1L initiation. Two subgroup analyses were performed among patients with high-risk cytogenetic markers (deletion 17p, 11q or unmutated IGHV) and those without IGHV testing. Results: Overall, the rate of testing for high-risk markers remain suboptimal, while cytogenetic testing for del17p or del11q improved from 52.3% to 74.3%, coinciding with approval of ibrutinib for del17p in 2014, IGHV testing remains infrequent and low at 37.7%. 1882 patients (61.4%) received 1L ibrutinib monotherapy (mean age 71, median follow-up 26 months), and 1182 (38.6%) received a CIT regimen (mean age 68, median follow-up 33 months). More patients treated with ibrutinib had a known high-risk cytogenetic marker (44% vs. 34%), especially in those with deletion 17p (15% vs. 4%), than those treated with CIT. Ibrutinib-treated patients significantly decreased risk of initiating a subsequent treatment by 51% (Table), the high-risk group by 60%, and those with unknown IGHV status by 49%. Conclusions: Consistent with clinical trial evidence, treatment with ibrutinib among 1L CLL patients resulted in a statistically significantly lower risk of initiating subsequent treatment than those treated with CIT, both overall and in the subgroups of patients with high-risk cytogenetic markers and patients without IGHV testing. Assessment of cytogenetic/molecular risk status for appropriate treatment is vital to optimize clinical outcomes, especially in the novel agent era. Recent IGHV testing in community practice to assess genetic risk in CLL remains suboptimal.[Table: see text]

e19056 Background: Ibrutinib is an oral, once daily Bruton’s tyrosine kinase inhibitor and is a targeted treatment that has demonstrated progression-free survival and overall survival benefits in multiple phase 3 trials across age, fitness, and high-risk markers for CLL/SLL. Despite ibrutinib established as a preferred first-line (1L) treatment option, anti-CD20 monotherapy (rituximab or obinutuzumab) has been prescribed as symptomatic or palliative therapy. This retrospective study compared outcomes between ibrutinib and anti-CD20 monotherapy for CLL/SLL patients who initiated a 1L of therapy in community oncology practice. Methods: The nationwide Flatiron Health Electronic Health Record-derived de-identified database (03/04/2016-08/31/2021) was used to select patients with CLL/SLL who had ≥2 clinic visits and started 1L therapy with ibrutinib or anti-CD20 monotherapy. Patient baseline characteristics prior to 1L initiation were compared between the two treatment groups. Propensity score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline differences between treatment groups. Kaplan-Meier (KM) analysis was used to evaluate time to next treatment (TTNT) from 1L initiation. Two subgroup analyses were performed among patients with high-risk cytogenetic markers (deletion 17p or 11q, or unmutated IGHV) and those without IGHV testing. Results: Overall, 3,226 patients were included in the analysis, of whom 2,188 (67.8%) received ibrutinib and 1,038 (32.2%) received an anti-CD20 antibody. The average age was 71.4 years for ibrutinib patients and 72.9 years among anti-CD20 users. Patients treated with ibrutinib were more likely to have high-risk cytogenetic markers (42.6% vs 27.9%). Ibrutinib-treated patients overall had a significant 70% risk reduction of initiating a subsequent treatment compared with anti-CD20 group (Table). Similar results were also found in subgroups of patients with high-risk and those without IGHV testing. Conclusions: IPTW-adjusted analysis showed that in the real-world community practice setting, treatment with ibrutinib resulted in a statistically significantly lower risk of initiating subsequent treatment than the anti-CD20 group including patients with high cytogenetic risk features and without IGHV testing.[Table: see text]

Vascular smooth muscle cell (VSMC) proliferation and migration are crucial events in the pathological course of atherosclerosis and restenosis after percutaneous coronary intervention (PCI). Dioscin has been shown to exhibit powerful cardiovascular protective effects and potent therapeutic potential in cancer owing to the inhibition of cell proliferation and migration. However, its effects on arterial wall hypertrophy-related diseases caused by VSMC proliferation and migration remain unclear. In this study, we investigated the effects of dioscin on intimal hyperplasia after balloon injury in vivo, its effects on VSMC proliferation and migration in vitro, and the mechanisms underlying these effects. Results showed that dioscin treatment significantly inhibited VSMC proliferation and intimal thickening after balloon injury. In cultured VSMCs, treatment with dioscin significantly decreased fetal bovine serum or platelet-derived growth factor-induced cell proliferation and migration. Moreover, dioscin inhibited the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and expression of Forkhead box M1 (FoxM1) and its downstream target genes. FoxM1 knockdown with shRNA partially counteracted the inhibitory effects of dioscin on cell proliferation and migration. In conclusion, we demonstrated that dioscin attenuated neointima formation in response to balloon injury by suppressing VSMC proliferation and migration through MAPK-FoxM1 pathway. Our data suggested that dioscin might be a potential therapeutic agent for atherosclerosis and restenosis after PCI.

The detection of cardiac markers is critical to the diagnosis of acute myocardial infarction, and immunochromatographic assays are a common tool for point-of-care analysis. Methods: We report a multiplexed lateral flow test strip for simultaneous quantitative detection of cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CKMB), and myoglobin (Myo). Hydrophilic, monodisperse, stable, and carboxyl-modified (COOH-) magnetic nanobeads (MNBs) were used to construct immunomagnetic probes specific to the three cardiac markers. The detection area of the sandwich-style complexes contained three test lines for cTnI, CKMB, and Myo. The magnetic signal intensity of the detection area in the nitrocellulose membrane was measured via a magnetic immunochromatography reader developed in house. Results: To optimize the assay, a modified working buffer was also investigated to improve the detection sensitivity, decrease the background noise, and shorten the detection time. The MNB-based immunochromatography test (MICT) strip offers a wide linear dynamic detection range, rapid detection, high sensitivity, and specificity. The limit of detection was 0.0089 ng/mL for cTnI, 0.063 ng/mL for CKMB, and 0.05 ng/mL for Myo with minimal cross-reactivity. There were 110 clinical human serum samples that were used to evaluate this platform with high correlation. Conclusion: MICT shows great potential as a supplemental method for in vitro diagnostics in the laboratory or in other point-of-care testing (POCT) applications.

Additional file 1: Supplementary Table 1. Adjusted relative risks of initial hospital encounters in the short-term following a PHQ-9 assessment. Supplementary Table 2. ICD-10 codes and descriptions for MDD diagnoses.

Aim: We evaluated the relationship between clinical and genomic characteristics and tumor mutational burden (TMB) in small cell lung cancer. Materials & methods: In a retrospective analysis of small cell lung cancer patients aged ≥18, we assessed treatment patterns and survival in relation to TMB; the association of clinical and genomic characteristics with TMB was determined by multivariate regression. High TMB (TMB-H) was defined as ≥10 mutations/megabase. Results: Among 186 patients, treatment patterns and overall survival were similar for TMB-H and non-TMB-H patients. TMB was determined for 179 patients, 41.9% of whom were TMB-H. Short variants of LRP1B, FAT3, MLL3, MED12 and NOTCH3 were significantly associated with TMB-H (p ≤ 0.01). Conclusion: Neither treatment patterns nor survival differed by TMB status.

Introduction/Background Despite high response rates to initial treatment, high recurrence rates remain a persistent challenge among patients with ovarian cancer (OC). There is limited data on overall survival (OS) rates and burden of disease with contemporary standard of care. We examined the treatment experience of real-world patients in the United States (U.S). Methodology Using a single-arm retrospective cohort study design, we identified OC patients from the SEER-Medicare database, aged ≥66 years and had completed 4–10 cycles of platinum-based first-line (1L) chemotherapy from January 2009 to December 2015. The descriptive outcomes were OS rates, rates of hospitalization, mean number of hospitalizations and length of hospital stay (LOS), receipt of bevacizumab, proportion of patients who initiated non-platinum therapies, and transition rates through lines of therapy at 1-, 2-, 3- and 4-year landmarks. Results We identified 2,262 patients (mean age was 74.6±6.2 years). 29.9 of patients had ≥1 non-cancer comorbidity. 90.2% of patients were white. At 1 year after initiating chemotherapy, 90.7% of patients were alive, 56.1% were hospitalized at least once with a mean LOS of 16 days; 10.2% had received bevacizumab and 20.5% had initiated a non-platinum-based therapy. At 4 years, 44.1% of patients were alive, 72.6% were hospitalized at least once with a mean LOS of 22 days; 31% had received bevacizumab and 56.2% had initiated a non-platinum-based therapy. The proportion of patients who had died, completed or were receiving 3 or more lines of therapy increased from 10.1% at 1 year to 74.2% at 4 years from initiating chemotherapy. Among 1,538 patients with known treatment or mortality status at 4 years, 251 (16.3%) had not received additional treatment following their initial course of chemotherapy. Conclusion The increasing burden of therapy and hospitalizations over time demonstrate the need for more effective front-line therapies to delay progression in ovarian cancer. Disclosure G Adeboyeje, K Desai, S Iqbal, J He, M Monberg are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.

BACKGROUND NF1-related PN can cause substantial morbidity, with no currently approved drug treatment available for PN treatment. Although surgery is the standard of care, complete resection of PN is often difficult due to encasement of vital structures and invasive and extensive PN growth. With limited real-world data among children with NF1-related PN, the study objectives were to describe the demographic, clinical characteristics, and treatment of these children. METHODS A cross-sectional analysis of existing CTF web-based, patient-entered, registry data collected between 2012–2018 was conducted. To be included in analysis, patients had to complete at least one registry survey, and be ≤ 19 years of age at the time of first survey completion, with patient- or parent/ guardian reported diagnosis of NF1 and at least 1 PN. Descriptive statistical analysis was conducted on data collected from the first survey for each patient, to describe patient characteristics and treatment patterns. Results were stratified by region (US, ex-US). RESULTS The sample included 943 pediatric patients (n=750 US, n=193 ex-US). The majority (85.9%) were less than 5 years of age at NF1 diagnosis (US: 87.6%; ex-US: 79.3%). Approximately half were male, and half reported more than 1 PN. The most common PN site include head (15.1%) and neck (12.6%). More than half of patients received no treatment (53.1%) for their PN. The most common treatments reported for PN were surgery (27.0%) and chemotherapy or drug therapy (10.0%). These results were generally consistent across regions. A malignant peripheral nerve sheath tumor (MPNST) and optic glioma (OG) were diagnosed in 21 (2.2%) and 308 (32.7%) patients, respectively; a large proportion of OG patients remained untreated (57.5%). Too few ex-US patients were available for detailed regional analysis. CONCLUSIONS This study demonstrated that a large proportion of children diagnosed with NF1-related PN remain untreated, highlighting a substantial unmet need.

298 Background: Guidelines recommend mutation testing prior to initiating first-line therapy (L1) for patients with advanced non-small cell lung cancer (aNSCLC), including testing for epidermal growth factor receptor (EGFR) mutations. Guidelines also recommend further testing after patients progress on targeted therapy to identify possible resistance mutations and inform selection of subsequent treatment. The present study characterized real-world (RW) EGFR testing patterns in aNSCLC patients. Methods: This retrospective observational cohort study evaluated an aNSCLC cohort (stage IIIB or higher) from the Flatiron Health database. Eligible patients were newly diagnosed, ≥18 years old, and received at least one line of therapy (LOT) during 2015-2020. Patients were followed to last activity, death, or end of the study period, whichever came first. Results: The final study cohort included a total of 22,726 patients. Of these, 17,165 (75.5%) had ≥1 EGFR test and 2,611 (15.2% of the tested study population) tested positive for EGFR mutations at any time during the study. The proportion of aNSCLC patients receiving EGFR testing prior to L1 initiation increased from 45.2% in 2015 to 56.6% in 2020. Among 11,791 patients who had an EGFR test prior to initiation of L1, 1,944 (16.5%) had positive results. Of these, the cumulative proportion of patients receiving a second EGFR test prior to L2, L3, and L4 (contingent on receiving the following LOT) was 36.3% (322 out of 888), 55.4% (241 out of 435), and 67.0% (146 out of 218), respectively. From 2015-2020, the median time from sample collection to EGFR test results decreased from 26 to 16 days for next generation sequencing (NGS) tests and from 17.5 to 12 days for polymerase chain reaction (PCR) tests. During this same period, the proportion of NGS EGFR tests increased from 27.6% to 75.0%. In addition, use of plasma samples for EGFR tests increased substantially (6.3% to 36.5%). Conclusions: The proportion of aNSCLC patients tested for EGFR mutations has increased over time (2015-2020). Median time to available EGFR test result has decreased for both NGS and PCR tests. NGS testing has become increasingly more common as has use of plasma samples. However, opportunities for improvement exist, including further increasing the proportion of patients tested prior to initiation of L1 therapy, as well as testing prior to the selection of subsequent therapy when indicated. As more targeted therapies emerge and resistance mutations to current therapies are further characterized, continued refinement of RW testing practices is required to optimize patient care.

Temozolomide (TMZ) is used to treat adult patients with glioblastoma multiforme (GBM). Cases of hepatotoxicity have been reported among patients using TMZ. The objective of the study was to assess the relation, if any, between exposure to TMZ and serious acute liver injury (SALI). We used the HealthCore Integrated Research Database to perform a case-control study nested within a retrospective cohort of adult patients aged 18-100 years with at least two diagnoses of brain cancer anytime between 2006 and 2014. Patients without continuous eligibility or with a SALI diagnosis within 6 months prior to the date of incident brain cancer diagnosis were excluded. Medical records were sought for potential SALI cases and reviewed by two hepatologists. Five controls were selected for each case using incidence density sampling, matched on age and calendar year of index date. The analysis included 61 confirmed SALI cases and 305 selected controls. Exposure to TMZ was classified according to dispensing date and days supply of medication dispensed. We estimated odds ratios using conditional logistic regression models. The odds ratio for any exposure to TMZ was 0.91 (95% CI 0.44-1.91), for recent exposure to TMZ was 0.62 (95% CI 0.21-1.85). There was no increased risk of SALI with increasing duration of exposure to TMZ. When patients with unconfirmed SALI were included in the analysis, results were similar (OR 1.04; 95% CI 0.70-1.54). In conclusion, this study did not find an association between TMZ and SALI risk among patients with brain cancer.

Context Understanding clinical characteristics and treatment selection for elderly patients is essential in the era of novel agents. informCLL ( NCT02582879 , September 2015 initiation) is an ongoing, US-based, prospective, real-world observational registry of patients with CLL. Objective To characterize overall demographics of previously untreated elderly CLL patients and compare clinical factors and treatment choice of those aged 65-74 years (Group 1) versus ≥75 years (Group 2). Design/Patients An interim analysis (November 2018 data cut) of previously untreated patients from the informCLL registry who were aged ≥65 years and received single-agent ibrutinib, chemoimmunotherapy, or immunotherapy at enrollment. Association between age groups and treatment choice was assessed by multinomial logistic regression after adjusting for comprehensive demographic and clinical factors. Results Analysis included 449 elderly patients (Group 1: 238; Group 2: 211); median age was 74 years. Most patients were male (64.1%), white (92.4%), treated in community settings (94.9%), and Medicare/Medicaid-insured (88.4%). Median time from initial diagnosis to first treatment was 2.0 years. The majority had an Eastern Cooperative Oncology Group (ECOG) score ≤ 1 (87.1%) and Charlson Comorbidity Index (CCI) score ≤ 1 (62.0%). The most common comorbidities were hypertension (69.3%), other cardiovascular disorders (29.2%), non-CLL malignancies (26.3%), and connective tissue diseases (24.5%). Documented cytogenetic/molecular testing rates were low: TP53, 6.01%; IGHV, 5.35%; CLL FISH, 17.8%; any of the three, 18.7%. 202 (45.0%) patients received ibrutinib, 170 (37.9%) received chemoimmunotherapy, and 77 (17.1%) received immunotherapy. Group 2 (vs Group 1) had poorer performance status (ECOG scores ≥2, 12.9% vs 5.7%, p=0.01), more comorbidities (CCI scores ≥2, 45.5% vs 31.1%, p Conclusions Previously untreated real-world CLL patients aged ≥75 years (vs 65-74 years) had poorer performance status, more comorbidities, lower cytogenetic/molecular testing rates, and a higher likelihood of receiving ibrutinib versus chemoimmunotherapy as initial treatment.

Purpose Few studies have examined patients with prediabetes in usual, “real-world” clinical practice settings. Among patients with impaired fasting glucose (IFG), we aimed to describe the rates of progression to diabetes and to examine the long-term reduction in diabetes risk associated with regression to normoglycemia at 1 year. Methods The UK-based study included 120 055 non-diabetic patients in Clinical Practice Research Datalink from 2001 to 2012 aged 25+ years and with ≥1 fasting plasma glucose (FPG) test between ≥6.1 and