tbuckley/cabot-search huggingface dataset:
Abstract 10244: Heartmatters Challenge: Therapeutic Lifestyle Program Reduces Cardiovascular Risk Factors and Weight in First Responders Using Personalized Nutrition, Phone-based Coaching and Online Food Journaling
Authors: Rosalynn D Gill, Ngoc H Thai, Briana E Jones, Debanjali Ghosh, Michael R Mehan, Kepra Jack, Megan M McCarthy, Michael L Dansinger
Journal: Circulation (2015)

Objective: Premature CVD death is common among first responders. Effective risk reduction programs are urgently needed to address this public health concern. We tested the one year effectiveness of a lifestyle-based intervention program in police officers and firefighters in the Boston and Phoenix areas. Methods: 173 participants with excess abdominal fat or CVD risk were assigned to a one year intervention or control group using cluster randomization by city. The intervention was comprised of a personalized nutrition plan based on an algorithm combining laboratory results with food preferences, phone coaching to encourage adherence to lifestyle recommendations including healthy eating and exercise and online food journaling. Results: 130 participants remained in the study for one year (68 intervention; 62 control). In the intervention group the mean weight loss from baseline was 4.8% (4.9 kg, p&lt;0.01) at 6 months and 3.1% (3.2 kg, p&lt;0.01) from baseline at 1 year; waist circumference reduction was 3.6% (4.1 cm, p&lt;0.01) at 6 months and 3.2% (3.6 cm, p&lt;0.01) at 1 year. Large HDL particles increased 64.4% (9.0 mg/dL, p&lt;0.01) at 6 months and 29.6% (3.8 mg/dL, p&lt;0.01) at 1 year; HDL-C increased 9.3% (3.3mg/dL, p&lt;0.01) at 6 months and 8.4% (3.5 mg/dL, p&lt;0.01); and LDL-C decreased 2.6% (5 mg/dL, NS) at 6 months and increased 1.7% (+0.2 mg/dL, NS) at 1 year. There was no meaningful change in the control group. Adherence to the lifestyle program was a major contributor to individual success over the year. An adherence score was developed based on coaching frequency. Participants with adherence scores above the mean (N=21) reduced LDL-C levels 8.8 mg/dL whereas participants with adherence scores below the mean (N=47) exhibited an increase of 4.2 mg/dL (p&lt;0.05). Other favorable trends included greater weight loss (5.4kg vs 2.1 kg, (NS)), greater increases in large HDL particles (5.9mg/dL vs 2.8 mg/dL (NS)) and greater waist circumference reduction ( 5.3 cm vs 2.6 cm (NS)). Conclusions: Clinically meaningful reductions in CVD risk are achievable in actual practice using carefully designed lifestyle programs in combination with phone-based coaching and online food journaling tools. These data support the use of such programs on a national level.
Adherent-invasive <i>Escherichia coli</i> in inflammatory bowel disease
Authors: Carolina Palmela, Caroline Chevarin, Zhilu Xu, Joana Torres, Gwladys Sevrin, Robert Hirten, Nicolas Barnich, Siew C Ng, Jean-Frederic Colombel
Journal: Gut (2017)

Intestinal microbiome dysbiosis has been consistently described in patients with IBD. In the last decades, Escherichia coli , and the adherent-invasive E coli (AIEC) pathotype in particular, has been implicated in the pathogenesis of IBD. Since the discovery of AIEC, two decades ago, progress has been made in unravelling these bacteria characteristics and its interaction with the gut immune system. The mechanisms of adhesion of AIEC to intestinal epithelial cells (via FimH and cell adhesion molecule 6) and its ability to escape autophagy when inside macrophages are reviewed here. We also explore the existing data on the prevalence of AIEC in patients with Crohn’s disease and UC, and the association between the presence of AIEC and disease location, activity and postoperative recurrence. Finally, we highlight potential therapeutic strategies targeting AIEC colonisation of gut mucosa, including the use of phage therapy, bacteriocins and antiadhesive molecules. These strategies may open new avenues for the prevention and treatment of IBD in the future.
NICE recommends routine NHS funding for new breast cancer drugs
Authors: Gareth Iacobucci
Journal: BMJ (2017)

The new breast cancer drugs palbociclib (Ibrance, Pfizer) and ribociclib (Kisqali, Novartis) should be routinely funded on the NHS, draft guidance from the National Institute for Health and Care Excellence (NICE) has recommended.

The guidance,1 published on 16 November, said that price discounts agreed with manufacturers for both of the drugs had made them cost effective options for people with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or secondary breast cancer. This is despite uncertainty about how long the drugs extend overall survival for.

NICE’s initial draft guidance on palbociclib, published in February, did not recommend the drug because its cost was too high in relation to its clinical …
Geographic clonal tracking in macaques provides insights into HSPC migration and differentiation
Authors: Chuanfeng Wu, Diego A. Espinoza, Samson J. Koelle, E. Lake Potter, Rong Lu, Brian Li, Di Yang, Xing Fan, Robert E. Donahue, Mario Roederer, Cynthia E. Dunbar
Journal: The Journal of Experimental Medicine (2017)

The geographic distribution of hematopoiesis at a clonal level is of interest in understanding how hematopoietic stem and progenitor cells (HSPCs) and their progeny interact with bone marrow (BM) niches during regeneration. We tagged rhesus macaque autologous HSPCs with genetic barcodes, allowing clonal tracking over time and space after transplantation. We found marked geographic segregation of CD34+ HSPCs for at least 6 mo posttransplantation, followed by very gradual clonal mixing at different BM sites over subsequent months to years. Clonal mapping was used to document local production of granulocytes, monocytes, B cells, and CD56+ natural killer (NK) cells. In contrast, CD16+CD56- NK cells were not produced in the BM, and in fact were clonally distinct from multipotent progenitors producing all other lineages. Most surprisingly, we documented local BM production of CD3+ T cells early after transplantation, using both clonal mapping and intravascular versus tissue-resident T cell staining, suggesting a thymus-independent T cell developmental pathway operating during BM regeneration, perhaps before thymic recovery.
Abstract 17358: Prognostic Value of Splenic Response Ratio in Rubidium-82 Positron Emission Tomography Myocardial Perfusion Imaging
Authors: Karan Bami, Shrankhala Tewari, Fadi Guirguis, Linda Garrard, Ann Guo, Terrence D Ruddy, Robert S Beanlands, Robert A deKemp, Benjamin J Chow, Girish Dwivedi
Journal: Circulation (2016)

Introduction: Cardiac magnetic resonance perfusion studies with adenosine stress have shown that splenic response may be a valuable tool to identify patients with inadequate pharmacologic stress. H...
The amazing brain drain
Authors: Marie Blanchette, Richard Daneman
Journal: The Journal of Experimental Medicine (2017)

In this issue of JEM, Antila et al. (https://doi.org/10.1084/jem.20170391) demonstrate that central nervous system lymphatics develop in the mouse meninges during early postnatal periods and display remarkable plasticity in adult periods through manipulation of VEGF-C–VEGFR3 signaling.
Peptide receptor radionuclide therapy as a new tool in treatment-refractory sarcoidosis - initial experience in two patients
Authors: Constantin Lapa, Malte Kircher, Heribert Hänscheid, Andreas Schirbel, Götz Ulrich Grigoleit, Erdwine Klinker, Markus Böck, Samuel Samnick, Theo Pelzer, Andreas K Buck
Journal: Theranostics (2017)

Sarcoidosis is a multisystem granulomatous disorder of unknown etiology that can involve virtually all organ systems. Whereas most patients present without symptoms, progressive and disabling organ failure can occur in up to 10% of subjects. Somatostatin receptor (SSTR)-directed peptide receptor radionuclide therapy (PRRT) has recently received market authorization for treatment of SSTR-positive neuroendocrine tumors. Methods: We describe the first case series comprising two patients with refractory multi-organ involvement of sarcoidosis who received 4 cycles of PRRT. Results: PRRT was well-tolerated without any acute adverse effects. No relevant toxicities could be recorded during follow-up. Therapy resulted in partial response accompanied by a pronounced reduction in pain (patient #1) and stable disease regarding morphology as well as disease activity (patient #2), respectively. Conclusion: Peptide receptor radionuclide therapy in sarcoidosis is feasible and might be a new valuable tool in patients with otherwise treatment-refractory disease. Given the long experience with and good tolerability of PRRT, further evaluation of this new treatment option for otherwise treatment-refractory sarcoidosis in larger patient cohorts is warranted.
Cranial electrotherapy stimulation for the management of depression, anxiety, sleep disturbance, and pain in patients with advanced cancer: A preliminary study.
Authors: Sriram Yennu, Duck Hee Kang, Wen-Jen Hwu, Nikhil S Padhye, Charles Masino, Diane D Liu, Seyedeh Dibaj, Janet L. Williams, Zhanni Lu, Eduardo Bruera
Journal: Journal of Clinical Oncology (2017)

229 Background: Cranial Electrotherapy Stimulation (CES) is a safe modulation of brain activity for treating depression, anxiety, insomnia, and pain. However, there are no published studies in patients with advanced cancer (ACP).The aim of the study was to determine the feasibility and preliminary efficacy of a 4-week CES intervention on depression, anxiety, sleep disturbance, and pain scores. Concurrent salivary biomarker studies were conducted. Methods: In this one group open label pre- and post-intervention study with a 4-week CES intervention, ACP’s with one or more of four moderate intensity (≥3/10) ESAS symptoms (depression, anxiety, sleep disturbance, and pain) were eligible. Adherence (0-100%), satisfaction rates(0-10), and safety were assessed. ESAS, HADS, PSQI, BPI, and salivary levels (cortisol, alpha amylase, CRP, and IL-1 beta and IL-6) were assessed from baseline to week 4. Results: 33/38(87%) completed the CES. Median (IQR) adherence for days with 60 min CES use and satisfaction scores were 93(89-100)% and 10(9-10) respectively. CES use was safe (no grade 3 or higher adverse events). HADS anxiety (p &lt; 0.001), HADS depression (p = 0.024), ESAS anxiety (p = 0.001), depression (p = 0.025), BPI pain (p = 0.013), PSQI daytime dysfunction (p = 0.002), and Medication use (p = 0.006) scores improved after 4 week CES treatment. There was no significant change in the salivary cortisol, alpha-amylase, CRP, IL-1β, and IL-6 levels after 4 weeks of CES. Conclusions: In this preliminary study we found that the use of cranial Electrotherapy stimulation (CES) was safe and feasible in ACP. The use of CES was associated with significant improvement of depression, anxiety, pain, and sleep scores. These findings support further studies of CES in ACP for symptom control.
Current and New Therapeutic Strategies for Relapsed and Refractory Multiple Myeloma: An Update
Authors: Inger S. Nijhof, Niels W. C. J. van de Donk, Sonja Zweegman, Henk M. Lokhorst
Journal: Drugs (2017)

Although survival of multiple myeloma patients has at least doubled during recent years, most patients eventually relapse, and treatment at this stage may be particularly complex. At the time of relapse, the use of alternative drugs to those given upfront is current practice. However, many new options are currently available for the treatment of relapsed multiple myeloma, including recently approved drugs, such as the second- and third-generation proteasome inhibitors carfilzomib and ixazomib, the immunomodulatory agent pomalidomide, the monoclonal antibodies daratumumab and elotuzumab and the histone deacetylase inhibitor panobinostat, but also new targeted agents are under active investigation (e.g. signal transduction modulators, kinesin spindle protein inhibitors, and inhibitors of NF-kB, MAPK, AKT). We here describe a new paradigm for the treatment of relapsed multiple myeloma. The final goal should be finding a balance among efficacy, toxicity, and cost and, at the end of the road, achieving long-lasting control of the disease and eventually even cure in a subset of patients.
P2.06-020 A Open-Label Randomised Controlled Trial of First-Line Genexol-PM/CrEL-Based Paclitaxel plus Cisplatin in Advanced NSCLC Patients
Authors: Baohui Han, Yi Long Wu, Meiqi Shi, Aiqin Gu, Xueyan Zhang, Bo Jin, Yanjie Niu, Yu Dong, Ping Gu
Journal: Journal of Thoracic Oncology (2017)
Loss of pleckstrin-2 reverts lethality and vascular occlusions in JAK2V617F-positive myeloproliferative neoplasms
Authors: Baobing Zhao, Yang Mei, Lan Cao, Jingxin Zhang, Ronen Sumagin, Jing Yang, Juehua Gao, Matthew J. Schipma, Yanfeng Wang, Chelsea Thorsheim, Liang Zhao, Timothy Stalker, Brady Stein, Qiang Jeremy Wen, John D. Crispino, Charles S. Abrams, Peng Ji
Journal: Journal of Clinical Investigation (2017)

V617F driver mutation of JAK2 is the leading cause of the Philadelphia-chromosome-negative myeloproliferative neoplasms (MPNs). Although thrombosis is a leading cause of mortality and morbidity in MPNs, the mechanisms underlying their pathogenesis are unclear. Here, we identified pleckstrin-2 (Plek2) as a downstream target of the JAK2/STAT5 pathway in erythroid and myeloid cells, and showed that it is upregulated in a JAK2V617F-positive MPN mouse model and in patients with MPNs. Loss of Plek2 ameliorated JAK2V617F-induced myeloproliferative phenotypes including erythrocytosis, neutrophilia, thrombocytosis, and splenomegaly, thereby reverting the widespread vascular occlusions and lethality in JAK2V617F-knockin mice. Additionally, we demonstrated that a reduction in red blood cell mass was the main contributing factor in the reversion of vascular occlusions. Thus, our study identifies Plek2 as an effector of the JAK2/STAT5 pathway and a key factor in the pathogenesis of JAK2V617F-induced MPNs, pointing to Plek2 as a viable target for the treatment of MPNs.
Identification of alpha‐gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis
Authors: M. C. Carter, K. N. Ruiz‐Esteves, L. Workman, P. Lieberman, T. A. E. Platts‐Mills, D. D. Metcalfe
Journal: Allergy (2017)

IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3-6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked.
Vigilancia de la resistencia antimicrobiana en los patógenos invasivos : la experiencia de Estonia
Authors: K Loivukene, K Kermes, E Sepp, V Adamson, P Mitt, Ü Kallandi, K Otter, P Naaber
Journal: Eurosurveillance (2006)

El objetivo del estudio que presentamos aqui fue evaluar la necesidad de vigilancia de los patogenos invasivos Gram-negativos en Estonia. Los datos de sensibilidad a los antibioticos de los aislamientos invasivos de Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella spp, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae y de los enterococos fueron recogidos siguiendo los protocolos del EARSS (European Antimicrobial Resistance Surveillance System). Aunque la tasa de patogenos Gram-positivos sea superior a la de Gram-negativos, la tasa de resistencia antimicrobiana en los Gram-positivos es menor. La tasa de resistencia mas alta estaba asociada particularmente con A. baumannii y P. aeruginosa. La proporcion de cepas produciendo betalactamasas de amplio espectro (BLEA) era del 23% para Klebsiella spp. y de 3,6% para E. coli. Incluir los patogenos invasivos Gram-negativos en la vigilancia de la resistencia antimicrobiana proporciona informacion util sobre la sensibilidad de los patogenos locales, asi como para el tratamiento empirico de infecciones sospechosas.
Abstract 05: Associations of Objectively-measured Sedentary Time And Physical Activity with Meeting Cardiovascular Risk Factor Control Goals in U.S. Hispanic/Latino Adults with Diabetes: The Hispanic Community Health Study/Study of Latinos (hchs/sol)
Authors: Qibin Qi, Xueyin Wang, Garrett Strizich, Daniela Sotres-Alvarez, Christina Buelna, Linda Gallo, Marc Gellman, Yasmin Mossavar-Rahmani, Matthew O’Brien, Mark Stoutenberg, Tao Wang, Larissa Aviles-Santa, Robert Kaplan
Journal: Circulation (2016)

Background: Cardiovascular risk factor (RF) control is a cornerstone of diabetes management. Little is known about whether objectively-measured sedentary time and physical activity are associated with meeting RF goals in individuals with diabetes. Methods: We examined cross-sectional associations of sedentary behaviors and moderate-to-vigorous physical activity (MVPA) with meeting RF goals in 1,699 adults who self-reported diagnosed diabetes from the HCHS/SOL, a population-based cohort of US Hispanics/Latinos conducted between 2008 and 2011. Sedentary time and MVPA were assessed by Actical accelerometers for 7 days. Five RF goals were defined: HbA1c &lt;7.0%; systolic/diastolic blood pressure &lt;140/80 mmHg; triglycerides &lt;150 mg/dL; LDL-cholesterol &lt;100mg/dL; HDL-cholesterol &gt;40/50 mg/dL for men/women. Results: The mean time spent in sedentary behaviors and MVPA was 12.5 hrs/day and 17.2 mins/day, respectively. Adults with diabetes meeting greater number of RF goals spent, on average, less time in sedentary behaviors, and the odds of meeting ≥ 3 RF goals, relative to meeting zero RF goal, was 3.31 (95% CI 1.27, 7.68) times by comparing the lowest and highest tertiles of sedentary time (Figure 1). Specifically, after adjustment for potentially confounding variables and MVPA, less sedentary time was associated with increased odds of meeting HbA1c (OR for the lowest vs highest tertile of sedentary time =1.81 [1.20, 2.72]; P for trend =0.005) and triglyceride (OR =2.07 [1.34, 3.20]; P for trend =0.001) goals. MVPA was not associated with meeting any RF goals (all P for trend &gt;0.21). Associations between sedentary time and meeting RF goals were consistent among adults meeting or not meeting MVPA recommendations. Conclusions: US Hispanics/Latino adults with diabetes who spend less sedentary time were more likely to meet RF goals, particularly HbA1c and triglyceride goals, regardless of MVPA. Our findings further emphasize the importance of reducing sedentary behaviors beyond increasing exercise in individuals with diabetes.
A study of rovalpituzumab tesirine in frontline treatment of patients with DLL3 expressing extensive small cell lung cancer.
Authors: Christine L. Hann, Daniel Morgensztern, Afshin Dowlati, Timothy Francis Burns, Robert M. Jotte, Nathan A. Pennell, Stephen Lane Richey, Juergen Wolf, Martin Sebastian, Tobias R. Overbeck, Mark A. Socinski, Satwant Lally, Daniel Da Costa, Sreeni Yalamanchili, D. Ross Camidge
Journal: Journal of Clinical Oncology (2017)

TPS2598 Background: Treatment and survival of SCLC patients (pts) has remained mostly unchanged over past decades with high response rates to initial therapy (cisplatin/carboplatin + etoposide), but relapse is near universal with median survival &lt; 1 year in extensive disease. Delta-like protein 3 (DLL3) is an inhibitory ligand of the Notch receptor family identified as a novel target in high-grade neuroendocrine tumors, and is highly expressed in SCLC but not in normal tissue. Rovalpituzumab tesirine (Rova-T™) is an antibody-drug conjugate targeting DLL3. A Phase I study of Rova-T monotherapy in 2 nd and 3 rd line SCLC pts demonstrated encouraging antitumor activity with an ORR of 18% in all pts, and an ORR of 38% in DLL3-high pts (Rudin et al., Lancet Oncol, 2016.). Methods: This is a Phase I, open-label, multicenter study (NCT02819999; no pts enrolled as of 7 February 2017).In Phase Ia (escalation), 15-34 previously untreated DLL3-high pts will be enrolled and randomized to 1 of 4 cohorts. The primary objective of the Phase Ia portion is assessment of safety and dose-limiting toxicities (DLTs). Phase Ib (expansion) will enroll up to 2 cohorts of 30 pts each, and its primary objective is to characterize antitumor activity of the selected cohort(s). Secondary objectives (Phase Ia/b) include assessment of pharmacokinetics and anti-therapeutic antibodies against Rova-T, and characterization of antitumor activity (Phase Ia). Eligible pts: adults with histologically or cytologically confirmed extensive DLL3-high SCLC based on immunohistochemistry; ECOG 0-1; and life expectancy ≥ 12 weeks. Clinical trial information: NCT02819999. [Table: see text]
Nut Consumption and Risk of Cardiovascular Disease
Authors: Marta Guasch-Ferré, Xiaoran Liu, Vasanti S. Malik, Qi Sun, Walter C. Willett, JoAnn E. Manson, Kathryn M. Rexrode, Yanping Li, Frank B. Hu, Shilpa N. Bhupathiraju
Journal: Journal of the American College of Cardiology (2017)
Right ventricular longitudinal strain is diminished in systemic sclerosis compared with idiopathic pulmonary arterial hypertension
Authors: Monica Mukherjee, Valentina Mercurio, Ryan J. Tedford, Ami A. Shah, Steven Hsu, Christopher J. Mullin, Takahiro Sato, Rachel Damico, Todd M. Kolb, Stephen C. Mathai, Paul M. Hassoun
Journal: European Respiratory Journal (2017)

Pulmonary arterial hypertension (PAH) is characterised by severe progressive remodelling of pulmonary arterioles resulting in chronic right ventricular (RV) overload [1]. Regardless of aetiology, RV adaptation to increased pressure load is the main determinant of outcome in PAH [2–4]; however, mortality because of RV failure is significantly higher in systemic sclerosis-related PAH (SSc-PAH) than in idiopathic PAH (IPAH) [5]. Using invasive pressure–volume assessments, we have previously shown that SSc-PAH patients have depressed RV contractility compared with IPAH at similar afterloads [6]. However, the invasive nature of pressure–volume haemodynamics along with the significant expense and technical expertise makes this technique less feasible for routine clinical practice. Although two-dimensional echocardiogram (2DE) is a useful screening tool in PH, RV dysfunction may be often undetected or underestimated, partly because of the complex geometric configuration of the RV chamber and misalignment of the Doppler beam for noninvasive haemodynamic assessment. Speckle-tracking echocardiography (STE), an echo-based imaging modality used in conjunction with 2DE, allows offline calculation of myocardial velocities and deformation parameters in the assessment of regional myocardial contractility [7]. Our group recently demonstrated a heterogeneous pattern of RV longitudinal systolic strain (RVLSS) utilising STE in SSc patients with variable afterloads, which was not appreciable by 2DE alone [8]. Our findings, however, were shown in a cross-sectional analysis of asymptomatic SSc patients without symptomatic RV failure, right heart catheterisation (RHC)-confirmed PAH or with echocardiographic evidence of RV dilatation. In the current study, we applied this STE-based technique to PAH patients with baseline RV dysfunction to determine whether there were global and regional differences in RVLSS that might distinguish SSc-PAH from IPAH at similar afterload. Our findings have been previously presented in abstract form [9]. Speckle tracking echo is a useful clinical tool to distinguish differential RV contractility between PAH subtypes <http://ow.ly/6Wyr30fVTeu>