tbuckley/cabot-search huggingface dataset:
PROGNOSIS OF SEVERE ASYMPTOMATIC AORTIC STENOSIS WITH AND WITHOUT SURGERY
Authors: John Campo, Andrea Tsoris, Jane Kruse, Azad Karim, Adin-Cristian Andrei, Zhi Li, Hangzhi Shi, Robert O. Bonow, Patrick McCarthy, S. Chris Malaisrie
Journal: Journal of the American College of Cardiology (2018)
A phase IB/II randomized study of mFOLFIRINOX (mFFOX) + pegylated recombinant human hyaluronidase (PEGPH20) versus mFFOX alone in patients with good performance status metastatic pancreatic adenocarcinoma (mPC): SWOG S1313 (NCT #01959139).
Authors: Ramesh K. Ramanathan, Shannon McDonough, Philip Agop Philip, Sunil R. Hingorani, Jill Lacy, Jeremy S. Kortmansky, Jaykumar Ranchodbhai Thumar, E. Gabriela Chiorean, Anthony Frank Shields, Deepti Behl, Paul Tracy Mehan, Rakesh Gaur, Tara Elisabeth Seery, Katherine Guthrie, Howard S. Hochster
Journal: Journal of Clinical Oncology (2018)

208 Background: PEGPH20 degrades hyaluronan (HA), a major component of the stroma, increases delivery of gemcitabine and prolongs survival in preclinical models. We evaluated the activity of PEGPH20 in combination with mFFOX in mPC , unselected for tumor HA. Methods: Pertinent eligibility: untreated mPC, PS of 0-1 and adequate organ function. Standard FFOX was modified to add prophylactic growth factor support and omit bolus 5FU. Due to increased thromboembolic (TE) events with PEGPH20, an amendment instituted LMWH prophylaxis in the PEGPH20 arm only. Following a dose finding cohort of mFFOX + PEGPH20, the Phase II study randomized patients (1:1) to the combination arm or mFFOX alone (n = 138). The primary endpoint was overall survival (OS), with a null median OS of 10 mo and an alternative of 15 mo (1-sided type 1 error 0.1, 80% power). Results: PEGPH20 at 3 mcg/kg, q2 weeks was more tolerable than twice weekly dosing. The randomized phase II study began May 2015. The planned interim futility analysis when 35 deaths occurred gave a HR of 0.44 favoring the standard arm, thus the study was closed to accrual (March 2017). As of August 22, 2017 (n = 111), the estimated median OS in the mFFOX arm was 15.1 mo (95% CI 10.1-15.7) vs 7.6 mo (95% CI 4.6-9.2) in the PEGPH20 arm. Conclusions: OS in the mFFOX control arm (15.1 mo) is longest yet reported. Addition of PEGPH20 to mFFOX is not recommended for further study and appears to be detrimental (HR = 0.48). The impact of PEGPH20 on OS was unexpected and in contrast to favorable results reported for the combination of gemcitabine/nab-paclitaxel + PEGPH20 especially in the HA high cohort (Hingorani S et al. A 4008, ASCO 2017). PEGPH20 with mFFOX caused increased toxicity (mostly GI and TE events) and decreased treatment duration compared to mFFOX alone. Tumor HA content will be analyzed. Funding: NIH/NCI grants CA180888, CA180819; and in part by Halozyme Inc. Clinical trial information: 01959139. [Table: see text]
THE IMPACT OF COMPUTERISED TOMOGRAPHY FOR PREDICTION OF CLINICAL ADVERSE EVENTS AFTER BALLOON PULMONARY ANGIOPLASTY FOR CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION
Authors: Nobutaka Ikeda, Shuji Kubota, Toru Okazaki, Raisuke Iijima, Hidehiko Hara, Yukio Hiroi, Masato Nakamura
Journal: Journal of the American College of Cardiology (2018)
Selective Laser Trabeculoplasty versus Argon Laser Trabeculoplasty in Glaucoma Patients Treated Previously with 360° Selective Laser Trabeculoplasty
Authors: Cindy Hutnik, Andrew Crichton, Bryce Ford, Marcelo Nicolela, Lesya Shuba, Catherine Birt, Enitan Sogbesan, Karim F. Damji, Michael Dorey, Hady Saheb, Neil Klar, Hui Guo, William Hodge
Journal: Ophthalmology (2018)
The occupational health smart card for doctors
Authors: Barbara Levy
Journal: BMJ (2005)

The innovative Occupational Health Smart Card (OHSC) programme continues to expand since it started in 2001. This secure and confidential system for transferring hospital doctors' personal data between NHS trusts, including health clearance information, carries the endorsement of the BMA junior doctors committee. By now, most of the 35 000 doctors in training will have had …
SAFETY AND EFFICACY OF NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS VERSUS WARFARIN IN PATIENTS UNDERGOING ATRIAL FIBRILLATION ABLATION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Nelson Telles Garcia, Khagendra Dahal, Nachiket Apte, Pratap Reddy, Paari Dominic
Journal: Journal of the American College of Cardiology (2018)
Lung abscess or empyema? Taking a closer look
Authors: Maged Hassan, Rachelle Asciak, Rana Rizk, Hany Shaarawy, Fergus V Gleeson, Najib M Rahman
Journal: Thorax (2018)

Maged Hassan (MH): I would like to present three cases of patients who presented with symptoms of lower respiratory tract infection, fever and cough productive of small amount of sputum. The three patients had complained of symptoms for at least 2 weeks before presentation. The chest X-rays showed large encysted collections (figure 1A) which required chest CT to delineate the source of the abnormality. The CT studies (case 1: figure 1B, C; case 2: figure 2A and case 3: figure 2C) caused prolonged discussion between the treating clinicians with opinions divided on the nature of the lesion in each case being either an encysted empyema or a large peripheral lung abscess. Clinically, the differentiation between empyema and lung abscess was important because empyema is treated with tube drainage which is only resorted to in limited situations in lung abscess with the attendant risk of creating a bronchopleural fistula or extending the infection to the pleura.



Figure 1 
Case 1. (A) Chest X-ray shows right side cavity with air-fluid level. (B) Chest CT with contrast, axial cut, shows right side spherical lesion with air-fluid level causing lung collapse at the hilum (hollow arrow). Note pleural enhancement and extrapleural fat hypertrophy (arrowheads). (C) Chest CT, coronal reconstruction in lung window shows the acute angle the lesion makes with the chest wall and the pushed distorted airways proximal to the lesion (hollow arrow). (D) Thoracic ultrasound shows multiple hyperechoic shadows inside an echogenic collection. (E) Follow chest X-ray 48 hours after chest tube insertion (seen in situ) shows lung re-expansion.





Figure 2 
Case 2. (A) Baseline CT chest with contrast, coronal cut showing large left collection that is making an acute angle with chest wall (arrow) and uniformly thin wall with smooth inner margins (hollow arrows). (B) Chest X-ray following chest tube removal. Note thickened visceral pleura (hollow arrows). …
Three Primary Carcinomas on 18F-FDG PET/CT
Authors: Dayong Wu, Yujing Hu, Qiang Wei, Congna Tian, Yanzhu Bian
Journal: Clinical Nuclear Medicine (2018)

Abstract A CT scan was performed on a 67-year-old man newly diagnosed with acute pancreatitis. The scan revealed a low-density lesion in the liver, a left renal nodule, and a right renal cystic mass. Intense 18 F-FDG uptake was observed in the liver lesion and left renal nodule. No abnormal uptake was observed in the right renal mass. In addition, another focal intense uptake was observed in segment VII of the liver. Biopsies revealed intrahepatic cholangiocarcinomas in the 2 liver lesions, papillary renal cell carcinoma in the left renal lesion and clear cell renal cell carcinoma in the right renal lesion.
Markers of cardiovascular autonomic dysfunction predict COPD in middle-aged subjects
Authors: Fabrizio Ricci, Per Wollmer, Gunnar Engström, Artur Fedorowski, Viktor Hamrefors
Journal: European Respiratory Journal (2018)

Autonomic dysfunction is commonly observed in chronic obstructive pulmonary disease (COPD) and may relate to the known comorbidity with coronary artery disease (CAD). We hypothesised that clinical markers of cardiovascular autonomic dysfunction predict COPD in the population, independently of CAD. In a population-based cohort of 24 768 subjects (mean age 45 years) without baseline airflow obstruction, we analysed the cross-sectional relationship of one-minute orthostatic systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes and resting heart rate with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ). Cox regression models were used to analyse the association of orthostatic SBP and DBP changes (SBP/DBP decrease) and resting heart rate with incident COPD over a 32-year follow-up. Baseline orthostatic SBP decrease (p=0.020) and DBP decrease (p=0.001) were associated with reduced FVC, whereas resting heart rate was associated with reduced FVC and FEV 1 (p&lt;0.001). After adjustment for smoking and baseline lung function, SBP decrease predicted COPD (hazard ratio (HR) 1.10 per 10 mmHg, 95% CI 1.03–1.18). Resting heart rate predicted COPD among smokers (HR 1.11 per 10 beats-per-minute increase, 95% CI 1.05–1.18). Results were similar in subjects without CAD. Subtle signs of cardiovascular autonomic dysfunction may precede the development of COPD in middle-aged subjects. This association is independent of the relationship between cardiovascular autonomic dysfunction and CAD.
Incidence of pulmonary hypertension and determining factors in patients with systemic sclerosis
Authors: J. Gerry Coghlan, Matthias Wolf, Oliver Distler, Christopher P. Denton, Martin Doelberg, Satenik Harutyunova, Alberto M. Marra, Nicola Benjamin, Christine Fischer, Ekkehard Grünig
Journal: European Respiratory Journal (2018)

The objective of this study was to evaluate the incidence of pulmonary hypertension (PH) and determining factors in patients with systemic sclerosis (SSc) and a diffusing capacity of the lung for carbon monoxide (DLCO) <60% predicted.In this bicentric, prospective cohort study, patients with SSc were clinically assessed at baseline and after 3 years, including right heart catheterisation (RHC). Analysis of determining factors for the development of PH was performed using univariate and multivariate analyses.96 patients with a mean pulmonary arterial pressure (mPAP) <25 mmHg at baseline were followed for 2.95±0.7 years (median 3 years). Of these, 71 had a second RHC; 18 of these 71 patients (25.3%) developed PH, and five (7%) developed SSc-associated pulmonary arterial hypertension. For patients with an mPAP of 21-24 mmHg at baseline, the likelihood of presenting with PH as opposed to normal pressures on follow-up was significantly higher (p=0.026). Pulmonary vascular resistance, tricuspid regurgitation velocity, diffusion capacity and the size of the inferior vena cava at baseline were independent predictors for the development of PH during follow-up.In a selected cohort of SSc patients with a DLCO <60%, pulmonary pressures appeared to rise progressively during follow-up. In this population, it was possible to identify manifest PH in almost 25% of patients using prospective RHC during follow-up. Therefore, regular clinical assessment including RHC might be useful in patients with SSc.
Concise neurology course
Authors: Ann Varghese
Journal: BMJ (2012)

This one day course is held on weekends at Leicester General Hospital and is mainly aimed at doctors in foundation training or core medical training. The course would suit anyone with an interest in neurology, however, and a number of general practitioners and general practitioner trainees attended because they often encounter patients with neurological symptoms in primary care.

There were a number of reasons. As a junior doctor I encounter patients presenting with neurological symptoms and signs during the acute medical take. Neurology is perceived …
Editor’s Choice: Evidence over anecdote
Authors: Tom Moberly
Journal: BMJ (2015)

The vitriol with which the government launched its latest contract negotiations with hospital doctors marked a new phase in hostilities between ministers and the medical profession. Doctors are exasperated not just about the proposed changes but also about the way in which the proposals have been communicated. Their anger is clear in the collection of views we published this week on what is likely to happen in …
68-Ga-PSMA-PET in the diagnosis of local recurrent disease after radiotherapy in patients with prostate cancer.
Authors: David Pfister, Matthias Schmidt, Tobias Kohl, Daniel Porres-Knoblauch, Axel Heidenreich
Journal: Journal of Clinical Oncology (2018)

213 Background: For planning salvage procedures in recurrent prostate cancer accurate diagnostic tools are needed. Till now in patients suspicious for isolated local recurrent cancer invasive biopsy was needed. 68-Ga-PSMA-PET is frequently used to identify even small metastatic deposits. We analyzed the diagnostic value to identify local recurrence in patients after radiotherapy undergoing salvage radical prostatectomy, sRPE. Methods: We retrospectively reviewed patients undergoing sRPE with 68-Ga-PSMA-PET as preoperative staging. All patients underwent sRPE and extended lymph node dissection. Sensitivity, Specificity, pos and neg predictive value had been calculated per patient and per prostate lobe. Results: 37 patients with preoperative 68-Ga-PSMA-PEt could be identified. In all but one at least in one lobe PSMA staining could be identified. Mean tumor volume per prostate lobe was 6.22 (0.1-24)ml. Sensitivity, Specificity, neg and pos predictive value per lobe is 80%, 75%, 32% and 96%. Sensitivity to identify cancer recurrence per person irrespective of the side is 95% with a pos predictive value of 100%. Conclusions: 68-Ga-PSMA-PET seems to have a very high diagnistic value to identify local recurrence after radiotherapy. After validation of our experience an invasive biopsy to proof cancer recurrence might be spared.
Spiral Blue practical procedures course
Authors: Gayathri Rabindra
Journal: BMJ (2008)

The practical procedures course is suitable for doctors at all levels who want to learn how to perform practical procedures in a supportive and relaxed environment.

I did the course as a foundation year 2 doctor.

Despite my eagerness to learn, I have found few opportunities to practise procedures such as inserting central lines and chest drains. This is partly because shifts are shorter than before, but also because so many jobs must be done in the working day that there is no opportunity to be supervised. Also, I have often …
Interleukin-6 is essential for glomerular immunoglobulin A deposition and the development of renal pathology in Cd37-deficient mice
Authors: Angelique L.W.M.M. Rops, Erik Jansen, Alie van der Schaaf, Elmar Pieterse, Nils Rother, Julia Hofstra, Henry B.P.M. Dijkman, Anne-Els van de Logt, Jack Wetzels, Johan van der Vlag, Annemiek B. van Spriel
Journal: Kidney International (2018)
Practice patterns and outcomes among patients with N0M0 prostate cancer and a very high prostate-specific antigen.
Authors: Vinayak Muralidhar, David Dewei Yang, Brandon Arvin Virgil Mahal, Brent Shane Rose, Clair Beard, Jason A. Efstathiou, Martin T. King, Neil E. Martin, Peter F. Orio, Paul L. Nguyen
Journal: Journal of Clinical Oncology (2018)

48 Background: There are limited data regarding practice patterns and outcomes among patients with a very high prostate-specific antigen (PSA) level ( &gt; = 98.0 ng/mL) but clinically localized (N0M0) prostate cancer. Methods: We used the National Cancer Database (NCDB) to identify 748,825 patients with prostate cancer diagnosed 2004-2012. We subdivided these patients by PSA level (0-9.9, 10-19.9, 20-39.9, 40-59.9, 60-79.9, 80-97.9, and &gt; = 98.0 ng/mL), nodal status (N0 vs N1) and the presence of distant metastases (M0 vs M1). We determined the rate of definitive LR therapy (pelvic and/or prostate radiation and/or radical prostatectomy) in each group. Overall survival was compared using Cox multivariable regression modeling after adjusting for patient race, income quartile, education quartile, age, and year of diagnosis. Results: Rates of definitive LR therapy for patients with PSA &gt; = 98.0 ng/mL and N0M0 disease were significantly lower than they were for those with N1M0 disease (52.6% vs 60.4%, p &lt; 0.001) or with PSA &lt; 98.0 ng/mL and N0M0 disease (52.6% vs 86.6%, p &lt; 0.001). Among patients with N0M0 disease, 5-year OS decreased with increasing PSA: for PSA levels of 0-9.9, 10-19.9, 20-39.9, 40-59.9, 60-79.9, 80-97.9, and &gt; = 98.0 ng/mL, 5-year OS was 91.6%, 84.3%, 80.2%, 84.1%, 81.8%, 80.2%, and 59.1%, respectively. Among those with N1M0 disease, 5-year OS was 63.2%, which in multivariable Cox regression modeling was not significantly different compared to those with PSA &gt; = 98.0 ng/mL N0M0 disease (adjusted hazard ratio [AHR] 0.99, 95% confidence interval 0.91-1.09, p = 0.942). The survival benefit associated with LR treatment was larger among those with N0M0 high-PSA disease than among those with N1M0 disease (AHR of 0.26 vs 0.41, p-interaction &lt; 0.001). Conclusions: Patients with clinically N0M0 disease but very high PSA ( &gt; = 98.0 ng/mL) have similar outcomes as patients with N1 disease but receive definitive LR therapy at a lower rate. It is possible that patients with N0M0 disease and PSA &gt; = 98.0 ng/mL represent a population that should be treated as more similar to the N1M0 population, rather than the M1 population, including consideration of LR therapy in appropriate contexts.
With regard to progression from staff and associate specialist grade to specialist registrar, should I actively apply or wait for the PMETB to consider experience for training?
Authors: Romeh Gupta
Journal: BMJ (2005)

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 (www.bmjcareers.com/advicezone) 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.
Facially amphiphilic polyionene biocidal polymers derived from lithocholic acid
Authors: Mitra S. Ganewatta, Md Anisur Rahman, Louis Mercado, Tinom Shokfai, Alan W. Decho, Theresa M. Reineke, Chuanbing Tang
Journal: Bioactive Materials (2018)

Bacterial infections have become a global issue that requires urgent attention, particularly regarding to emergence of multidrug resistant bacteria. We developed quaternary amine-containing antimicrobial poly(bile acid)s that contain a hydrophobic core of lithocholic acid in the main-chain. Interestingly, by choosing appropriate monomers, these cationic polymers can form core-shell micelles. These polymers exhibited biocidal activity against both Gram-positive and Gram-negative bacterial species. It is demonstrated that the micelles can deliver hydrophobic antibiotics that functionally have dual antimicrobial activities. Cytotoxicity assays against HeLa cells showed dosage-dependent toxicity for polymers with longer linkers.
Abstract ES7-1: Challenges in the management of locoregional recurrence
Authors: M Morrow
Journal: Cancer Research (2018)

Abstract The increasing trend toward tailoring treatment of the primary breast cancer with limited surgery of both the breast and axilla has increased the challenge of managing locoregional recurrence (LRR). In the era when patients uniformly had axillary dissection, the appropriateness of repeat sentinel node biopsy was not a question. Similarly, the dogma that all ipsilateral breast tumor recurrences must be treated with mastectomy if the breast has been previously irradiated is also being challenged. LRR events are infrequent with modern multi-modality therapy, and there are no randomized trials to address these questions. Re-operative sentinel node (SN) biopsy after breast conserving surgery therapy (BCT) has been shown to be feasible, with the likelihood of identifying additional SNs related to the number of nodes excised at the time of initial SN biopsy. The accuracy of SN biopsy after mastectomy is less clear. However, the impact of identification of nodal disease on management of LRR is controversial. In a study of 12 patients with isolated chest wall recurrence post mastectomy, 10/12 had successful mapping and 7/10 had an axillary SN. The absence of nodal metastases was an indication to avoid supraclavicular RT (Johnson J. Ann Surg Oncol 2016;23:715). In a study of 83 patients with in breast (n=79) or chest wall recurrence who were clinically node negative, 47 had axillary surgery and 36 did not. At a median of 4.2 years after LR, rates of axillary and non-axillary local recurrence, distant metastases, and death did not differ significantly between groups (Ugras S. Ann Surg Oncol 2016). With the findings of the CALOR trial that systemic chemotherapy is beneficial in the management of LRR, the finding of axillary metastases is less likely to influence systemic therapy than in the past and repeat axillary staging could potentially be avoided. In the untreated breast, drainage to the contralateral axilla is very rare and contralateral axillary metastases classify a patient as Stage IV. After initial axillary dissection, between 4% and 33% of patients with local recurrence will have contralateral axillary drainage. In a systemic review of 48 cases of contralateral nodal recurrence without other distant metastatic disease, at a mean follow-up of 50.3 months disease free survival was 65% and overall survival 83% after treatment that included both local and systemic therapy (Moossdorff M. Eur J Surg Oncol 2015;41:1128). These findings raise the possibility that in the setting of LR, contralateral axillary metastases should be treated aggressively for cure after excluding distant metastases. Citation Format: Morrow M. Challenges in the management of locoregional recurrence [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr ES7-1.
Identification of transcriptional targets of GSK3 involved in glioblastoma invasion
Authors: Anke Bruning-Richardson, Alastair Droop, Dan Tams, Marjorie Boissinot, Josie Hayes, Vinton Cheng, Julia Cockle, Azzam Ismail, Ruth Morton, Filomena Esteves, Michel Mittelbronn, Sean Lawler, Susan Short, Georgia Mavria
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme remains one of the most difficult to treat cancers due to the highly infiltrative nature of cancer cells. Targeting the invasive properties of glioblastoma presents a novel treatment avenue. Recently, specific GSK-3 beta (GSK3b) inhibitors such as Bio-Indirubin (BIO), have been described that inhibit the migratory activity of glioma cells. In this study, the GSK-3b downstream targets were investigated. Genome-wide transcriptional profiling was used in order to identify GSK3b-driven target genes, and a transcriptional signature for glioblastoma invasion. U251 cells and patient-derived GBM1 cells were treated with the GSK3b inhibitor BIO. Microarray data obtained was mined for deregulated genes with known migratory roles. The up-regulation or down-regulation of candidate genes was confirmed by Western blotting and immunofluorescence. Knockdown of two candidate genes by RNAi, ARHGAP12 and ARHGAP29 was performed, and the effects on invasive properties and characteristics were assessed by 3D spheroid assays, live cell imaging and immunofluorescence, in order to investigate the effects of knockdowns on invasion. We have identified an invasion signature downstream of GSK3b, which includes activators and inactivators of the Rho family of small GTPases. Knockdown of the Rac1 inactivator ARHGAP12 increased migration, whereas knockdown of the RhoA inactivator ARHGAP29 decreased migration as assessed by live cell imaging and 3D spheroid invasion assays. This study, which for the first time investigates downstream targets of GSK-3b in glioblastoma, has identified an invasion signature which includes regulators of the Rho family of small GTPases. Identified genes will be potential candidates for genetic involvement in glioblastoma progression, and candidate diagnostic and prognostic biomarkers. Candidates will be assessed as potential therapeutic targets.
IMPACT OF PRE-HOSPITAL RESUSCITATION ON SHORT- AND LONG-TERM MORTALITY IN PATIENTS WITH CARDIOGENIC SHOCK UNDERGOING REVASCULARIZATION: RESULTS OF THE IABP-SHOCK STUDY
Authors: Uwe Zeymer, Steffen Schneider, Ralf Zahn, Karl Werdan, Suzanne de Waha, Steffen Desch, Georg Fuernau, Holger Thiele, Klinikum Ludwigshafen
Journal: Journal of the American College of Cardiology (2018)