tbuckley/cabot-search huggingface dataset:
Phase II multicenter pilot study of safety, efficacy, and immune cell profiling in advanced hepatocellular carcinoma (HCC) on combination of sorafenib (SOR) plus nivolumab (NIVO).
Authors: Bridget Keenan, Madeline J Griffith, Kelly Bauer, Paige M. Bracci, Spencer Behr, Sarah E Umetsu, John Dozier Gordan, Zoe Ngo, Syma Iqbal, Diana L. Hanna, Alan P. Venook, Anthony B. El-Khoueiry, Lawrence Fong, Robin Kate Kelley
Journal: Journal of Clinical Oncology (2019)

TPS464 Background: The antiangiogenic tyrosine kinase inhibitor (TKI) SOR prolongs survival in advanced HCC, but responses occur in fewer than 5% of patients (pts) and median progression-free survival (PFS) is less than 6 months. Immune checkpoint inhibition (CPI) with the PD-1 inhibitor, NIVO, achieved an overall response rate (ORR) of approximately 20% in sorafenib-naïve pts enrolled on CheckMate 040 trial though most pts had progression. In preclinical studies, TKI can inhibit regulatory T cells and myeloid derived suppressor cells, immune cell subsets which may contribute to CPI resistance. CD8 + T cells in sorafenib-resistant tumors are characterized by PD-1 expression, providing rationale for a combined approach. The combination of TKI or the anti-angiogenic bevacizumab with CPI improves anti-tumor activity in HCC mouse models and in preliminary clinical studies. This study will examine the safety, maximum tolerated dose (MTD), and ORR of the combination of SOR plus NIVO in advanced HCC pts, along with correlative analyses of tumor and circulating immune cells. Methods: Eligible pts must have Child-Pugh A liver function and advanced HCC, without prior systemic therapy and measurable by RECIST 1.1. In Part 1 (3+3 dose escalation), SOR dose will be 400 mg QD or BID plus NIVO 240 mg IV Q2 weeks. In Part 2, Arm 1, pts will start NIVO Cycle 1, Day 1 (C1D1), with addition of SOR at MTD on C1D15; in Part 2, Arm 2, SOR is given at MTD on C1D1 with addition of NIVO on C1D15. Primary endpoints are MTD of SOR (Part 1) and ORR by RECIST 1.1 with H 0 7.5% vs. H 1 25% (Part 2). For expected sample size of 24 evaluable pts in Part 2, the power is 83% with 1-sided alpha 5% to determine ORR &gt;25% by Chi-square tests. Secondary endpoints are safety, duration of response, PFS, and overall survival. Exploratory endpoints include peripheral and tumor immune cell profiling, PD-L1 expression, and alpha-fetoprotein (AFP) response. An interim safety analysis will be performed after 50% enrollment in Part 2. Optional paired biopsies in Part 2 will allow for investigation of the tumor microenvironment on SOR, NIVO, and combination. Clinical trial information: NCT03439891.
Abstract 18574: Physical Activity Has Favorable Effects on Cardiovascular Risk Factors and Arterial Stiffness: Insights From Corinthia Study
Authors: Evangelos Oikonomou, Georgios Lazaros, Evgenia Christoforatou, Christos Chasikidis, George-Angelo Papamikroulis, Konstantinos Mourouzis, Georgia Vogiatzi, Sotirios Tsalamandris, Evgenia Bourouki, Savvas Mazaris, Aimilios Kalampogias, Charililia Ververeli, Petros Fountoulakis, Georgios Georgiopoulos, Dimitrios Tousoulis
Journal: Circulation (2017)

Introduction: Arterial stiffness significantly contributes to atherosclerosis progression and adversely affect cardiovascular prognosis Hypothesis: Increased physical activity (PA) may attenuate th...
One Size Does Not Fit to All: Intolerant or Resistant CML Patients Could Benefit from Different Ponatinib Starting Dose Strategies. Multicenter Italian Experience
Authors: Gianni Binotto, Fausto Castagnetti, Gabriele Gugliotta, Elisabetta Abruzzese, Massimo Breccia, Alessandra Iurlo, Fabio Stagno, Antonella Gozzini, Patrizia Pregno, Sara Galimberti, Carmen Fava, Alessandro Isidori, Gaetano La Barba, Mario Tiribelli, Massimiliano Bonifacio, Mario Annunziata, Luigiana Luciano, Isabella Capodanno, Monica Bocchia, Francesca Lunghi, Luciano Levato, Luca Frison, Monika Trawinska Malgorzata, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Gianpietro Semenzato, Gianantonio Rosti
Journal: Blood (2018)
Genetic Profiling and Novel Recurrent Chromosomal Alterations in Patients with Light Chain Amyloidosis
Authors: Isabel Cuenca, Beatriz Sanchez-Vega, Bruno Paiva, David Gomez-Sanchez, Santiago Barrio, Diego Alignani, Marta Lasa, Ramon Lecumberri, Felipe Prosper, Enrique M. Ocio, Maria Esther González, Alfonso García de Coca, Javier De La Rubia, Mercedes Gironella, Luis Palomera, Albert Oriol, Maria Casanova, Valentin Cabañas, Francisco Taboada, Albert Pérez, Felipe De Arriba, Noemi Puig, Juan Jose Lahuerta, Maria-Victoria Mateos, Jesus F San-Miguel, Joaquin Martinez Lopez
Journal: Blood (2018)
Suboptimal Nocturnal Glucose Control Is Associated With Large for Gestational Age in Treated Gestational Diabetes Mellitus
Authors: Graham R. Law, Alia Alnaji, Lina Alrefaii, Del Endersby, Sarah J. Cartland, Stephen G. Gilbey, Paul E. Jennings, Helen R. Murphy, Eleanor M. Scott
Journal: Diabetes Care (2019)

Continuous glucose monitoring (CGM) provides far greater detail about fetal exposure to maternal glucose across the 24-h day. Our aim was to examine the role of temporal glucose variation on the development of large for gestational age (LGA) infants in women with treated gestational diabetes mellitus (GDM).We performed a prospective observational study of 162 pregnant women with GDM in specialist multidisciplinary antenatal diabetes clinics. Participants undertook 7-day masked CGM at 30-32 weeks' gestation. Standard summary indices and glycemic variability measures of CGM were calculated. Functional data analysis was applied to determine differences in temporal glucose profiles. LGA was defined as birth weight ≥90th percentile adjusted for infant sex, gestational age, maternal BMI, ethnicity, and parity.Mean glucose was significantly higher in women who delivered an LGA infant (6.2 vs. 5.8 mmol/L, P = 0.025, or 111.6 mg/dL vs. 104.4 mg/dL). There were no significant differences in percentage time in, above, or below the target glucose range or in glucose variability measures (all P > 0.05). Functional data analysis revealed that the higher mean glucose was driven by a significantly higher glucose for 6 h overnight (0030-0630 h) in mothers of LGA infants (6.0 ± 1.0 mmol/L vs. 5.5 ± 0.8 mmol/L, P = 0.005, and 108.0 ± 18.0 mg/dL vs. 99.0 ± 14.4 mg/dL).Mothers of LGA infants run significantly higher glucose overnight compared with mothers without LGA infants. Detecting and addressing nocturnal glucose control may help to further reduce rates of LGA in women with GDM.
Pericholecystic Rim Sign and Gallbladder Nonvisualization Indicating Acute Gangrenous Cholecystitis on 99mTc-MIBI Myocardial Perfusion SPECT
Authors: Mohsen Qutbi, Reyhana Ahmadi
Journal: Clinical Nuclear Medicine (2019)

Rim sign is assumed as an ominous sign of gangrenous cholecystitis and mandates an urgent surgery. The main mechanism by which this phenomenon arises is increased regional blood flow as a result of an inflammatory process. Therefore, it is expected that this finding be visualized in varieties of scans with various radiopharmaceuticals, including myocardial perfusion scan with Tc-MIBI as an extracardiac finding. Herein, we present a case of acute cholecystitis with a rim sign on preoperative myocardial perfusion SPECT using Tc-MIBI, which posed the possibility of gangrene and perforation and thus the need for urgent surgical intervention.
Prevalence of infection among asymptomatic and paucisymptomatic contact persons exposed to Ebola virus in Guinea: a retrospective, cross-sectional observational study
Authors: Mamadou Saliou Kalifa Diallo, Muriel Rabilloud, Ahidjo Ayouba, Abdoulaye Touré, Guillaume Thaurignac, Alpha Kabinet Keita, Christelle Butel, Cécé Kpamou, Thierno Alimou Barry, Mariama Djouldé Sall, Ibrahima Camara, Sandrine Leroy, Philippe Msellati, René Ecochard, Martine Peeters, Mamadou Saliou Sow, Eric Delaporte, Jean-François Etard, Diaby ABOUBACAR, Alseny BALDE, Ibrahima BALDE, Amara BAMBA, Amadou CAMARA, Aboubacar Mamy CONTE, Jean-François DELFRAISSY, Amadou Bailo DIALLO, Saran DOUMBOUYA, Emile Souro KAMANO, Joel Balle KOIVOGUI, Charlotte LANIECE-DELAUNAY, Yves LEVY, Jean Louis MONEMOU, Moriba POVOGUI, Maou SAKOUVOGUI, Abdoul Karim SOUMAH, Fabien SUBTIL, Aboubacar Hawa SYLLA, Bernard TAVERNE, Yazdan YAZDANPANAH
Journal: The Lancet Infectious Diseases (2019)
Abstract 12773: Dose-dependence of Beta-blocker Therapy on Subsequent Mortality in One Year Survivors After Myocardial Infarction
Authors: Jeffrey Goldberger
Journal: Circulation (2015)

Background: Beta-blocker (BB) therapy after acute myocardial infarction (MI) improves survival. The benefits of long term treatment remain debated. Methods: Of 7058 patients enrolled in the OBTAIN prospective multi-center registry of patients with acute MI, follow-up BB dosing information was available in 2822 patients who survived ≥1 year. BB dose was indexed to the target BB dose used in RCTs (when available), reported as %; only BBs studied in RCTs were included in this analysis. Dosage groups were No BB (n=302), ≤12.5% (n=557), 12.6-25% (n=848), 26-50% (n=687), and &gt;50% (n=428) of target dose respectively. Vital status was obtained by chart review, Social Security Death Index, or direct contact. Adjustment for baseline differences among groups was achieved by propensity score analysis (predicted 1-year BB dose as control variable). Results: In the 5 groups, mean age was 62-64 years, with significant differences in gender, clinical, and MI characteristics. Mean ejection fractions were 47-50%. The figure shows Kaplan-Meier survival curves (unadjusted, p=0.06). Propensity score analysis showed an independent effect of BB dose on mortality (p=0.047). Compared to No BB, only the 12.6-25% dose group had a significant mortality reduction (HR 0.46, 95% CI 0.25-0.86, p=0.014). Conclusions: At one year after MI, continued BB therapy may be associated with lower mortality, but there appears to be a dose-dependence to this effect. Further studies are needed to optimize BB dosing strategies for long-term treatment after MI.
Abstract 16423: Functional Outcomes of Adult Extracorporeal Membrane Oxygenation Survivors
Authors: Fenton H McCarthy, Katherine M McDermott, Justin George, Jennifer Kim, Ashley C Hoedt, Joyce W Wald, Wilson Y Szeto, Pavan Atluri, Prashanth Vallabhajosyula, Jacob T Gutsche, Michael A Acker, Nimesh D Desai
Journal: Circulation (2015)

Objectives: Little is known regarding the functional outcomes of ECMO survivors and the health-related quality of life comparing Arterio-Venous (AV) versus Veno-Venous (VV) ECMO survivors in the current era. Methods: All adults who underwent AV or VV ECMO from 2007 to 2014 and were subsequently discharged alive at a single institution between were surveyed. The survey included the validated SF-36 and EQ-5D-5L questionnaires, and ECMO related outcomes. Results: We surveyed 64 patients including 44 AV and 20 VV ECMO survivors. Patients were discharged home in 59% of cases and to a rehab or another healthcare facility in 41% of cases. One-year survival was 93%. Responses were obtained from 33 patients (54% response rate), including 21 AV survivors and 12 VV survivors. The average age was 46.2 ± 14.6 years. VV ECMO survivors were supported for a longer period of time compared to AV ECMO survivors (10 ± 8.6 days v. 4.71 ± 5.5 days, p = 0.02). AV ECMO survivors had a significantly higher Mental Composite Summary (MCS) compared to VV ECMO survivors (50.4 ± 8.2 v 43.16 ± 10.9, p=0.04). There were no other significant differences in the SF-36 or the EQ-5D-5L scores (Table 1, Figure 1). Of surveyed patients, 41% continue to work and 32% work at their same pre-ECMO job. Rehospitalization occurred in 59% of patients. Only 34% of surviving patients had living wills, with just two patients requesting no mechanical ventilation or ECMO. Conclusions: Functional outcomes among ECMO survivors are generally high and similar between AV and VV ECMO survivors. VV ECMO survivors demonstrated perhaps some areas of lower health-related quality of life with lower SF-36 scores on the Mental Composite Summary.
Enhancing the Sgarbossa Criteria for the Diagnosis of ST Elevation Myocardial Infarction
Authors: Timothy F. Simpson, Salman Rahman, Nora Goldschlager
Journal: JAMA Internal Medicine (2019)

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Abstract 20430: Potential of Circulating MicroRNA-1 as New Perioperative Biomarker of Short-Term Outcome After Pediatric Congenital Heart Surgery
Authors: Dan M Dorobantu, Serban Stoica, Antonella Vardeu, Domenico Bruno, Mustafa Zakkar, Andrew Mumford, Gianni Angelini, Massimo Caputo, Costanza Emanueli
Journal: Circulation (2017)

Background: MicroRNA-1 (miR-1) is enriched in the myocardium and increases in the circulation after acute myocardial infarct and open-heart cardiac surgery in adults. In clinical practice, the pred...
Glycemic Variability Is a Powerful Independent Predictive Factor of Midterm Major Adverse Cardiac Events in Patients With Diabetes With Acute Coronary Syndrome
Authors: Edouard Gerbaud, Romain Darier, Michel Montaudon, Marie-Christine Beauvieux, Christine Coffin-Boutreux, Pierre Coste, Hervé Douard, Alexandre Ouattara, Bogdan Catargi
Journal: Diabetes Care (2019)

Acute glucose fluctuations are associated with hypoglycemia and are emerging risk factors for cardiovascular outcomes. However, the relationship between glycemic variability (GV) and the occurrence of midterm major cardiovascular events (MACE) in patients with diabetes remains unclear. This study investigated the prognostic value of GV in patients with diabetes and acute coronary syndrome (ACS).This study included consecutive patients with diabetes and ACS between January 2015 and November 2016. GV was assessed using SD during initial hospitalization. MACE, including new-onset myocardial infarction, acute heart failure, and cardiac death, were recorded. The predictive effects of GV on patient outcomes were analyzed with respect to baseline characteristics and cardiac status.A total of 327 patients with diabetes and ACS were enrolled. MACE occurred in 89 patients (27.2%) during a mean follow-up of 16.9 months. During follow-up, 24 patients (7.3%) died of cardiac causes, 35 (10.7%) had new-onset myocardial infarction, and 30 (9.2%) were hospitalized for acute heart failure. Multivariable logistic regression analysis showed that GV >2.70 mmol/L, a Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) score >34, and reduced left ventricular ejection fraction of <40% were independent predictors of MACE, with odds ratios (ORs) of 2.21 (95% CI 1.64-2.98; P < 0.001), 1.88 (1.26-2.82; P = 0.002), and 1.71 (1.14-2.54; P = 0.009), respectively, whereas a Global Registry of Acute Coronary Events (GRACE) risk score >140 was not (OR 1.07 [0.77-1.49]; P = 0.69).A GV cutoff value of >2.70 mmol/L was the strongest independent predictive factor for midterm MACE in patients with diabetes and ACS.
Abstract P297: Intensity-specific Physical Activity Measured by Accelerometry and Mortality in Women: The OPACH Study
Authors: Michael J LaMonte, Eileen Rillamas-Sun, Kelly R Evenson, I-Min Lee, David M Buchner, Chongzhi Di, Andrea Z LaCroix
Journal: Circulation (2017)

Background: Associations for cardiovascular disease (CVD) and all-cause mortality with intensity-specific physical activity (PA) exposures assessed by questionnaire may be underestimated by exposure measurement error, especially in older adults. We examined accelerometer measured PA and CVD and all-cause mortality in 6,374 race-ethnically diverse women (White, 49.4%, Black 33.7%, Hispanic 16.9%) ages 63-91 (mean 78.7 years) followed a mean of 2.5 years as part of the Objective Physical Activity and Cardiovascular Health (OPACH) Study. Methods: Vector magnitude counts/15-sec epoch from hip worn Actigraph GT3X+ triaxial accelerometers (required ≥4 of 7 days with ≥10 hr/day wear time) were used to define time spent in low light (LLPA; 19-225 counts/15-sec), high light (HLPA; 226-518), and moderate-to-vigorous (MVPA; ≥519) PA based on cutpoints determined from a calibration study among similarly aged women. Cox regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for these associations. Results: There were 270 (4.2%) all-cause deaths and 78 (1.2%) CVD deaths during 14,205 person-years of follow-up. Adjusting for awake-time accelerometer wear-time, age, and race, HRs (CI) for CVD mortality associated with a 30-min/day increment in PA were 0.82 (0.71,0.96) for LLPA; 0.48 (0.38,0.61) for HLPA; and 0.53 (0.38, 0.74) for MVPA; and for all-cause mortality were 0.86 (0.79, 0.93), 0.61 (0.54, 0.69), and 0.57 (0.48, 0.67) respectively. These associations were similar following additional adjustments for smoking, age at menopause, and number of prevalent comorbidities (CVD HRs = 0.83, 0.49, 0.54, respectively, P≤0.01 all; all-cause HRs = 0.86, 0.62, 0.58, respectively, P&lt;0.001 all). Similar results were observed after discarding the first 6 months of follow-up (CVD HRs = 0.84, 0.49, 0.50; all-cause HRs = 0.87, 0.63, 0.59). In a final model mutually adjusting for total light PA (LLPA and HLPA combined) and MVPA, each 30-min increment in light PA and MVPA was associated with HRs for CVD mortality of 0.84 (0.75, 0.93) and 0.67 (0.47, 0.96) respectively; and with all-cause mortality of 0.90 (0.85, 0.95) and 0.66 (0.55, 0.80), respectively. Conclusions: Higher levels of both light intensity PA and MVPA measured by accelerometry are associated with lower CVD and all-cause mortality in older women. Because light intensity PA accounts for the majority of daily PA energy expenditure in older women’s lives, these results could have important public health implications and should be confirmed.
Is Adjuvant Chemotherapy Efficient in Colon Cancer with High Microsatellite Instability? A Look Towards the Future
Authors: Guido V. Schiappacasse Cocio, Enrico D. Schiappacasse
Journal: Cancer Research (2019)

The high microsatellite instability (MSI-H) is frequently observed in localized colorectal adenocarcinoma. MSI-H is a good prognostic factor in nonmetastatic colon adenocarcinoma. However, MSI-H is not a predictive factor because it is not related with better survival in patients with colon cancer with adjuvant chemotherapy. MSI-H should be a predictive factor because it is associated with a higher expression of enzymes, which are inhibited by cytotoxic agents. Here, we analyze this controversy. We conclude MSI-H is not a predictive factor because the adjuvant therapy based on traditional cytotoxic agents does not act on either immune signaling pathways or BRAF mutation.
Clare Gerada: Unhealthy perfectionism
Authors: Clare Gerada
Journal: BMJ (2019)

Recently, just before giving a lecture at my old medical school, I was handed my student report card.In the corner was a small passport photo of the young me, and below were the grades I achieved during each attachment, including my elective and student locum.No comments, just grades.My scores were average: mainly Bs and B+s, a few C+s, even a C. Seeing this card nearly 40 years later was a surprise.I had no idea that each clinical firm was graded, and I'd assumed that the only scores we
Defining Minimal Clinically Important Differences (MCID) on the Leicester Cough Questionnaire (LCQ): Analyses of a Phase 2 Randomized Controlled Trial in Chronic Cough
Authors: Surinder Birring, David Muccino, Elizabeth D. Bacci, Margaret K. Vernon, Allison M. Nguyen
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract P2-01-05: Targeting of casein kinase 1δ inhibits triple negative breast cancer metastasis
Authors: S Bayle, M Lafitte, V Quereda, WR Roush, DR Duckett
Journal: Cancer Research (2019)

Abstract Metastasis is responsible for most breast cancer mortalities and 30% of the patients with breast cancer will develop metastases. Despite the establishment of efficient targeted therapies for breast cancer, there is no cure for metastatic disease. Our research team have developed a potent, highly selective, small molecule inhibitor of casein kinase-1 delta (CK1δ), a serine/threonine kinase. We have demonstrated that our lead molecule (SR-3029) provokes tumor specific cell death and tumor regression in pre-clinical orthotopic xenograft models of triple negative breast cancer (TNBC) including, basal-like patient derived (PDX) breast cancer models. Herein, we demonstrate that targeting CK1δ inhibits tumor cell invasion in cell based studies and markedly reduces both the number and size of metastasis lesions spreading from the breast to the lung in vivo. We show that invasion impairment is due to the inhibition of key effectors of the epithelial-mesenchymal transition. We have developed Lumifluor patient-derived xenograft models and assessed the effect of our inhibitors at various stages during the process of metastases. We have identified CK1δ as an efficacious therapeutic target with dual potential for triggering apoptosis of breast tumor cells and impairing metastatic spread from the primary tumor. Citation Format: Bayle S, Lafitte M, Quereda V, Roush WR, Duckett DR. Targeting of casein kinase 1δ inhibits triple negative breast cancer metastasis [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-01-05.
The Absolute Count of Lymphocytes Is a Strong Predictive Factor for Relapse/Regrowth Events and Outcomes in Patients with Regressive Methotrexate-Associated Lymphoproliferative Disorders
Authors: Michihide Tokuhira, Yuta Kimura, Yuka Tanaka, Yasuyuki Takahashi, Tatsuki Tomikawa, Junichi Watanabe, Tomoe Anan-Nemoto, Morihiko Sagawa, Shuji Momose, Morihiro Higashi, Tabayashi Takayuki, Reiko Nakaseko, Jun-ichi Tamaru, Masahiro Kizaki
Journal: Blood (2018)
Higher Positive End-Expiratory Pressures Affect The Distribution Of Lung Inflammation During Spontaneous Breathing In An Experimental Model Of Severe Acute Respiratory Distress Syndrome
Authors: C. C. A. Morais, G. Plens, M. R. Tucci, T. Yoshida, João Batista Borges, O. P. Ramos, S. M. Pereira, C. A. S. Lima, S. Gomes, M. Vidal Melo, M. B. P. Amato, E. L. V. Costa
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Higher Positive End-Expiratory Pressures Affect The Distribution Of Lung Inflammation During Spontaneous Breathing In An Experimental Model Of Severe Acute Respiratory Distress Syndrome