tbuckley/cabot-search huggingface dataset:
Increase in Diabetes Mortality Associated With COVID-19 Pandemic in the U.S.
Authors: Jinjun Ran, Shi Zhao, Lefei Han, Yang Ge, Marc K.C. Chong, Wangnan Cao, Shengzhi Sun
Journal: Diabetes Care (2021)

The coronavirus disease 2019 (COVID-19) pandemic has claimed a notable number of deaths in the U.S. The COVID-19 death toll could not wholly explain the substantial increase in all-cause mortality during the pandemic (1), suggesting that the pandemic has indirect impacts on susceptible populations with underlying medical problems, such as cardiovascular diseases (2).Diabetes is a chronic illness that requires continuing close monitoring, primary care support, and medication.Due to fear of COVID-19 infection and lack of health care resources, patients with diabetes might die prematurely without timely treatment.Accordingly, we aimed to assess whether diabetes mortality changed during the pandemic period in the U.S.We obtained weekly death data between 1 January 2015 and 2 November 2020
Correction to: The long non-coding RNA CRNDE regulates growth of multiple myeloma cells via an effect on IL6 signaling
Authors: Antoine David, Simone Zocchi, Alexis Talbot, Caroline Choisy, Ashley Ohnona, Julien Lion, Wendy Cuccuini, Jean Soulier, Bertrand Arnulf, Jean-Christophe Bories, Michele Goodhardt, David Garrick
Journal: Leukemia (2021)
Association of Branded Prescription Drug Rebate Size and Patient Out-of-Pocket Costs in a Nationally Representative Sample, 2007-2018
Authors: Kai Yeung, Stacie B. Dusetzina, Anirban Basu
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Over the past decade, branded prescription drug manufacturers have substantially increased list prices while offering larger rebate payments to health care insurers. Whereas larger rebates can partially offset increases in list prices for insurers, patient out-of-pocket costs may be directly associated with list prices for individuals without insurance and indirectly associated with list prices for individuals with insurance through deductibles or coinsurance. <h3>Objective</h3> To investigate the association between rebates and patient out-of-pocket costs and whether this association differs by coverage type (ie, Medicare, commercial, or uninsured) and before and after 2014. <h3>Design, Setting, and Participants</h3> This cross-sectional study was conducted using data from the Medical Expenditure Panel Survey (MEPS) combined with pricing data for single-source branded drugs from SSR Health from 2007 through 2018. The study was conducted among a nationally representative sample of the noninstitutionalized civilian US population. Included individuals were respondents to MEPS with at least 1 prescription for a single-source branded drug who were covered by Medicare or commercial insurance or were uninsured during an entire year. Data analyses were conducted from August 2019 through March 2021. <h3>Exposures</h3> Estimated rebate size. <h3>Main Outcomes and Measures</h3> Out-of-pocket costs per prescription were calculated, adjusting for year and drug. <h3>Results</h3> Among 38 131 individuals with at least 1 prescription, the mean age was 54 years (95% CI, 54 to 55 years), with 22 044 women (57.8%) and 29 086 White individuals (76.3%). The sample included 444 unique drugs with a survey-weighted total of 4.7 billion prescriptions. Estimated mean (SE) rebates increased from $34 ($1) per prescription in 2007 to $374 ($9) per prescription in 2018. The rebate sizes were associated with statistically significant mean out-of-pocket increases per branded prescription of $4 (95% CI, $4 to $4) from 2007 to 2013 and $11 (95% CI, $10 to $12) from 2014 to 2018. From 2014 to 2018, rebate sizes were associated with statistically significant mean increases in out-of-pocket costs per prescription of $13 (95% CI, $12 to $13) for individuals with Medicare, $6 (95% CI, $6 to $7) for individuals with commercial insurance, and $39 (95% CI, $34 to $44) for individuals without insurance. After adjusting for list prices, there was no association between rebates and out-of-pocket costs, with a change from 2014 to 2018 of −$0.01 (95% CI, −$0.04 to $0.02). <h3>Conclusions and Relevance</h3> These findings suggest that drug manufacturers may have provided larger rebates to insurers primarily by increasing list prices and that individuals without insurance had greater cost increases. The results emphasize the need for policy solutions that decouple list prices and out-of-pocket costs.
Pyrexia-related outcomes upon application of an adapted pyrexia management algorithm in patients (pts) with <i>BRAF</i> V600: Mutant unresectable or metastatic melanoma treated with dabrafenib plus trametinib (DabTram) in the COMBI-i trial.
Authors: Paolo Antonio Ascierto, Caroline Robert, Paul D. Nathan, Reinhard Dummer, Hussein Abdul-Hassan Tawbi, Keith T. Flaherty, Antoni Ribas, Dirk Schadendorf, Steven Green, Lali Sandalic, Mike R. Lau, Tonatiuh Romero, Georgina V. Long
Journal: Journal of Clinical Oncology (2021)

9560 Background: First-line DabTram has shown long-term efficacy in pts with BRAF V600–mutant unresectable or metastatic melanoma in the Phase III COMBI-d and COMBI-v trials. Data from the Phase III COMBI-i trial comparing spartalizumab plus DabTram vs placebo plus DabTram (pbo-DabTram) demonstrated efficacy in the pbo-DabTram arm, consistent with historical data. Pyrexia (single preferred term [PT]) is the most common adverse event (AE) reported with DabTram (pooled COMBI-d [data cutoff: Jan 12, 2015] and COMBI-v [data cutoff: Apr 17, 2014]: any grade, 54.2%; grade ≥ 3, 5.4%; serious pyrexia AEs leading to hospitalization, 11.8%). A new pyrexia management algorithm was implemented in the COMBI-i trial to improve pyrexia-related outcomes. We report pyrexia-related outcomes in pts treated with pbo-DabTram in the control arm of COMBI-i part 3. Methods: COMBI-i (NCT02967692) part 3 is a double-blind, Phase III trial in which pts with previously untreated BRAF V600–mutant unresectable or metastatic melanoma were randomized 1:1 to receive spartalizumab (400 mg intravenously every 4 weeks) plus Dab (150 mg orally twice daily) and Tram (2 mg orally once daily) vs pbo-DabTram. In the adapted pyrexia management algorithm, both Dab and Tram are interrupted promptly at the first symptom of pyrexia or its associated prodrome (ie, chills, rigors, night sweats, or influenza-like symptoms). Treatment at the same dose level is restarted upon the improvement of symptoms if pts are symptom free for ≥ 24 hours. Pyrexia incidence rates presented are for the single PT of pyrexia. Results: At data cutoff (July 1, 2020), median follow-up was 27.2 mo for all pts enrolled in COMBI-i part 3 (N = 532). In the DabTram control arm, 52.7% (139/264) and 3.0% (8/264) of pts had any-grade and grade ≥ 3 pyrexia, respectively. Serious pyrexia AEs were reported in 6.1% (16/264), which led to hospitalization in 5.3% (14/264). Pyrexia led to dose interruption of both Dab and Tram in 39.0% (103/264), with 1.5% (4/264) permanently discontinuing both agents. Median relative dose intensity was 97.8% for Dab and 97.7% for Tram. Conclusions: Pyrexia-related outcomes, including grade ≥ 3 pyrexia (3.0% vs 5.4%) and serious pyrexia AEs leading to hospitalization (5.3% vs 11.8%), were improved in pts treated with DabTram in COMBI-i part 3 compared with historical data from COMBI-d/v. The adapted algorithm offers a simplified approach for managing pyrexia, thereby reducing the incidence of severe pyrexia while maintaining consistent efficacy with DabTram. Clinical trial information: NCT02967692.
Comprehensive ambulatory monitoring during immunotherapy in patients with advanced melanoma: A prospective trial (CAMP-IT).
Authors: Milan Kos, Laurien Buffart, Jan Willem de Groot, Hans Westgeest, Wouter Dercksen, Hanneke W.M. Van Laarhoven, Martijn G.H. van Oijen
Journal: Journal of Clinical Oncology (2021)

TPS1589 Background: The emergence of immune checkpoint inhibitors has improved survival outcomes for patients with advanced melanoma. However, these treatment modalities are also associated with specific immune-related toxicities. These are often reversible after prompt recognition and initiation of appropriate management, but can result in severe morbidity and hamper health-related quality of life (HRQoL) if left undetected. Hence, accurate and regular monitoring of these patients is critical. Recent advances in mHealth technologies and the rapidly expanding armamentarium of wearable devices allow for real-time objective (vital signs and physical activity) data and patient-reported outcome measurement (PROMs) collection and, hence, serve this purpose. We hypothesize that collection of real-time objective data adds to the early detection of disease- and treatment-related adverse events. The primary objective of this study is to determine the feasibility of collecting real-time PROMs, vital signs, and physical activity data in advanced melanoma patients receiving immunotherapy using a comprehensive ambulatory monitoring platform (CAMP) that consists of a smartphone app, activity monitor, digital thermometer, and online dashboard for physicians. Methods: In this prospective multi-center trial, patients (n = 50) with advanced melanoma, scheduled to receive immunotherapy with immune checkpoint inhibitors, and with access to a smartphone are eligible for inclusion. Consenting patients will be asked to wear a FitBit Versa 2.0 during waking hours, collect daily temperature measurements using a Withings Smart Temporal thermometer, and answer weekly toxicity questionnaires (NCI PRO-CTCAE) using the smartphone app for the duration of the study (12 weeks). Primary outcome is feasibility in terms of (i) participation rates, (ii) wear-time, (iii) compliance rates with in-app questionnaires and temperature measurements, and (iv) satisfaction with the platform. Secondary exploratory outcomes include associations between CAMP-derived parameters and clinical outcomes: performance status (PS), HR-QoL scores (EORTC QLQ-C30 questionnaire), unplanned hospitalizations, physician-assessed adverse events, and 1-year survival outcomes. PS and HR-QoL will be rated at baseline, mid-study, and end-of-study. The occurrence of adverse events will be documented up to 12 months from baseline. Survival outcomes will be compared to a propensity score matched group from the Netherlands Cancer Registry. Accrual has started in February 2021. Clinical trial information: NL8827.
Efficacy of Tyrosine Kinase Inhibitors (TKIs) as Third Line Therapy In Patients with Chronic Myeloid Leukaemia In Chronic Phase Who Have Failed Two Prior TKIs
Authors: Amr R Ibrahim, Marco Bua, Jamshid S Khorshad, Dragana Milojkovic, Lina Eliasson, Richard Szydlo, Letizia Foroni, Alistair Reid, Hugues de Lavallade, Katayoun Rezvani, John M. Goldman, Jane Apperley, David Marin
Journal: Blood (2010)
肝線維症の解像度に現れるアルファ平滑筋アクチン-およびMMP1-陽性細胞の両方に分化するムサシ-1-陽性細胞(幹/始原細胞)
Authors: Watanabe T, Niioka M, Inagaki Y, Sugioka Y, Kanagawa I, Okano H, Okazaki I
Journal: Hepatology (2003)
IDH1/2 -Mutated Acute Myeloid Leukemia Has Impaired DNA Damage Response and Is Sensitive to Monotherapy with the PARP Inhibitior Olaparib
Authors: Remco J Molenaar, Tomas Radivoyevitch, Yasunobu Nagata, Bartlomiej P. Przychodzen, Hideki Makishima, Hetty E. Carraway, Sudipto Mukherjee, Mikkael A. Sekeres, Cornelis van Noorden, Jaroslaw P. Maciejewski
Journal: Blood (2017)
The feasibility and potential role of pharmacogenetics to improve drug safety in patients with advanced cancers.
Authors: Sourat Darabi, Chelsey Weatherill, Valentina Dalili-Shoaie, Burton Larry Eisenberg, Michael J. Demeure
Journal: Journal of Clinical Oncology (2021)

e22522 Background: Pharmacogenetics is the study of genetic variants that define drug metabolism and dosing requirements, response or toxicity. Knowledge regarding drug-drug interactions and individual variations in genes involved in drug metabolism is increasing. Since patients with cancer often take several drugs (polypharmacy), they have a higher risk of severe drug interactions. The FDA lists several pharmacogenetic biomarkers in drug labeling, including genetic variants that impact how certain medications are prescribed. The drugs listed span multiple medical applications, including but not limited to oncology, primary care, psychiatry, neurology, cardiology, and many more. Adverse drug reactions are a significant cause of morbidity and mortality, yet the use of pharmacogenetic testing has not yet become established as a routine in clinical practice. Herein we sought to study the feasibility of applied pharmacogenetics in a pilot drug safety program in patients with advanced cancer. Methods: We enrolled patients in a prospective single-center IRB approved study. Patients with advanced cancer on three or more drugs about to begin chemotherapy at the Hoag Family Cancer Institute were eligible. Informed consent was obtained from the study participants, and their samples were sent to a CLIA laboratory to conduct a 25-gene pharmacogenetics testing panel, which includes “major drug-metabolizing enzymes” CYP2D6, CYP2C19, CYP2C9, CYP3A4, and CYP3A5 as well as other genes with known drug implications. We recorded patients’ demographics and clinical information. In addition, participant’s drug lists were assessed for potential polypharmacy interactions. Results: We analyzed the results from 36 patients, 20 females and 16 males, enrolled between December 2017 and June 2020. Pharmacogenetics results from these patients showed that 61% (22 patients) had a variant with gene drug interaction indication. The most common variants were identified in the CYP2D6 gene, followed by CYP2C19, CYP3A4, and CYP3A5. Of these 22 patients, seven patients had at least one major criterion (drug interactions may lead to severe clinical effects), and eight patients with reported moderate criteria (may lead to substantial clinical effects). Additionally, seven patients had variants with both major and moderate criteria. Patients were taking an average of 10 medications per person ranging from 3-19 drugs. No patient, however, experienced significant drug toxicity during the observation interval. Conclusions: Patients with advanced cancer are at particular risk for polypharmacy and adverse drug reactions. Our data report supports pharmacogenetics testing as being feasible for oncology patients. Therefore, programs to prevent or limit the frequency and severity of drug reactions warrant further exploration as they offer the potential to improve patient safety and decrease healthcare costs.
Features of genes copy number in normal, primary tumor, and lymph nodes metastases cells in patients with cervical cancer.
Authors: Madina M. Kecheryukova, Aleksandr V. Snezhko, Ekaterina V. Verenikina, Anna P. Menshenina, Meri L. Adamyan, Anna Yu. Ardzha, Oleg I. Kit, Denis S. Kutilin
Journal: Journal of Clinical Oncology (2021)

e17503 Background: Early stages of cervical cancer (CC) can be treated with surgery or radiation therapy, metastatic CC is incurable, and therefore new diagnostic approaches based on highly effective molecular markers are required. As such markers, the Copy Number Variation (CNV) is of great interest. Purpose of the study: to analyze the peculiarities of genes CNV in normal cells, primary tumor and lymph nodes tumor metastases cells in patients with CC. Methods: Tissue sections from FFPE-blocks of 300 patients with CC were used for the study. Primary tumor, tumor metastatic and normal cells were isolated using non-contact laser microdissection (Palm MicroBeam, Carl Zeiss). DNA was extracted from the cells using the phenol-chloroform method. Determination of 14 genes CNV (LAMP3, PRKAA1, TORC2, FOXO3, HDAC5, MEF2C, MLXIPL, EP300, HNF4A, TP53, SREBF1, SREBF2, PPARGC1A, and CCND1) was performed by Real-Time qPCR method. Statistical analysis was performed using the Mann-Whitney test; Bonferroni's correction was applied to correct multiple comparisons. Results: An increase in the CNV of LAMP3 and TORC2 genes by 2.5 and 3.2 times (p &lt; 0.05), respectively, and a decrease in the CNV of TP53 and FOXO3 genes by 2.3 and 2.0 times (p &lt; 0.05), respectively, were found in the primary tumor cells relative to normal cells. The effect of the simultaneous change in the CNV of LAMP3, TORC2, TP53 and FOXO3 genes was observed in 60% of the sample, and LAMP3 and TP53 genes - in 80%. In cells of lymph nodes tumor metastases an increase in the CNV of CCND1 and TORC2 genes by 2.0 and 3.5 times (p &lt; 0.05), respectively, was found, as well as a decrease in the CNV of PPARGC1A gene by 2.1 times (p &lt; 0.05) relative to normal cells. A simultaneous change in the CNV of CCND1, TORC2, and PPARGC1A was observed in 70% of the sample, and CNV of CCND1 and TORC2 genes - in 85%. Primary tumor and metastases cells differed in the CNV of CCND1 (2.5 times higher in metastatic cells), LAMP3 (3.0 times lower in metastatic cells) and FOXO3 genes (2.0 times higher in metastatic cells). Conclusions: Thus, the primary tumor and lymph nodes metastases cells differ in the level of genes CNV from normal cervix cells. Accordingly, the CNV of LAMP3, TORC2, TP53 and FOXO3 genes may have the potential for diagnosing a primary cervical tumor, and the CNV of CCND1, TORC2 and PPARGC1A genes for diagnosing its metastases to regional lymph nodes.
Expression of mutant EGFR in ovarian cancer
Authors: Robert B. Montgomery, Andres Klein-Szanto, Eric Ross, Andrew Godwin
Journal: Cancer Research (2004)

1800  The epidermal growth factor receptor (EGFR) and its mutants are potentially important targets in human malignancy. The expression of the oncogenic, constitutively active EGFR mutant, EGFRvIII, in epithelial malignancies outside of tumors of the central nervous system has been poorly described. We examined the expression of wild type EGFR and mutant EGFRvIII in 39 ovarian carcinomas by immunohistochemistry, RT-PCR and sequencing of PCR transcripts. The wild type EGFR was overexpressed in 10/32 (31%) and EGFRvIII was expressed in 12/32 (38%) of ovarian tumors by immunohistochemistry. RT-PCR analysis demonstrated the presence of transcripts which were verified to be EGFRvIII by sequencing in 16/37 (43%) of metastatic and primary ovarian tumors. A higher percentage of metastatic lesions expressed EGFRvIII (80%) vs. primary tumors (40%) (p=0.06). Analysis of the outcome for 17 patients with stage III ovarian cancer at diagnosis revealed that all patients who suffered a local relapse had tumors which expressed EGFRvIII and 78% of the tumors from patients who remained disease free did not express EGFRvIII (p=0.055). Two peritoneal mesotheliomas expressed EGFRvIII by IHC and PCR. We conclude that EGFRvIII is a relevant target in human ovarian cancer and expression of EGFRvIII may have an impact on patterns of relapse in patients with advanced disease.
Albumin-bilirubin grade as a significant prognostic factor in patients with non-small cell lung cancer treated with anti-PD-1-based therapy: A multicenter retrospective study.
Authors: Shinkichi Takamori, Kazuki Takada, Mototsugu Shimokawa, Gouji Toyokawa, Shinichiro Shimamatsu, Fumihiko Hirai, Tetsuzo Tagawa, Tatsuro Okamoto, Motoharu Hamatake, Yuko Tsuchiya-Kawano, Kohei Otsubo, Koji Inoue, Yasuto Yoneshima, Kentaro Tanaka, Isamu Okamoto, Yoichi Nakanishi, Masaki Mori
Journal: Journal of Clinical Oncology (2021)

e21125 Background: Albumin-bilirubin (ALBI) grade is calculated from albumin and bilirubin values as continuous variables, allowing an accurate evaluation of liver function. Some studies showed that ALBI grade was a prognostic and predictive biomarker for the efficacy of chemotherapy in cancer patients. However, no report has examined the association between ALBI grade and outcome in patients with non-small cell lung cancer (NSCLC) treated with anti-programmed cell death-1 (PD-1)-based therapy. Methods: We retrospectively enrolled 452 patients with advanced or recurrent NSCLC treated with anti-PD-1-based therapy (nivolumab or pembrolizumab monotherapy or pembrolizumab combination therapy) between 2016 and 2019 at three medical centers in Japan. With reference to previous reports, ALBI score was calculated using the formula (log 10 (total bilirubin [mg/dL] x 17.1) x 0.66) + (albumin [g/dL] x 10 x −0.085), and the score was stratified as grade 1 (≤ −2.60), grade 2 (more than −2.60 to ≤ −1.39), and grade 3 (more than −1.39). We examined the clinical impact of ALBI grade on outcome in patients with NSCLC receiving anti-PD-1-based therapy using Kaplan–Meier survival analysis with the log-rank test and Cox proportional hazards regression analysis. Results: Of the 452 patients, 158 (35.0%) patients were classified as grade 1, 271 (60.0%) as grade 2, and 23 (5.0%) as grade 3. ALBI grade was strongly correlated with performance status (PS), clinical stage, and body mass index, and mutation status ( P &lt; 0.0001, P = 0.0077, P = 0.0050, and P = 0.0302, respectively). The Kaplan–Meier curves showed that ALBI grade was significantly associated with progression-free survival (PFS) and overall survival (OS) ( P &lt; 0.0001 and P &lt; 0.0001, respectively). Multivariate analyses showed that PS ( P = 0.0044), combination therapy of anti-PD-1 and chemotherapy ( P = 0.0004), programmed cell death-ligand 1 (PD-L1) expression status ( P &lt; 0.0001), and ALBI grade ( P &lt; 0.0001) were independent prognostic factors for PFS. Multivariate analyses also showed that PS ( P = 0.0008), combination therapy of anti-PD-1 and chemotherapy ( P = 0.0066), PD-L1 expression status ( P = 0.0006), and ALBI grade ( P &lt; 0.0001) were independent prognostic factors for OS. In the subgroup analysis, ALBI grade effectively stratified PFS and OS regardless of PD-L1 expression status. Conclusions: We report for the first time that ALBI grade was an independent prognostic factor for PFS and OS in patients with advanced or recurrent NSCLC receiving anti-PD-1-based therapy. These findings should be validated prospectively.