tbuckley/cabot-search huggingface dataset:
Letter to the Editor: Statins and Reduced Risk of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B
Authors: Rui Huang, Jian Wang, Weihua Wu, Xiaomin Yan, Chao Wu
Journal: Hepatology (2019)

The study was supported by the National Science and Technology Major Project of China (2018ZX10302205), National Natural Science Foundation of China (81672025 and 81702011), Jiangsu Science and Technology Development Plan (BE2017605), Jiangsu Provincial Medical Innovation Team (CXTDA2017005), and Nanjing Medical Science and Technique Development Foundation (QRX17121). Potential conflict of interest: Nothing to report. To the Editor: We read with great interest the article by Goh et al.1 We should applaud their work for demonstrating the remarkable reduction in hepatocellular carcinoma (HCC) risk by the addition of statins in patients with chronic hepatitis B (CHB). However, several points need further clarification. First, although the investigators had adjusted for some potentially beneficial medications of HCC prevention including antiviral therapy and antiplatelet therapy, they failed to adjust for the concomitant use of antidiabetic medications.1 We noted that 39.6% of patients in the statin cohort and 10.9% of patients in the non‐statin cohort had diabetes mellitus in the study.1 Antidiabetic medications are proved to have inherent cancer‐modifying effects on HCC and may bias the results.2 Moreover, coffee consumption is also demonstrated to reduce the risk of HCC and should be adjusted.3 Second, although antiviral treatment was adjusted by the investigators, these patients were not stratified by types of antiviral drugs. Antiviral drugs may have different effectiveness in the prevention of HCC in CHB.4 For example, tenofovir treatment is reported to be associated with a lower HCC risk than entecavir treatment in CHB patients.4 Thus, the effects of types of antiviral drugs need to be taken into consideration. Third, by using ultrasonography or computed tomography or magnetic resonance image criteria, the authors might not be able to correctly identify liver cirrhosis, which is the single most important risk factor for HCC in CHB. It is possible that cirrhosis, especially compensated cirrhosis, may not have been diagnosed or recorded in most practice settings. Although liver biopsy might not be available for all patients, noninvasive tests such as liver stiffness measurement, aspartate aminotransferase–to‐platelet ratio index, and fibrosis‐4 index can predict CHB‐related cirrhosis with moderate to high sensitivity and accuracy.5 Therefore, if the authors could identify cirrhosis by noninvasive tests, the study would be more convincing. Finally, regarding their endpoints under analysis, results for statins are only shown for HCC risk. No data are presented for the effects of statins on fibrosis progression or risk of cirrhosis. These outcomes should be subsequently analyzed to help guide both clinicians and researchers on the choice of statins.
Pharmacologic Acute and Preventive Treatment for Migraine in Children and Adolescents
Authors: Christina L. Szperka, Juliana H. VanderPluym, Christopher B. Oakley
Journal: JAMA Neurology (2019)

This guideline summary provides a review of the American Academy of Neurology and the American Headache Society's guidelines on Acute Treatment of Migraine in Children and Adolescents and Pharmacologic Treatment for Pediatric Migraine Prevention.
Incorporation of Biomarkers Into Risk Assessment for Allocation of Antihypertensive Medication According to the 2017 ACC/AHA High Blood Pressure Guideline
Authors: Ambarish Pandey, Kershaw V. Patel, Wanpen Vongpatanasin, Colby Ayers, Jarett D. Berry, Robert J. Mentz, Michael J. Blaha, John W. McEvoy, Paul Muntner, Muthiah Vaduganathan, Adolfo Correa, Javed Butler, Daichi Shimbo, Vijay Nambi, Christopher deFilippi, Stephen L. Seliger, Christie M. Ballantyne, Elizabeth Selvin, James A. de Lemos, Parag H. Joshi
Journal: Circulation (2019)

Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear. Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/<100 mm Hg) were further stratified by biomarker status. Cumulative incidence rates for CV event (atherosclerotic cardiovascular disease or heart failure), and the corresponding 10-year number needed to treat to prevent 1 event with intensive BP lowering (to target systolic BP <120 mm Hg), were estimated for BP and biomarker-based subgroups. The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP <160/100 mm Hg, those with versus without an elevated biomarker had a 10-year CV incidence rate of 15.1% and 7.9%, with a 10-year number needed to treat to prevent 1 event of 26 and 49, respectively. Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk.
A Rare Case of Primary Ventricular Lymphoma Presented on FDG PET/CT
Authors: Dong Wang, Min Su, JingXing Xiao
Journal: Clinical Nuclear Medicine (2019)

Primary ventricular lymphoma is a rare form of non-Hodgkin lymphoma confined to the central nervous system. A 51-year-old woman presented with a 4-month history of unsteady gait and progressive decline in memory. An outside brain MRI showed multiple space-occupying lesions in the ventricles, which suggested malignancy. Staging with FDG PET/CT demonstrated not only hypermetabolic masses in the lateral, third, and fourth ventricles but also a hypermetabolic lesion in the spinal cord. A biopsy of the right lateral ventricle tumor confirmed diffuse large B-cell lymphoma.
Breast Cancer Mortality After Implementation of Organized Population-Based Breast Cancer Screening in Norway
Authors: Sofie Sebuødegård, Edoardo Botteri, Solveig Hofvind
Journal: JNCI Journal of the National Cancer Institute (2019)

We estimated breast cancer (BC) mortality reduction associated with invitations to a nationwide population-based screening program and with changes in treatment.BreastScreen Norway started in 1996 and became nationwide in 2005. It invites women aged 50-69 years to biennial mammographic screening. We retrieved individual-level data for 1 340 333 women from national registries. During 1996-2014 (screening window), women contributed person-years in noninvited and invited periods. We created comparable periods for 1977-1995 (prescreening window) by dividing the follow-up time for each woman into pseudo-noninvited and pseudo-invited periods. We estimated BC mortality for the four periods, using the so-called evaluation model: counting BC deaths in each period for all women diagnosed within the period and counting BC deaths and person-years after screening-age for those diagnosed within screening age. We used a multivariable flexible parametric survival model to estimate hazard ratio (HR) for the effect of invitation and improved treatment.Using the regression approach, we found 5818 BC deaths across 16 533 281 person-years. Invitations to screening reduced BC mortality by 20% (HR = 0.80, 95% confidence interval [CI] = 0.70 to 0.91) among women 50 years and older and by 25% (HR = 0.75, 95% CI = 0.65 to 0.86) among screening-aged women. The treatment effect was 23% (HR = 0.77, 95% CI = 0.65 to 0.92) for women 50 years and older and 17% (HR = 0.83, 95% CI = 0.74 to 0.94) for screening-aged women.We observed a similar reduction in BC mortality associated with invitations to screening and improvements in treatment during 1977-2014, among women 50 years and older.
Mutation-derived Neoantigen-specific T-cell Responses in Multiple Myeloma
Authors: Deepak Perumal, Naoko Imai, Alessandro Laganà, John Finnigan, David Melnekoff, Violetta V. Leshchenko, Alexander Solovyov, Deepu Madduri, Ajai Chari, Hearn Jay Cho, Joel T. Dudley, Joshua D. Brody, Sundar Jagannath, Benjamin Greenbaum, Sacha Gnjatic, Nina Bhardwaj, Samir Parekh
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Somatic mutations in cancer cells can give rise to novel protein sequences that can be presented by antigen-presenting cells as neoantigens to the host immune system. Tumor neoantigens represent excellent targets for immunotherapy, due to their specific expression in cancer tissue. Despite the widespread use of immunomodulatory drugs and immunotherapies that recharge T and NK cells, there has been no direct evidence that neoantigen-specific T-cell responses are elicited in multiple myeloma. Experimental Design: Using next-generation sequencing data we describe the landscape of neo-antigens in 184 patients with multiple myeloma and successfully validate neoantigen-specific T cells in patients with multiple myeloma and support the feasibility of neoantigen-based therapeutic vaccines for use in cancers with intermediate mutational loads such as multiple myeloma. Results: In this study, we demonstrate an increase in neoantigen load in relapsed patients with multiple myeloma as compared with newly diagnosed patients with multiple myeloma. Moreover, we identify shared neoantigens across multiple patients in three multiple myeloma oncogenic driver genes (KRAS, NRAS, and IRF4). Next, we validate neoantigen T-cell response and clonal expansion in correlation with clinical response in relapsed patients with multiple myeloma. This is the first study to experimentally validate the immunogenicity of predicted neoantigens from next-generation sequencing in relapsed patients with multiple myeloma. Conclusions: Our findings demonstrate that somatic mutations in multiple myeloma can be immunogenic and induce neoantigen-specific T-cell activation that is associated with antitumor activity in vitro and clinical response in vivo. Our results provide the foundation for using neoantigen targeting strategies such as peptide vaccines in future trials for patients with multiple myeloma.
Abstract 16455: Heart Failure Outcomes Among Veterans With Human Immunodeficiency Virus Infection
Authors: Sebhat Erqou, Lan Jiang, Michelle Lally
Journal: Circulation (2019)

Background: Data on patient characteristic, prognosis, and predictors of outcomes of heart failure (HF) in people living with HIV (PLHIV) are limited. Methods: We conducted a retrospective cohort a...
Revascularisation: reducing variation in waiting times could reduce amputations, audit finds
Authors: Elisabeth Mahase
Journal: BMJ (2019)

All patients admitted as an emergency with critical limb ischaemia should have a revascularisation procedure within five days, an audit has recommended.1

The National Vascular Registry annual report, developed by the Royal College of Surgeons of England, the Vascular Society of Great Britain and Ireland, and the British Society of Interventional Radiology, found that many patients currently had their bypass within five days but that this varied widely among trusts.

Jon Boyle, a consultant vascular surgeon, clinical lead for the National Vascular Registry, and chair of the Audit and Quality Improvement Committee of the Vascular Society, said, “My hope is that vascular units, at NHS hospitals across the UK, will use today’s report to address variations in wait times for treatment, and in doing so will reduce amputation rates among this group of patients.”

The report examined current UK-wide standards of care in lower …
Guidelines for benchmarking of optimization-based approaches for fitting mathematical models
Authors: Clemens Kreutz
Journal: Genome biology (2019)

Abstract Insufficient performance of optimization-based approaches for the fitting of mathematical models is still a major bottleneck in systems biology. In this article, the reasons and methodological challenges are summarized as well as their impact in benchmark studies. Important aspects for achieving an increased level of evidence for benchmark results are discussed. Based on general guidelines for benchmarking in computational biology, a collection of tailored guidelines is presented for performing informative and unbiased benchmarking of optimization-based fitting approaches. Comprehensive benchmark studies based on these recommendations are urgently required for the establishment of a robust and reliable methodology for the systems biology community.
Cardiovascular Risk Factors and Disease After Male Germ Cell Cancer
Authors: Jakob Lauritsen, Merete Kjaer Hansen, Mikkel Bandak, Michael Bay Kreiberg, Julie Wang Skøtt, Thomas Wagner, Maria Gry Gundgaard Kier, Niels Vilstrup Holm, Mads Agerbæk, Ramneek Gupta, Christian Dehlendorff, Klaus Kae Andersen, Gedske Daugaard
Journal: Journal of Clinical Oncology (2019)

PURPOSE To analyze the risk of cardiovascular disease (CVD) after treatment of male germ cell cancer (GCC). METHODS Clinical data were extracted from the Danish Testicular Cancer database. For each patient, 10 men matched on date of birth were identified in the Danish normal population by risk-set sampling. Cardiovascular risk factors, CVD, and associated deaths were identified in Danish registries. The association between treatment and outcomes was analyzed by separate Cox models for each outcome. Cancer treatment was included as a time-varying covariate. RESULTS We included 5,185 patients with GCC and 51,850 men in the normal population. Median follow-up was 15.8 years. Treatment with bleomycin-etoposide-cisplatin (BEP; n = 1,819) was associated with increased risks of hypertension and hypercholesterolemia. Hazard ratios (HRs) of CVD &lt; 1 year after initiation of BEP treatment were as follows: myocardial infarction (HR, 6.3; 95% CI, 2.9 to 13.9), cerebrovascular accident (HR, 6.0; 95% CI, 2.6 to 14.1), and venous thromboembolism (HR, 24.7; 95% CI, 14.0 to 43.6). One year after BEP treatment, the risk of CVD decreased to normal levels, but after 10 years, increasing risks were found for myocardial infarction (HR, 1.4; 95% CI, 1.0 to 2.0) and cardiovascular death (HR, 1.6; 95% CI, 1.0 to 2.5). Radiotherapy (n = 780) increased the risk of diabetes at long-term follow-up (HR, 1.4; 95% CI, 1.0 to 2.0) but not that of other outcomes. With surveillance (n = 3,332), cardiovascular risk factors, CVD, and cardiovascular death data were comparable to that of the normal population. CONCLUSION Treatment with BEP was associated with highly increased risks of CVD &lt; 1 year after treatment start and mildly increased risks after 10 years of follow-up. Radiotherapy increased the risk of diabetes but not incident CVD. The risk of CVD in patients followed in a surveillance program was comparable to that of the normal population.
Safety and Effectiveness of Apixaban, LMWH, and Warfarin Among Venous Thromboembolism Patients with Active Cancer: A Retrospective Analysis Using Four US Claims Databases
Authors: Alexander T Cohen, Allison Keshishian, Theodore Lee, Gail Wygant, Lisa Rosenblatt, Patrick Hlavacek, Jack Mardekian, Daniel Wiederkehr, Janvi Sah, Xuemei Luo
Journal: Blood (2019)
Abstract I17: Genomic loss of the wild-type KRAS allele in pancreatic tumor progression and metastasis
Authors: Han Yan, Chih-Chieh Yu, Stuart Fine, Ayman Lee, Ye-Ran Yang, Juan Yan, Dario Garcia-Carracedo, Dillon Karg, Edwin Cheung, Richard Friedman, Emily Chen, Ji Luo, Yi Miao, Wanglong Qiu, Gloria Su
Journal: Cancer Research (2019)

Abstract KRAS is a major oncogenic driver in pancreatic ductal adenocarcinoma (PDAC). Intriguingly, human tumors with RAS mutations often display loss of the remaining wild-type (WT) allele, including PDAC. We previously reported that selective loss of WT Kras allele is associated with PDAC progression to metastasis in both mice and humans. These data suggest that WT KRAS functions as a tumor suppressor in the context of mutant KRAS and loss of WT KRAS offers growth advantage in clonal evolution and tumor progression to metastasis. To investigate the underlying mechanism, we have examined the impact of inducible WT KRAS expression on human PDAC cell lines that had spontaneously lost the WT allele. We observed re-expression of WT KRAS significantly attenuated the malignancy of pancreatic cancer cells in vitro and in vivo. RNA-Seq and proteomic analyses identified HIPPO signaling, specifically YAP1 activation, is inhibited by WT KRAS restoration. We observed a marked reduction of YAP1 nuclear localization and a consequent inhibition of YAP1 transcriptional activity upon restoration of WT KRAS. Expression of constitutively activated YAP1 mitigated the growth-inhibitory effects of WT KRAS, confirming that YAP1 is a downstream effector of the pathway. Furthermore, YAP1 nuclear localization was found to be associated with poor prognosis in PDAC patients. Together, these results offer a novel mechanism that WT KRAS suppresses tumor metastasis via inhibition of YAP1 activation and further demonstrate that genomic loss of the WT KRAS allele is not a mere consequence of genomic instability but rather a selective event that promotes pancreatic tumor progression to metastasis. Citation Format: Han Yan, Chih-Chieh Yu, Stuart Fine, Ayman Lee, Ye-Ran Yang, Juan Yan, Dario Garcia-Carracedo, Dillon Karg, Edwin Cheung, Richard Friedman, Emily Chen, Ji Luo, Yi Miao, Wanglong Qiu, Gloria Su. Genomic loss of the wild-type KRAS allele in pancreatic tumor progression and metastasis [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr I17.
Are we missing the target? Are we aiming too low? What are the aerobic exercise prescriptions and their effects on markers of cardiovascular health and systemic inflammation in patients with knee osteoarthritis? A systematic review and meta-analysis
Authors: Jenna M Schulz, Trevor B Birmingham, Hayden F Atkinson, Emilie Woehrle, Codie A Primeau, Michael J Lukacs, Baraa K Al-Khazraji, Michaela C M Khan, Bryn O Zomar, Robert J Petrella, Frank Beier, C Thomas Appleton, J Kevin Shoemaker, Dianne M Bryant
Journal: British Journal of Sports Medicine (2019)

Objectives We systemically reviewed published studies that evaluated aerobic exercise interventions in patients with knee osteoarthritis (OA) to: (1) report the frequency, intensity, type and time (FITT) of exercise prescriptions and (2) quantify the changes in markers of cardiovascular health and systemic inflammation. Data sources PubMed, CINAHL, Scopus; inception to January 2019. Eligibility criteria Randomised clinical trials (RCT), cohort studies, case series. Design We summarised exercise prescriptions for all studies and calculated effect sizes with 95% CIs for between-group (RCTs that compared exercise and control groups) and within-group (pre-post exercise) differences in aerobic capacity (VO 2 ), heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and inflammatory markers (interleukin-6 (IL-6), tumour necrosis factor-alpha). We pooled results where possible using random effects models. Results Interventions from 49 studies were summarised; 8% (4/49) met all FITT guidelines; 16% (8/49) met all or most FITT guidelines. Fourteen studies (10 RCTs) reported at least one marker of cardiovascular health or systemic inflammation. Mean differences (95% CI) indicated a small to moderate increase in VO 2 (0.84 mL/min/kg; 95% CI 0.37 to 1.31), decrease in HR (−3.56 beats per minute; 95% CI −5.60 to −1.52) and DBP (−4.10 mm Hg; 95% CI −4.82 to −3.38) and no change in SBP (−0.36 mm Hg; 95% CI −3.88 to 3.16) and IL-6 (0.37 pg/mL; 95% CI −0.11 to 0.85). Within-group differences were also small to moderate. Conclusions In studies of aerobic exercise in patients with knee OA, very few interventions met guideline-recommended dose; there were small to moderate changes in markers of cardiovascular health and no decrease in markers of systemic inflammation. These findings question whether aerobic exercise is being used to its full potential in patients with knee OA. PROSPERO registration number CRD42018087859.
Symptomatic Heart Failure in Acute Leukemia Patients Treated With Anthracyclines
Authors: Yu Kang, Bruna Leal Assuncao, Srinivas Denduluri, Shannon McCurdy, Selina Luger, Bénédicte Lefebvre, Joseph Carver, Marielle Scherrer-Crosbie
Journal: JACC CardioOncology (2019)

The purpose of this study was to investigate the occurrence and develop a risk score for heart failure (HF) in acute leukemia. Knowledge is scarce regarding the incidence and risk factors of symptomatic HF in patients with acute leukemia. Baseline clinical and echocardiographic parameters, including indices of cardiac function (left ventricular ejection fraction and myocardial strain [global longitudinal strain; GLS]), were obtained in 450 patients with acute leukemia treated with anthracyclines, before chemotherapy initiation. Potential risk factors for HF were evaluated using Fine and Gray's regression analysis, and from this, a 21-point risk score was generated. Forty patients (8.9%) developed HF. The HF risk score included a baseline GLS >−15% (indicative of greater impairment) (6 points), baseline left ventricular ejection fraction <50%, pre-existing cardiovascular disease, acute myeloid leukemia (4 points each), cumulative anthracycline dose ≥250 mg/m2 (2 points), and age >60 years (1 point). Patients were stratified into low (score 0 to 6), moderate (score 7 to 13), and high risk (score 14 to 21). The estimated 1-year cumulative incidence of HF for low-, moderate-, and high-risk groups was 1.0%, 13.6%, and 35.0%, respectively (p < 0.001). The HF risk score was also predictive of all-cause mortality (p < 0.001). After adjustment for age and leukemia type, however, only GLS was significantly associated with all-cause mortality (hazard ratio: 1.73; 95% confidence interval: 1.30 to 2.31; p < 0.001). We developed a baseline risk score to determine risk of HF in patients with acute leukemia. Additional studies are needed to determine the external validity of these findings.
No doing without time
Authors: Shen Pan, Peter Carruthers
Journal: Behavioral and Brain Sciences (2019)

Abstract Hoerl &amp; McCormack claim that animals don't represent time. Because this makes a mystery of established findings in comparative psychology, there had better be some important payoff. The main one they mention is that it explains a clash of intuition about the reality of time's passage. But any theory that recognizes the representational requirements of agency can do likewise.