tbuckley/cabot-search huggingface dataset:
Granulocyte-colony stimulating factor (G-CSF) to treat acute-on-chronic liver failure: A multicenter randomized trial (GRAFT study)
Authors: Cornelius Engelmann, Adam Herber, Annegret Franke, Tony Bruns, Philipp Reuken, Ingolf Schiefke, Alexander Zipprich, Stefan Zeuzem, Tobias Goeser, Ali Canbay, Christoph Berg, Jonel Trebicka, Frank E. Uschner, Johannes Chang, Tobias Mueller, Niklas Aehling, Moritz Schmelzle, Katrin Splith, Frank Lammert, Christian M. Lange, Christoph Sarrazin, Christian Trautwein, Michael Manns, Dieter Häussinger, Jan Pfeiffenberger, Peter R. Galle, Anett Schmiedeknecht, Thomas Berg
Journal: Journal of Hepatology (2021)

Based on positive results from small single center studies, granulocyte-colony stimulating factor (G-CSF) is being widely used for the treatment of patients with acute-on-chronic liver failure (ACLF). Herein, we aimed to evaluate the safety and efficacy of G-CSF in patients with ACLF.In this multicenter, prospective, controlled, open-label phase II study, 176 patients with ACLF (EASL-CLIF criteria) were randomized to receive G-CSF (5 μg/kg daily for the first 5 days and every third day thereafter until day 26) plus standard medical therapy (SMT) (n = 88) or SMT alone. The primary efficacy endpoint was 90-day transplant-free survival analyzed by Cox regression modeling. The key secondary endpoints were overall and transplant-free survival after 360 days, the development of ACLF-related complications, and the course of liver function scores during the entire observation period.Patients treated with G-CSF had a 90-day transplant-free survival rate of 34.1% compared to 37.5% in the SMT group (hazard ratio [HR] 1.05; 95% CI 0.711-1.551; p = 0.805). Transplant-free and overall survival at 360 days did not differ between the 2 arms (HR 0.998; 95% CI 0.697-1.430; p = 0.992 and HR 1.058; 95% CI 0.727-1.548; p = 0.768, respectively). G-CSF did not improve liver function scores, the occurrence of infections, or survival in subgroups of patients without infections, with alcohol-related ACLF, or with ACLF defined by the APASL criteria. Sixty-one serious adverse events were reported in the G-CSF+SMT group and 57 were reported in the SMT group. In total, 7 drug-related serious adverse reactions occurred in the G-CSF group. The study was prematurely terminated due to futility after conditional power calculation.In contrast to previous findings, G-CSF had no significant beneficial effect on patients with ACLF in this multicenter controlled trial, which suggests that it should not be used as a standard treatment for ACLF. CLINICALTRIALS.NCT02669680 LAY SUMMARY: Granulocyte-colony stimulating factor was considered as a novel treatment for acute-on-chronic liver failure (ACLF). We performed the first randomized, multicenter, controlled phase II trial, which showed that G-CSF did not improve survival or other clinical endpoints in patients with ACLF. Therefore, G-CSF should not be used to treat liver disease outside clinical studies.
Non-coeliac gluten sensitivity: are we closer to separating the wheat from the chaff?
Authors: Maria Ines Pinto-Sánchez, Elena F Verdú
Journal: Gut (2016)

There is growing interest in the role of food as a trigger of functional bowel disorders such as IBS. Indeed, more than 60% of patients with IBS relate the occurrence of bloating and abdominal pain after the ingestion of certain foods.1 Despite intense research in the area, the identification of specific food triggers has remained elusive and this has hampered our understanding of the underlying pathophysiology of these conditions.

One clinical entity that embodies the complex relationship between food and gut functional symptoms is non-coeliac gluten sensitivity or non-coeliac wheat sensitivity (NCGS/NCWS) (figure 1). The two names reveal the existing ambiguity regarding the exact component/s in wheat responsible for the worsening or onset of the associated functional symptoms. NCGS/NCWS is thus a clinical descriptor of patients, in whom coeliac disease and wheat allergy have been ruled out, that present with intestinal and/or extra-intestinal symptoms after ingestion of gluten-containing foods.2 One of the dilemmas related to this condition is that this broad definition potentially includes patients with different underlying pathogenesis, leading to confusion in clinical practice and in research studies. Although gluten has been recognised as a trigger of functional symptoms in mice3 and in a subgroup of patients with IBS,4 it is unclear whether non-gluten protein fractions in wheat could also be responsible for symptom generation. While gluten proteins …
Transfusion Practices and Infections At Four Level III Neonatal Intensive Care Units
Authors: Elizabeth M Margolskee, Melissa M. Cushing, Yu-Hui Ferng, David Friedman, Debra Kessler, Joseph Schwartz, Deborah Sesok-Pizzini, Beth H Shaz, Yong Zhao, Lisa Saiman, Eldad A. Hod
Journal: Blood (2013)
Preparing for when things go wrong
Authors: Daniel Sokol
Journal: BMJ (2016)

What doctors can learn from astronauts



During his basic training as a fighter pilot, the astronaut Chris Hadfield was flying his jet in close formation, with jets immediately to his right and left, when he noticed a bee inside his helmet. Losing his cool would have endangered his life and those of his colleagues. Years later, in 2001, Hadfield was out on a space walk, holding on to the side of a spaceship travelling at more than 28 000 km an hour around the earth. He first lost his vision in one eye, and then the other. Again he kept calm. About 20 minutes later he recovered enough sight to complete the mission. He had been blinded by the anti-fog detergent used the evening before to clean his visor. …
Off-label and approved use of bevacizumab in elderly patients with colon cancer.
Authors: A. I. Neugut, D. J. Becker, D. Buono, A. Kershenbaum, D. L. Hershman
Journal: Journal of Clinical Oncology (2010)

e14038 Background: Bevacizumab was approved by the FDA for use in the first-line treatment of metastatic colon cancer in February, 2004. Trial results presented at ASCO 2009 suggested that bevacizumab has no overall survival benefit when added to FOLFOX as adjuvant treatment. We used a population-based sample of elderly patients with colon cancer to investigate the approved use of bevacizumab in the metastatic setting and its off-label use in the adjuvant setting. Methods: We identified patients ≥ 65 yrs diagnosed with stage II or III colon cancer, 9/1/04- 12/31/05, in the SEER-Medicare database (adjuvant therapy group) who were treated + bevacizumab within 6 months of diagnosis. We also identified patients ≥ 65 yrs diagnosed with stage IV or recurrent colon cancer, 1/1/05-12/31/05 (metastatic group) treated ± bevacizumab from the time of diagnosis. We developed multivariable logistic regression models to assess the relationship between patient age, gender, race, grade, marital status, residence, socio-economic status, comorbidity score, and receipt of bevacizumab. Results: Among 2737 patients with stage II colon cancer, 371 (14%) received adjuvant chemotherapy of whom 26 (7.0%) were treated with bevacizumab. Among 2,223 patients with stage III colon cancer, 1056 (48%) were treated with chemotherapy of whom 79 (7.5%) were treated with bevacizumab. Among 1,011 patients with stage IV or recurrent colon cancer treated with chemotherapy, 494 (49%) were treated with bevacizumab. Use of bevacizumab was not significantly associated with any of the evaluated demographic or clinical characteristics. Conclusions: Of patients receiving adjuvant chemotherapy for colon cancer, only a small proportion received off-label use of bevacizumab. In contrast, in the first year after its approval, half of patients receiving chemotherapy for metastatic colon cancer received the drug. No significant financial relationships to disclose.
Prochlorperazine and 5HT3 antagonists for the treatment of breakthrough chemotherapy-induced nausea and vomiting occurring despite prophylactic antiemetic therapy.
Authors: J. M. Jones, R. Qin, A. Bardia, B. Linquist, S. L. Wolf, C. L. Loprinzi
Journal: Journal of Clinical Oncology (2010)

e19590 Background: Chemotherapy-induced nausea and vomiting (CINV) is one of the most debilitating side effects of cancer therapy. Previous studies have primarily focused on prophylactic therapy, which have reduced the incidence of CINV to 15-40%, but no previous studies have been performed to evaluate treatment of breakthrough CINV. Methods: A prospective, observational pilot study was performed to evaluate the efficacy of individual agents prescribed for the treatment of CINV that occurred despite the use of prophylactic agents. Enrolled patients (pts) were receiving moderately or highly emetogenic chemotherapy and prophylactic treatment of CINV consistent with current NCCN, ASCO, or MASCC guidelines and were prescribed an antiemetic for breakthrough CINV. If pts had nausea, that occurred within the first 3 days of chemotherapy administration and that required their anti-emetic medication, they were instructed to complete a questionnaire every 30 minutes for 4 hours with the start of anti-emetic medication. Levels of nausea (0-10), vomiting and side effects were self recorded by the patients. Results: Of the 96 pts enrolled, 27 reported breakthrough nausea and were included in the final analysis. Of these, 88% (N= 24) reported use of prochlorperazine and 12% (N=3) reported use of 5HT3 for treatment of breakthrough nausea. Patients in both arms experienced a reduction of nausea from baseline (Table). Unexpectedly, drowsiness also improved, by 25% for those receiving prochlorperazine. Side effects of prochlorperazine were minimal and included abdominal cramping, dry mouth and blurry vision. No toxicities were reported in the 3 pts taking 5HT3 antagonists. Conclusions: Prochlorperazine and 5HT3 antagonists were associated with a 75% reduction in breakthrough nausea. This supports the use of these drugs for breakthrough CINV. Placebo-controlled randomized control trials could be performed to confirm these observations. Median nausea reductions after taking an antiemetric (percent of baseline) Time (minutes) 30 60 120 180 240 Prochlorperazine (n = 24) 46% 50% 75% 67% 75% 5HT3RA (n = 3) 71% 75% 63% 50% 75% No significant financial relationships to disclose.
Prospective Molecular Monitoring of Minimal Residual Disease after Non-Myeloablative Allografting in Newly Diagnosed Multiple Myeloma
Authors: Benedetto Bruno, Simone Ferrero, Daniela Drandi, Moreno Festuccia, Francesca Patriarca, Nicola Mordini, Silvia Cena, Daniela Barbero, Luigia Monitillo, Federica Ferrando, Lucia Brunello, Renato Fanin, Paola Ghione, Paola Omedè, Luisa Giaccone, Antonio Palumbo, Roberto Passera, Mario Boccadoro, Marco Ladetto
Journal: Blood (2014)
Sixty seconds on . . . CBT apps
Authors: Sue Mayor
Journal: BMJ (2016)

If you search online for “apps for depression” you’ll get more than a million hits. “People are starting to assume you can get therapy on a smartphone and we won’t need CBT to be provided by health services anymore,” explained Rona Moss-Morris, King’s College London professor of psychology as applied to medicine, at a media update on cognitive behavioural therapy this week. But most people, when asked, choose …
De Subitaneis Mortibus
Authors: THOMAS N. JAMES, DONALD B. HACKEL, THOMAS K. MARSHALL
Journal: Circulation (1974)

Two cases of sudden death are described, a boy of 16 and a woman of 34. Both had marked narrowing of the atrioventricular (A-V) node artery and fibrosis in the His bundle. Whereas he had been known to have complete heart block for several years, she was thought to be in excellent health until her sudden unexpected death. The degree of fibrosis in his His bundle was so extensive that one can doubt any effective transmission of a sinus impulse. Her His bundle was much less involved, but this may have been the consequence of her death during an initial mal-function of this crucial region of the heart, whereas prolonged survival of the boy (by electronic pacing) permitted a final view of the later histological consequences of the same initial arterial lesion. Both also had a mild degree of myocarditis and narrowing of a few other small coronary arteries (the large ones were normal). The possible functional inter-relationship of these factors is discussed.
Association of Infection in Early Life and Risk of Developing Type 1 Diabetes
Authors: Hakim Rahmoune, Nada Boutrid, Belkacem Bioud
Journal: JAMA (2016)

To the Editor A research letter by Dr Beyerlein and colleagues focused on infections in early life and the risk of developing type 1 diabetes (T1D) in a large pediatric cohort.1 We would like to address some relevant points about this study.
Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials
Authors: William Herrington, Jonathan Emberson, Borislava Mihaylova, Lisa Blackwell, Christina Reith, Marit Solbu, Patrick Mark, Bengt Fellström, Alan Jardine, Christoph Wanner, Hallvard Holdaas, Jordan Fulcher, Richard Haynes, Martin Landray, Anthony Keech, John Simes, Rory Collins, Colin Baigent
Journal: The Lancet Diabetes & Endocrinology (2016)

Statin therapy is effective for the prevention of coronary heart disease and stroke in patients with mild-to-moderate chronic kidney disease, but its effects in individuals with more advanced disease, particularly those undergoing dialysis, are uncertain.We did a meta-analysis of individual participant data from 28 trials (n=183 419), examining effects of statin-based therapy on major vascular events (major coronary event [non-fatal myocardial infarction or coronary death], stroke, or coronary revascularisation) and cause-specific mortality. Participants were subdivided into categories of estimated glomerular filtration rate (eGFR) at baseline. Treatment effects were estimated with rate ratio (RR) per mmol/L reduction in LDL cholesterol.Overall, statin-based therapy reduced the risk of a first major vascular event by 21% (RR 0·79, 95% CI 0·77-0·81; p<0·0001) per mmol/L reduction in LDL cholesterol. Smaller relative effects on major vascular events were observed as eGFR declined (p=0·008 for trend; RR 0·78, 99% CI 0·75-0·82 for eGFR ≥60 mL/min per 1·73 m(2); 0·76, 0·70-0·81 for eGFR 45 to <60 mL/min per 1·73 m(2); 0·85, 0·75-0·96 for eGFR 30 to <45 mL/min per 1·73 m(2); 0·85, 0·71-1·02 for eGFR <30 mL/min per 1·73 m(2) and not on dialysis; and 0·94, 0·79-1·11 for patients on dialysis). Analogous trends by baseline renal function were seen for major coronary events (p=0·01 for trend) and vascular mortality (p=0·03 for trend), but there was no significant trend for coronary revascularisation (p=0·90). Reducing LDL cholesterol with statin-based therapy had no effect on non-vascular mortality, irrespective of eGFR.Even after allowing for the smaller reductions in LDL cholesterol achieved by patients with more advanced chronic kidney disease, and for differences in outcome definitions between dialysis trials, the relative reductions in major vascular events observed with statin-based treatment became smaller as eGFR declined, with little evidence of benefit in patients on dialysis. In patients with chronic kidney disease, statin-based regimens should be chosen to maximise the absolute reduction in LDL cholesterol to achieve the largest treatment benefits.UK Medical Research Council, British Heart Foundation, Cancer Research UK, European Community Biomed Programme, Australian National Health and Medical Research Council, Australian National Heart Foundation.
Presidential Disability and the Twenty-fifth Amendment
Authors: Mark G. Jameson
Journal: JAMA (1995)

<h3>To the Editor.</h3> —Two questions in response to the excellent article by Drs Aaron and Rockoff.<sup>1</sup> <h3>Question:</h3> What is shaped like a dime, weighs less than a nickel, costs barely a penny, triggers a constitutional crisis, and generates hundreds of thousands of dollars of medical bills? <h3>Answer:</h3> The.22-caliber bullet removed from President Reagan. Easily purchased, even today it requires no license, identification, background check, or safety training. <h3>Question:</h3> When will they ever learn?
Dedicator of cytokinesis 8–deficient CD4 + T cells are biased to a T H 2 effector fate at the expense of T H 1 and T H 17 cells
Authors: Stuart G. Tangye, Bethany Pillay, Katrina L. Randall, Danielle T. Avery, Tri Giang Phan, Paul Gray, John B. Ziegler, Joanne M. Smart, Jane Peake, Peter D. Arkwright, Sophie Hambleton, Jordan Orange, Christopher C. Goodnow, Gulbu Uzel, Jean-Laurent Casanova, Saul Oswaldo Lugo Reyes, Alexandra F. Freeman, Helen C. Su, Cindy S. Ma
Journal: Journal of Allergy and Clinical Immunology (2016)
Language processing is not a race against time
Authors: Giosuè Baggio, Carmelo M Vicario
Journal: Behavioral and Brain Sciences (2016)

Abstract We agree with Christiansen &amp; Chater (C&amp;C) that language processing and acquisition are tightly constrained by the limits of sensory and memory systems. However, the human brain supports a range of cognitive functions that mitigate the effects of information processing bottlenecks. The language system is partly organised around these moderating factors, not just around restrictions on storage and computation.
Strategies to increase access to quality genetic testing services: Case study of <i>BRCA1/2</i> testing.
Authors: B. Kim, T. G. Bentley, S. S. Olmsted, S. Wooding, E. Eiseman, M. T. Scheuner
Journal: Journal of Clinical Oncology (2010)

6081 Background: Strategies designed to increase access to quality genetic testing services have not been well-studied. Methods: We developed a clinical framework of the genetic testing delivery process and built a decision-analytic model of predisposition testing for hereditary breast and ovarian cancer. We used Markov microsimulation models to simulate 1,000,000 unaffected, American, non-Ashkenazi Jewish women meeting USPSTF criteria for BRCA1/2 testing, estimating base case probabilities using the literature and expert opinion to represent current practice. Individual women entered the model with primary care providers (PCPs), who could then refer patients to specialists. Primary outcomes of interest were: identification of at-risk women, BRCA1/2 test uptake, and receipt of risk-appropriate recommendations. We identified key bottlenecks in the delivery process and varied parameter estimates accordingly to evaluate alternative quality improvement strategies. Results: We identified 2 bottlenecks in the base case (bold in Table) delivery process: low (20%) identification of at-risk women at the first step and few (17%) referrals to specialists at the next step. We modeled various combinations of 3 quality improvement strategies: PCP education; and increasing use of clinical decision support (CDS) and referrals to specialists. Incorporating 95% CDS use, or combining PCP education with 50% use of CDS and referrals, resulted in similar improved outcomes (italics), while PCP education + 95% use of CDS and referrals yielded the highest outcomes (bold italics). Conclusions: There is underutilization of genetic testing services for women at high risk for breast and ovarian cancer. Several strategies can improve access to these services and result in substantial increases in recommendations, which ultimately can lead to improved health outcomes. Implementing an optimal approach will depend on health system characteristics and require evaluation of costs and outcomes. No PCP Ed 17% Refer 15% CDS PCP Ed 50% CDS 95% CDS 50% Refer 95% Refer PCP Ed +50% Refer +50% CDS PCP Ed +95% Refer +95% CDS Women identified 20% 76% 47% 74% 20% 20% 80% 84% Opting to test 4% 28% 14% 25% 7% 9% 33% 37% Appropriate recs 6% 32% 21% 46% 10% 15% 44% 60% No significant financial relationships to disclose.
Abstract 19021: Abnormalities of Ventricular Morphology and Compaction Are Prevalent in Adults With Coarctation of the Aorta - A Two-centre Cardiac Magnetic Resonance Imaging (CMR) Study
Authors: Preeti Choudhary, Christian Hamilton-Craig, Wendy Strugnell, Rajesh Puranik, David S Celermajer
Journal: Circulation (2014)

Introduction:  Coarctation of the aorta (CoA) is associated with valvular and aortic disease but abnormalities of ventricular morphology are less well understood. Echocardiographic case series suggest a high prevalence of left ventricular non-compaction (LVNC) however; this has not been clarified by cardiac magnetic resonance imaging (CMR).   Methods:  CMR images of CoA adults were collated from two statewide tertiary referral centres in Australia. LVNC was defined as ratio of non-compacted to compacted myocardium of greater than 2.3 and abnormal compaction (LVAC) was defined by a ratio of 1.5-2.3 in end-diastole. Clinical information, volumetric data and mass calculations were obtained.   Results:  CMR scans of 293 CoA patients were analysed (Mean age 30+/-13 years; 50% male). 140 patients (48%) had bicuspid aortic valves (BAV) and 14 had unrepaired CoA. LVAC was evident in 78 % of patients and LVNC in 15 %. The most prevalent abnormality was mid-ventricular septal trabeculation in 40 patients. Patients with LVNC had significantly higher indexed end-diastolic (97+/-24 mL/m2 vs. 119+/-29 mL/m2; p=0.006) and end-systolic volumes (58+/-19 mL/m2 vs. 47+/-16 mL/m2; p = 0.03) compared to normally compacted ventricles, irrespective of the severity of aortic valvular disease. Ejection fraction did not significantly differ between the LVAC and normally compacted patients. (EF 60+/-6% vs. abnormally compacted EF 52+/-1; p = 0.30). Age, gender or presence of BAV did not correlate with presence of NC. In a subset of 148 cases, detailed short axis LV cine stacks were performed, revealing abnormalities of the mitral valve leaflets in 10, papillary muscles in 17 and myocardial clefts in 28 patients.   Conclusions:  Abnormal ventricular morphology is prevalent in CoA and should be considered in addition to the known valvular and vascular complications. LVNC correlates with increased end-diastolic volumes and may impact on ventricular function over time.