tbuckley/cabot-search huggingface dataset:
Cause of radium 223 treatment discontinuation in elderly mCRPC patients.
Authors: Renato Patrizio Costa, Fabio Raiti, Sebastiano Bordonaro, Vincenzo Tripoli, Alessandra Murabito, Maria Licari, Paolo Tralongo
Journal: Journal of Clinical Oncology (2018)

376 Background: Prostate cancer is the most common cancer among adult men. Bones are the main metastatic site of prostate cancer. Radium-223 is indicated to treat metastatic castrate-resistant prostate cancer ( mCRPC) with symptomatic skeletal metastases. We evaluate the tolerability of Ra223 treatment in real life setting. Methods: We reported the cases of 38 consecutive non-selected patients with mCRPC symptomatic bone metastases treated in two Italian hospital cancer center from August 2016 to October 2017. The cause of Ra 223 treatment discontinuation in elderly prostate cancer patients were evaluated. Results: due bones metastases, 38 patients were treated with Radium-223; 20 were ≥75 years old (range 75-85 yrs). Patients characteristics and main toxicity are reported (Table). Regarding the elderly patients, hematologic toxicity were the most common adverse events reported. Anemia G2-G3 was observed in 10 pts (50%), thrombocytopoenia G3 in 2 patients (10%) and neutropenia G3 in 4 patients (20%); 12/20 patients interrupted the treatment, of which 10 were ECOG PS2. The number of patients who discontinued the drug because of hematologic adverse events was higher than ALSYMPCA clinical trial. Fatigue G1-G2 incidence was 32%. Unexpectedly we did not record any cases of gastrointestinal toxicity (diarrhea, nausea or constipation). Conclusions: In patients ≥75 years old, anemia G2-G3 was more frequent than data reported in literature, while diarrhea is not found. The data of this experience suggest that elderly vulnerable patients are more exposed to hematologic toxicity that may compromise the outcome of the treatment. For these patients surveillance for early supportive care is relevant. Characteristics of patients with ≥75y. [Table: see text]
HIGH HOSPITAL VARIABILITY IN MORTALITY AFTER TAVR CAN BE EXPLAINED BY DIFFERENCES IN FAILURE TO RESCUE FROM POST PROCEDURAL COMPLICATIONS
Authors: Muath Bishawi, Zhuokai Li, Morgan Cox, Andrzej Kosinski, Frederick Grover, Kevin Harrison, Vinod H. Thourani, Ajay Kirtane, Joseph Bavaria, Sreekanth Vemulapalli, Chad Hughes
Journal: Journal of the American College of Cardiology (2018)
Phase 2 study of carfilzomib for the treatment of patients with advanced neuroendocrine cancers.
Authors: Jaswinder Singh, Dianna Shipley, Jennifer Cultrera, Cynthia Chua, Allen Lee Cohn, Andres O. Soriano, Johanna C. Bendell
Journal: Journal of Clinical Oncology (2018)

382 Background: Carfilzomib (CFZ) is an irreversible proteasome inhibitor (PI) that exhibits anti-proliferative and pro-apoptotic activity in solid and hematologic tumor cells i n vitro, and is US FDA approved for multiple myeloma. Proteasomes degrade cell cycle inhibitor proteins and inhibition of these proteins offers a novel therapy for the treatment of patients with neuroendocrine tumors (NET). This phase 2 study evaluated the efficacy of CFZ for patients with advance NETs. Methods: Pts with biopsy-proven, advanced, well-to-moderately differentiated NETs, including typical carcinoid and pancreatic islet cell tumors, were treated with CFZ 20 mg/m 2 IV Days (D) 1 and 2, then 56 mg/m 2 IV D 8, 9, 15, and 16 of Cycle (C) 1, followed by CZF 56 mg/m 2 IV D 1, 2, 8, 9, 15, and 16 of C 2 and beyond. Pts continued study treatment (tx) until intolerable toxicity, disease progression, or withdrawal of consent. Restaging occurred every 3 cycles. The primary endpoint was overall response rate (ORR); secondary endpoints were disease control rate (DCR), progression free survival (PFS), and toxicity. Results: 62 pts were enrolled: median age 63 yrs, 61% female, 50% ECOG 0/50% ECOG 1. 65% of pts had carcinoid tumors and 35% of pts had pancreatic NET. The most common primary sites of disease were the pancreas (34%) and the small intestines (21%). 74% of pts had prior systemic therapy, 42% had prior surgery and 16% had prior radiotherapy. Median tx duration was 11 wks. At the time of data cutoff, 31% of pts remained on tx. 32% of pts discontinued due to progressive disease, 16% due AE, and 21% due to pt or physician decision. Two pts (3%) had a confirmed partial response (PR) and 1 pt (2%) had an unconfirmed PR; 4 ongoing patients have not yet been evaluated for response. The ORR was 3.23% (95% CI 0.4%, 11.2%), the DCR was 53.23% (CI 95% 40.1%, 66.0%), and median PFS was 8.1 months. The most frequently reported tx-related AEs were nausea (52%; Grade 3/4 [G3/4], 2%), fatigue (42%; G3/4, 3%), vomiting (36%; G3/4, 2%), and diarrhea (27%; G3/4, 5%). Conclusions: CFZ tx was well-tolerated in this pt population. Future plans will be determined once response data are available on all patients. Updated results will be presented. Clinical trial information: NCT02318784.
IL-25 enhances TH17 cell–mediated contact dermatitis by promoting IL-1β production by dermal dendritic cells
Authors: Hajime Suto, Aya Nambu, Hideaki Morita, Sachiko Yamaguchi, Takafumi Numata, Takamichi Yoshizaki, Eri Shimura, Ken Arae, Yousuke Asada, Kenichiro Motomura, Mari Kaneko, Takaya Abe, Akira Matsuda, Yoichiro Iwakura, Ko Okumura, Hirohisa Saito, Kenji Matsumoto, Katsuko Sudo, Susumu Nakae
Journal: Journal of Allergy and Clinical Immunology (2018)
Hospital overspends are mostly due to temporary staffing costs, says Stevens
Authors: Abi Rimmer
Journal: BMJ (2015)

Overspending by hospital trust is almost entirely due to a rise in the amount they are spending on temporary staff, NHS England’s chief executive has said.

Speaking at the British Association of Physicians of Indian conference in Birmingham on Sunday 1 November, Stevens said that temporary staffing costs had greatly increased in the past few years.

“The pressures in the …
More doctors are raising concerns about social media
Authors: Abi Rimmer
Journal: BMJ (2013)

More doctors are raising concerns about images, comments, and friendship requests on social media, the Medical Defence Union (MDU) has said.

The MDU said that the number of doctors contacting it with concerns about Facebook, blogs, and other websites rose by 40% from 2011 to 2012, from 36 in 2011 to 60 in 2012. Common concerns included complaints and …
BMA seeks to bolster confidence in professional exams
Authors: Caroline White
Journal: BMJ (2013)

The BMA has moved to bolster doctors’ confidence in professional exams after an independent review highlighted differences across ethnic groups in pass rates for the Royal College of General Practitioners’ (RCGP) membership exam.1

The review, published last month, was commissioned by the General Medical Council after questions were raised about the fairness of the membership exam after a change in its format in 2010.2 The review found that black and minority ethnic doctors who qualified in the United Kingdom were more likely than white doctors to fail the clinical skills assessment (CSA) element of the exam at their first …
MYOCARDIAL SCAR PATTERNS IN WOMEN WITH SUSPECTED CORONARY VASOMOTOR DYSFUNCTION: A REPORT FROM THE WOMEN’S ISCHEMIA SYNDROME EVALUATION
Authors: Parham Zarrini, Sawan Jalnapurkar, Janet Wei, Sandy Joung, Reddy Sailaja Marpuri, Ahmed AlBadri, David Anderson, Eileen Handberg, George Sopko, Carl Pepine, John Petersen, Daniel Berman, Louise Thomson, C. Noel Bairey Merz
Journal: Journal of the American College of Cardiology (2018)
The burden of chemotherapy-induced nausea and vomiting in the Asia Pacific (AP) region: The Pan Australasian chemotherapy-induced emesis study.
Authors: Hoon-Kyo Kim, Alexandre Chan, Ruey Kuen Hsieh, Shi Ying Yu, Ana Banos Hernandez, Thomas A. Burke, Dorothy Mary Kate Keefe
Journal: Journal of Clinical Oncology (2013)

e20580 Background: There are limited data on CINV in AP, a region diverse in healthcare systems and standards of care. The primary objective was to estimate the country-specific percentage of patients with complete response (CR: no emesis and no use of rescue medication) in the overall phase (0-120 hours) during cycle 1 by regimen emetogenicity. Methods: This was a prospective, observational study of highly and moderately emetogenic chemotherapy (HEC/MEC)-naive adults from 6 AP countries. Patients completed a diary over a 120 hour period following chemotherapy. The study was designed to enroll a minimum of 45 patients by HEC/MEC and country to describe CR with a 95% CI +/-15%. Results: There were 648 evaluable patients enrolled at 31 sites from Aug. 2011 - Jul. 2012. The mean age was 55.8. 57.7% were female. The most common regimens were cisplatin-based (168/318; 52.8%) for HEC, and oxaliplatin-based (156/330; 47.3%) for MEC. Site of chemotherapy administration was outpatient/day case (51.4%; 333/648) and inpatient (48.6%; 315/648). Outpatient/day case chemotherapy administration was used for all patients in Australia and Singapore. Inpatient administration was common in China (85%, 130/153) and S. Korea (64.2%, 97/151). ASCO QOPI-recommended antiemetic prophylaxis was used in 38.7% (123/318) of HEC (5HT3-RA/steroid/NK1-RA) and 83.9% (277/330) of MEC (5HT3-RA/steroid). Prophylaxis differed between countries (p&lt;0.001). CR is shown below. Conclusions: CINV outcomes, use of guideline-recommended prophylaxis, and site of chemotherapy administration significantly varied across AP countries. There is considerable room to improve CINV outcomes and use of recommended antiemetic prophylaxis in the region. [Table: see text]
Glycosylation Profile of Immunoglobulin G Is Cross-Sectionally Associated With Cardiovascular Disease Risk Score and Subclinical Atherosclerosis in Two Independent Cohorts
Authors: Cristina Menni, Ivan Gudelj, Erin Macdonald-Dunlop, Massimo Mangino, Jonas Zierer, Erim Bešić, Peter K. Joshi, Irena Trbojević-Akmačić, Phil J. Chowienczyk, Tim D. Spector, James F. Wilson, Gordan Lauc, Ana M. Valdes
Journal: Circulation Research (2018)

One measure of protein glycosylation (GlycA) has been reported to predict higher cardiovascular risk by reflecting inflammatory pathways.The main objective of this study is to assess the role of a comprehensive panel of IgG glycosylation traits on traditional risk factors for cardiovascular disease and on presence of subclinical atherosclerosis in addition to GlycA.We measured 76 IgG glycosylation traits in 2970 women (age range, 40-79 years) from the TwinsUK cohort and correlated it to their estimated 10-year atherosclerotic cardiovascular disease risk score and their carotid and femoral plaque measured by ultrasound imaging. Eight IgG glycan traits are associated with the 10-year atherosclerotic cardiovascular disease risk score after adjusting for multiple tests and for individual risk factors-5 with increased risk and 3 with decreased risk. These glycans replicated in 967 women from ORCADES cohort (Orkney Complex Disease Study), and 6 of them were also associated in 845 men. A linear combination of IgG glycans and GlycA is also associated with presence of carotid (odds ratio, 1.55; 95% confidence interval, 1.25-1.93; P=7.5×10-5) and femoral (odds ratio, 1.32; 95% confidence interval, 1.06-1.64; P=0.01) plaque in a subset of women with atherosclerosis data after adjustment for traditional risk factors. One specific glycosylation trait, GP18-the percentage of FA2BG2S1 glycan in total IgG glycans, was negatively correlated with very-low-density lipoprotein and triglyceride levels in serum and with presence of carotid plaque (odds ratio, 0.60; 95% confidence interval, 0.50-0.71; P=5×10-4).We find molecular pathways linking IgG to arterial lesion formation. Glycosylation traits are independently associated with subclinical atherosclerosis. One specific trait related to the sialylated N-glycan is negatively correlated with cardiovascular disease risk, very-low-density lipoprotein and triglyceride serum levels, and presence of carotid plaque.
Luminal and basal subtyping of metastatic castration-resistant prostate cancer (mCRPC) and its clinical implications.
Authors: Won Kim, Eric Jay Small, Rahul Raj Aggarwal, Robert Benjamin Den, Jonathan Lehrer, Li Zhang, Jack Youngren, Theodore C Goldstein, Joshi J. Alumkal, Martin Gleave, Matthew Rettig, Christopher P. Evans, Tomasz M. Beer, Robert Evan Reiter, Jiaoti Huang, George V. Thomas, Elai Davicioni, Charles J. Ryan, Daniel Eidelberg Spratt, Felix Y Feng
Journal: Journal of Clinical Oncology (2018)

197 Background: The PAM50 gene expression classifier (PAM50) identifies luminal and basal subtypes and predicts response to androgen deprivation therapy in localized prostate cancer. The clinical utility of using PAM50 to molecularly subtype mCRPC was evaluated. Methods: PAM50 was applied to RNA expression data from 86 metastatic tumor biopsies from the SU2C-AACR-PCF West Coast Prostate Cancer Dream Team (WCDT; NCT02432001). Overall survival (OS) differences between luminal A (LuA), luminal B (LuB), or basal patients (pts) were determined using Kaplan-Meier analyses. PAM50 was also applied to 15,136 prospectively collected radical prostatectomy (RP) samples from the Decipher GRiD database (NCT02609269). Drug response signatures (DRS) for 89 drugs were derived using publicly available data from the NCI60 cell line panel, and applied to gene expression data from the RP samples to predict patient-specific drug sensitivities. Differences in DRS as a function of PAM50 subtype were assessed using the Pearson’s chi-squared test. Results: The application of PAM50 to mCRPC transcriptional data segregated pts into LuA, LuB, and basal populations (43%, 14%, and 43%, respectively). The median OS for LuA, LuB, and basal pts was 20.6 months, 9.5 months, and 10.4 months, respectively (p=0.04), which was consistent with localized prostate cancer where LuB pts have the worst prognosis. DRS analyses revealed statistically significant differences in drug sensitivities, with LuA and LuB pts predicted to be markedly more sensitive to docetaxel than basal pts (p&lt;0.00001), and basal pts predicted to be markedly more sensitive to platinums and etoposide than LuA and LuB pts (p&lt;0.00001). Conclusions: PAM50 subtyping is prognostic in mCRPC, with LuA pts demonstrating the longest OS. Luminal and basal subtypes have distinct in silico drug response profiles that may be associated with response to mCRPC therapies. Prospective testing of DRS as a biomarker to guide treatment in mCRPC is warranted. Clinical trial information: NCT02432001, NCT02609269.
Disrupting CD147-RAP2 interaction abrogates erythrocyte invasion by Plasmodium falciparum
Authors: Meng-Yao Zhang, Yang Zhang, Xiao-Dong Wu, Kun Zhang, Peng Lin, Hui-Jie Bian, Min-Min Qin, Wan Huang, Ding Wei, Zhao Zhang, Jiao Wu, Ruo Chen, Fei Feng, Bin Wang, Gang Nan, Ping Zhu, Zhi-Nan Chen
Journal: Blood (2018)
TRIGLYCERIDES ≥150 MG/DL ASSOCIATED WITH GREATER RISK OF CARDIOVASCULAR EVENTS, COSTS AND RESOURCE UTILIZATION IN HIGH-RISK STATIN-TREATED PATIENTS WITH CONTROLLED LOW-DENSITY LIPOPROTEIN CHOLESTEROL: A REAL-WORLD ANALYSIS
Authors: Peter Toth, Craig Granowitz, Michael Hull, Djibril Liassou, Amy Anderson, Sephy Philip
Journal: Journal of the American College of Cardiology (2018)
NON-ALCOHOLIC FATTY LIVER DISEASE SIGNIFICANTLY PREDICTS FUTURE DECLINE IN KIDNEY FUNCTION IN ANGIOGRAPHIED CORONARY PATIENTS
Authors: Christina Lins, Alexander Vonbank, Daniela Zanolin, Andreas Leiherer, Axel Muendlein, Philipp Rein, Heinz Drexel, Christoph Saely
Journal: Journal of the American College of Cardiology (2018)
Efficacy and Safety of Defibrotide in Pediatric Patients with Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome (VOD/SOS) after Hematopoietic Stem Cell Transplantation (HSCT): Final Results from the Expanded-Access Program
Authors: Nancy A. Kernan, Angela R. Smith, Brandon Triplett, Leslie Lehmann, Robert J. Ryan, Wei Liang, Robin L. Hume, William Martin Tappe, Stephan A Grupp
Journal: Blood (2017)
PALLIATIVE CARE CONSULTATION REDUCES 30-DAY READMISSION RATES FOR HOSPITALIZED PATIENTS WITH HEART FAILURE: A SINGLE-CENTER EXPERIENCE
Authors: Kalyan Potu, Jay Patel, Sandeep Banga, Sravani Avula, Ashish Roy, Barry Clemson, Chetan Bhardwaj, Sudhir Mungee
Journal: Journal of the American College of Cardiology (2018)
Will we be singing a different tune on combined post- and pre-capillary pulmonary hypertension?
Authors: Steven Hsu, Ryan J. Tedford
Journal: European Respiratory Journal (2018)

There have been many well-intended pursuits in medicine that should have panned out, but did not. Case in point: premature ventricular complexes (PVC) post-myocardial infarction were noted to be associated with increased risk of death, and thus the Cardiac Arrhythmia Suppression Trial (CAST) Study investigated if pharmacological PVC suppression with class I anti-arrhythmics would reduce the rate of arrhythmic death [1]. Surprisingly, the study showed that although PVCs were successfully suppressed, there were excess deaths due to arrhythmia and shock in such patients treated with encainide or flecainide [1]. More uncertainty in treating CpcPH with PAH specific therapy <http://ow.ly/W2XU30hMwGl>
Identification of specifically reduced Th2 cell subsets in allergic rhinitis patients after sublingual immunotherapy
Authors: F. Ihara, D. Sakurai, S. Yonekura, T. Iinuma, R. Yagi, T. Sakurai, T. Ito, A. Matsuura, Y. Morimoto, T. Arai, S. Suzuki, K. Katayama, T. Nakayama, Y. Okamoto
Journal: Allergy (2018)

Abstract Background Although Th2 cells are well known to play important roles in allergic diseases including allergic rhinitis ( AR ), the factors that induce and sustain the pathogenesis of AR remain unclear. The recent development of sublingual immunotherapy ( SLIT ) is expected to allow changes to the underlying pathogenesis of AR . However, which Th2 cell subsets are important in house dust mite‐induced AR ( HDM ‐ AR ), the influence of SLIT on the pathogenic Th2 cells, and the association of Th2 cell subsets with SLIT efficacy have not been clarified. Methods The cytokine production and frequency of HDM ‐reactive T‐cell subsets in peripheral blood mononuclear cells ( PBMC s) were evaluated using flow cytometry in 89 HDM ‐ AR patients (placebo [n = 43] and HDM 300 IR [n = 46]) who participated in a placebo‐controlled study of SLIT with HDM tablets. All patients provided samples both before treatment as a baseline and at the end of the 52‐week study. The PBMC s were stained with CellTrace™ Violet ( CTV ) before culture with HDM extract, and HDM ‐reactive T cells were detected as the proliferated cells with diminished CTV . Results HDM ‐reactive IL ‐5 + IL ‐13 + CD 27 − CD 161 + CD 4 + cells and ST 2 + CD 45 RO + CD 4 + cells were observed in the peripheral blood from each patient with HDM ‐ AR ; these cells significantly decreased after SLIT in the group treated with active tablets. HDM ‐reactive ST 2 + CD 45 RO + CD 4 + cells were significantly lower in active‐responders. Conclusion Allergen‐reactive ST 2 + CD 45 RO + CD 4 + cells or those combined with IL ‐5 + IL ‐13 + CD 27 − CD 161 + CD 4 + cells may be useful as markers indicating the successful treatment of SLIT . These cells may play a crucial role in the pathogenesis of AR as pathogenic memory Th2 cells.
Time to Release Medicare Advantage Claims Data
Authors: Niall Brennan, Charles Ornstein, Austin B. Frakt
Journal: JAMA (2018)

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The dynamics of episodic memory functions
Authors: Dorthe Berntsen
Journal: Behavioral and Brain Sciences (2018)

Abstract There is no doubt that episodic memory serves communicative functions, but Mahr &amp; Csibra (M&amp;C) overlook that this is not the only function served by memories of past events. Autobiographical memory research has identified several other functions, including purely directive functions. The functionality of episodic memory is not stable across situations; it varies dynamically with the demands of the retrieval context.
Harrogate experience in leadership and management course
Authors: Charlie Talbot
Journal: BMJ (2012)

The two day Harrogate experience in leadership and management (HELM) course covers aspects of medical leadership and management and helps to bridge the perceived gap between clinicians and managers by using local examples to illustrate the relevance of key topics to clinicians.

The course is aimed at senior level trainees in all hospital specialties who want to increase and formalise their knowledge and understanding of medical leadership and management and of the structure of the NHS. The workshops on CV preparation and interview skills will also appeal to trainees heading towards consultant applications and interviews.

I attended the inaugural course in April …