tbuckley/cabot-search huggingface dataset:
One-Time Fecal Immunochemical Screening for Advanced Colorectal Neoplasia in Patients with CKD (DETECT Study)
Authors: Germaine Wong, Richard L. Hope, Kirsten Howard, Jeremy R. Chapman, Antoni Castells, Simon D. Roger, Michael J. Bourke, Petra Macaskill, Robin Turner, Gabrielle Williams, Wai Hon Lim, Charmaine E. Lok, Fritz Diekmann, Nicholas B. Cross, Shaundeep Sen, Richard D.M. Allen, Steven J. Chadban, Carol A. Pollock, Allison Tong, Armando Teixeira-Pinto, Jean Y.H. Yang, Narelle Williams, Eric Hoi Kit Au, Anh Kieu, Laura James, Jonathan C. Craig
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement Colorectal cancer screening using fecal immunochemical testing (FIT) is recommended for patients with CKD, whose risk of developing and dying from this malignancy is at least 1.5 times higher than that of the sex- and age-matched general population. However, FIT accuracy in this setting is unknown and is likely to be affected by occult gastrointestinal bleeding from dysfunctional platelets and increased bleeding sensitivity to aspirin. In a large, multinational study, the authors found that FIT appears to be an accurate screening test for patients with CKD, but the risk of major complications from work-up colonoscopies (1.5%) is high compared with this risk in the general population. These findings provide useful estimates of harms and test accuracies to inform colorectal cancer screening decisions across the full spectrum of CKD. Background In patients with CKD, the risk of developing colorectal cancer is high and outcomes are poor. Screening using fecal immunochemical testing (FIT) is effective in reducing mortality from colorectal cancer, but performance characteristics of FIT in CKD are unknown. Methods To determine the detection rates and performance characteristics of FIT for advanced colorectal neoplasia (ACN) in patients with CKD, we used FIT to prospectively screen patients aged 35–74 years with CKD (stages 3–5 CKD, dialysis, and renal transplant) from 11 sites in Australia, New Zealand, Canada, and Spain. All participants received clinical follow-up at 2 years. We used a two-step reference standard approach to estimate disease status. Results Overall, 369 out of 1706 patients who completed FIT (21.6%) tested positive; 323 (87.5%) underwent colonoscopies. A total of 1553 (91.0%) completed follow-up; 82 (4.8%) had died and 71 (4.2%) were lost. The detection rate of ACN using FIT was 6.0% (5.6%, 7.4%, and 5.6% for stages 3–5 CKD, dialysis, and transplant). Sensitivity, specificity, and positive and negative predictive values of FIT for ACN were 0.90, 0.83, 0.30, and 0.99, respectively. Of participants who underwent colonoscopy, five (1.5%) experienced major colonoscopy-related complications, including bowel perforation and major bleeding. Conclusions FIT appears to be an accurate screening test for patients with CKD, such that a negative test may rule out the diagnosis of colorectal cancer within 2 years. However, the risk of major complications from work-up colonoscopy are at least ten-fold higher than in the general population.
Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program
Authors: Elena Verzoni, Giacomo Cartenì, Enrico Cortesi, Diana Giannarelli, Andrea De Giglio, Roberto Sabbatini, Sebastiano Buti, Sabrina Rossetti, Francesco Cognetti, Francesca Rastelli, Alberto Sobrero, Daniele Turci, Cora N. Sternberg, Camillo Porta, Federico Cappuzzo, Giampaolo Tortora, Davide Tassinari, Stefano Panni, Antonio Pazzola, Gianmarco Surico, Alessandra Raimondi, Ugo De Giorgi, Giuseppe Procopio
Journal: Journal for ImmunoTherapy of Cancer (2019)

Background: The Italian Renal Cell Cancer Early Access Program was an expanded access program that allowed access to nivolumab, for patients (pts) with metastatic renal cell carcinoma (mRCC) prior to regulatory approval.Methods: Pts with previously treated advanced or mRCC were eligible to receive nivolumab 3 mg/kg every 2 weeks.Pts included in the analysis had received ≥1 dose of nivolumab and were monitored for drug-related adverse events (drAEs) using CTCAE v.4.0.Immune-related (ir) AEs were defined as AEs displaying a certain, likely or possible correlation with immunotherapy (cutaneous, endocrine, hepatic, gastro-intestinal and pulmonary).The association between overall survival (OS) and irAEs was assessed, and associations between variables were evaluated with a logistic regression model.Results: A total of 389 pts were enrolled between July 2015 and April 2016.Overall, the objective response rate was 23.1%.At a median follow-up of 12 months, the median progression-free survival was 4.5 months (95% CI 3.7-6.2) and the 12-month overall survival rate was 63%.Any grade and grade 3-4 drAEs were reported in 124 (32%) and 27 (7%) of pts, respectively, and there were no treatment-related deaths.Any grade irAEs occurred in 76 (20%) of patients, 8% cutaneous, 4% endocrine, 2% hepatic, 5% gastro-intestinal and 1% pulmonary.Of the 22 drAEs inducing treatment discontinuation, 10 (45%) were irAEs.Pts with drAEs had a significantly longer survival than those without drAEs (median OS 22.5 versus 16.4 months, p = 0.01).Pts with irAEs versus without irAEs had a more significant survival benefit (median OS not reached versus 16.8 months, p = 0.002), confirmed at the landmark analysis at 6 weeks.The occurrence of irAEs displayed a strong association with OS in univariable (HR 0.48, p = 0. 003) and multivariable (HR 0.57, p = 0.02) analysis.
Road traffic mortality in China: analysis of national surveillance data from 2006 to 2016
Authors: Lijun Wang, Peishan Ning, Peng Yin, Peixia Cheng, David C Schwebel, Jiangmei Liu, Yue Wu, Yunning Liu, Jinlei Qi, Xinying Zeng, Maigeng Zhou, Guoqing Hu
Journal: The Lancet Public Health (2019)

BackgroundSustainable Development Goal (SDG) 3.6 is to halve the number of global deaths and injuries from road traffic accidents by 2020. We aimed to investigate progress in reducing mortality rates from road traffic injury in China from 2006 to 2016.MethodsWe obtained data from national disease surveillance points. Crude and age-standardised mortality were calculated, with SEs. Joinpoint regression analysis was used to examine and quantify trends in overall and subgroup road traffic mortality from 2006 to 2016. Subgroup analyses were done by place (urban and rural), sex, age group, geographical location (province), and road user, and by type of vehicle for motor vehicle occupant deaths.FindingsIn 2016 in China, crude road traffic mortality was 11·0 (SE 0·11) deaths per 100 000 population. Overall age-adjusted road traffic mortality increased from 12·6 (SE 0·03) deaths per 100 000 population in 2006 to 15·5 (0·03) deaths per 100 000 population in 2011 then decreased to 10·4 (0·03) deaths per 100 000 population in 2016. Subgroup mortality rates generally followed similar trends. Males, older adults, and rural areas consistently had higher road traffic mortality rates than did females, younger people, and urban areas. Mortality changes varied across urban and rural areas and by sex, age group, and province between 2006 and 2016, revealing large urban–rural and provincial disparities and highlighting pedestrians as the most vulnerable road users. Deaths among occupants of cars and three-wheeled motor vehicles constituted 48% and 20%, respectively, of total occupant mortality from road traffic accidents between 2006 and 2016.InterpretationDespite a substantial decrease in road traffic mortality since 2011, the SDG target to halve deaths and injuries from road traffic accidents by 2020 is unlikely to be reached in China. Systematic and sustainable efforts are needed to accelerate progress in road traffic safety in China.FundingNational Natural Science Foundation of China.
Medics worldwide: news and opportunities from the IFMSA
Authors: Emily Spry
Journal: BMJ (2005)

Students contribute to tsunami relief - As news of the devastation in Asia broke, students from the International Federation of Medical Students' Associations (IFMSA) responded as best they could, even if it was just to send expressions of concern and solidarity to their colleagues in affected areas. Our member organisation in Indonesia has been collecting money and materials, and medical students all over the world have taken part in collections organised by disaster relief organisations in their own countries. Contact norp_cimsa@yahoo.com for more information on the Indonesian project.

Algerian medical students nominated for world prize - The Algerian medical students' association, “Le Souk,” has been nominated for the prize of …
Prognostic Factors and the Impact of Frontline Therapy in Peripheral T-Cell Lymphoma: A Multicenter Australian Study
Authors: James Anton Kuzich, Andrew Peter Hutchison, Kenneth Lim, Matthew P.F. Wright, Gavin Cull, Michael F. Leahy, David John Longstaff Joske, Dejan Radeski, Duncan Purtill
Journal: Blood (2017)
Clinical skills for medical students: a hands–on guide
Authors: Andrew Moscrop
Journal: BMJ (2002)

There is a new contender in the fight for a place in your white coat pocket. Comprehensive and comprehensible, Clinical skills for medical students describes the procedure for examining each of the five major systems: cardiovascular, respiratory, alimentary, musculoskeletal, and nervous. The accompanying illustrations are not great, but they are usefully incorporated into the text on the appropriate page, so the reader never faces the frustration of flipping repeatedly from cover to cover in search of an elusive “figure X.” There are boxed sections containing essential learning points, tips on techniques, and acronyms to aid learning. And within its …
Clinical trials of dual-target CAR T cells, donor-derived CAR T cells, and universal CAR T cells for acute lymphoid leukemia
Authors: Juanjuan Zhao, Yongping Song, Delong Liu
Journal: Journal of Hematology & Oncology (2019)

The current treatment for pediatric acute lymphoblastic leukemia (ALL) is highly successful with high cure rate. However, the treatment of adult ALL remains a challenge, particularly for refractory and/or relapsed (R/R) ALL. The advent of new targeted agents, blinatumomab, inotuzumab ozogamycin, and chimeric antigen receptor (CAR) T cells, are changing the treatment paradigm for ALL. Tisagenlecleucel (kymriah, Novartis) is an autologous CD19-targeted CAR T cell product approved for treatment of R/R B cell ALL and lymphoma. In an attempt to reduce the relapse rate and treat those relapsed patients with antigen loss, donor-derived CAR T cells and CD19/CD22 dual-target CAR T cells are in clinical trials. Gene-edited "off-the-shelf" universal CAR T cells are also undergoing active clinical development. This review summarized new clinical trials and latest updates at the 2018 ASH Annual Meeting on CAR T therapy for ALL with a focus on dual-target CAR T and universal CAR T cell trials.
Contaminating viral sequences in high-throughput sequencing viromics: a linkage study of 700 sequencing libraries
Authors: M. Asplund, K.R. Kjartansdóttir, S. Mollerup, L. Vinner, H. Fridholm, J.A.R. Herrera, J. Friis-Nielsen, T.A. Hansen, R.H. Jensen, I.B. Nielsen, S.R. Richter, A. Rey-Iglesia, M.L. Matey-Hernandez, D.E. Alquezar-Planas, P.V.S. Olsen, T. Sicheritz-Pontén, E. Willerslev, O. Lund, S. Brunak, T. Mourier, L.P. Nielsen, J.M.G. Izarzugaza, A.J. Hansen
Journal: Clinical Microbiology and Infection (2019)

ObjectivesSample preparation for high-throughput sequencing (HTS) includes treatment with various laboratory components, potentially carrying viral nucleic acids, the extent of which has not been thoroughly investigated. Our aim was to systematically examine a diverse repertoire of laboratory components used to prepare samples for HTS in order to identify contaminating viral sequences.MethodsA total of 322 samples of mainly human origin were analysed using eight protocols, applying a wide variety of laboratory components. Several samples (60% of human specimens) were processed using different protocols. In total, 712 sequencing libraries were investigated for viral sequence contamination.ResultsAmong sequences showing similarity to viruses, 493 were significantly associated with the use of laboratory components. Each of these viral sequences had sporadic appearance, only being identified in a subset of the samples treated with the linked laboratory component, and some were not identified in the non-template control samples. Remarkably, more than 65% of all viral sequences identified were within viral clusters linked to the use of laboratory components.ConclusionsWe show that high prevalence of contaminating viral sequences can be expected in HTS-based virome data and provide an extensive list of novel contaminating viral sequences that can be used for evaluation of viral findings in future virome and metagenome studies. Moreover, we show that detection can be problematic due to stochastic appearance and limited non-template controls. Although the exact origin of these viral sequences requires further research, our results support laboratory-component-linked viral sequence contamination of both biological and synthetic origin.
Targeting interleukin-6 as a strategy to overcome stroma-induced resistance to chemotherapy in gastric cancer
Authors: In-Hye Ham, Hye Jeong Oh, Hyejin Jin, Cheong A Bae, Sang-Min Jeon, Kyeong Sook Choi, Sang-Yong Son, Sang-Uk Han, Rolf A. Brekken, Dakeun Lee, Hoon Hur
Journal: Molecular Cancer (2019)

Although the tumor stroma in solid tumors like gastric cancer (GC) plays a crucial role in chemo-resistance, specific targets to inhibit the interaction between the stromal and cancer cells have not yet been utilized in clinical practice. The present study aims to determine whether cancer-associated fibroblasts (CAFs), a major component of the tumor stroma, confer chemotherapeutic resistance to GC cells, and to discover potential targets to improve chemo-response in GC. To identify CAF-specific proteins and signal transduction pathways affecting chemo-resistance in GC cells, secretome and transcriptome analyses were performed. We evaluated the inhibiting effect of CAF-specific protein in in vivo and in vitro models and investigated the expression of CAF-specific protein in human GC tissues. Secretome and transcriptome data revealed that interleukin-6 (IL-6) is a CAF-specific secretory protein that protects GC cells via paracrine signaling. Furthermore, CAF-induced activation of the Janus kinase 1-signal transducer and activator of transcription 3 signal transduction pathway confers chemo-resistance in GC cells. CAF-mediated inhibition of chemotherapy-induced apoptosis was abrogated by the anti-IL-6 receptor monoclonal antibody tocilizumab in various experimental models. Clinical data revealed that IL-6 was prominently expressed in the stromal portion of GC tissues, and IL-6 upregulation in GC tissues was correlated with poor responsiveness to chemotherapy. Our data provide plausible evidence for crosstalk between GC cells and CAFs, wherein IL-6 is a key contributor to chemoresistance. These findings suggest the potential therapeutic application of IL-6 inhibitors to enhance the responsiveness to chemotherapy in GC.
U-turn on blood policy
Authors: Navin Chohan
Journal: BMJ (2000)

Jehovah's Witnesses are now allowed to accept blood transfusions without facing excommunication from their faith.

Following a secret meeting of the following's 12 member global governing body at their New York headquarters, a change in practice was decreed and blood transfusion was officially downgraded to a “non-disfellowshipping event.” Jehovah's Witnesses may now consent to and accept blood transfusions in life or death situations without facing expulsion from the movement. This is …
First Pharmfree Day launched
Authors: Raghav Chawla
Journal: BMJ (2005)

The first nationwide Pharmfree Day has been launched by The American Medical Student Association on 8 December 2004.

Doctors and students joined together on more than 34 campuses, urging their peers to resist aggressive marketing efforts by pharmaceutical companies. “Prescribing should be based on clinical evidence not on marketing strategies,” Brian Palmer, president of the association, told the studentBMJ .

An event was held at New York University with speakers such as Gene Carbona, former regional manager for Merck, and Bob Goodman, founder of No Free Lunch, an organisation of healthcare providers devoted to combating the influence of pharmaceutical promotion on clinical practice.

Dr Carbona said Merck paid doctors up to $20 000 (£10 404; a15 062) for holding a …
Intracellular Calcium and Myocardial Contractility
Authors: JOSEF SUKO, YASUYUKI UEBA, CHARLES A. CHIDSEY
Journal: Circulation Research (1970)

Postextrasystolic potentiation was studied in the isolated perfused rabbit heart to determine its effect on intracellular calcium, sodium, and potassium concentration, 45 Ca uptake, and calcium distribution in mitochondria and microsomes. Paired stimulation at 80/min augmented myocardial contractility with a gradually developing increase in total intracellular calcium and sodium. A greater 45 Ca uptake was also observed and this was proportionate to the increase of intracellular calcium so that no change in exchangeable calcium occurred. A small but statistically insignificant increment was observed in mitochondrial and microsomal calcium. An increase of the rate of single stimuli to 160/min produced a minimal change in myocardial contractility compared to paired stimulation at 80/min, no change in total intracellular calcium, and a greater calcium uptake so that there was a significant increment in exchangeable calcium. Although these experiments do not identify the cellular processes responsible for the positive inotropic response to paired stimulation, they suggest that an alteration of myocardial calcium metabolism is involved. Furthermore, it is apparent that this alteration is distinct from that occurring during a comparable increase in the rate of delivery of single stimuli to the heart.
Active Surveillance of Low-Risk Thyroid Cancer
Authors: Kyle A. Zanocco, Jerome M. Hershman, Angela M. Leung
Journal: JAMA (2019)

This JAMA Insights Clinical Update reviews use of active ultrasonography surveillance of patients with thyroid cancer as a way to postpone or avoid thyroidectomy in patients with lower-risk tumors for whom surgery is more likely to be harmful than beneficial.
AIDS activists bring antiretrovirals into South Africa
Authors: Debbie Cohen
Journal: BMJ (2002)

South African AIDS activist protests over the availability of drugs, by lying in a pile of crosses representing dead HIV victims



Generic antiretroviral drugs have been imported into South Africa from Brazil by a leading AIDS activist group to highlight the need for affordable treatment for the country's sufferers.

Members of the Treatment Action Campaign (TAC) imported two shipments of the drugs …
Abstract 19146: The Prognostic Role of Change in End-Diastolic Pressure in Patients With Severe Aortic Stenosis Who Undergo Transcatheter Aortic Valve Replacement
Authors: Petar Saric, Jerry Lipinski, Toral Patel, Sandeep Patel, Thomas Ladas, Guilherme Attizzani
Journal: Circulation (2017)

Introduction: In severe aortic stenosis (AS), the pressure gradient across the aortic valve during ejection can be severely elevated. This high pressure gradient can result in left ventricular hype...
Nanofiber-hydrogel composite–mediated angiogenesis for soft tissue reconstruction
Authors: Xiaowei Li, Brian Cho, Russell Martin, Michelle Seu, Chi Zhang, Zhengbing Zhou, Ji Suk Choi, Xuesong Jiang, Long Chen, Gurjot Walia, Jerry Yan, Megan Callanan, Huanhuan Liu, Kevin Colbert, Justin Morrissette-McAlmon, Warren Grayson, Sashank Reddy, Justin M. Sacks, Hai-Quan Mao
Journal: Science Translational Medicine (2019)

Soft tissue losses from tumor removal, trauma, aging, and congenital malformation affect millions of people each year. Existing options for soft tissue restoration have several drawbacks: Surgical options such as the use of autologous tissue flaps lead to donor site defects, prosthetic implants are prone to foreign body response leading to fibrosis, and fat grafting and dermal fillers are limited to small-volume defects and only provide transient volume restoration. In addition, large-volume fat grafting and other tissue-engineering attempts are hampered by poor vascular ingrowth. Currently, there are no off-the-shelf materials that can fill the volume lost in soft tissue defects while promoting early angiogenesis. Here, we report a nanofiber-hydrogel composite that addresses these issues. By incorporating interfacial bonding between electrospun poly(ε-caprolactone) fibers and a hyaluronic acid hydrogel network, we generated a composite that mimics the microarchitecture and mechanical properties of soft tissue extracellular matrix. Upon subcutaneous injection in a rat model, this composite permitted infiltration of host macrophages and conditioned them into the pro-regenerative phenotype. By secreting pro-angiogenic cytokines and growth factors, these polarized macrophages enabled gradual remodeling and replacement of the composite with vascularized soft tissue. Such host cell infiltration and angiogenesis were also observed in a rabbit model for repairing a soft tissue defect filled with the composite. This injectable nanofiber-hydrogel composite augments native tissue regenerative responses, thus enabling durable soft tissue restoration outcomes.
The Transferrin Receptor CD71 Delineates Functionally Distinct Airway Macrophage Subsets during Idiopathic Pulmonary Fibrosis
Authors: Sarah J. Allden, Patricia P. Ogger, Poonam Ghai, Peter McErlean, Richard Hewitt, Richard Toshner, Simone A. Walker, Peter Saunders, Shaun Kingston, Philip L. Molyneaux, Toby M. Maher, Clare M. Lloyd, Adam J. Byrne
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Idiopathic pulmonary fibrosis (IPF) is a devastating progressive disease with limited therapeutic options. Airway macrophages (AMs) are key components of the defense of the airways and are implicated in the pathogenesis of IPF. Alterations in iron metabolism have been described during fibrotic lung disease and in murine models of lung fibrosis. However, the role of transferrin receptor 1 (CD71)-expressing AMs in IPF is not known.
How failure changed my life
Authors: Seye Abimbola
Journal: BMJ (2008)

My only ambition at medical school was to pass with distinction. Nothing else mattered. True to purpose, I passed the second MB (preclinical exams) at the top of my class. I was hardheaded and arrogant, and I made friends with my fellow straight A students only. I was on my way to becoming a brash and brilliant scientist; another James Watson of the DNA double helix fame, radiating contempt in all directions. But medical school was only blissful while the scientific disciplines lasted.

Everything came to a grand halt when clinical rotations began. I had …
Central venous access: anatomy and ultrasound
Authors: Alexander Davey, Christopher Boyd
Journal: BMJ (2006)

As a simulated patient in a recent course on ultrasound guided central venous access I learnt the basics of gross and surface anatomy of the venous system; the use of ultrasound imaging to view blood vessels; and the use of ultrasound guidance for venepuncture and insertion of central venous and peripherally inserted central catheters. This quiz covers gross, surface, and ultrasound anatomy of the internal jugular vein with regard to central venous access.

Consider the clinical scenario of a patient who has recurrent deep vein thrombosis and cannot receive oral anticoagulants. The patient will need central venous access to place a filter in the inferior vena cava to prevent pulmonary embolism.





Central veins, such as the superior vena cava and inferior vena cava are accessed through major veins in the anterior triangle, axilla, and femoral triangle. The target vessels in these areas are the femoral, axillary, subclavian, and internal jugular veins. Access to central veins is necessary for many purposes, such as haemodialysis, …