tbuckley/cabot-search huggingface dataset:
Gaps in caregiving for young-onset colorectal cancer patients.
Authors: Kim Lynn Newcomer, Ronit Yarden, Danielle Peterson
Journal: Journal of Clinical Oncology (2020)

82 Background: The rise of young-onset colorectal cancer (YO-CRC) is an alarming public health issue. Interestingly, the proportion of new cases diagnosed in young people (20-49) had increased from 6% in 1990 to 11% in 2013 and coincides with the declining CRC cases in older people. YO-CRC patients face unique clinical challenges as many are diagnosed at advanced stages of the disease and subjected to aggressive treatments. In addition, diagnosis often disrupts early family and career developmental tasks and goals, suggesting the need for additional psychosocial support. Caregivers are an important part of the patient journey. Caregivers serve as liaisons with the medical community and the patient’s social network. The goal of this study is to cast light and explore the experience of caregivers who were caring for YO-CRC patients. Methods: The online survey was completed by 208 caregivers, diverse in age, gender, and race/ethnicity. Participants indicated their relationship as either: spouse/partner, parents, siblings, children, and non-family members. Results: Caregivers self-report they do not understand the important aspects of patients' medical needs despite 79% of caregivers are college graduates and 43% had an advanced degree. Most of the respondents (76%) lack understanding about treatment options and 56% did not feel confident they understood healthcare decisions. Overall, caregivers needed more information and guidance for managing the side-effects of treatment, A majority of caregivers (93%) reported fatigue due to lack of sleep and 63% reporting they missed eight hours or more of work each month. Participants (73%) reported they needed help for panic and anxiety and employed different coping mechanisms to deal with the toll of caregiving. Conclusions: Our survey indicates we must recognize caregivers as the patient's healthcare partners and engage them in the entire plan of care. A growing population of YO-CRC patients means a growing population of caregivers who are navigating work, parenthood, impacts on sexual health, and role changes right along with that patient. Such understanding could help in developing appropriate interventions for caregivers aimed at reducing their burden and stress in caring for patients with YO-CRC.
Omecamtiv Mecarbil in Chronic Heart Failure With Reduced Ejection Fraction
Authors: John R. Teerlink, Rafael Diaz, G. Michael Felker, John J.V. McMurray, Marco Metra, Scott D. Solomon, Jason C. Legg, Gustavo Büchele, Claire Varin, Christopher E. Kurtz, Fady I. Malik, Narimon Honarpour
Journal: JACC Heart Failure (2020)

A central factor in the pathogenesis of heart failure (HF) with reduced ejection fraction is the initial decrease in systolic function. Prior attempts at increasing cardiac contractility with oral drugs have uniformly resulted in signals of increased mortality at pharmacologically effective doses. Omecamtiv mecarbil is a novel, selective cardiac myosin activator that has been shown to improve cardiac function and to decrease ventricular volumes, heart rate, and N-terminal pro-B-type natriuretic peptide in patients with chronic HF. The GALACTIC-HF (Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure) trial tests the hypotheses that omecamtiv mecarbil can safely improve symptoms, prevent clinical HF events, and delay CV death in patients with chronic HF. The GALACTIC-HF trial is an international, multicenter, randomized, double-blind, placebo-controlled, event-driven cardiovascular outcomes trial. More than 8,000 patients with chronic symptomatic (New York Heart Association functional class II to IV) HF, left ventricular ejection fraction ≤35%, elevated natriuretic peptides, and either current hospitalization for HF or history of hospitalization or emergency department visit for HF within a year of screening will be randomized to either oral placebo or omecamtiv mecarbil employing a pharmacokinetic-guided dose titration strategy using doses of 25, 37.5, or 50 mg twice daily. The primary efficacy outcome is the time to cardiovascular death or first HF event. The study has 90% power to assess a final hazard ratio of approximately 0.80 in cardiovascular death, the first secondary outcome. The GALACTIC-HF trial is the first trial examining whether selectively increasing cardiac contractility in patients with HF with reduced ejection fraction will result in improved clinical outcomes. (Registrational Study With Omecamtiv Mecarbil/AMG 423 to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).
NSABP FC-10: Phase IB study of pembrolizumab in combination with premetrexed + oaliplatin in patients (pts) with chemo-refractory metastatic colorectal cancer (mCRC).
Authors: James J. Lee, Greg Yothers, Thomas J. George, John C. Krauss, Bassam Nabih Maalouf, Hiral D. Parekh, Anuradha Krishnamurthy, Kelly R. Vehec, Norman Wolmark, Carmen Joseph Allegra, Samuel A. Jacobs
Journal: Journal of Clinical Oncology (2020)

TPS262 Background: The majority of mCRC pts are microsatellite stable (MSS), have poor intratumoral CD8 + T cell infiltration, and no clinical response to immunotherapy checkpoint inhibitors. Preclinical studies suggest that chemotherapy may synergize with anti-PD-1. In non-small cell lung cancer (NSCLC), the combination of pembrolizumab (PemB), pemetrexed (PemT), + carboplatin demonstrated synergistic activity. This study will combine PemB with PemT, then that combination + oxaliplatin (Ox). The rationale for addition of Ox to PemT is that enhanced immunogenic cell death may induce CD8 + T cell infiltration into CRC tumors and model the mechanism of cytotoxicity seen in NSCLC. Thus, the combination of PemB+ PemT + Ox may induce synergistic antitumor immune activity. Methods: This multi-center phase Ib trial is actively enrolling pts with incurable mCRC with prior treatment for mCRC including fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, and if RAS wild-type, anti-EGFR therapy. Measurable disease by imaging (RECIST 1.1) is required. Standard ineligibility includes active infections, systemic steroid use, or other conditions contraindicating immunotherapy. Cohort 1 will receive PemB + PemT; Cohort 2 will receive PemB + PemT + dose-escalated Ox. Imaging will be performed every 6 wks. The primary aim of Cohort 1: to evaluate for safety and efficacy using doses of PemB and PemT that have been studied in NSCLC. The primary aim of Cohort 2: to evaluate the safety, tolerability, and efficacy of PemB in combination with PemT + Ox. The RP2D of the 3-drug combination will be at the MTD taking into account toxicity profiles of study therapy agents. Secondary aims: to evaluate the clinical benefit rate of the doublet and triplet combinations in pts with chemo-refractory MSS mCRC and to estimate progression-free survival and overall survival in pts with MSS mCRC treated with these combinations. The cohorts will be analyzed separately with descriptive intent only. Maximum enrollment is 33 pts. Support: Merck; Lilly; NSABP Foundation, Inc. Clinical trial information: NCT03626922.
A Successful but Underused Strategy for Reducing Low-Value Care: Stop Paying for It
Authors: Sanket S. Dhruva, Rita F. Redberg
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Colorectal cancer prevalence and risk factors among the uninsured of Tampa Bay: A free clinic study.
Authors: Ethan Song, Artish Patel, Justin Swanson, Alexandra Aponte, Madeline MacDonald, Daniel Segarra, Nirav Shah, Noura Ayoubi, Abu-Sayeef Mirza
Journal: Journal of Clinical Oncology (2020)

61 Background: Uninsured patients with low socioeconomic status are at higher risk for developing colorectal cancer. There is limited quantifiable data regarding risk factors and prevalence of colorectal cancer in this vulnerable population. The purpose of this study is to assess the risk factors for colorectal cancer in the low income and uninsured patient population across nine free clinics around Tampa Bay, Florida. Methods: An IRB-approved manually extracted retrospective query of several medical record systems from nine free clinics in the Tampa Bay area in 2017 revealed 1,836 (36.1%) of 5,076 total patients who are over 50 years old. Patient demographics, weight, smoking status, alcohol use, type 2 diabetes status, inflammatory bowel disease and colorectal cancer prevalence were also extracted and analyzed. Results: Among patients over 50, the majority of patients were female (n = 1073, 58.4%) and of Hispanic ethnicity (n = 752, 41.0%). Of the 1,349 patients who reported their smoking status, 213 (15.8%) were active smokers and 218 (16.2%) were past smokers, with a mean 16.3 (SD = 15.5) pack year history. Of the 1,124 patients who reported their history of alcohol consumption, 217 (19.3%) were current consumers and 40 (3.6%) were past consumers. The average BMI of patients over 50 years was 30.2 (SD = 6.9), with 558 (30.4%) cases of diabetes. Eleven patients (0.6%) had a history of inflammatory bowel disease. The prevalence of documented colorectal cancer in this sample was 0.6% (n = 11) in our sample population. Conclusions: There is a high prevalence of risk factors for colorectal cancer in this sample of uninsured patients but a lower reported prevalence of colorectal cancer compared to the general population. Additionally, many known risk factors for colorectal cancer, such as diet, physical activity, or family history, are not routinely documented by free clinics. As these clinics provide opportune points of primary care, this baseline data should prompt more attention to colorectal screening and risk factor modification in this vulnerable population.
Survival outcomes based on sequence of therapy using FOLFIRINOX and nab-paclitaxel + gemcitabine in metastatic pancreatic ductal adenocarcinoma.
Authors: Kelsey Baron, Christopher Duane Nevala-Plagemann, Justin Moser, Benjamin Haaland, Xuechen Wang, Ignacio Garrido-Laguna
Journal: Journal of Clinical Oncology (2020)

657 Background: Optimal sequence of therapy for patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) is unknown. FOLFIRINOX (FFX) and Gemcitabine + Nab-paclitaxel (AG) are standard first line (1L) therapies. They have never been prospectively compared. Therefore, we retrospectively compared the overall survival (OS) of patients treated with 1L AG and second line (2L) FFX compared to those treated with 1L FFX and 2L AG. Methods: Patients with mPDAC treated with 1L FFX followed by 2L AG, or vice versa were identified using the Flatiron Health EHR-derived nationwide database. To avoid immortal time bias, patients who received no 2L were included. OS from the initiation of 1L was compared with Kaplan Meier curves and log rank analysis. A cox model, stratified by deciles of propensity score (PS), was used to estimate the effect of treatment on OS with adjustment for differences between the groups. Results: 3,042 patients were identified. 2001 patients received 1L AG. Among these patients, 1446 received 2L FFX, and 555 received no 2L. 1041 patients received 1L FFX. Among these patients, 496 received 2L AG, and 545 received no 2L. Median OS and 1-year OS for those treated with 1L AG followed by 2L FFX or no therapy was 6.1 months (95% CI:5.6 – 6.5) and 25% (95% CI: 0.23 – 0.28). Median OS and 1-year OS for patients treated with 1L FFX followed by AG or no therapy was 8.7 months (95% CI: 7.9 – 9.2) and 36% (95% CI: 0.33 – 0.39). The propensity stratified hazard ratio between these two groups was 0.76 (95% CI: 0.69 – 0.83), favoring 1L FFX. Median OS for patients treated with 1L FFX and 2L AG versus 1L AG and 2L FFX was not significantly different (12.0 m vs. 12.5 m; HR 1.04; 95% CI: 0.90 - 1.20). Conclusions: In this analysis of real-world data, 1L FFX was associated with increased OS in propensity analysis. For patients who received both FFX and AG, median OS was similar, regardless of the sequence.
Optimal timing of radiotherapy for incomplete transarterial chemoembolization in BCLC stage B hepatocellular carcinoma.
Authors: Hwa Kyung Byun, Nalee Kim, Jinsil Seong
Journal: Journal of Clinical Oncology (2020)

521 Background: Numerous studies have reported on the efficacy of radiotherapy (RT) after incomplete transarterial chemoembolization (TACE). However, the optimal timing of RT remains unclear. This study investigated the optimal time of initiating RT for incomplete TACE in patients with BCLC stage B hepatocellular carcinoma (BCLC-B HCC). Methods: Between 2001 and 2016, 116 lesions in 104 patients with BCLC-B HCC were treated with RT after TACE. The time interval between the last session of TACE and initiation of RT was obtained from medical records and analyzed retrospectively. The optimal cut-off time-interval that maximized the difference in local failure-free rate (LFFR) was determined using maximally selected rank statistics. Results: The median duration between TACE and RT was 26 (range: 2–165) days. Median number of TACE treatments on the target lesion before RT was 2; median tumor size was 7 cm. At a median follow-up of 18 (range: 3–160) months, the median overall survival was 18 months. The probability of local control increased as the time interval between TACE and RT decreased. The optimal cut-off value of the time interval was 5 weeks. With the cut-off of 5 weeks, 65 and 39 patients were classified into early and late RT groups, respectively. The early RT group had significantly poorer Child-Pugh class and higher alpha-fetoprotein levels. Most characteristics including tumor size (7 cm vs. 6 cm; P = .144) were not significantly different between the groups. One-year LFFR was significantly higher in the early RT group (94.6% vs. 70.8%; P = .005). On multivariate analysis, early RT was an independent predictor of favorable LFFR (hazard ratio: 3.82, 95% confidence interval: 1.64–8.88, P = .002). Conclusions: The optimal time for the administration of RT for incomplete TACE is within 5 weeks following TACE. Early administration of RT within 5 weeks after TACE was associated with better local control.
Neutrophil-to-lymphocyte ratio as a prognostic factor and its relationship to patient (pt) outcomes in the RAINBOW trial.
Authors: Kei Muro, Jaffer A. Ajani, Zev A. Wainberg, Holly Knoderer, Ran Wei, Anindya Chatterjee, Paolo Abada, Atsushi Ohtsu
Journal: Journal of Clinical Oncology (2020)

438 Background: Neutrophil-to-lymphocyte ratio (NLR/N) reflects underlying levels of systemic inflammation and has prognostic value in advanced gastric cancer (G/GEJ). We investigated the relationship between pretreatment NLR and clinical outcomes in the RAINBOW study of ramucirumab (R) with paclitaxel (P) in G/GEJ. Methods: NLR is defined as the ratio of absolute neutrophil count and absolute lymphocyte count from peripheral blood. Pts in ITT population with baseline NLR were analyzed. As no clear NLR cutoff is established in G/GEJ, multiple cutoffs (4, 5, 6) were evaluated and relationships between baseline NLR and efficacy endpoints examined. Median OS, PFS were estimated using Kaplan Meier method; prognostic effects on OS/PFS of baseline NLR subgroups (sg) and treatment effects on OS/PFS within each baseline NLR sg were evaluated using univariate Cox PH models. Results: Baseline characteristics were generally balanced between high NLR sg. Higher baseline NLR groups were associated with worse outcomes regardless of cutoff [mOS N &lt; 4 vs ≥4: 9.2 (8.1, 10.3) vs 5.6 (4.8, 6.6), HR = 0.61 (0.49, 0.75); N &lt; 5 vs ≥5: 8.6 (7.8, 9.6) vs 5.3 (4.5, 6.5), HR = 0.59 (0.47, 0.75); N &lt; 6 vs ≥6: 8.6 (7.8, 9.6) vs 4.7 (4.2, 5.9), HR = 0.55 (0.43, 0.70)]. Consistent treatment benefits (R+P vs Placebo (PB)+P) were observed within high baseline NLR sg (Table). No new safety signals were observed. Conclusions: In this exploratory analysis of RAINBOW, pretreatment NLR ( &lt; 4, 5, 6) were independent prognostic factors of improved survival. Treatment benefits with R+P was preserved within high baseline NLR levels defined by different cutoffs and was consistent with ITT results. Clinical trial information: NCT01170663. [Table: see text]
The role of gene–environment interactions in lung disease: the urgent need for the exposome
Authors: Craig E. Wheelock, Stephen M. Rappaport
Journal: European Respiratory Journal (2020)

<b>Genetic susceptibility can alter the initiation of lung diseases, but environmental triggers are vital determinants. There is an urgent need to study the exposome – the sum total of environmental exposures – to understand the aetiology of lung diseases.</b>http://bit.ly/2YG5XpP
統合分析は,結節性硬化性ホジキンリンパ腫と原発性縦隔大細胞型B細胞リンパ腫における,選択的9p24.1増幅,PD-1リガンド発現の増大,およびJAK2を介したさらなる誘導を示す
Authors: R Green Michael, Monti Stefano, J Rodig Scott, Juszczynski Przemyslaw, Currie Treeve, O’Donnell Evan, Chapuy Bjoern, Takeyama Kunihiko, Neuberg Donna, R Golub Todd, L Kutok Jeffery, A Shipp Margaret
Journal: Blood (2010)
VGF-derived peptide TLQP-21 modulates microglial function through C3aR1 signaling pathways and reduces neuropathology in 5xFAD mice
Authors: Farida El Gaamouch, Mickael Audrain, Wei-Jye Lin, Noam Beckmann, Cheng Jiang, Siddharth Hariharan, Peter S. Heeger, Eric E. Schadt, Sam Gandy, Michelle E. Ehrlich, Stephen R. Salton
Journal: Molecular Neurodegeneration (2020)

Multiomic studies by several groups in the NIH Accelerating Medicines Partnership for Alzheimer's Disease (AMP-AD) identified VGF as a major driver of Alzheimer's disease (AD), also finding that reduced VGF levels correlate with mean amyloid plaque density, Clinical Dementia Rating (CDR) and Braak scores. VGF-derived peptide TLQP-21 activates the complement C3a receptor-1 (C3aR1), predominantly expressed in the brain on microglia. However, it is unclear how mouse or human TLQP-21, which are not identical, modulate microglial function and/or AD progression.We performed phagocytic/migration assays and RNA sequencing on BV2 microglial cells and primary microglia isolated from wild-type or C3aR1-null mice following treatment with TLQP-21 or C3a super agonist (C3aSA). Effects of intracerebroventricular TLQP-21 delivery were evaluated in 5xFAD mice, a mouse amyloidosis model of AD. Finally, the human HMC3 microglial cell line was treated with human TLQP-21 to determine whether specific peptide functions are conserved from mouse to human.We demonstrate that TLQP-21 increases motility and phagocytic capacity in murine BV2 microglial cells, and in primary wild-type but not in C3aR1-null murine microglia, which under basal conditions have impaired phagocytic function compared to wild-type. RNA sequencing of primary microglia revealed overlapping transcriptomic changes induced by treatment with TLQP-21 or C3a super agonist (C3aSA). There were no transcriptomic changes in C3aR1-null or wild-type microglia exposed to the mutant peptide TLQP-R21A, which does not activate C3aR1. Most of the C3aSA- and TLQP-21-induced differentially expressed genes were linked to cell migration and proliferation. Intracerebroventricular TLQP-21 administration for 28 days via implanted osmotic pump resulted in a reduction of amyloid plaques and associated dystrophic neurites and restored expression of subsets of Alzheimer-associated microglial genes. Finally, we found that human TLQP-21 activates human microglia in a fashion similar to activation of murine microglia by mouse TLQP-21.These data provide molecular and functional evidence suggesting that mouse and human TLQP-21 modulate microglial function, with potential implications for the progression of AD-related neuropathology.
Family history (FH) of gastrointestinal (GI) cancer and behavioral risks: Analysis of an Internet-based risk assessment tool.
Authors: Ryan M. O'Keefe, Michael Joseph Lariviere, Isabella Amaniera, Carolyn Vachani, Margaret K. Hampshire, Christina Bach, Karen Arnold-Korzeniowski, James M. Metz, Christine E. Hill-Kayser
Journal: Journal of Clinical Oncology (2020)

807 Background: Certain behaviors are known modifiable risk factors for development of GI cancers. The relationship between family history (FH) of GI cancers and individuals’ behaviors is not well understood, but is important for risk assessment/ counseling. Methods: The OncoLink “Reduce My Risk” tool is a publicly available online survey created in 2009 to provide customized information regarding cancer risk. Details of this survey have been reported; research is IRB-approved. Differences between those with v. without FH of GI cancers were analyzed using chi-square test. Results: 28,001 surveys were submitted. Median age was 26y (18-101), 60% female, 87% lived in North America, 76% White/Non-Hispanic, 64% reported FH of cancer. Individuals with FH of CRC reported eating less red meat (31% v. 34%, p = 0.007), processed grains (55% v. 59%, p &lt; 0.001), or charred meats (14% v. 19%, p &lt; 0.001), but were equally likely to be vegetarian (9% v. 10%, p = 0.059). Those with FH of esophageal cancer were more likely to have GERD (16% v. 9%), smoke &gt; = 1 pack per day (7% vs. 4%) and drink alcohol (63% v. 55%) (p &lt; 0.001 for all). Those with FH of gastric cancer were more likely to have H. Pylori or gastric ulcers (5% v. 3%, p &lt; 0.001), but no difference in the consumption of smoked/salted foods (27% v. 25%, p = 0.20). Those with FH of HCC reported no differences in alcohol consumption (56% v. 55%, p = 0.41) or hepatitis B virus (HBV) vaccination (62% v. 62%, p = 0.66). Those with FH of anal cancer were more likely to have receptive anal intercourse (26% v. 16%, p &lt; 0.001) but showed no differences in human papillomavirus (HPV) vaccination (21% v. 22%, p = 0.91). Those with FH of HCC (15% v. 13%, p = 0.035), gastric (16% v. 13%, p = 0.001), esophageal (17% v. 13%, p &lt; 0.001), and anal (21% vs. 13%, p &lt; 0.001) cancers were more likely to be smokers; those with a FH of CRC were less likely (11% v. 13%, p = 0.006), and those with FH of pancreatic (12% vs. 13%, p = 0.71) or cholangiocarcinoma (15% vs. 13%, p = 0.59) showed no difference. Conclusions: Many individuals with a FH of GI cancers engage in behavioral and other modifiable risk factors that increase risk for GI and other cancers. Future work should explore utility of targeted intervention and screening.
カテーテルアブレーションにて治療したincision flutterの一例 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: 鳥越勝行, 松野匡克, 都築通孝, 井関淳, 金子鎮二, 篠田政典, 金山均
Journal: Circulation (2002)