tbuckley/cabot-search huggingface dataset:
Effect of On-Demand vs Routine Nebulization of Acetylcysteine With Salbutamol on Ventilator-Free Days in Intensive Care Unit Patients Receiving Invasive Ventilation
Authors: David M. P. van Meenen, Sophia M. van der Hoeven, Jan M. Binnekade, Corianne A. J. M. de Borgie, Maruschka P. Merkus, Frank H. Bosch, Henrik Endeman, Jasper J. Haringman, Nardo J. M. van der Meer, Hazra S. Moeniralam, Mathilde Slabbekoorn, Marcella C. A. Muller, Willemke Stilma, Bart van Silfhout, Ary Serpa Neto, Hans F. M. ter Haar, Jan Van Vliet, Jan Willem Wijnhoven, Janneke Horn, Nicole P. Juffermans, Paolo Pelosi, Marcelo Gama de Abreu, Marcus J. Schultz, Frederique Paulus
Journal: JAMA (2018)

<h3>Importance</h3> It remains uncertain whether nebulization of mucolytics with bronchodilators should be applied for clinical indication or preventively in intensive care unit (ICU) patients receiving invasive ventilation. <h3>Objective</h3> To determine if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization. <h3>Design, Setting, and Participants</h3> Randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands. <h3>Interventions</h3> On-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473). <h3>Main Outcomes and Measures</h3> The primary outcome was the number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of −0.5 days. Secondary outcomes included length of stay, mortality rates, occurrence of pulmonary complications, and adverse events. <h3>Results</h3> Nine hundred twenty-two patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years) were enrolled and completed follow-up. At 28 days, patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days (1-sided 95% CI, −0.00003 to ∞). There was no significant difference in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups. Adverse events (13.8% vs 29.3%; difference, −15.5% [95% CI, −20.7% to −10.3%];<i>P</i> &lt; .001) were more frequent with routine nebulization and mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, −13.4% [95% CI, −18.4% to −8.4%];<i>P</i> &lt; .001) and agitation (0.2% vs 4.3%; difference, −4.1% [95% CI, −5.9% to −2.2%];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> Among ICU patients receiving invasive ventilation who were expected to not be extubated within 24 hours, on-demand compared with routine nebulization of acetylcysteine with salbutamol did not result in an inferior number of ventilator-free days. On-demand nebulization may be a reasonable alternative to routine nebulization. <h3>Trial Registration</h3> clinicaltrials.gov Identifier:NCT02159196
The role of zinc and nutritional immunity in<i>Clostridium difficile</i>infection
Authors: Joseph P. Zackular, Eric P. Skaar
Journal: Gut Microbes (2018)

Clostridium difficile in one of the most commonly reported nosocomial pathogens worldwide. Beyond antibiotic use, little is known about the host, microbiota, and environmental factors that contribute to susceptibility to and severity of C. difficile infection (CDI). We recently observed that in a mouse model of CDI, excess dietary zinc (Zn) alters the gut microbiota and decreases resistance to CDI. Moreover, we determined that high levels of Zn exacerbate C. difficile-associated disease and calprotectin-mediated Zn limitation is an essential host response to infection. In this addendum, we discuss how these findings add to our understanding of CDI and consider the potential implications of excess metal intake on the microbiota and infection.
CAR T-cells targeting FLT3 have potent activity against FLT3−ITD+ AML and act synergistically with the FLT3-inhibitor crenolanib
Authors: Hardikkumar Jetani, Irene Garcia-Cadenas, Thomas Nerreter, Simone Thomas, Julian Rydzek, Javier Briones Meijide, Halvard Bonig, Wolfgang Herr, Jordi Sierra, Hermann Einsele, Michael Hudecek
Journal: Leukemia (2018)
Malignant pleural mesothelioma immune microenvironment and checkpoint expression: correlation with clinical–pathological features and intratumor heterogeneity over time
Authors: G. Pasello, G. Zago, F. Lunardi, L. Urso, I. Kern, G. Vlacic, F. Grosso, M. Mencoboni, G.L. Ceresoli, M. Schiavon, F. Pezzuto, A. Pavan, S.E. Vuljan, P. Del Bianco, P. Conte, F. Rea, F. Calabrese
Journal: Annals of Oncology (2018)
Consultant Mark Porter is elected as chairman of BMA council
Authors: Helen Jaques
Journal: BMJ (2012)

Consultant anaesthetist Mark Porter has been elected as the new chairman of the BMA’s governing council, replacing outgoing chairman and general practitioner Hamish Meldrum.

Porter has been a consultant in obstetric anaesthesia at University Hospitals Coventry and Warwickshire NHS Trust since 1998, where he was also a clinical …
RELATIONSHIP BETWEEN UNDERLYING PLAQUE MORPHOLOGY EVALUATED BY NEAR-INFRARED SPECTROSCOPY AND THE DEGREE OF CORONARY ARTERY STENOSIS: THE COLOR REGISTRY
Authors: Masaru Ishida, Giora Weisz, Myong Hwa Yamamoto, Mitsuaki Matsumura, Aaron Crowley, Stephen Nicholls, Gregg Stone, Gary Mintz, James Muller, Akiko Maehara
Journal: Journal of the American College of Cardiology (2018)
Acute care problems will not be addressed by Shape of Training review’s proposals, say royal colleges
Authors: Abi Rimmer
Journal: BMJ (2014)

Proposed changes to medical training set out in the Shape of Training review will not address current problems in acute care, three medical royal colleges have warned.

The Royal College of Physicians of London, the Royal College of Physicians of Edinburgh, and the Royal College of Physicians and Surgeons of Glasgow have issued a joint statement with the Joint Royal Colleges of Physicians Training Board in response to David Greenaway’s Shape of Training review.1

The statement warned that the Shape of Training review, which recommends that postgraduate medical training should “train all doctors to provide care in community and acute care settings,” would not address the immediate challenges in acute care. “The view that these proposals will address the current problems in acute care …
Methotrexate restores the function of peripheral blood regulatory T cells in psoriasis vulgaris via the CD73/AMPK/mTOR pathway
Authors: K. Yan, W. Xu, Y. Huang, Z. Zhang, Q. Huang, K.Z. Xin, Y. Ma, L. Han
Journal: British Journal of Dermatology (2018)

Methotrexate (MTX) is used to treat psoriasis, a chronic inflammatory skin disease.To investigate the molecular mechanism of MTX in the treatment of psoriasis.Regulatory T cells (Tregs) and effector T (Teff) cells were isolated from the blood of patients with psoriasis and healthy controls. The proliferation of Teff cells was detected by carboxyfluorescein succinimidyl ester assay. The interferon (IFN)-γ and interleukin (IL)-17 levels were analysed by enzyme-linked immunosorbent assay. The expression of CD73 and FoxP3 were determined by flow cytometry. The expression of proteins in the AMPK/mTOR pathway were detected by Western blot analysis.The data suggested that patients with psoriasis have Tregs with decreased immune suppression function and reduced expression of CD73 compared with healthy controls. Moreover, MTX could significantly restore the immunosuppressive function of IL-17-secreting Tregs. This, in turn, inhibits aberrant proliferation of Teff cells in patients with psoriasis, reverses downregulation of CD73, upregulates phosphorylated AMPK and inhibits phosphorylated mTOR, and downregulates IL-17 and IFN-γ levels.We speculate that MTX can restore the immunosuppressive function of Tregs through upregulating CD73, activating AMPK and inactivating the mTOR pathway. These findings may partly explain the mechanism by which MTX treats psoriasis.
Staff in the NHS are, first and foremost, people
Authors: Peter W Johnston, Jennifer Cleland
Journal: BMJ (2018)

The UK NHS is about people, for people, by people. This is the nature of healthcare—we need people to look after us when we are sick. Responses to rising patient demand, financial constraints, and political dogma in the UK may be well intended and focus on patient need, but they fail to respect the human nature of the professional groups on whom …
RECURRENT PULMONARY EMBOLISM: DUPLICATE INFERIOR VENA CAVA (IVC) THE CULPRIT
Authors: Hiten R. Patel, Upamanyu Rampal, Rahul Vasudev, Priyank Shah, Fayez Shamoon, Hartaj Virk, Mahesh Bikkina
Journal: Journal of the American College of Cardiology (2018)
Phytochemicals - an alternative therapy for glioblastoma?
Authors: Shofiya Salim, Tim Snape, Philip Welsby, Gail Welsby
Journal: Neuro-Oncology (2018)

Glioblastoma is the most common and malignant primary brain tumour in adults. Despite current treatment options including surgery followed by radiation and chemotherapy with temozolomide (TMZ) and cisplatin, median survival rates remain low (<16 months). Combined with increasing drug resistance and the inability of some compounds to cross the blood brain barrier (BBB), novel compounds are being sought for the treatment of this disease. Phytochemicals are bioactive, non-nutrient plant chemicals which are structurally sub-divided into 5 groups. Of these groups, phenolics are the most common and widely studied, with flavonoids being the most abundant. With their reduced side-effect profile and ability to cross the BBB, phytochemicals offer potential to improve current glioblastoma treatment options. High performance liquid chromatography (HPLC) was undertaken to identify and measure individual polyphenols present in five freeze-dried fruit samples (acai berry, maqui berry, goji berry, strawberry and cranberry). Subsequently, SVG-p12 and U87-MG cells were treated with varying concentrations of cisplatin, punicalagin or cyanidin-3-glucoside over a 3-day period. Concentration dependent effects of each treatment on cell viability were measured by the addition of PrestoBlue® reagent. Fluorescence was measured at Ex 535nm/Em 612nm. Following treatment, a time and concentration-dependent reduction in cell viability was observed. In U87-MG and SVG-p12 cells after 48 hours of treatment, IC50 values for punicalagin were 46 and 49µM respectively. Interestingly, cyanidin-3-glucoside did not reduce cell viability in SVG-p12 cells to the same extent as in U87-MG cells with IC50 values of 109 and 46µM respectively. Cisplatin showed similar efficacy in both cells lines following 48 hours of treatment with IC50 values of 10µM and 7mM in SVG-p12 and U87-MG cells respectively. This data suggests that the phenolic compounds punicalagin and cyanidin-3-glucoside have cytotoxic effects on glioma cell lines and have the potential to become alternative treatments for glioblastoma.
Survivin Monoclonal Antibodies Detect Survivin Cell Surface Expression and Inhibit Tumor Growth <i>In Vivo</i>
Authors: Robert A. Fenstermaker, Sheila A. Figel, Jingxin Qiu, Tara A. Barone, Sanam S. Dharma, Evan K. Winograd, Phillip M. Galbo, Laura M. Wiltsie, Michael J. Ciesielski
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Survivin is an inhibitor of apoptosis protein (IAP) that is highly expressed in many cancers and represents an attractive molecule for targeted cancer therapy. Although primarily regarded as an intracellular protein with diverse actions, survivin has also been identified in association with circulating tumor exosomes. Experimental Design: We have reported that active, specific vaccination with a long peptide survivin immunogen leads to the development of survivin-specific CD8-mediated tumor cell lysis and prolongation of survival in tumor-bearing mice. In addition to cellular antitumor responses, circulating anti-survivin antibodies are detected in the serum of mice and human glioblastoma patients following vaccination with the survivin immunogen. Results: Here we demonstrate that survivin is present on the outer cell membrane of a wide variety of cancer cell types, including both murine and human glioma cells. In addition, antibodies to survivin that are derived from the immunogen display antitumor activity against murine GL261 gliomas in both flank and intracranial tumor models and against B16 melanoma as well. Conclusions: In addition to immunogen-induced, CD8-mediated tumor cell lysis, antibodies to the survivin immunogen have antitumor activity in vivo. Cell-surface survivin could provide a specific target for antibody-mediated tumor immunotherapeutic approaches. Clin Cancer Res; 24(11); 2642–52. ©2018 AACR.
A R Gatrad: cross cultural medical care in the UK
Authors: Salmaan Khan
Journal: BMJ (2010)

#### A R Gatrad

There seemed to be an excess of Asian children with complex congenital heart disease when I worked as a cardiology registrar in Manchester in the ’70s. I confirmed through research that most parents of these children were consanguineous Muslims. This generated a lot of interest because there was little literature on patients from South Asia at that time.

Yes. In Manchester I was told by a professor that I should become a general practitioner and not pursue anything academic because my colour was not right. Also, when I approached the University of Birmingham to study at doctorate level, “Growth patterns in sub-groups of South Asian children,” I was told that to complete a PhD while a full time consultant paediatrician was impossible.

Because of the nature of the topic it is difficult to narrow down. However, my main interests have been educating the Muslim community about consanguineous marriages and at the same time studying and disseminating information on birth customs, end of life issues, patterns of growth among subgroups of South Asians, prevention of disease …
When is the best time to do VSO?
Authors: Shelley Heard
Journal: BMJ (2006)

Have a career or related problem that needs answering? Can9t find the right person to point you in the right direction? Log on to the Advice Zone for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site. <b>www.bmjcareers.com/advicezone</b>
Inpatient admissions related to immune-related adverse effects (irAE) among patients treated with immune checkpoint inhibitors for advanced malignancy: A tsunami is coming, but are we ready?
Authors: Kerry Lynn Reynolds, Justine Vanessa Cohen, Sienna Durbin, Molly Thomas, Michael Dougan, Holly S Martinson, Alex Faje, Amanda Guidon, Colleen Channick, Steven T Chen, Jennifer Lo, Sara Schoenfeld, Meghan Sise, Rebecca Leaf, Tomas G Neilan, Magid Awadalla, Aidan Long, Ryan J. Sullivan, Aditya Bardia
Journal: Journal of Clinical Oncology (2018)

127 Background: Disruption of the immune system with immune checkpoint inhibitors can result in a multitude of immune-related adverse effects (irAE). While irAEs have been well-reported in clinical trials, the impact and magnitude of irAE’s in the real-world, particularly inpatient is unclear. Methods: Data was collected on patients with advanced malignancy who experienced a suspected irAE needing admission to an academic hospital (Feb 2011 to June 2017). Each case was reviewed comprehensively by minimum of two reviewers, including one sub-specialist. In addition, oncologists at our institution were surveyed regarding their confidence about managing patients with irAEs. Results: Over a span of 6 years, there were 343 hospitalizations for suspected irAEs and the majority (65%; N = 223) were confirmed irAEs that required treatment with immunosuppression or therapy stopped as result. The mean length of stay was 6.3 days (range 1 to 31 days), readmission rate for another irAE event 25%, total readmission rate 61.7%, and inpatient mortality 8%. The most common irAEs were enterocolitis (43.9%), pulmonary (16%), hepatic (15%), neurological (8.9%), endocrinopathies (7.1%), rheumatological (4%), dermatological (3%), cardiovascular (3%), renal (1.8%), and allergy (1.3%). Over the past 5 years, there was a significant increase in admissions due to irAEs (admissions in 2016 vs 2011, odds ratio = 3.07; p &lt; 0.01). The Cancer Center survey (N = 26) revealed majority of oncologists do not feel very comfortable managing irAEs, and 48% felt that irAE complications should be managed on a different service. Conclusions: irAEs from immune checkpoint inhibitors can result in prolonged hospitalizations, high rate of readmissions, and mortality. The number of patients admitted due to irAEs has significantly increased by more than three-fold in the recent years, but majority of oncologists do not feel very comfortable managing irAEs. Consequently, there is a critical need for coordinated multidisciplinary approach, comprehensive provider education, and translational research program for early detection and intervention.
Consultants launch support network for junior doctors
Authors: Abi Rimmer
Journal: BMJ (2016)

A group of senior doctors have come together to offer one-to-one support and advice to junior doctors.

The James Paget Hospital “Tea and Empathy” service was established by Jim Crawfurd and Donna Wade, who are both emergency medicine consultants. It takes its name from the Tea and Empathy Facebook page set up by junior doctors earlier this year. It comprises 15 consultants and a senior specialty doctor who have all agreed to be contacted by junior doctors for advice. The group has a weekday rota, based on each doctors’ administrative sessions, so that a …
Is BMI a risk factor for active surveillance progression in patients with prostate cancer diagnosed by MRI-Trus fusion biopsy?
Authors: Kareem Rayn, Samuel Gold, Graham R. Hale, Joey Baiocco, Jonathan Bloom, Vladimir Valera, Brad J. Wood, Baris Turkbey, Peter A. Pinto
Journal: Journal of Clinical Oncology (2018)

124 Background: MRI−TRUS fusion biopsy (FBx) use in the diagnosis of prostate cancer (PCa) results in a more accurate assessment of disease burden and has increasingly been incorporated into urologic practice. In addition, with more men choosing active surveillance (AS) and the reports of increased PCa aggressiveness with obesity, we wanted to study the impact of obesity on the risk of PCa progression in men on AS diagnosed and followed by MRI and MRI−TRUS FBx. Methods: A retrospective review was performed on a prospectively maintained database of all men who underwent MRI−TRUS FBx at our institution from January 2007 to May 2015. Patient demographics, clinical data, imaging, pathology, treatment and outcomes were recorded. Patients who enrolled on AS were stratified by BMI into normal weight (BMI 18.5−24.9), overweight (BMI 25.0−29.9), and obese (BMI ≥ 30.0). Statistical analysis was performed using SPSS software. Results: 204 men were enrolled in AS. Within the AS cohort, 51 (25%) had a normal weight, 101 (49.5%) were overweight, and 52 (25.5%) were obese. Age, BMI, PSA and mean estimated progression free survival time are described for each of these groups in Table 1. The overall rate of progression was 32.8%. Of the patients who progressed, 18 (26.9%) were normal weight, 32 (15.7%) were overweight and 17 (25.4%) were obese. On multivariate analysis, BMI was not a risk factor for AS progression, HR = 1.00 (p = 0.99, 95% CI = 0.95−1.06). Conclusions: There is evidence of increased risk of aggressive PCa specific death in obese patients. However, we demonstrate that in patients diagnosed by FBx, obesity does not confer an additional risk of progression on AS. This may be due to the improved characterization of cancer volume and grade by MRI−TRUS fusion biopsy. Further study is required to determine risk factors for AS progression in patients undergoing FBx. This research was supported by the Intramural Research Program of the National Cancer Institute, NIH, Medical Research Scholars Program.
GP inspections: are sanctions holding back improvement in poor areas?
Authors: Gareth Iacobucci
Journal: BMJ (2018)

The BMJ has found a relation between levels of deprivation and the likelihood of CQC sanctions. Gareth Iacobucci considers the consequences GP partners working in England’s deprived areas who have had negative feedback after inspections by the health and social services regulator have told The BMJ how they were left feeling demoralised, unsupported, and on the brink of giving up. One GP said he thought that the Care Quality Commission failed to take account of the challenges his practice faced, another that being put under special measures made hiring staff even more difficult and improvements near impossible to achieve (box 1). Box 1 ### GPs’ responses: CQC criticism was like “a kick in the teeth” The BMJ spoke to a partner at one practice that the CQC placed under “special measures” and that remains under scrutiny. The GP, who wished to remain anonymous, said the inspection that led to the action had been “particularly unsupportive.” The sanction felt like “a kick in the teeth,” the partner said, and made it hard to hire new staff. “We were being inspected for a second time, and all the staff thought we were in a much better place than we had been on the previous inspection. But then we got absolutely hammered. Speaking to other people, we found that the reasons we were put into special measures were not consistent compared with other practices. “Being rated in special measures was almost what tipped us over the edge, because it suddenly meant that recruitment was incredibly difficult. I seriously considered handing back the contract at that point. Having worked incredibly hard to try to turn round the practice and worked all the hours that God sent, to then be told that you’re the worst of the worst was pretty demoralising.” Another GP … RETURN TO TEXT
COMPARATIVE PERFORMANCE OF VARC-2 AND BARC BLEEDING CRITERIA IN PREDICTING CLINICAL OUTCOMES AFTER TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Adrian DaSilva-DeAbreu, Yelin Zhao, Astrid Serauto-Canache, Bader Aldeen Alhafez, Prakash Balan, Pranav Loyalka, Biswajit Kar, Richard Smalling, H. Vernon Anderson, Abhijeet Dhoble, Salman Arain
Journal: Journal of the American College of Cardiology (2018)