tbuckley/cabot-search huggingface dataset:
Abstract 9: Temperature-responsive Cell Delivery Biopolymers for Cardiac Tissue Engineering
Authors: Brisa Pena, Valentina Martinelli, Susanna Bosi, Carmen Sucharov, Mark Jeong, Matthew R Taylor, Maurizio Prato, Carlin S Long, Robin Shandas, Daewon Park, Luisa Mestroni
Journal: Circulation Research (2015)

Background: Advances in cell therapy and material science have made tissue engineering a promising strategy for heart regeneration. We developed an injectable biomimetic reverse thermal gel (RTG) that is liquid at room temperature but gel-like at body temperature, with the ultimate goal of being able to serve as a vehicle for cell-based delivery (liquid) to targeted tissue areas (gel-phase at 37°C). In this study we tested the suitability of this biomimetic RTG on cell viability. Methods and results: We tested different biomimetic RTG systems with and without the chemical incorporation of lysine. In vitro 3D culture experiments were performed with neonatal rat ventricular myocytes (NRVM) by mixing 3x104 cells with 50 μl of polymeric solution and allowing gel formation at 37°C. The cultured cells were incubated for 21 days. For controls we used NRVMs plated on 2D traditional gelatin coated dishes. We found that the 3D polymeric matrix induces rapid coordinated contraction with improved functionality when compared with standard 2D-cultured NRVM. By immunostaining for the morphology of the sarcomere (alpha-actinin) and DAPI, we also observed that the 3D polymeric matrix stimulates cells to spread and form 3D syncytia. Conclusion: These proof-of-concept results demonstrate long-term cell viability in this unique biomimetic system and therefore provide feasibility of a polymeric cell delivery system that permits reversible liquid-to-gel transition at body temperature. These results offer potential for a tissue engineering approach to cardiac regeneration.
Abstract 17300: Changes in Natriuretic Peptides After Hospitalization for Heart Failure With Preserved Ejection Fraction: A Feasible Surrogate Endpoint? A Report From the Prospective Karen Study
Authors: Gianluigi Savarese, Erwan Donal, Camilla Hage, Emmanuel Oger, Hans Persson, Jean-Claude Daubert, Cecilia Linde, Lars H Lund
Journal: Circulation (2016)

Introduction:  Changes in natriuretic peptide (NP) have been demonstrated to correlate with outcomes in patients with heart failure (HF). However, it is unknown whether the variations between their levels at the time of hospitalization for decompensation of HF with preserved ejection fraction (HFPEF) and at the follow-up visit could represent a prognostic tool and thus also a potential surrogate end-point for randomized trials assessing the efficacy of drugs initiated in the acute phase of HFPEF.   Hypothesis:  To assess: (1)what clinical characteristics in the acute setting were associated with lower NPs in the acute setting and with the improvement in NP levels at the follow-up; (2)whether changes in NPs from hospitalization to follow-up are associated with outcomes.   Methods:  Patients hospitalized for decompensated HFPEF enrolled in the Karolinska Rennes (KaRen) study and reporting N-terminal pro-B-type NP or B-type NP assessment at baseline and at 4-8 weeks follow-up were prospectively studied. Logistic regression analyses were performed to detect the predictors of baseline and changes in NPs. Cox’s regression models were performed using mortality and the composite of mortality and HF hospitalization as outcomes to detect any difference in prognosis between patients reporting a decrease vs. an increase in NPs.   Results:  Of 361 patients (median follow-up 585 days), 267(74%) reported an improve in NPs, while 94(26%) reported a worsening. At the baseline, the only independent predictor of lower NPs was higher glomerular filtration rate (OR:1.013; 95%CI:1.005-1.021), while the improve of NPs at the follow-up was predicted by higher heart rate (OR:1.014; 95%CI:1.003-1.025). After adjustments, the hazard ratio for all-cause death was 0.705 (95%CI:0.439-1.132) and that for the composite outcome was 0.820 (95%CI: 0.586-1.148) in patients improving vs. those worsening NPs at follow-up.   Conclusions:  Changes in NPs from the hospital admission to the follow-up evaluation were not associated to mortality and morbidity in decompensated HFPEF. This evidence does not support the evaluation of changes in NPs as a prognostic tool or as a surrogate end-point for randomized trials assessing the efficacy of drugs initiated in the acute phase of HFPEF.
Incidence and characteristics of melanoma brain metastases appearing during vemurafenib treatment.
Authors: Lucie Peuvrel, Melanie Saint-Jean, Gaelle Quereux, Anabelle Brocard, Amir Khammari, Anne-Chantal Knol, Brigitte Dreno
Journal: Journal of Clinical Oncology (2014)

9042 Background: Melanoma brain metastases are frequent and severe. We studied their characteristics in a retrospective cohort of patients treated with vemurafenib, a BRAF inhibitor indicated in V600-mutant metastatic melanoma. Methods: We included in this study all patients receiving vemurafenib in our department between November 2010 and November 2013 without melanoma brain metastases at initiation of treatment. Brain scans were performed after 2 months, and then every 3 months or in case of neurologic symptoms. RMI could be performed to confirm scan result. Our primary endpoint was the brain metastases incidence. Secondary endpoints were associated risk factors, onset modalities and clinical evolution. Results: In our cohort of 86 patients, incidence of brain metastases was 20% after a median follow-up of 9 months (1 to 26 months). They appeared after a mean of 5.3 months of vemurafenib exposure (1 to 15 months). The only identified risk factor was a high number of metastases before treatment (p=0.045). Radiological exams revealed 41% of miliary brain metastases. Occurence of brain metastases was associated with a trend toward a decrease in overall survival from 12.8 months (95% CI: 9.2-16.7) to 8.5 months (95% CI: 4.5-11.5) (p=0.07) and with a significant decrease in progression free survival from 7 months (95% CI: 5-8) to 5 months (95% CI: 3-8) (p=0.04). Among patients with brain metastases, 82% were died at time of analysis after a median of 2.7 months (0.2 to 7.2 months). Comparatively, only 58% of the patients without brain metastases died during the same period. The extra cerebral disease was well controlled in 59% of patients at the time of diagnosis of brain metastases. Conclusions: Our study shows that melanoma brain metastases appearing in patients during vemurafenib are frequent in real life conditions and associated with a very poor prognosis. Systematic brain explorations must thus be performed during vemurafenib treatment, even in patients with good extra cerebral responses. RMI should be preferred to scan due to the high frequency of miliary metastases. Specific resistance mechanisms are likely in this location due to the high number of dissociated responses between cerebral and extra cerebral metastases.
Beware of geeks bearing gifts
Authors: Kamran Abbasi
Journal: BMJ (2017)

The NHS is in crisis. That much we knew. That the latest crisis (doi:10.1136/bmj.j2357) was caused by a failure of cyber-security is an unexpected twist in the organisation’s struggle against chronic underfunding. WannaCrypt or WannaCry, a Trojan malware or ransomware, disables computer systems by stealing and encrypting data and locking out users. On payment of a ransom in the crypto-currency of bitcoin, your data will be returned to you and your computer unlocked. The ransomware hides in a seductive email and hijacks your computer when you open it. In this era of cyber-threats, beware of geeks bearing …
PMO-040 The development and validation of a nutritional prioritising tool for use in patients with chronic liver disease: Abstract PMO-040 Figure 1
Authors: S Arora, C Mattina, M Catherine, N O'Sullivan, L McGeeney, C Nina, G Gatiss, B Davidson, B Engel, M Morgan
Journal: Gut (2012)

<h3>Introduction</h3> Patients with cirrhosis are frequently malnourished and this has a detrimental effect on outcome in terms of complications, survival after liver transplantation and overall liver-related mortality. The detection of malnutrition and its active management is, therefore, pivotal to these patients9 well-being and survival. The aim of this study was to design and develop a simple, nutritional screening tool for use in patients with cirrhosis -The Royal Free Nutritional Prioritising Tool (RFH-NPT)—and to validate its use against the Royal Free Hospital Global Assessment (RFH-GA) which is the accepted gold standard for nutritional assessment of cirrhotic patients in the UK. <h3>Methods</h3> The RFH-NPT was devised and piloted; interobserver performance agreement was excellent. Validation was undertaken in a cohort of patients with cirrhosis on transplant units throughout the UK and Southern Ireland. Patients9 nutritional status was determined and categorised, by nursing staff, using the RFH-NPT (completion time 3 min). The results were compared with the categorisation of nutritional status determined by dietitians using the RFH-GA (completion time 45 min). The analysis of descriptive data, cross-tabulation, performance variables, 95% CIs and κ values were calculated using standard methods. κ Values were interpreted according to Altman, 1999. <h3>Results</h3> The patient population comprised 133 patients with cirrhosis (98 men: 35 women; mean [range] age 56 [23–73] yr). Overall 49 (37 %) patients were classified, using the RFH-GA, as adequately nourished; 46 (35%) as moderately malnourished and 38 (29%) as severely malnourished. The RFH-NPT identified patients who were at high risk for malnutrition with a diagnostic sensitivity of 100% (95% CI 89 to 100) and specificity of 73% (95% CI 63 to 81) (κ value 0.41, 95% CI 29 to 53). <h3>Conclusion</h3> The RFH-NPT is a simple, quick and validated method for identifying patients with cirrhosis who at high risk for malnutrition. Further multicentre validation is warranted. <h3>Competing interests</h3> None declared.
Physician age and outcomes in elderly patients in hospital in the US: observational study
Authors: Yusuke Tsugawa, Joseph P Newhouse, Alan M Zaslavsky, Daniel M Blumenthal, Anupam B Jena
Journal: BMJ (2017)

<b>Objectives</b>&nbsp;To investigate whether outcomes of patients who were admitted to hospital differ between those treated by younger and older physicians. <b>Design</b>&nbsp;Observational study. <b>Setting</b>&nbsp;US acute care hospitals. <b>Participants</b>&nbsp;20% random sample of Medicare fee-for-service beneficiaries aged ≥65 admitted to hospital with a medical condition in 2011-14 and treated by hospitalist physicians to whom they were assigned based on scheduled work shifts. To assess the generalizability of findings, analyses also included patients treated by general internists including both hospitalists and non-hospitalists. <b>Main outcome measures</b>&nbsp;30 day mortality and readmissions and costs of care. <b>Results</b>&nbsp;736 537 admissions managed by 18 854 hospitalist physicians (median age 41) were included. Patients’ characteristics were similar across physician ages. After adjustment for characteristics of patients and physicians and hospital fixed effects (effectively comparing physicians within the same hospital), patients’ adjusted 30 day mortality rates were 10.8% for physicians aged &lt;40 (95% confidence interval 10.7% to 10.9%), 11.1% for physicians aged 40-49 (11.0% to 11.3%), 11.3% for physicians aged 50-59 (11.1% to 11.5%), and 12.1% for physicians aged ≥60 (11.6% to 12.5%). Among physicians with a high volume of patients, however, there was no association between physician age and patient mortality. Readmissions did not vary with physician age, while costs of care were slightly higher among older physicians. Similar patterns were observed among general internists and in several sensitivity analyses. <b>Conclusions</b>&nbsp;Within the same hospital, patients treated by older physicians had higher mortality than patients cared for by younger physicians, except those physicians treating high volumes of patients.
IRON ABSORPTION. IV. THE ABSORPTION OF HEMOGLOBIN IRON*
Authors: Adam Turnbull, Frans Cleton, Clement A. Finch
Journal: Journal of Clinical Investigation (1962)

The absorption of radioiron in rabbit hemoglobin, hemin, and ferritin has been compared to that of ferrous salt in healthy volunteers and in subjects with iron-deficiency anemia. At a dosage level of 5 mg elemental iron, hemoglobin iron was as well or better absorbed than ferrous salts in the normal subject. Absorption of hemoglobin iron increased less, however, in the iron-depleted or iron-deficient subject. In contrast to the absorption of ferrous salts, that of hemoglobin iron was not decreased by food or by phytate nor increased by ascorbic acid. The absorption of hemin iron was also not decreased by food. Iron absorbed from hemoglobin appeared in the plasma later than that from ferrous salts, but was found to be similarly dialyzable at acid pH with EDTA. These findings suggest that iron in heme complexes is absorbed as a porphyrin complex without conversion to the free ionized form. It is further apparent that there is less effective mucosal regulation of absorption of iron in this form. Finally, the present hypothesis of iron absorption based on the behavior of iron salts is not adequate for all types of food iron.
VICTOR: A phase III placebo-controlled trial of rofecoxib in colorectal cancer patients following surgical resection
Authors: D. J. Kerr, J. A. Dunn, M. J. Langman, J. L. Smith, R. S. Midgley, C. L. Iveson, C. C. McConkey
Journal: Journal of Clinical Oncology (2008)

4038 Background: The cyclo-oxygenase-2 inhibitor, rofecoxib (R) was hypothesised to improve survival in cancer patients who had undergone surgery for colorectal cancer (CRC). This trial recruited from April 2002 until September 2004 when R was withdrawn over concerns about its cardiovascular safety (CVS). This report provides preliminary efficacy results. Methods: Recruited patients had undergone Ro resection of a stage II/III CRC and completion of adjuvant therapy (radiotherapy/chemotherapy/both/neither) less than 12 weeks previously. Excluded patients were those with active peptic ulceration, gastro-intestinal bleeding and those receiving long-term NSAID therapy (except low dose aspirin). 7,000 patients were planned to receive 25mg R daily or an identical placebo (P) for 2 or 5 years, with the goal of detecting a reduction in risk of death - hazard ratio (HR) 0.82. After the trial’s premature closure, a modified protocol of the post- treatment follow-up phase and revised statistical analysis plan permitted the detection of a reduction (HR=0.75) in risk of death with 87% power, type I error 0.05, with one pre-planned event-driven interim analysis. Overall survival (OS) and disease-free survival (DFS) were both measured from randomisation, with DFS defined as the time to recurrence or death from any cause. Results: 1,167 of 1,217 patients randomised to R and 1,160 0f 1,217 randomised to P received treatment with median durations of 7.4 months and 8.2 months respectively. Median follow-up was 3.0 and 3.1 years in the two arms (R vs P), with 177 vs 191 deaths and 291 vs 316 DFS events. This pre-planned Kaplan-Meier and log- rank analysis demonstrated that the R patients had slightly longer OS than the P patients, HR 0.94 (95% CI 0.77–1.16; p=0.57). Similarly DFS was slightly higher in the R patients, HR 0.91 (95% CI 0.78–1.07; p=0.25). 19 patients in each arm died without recurrence of CRC. Conclusions: In this study of short treatment duration treatment with R is unlikely to result in a substantial improvement in OS but a small protective effect against recurrence is suggested. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck and Co. Inc Merck & Co Inc
Immunotherapies for Lung Cancer
Authors: Matthew A. Gubens
Journal: Journal of the National Comprehensive Cancer Network (2017)

In 2017, immunotherapy is the standard of care for patients with non–small cell lung cancer (NSCLC) either in the first or second line depending on programmed death ligand-1 (PD-L1) and mutation status. For first-line therapy, pembrolizumab is currently the standard of care for patients whose tumors express PD-L1 >50%. All patients with NSCLC should undergo PD-L1 testing before initiating treatment on pembrolizumab. For patients not eligible in the first line, immunotherapy is the standard of care for most in the second line. Nivolumab and atezolizumab are approved in all patients as second-line therapies after platinum-based doublet failure regardless PD-L1 expression level, although pembrolizumab is approved as second-line therapy for those whose tumors express PD-L1 >1%.
Requiem for the cholecystokinin provocation test Reply
Authors: W R MURRAY, A W MAJEED
Journal: Gut (1999)

cacy of combining these drugs might be of great help.Presently, the data in the three meta-analyses constitutes a sound, objective basis on which to tackle therapeutic decisions.The statement endorsed by the working party seems to reflect the common belief shared by leading authorities in this field that these agents are ineVective in the treatment of acute pancreatitis.This may be because the drugs are believed to act through their antisecretory or protease inhibitory activity.However, other relevant properties of somatostatin and octreotide, namely the haemodynamic eVects on reducing splanchnic blood flow, the stimulation of the hepatic reticuloendothelial system, and the modulation of the cytokine cascade, are usually forgotten.It has been hypothesised that the eYcacy of somatostatin and octreotide in acute pancreatitis might be better explained by all these properties rather than its capability of inhibiting pancreatic secretion.
Inhibin as a Marker for Granulosa-Cell Tumors
Authors: Richard E. Lappöhn, Henry G. Burger, Joke Bouma, Mohan Bangah, Mindert Krans, Henk W.A. De Bruijn
Journal: New England Journal of Medicine (1989)

Inhibin is a peptide hormone normally produced by ovarian granulosa cells. It reaches a peak of 772±38 U per liter in the follicular phase of the menstrual cycle and is undetectable in the serum of menopausal women. To determine whether measurements of serum inhibin levels would provide a biochemical marker of the presence or progression of ovarian granulosa-cell tumors and their metastases, we measured the serum immunoreactive inhibin concentrations in six women with such tumors. Three women had been treated by hysterectomy and bilateral salpingo-oophorectomy. In the two women with residual or recurrent disease, the serum inhibin levels were abnormally elevated 5 and 20 months before the clinical manifestations of recurrence became evident. The maximal concentrations approached 3000 U per liter. The serum inhibin level remained undetectable in one patient who was disease-free for 11 years. Serum inhibin concentrations were also elevated in three women with amenorrhea and infertility that resulted from small granulosa-cell tumors. After the removal of the tumors, the serum inhibin levels in these women became normal, and fertility returned. There was a significant negative correlation between the serum concentrations of inhibin and follicle-stimulating hormone, in a manner consistent with the autonomous production of inhibin by granulosa-cell tumors. We conclude that granulosa-cell tumors produce inhibin. Since serum inhibin levels reflect the size of the tumor, measurements of inhibin can be used as a marker for primary as well as recurrent disease. (N Engl J Med 1989; 321:790–3.)
The emerging roles and therapeutic potential of exosomes in epithelial ovarian cancer
Authors: Xiaoduan Li, Xipeng Wang
Journal: Molecular Cancer (2017)

Ovarian cancer (OC) is one of the three types of malignant tumors in the female reproductive system, and epithelial ovarian cancer (EOC) is its most typical form. Due to the asymptomatic nature of the early stages and resistance to chemotherapy, EOC has both a poor prognosis and a high fatality rate. Current treatments for OC are very limited, and the 5-years survival rate is approximately 30%. Exosomes, which are microvesicles ranging from approximately 30–100 nm in size that are secreted by living cells, can be produced from different cell types and detected in various body fluids. Cancer cells can secrete more exosomes than healthy cells, and more importantly, the content of cancer cell-derived exosomes is distinct. The exosomes shedding from tumor cells are considered to be involved in tumor progression and metastasis. As such, exosomes are expected to be potential tools for tumor diagnosis and treatment. In this review, we briefly present the emerging roles of exosomes in OC and summarize related articles about their roles as diagnostic or prognostic biomarkers and in the treatment and drug resistance of OC.
New Treatment Options for the Management of Multiple Myeloma
Authors: Shaji K. Kumar
Journal: Journal of the National Comprehensive Cancer Network (2017)

Multiple myeloma (MM) is a complex disease characterized by considerable genetic heterogeneity. The updated NCCN Guidelines for MM have added new "preferred" regimens for transplant and nontransplant candidates, and have moved some formerly "preferred" regimens to the "other" category. Supportive care has improved outcomes for patients, and new treatments in combination have extended survival for patients with MM. Novel agents on the horizon are poised to raise the bar even further.
Abstract 13608: Center Variation in Home Time Following Acute Ischemic Stroke
Authors: Emily C O’Brien, Ying Xian, Jingjing Wu, Jeffrey L Saver, Eric E Smith, Lee H Schwamm, Eric D Peterson, Mathew J Reeves, Deepak L Bhatt, Janet Prvu-Bettger, Deidre Hannah, Lesley Maisch, Brianna Lindholm, Adrian F Hernandez, Gregg C Fonarow
Journal: Circulation (2015)

Background: Stroke survivors have identified that home time is a high priority outcome, but there are limited data on factors associated with time at home following stroke as well as the degree to which home time varies among discharging hospitals. Methods: PROSPER is a PCORI-funded program designed with stroke survivors to evaluate post-stroke therapies and outcomes. We linked data for patients &gt;65 years old who were enrolled in the GWTG-Stroke Registry to Medicare claims to ascertain home time, defined as time spent alive and out of a hospital or skilled nursing facility, at 90 days and 1 year after discharge for ischemic stroke. We used generalized mixed models with random effects to estimate adjusted mean home time for each hospital, accounting for patient characteristics. We then used linear regression to assess hospital factors associated with risk-adjusted home time. Results: From 2007-2011, 156,869 ischemic stroke patients at 1417 hospitals were linked to Medicare claims. Home time varied among hospitals, with overall unadjusted median home time (IQR) of 59.5 days (55.7-63.2) over the first 90 days and 270 days (256.0-281.1) over the first year. Hospital factors associated with more home time over 90 days included higher annual stroke volume; South, West, or Midwest geographic regions (vs. Northeast); and rural location (Table). Similar patterns were observed at 1 year. Compared with patients in the highest hospital home time quartile, patients in the lowest were older, more likely to be female, had more comorbidities, and had more severe strokes by NIHSS. Home time variation decreased after adjustment, with a median of 59.3 days (57.4-61.4) over 90 days and 270 days (266.3-274.2) over 1 year. Conclusions: In a population of older ischemic stroke survivors, home time after discharge varies by hospital stroke volume, severity case mix, and region. In adjusted analyses, hospital stroke volume and rural location were associated with more days at home following stroke.