tbuckley/cabot-search huggingface dataset:
Abstract 18353: A Real-world Study Evaluating the Utility of an Innovative Digital Health Feedback Device in Patients With Uncontrolled Hypertension
Authors: Lorenzo DiCarlo, Ravin Naik, Neil Macey, Richard J West, Peter Godbehere, Stephen C Thurston, Robin Fox, Indy Singh, Weina Xiang, Yoona Kim
Journal: Circulation (2015)

Introduction: For patients with uncontrolled blood pressure (BP), differentiation of pharmacological resistance from inadequate or improper medication use is key to clinical management. A digital health feedback device (DHFD) has been developed, utilizing an Ingestible Sensor (IS) and Wearable Sensor (WS) to passively record medication taking and timing, and measure physiological and behavioral metrics such as heart rate, step count, activity and rest patterns. This study evaluated DHFD use in diagnosing the cause of persistent BP elevation. Methods: Patients with a history of BP (≥140/90) on ≥2 anti-hypertensives (AHs) at 6 primary care centers in the United Kingdom were prescribed the DHFD for 14 days. Patients co-ingested the IS along with their prescribed BP medications while continuously wearing the WS. BP was assessed on days 1 and 14. Results: A total of 151 patients were enrolled; 38% were taking ≥3 AHs at baseline; 144 patients (95%) completed the 2 planned weeks of DHFD use. Root cause of treatment unresponsiveness was identified by DHFD in 100% of completers; 58% had pharmacological resistance, and 42% had inadequate AH use. During DHFD use, mean systolic BP decreased significantly by -10±17 (p&lt;0.001) and mean diastolic BP decreased significantly by -5±9 mmHg (p&lt;0.001); 38% of subjects achieved BP control on their current therapy. Subsequent management included: medicines reviews and/or adherence counselling with no AH changes in 81%, medication changes in 13%, referrals to specialists in 1%, and no additional actions were taken in 6%. Majority of practices (75%) found the DHFD added value, and 83% of patients expressed a positive experience. Side effects were minimal, consisting of mainly minor skin irritation (8%), or gastrointestinal symptoms (3%). Two patients withdrew due to possibly-related adverse events. Conclusions: In subjects using the DHFD for uncontrolled BP while prescribed AHs, all received a more informed therapeutic intervention from their providers following DHFD use. BP control was achieved in 38% within 2 weeks. DHFD can facilitate evidence-based progression through the BP treatment pathway by differentiating which patients can achieve treatment goals with prescribed therapy from those who may require AH changes.
Prophylactic irradiation to the contralateral breast for BRCA mutation carriers with early-stage breast cancer
Authors: E. Evron, A.M. Ben-David, H. Goldberg, G. Fried, B. Kaufman, R. Catane, M.R. Pfeffer, D.B. Geffen, P. Chernobelsky, T. Karni, R. Abdah-Bortnyak, O. Rosengarten, D. Matceyevsky, M. Inbar, A. Kuten, B.W. Corn
Journal: Annals of Oncology (2018)

BackgroundWomen who carry germ-line mutations in BRCA1/2 are at very high risk of developing breast and ovarian cancer. Breast conserving therapy is associated with a similar risk of ipsilateral cancer recurrence in BRCA carriers compared with non-carriers. However, the risk of subsequent contralateral breast cancer in carriers is markedly increased. Therefore, mastectomy of the diseased breast along with risk reducing mastectomy of the contralateral breast is often advocated for BRCA carriers who are treated for early breast cancer. Yet, many BRCA carriers forgo this option for fear of harmful effects and choose breast conserving treatment and observation instead. In Israel, BRCA-associated breast cancer is relatively common. Accordingly, a national protocol was devised for this enriched population.Patients and methodsIn this Institutional Review Board-approved phase II trial, the option of prophylactic irradiation to the contralateral breast, in addition to standard loco-regional treatment, was offered to BRCA carrier patients treated for early breast cancer who declined contralateral mastectomy. The primary end point was contralateral breast cancer.ResultsBetween May 2007 and October 2017, 162 patients were enrolled. Eighty-one patients opted for standard loco-regional treatment including surgery and radiation to the involved side (control arm) and 81 patients chose additional contralateral breast irradiation (intervention arm). At a median follow-up of 58 months, 10 patients developed contralateral breast cancer in the control arm at a median of 32 months, as compared with 2 patients in the intervention arm who developed contralateral breast cancer 80 and 105 months after bilateral breast irradiation (log-rank P = 0.011).ConclusionsAmong BRCA carrier patients treated for early breast cancer, the addition of contralateral breast irradiation was associated with a significant reduction of subsequent contralateral breast cancers and a delay in their onset.Clinical trialPhase II, comparative two-arm trial (NCT00496288).
Variations in Risk of End-Stage Renal Disease and Risk of Mortality in an International Study of Patients With Type 1 Diabetes and Advanced Nephropathy
Authors: Jan Skupien, Adam M. Smiles, Erkka Valo, Tarunveer S. Ahluwalia, Beata Gyorgy, Niina Sandholm, Stephanie Croall, Maria Lajer, Kevin McDonnell, Carol Forsblom, Valma Harjutsalo, Michel Marre, Andrzej T. Galecki, David-Alexandre Tregouet, Chun Yi Wu, Josyf C. Mychaleckyj, Helen Nickerson, Marlon Pragnell, Stephen S. Rich, Marcus G. Pezzolesi, Samy Hadjadj, Peter Rossing, Per-Henrik Groop, Andrzej S. Krolewski
Journal: Diabetes Care (2018)

Patients with type 1 diabetes and diabetic nephropathy are targets for intervention to reduce high risk of end-stage renal disease (ESRD) and deaths. This study compares risks of these outcomes in four international cohorts.In the 1990s and early 2000s, Caucasian patients with type 1 diabetes with persistent macroalbuminuria in chronic kidney disease stages 1-3 were identified in the Joslin Clinic (U.S., 432), Finnish Diabetic Nephropathy Study (FinnDiane) (Finland, 486), Steno Diabetes Center Copenhagen (Denmark, 368), and INSERM (France, 232) and were followed for 3-18 years with annual creatinine measurements to ascertain ESRD and deaths unrelated to ESRD.During 15,685 patient-years, 505 ESRD cases (rate 32/1,000 patient-years) and 228 deaths unrelated to ESRD (rate 14/1,000 patient-years) occurred. Risk of ESRD was associated with male sex; younger age; lower estimated glomerular filtration rate (eGFR); higher albumin/creatinine ratio, HbA1c, and systolic blood pressure; and smoking. Risk of death unrelated to ESRD was associated with older age, smoking, and higher baseline eGFR. In adjusted analysis, ESRD risk was highest in Joslin versus reference FinnDiane (hazard ratio [HR] 1.44, P = 0.003) and lowest in Steno (HR 0.54, P < 0.001). Differences in eGFR slopes paralleled risk of ESRD. Mortality unrelated to ESRD was lowest in Joslin (HR 0.68, P = 0.003 vs. the other cohorts). Competing risk did not explain international differences in the outcomes.Despite almost universal renoprotective treatment, progression to ESRD and mortality in patients with type 1 diabetes with advanced nephropathy are still very high and differ among countries. Finding causes of these differences may help reduce risk of these outcomes.
Establishment of orthotopically implanted malignant mesothelioma model which represents intrathoracic tumors and bloody pleural effusions
Authors: Seiji Yano, Emiko Nakataki, Hiroaki Muguruma, Hideki Tomimoto, Soji Kakiuchi, Saburo Sone
Journal: Cancer Research (2005)

1054  Malignant mesothelioma (MM) is an aggressive tumor that frequently spread thoracic cavity. In addition, since it is refractory to conventional chemotherapy and radiotherapy, prognosis of patients with MM is very limited. To clarify the molecular pathogenesis of MM and develop novel, more effective therapeutic modalities, experimental animal models which resemble clinical behavior of MM are indispensable. Here, we report orthotopic-implantation SCID-mouse model of human MM cells. In the present study, we used two human MM cell lines, named EHMES-1 and EHMES-10, established from two different patients. EHMES-10 cells secreated 10 times higher level of vascular endothelial growth factor (VEGF) protein compared with EHMES-1 cells. Both two cell lines overexpressed epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2). When MM cells were inoculated into thoracic cavity (orthotopic site) of SCID mice, EHMES-1 cells did not produce any tumors or pleural effusions by day 84. On the other hand, EHMES-10 cells reproducibly produced tumors (2-5 mm in diameter) accompanying with pleural dissemination and bloody pleural effusions (up to 1ml/mouse) by day 35. Treatment of EHMES-10-bearing SCID mice with cisplatin or gemcitabine, those are considered as effective chemotherapeutic agents for MM patients, on day 7 inhibited production of pleural tumors and pleural effusion. These results suggest that pattern of progression and chemosensitivity of orthotopically implanted EHMES-10 cells resemble those of MM patients. Therefore, our patient-like orthotopic model with EHMES-10 cells may be useful for examining molecular pathogenesis and contribute to develop the novel treatment strategy for MM.
FBXO11 Activates Erythroid Gene Transcription By Degrading Heterochromatin-Associated Protein BAHD1
Authors: Peng Xu, Daniel C. Scott, Xing Tang, Yu Yao, Yong-Dong Wang, Wenjian Bi, Lance E. Palmer, Ruopeng Feng, Arno F. Alpi, Chunliang Li, Yong Cheng, Brenda A. Schulman, Mitchell J. Weiss
Journal: Blood (2018)
ET190L1-ArtemisTM T Cell Therapy Results in Durable Disease Remissions with No Cytokine Release Syndrome or Neurotoxicity in Patients with Relapsed and Refractory B-Cell Lymphoma
Authors: Zhitao Ying, Li Long, Hong Liu, Yuqin Song, David A. Rizzieri, Bijan Nejadnik, Jun Zhu, Cheng Liu
Journal: Blood (2018)
Abstract P135: Prevalence of Peripheral Vascular Disease: Results of the Global Burden of Disease 2016 Study
Authors: Catherine O Johnson, Minh Nguyen, Benjamin Zipkin, Tahiya Alam, Gregory A Roth
Journal: Circulation (2018)

Introduction: Peripheral arterial disease (PAD) is a common condition among older adults. While many patients are asymptomatic, a substantial proportion experience intermittent claudication or critical limb ischemia and require revascularization or bypass surgery. PAD has also been associated with higher rates of cardiovascular and all-cause mortality. Estimates of the prevalence of PAD are essential to a complete understanding of the burden of atherosclerotic disease. We produced national and global estimates of PAD as part of the Global Burden of Disease 2016 Study. Methods: We used national health surveys which assessed ankle-brachial index, commercial insurance claims databases, and published literature on population-based studies as input data. Our analyses corrected for readmission rates and variation in the use of diagnosis codes. Geospatial disease meta-regression software (DisMod-MR 2.1) was used to generate models separately by sex, location, and year to produce consistent estimates of prevalence. Uncertainty intervals (UI) were estimated using 1000 draws from the posterior distribution of each model. A country-level socio-demographic index (SDI), combining national income per capita, mean years of schooling, and total fertility rate, was used to examine disease burden by level of development. Results: In 1990, there were an estimated 395 (95%UI: 345 to 453) million prevalent cases of PAD globally in women and 265 (95%UI: 231 to 307) million cases in men. By 2016, these numbers had increased to 695 (95%UI: 613 to 797) million cases in women and 506 (95%UI: 444 to 583) million cases in men. Age-standardized global rates in 1990 were 2106 (95%UI 1847 to 2415) per 100,000 and 1773 (95%UI: 1561 to 2037) per 100,000 in women and men, respectively. In 2016, these rates were 1930 (95%UI: 1702 to 2202) per 100,000 for women and 1658 (95%UI: 1457 to 1900) per 100,000 for men. The largest change in total number of prevalent cases from 1990 to 2016 was seen in middle-SDI countries with a 136% (95%UI: 131% to 137%) change in women and 140% (95%UI: 137% to 143%) change in men, indicating that the overall atherosclerotic burden in these countries is increasing. Comparisons indicate that these changes are largely being driven by population aging in high-SDI countries and by population growth in other locations. Conclusions: The prevalence of PAD is increasing worldwide, with large increases in low- and middle-SDI countries in particular. These estimates of prevalence provide important estimates of the number of people who may benefit from medical therapies to reduce cardiovascular events.
Surgery vs Radiotherapy in the Management of Biopsy Gleason Score 9-10 Prostate Cancer and the Risk of Mortality
Authors: Derya Tilki, Ming-Hui Chen, Jing Wu, Hartwig Huland, Markus Graefen, Michelle Braccioforte, Brian J. Moran, Anthony V. D’Amico
Journal: JAMA Oncology (2018)

It is unknown how treatment with radical prostatectomy (RP) and adjuvant external beam radiotherapy (EBRT), androgen deprivation therapy (ADT), or both (termed MaxRP) compares with treatment with EBRT, brachytherapy, and ADT (termed MaxRT).To investigate whether treatment of Gleason score 9-10 prostate cancer with MaxRP vs MaxRT was associated with prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) risk.The study cohort comprised 639 men with clinical T1-4,N0M0 biopsy Gleason score 9-10 prostate cancer. Between February 6, 1992, and April 26, 2013, a total of 80 men were consecutively treated with MaxRT at the Chicago Prostate Cancer Center, and 559 men were consecutively treated with RP and pelvic lymph node dissection at the Martini-Klinik Prostate Cancer Center. Follow-up started on the day of prostate EBRT or RP and concluded on October 27, 2017.Of the 559 men managed with RP and pelvic lymph node dissection, 88 (15.7%) received adjuvant EBRT, 49 (8.8%) received ADT, and 50 (8.9%) received both.Treatment propensity score-adjusted risk of PCSM and ACM and the likelihood of equivalence of these risks between treatments using a plausibility index.The cohort included 639 men, with a mean (SD) age of 65.83 (6.52) years. After median follow-ups of 5.51 years (interquartile range, 2.19-6.95 years) among 80 men treated with MaxRT and 4.78 years (interquartile range, 4.01-6.05 years) among 559 men treated with RP-containing treatments, 161 men had died, 106 (65.8%) from prostate cancer. There was no significant difference in the risk of PCSM (adjusted hazard ratio, 1.33; 95% CI, 0.49-3.64; P = .58) and ACM (adjusted hazard ratio, 0.80; 95% CI, 0.36-1.81; P = .60) when comparing men who underwent MaxRP vs MaxRT, with plausibility indexes for equivalence of 76.75% for the end point of the risk of PCSM and 77.97% for the end point of the risk of ACM. Plausibility indexes for all other treatment comparisons were less than 63%.Results of this study suggest that it is plausible that treatment with MaxRP or MaxRT for men with biopsy Gleason score 9-10 prostate cancer can lead to equivalent risk of PCSM and ACM.
Real-world data of EGFR minor mutated NSCLC treated with EGFR-TKI: Comparative analysis including compound mutation and de novo T790M mutation
Authors: K. Tanaka, N. Inui, K. Asada, T. Abe, O. Hataji, S. Hayai, K. Ito, K. Imaizumi, T. Kimura, A. Kubo, E. Kunii, K. Murotani, M. Okuno, Y. Oya, J. Shindoh, H. Taniguchi, T. Tsuda, T. Yamaguchi, T. Hida, T. Suda
Journal: Annals of Oncology (2018)
Osimertinib vs standard of care (SoC) EGFR-TKI as first-line therapy in patients (pts) with untreated EGFRm advanced NSCLC: FLAURA post-progression outcomes
Authors: D. Planchard, M. Boyer, J.-S. Lee, A. Dechaphunkul, P. Cheema, T. Takahashi, A. Todd, A. McKeown, Y. Rukazenkov, Y. Ohe
Journal: Annals of Oncology (2018)
Abstract 16536: Construction and Validation of a New Termination-of-Resuscitation Rule for Out-of-Hospital Cardiac Arrest in the Japanese Population
Authors: Katsutaka Hashiba, Yoshio Tahara, Kazuo Kimura, Satoshi Yasuda, Sunao Kojima, Hisao Ogawa, Naohiro Yonemoto, Hiroshi Nonogi, Keijirou Saku, Ken Nagao
Journal: Circulation (2016)

Background: Termination of resuscitation (TOR) rules for out-of-hospital cardiac arrest (OHCA) have been constructed for better utilization of hospital healthcare resources and increasing the availability of care for other patients. Objective: To validate the TOR-ALS rule in the Japanese population and to establish a new TOR rule for terminating ongoing resuscitation just after hospital arrival. Methods: Data from a nationwide database of a prospective population-based cohort using an Utstein-style template for OHCA patients during January 2005 to December 2014 as used for the current analysis. We constructed a new TOR rule consisting of 5 factors (no-witness, no-ROSC, asystole for the initial rhythm, no-defibrillation, age) including the patients during 2005 to 2012 (derivation cohort). Statistical values to predict death and unfavorable neurological outcome(UNO) at one-month were calculated for the TOR-ALS rule (no-witness, no-bystander, no-return of spontaneous circulation (ROSC), no-defibrillation bef...
The coronary circulation in acute myocardial ischaemia/reperfusion injury: a target for cardioprotection
Authors: Derek J Hausenloy, William Chilian, Filippo Crea, Sean M Davidson, Peter Ferdinandy, David Garcia-Dorado, Niels van Royen, Rainer Schulz, Gerd Heusch
Journal: Cardiovascular Research (2018)

The coronary circulation is both culprit and victim of acute myocardial infarction. The rupture of an epicardial atherosclerotic plaque with superimposed thrombosis causes coronary occlusion, and this occlusion must be removed to induce reperfusion. However, ischaemia and reperfusion cause damage not only in cardiomyocytes but also in the coronary circulation, including microembolization of debris and release of soluble factors from the culprit lesion, impairment of endothelial integrity with subsequently increased permeability and oedema formation, platelet activation and leucocyte adherence, erythrocyte stasis, a shift from vasodilation to vasoconstriction, and ultimately structural damage to the capillaries with eventual no-reflow, microvascular obstruction (MVO), and intramyocardial haemorrhage (IMH). Therefore, the coronary circulation is a valid target for cardioprotection, beyond protection of the cardiomyocyte. Virtually all of the above deleterious endpoints have been demonstrated to be favourably influenced by one or the other mechanical or pharmacological cardioprotective intervention. However, no-reflow is still a serious complication of reperfused myocardial infarction and carries, independently from infarct size, an unfavourable prognosis. MVO and IMH can be diagnosed by modern imaging technologies, but still await an effective therapy. The current review provides an overview of strategies to protect the coronary circulation from acute myocardial ischaemia/reperfusion injury. This article is part of a Cardiovascular Research Spotlight Issue entitled 'Cardioprotection Beyond the Cardiomyocyte', and emerged as part of the discussions of the European Union (EU)-CARDIOPROTECTION Cooperation in Science and Technology (COST) Action, CA16225.
Association of System-Level Factors With Secondary Overtriage in Trauma Patients
Authors: Priti P. Parikh, Pratik Parikh, Logan Mamer, Mary C. McCarthy, Joseph V. Sakran
Journal: JAMA Surgery (2018)

<h3>Importance</h3> Studies show that secondary overtriage (SO) contributes significantly to the economic burden of injured patients; thus, the association of SO with use of the trauma system has been examined. However, the association of the underlying trauma system design with such overtriage has yet to be evaluated. <h3>Objectives</h3> To evaluate whether the distribution of trauma centers in a statewide trauma system is associated with SO and to identify clinical and demographic factors that may lead to SO. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was performed using 2008-2012 data from the Ohio Trauma and Emergency Medical Services registries. All patients taken to level III or nontrauma centers from the scene of the injury with an Injury Severity Score less than 15 and discharged alive were included. Among these patients, those with SO were identified as those who were subsequently transferred to a level I or II trauma center, had no surgical intervention, and were discharged alive within 48 hours of admission. The SO group was analyzed descriptively. Multiple logistic regression was used to identify system-level factors associated with SO. Statistical analysis was performed from August 1, 2017, to January 31, 2018. <h3>Main Outcomes and Measures</h3> The primary outcome was the occurrence of SO. <h3>Results</h3> Of 34 494 trauma patients able to be matched in the 2 registries, 7881 (22.9%) met the inclusion criteria, of whom 965 (12.2%) had SO. The median age in the SO group was 40 years (interquartile range, 26-55 years), with 299 women and 666 men. After adjusting for age, sex, comorbidities, injury type, and insurance status, the study found that system-level factors (number of level I or II trauma centers in the region [&gt;1]) were significantly associated with SO (adjusted odds ratio, 1.98; 95% CI, 1.64-2.38;<i>P</i> &lt; .001; area under the curve, 0.89). The reasons for choice of destination by emergency medical services (specifically, choosing the closest facility: adjusted odds ratio, 1.65; 95% CI, 1.37-1.98;<i>P</i> &lt; .001) and use of a field trauma triage protocol (adjusted odds ratio, 2.21; 95% CI, 1.70-2.87;<i>P</i> &lt; .001), significantly increased the likelihood of SO. <h3>Conclusions and Relevance</h3> This study's findings suggest that the distribution of major trauma centers in the region is significantly associated with SO. Subsequent investigation to identify the optimal number and distribution of trauma centers may therefore be critical. Specific outreach and collaboration of level III trauma centers and nontrauma centers with level I and II trauma centers, along with the use of telemedicine, may provide further guidance to level III trauma centers and nontrauma centers on when to transfer injured patients.
Variable BCL2/BCL2L1 ratio in multiple myeloma with t(11;14)
Authors: Alice Cleynen, Mehmet Samur, Aurore Perrot, Laure Buisson, Sabrina Maheo, Mariateresa Fulciniti, Michel Attal, Nikhil Munshi, Hervé Avet-Loiseau, Jill Corre
Journal: Blood (2018)
Safety and Efficacy of Emapalumab in Pediatric Patients with Primary Hemophagocytic Lymphohistiocytosis
Authors: Franco Locatelli, Michael B. Jordan, Carl E. Allen, Simone Cesaro, Carmelo Rizzari, Anupama Rao, Barbara Degar, Timothy Garrington, Julian Sevilla, Maria Caterina Putti, Franca Fagioli, Martina Ahlmann, Jose-Luis Dapena, Alexei A. Grom, Fabrizio De Benedetti, Walter Giovanni Ferlin, Maria Ballabio, Cristina De Min
Journal: Blood (2018)