tbuckley/cabot-search huggingface dataset:
Mode of Death Among Japanese Adults With Heart Failure With Preserved, Midrange, and Reduced Ejection Fraction
Authors: Takeshi Kitai, Chisato Miyakoshi, Takeshi Morimoto, Hidenori Yaku, Ryosuke Murai, Shuichiro Kaji, Yutaka Furukawa, Yasutaka Inuzuka, Kazuya Nagao, Yodo Tamaki, Erika Yamamoto, Neiko Ozasa, W. H. Wilson Tang, Takao Kato, Takeshi Kimura
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Despite intensive treatment, hospitalized patients with acute decompensated heart failure (ADHF) have a substantial risk of postdischarge mortality. Limited data are available on the possible differences in the incidence and mechanisms of death among patients with heart failure with reduced ejection fraction (HFrEF), heart failure with midrange ejection fraction (HFmrEF), and heart failure with preserved ejection fraction (HFpEF). <h3>Objectives</h3> To examine the incidences and mode of postdischarge mortality among patients with ADHF and to compare the risk profile among patients with HFrEF, HFmrEF, and HFpEF. <h3>Design, Setting, and Participants</h3> This prospective cohort study of 4056 patients hospitalized for ADHF analyzed data from 3717 patients who were discharged from October 1, 2014, to March 31, 2016. Data analysis was performed from April 1 to August 31, 2019. <h3>Exposures</h3> Death among patients with ADHF after hospital discharge. <h3>Main Outcomes and Measures</h3> All-cause death and cause of postdischarge mortality after the index hospitalization by left ventricular ejection fraction (LVEF) subgroup. <h3>Results</h3> A total of 3717 patients (mean [SD] age, 77.7 [12.0] years; 2049 [55.1%] male) were included in the study. The mean (SD) LVEF at baseline was 46.4% (16.2%). Among 3717 enrolled patients, 1383 (37.2%) were categorized as having HFrEF (LVEF, &lt;40%), 703 (18.9%) as having HFmrEF (LVEF, 40%-49%), and 1631 (43.9%) as having HFpEF (LVEF, ≥50%). The incidence and causes of death were evaluated after discharge from the index hospitalization. The median follow-up period was 470 days (interquartile range, 357-649 days), and the 1-year follow-up rate was 96%. During follow-up, all-cause death occurred in 848 patients (22.8%; HFrEF group: 298 [21.5%; 95% CI, 19.5%-23.8%]; HFmrEF group: 158 [22.5%; 95% CI, 19.5%-25.7%]; and HRpEF group: 392 [24.0%; 95% CI, 22.0%-26.2%];<i>P</i> = .26), cardiovascular deaths occurred in 523 patients (14.1%; HFrEF group: 203 [14.7%; 95% CI, 12.9%-16.6%]; HFmrEF group: 97 [13.8%; 95% CI, 11.4%-16.5%]; and HFpEF group: 223 [13.7%; 95% CI, 12.1%-15.4%];<i>P</i> = .71), and sudden cardiac death occurred in 98 patients (2.6%; HFrEF group: 44 [3.2%; 95% CI, 2.4%-4.2%]; HFmrEF group: 14 [2.0%; 95% CI, 1.2%-3.3%]; and HFpEF group: 40 [2.5%; 95% CI, 1.8%-3.3%];<i>P</i> = .23). The risks of causes of death were similar among the subtypes. <h3>Conclusions and Relevance</h3> The mode of death was similar among the heart failure subtypes. Given the nonnegligible incidence of sudden cardiac death in patients with HFpEF found in this study, further studies appear to be warranted to identify a high-risk subset in this population.
Clinical Applications of Nuclear Cardiology
Authors: Maria João Vidigal Ferreira, Manuel D. Cerqueira
Journal: Clinical Nuclear Medicine (2020)

Nuclear cardiology has continued to expand its already established role in the evaluation of cardiac patients with advances in hardware, software, new radiotracers, and clinical indications. These advances include high temporal and spatial resolution SPECT and PET cameras, hybrid imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and high-sensitivity detectors and new radiotracers that allow not only the evaluation of myocardial perfusion, viability, and function but also risk stratification for sudden death and the characterization of myocardial and vascular inflammation. This chapter will focus on the clinical applications of nuclear cardiology.
Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis
Authors: G Baroni
Journal: Hepatology (1996)

Interferon gamma (IFN-γ) inhibits in vitro the activation of hepatic stellate cells (HSC), the primary extracellular matrix-producing cells in liver fibrosis. This study was undertaken to determine in vivo the effect of IFN-γ in the rat model of liver fibrosis induced by dimethylnitrosamine (DMN), where HSC activation represents an early response to cell injury. Rats were killed after 1 or 3 weeks of treatment with DMN, IFN-γ, DMN + IFN-γ, or saline. Immunohistochemistry was used to identify proliferating (desmin- positive/bromodeoxyuridine (BrdU)-positive cells) and activated (α- smooth-muscle actin [α-SMA]-positive cells) HSCs. Collagen deposition was determined colorimetrically and by morphometry. The parenchymal extension of desmin- and actin-positive cells and of fibrotic tissue was measured by point-counting technique and expressed as a percentage of area. Western blot was used to determine laminin and fibronectin accumulation. The levels of messenger RNA (mRNA) for procollagen type I, fibronectin, and laminin were evaluated by Northern blot. No differences were observed in rats treated with either saline or IFN-γ alone. IFN-γ reduced HSC activation induced by liver injury, as shown by the decreased number of proliferating HSC and the reduction of parenchymal area occupied by α-SMA-positive cells observed in DMN + IFN-γ-treated animals compared with the DMN group. This was associated with reduced collagen, laminin, and fibronectin accumulation and lower levels of mRNA for procollagen type I, fibronectin, and laminin in the DMN + IFN-γ group. Thus, this study indicates that IFN-γ reduces extracellular matrix deposition in vivo by inhibition of HSC activation.
Long-term results of a phase II study of synchronous chemo radiotherapy in muscle invasive bladder cancer
Authors: S. A. Hussain, D. D. Stocken, D. R. Peake, J. G. Glaholm, A. Zarkar, D. M. A. Wallace, N. D. James
Journal: Journal of Clinical Oncology (2004)

4585 Background: We conducted a phase I/II study investigating synchronous chemoradiotherapy with mitomycin C and infusional 5-fluorouracil in muscle invasive bladder cancer. Early dose escalation results were previously published (Hussain et al Annals of Oncology 12: 929–935, 2001). We report the long term toxicity and efficacy results with the optimised regimen. Methods: Patients with muscle invasive bladder cancer with GFR > 25ml/minute were eligible. Mitomycin (12mg/m2 on day 1 only) and infusional 5-FU (500mg/m2/day) for 5 days was administered during weeks 1 and 4 of radiotherapy given to 55 Gy in 20 fractions. Results: Forty-one patients were enrolled, median age was 68 years, 33 male, 8 female. 20/41 (49%) patients had hydronephrosis at presentation and 25/41 (62%) had T3b or T4 disease. Four patients experienced Grade III thrombocytopenia and three patients had Grade III neutropenia. There were no episodes of febrile neutropenia. 4 patients experienced Grade III diarrhoea and 1 Grade III urgency and dysuria. 6 patients did not undergo cystoscopic evaluation due to early metastatic spread though there was no clinical suggestion of bladder failure. 25/35 evaluable patients (71%) had macroscopic complete response at 3-month cystoscopy, biopsy confirmed in 24/25. 16 (39%) patients remain alive with median follow-up of 50.7 (range 23.5–68.8) months - 14 of them with a functioning bladder with no reported long term treatment related bladder or bowel toxicity. 5/41 patients have undergone salvage cystectomy; 2 for persistent CIS, 2 T1 and 1 muscle invasive recurrence. 4 patients have received intra-vesical chemotherapy, of whom 2 remain alive with a functioning bladder. Overall 12, 24, 60 month (m) survival rates were 68% 49% and 36%. Local and distant progression free rates were 82% and 86% at 12-m and 79% and 75% at 24-m. Conclusions: Organ preservation using multimodality therapy is feasible and safe, even in patients with poor renal reserve, and does not compromise salvage therapies. A national phase III trial BC2001 (www.bc2001.org.uk) exploring the effects of synchronous chemo radiotherapy with this regimen is currently recruiting. No significant financial relationships to disclose.
Insulin-induced vascular redox dysregulation in human atherosclerosis is ameliorated by dipeptidyl peptidase 4 inhibition
Authors: Ioannis Akoumianakis, Ileana Badi, Gillian Douglas, Surawee Chuaiphichai, Laura Herdman, Nadia Akawi, Marios Margaritis, Alexios S. Antonopoulos, Evangelos K. Oikonomou, Costas Psarros, Nikolaos Galiatsatos, Dimitris Tousoulis, Attila Kardos, Rana Sayeed, George Krasopoulos, Mario Petrou, Uwe Schwahn, Paulus Wohlfart, Norbert Tennagels, Keith M. Channon, Charalambos Antoniades
Journal: Science Translational Medicine (2020)

Vascular oxidative stress in human atherosclerosis is reversed by restoring vascular insulin sensitivity using a dipeptidyl peptidase 4 inhibitor.
A hard choice for Tomasello
Authors: Philip Pettit
Journal: Behavioral and Brain Sciences (2020)

Abstract Michael Tomasello explains the human sense of obligation by the role it plays in negotiating practices of acting jointly and the commitments they underwrite. He draws in his work on two models of joint action, one from Michael Bratman, the other from Margaret Gilbert. But Bratman's makes the explanation too difficult to succeed, and Gilbert's makes it too easy.
Inflammatory Type 2 cDCs Acquire Features of cDC1s and Macrophages to Orchestrate Immunity to Respiratory Virus Infection
Authors: Cedric Bosteels, Katrijn Neyt, Manon Vanheerswynghels, Mary J. van Helden, Dorine Sichien, Nincy Debeuf, Sofie De Prijck, Victor Bosteels, Niels Vandamme, Liesbet Martens, Yvan Saeys, Els Louagie, Manon Lesage, David L. Williams, Shiau-Choot Tang, Johannes U. Mayer, Franca Ronchese, Charlotte L. Scott, Hamida Hammad, Martin Guilliams, Bart N. Lambrecht
Journal: Immunity (2020)
Phase I study of pemetrexed (P) and pegylated liposomal doxorubicin (PLD) in patients with refractory breast, ovarian, primary peritoneal, or fallopian tube cancer
Authors: D. A. Richards, D. Loesch, S. J. Vukelja, H. H. Wu, W. J. Hyman, J. Nieves, Y. Wang, S. Hu, O. Shonukan, D. Tai
Journal: Journal of Clinical Oncology (2009)

e13515 Background: P and PLD are clinically active as single agents and synergistic in preclinical models. This phase I, open-label trial determined the maximum tolerated dose (MTD) and safety profile of P followed by PLD in patients (pts) with breast or gynecologic cancers. Methods: Using standard phase I (3+3 dose escalation) study design, cohorts of 3–9 pts received escalating doses of P followed by PLD in 28-day cycles: P 400–500 mg/m 2 on Days 1 and 15 and PLD 30–45 mg/m 2 on Day 1. All pts received folic acid (350–1000 μg daily) and vitamin B 12 (1000 μg) until 21 days after last dose of P. Pts continued until dose-limiting toxicity (DLT) or disease progression (PD) occurred. Results: From 11/05 to 1/08, 29 pts were registered/treated. Median age: 60.6 years (range, 47.5–80.1); ECOG performance status 0/1: 28%/72%; primary disease sites: ovarian (55%), breast (35%), peritoneal (10%); prior therapies: chemotherapy (100%), surgery (72%), hormones/biologics (35%), radiation (21%). Dosing results are shown below. At dose level (L) 2 and L3, 1 pt/cohort had DLTs; L5 was added and 3/3 pts had DLTs; 4 more pts were treated at L4 (1 pt replaced). Most frequent drug-related Grade 3–4 hematologic toxicities: neutropenia (86%), leukopenia (59%), thrombocytopenia (48%), anemia (41%). Most frequent drug-related Grade 3–4 nonhematologic toxicities: hand-foot syndrome (14%), hypokalaemia (10%). Major reasons for discontinuation: PD (48%), toxicity (28%), pt request (14%). Overall best responses (n=24): 5 pts (21%) had partial response (PR), 14 pts (58%) had stable disease (SD), 2 pts (8%) had PD, 3 pts (13%) were not evaluable. All 5 PR and 8 SD pts were ovarian; 5 SD and both PD pts were breast. Conclusions: P followed by PLD was reasonably tolerated in this heavily-pretreated population. The MTD was P 500 mg/m 2 and PLD 40 mg/m 2 . These dose levels may be carried forward to phase II studies in more specific patient populations. [Table: see text] [Table: see text]
Compelled Disclosure of Health Information
Authors: Mark A Rothstein, Meghan K Talbott
Journal: JAMA (2006)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Diagnostic Work-Up of Contralateral Breast Cancers Has Not Improved over Calendar Period.
Authors: M. Sandberg, M. Hartman, P. Hall, K. Czene
Journal: Cancer Research (2009)

Abstract Background: Contralateral breast cancer (CBC) is diagnosed in 1-2.6 % of all breast cancer patients directly at diagnosis, after that the risk still remains high (0.7% per year) throughout life of the patient. Breast cancer patients are followed up by palpation and clinical mammography after their diagnosis, partly to be able to diagnose a possible CBC. The aim of this study is to investigate if the diagnostic work-up of patients with breast cancer has improved over the last thirty years and resulted in earlier CBC diagnosis.Materials and Methods: Synchronous contralateral breast cancer is here defined as two cancers occurring maximum 3 months apart, cancers with longer latency time are defined as metachronous. The study population is restricted to patients with maximum three years between the two cancer diagnoses. In this study we used two cohorts; all CBCs in Sweden 1976-2004 (N: 3260), and all CBCs in Stockholm during 1976-2005 (N: 688), the smaller cohort had more detailed information. The study participants were selected from two population-based registers (Sweden Cancer Register and Stockholm Breast Cancer Register). With logistic regression we calculated the odds ratio of being diagnosed synchronously, as compared to metachronously, adjusted for calendar period and age at first diagnosis.Results: The risk of synchronous diagnosis was increased by 27% per each 5-year period, the change was statistically significant. We then investigate if this risk increase by calendar period was due to improved clinical work-up, by including detection mode in the model. We found that the risk estimates for calendar period persisted, thus giving no evidence for improvement of clinical work-up during the study period. This result did not change when stratifying the study population by age at first diagnosis (below/above 55). Next, we instead included adjuvant therapy for the first cancer in the model and the association with calendar period decreased to non-significant levels. We also showed that the proportion of CBCs detected trough clinical work-up has not increased over calendar period (p=0.89), neither when including, nor excluding, screening mammography as part of the work-up. The mean tumour size of the contralateral breast cancer was 16.0 mm and has not decreased over the study period (p:0.62)Discussion: We found an increase in the proportion of synchonous CBCs compared to metachronous over calendar period, this change is not associated with clinical work-up, but with adjuvant therapy. This study gives no indications of any improvement in diagnostic work-up of contralateral breast cancer over the last thirty years. Such an improvement would potentially be very important for survival of the growing population of (first) breast cancer survivors. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4011.
Factors Determining Utilization of Stem Cell Transplant (SCT) for Initial Therapy of Multiple Myeloma (MM) By Patient Race: Exploring Intra-Racial Healthcare Disparities
Authors: Sikander Ailawadhi, Ryan D. Frank, Nicolette T. Chimato, Zahara Meghji, Raj Patel, Prachi Jani, Tanya S. Kakar, Mark A. Fiala, Sonikpreet Aulakh, David O. Hodge, Taimur Sher, Vivek Roy, Prakash Vishnu, Meghna Ailawadhi, Victoria R. Alegria, Aneel Paulus, Asher A. Chanan-Khan
Journal: Blood (2017)
Durable Complete Response With Immune Checkpoint Inhibitor in Breast Cancer With High Tumor Mutational Burden and APOBEC Signature
Authors: Saranya Chumsri, Ethan S. Sokol, Aixa E. Soyano-Muller, Ricardo D. Parrondo, Gina A. Reynolds, Aziza Nassar, E. Aubrey Thompson
Journal: Journal of the National Comprehensive Cancer Network (2020)

Increasing data support the importance of preexisting host immune response and neoantigen burden for determining response to immune checkpoint inhibitors (ICIs). In lung cancer and melanoma, tumor mutational burden (TMB) has emerged as an independent biomarker for ICI response. However, the significance of TMB in breast cancer, particularly in the context of PD-L1 negativity, remains unclear. This report describes a patient with HER2-negative breast cancer with high TMB and an apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) trinucleotide signature; her disease was refractory to multiple lines of treatments but achieved durable complete response using ICIs and capecitabine. Additional analysis of the tumor revealed a low amount of stromal tumor-infiltrating lymphocytes (sTILs) and PD-L1 negativity, reflecting a poor preexisting host immune response. In collaboration with Foundation Medicine, comprehensive genomic profiling from 14,867 patients with breast cancer with the FoundationOne test was evaluated. Using the cutoff of ≥10 mutations/megabase (mut/Mb) for high TMB, PD-L1 positivity and TMB-high populations were not significantly overlapping (odds ratio, 1.02; P =.87). Up to 79% of TMB-high tumors with &gt;20 mut/Mb were PD-L1–negative. Our study highlights that despite having low TILs and PD-L1 negativity, some patients may still experience response to ICIs.
Systemic immune-inflammation index to predict the clinical outcome in patients with metastatic renal cell cancer treated with sunitinib.
Authors: Cristian Lolli, Marco Maruzzo, Lisa Derosa, Teodoro Sava, Matteo Santoni, Francesco Massari, Matthew James Wheater, Michele Aieta, Emanuela Scarpi, Francesca La Russa, Simon J. Crabb, Stefano Cascinu, Luca Galli, Umberto Basso, Ugo De Giorgi
Journal: Journal of Clinical Oncology (2016)

547 Background: A systemic immune-inflammatory index (SII) based on lymphocyte (L), neutrophil (N), and platelet (P) counts has been recently developed. In this retrospective analysis, we explored its prognostic and predictive value at baseline and changes at week 6 during first-line sunitinib in patients (pts) with metastatic renal cell cancer (mRCC). Methods: We included 335 consecutive pts mRCC treated with first-line sunitinib for which P,N, and L data were available at start of therapy, and 6 weeks thereafter. The SII was defined as follows: SII = P x N/L. The X-tile 3.6.1 software (Yale University, New Haven, CT) was used for bioinformatic analysis of the baseline data to determine the cutoff value of SII. Progression-free survival (PFS), overall survival (OS) and their 95% confidence interval (95% CI) were estimated by Kaplan-Meier method and compared with logrank test. The impact of SII conversion on PFS and OS was evaluated by Cox regression analyses. Results: An optimal cutoff point for the SII of 730 x 10 9 stratified these pts into high (≥ 730) and low SII (&lt;730) groups. Median age was 63 years (range, 27 to 88); histotype clear cell carcinoma was reported in 94% of cases; 29.6%, 59.4% and 11% were classified in the favorable, intermediate and poor Motzer prognostic groups, respectively. The median PFS was 6.2 months (mo) (95% CI=5.5-9.5) in pts with baseline SII ≥730 and 17.7 mo (14.3-21.8) in those with SII &lt;730, P&lt;0.0001. The median OS was 13.7 mo (95% CI=9.6-20.3) in pts with baseline SII ≥730 and 41.8 mo (95% CI=34.5-51.8) in those with baseline SII &lt;730, P&lt;0.0001. Data for SII at baseline and change in SII by week 6 using a cut-off of 730 are shown in the table. Conclusions: The SII is a powerful prognostic and predictive indicator of poor outcome in pts with mRCC. A validation study from prospective data is warranted. [Table: see text]
Clinical trials for COVID-19 should include sex as a variable
Authors: Evelyne Bischof, Jeannette Wolfe, Sabra L. Klein
Journal: Journal of Clinical Investigation (2020)

The number of COVID-19 cases appears to be comparable between men and women, but the severity of disease and death is two times greater for men than for women (1, 2).History, including the 1918 influenza pandemic, warned us that male biases in COVID-19 could occur.In this Viewpoint, we focus on biological explanations, with a forward look at why clinicians and biomedical researchers should consider sex as a biological variable that will affect treatment outcomes for COVID-19.There is a long history of not analyzing or reporting differences between women and men in the prophylactic or therapeutic treatment of infectious diseases.We seek to reverse this trend and call on investigators developing and testing therapeutic and prophylactic approaches for COVID-19 to design studies that are inclusive of male versus female differences in drug responses, immunotherapies, vaccines, and nonpharmacological interventions.
Abstract 9719: Insurance Disparity in Cardiovascular Mortality Among Early Stage, Non-elderly Cancer Survivors in the US
Authors: Tiantian Shi, Changchuan Jiang, Stuart W Zarich
Journal: Circulation (2019)

Background: Cancer and cardiovascular diseases (CVD) are the two leading causes of death in the US. Non-elderly, early-stage cancer(NEESC) patients have the most promising prognosis with appropriat...
Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis
Authors: Mauro Chiarito, Jorge Sanz-Sánchez, Francesco Cannata, Davide Cao, Matteo Sturla, Cristina Panico, Cosmo Godino, Damiano Regazzoli, Bernhard Reimers, Raffaele De Caterina, Gianluigi Condorelli, Giuseppe Ferrante, Giulio G Stefanini
Journal: The Lancet (2020)